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Life, Volume 16, Issue 6 (June 2026) – 175 articles

Cover Story (view full-size image): Traumatic nerve injuries often cause persistent motor, sensory, and autonomic deficits, while current repair options are limited by donor site morbidity, tissue availability, and inconsistent recovery. This review synthesizes 12 preclinical studies of silk-derived 3D-bioprinted scaffolds for neural repair and nerve regeneration. Silk fibroin acts as a tunable biomaterial backbone that can be paired with collagen, decellularized extracellular matrices, exosomes, small molecules, or conductive polymers to meet defect-specific demands. Across central and peripheral nerve models, these scaffolds support architectural guidance, localized therapeutic delivery, reduced neuroinflammation, axonal regeneration, myelination, synaptic reconnection, and motor or electrophysiologic recovery. Silk-based 3D bioprinting may offer a promising platform for patient-specific nerve repair. View this paper
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17 pages, 838 KB  
Systematic Review
Beyond HPV in Eastern Europe: Genotype Distribution, Molecular Biomarkers, Vaginal Microbiome, and Implications for Cervical Cancer Prevention
by Eugenia-Alina Radu, Corina-Ioana Anton, Cristian-Sorin Sima and Adrian Streinu-Cercel
Life 2026, 16(6), 1039; https://doi.org/10.3390/life16061039 - 22 Jun 2026
Viewed by 249
Abstract
Human papillomavirus (HPV) infection remains the principal etiological factor in cervical cancer development worldwide, with Eastern Europe continuing to demonstrate disproportionately high cervical cancer incidence and mortality rates. Regional disparities in screening implementation, vaccination coverage, and HPV genotype distribution contribute substantially to the [...] Read more.
Human papillomavirus (HPV) infection remains the principal etiological factor in cervical cancer development worldwide, with Eastern Europe continuing to demonstrate disproportionately high cervical cancer incidence and mortality rates. Regional disparities in screening implementation, vaccination coverage, and HPV genotype distribution contribute substantially to the persistent burden of HPV-related disease. In recent years, increasing attention has focused on molecular biomarkers and the vaginal microbiome as complementary approaches for improving cervical cancer prevention strategies. This systematic review aimed to evaluate recent evidence regarding HPV genotype distribution, molecular biomarkers, vaginal microbiome composition, and their implications for cervical cancer prevention in Eastern Europe. A systematic literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science, Embase, and the Cochrane Library for studies published between January 2020 and May 2026. This systematic review was conducted in accordance with the PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420261391136). Studies from Eastern European populations reporting data on HPV genotype distribution, screening strategies, vaccination, molecular biomarkers, or vaginal microbiome composition were included. HPV prevalence in screening populations ranged from approximately 12% to over 20%, with HPV16 consistently identified as the predominant genotype across all included studies. However, non-16/18 high-risk genotypes, particularly HPV31, HPV51, HPV52, HPV66, and HPV68, represented a substantial proportion of infections in several Eastern European cohorts. Studies evaluating CINtec PLUS cytology and HPV E6/E7 mRNA testing demonstrated improved specificity for identifying clinically significant cervical lesions compared with HPV DNA testing alone. Emerging evidence also suggested associations between vaginal dysbiosis, increased microbial diversity, persistent high-risk HPV infection, and progression to cervical intraepithelial neoplasia. Although the 9-valent HPV vaccine provides coverage for most circulating high-risk genotypes identified in the region, vaccination uptake remains inconsistent throughout Eastern Europe. The findings of this systematic review support the growing importance of extended HPV genotyping, molecular biomarkers, and microbiome-related approaches in cervical cancer prevention strategies in Eastern Europe. Strengthening organized screening programs, expanding vaccination coverage, and improving access to molecular diagnostic technologies remain essential priorities for reducing the regional burden of HPV-related disease. Full article
(This article belongs to the Section Physiology and Pathology)
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16 pages, 277 KB  
Article
Blood Group Antigen Combinations and COVID-19: Complexity, Associations and Possible Clinical Relevance
by Jolanta Wrobel, Ewa Jablonska, Krzysztof Matuk, Agnieszka Zebrowska, Piotr Radziwon and Wioletta Ratajczak-Wrona
Life 2026, 16(6), 1038; https://doi.org/10.3390/life16061038 - 22 Jun 2026
Viewed by 288
Abstract
Background: The aim of the study was to investigate whether red blood cell antigens (A, B, D, Cw, C, c, E, e, K, k, Jka, Jkb, Fya, Fyb, Lea, Leb [...] Read more.
Background: The aim of the study was to investigate whether red blood cell antigens (A, B, D, Cw, C, c, E, e, K, k, Jka, Jkb, Fya, Fyb, Lea, Leb, M, N, S, s, and P1) from clinically relevant blood group systems were associated with susceptibility to COVID-19. Methods: This exploratory case-control study was carried out on a group of 263 donors from the Regional Center for Transfusion Medicine, Bialystok, Poland (including 121 convalescents and 142 healthy subjects). The microplate method was applied to examine the expression of 21 antigens from eight clinically relevant systems in the donors’ red blood cells. Results: No significant correlation was found between any single blood group and susceptibility to COVID-19. For a more detailed analysis, we adopted an approach involving 3-, 4- and 5-element mutual combinations of antigens. In this exploratory analysis of multi-antigen combinations, nominal statistical significance was found for a number of associations, but none remained statistically significant after adjustment for multiple testing. In the case of three-antigen associations, the strongest association was observed for cc combined with Ee and kk, with the effect size showing approximately 4× higher odds of COVID-19 (OR = 4.49, p = 0.020); in the case of four-antigen combinations, the strongest association was found for RhD(+) combined with kk, Fyb and P1(−), as well as RhD(+) combined with cc, Ee and kk, also indicating 4× higher odds of COVID-19 (OR = 4.49 p = 0.016). For five-antigen combinations, the strongest association was observed for blood type O combined with kk, Leb, P1(+) and MM, with the association strength reaching an OR = 4.44, p = 0.025. Conclusions: The findings suggest that analyses based solely on single blood group antigens may have limited value for assessing the susceptibility to COVID-19. In contrast, combinations of red blood cell antigens may provide more reliable correlations with the susceptibility to COVID-19. However, these findings should be interpreted with caution and require confirmation on larger and more representative populations. Full article
(This article belongs to the Collection COVID-19 and Life)
20 pages, 5879 KB  
Article
Therapeutic Effects of Scutellaria baicalensis Georgi Extract and Baicalein on Olfactory Dysfunction and Neurobehavioral Alterations in a Methimazole-Induced Injury Model
by Manh Nguyen Dao, Hang Thi Nguyet Pham, Nam Duy Pham and Cuong Viet Vo
Life 2026, 16(6), 1037; https://doi.org/10.3390/life16061037 - 22 Jun 2026
Viewed by 249
Abstract
Background: Olfactory dysfunction is a pathology associated with viral infections, toxic damage, aging, and neurodegenerative diseases. Damage to the olfactory epithelium impairs olfactory function and related neurological behaviors. This study evaluated the restorative effects of Scutellaria baicalensis Georgi (SBG) extract and baicalein in [...] Read more.
Background: Olfactory dysfunction is a pathology associated with viral infections, toxic damage, aging, and neurodegenerative diseases. Damage to the olfactory epithelium impairs olfactory function and related neurological behaviors. This study evaluated the restorative effects of Scutellaria baicalensis Georgi (SBG) extract and baicalein in a methimazole-induced olfactory dysfunction model. Methods: Olfactory epithelial damage was induced in mice with methimazole, followed by treatment with SBG extract or baicalein. Olfactory and neurobehavioral functions were assessed using odor-finding, novel object recognition (NOR), Morris water maze (MWM), open field (OFT), and elevated plus maze tests (EPM). Histological, immunohistochemical, and in vitro analyses were performed to evaluate epithelial regeneration, mature olfactory sensory neurons (OSNs) expressing olfactory marker protein (OMP), and proliferative activity. Results: Methimazole induced severe olfactory epithelial damage, impairing olfactory behavior and reducing learning and memory. Treatment with SBG extract and baicalein significantly improved olfactory and cognitive functions. Histological and immunohistochemical analyses confirmed restoration of epithelial structure and olfactory neurons. In vitro, SBG extract increased epithelial cell density and modulated proliferative activity. Conclusions: SBG extract and baicalein promote recovery of olfactory function and improve neurobehavioral outcomes, indicating their potential as therapies for olfactory dysfunction. Full article
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15 pages, 2396 KB  
Article
The Effects of Unstable Strength Training on Lower Limb Stability in Adolescent Volleyball Players in China
by Kaiyuan Dong and Borhannudin Bin Abdullah
Life 2026, 16(6), 1036; https://doi.org/10.3390/life16061036 - 22 Jun 2026
Viewed by 204
Abstract
Background: This study aimed to compare the effects of unstable strength training (UST) and traditional strength training (TST) on lower-body stability in adolescent volleyball players in China. Methods: This stratified randomized controlled trial recruited 62 eligible athletes from Shandong Province. Participants were assigned [...] Read more.
Background: This study aimed to compare the effects of unstable strength training (UST) and traditional strength training (TST) on lower-body stability in adolescent volleyball players in China. Methods: This stratified randomized controlled trial recruited 62 eligible athletes from Shandong Province. Participants were assigned to either the UST group or the TST group, and both groups completed a 10-week training program. Results: Multivariate analysis of variance (MANOVA) for within-group effects revealed statistically significant improvements in all dependent variables for both the UST and TST groups (p < 0.05), FMS [F = 35.112, p < 0.001, η2 = 0.377]; and balance ability differences, left-side score (LS) [F = 8.268, p < 0.001, η2 = 0.125], right-side score (RS) [F = 8.094, p < 0.001, η2 = 0.122]. Furthermore, after controlling for covariates, MANCOVA analysis for between-group effects still showed statistically significant differences between the UST and TST groups on all post-test dependent variables. These differences included: functional differences, FMS [F = 34.412, p < 0.001, η2 = 0.389]; LS [F = 8.079, p < 0.01, η2 = 0.130]; and RS [F = 8.532, p < 0.001, η2 = 0.136]. Conclusion: UST is more effective than TST in improving athletes’ lower-body stability performance. Future studies should explore the application of UST in other sports and examine its effects on parameters beyond functional movement and balance. Full article
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10 pages, 2056 KB  
Article
Herpes Encephalitis as a Differential Diagnosis of Atypical Intracerebral Hemorrhage: A Case Series and Systematic Review
by Mark Christian Link and Judith N. Wagner
Life 2026, 16(6), 1035; https://doi.org/10.3390/life16061035 - 22 Jun 2026
Viewed by 242
Abstract
Herpes simplex virus encephalitis (HSVE) is the most common infectious encephalitis and is associated with high morbidity and mortality when not treated in time. Symptoms include fever, headache, fatigue, neurological deficits such as aphasia and epileptic seizures. While hemorrhagic transformation is a common [...] Read more.
Herpes simplex virus encephalitis (HSVE) is the most common infectious encephalitis and is associated with high morbidity and mortality when not treated in time. Symptoms include fever, headache, fatigue, neurological deficits such as aphasia and epileptic seizures. While hemorrhagic transformation is a common complication in HSVE, intracerebral hematoma (ICH) as the initial or main presentation is rare. We present two patients with HSVE who displayed a large temporal hematoma as the main finding on cerebral imaging. We further conducted a systematic literature review to identify all published cases of ICH in HSVE. Forty-nine publications met the inclusion criteria, describing a total of 55 patients. In 38 of these, HSVE could be definitely confirmed by brain biopsy, autopsy or PCR. We analyzed these cases according to age, gender, lag from symptom onset to hospital admission, lag from hospital admission to detection of hemorrhage, location of encephalitis and hemorrhage, received treatment and outcome. With a median age of 45 years, this cohort is significantly younger than general HSVE populations described previously. In conclusion, our review shows that, albeit rare, awareness about ICH complicating HSVE is highly relevant as failure to recognize an atypical course of HVSE may result in a delay of effective antiviral treatment, which is related to an unfavorable or even fatal outcome. Full article
(This article belongs to the Special Issue Encephalitis: From Molecular Pathophysiology to Therapy)
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19 pages, 877 KB  
Article
Chromosomal Microarray Analysis in Critically Ill Neonates and Children: Diagnostic Yield and Clinical Utility
by Joshua Meyer, Emily Hershman, Ananditha Sivakumaran, Vinisha Venugopal, Derek Neilson, Theresa A. Grebe and Theru A. Sivakumaran
Life 2026, 16(6), 1034; https://doi.org/10.3390/life16061034 - 22 Jun 2026
Viewed by 271
Abstract
Chromosomal microarray analysis (CMA) is widely used to detect chromosomal aneuploidies and copy number variants (CNVs) in pediatric patients with congenital anomalies or developmental concerns. However, its diagnostic utility in critically ill neonates and children admitted to intensive care units (ICUs) remains undercharacterized. [...] Read more.
Chromosomal microarray analysis (CMA) is widely used to detect chromosomal aneuploidies and copy number variants (CNVs) in pediatric patients with congenital anomalies or developmental concerns. However, its diagnostic utility in critically ill neonates and children admitted to intensive care units (ICUs) remains undercharacterized. We conducted a retrospective review of 679 patients admitted to the neonatal, pediatric, or cardiovascular intensive care units (NICU, PICU, CVICU) at Phoenix Children’s Hospital between 2019 and 2024 who underwent CMA. Demographic data, clinical indications, and CMA results were extracted from electronic medical records to assess diagnostic yield and variant patterns. CMA identified a clinically relevant finding in 102 of 679 patients, resulting in an overall diagnostic yield of 15.0% (95% CI: 12.3–17.7%). Clinically relevant findings included pathogenic (P) variants (n = 88), likely pathogenic (LP) variants (n = 12), and large regions of absence of heterozygosity (AOH) consistent with uniparental disomy (UPD) (n = 2). A variant of uncertain significance (VUS) was detected in 139 patients (20.5%). Among the pathogenic and likely pathogenic variants, CMA identified recurrent CNVs (n = 49), nonrecurrent CNVs (n = 17), aneuploidies (n = 22), and patients with two pathogenic or likely pathogenic CNVs (n = 10). Diagnostic yields of 48.4% (95% CI: 38.5–58.4%) and 8.4% (95% CI: 6.0–11.5%) were observed in patients with single or multiple congenital anomalies including a congenital heart defect (CA + CHD), and in patients with an isolated CHD, respectively. CMA demonstrates significant diagnostic value in critically ill neonates and children, particularly among those with multisystem congenital anomalies. These findings support the routine integration of CMA in genomic evaluation protocols for ICU populations to guide diagnosis, management, and counseling. Full article
(This article belongs to the Special Issue Updates in Human Disease Genetic Research)
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45 pages, 2572 KB  
Review
The Maternal Microbiome in Pregnancy: From Physiological Changes to Dysbiosis and Obstetrical Complications—Therapeutic Perspectives
by Lucia Maria Procopciuc, Gabriela Valentina Caracostea, Adriana Corina Hangan and Roxana Liana Lucaciu
Life 2026, 16(6), 1033; https://doi.org/10.3390/life16061033 - 21 Jun 2026
Viewed by 243
Abstract
During pregnancy, hormonal, metabolic, and immunological changes influence the composition and function of maternal microbial communities. Increasing evidence suggests that the maternal microbiota—particularly in the vaginal, gut, and oral environments—plays a significant role in maintaining pregnancy homeostasis and supporting fetal development. In healthy [...] Read more.
During pregnancy, hormonal, metabolic, and immunological changes influence the composition and function of maternal microbial communities. Increasing evidence suggests that the maternal microbiota—particularly in the vaginal, gut, and oral environments—plays a significant role in maintaining pregnancy homeostasis and supporting fetal development. In healthy pregnancies, the vaginal microbiota is typically dominated by Lactobacillus species, which help maintain a low vaginal pH and protect against ascending infections. However, disruption of this balance (vaginal dysbiosis) has been associated with obstetrical complications such as intrauterine infection and preterm birth. Similarly, the maternal gut microbiota undergoes trimester-specific changes that contribute to metabolic adaptations required for fetal growth, while alterations in microbial composition have been linked to metabolic disorders including gestational diabetes mellitus and preeclampsia. Changes in oral microbiota and periodontal disease have also been associated with adverse pregnancy outcomes through systemic inflammatory pathways and potential microbial translocation to the placenta. Recent advances in sequencing technologies have improved the understanding of host–microbiome interactions in pregnancy, although the existence of a placental microbiome remains controversial. Overall, maternal microbiota plays an important role in pregnancy physiology, and its dysregulation may contribute to obstetrical complications. Understanding these mechanisms may facilitate the development of microbiome-based diagnostic and therapeutic strategies in maternal–fetal medicine. Full article
(This article belongs to the Special Issue The Microbiome and Dysbiosis in Various Pathologies)
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23 pages, 1144 KB  
Review
Responsible Use of Large Language Models in Microbial Genomics and Bioinformatics: A Life-Science Framework for Reliability, Reproducibility, and Risk-Aware Interpretation
by Mia Yang Ang, Li Chen, Lanni Song, Leonard Lipovich and Siew Woh Choo
Life 2026, 16(6), 1032; https://doi.org/10.3390/life16061032 - 20 Jun 2026
Viewed by 387
Abstract
Large language models (LLMs) are increasingly adopted in life-science research for scientific writing, coding, literature synthesis, workflow troubleshooting, and preliminary data interpretation. In microbial genomics and bioinformatics, their appeal is clear because researchers routinely integrate genome annotations, antimicrobial resistance profiles, virulence determinants, taxonomic [...] Read more.
Large language models (LLMs) are increasingly adopted in life-science research for scientific writing, coding, literature synthesis, workflow troubleshooting, and preliminary data interpretation. In microbial genomics and bioinformatics, their appeal is clear because researchers routinely integrate genome annotations, antimicrobial resistance profiles, virulence determinants, taxonomic assignments, microbiome outputs, workflow scripts, and primary literature. Yet this domain also highlights major risks, including hallucinated biological claims, inaccurate citations, irreproducible code, unsupported genotype-to-phenotype inference, and inappropriate clinical or public health framing. This narrative review examines responsible LLM use in microbial genomics as a representative life-science setting where interpretation depends on database provenance, validated workflows, expert assessment, and reproducible evidence chains. It considers applications in genome annotation, antimicrobial resistance interpretation, virulence analysis, microbiome and metagenomics workflows, coding support, and scientific writing. The review further presents MicrobeGuardGPT as a conceptual reliability framework for assessing LLM-assisted microbial genomics outputs before scientific, clinical, or public health use. By connecting task domains, evidence verification, expert validation, and reliability classification, the framework supports risk-aware LLM integration in bioinformatics. Responsible implementation will require domain-specific benchmarks, curated database linkage, transparent reporting, reproducible workflows, human oversight, and governance standards tailored to biological interpretation across research, diagnostic, surveillance, outbreak-response, educational, and translational contexts. Full article
(This article belongs to the Section Artificial Intelligence in the Life Sciences)
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17 pages, 2061 KB  
Article
Tissue-Specific Redistribution of Free Amino Acids in Mandarin Fish (Siniperca chuatsi) Under Acute Salinity, Alkalinity and Combined Saline–Alkaline Stress
by Yan Li, Longyi Li, Yiming Li, Qiang Ji, Zongli Yao, Pengcheng Gao, Kai Zhou, Zhen Sun, Yuxing Wei and Qifang Lai
Life 2026, 16(6), 1031; https://doi.org/10.3390/life16061031 - 19 Jun 2026
Viewed by 207
Abstract
Free amino acids (FAAs) are important low-molecular-weight metabolites involved in osmotic regulation, acid–base balance, and nitrogen metabolism in fish exposed to saline–alkaline environments. To characterize tissue-specific FAA responses in mandarin fish (Siniperca chuatsi), 10 cm juveniles were exposed for 96 h [...] Read more.
Free amino acids (FAAs) are important low-molecular-weight metabolites involved in osmotic regulation, acid–base balance, and nitrogen metabolism in fish exposed to saline–alkaline environments. To characterize tissue-specific FAA responses in mandarin fish (Siniperca chuatsi), 10 cm juveniles were exposed for 96 h to freshwater control (FW), salinity stress (S, salinity 8), alkalinity stress (A, alkalinity 20 mmol/L), or combined saline–alkaline stress (SA, salinity 8 + alkalinity 20 mmol/L). The contents of 19 FAAs were compared among plasma, muscle, liver, brain, and kidney. FAA profiles showed clear tissue specificity. Total FAA (17) decreased in plasma under all stress treatments, increased in muscle under S and SA but decreased under A, increased in liver and kidney, and decreased under single stress but increased under combined stress in brain. Distinct tissue distribution patterns were observed for functional FAA groups. Under salinity stress, osmoregulation-related FAAs, particularly Ala and Pro, showed higher contents mainly in muscle, liver, and kidney. Under alkalinity stress, kidney showed concurrent increases in multiple FAAs, including Ala, Pro, Glu, Gln, Val, Ile, and Leu, whereas brain was characterized by a high Gln content. Under combined saline–alkaline stress, liver was the main tissue in which multiple functional FAA groups increased simultaneously, kidney maintained elevated levels of several FAAs, and brain showed treatment-specific high levels of Gln and Tau. Redundancy analysis (RDA) indicated weak constrained explanatory power of salinity and alkalinity for the overall FAA profile, whereas tissue-specific differentiation was evident. Glu, Gln, and Pro showed directional consistency with the salinity vector, whereas Val and Leu tended to align with the alkalinity-related ordination direction. Overall, acute saline–alkaline exposure induced a functional and tissue-specific distribution pattern of FAAs rather than a uniform whole-body shift in mandarin fish. Full article
(This article belongs to the Section Animal Science)
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17 pages, 1028 KB  
Systematic Review
Improving Obstetric Safety in Postpartum Hemorrhage: Impact of Protocol-Based Conservative Management
by Martina Cheli Basurte, Marta Blasco Alonso, Isidoro Narbona Arias, Lorena Sabonet Moriente, Marta Martínez Diez and Jesus S. Jimenez Lopez
Life 2026, 16(6), 1030; https://doi.org/10.3390/life16061030 - 19 Jun 2026
Viewed by 206
Abstract
Background: Postpartum hemorrhage (PPH) remains a leading cause of maternal morbidity and mortality worldwide, accounting for approximately 27% of maternal deaths. In Spain, its incidence ranges from 2.5% to 5.2%. Clinical management has evolved toward a stepwise approach integrating pharmacological, mechanical, and surgical [...] Read more.
Background: Postpartum hemorrhage (PPH) remains a leading cause of maternal morbidity and mortality worldwide, accounting for approximately 27% of maternal deaths. In Spain, its incidence ranges from 2.5% to 5.2%. Clinical management has evolved toward a stepwise approach integrating pharmacological, mechanical, and surgical interventions. This study aims to analyze the evolution of these techniques during the 2020–2024 period to optimize decision-making and maternal outcomes. Methods: A systematic review was conducted following the PRISMA 2020 guidelines. Comprehensive searches were performed in PubMed, Scopus, and the Cochrane Library for studies published between 2020 and 2024 in English and Spanish. The PICO framework was utilized to evaluate interventions including intrauterine balloon tamponade (UBT), compression sutures, and arterial embolization, prioritizing outcomes such as bleeding control and fertility preservation. Out of 34 identified records, 13 studies met the final inclusion criteria. Results: The findings demonstrate a clear trend toward conservative management. Intrauterine balloon tamponade reported success rates of 80–90% in controlling refractory bleeding and significantly reduced the hysterectomy rates. B-Lynch compression sutures showed success rates between 68.4% and 100%, with generally favorable fertility outcomes. However, combining these sutures with devascularization increased the risk of uterine necrosis. Additionally, the early administration of tranexamic acid (TXA) within 3 h of birth was confirmed as a critical factor in reducing mortality. Conclusions: Acute PPH management has shifted toward protocol-based, sequential, and less invasive strategies. The implementation of standardized algorithms, care bundles, and simulation-based training is essential to reduce decision inertia and improve obstetric safety. While conservative mechanical and surgical techniques are effective, institutional protocols must be regularly updated to consolidate these technological and organizational advances. Full article
(This article belongs to the Section Physiology and Pathology)
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14 pages, 6185 KB  
Article
Inhibitory Effects of Oxytocin on Jejunal Migrating Myoelectric Complex Activity in Fasted Rats: Role of Oxytocin and GLP-1 Receptors
by Hakan Balcı, Özge Darakcı Saltık, Burcu Hatipoğlu Aktemur, Rümeysa Abdullahoğlu and Ayhan Bozkurt
Life 2026, 16(6), 1029; https://doi.org/10.3390/life16061029 - 19 Jun 2026
Viewed by 302
Abstract
The migrating myoelectric complex (MMC) is the electrical basis of fasting small intestinal motility. Although oxytocin (OT) regulates gastrointestinal functions through oxytocin receptors (OTRs), its effect on jejunal MMC activity during fasting remains unclear. This study investigated the effects of OT on jejunal [...] Read more.
The migrating myoelectric complex (MMC) is the electrical basis of fasting small intestinal motility. Although oxytocin (OT) regulates gastrointestinal functions through oxytocin receptors (OTRs), its effect on jejunal MMC activity during fasting remains unclear. This study investigated the effects of OT on jejunal MMC activity in fasted rats and evaluated the involvement of OTRs, glucagon-like peptide-1 receptors (GLP-1Rs), and nitric oxide (NO) pathways. Bipolar electrodes were implanted at three jejunal sites in adult male Sprague Dawley rats for MMC recordings. After recovery and 18 h fasting, OT was administered intraperitoneally (4–32 µg/kg) following one hour of basal recording. To assess mechanisms, rats were pretreated with the OTR antagonist atosiban (2 mg/kg), the GLP-1R antagonist exendin (9–39) (200 µg/kg), or the nitric oxide synthase inhibitor NG-nitro-L-arginine (L-NNA; 5 mg/kg) before OT (16 µg/kg). Oxytocin dose-dependently reduced spike frequency and MMC cycle number (p < 0.05–0.001 vs. vehicle). Atosiban completely reversed these effects (p < 0.001 vs. OT), while exendin (9–39) partially attenuated them (p < 0.01–0.001 vs. OT). L-NNA showed no significant effect. These findings indicate that OT inhibits jejunal MMC activity via OTR-dependent mechanisms with partial involvement of GLP-1R signaling but not NO pathways. Full article
(This article belongs to the Section Physiology and Pathology)
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19 pages, 734 KB  
Article
The Effectiveness of Janus Kinase Inhibitors for the Management of Relapsing Takayasu Arteritis: A Spanish Real-World Study and Comprehensive Review of the Literature
by Javier Loricera, Javier Narváez, Susana Romero-Yuste, Valentina Emperiale, Iván Ferraz-Amaro, Carmen Secada-Gómez, Adrián Martín-Gutiérrez and Ricardo Blanco
Life 2026, 16(6), 1028; https://doi.org/10.3390/life16061028 - 19 Jun 2026
Viewed by 255
Abstract
Background: A significant proportion of individuals with Takayasu arteritis (TA) experience relapses notwithstanding standard treatment with glucocorticoids, and conventional synthetic or biologic disease-modifying antirheumatic drugs (DMARDs). As the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway contributes to the pathogenesis [...] Read more.
Background: A significant proportion of individuals with Takayasu arteritis (TA) experience relapses notwithstanding standard treatment with glucocorticoids, and conventional synthetic or biologic disease-modifying antirheumatic drugs (DMARDs). As the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway contributes to the pathogenesis of TA, JAK inhibitors (JAKi) could represent a viable therapeutic alternative. This study assessed the effectiveness of JAKi in patients with relapsing TA within a real-world setting in a country with a low incidence of TA such as Spain and included a comprehensive review of the literature. Methods: we conducted a retrospective analysis of TA patients managed with JAKi for recurrent disease across three Spanish centers. Evaluated outcomes comprised clinical remission, clinical and analytical remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A systematic literature search was performed to identify further cases of TA treated with JAKi. Results: six patients (83.3% females) with a mean age 48.5 years and relapsing TA received JAKi therapy: baricitinib (n = 2); tofacitinib (n = 2), and upadacitinib (n = 2). Before JAKi therapy, all (100%) patients had received conventional synthetic immunosuppressants, and four (66.7%) biologics. Clinical remission was achieved in 2/6 (33.3%), 3/5 (60%), 3/5 (60%), 2/3 (66.7%), and 2/2 (100%) patients at 1, 3, 6, 12 and 18 months, respectively. Clinical + analytical remission was observed in 1/6 (16.7%), 2/5 (40%), 2/5 (40%), 2/3 (66.7%), and 2/2 (100%) patients, respectively. Two patients who underwent a follow-up PET/CT imaging showed partial improvement in both. After a median (IQR) follow-up of 9.5 (6.0–16.7) months, one (16.7%) patient discontinued the initial JAKi due to no improvement and one patient discontinued it because was diagnosed with tonsillar neoplasia. The literature search identified another 166 JAKi-treated TA cases with clinical improvement reported for the majority of them. Conclusions: this real-world analysis and literature review suggest that JAKi could be effective in the management of TA, including for those patients who have failed established glucocorticoid-sparing strategies. Full article
(This article belongs to the Special Issue Autoimmune Disorders: From Pathophysiology to Therapeutics)
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19 pages, 2600 KB  
Article
Impact of Radiomics Parameters and Clinical Integration on Prognostication in Head and Neck Squamous Cell Carcinoma: A Multicenter Study
by Hajar Moradmand, Jason Molitoris, Ranee Mehra, Lisa Schumaker, Erin Allor, Daria A. Gaykalova and Lei Ren
Life 2026, 16(6), 1027; https://doi.org/10.3390/life16061027 - 19 Jun 2026
Viewed by 299
Abstract
Radiomics has the potential to improve risk stratification in head and neck squamous cell carcinoma (HNSCC), but clinical adoption is limited by inconsistent performance across institutions. A key source of variability is how radiomic features are generated, preprocessed, and selected prior to model [...] Read more.
Radiomics has the potential to improve risk stratification in head and neck squamous cell carcinoma (HNSCC), but clinical adoption is limited by inconsistent performance across institutions. A key source of variability is how radiomic features are generated, preprocessed, and selected prior to model development. This multicenter study evaluated how radiomics parameterization and feature selection strategies affect external model performance, feature stability, and time-to-event risk stratification. We studied pre-treatment CT scans from 752 patients with primary HNSCC from three hospitals. For each scan, 1648 radiomic features were computed using 20 different preparation methods that varied in scaling, outlier removal, and gray-level bin width. We compared five feature selection methods: Graph-FS with connected components, Boruta, Lasso, RFE-RF, and mRMR. The classification models used were Random Forest, XGBoost, CatBoost, and Logistic Regression. We measured performance using external ROC-AUC, bootstrap confidence intervals, Brier score, and RobustScore. Stability of feature selection was assessed using the Kuncheva and Jaccard indices. Cox proportional hazards models confirmed time-to-event results, and consensus SHAP analysis helped explain the models. Radiomics parameterization influenced model performance, and no single configuration was optimal across all analyses. Radiomics-only models outperformed clinical-only models, while clinical–radiomics models achieved the highest overall performance. mRMR and Lasso produced the highest average external AUCs, while Graph-FS showed the greatest stability. The best classification model achieved an external AUC of 0.817. In Cox validation, the best clinical–radiomics configuration achieved an external C-index of 0.662 and separated high- and low-risk patients in the external cohort. Full article
(This article belongs to the Special Issue Breakthroughs in Radiotherapy for Cancer)
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13 pages, 860 KB  
Article
Preoperative Transcranial Doppler Findings and Postoperative Delirium After Cardiac Surgery in Elderly Patients: A Prospective Observational Study
by Astrid Bergmann, Yurii Ruzhyn, Jan Wiesemann, Nikolai Hulde, Janis Fliegenschmidt, Alexander Krannich and Vera von Dossow
Life 2026, 16(6), 1026; https://doi.org/10.3390/life16061026 - 19 Jun 2026
Viewed by 282
Abstract
Postoperative delirium (POD) is a common neurocognitive complication after cardiac surgery in elderly patients and is associated with adverse clinical outcomes. Impaired cerebral autoregulation and reduced cerebrovascular reserve may contribute to POD development. Automated transcranial Doppler sonography (TCD) enables non-invasive assessment of intracranial [...] Read more.
Postoperative delirium (POD) is a common neurocognitive complication after cardiac surgery in elderly patients and is associated with adverse clinical outcomes. Impaired cerebral autoregulation and reduced cerebrovascular reserve may contribute to POD development. Automated transcranial Doppler sonography (TCD) enables non-invasive assessment of intracranial hemodynamics and may provide additional information for perioperative risk assessment. In this prospective single-center observational study, 108 patients aged >70 years scheduled for elective cardiac surgery with cardiopulmonary bypass were enrolled. Patients who had pre-existing neurological disease, had a pathological carotid Doppler ultrasound, underwent emergency surgery, or were unable to undergo delirium screening were excluded. Preoperative bilateral TCD of the middle cerebral arteries was performed using an automated WAKIe R3 system. POD was assessed on postoperative days 1–3 using the CAM-ICU. The primary endpoint was the occurrence of POD. Twenty-one patients were excluded, leaving 87 patients for analysis. POD occurred in 14 patients (16%). All patients who developed POD had pathological preoperative TCD findings, whereas no POD occurred among patients with normal TCD examinations. Overall, 82 patients (94%) demonstrated pathological intracranial hemodynamic findings despite normal carotid Doppler ultrasound. In multivariable Firth logistic regression adjusted for age and sex, pathological TCD findings remained associated with POD; however, interpretation was limited by the small number of outcome events and quasi-complete separation. In elderly patients undergoing cardiac surgery with cardiopulmonary bypass, pathological preoperative TCD findings were frequently observed and may be associated with an increased risk of postoperative delirium. The marked discrepancy between normal carotid ultrasound and abnormal intracranial hemodynamics suggests that TCD may provide complementary information regarding cerebrovascular function. Given the limited sample size and event rate, these findings should be considered exploratory and require confirmation in larger multicenter studies. Full article
(This article belongs to the Section Medical Research)
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18 pages, 324 KB  
Review
Radiofrequency Ablation for Hemorrhoidal Disease
by Eremeev Spiridon, Cristian Ichim, Paula Anderco and Ciprian Tanasescu
Life 2026, 16(6), 1025; https://doi.org/10.3390/life16061025 - 18 Jun 2026
Viewed by 237
Abstract
Hemorrhoidal disease is a common anorectal condition that may require treatment when bleeding, prolapse or persistent symptoms fail to respond to conservative or office-based therapy. Radiofrequency ablation (RFA) has emerged as a minimally invasive, tissue-sparing technique for symptomatic internal hemorrhoids, based on controlled [...] Read more.
Hemorrhoidal disease is a common anorectal condition that may require treatment when bleeding, prolapse or persistent symptoms fail to respond to conservative or office-based therapy. Radiofrequency ablation (RFA) has emerged as a minimally invasive, tissue-sparing technique for symptomatic internal hemorrhoids, based on controlled delivery of high-frequency energy into hemorrhoidal tissue. The resulting thermal effect induces coagulative necrosis, fibrosis, mucosal fixation and progressive reduction in hemorrhoidal volume, without excisional removal of anoderm or rectal mucosa. This narrative review summarizes the mechanism, technical principles, clinical advantages, comparative evidence and remaining uncertainties surrounding RFA, with particular attention to the Rafaelo procedure and related radiofrequency-based approaches. Current evidence suggests that RFA may reduce postoperative pain, analgesic requirements, wound-related morbidity, hospital stay and time to return to normal activity compared with conventional hemorrhoidectomy, while maintaining acceptable short- and mid-term symptom control in selected patients, especially those with grade II–III internal hemorrhoids. However, available studies remain heterogeneous in design, technique, patient selection, outcome definitions and follow-up duration. The relationship between modern probe-based RFA and earlier radiofrequency-based approaches, including Ellman surface coagulation, Celon bipolar radiofrequency-induced thermotherapy and radiofrequency-assisted hemorrhoidectomy, remains insufficiently standardized in the literature. Further randomized trials, standardized outcome reporting, long-term recurrence data and cost-effectiveness analyses are required to define the optimal indications and therapeutic position of RFA. Full article
(This article belongs to the Section Medical Research)
18 pages, 7874 KB  
Article
Transcriptomic Profiling of Adipose Tissues in Sujiang Pigs Reveals Candidate Genes Associated with Tissue-Specific Fat Deposition
by Huizhen Gao, Shubin Zhu, Ligang Ni, Feixiang Cao and Pan Xu
Life 2026, 16(6), 1024; https://doi.org/10.3390/life16061024 - 18 Jun 2026
Viewed by 204
Abstract
In addition to its role in energy storage, adipose tissue contributes substantially to energy metabolism, endocrine regulation, and inflammatory processes. Sujiang pigs, a hybrid breed approved by the National Livestock and Poultry Genetic Resources Committee of China as a new national breed in [...] Read more.
In addition to its role in energy storage, adipose tissue contributes substantially to energy metabolism, endocrine regulation, and inflammatory processes. Sujiang pigs, a hybrid breed approved by the National Livestock and Poultry Genetic Resources Committee of China as a new national breed in 2013, possess a genetic predisposition for substantial fat deposition, making them an ideal model for investigating the mechanisms underlying adipose tissue accumulation. In this study, back fat (BF; subcutaneous adipose tissue), greater omentum (GOM; visceral adipose tissue), and mesenteric adipose tissue (MAD; visceral adipose tissue) were collected from three 6-month-old male Sujiang pigs for RNA-seq analysis. Comparative analyses identified 3005 differentially expressed genes (DEGs) between BF and GOM, 975 DEGs between BF and MAD, and 892 DEGs between GOM and MAD. To validate the reliability of the sequencing data, five DEGs were randomly selected for RT-qPCR verification. The DEGs were further subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. By integrating protein–protein interaction (PPI) networks with bioinformatics analyses, we identified candidate genes potentially associated with lipid metabolism (e.g., WNT9A, WNT5A, and PDGFRA) and inflammatory responses in adipose tissue (e.g., CSF1R, C1QB, and CD4). These findings indicate potential molecular differences between porcine visceral and subcutaneous adipose tissues and may serve as a reference for further studies on the molecular regulation of adipose tissue metabolism. Full article
(This article belongs to the Section Animal Science)
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46 pages, 21575 KB  
Article
Diversity and Ethnobotany of the Family Zingiberaceae in Lop Buri Province, Thailand, with Notes on a Putative Natural Hybrid
by Thawatphong Boonma, Surapon Saensouk, Piyaporn Saensouk and Tepkanya Promkatkeaw
Life 2026, 16(6), 1023; https://doi.org/10.3390/life16061023 - 18 Jun 2026
Viewed by 317
Abstract
Zingiberaceae is an ecologically, economically, and culturally important plant family in tropical Asia, yet its diversity and ethnobotanical significance remain insufficiently documented in several parts of Thailand. This study investigated the diversity, traditional uses, preliminary regional conservation status, and selected taxonomic aspects of [...] Read more.
Zingiberaceae is an ecologically, economically, and culturally important plant family in tropical Asia, yet its diversity and ethnobotanical significance remain insufficiently documented in several parts of Thailand. This study investigated the diversity, traditional uses, preliminary regional conservation status, and selected taxonomic aspects of Zingiberaceae in Lop Buri Province, central Thailand. Field surveys, herbarium studies, morphological comparisons, informal ethnobotanical interviews, quantitative use analyses, and preliminary conservation assessments were conducted from 2024 to 2025. A total of 110 taxa, comprising 109 species and one putative natural hybrid, were recorded in 13 genera and three tribes. These included wild, cultivated, introduced, and locally utilized taxa documented from natural habitats, home gardens, agricultural areas, and other human-associated habitats. Among them, 43 taxa were recorded from natural habitats as wild or naturally occurring populations, whereas 95 taxa were newly documented for Lop Buri Province. Natural habitats, particularly limestone areas, mixed deciduous forests, and dry evergreen forests, supported important native and endemic taxa. Ethnobotanical data from 110 informants documented 5113 use reports for 106 taxa, covering food, spice, medicinal, ornamental, ritual and belief-based, cosmetic, and commercial uses. Curcuma and Alpinia turned out to be the most frequently utilized genera. A putative natural hybrid, Curcuma × lopburiensis, is also described. These findings highlight Lop Buri Province as a hot spot for Zingiberaceae diversity and an important area for traditional plant knowledge and conservation in central Thailand. Full article
(This article belongs to the Section Plant Science)
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16 pages, 361 KB  
Review
Polyphenols and ADPKD: A Further Aid from Nature?
by Caterina Carollo, Alessandra Sorce, Maria Elena Ciuppa, Emanuele Cirafici, Nicola Sinatra, Giulio Geraci, Valentina Paternò, Paola Di Carlo, Rosalia Lo Presti, Giuseppe Mulè and Gregorio Caimi
Life 2026, 16(6), 1022; https://doi.org/10.3390/life16061022 - 18 Jun 2026
Viewed by 568
Abstract
Treating autosomal dominant polycystic kidney disease (ADPKD) has always been a challenge because the disease is too complex for single-target drugs, which are often held back by side effects. This narrative review explores a different strategy: using plant-derived polyphenols to target multiple disease [...] Read more.
Treating autosomal dominant polycystic kidney disease (ADPKD) has always been a challenge because the disease is too complex for single-target drugs, which are often held back by side effects. This narrative review explores a different strategy: using plant-derived polyphenols to target multiple disease pathways at the same time. Looking at research from 2005 to 2026, we break down how key compounds like resveratrol, curcumin, naringenin, quercetin, and epigallocatechin-3-gallate (EGCG) actually work. Preclinical studies show these molecules can slow down cyst growth by tackling inflammation, rapid cell division, and tissue scarring all at once, while also resetting the skewed energy metabolism of cystic cells. Some mechanisms are strikingly specific, such as naringenin’s direct interaction with polycystin-2 and quercetin’s ability to clear senescent cells. Yet, the real-world hurdle is poor absorption; a recent clinical trial with standard curcumin fell short simply because the compound could not reach the kidneys in high enough concentrations. Moving forward, the field needs to focus on testing these compounds in realistic animal models, designing smart nanoformulations to improve bioavailability, and exploring combinations that could safely complement current therapies like tolvaptan. Full article
5 pages, 169 KB  
Correction
Correction: Yalçın et al. Impact of SGLT2 Inhibitors on Cardiovascular Risk Scores, Metabolic Parameters, and Laboratory Profiles in Type 2 Diabetes. Life 2025, 15, 722
by Nazif Yalçın, Selman Aktaş, Seyit Uyar and Nizameddin Koca
Life 2026, 16(6), 1021; https://doi.org/10.3390/life16061021 - 18 Jun 2026
Viewed by 175
Abstract
Text Correction [...] Full article
(This article belongs to the Section Medical Research)
20 pages, 710 KB  
Article
The Impact of Artificial Intelligence on BI-RADS Classification and Diagnostic Confidence in Mammography Interpretation by Radiology Residents
by Ioana-Andreea Cîrlig, Alexandru-Marian Olaru, Mihai-Alexandru Ene, Aurelia-Ștefania Domenco, Rossy-Vlăduț Teică, Cristina-Mihaela Ciofiac, Raluca-Elena Nica, Violeta-Maria Novac, Mădălin Mămuleanu, Lucian-Mihai Florescu and Ioana-Andreea Gheonea
Life 2026, 16(6), 1020; https://doi.org/10.3390/life16061020 - 17 Jun 2026
Viewed by 264
Abstract
Background: Artificial intelligence (AI) is increasingly used as a decision-support tool in mammography, but its influence on radiology residents’ interpretive behavior remains insufficiently characterized. This study evaluated the impact of AI assistance on BI-RADS classification and diagnostic confidence among radiology residents. Methods: This [...] Read more.
Background: Artificial intelligence (AI) is increasingly used as a decision-support tool in mammography, but its influence on radiology residents’ interpretive behavior remains insufficiently characterized. This study evaluated the impact of AI assistance on BI-RADS classification and diagnostic confidence among radiology residents. Methods: This retrospective, single-center, multi-reader paired study included 112 diagnostic mammography examinations, corresponding to 223 assessable breasts and 2230 resident-breast readings. Ten radiology residents interpreted 2D mammography and digital breast tomosynthesis examinations first without AI assistance and subsequently with access to AI output. Changes in the BI-RADS category, diagnostic confidence, reasons for modification, and agreement with an expert-consensus BI-RADS reference standard were analyzed. Results: AI-assisted reassessment changed the BI-RADS classification in 9.7% of readings and diagnostic confidence in 19.2%, with any AI-associated modification observed in 24.3% of instances. Upgrades were more frequent than downgrades, particularly for medium- and high-suspicion AI outputs. Confidence increased more often than it decreased. Expert-reference agreement improved modestly, and BI-RADS 4+ sensitivity increased from 72.0% to 82.3%, with stable negative agreement, but these metrics reflect agreement with expert BI-RADS consensus rather than pathology-confirmed cancer detection. Conclusions: AI assistance influenced both BI-RADS reassessment and diagnostic confidence among radiology residents, producing modest but directionally favorable changes. These findings support cautious, supervised integration of AI into breast imaging training, with attention to confidence calibration and potential overreliance. Full article
(This article belongs to the Section Medical Research)
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11 pages, 233 KB  
Article
Sub-Tenon Block with Bolus-Free Dexmedetomidine Sedation for Penetrating Keratoplasty: A Retrospective Clinical Case Series of 50 High-Risk Patients
by Margita Lucic, Borivoje Savic, Jelena Kostic, Sanja Petrovic Pajic, Tiana Petrovic, Dolika D. Vasovic and Tanja Kalezic
Life 2026, 16(6), 1019; https://doi.org/10.3390/life16061019 - 17 Jun 2026
Viewed by 283
Abstract
Background: Penetrating keratoplasty (PK) is a technically demanding corneal transplant procedure frequently performed in elderly patients with substantial systemic comorbidities. In this population, an anesthetic strategy that ensures hemodynamic stability, cooperative sedation, adequate analgesia, and preserved spontaneous ventilation is highly desirable. Dexmedetomidine, [...] Read more.
Background: Penetrating keratoplasty (PK) is a technically demanding corneal transplant procedure frequently performed in elderly patients with substantial systemic comorbidities. In this population, an anesthetic strategy that ensures hemodynamic stability, cooperative sedation, adequate analgesia, and preserved spontaneous ventilation is highly desirable. Dexmedetomidine, a highly selective alpha2-adrenergic agonist, provides “cooperative” sedation with minimal risk of respiratory depression and additional sympatholytic benefits. Methods: This single-center retrospective observational case series included 50 consecutive patients (American Society of Anesthesiologists [ASA] II–III, age 50–90 years) undergoing PK under sub-Tenon block combined with continuous dexmedetomidine infusion. Dexmedetomidine was administered without a loading bolus at 0.7 mcg/kg/h for 10–15 min, then reduced to 0.5 mcg/kg/h, targeting a Ramsay Sedation Scale (RSS) score of 2–3. The sub-Tenon block was performed using a mixture of levobupivacaine 0.5% and lidocaine 2% (3–5 mL). Heart rate (HR), mean arterial pressure (MAP), oxygen saturation (SpO2) and RSS were recorded in nine predefined perioperative phases. Data were analyzed descriptively. Results: The mean age was 72 ± 9 years; 52% of patients were ASA III. Hypertension was present in all patients; 30% had cardiovascular disease, 28% diabetes mellitus type II, and 30% chronic obstructive pulmonary disease. Progressive, controlled bradycardia was observed (mean HR decreased from 76 to 57 beats/min during graft transplantation), while MAP gradually decreased from hypertensive baseline values (150–160 mmHg) to an optimal intraoperative range of 115–130 mmHg, without episodes of clinically significant hypotension. SpO2 remained stable at 98–99% throughout all phases, with no episodes of desaturation or need for airway intervention or supplemental oxygen. Target sedation (RSS 2–3) was achieved in all patients (median RSS 3), with preserved spontaneous breathing and cooperation. Sub-Tenon block-related bulging occurred in 6% of cases. No episodes of clinically significant bradycardia, malignant arrhythmia, respiratory compromise, or need to discontinue dexmedetomidine were recorded. No opioids or non-steroidal analgesics were required intraoperatively or in the early postoperative period. Conclusions: The combination of sub-Tenon block and continuous dexmedetomidine sedation without a loading bolus represents a hemodynamically stable and respiratory-safe anesthetic strategy for PK in elderly, high-risk patients. These preliminary, hypothesis-generating findings suggest that the protocol provides stable surgical conditions and a favorable safety profile, justifying future prospective randomized controlled trials to establish its comparative efficacy against general anesthesia or standard sedative regimens. Full article
(This article belongs to the Section Medical Research)
23 pages, 1326 KB  
Review
The Current Role of Physiotherapy in Systemic Light-Chain (AL) Amyloidosis and Multiple Myeloma
by Ana Ríos-Sánchez, María Angustias Riazzo-Benítez and Rafael Ríos-Tamayo
Life 2026, 16(6), 1018; https://doi.org/10.3390/life16061018 - 17 Jun 2026
Viewed by 225
Abstract
Physiotherapy is an evidence-based healthcare occupation aiming to collaborate in the diagnosis, prevention and treatment of a myriad of diseases and clinical scenarios throughout all stages of human life. Its development has been accelerated over the last two decades. The scope of physiotherapy [...] Read more.
Physiotherapy is an evidence-based healthcare occupation aiming to collaborate in the diagnosis, prevention and treatment of a myriad of diseases and clinical scenarios throughout all stages of human life. Its development has been accelerated over the last two decades. The scope of physiotherapy is continuously evolvig. However, the accumulated evidence in the context of rare diseases is scarce. Remarkably, the opportunity for improvement and potential benefit for complex diseases with low prevalence is also very high, both as an isolated approach or within multidisciplinary specialized units. Systemic light-chain (AL) amyloidosis is a rare, chronic, complex, heterogeneous, incurable, and challenging disease, which may involve different organs and systems, including the heart, kidney, liver, peripheral nerves, lung, muscle, skin, and others. Heart is the most frequently involved organ leading to failure and arrhythmias. Peripheral neuropathy is a relatively frequent symptom. Renal, respiratory, and hepatic failure may also occur. The aim of this narrative review is summarizing, updating, and critically underlining potential new avenues of development on the role of physiotherapy in systemic light-chain (AL) amyloidosis, compared with its application in multiple myeloma, a closely related but not so rare entity. Full article
(This article belongs to the Section Medical Research)
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17 pages, 6075 KB  
Article
Multi-Omics Integration Uncovers That Tenofovir Disoproxil Fumarate Is Linked to Hepatic Metabolic Reprogramming Independent of Viral Infection
by Yuanqin Duan, Yunling Xue, Jing Tang, Teng Long, Zhiwei Chen, Mingli Peng and Peng Hu
Life 2026, 16(6), 1017; https://doi.org/10.3390/life16061017 - 17 Jun 2026
Viewed by 279
Abstract
Background and Aims: TDF is a first-line antiviral for CHB with pleiotropic effects including immunomodulation and fibrosis regression, but its virus-independent mechanisms are unclear. This study delineates TDF’s direct molecular and metabolic landscape in vivo using multi-omics. Methods: Wild-type mice received TDF or [...] Read more.
Background and Aims: TDF is a first-line antiviral for CHB with pleiotropic effects including immunomodulation and fibrosis regression, but its virus-independent mechanisms are unclear. This study delineates TDF’s direct molecular and metabolic landscape in vivo using multi-omics. Methods: Wild-type mice received TDF or vehicle for 4 months. Liver tissues underwent RNA-seq and targeted metabolomics, followed by integrative systems biology. Results: TDF caused no hepatotoxicity but induced transcriptomic reprogramming: broad upregulation of immune/inflammatory pathways and suppression of metabolic pathways. Metabolomics confirmed perturbations in amino acid and fatty acid homeostasis. Multi-omics revealed coordinated downregulation of arginine/proline, alanine/aspartate/glutamate, and phenylalanine metabolism, restricting fibrogenic amino acids. TDF also suppressed the TCA cycle (downregulating Idh, Sdh, and Mdh), suggesting a metabolic bottleneck that was associated with paradoxically accumulated succinate and oxoglutarate—immunomodulatory danger signals. Conclusions: This first integrated atlas shows TDF actively remodels the hepatic microenvironment independent of viral infection, bridging metabolic suppression with immune activation. These findings provide an immunometabolic framework that offers new perspectives for understanding the clinical application of TDF and identifies potential biomarkers for CHB therapy. explaining TDF’s clinical superiority and identifying potential biomarkers for CHB therapy. Full article
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25 pages, 3955 KB  
Article
The Maximum Growth Temperature for Eukaryotes Is Thermodynamically Driven but Ecologically Contingent
by William Bains
Life 2026, 16(6), 1016; https://doi.org/10.3390/life16061016 - 17 Jun 2026
Viewed by 370
Abstract
Temperature is a state variable that affects all life. While it is known that archaea can grow at 120 °C and many bacteria can grow at over 100 °C, no eukaryote is known to complete a life cycle at above 65 °C. This [...] Read more.
Temperature is a state variable that affects all life. While it is known that archaea can grow at 120 °C and many bacteria can grow at over 100 °C, no eukaryote is known to complete a life cycle at above 65 °C. This paper explores why the difference in the maximum temperature of eukaryotes and other kingdoms of life might occur. It finds that chemical and genome structural differences between the domains of life are unlikely to explain the difference in maximum growth temperature, with the exception of the Saccharomycotina, which are different from other fungi, possibly because of their unique ecology. The distribution of inherently disordered proteins (IDPs), however, is significantly correlated with maximum and minimum growth temperature in fungi, and with the range of temperatures over which fungi can grow. I also demonstrate that the range of temperatures over which a species can grow is correlated with its maximum temperature. I postulate that the range is correlated with maximum temperature because all real-world ecologies fluctuate between elevated and average surface temperatures, and the thermodynamics of IDP-based structures in eukaryotes inherently limits the range over which they can operate. Thus, the 65 °C maximum temperature limit for eukaryotes is a result of a combination of thermodynamic properties of their organization and the temperature regime on the modern Earth; I suggest an experimental approach to testing this. Full article
(This article belongs to the Section Microbiology)
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19 pages, 4966 KB  
Article
HiFi-Assembled Mitogenomes of Four Pygmy Grasshoppers Reveal Mito–Nuclear Discordance in Zhengitettix transpicula and Lineage-Specific Mitochondrial Intergenic Length Variation
by Rongjiao Zhang, Taihang Xu, Delong Guan and Weian Deng
Life 2026, 16(6), 1015; https://doi.org/10.3390/life16061015 - 17 Jun 2026
Viewed by 260
Abstract
Mitochondrial genomes are widely used in insect taxonomy and phylogenetics, but their signals may conflict with morphology and nuclear genomic evidence because the mitochondrial genome represents a single maternally inherited locus. Here, we assembled complete mitochondrial genomes of four pygmy grasshoppers, Zhengitettix transpicula [...] Read more.
Mitochondrial genomes are widely used in insect taxonomy and phylogenetics, but their signals may conflict with morphology and nuclear genomic evidence because the mitochondrial genome represents a single maternally inherited locus. Here, we assembled complete mitochondrial genomes of four pygmy grasshoppers, Zhengitettix transpicula, Formosatettix sp., Gibbotettix parvipulvillus, and Bolivaritettix sp., using PacBio HiFi reads. The four mitogenomes ranged from 15,152 to 17,976 bp and contained the typical 37 mitochondrial genes. Mitochondrial phylogenies inferred by maximum likelihood and Bayesian methods were topologically identical and recovered several well-supported tetrigid relationships, including a close relationship between Formosatettix sp. and Bolivaritettix sp. However, Z. transpicula was unexpectedly placed near Macromotettixoides rather than close to other Zhengitettix representatives. In contrast, a morphology-based tree recovered Z. transpicula with Z. triangularis, and comparison with a published nuclear single-copy ortholog tree based on 1962 loci supported a non-mitochondrial placement of Zhengitettix inconsistent with the anomalous mitochondrial position of Z. transpicula. Independent assembly from the original HiFi reads, read-depth inspection, protein-coding gene checks, and nuclear-genome screening for NUMT-like sequences supported the authenticity of the assembled Z. transpicula mitogenome. These results document mito–nuclear and cyto-morphological discordance in Tetrigidae and highlight the need for integrative interpretation of mitochondrial phylogenies in taxonomically complex insect groups. Full article
(This article belongs to the Special Issue Insect Taxonomy in the Era of Mitogenomics)
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26 pages, 1203 KB  
Review
Fiber-Degrading Microorganisms: Types, Screening and Applications
by Haiying Yang, Baoyan Yang, Wenjie Zhang, Mengrong Su, Qindan Dai and Jian Ma
Life 2026, 16(6), 1014; https://doi.org/10.3390/life16061014 - 17 Jun 2026
Viewed by 301
Abstract
Fiber-degrading microorganisms are widely recognized for their potential to convert renewable lignocellulosic biomass into animal feed. However, translating this potential into practical application faces five critical yet underappreciated challenges. First, current screening methods, primarily including plate dilution and Congo red staining, are low-throughput, [...] Read more.
Fiber-degrading microorganisms are widely recognized for their potential to convert renewable lignocellulosic biomass into animal feed. However, translating this potential into practical application faces five critical yet underappreciated challenges. First, current screening methods, primarily including plate dilution and Congo red staining, are low-throughput, poorly reproducible and fail to capture the synergistic actions of natural microbial consortia. Second, the lack of standardized assays for quantifying cellulolytic activity compromises the reliability of cross-study comparisons. Third, safety assessments for fiber-degrading microorganisms remain superficial, with most studies neglecting mycotoxin production, antibiotic resistance gene transfer and long-term colonization risks. Fourth, fundamental differences between fungal and bacterial degradative systems, such as enzyme multiplicity, oxygen requirements and cellulosome assembly, are rarely considered in strain selection, leading to suboptimal application outcomes. Finally, the vast majority of positive in vitro degradation results fail to translate into improved animal performance in vivo, owing to poor microbial survival in the gastrointestinal tract, mismatched enzyme activity with gut pH and temperature, coupled with the absence of dose–response validation. This review critically evaluates these five bottlenecks across fiber-degrading microorganism types, screening platforms and practical livestock production applications. Overall, future progress should depend less on discovering “novel” strains and more on establishing standardized screening pipelines, rigorous safety frameworks and mechanistic understanding of in vivo efficacy, including direct head-to-head comparisons between fungal enzymes and bacterial probiotics under identical conditions. Full article
(This article belongs to the Special Issue Gut Health and Nutritional Strategies in Animals)
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29 pages, 4368 KB  
Article
Effects of a 6-Week Hip and Ankle Mobility-Based Rehabilitation Program on Clinical, Neuromuscular, and Functional Outcomes in Male Collegiate Athletes with Patellofemoral Pain: A Randomized Controlled Trial
by Hengquan Xu, Zhaozhi Feng, Yue Dou and Gang Wang
Life 2026, 16(6), 1013; https://doi.org/10.3390/life16061013 - 17 Jun 2026
Viewed by 333
Abstract
Patellofemoral pain (PFP) in athletes is associated with lower-limb kinetic-chain constraints, yet rehabilitation strategies targeting both hip and ankle mobility remain insufficiently examined. This assessor-blinded randomized controlled trial investigated the effects of a 6-week hip and ankle mobility-based rehabilitation program in male collegiate [...] Read more.
Patellofemoral pain (PFP) in athletes is associated with lower-limb kinetic-chain constraints, yet rehabilitation strategies targeting both hip and ankle mobility remain insufficiently examined. This assessor-blinded randomized controlled trial investigated the effects of a 6-week hip and ankle mobility-based rehabilitation program in male collegiate athletes with PFP. Forty-eight participants were assigned using computer-generated 1:1 randomization to an intervention group (n = 24) or a control group (n = 24). The intervention group completed supervised hip and ankle mobility rehabilitation three times weekly, whereas the control group maintained regular sport-specific training only. Co-primary outcomes were pain intensity assessed using a 10-cm visual analog scale (VAS) and knee-related function assessed using the Kujala score. Secondary outcomes included hip rotation range of motion, weight-bearing ankle dorsiflexion, vastus medialis–vastus lateralis (VM–VL) onset timing, Y-Balance Test (YBT) composite score, and countermovement jump (CMJ) height. Significant group × time interactions favored the intervention group for VAS (p < 0.0001; partial η2 = 0.436; change difference: −1.54 cm; 95% CI: −2.06 to −1.02) and Kujala score (p < 0.0001; partial η2 = 0.285; change difference: 8.00 points; 95% CI: 4.24 to 11.76). Significant interactions were also observed for hip internal and external rotation range of motion, weight-bearing ankle dorsiflexion, VM–VL onset timing during a controlled squat task, and YBT composite score (all p ≤ 0.0405; partial η2 = 0.088–0.374). No significant group × time interaction was observed for CMJ height (p = 0.0511; partial η2 = 0.080). These findings suggest that, compared with regular sport-specific training alone, adding a supervised hip and ankle mobility-based rehabilitation program may improve pain, knee-related function, targeted mobility outcomes, VM–VL onset timing during a controlled squat task, and dynamic balance in the short term. However, because the control group did not receive an active or attention-matched intervention, these findings should be interpreted as the added effect of the supervised rehabilitation program rather than as definitive evidence of mobility-specific treatment effects. In addition, because patellar tracking, knee kinematics, joint kinetics, and patellofemoral joint loading were not directly measured, the findings should be interpreted as clinical and functional outcome changes rather than direct evidence of a confirmed biomechanical mechanism. Trial registration: NCT07542236. Full article
(This article belongs to the Special Issue Sports Biomechanics, Injury, and Physiotherapy)
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26 pages, 14645 KB  
Article
Glutamine and Its Precursors Supplementation Improve Growth Performance and Immunity and Regulate Gastrointestinal Microbiota of Suckling Lambs
by Wenjie Zhang, Feier Ren, Zhonghao Wang, Weibing Zhang, Kai Feng, Yulong Zhao, Hailiang Wang, Hongyan Hou, Shiyin Wang and Wei Zhang
Life 2026, 16(6), 1012; https://doi.org/10.3390/life16061012 - 16 Jun 2026
Viewed by 290
Abstract
This study systematically compared the effects of dietary supplementation with glutamine (Gln) and its precursors, including glutamic acid (GA) and α-ketoglutarate (AKG), on growth performance, serum antioxidant and immune parameters, and multi-region gastrointestinal microbiota in suckling lambs. Forty healthy suckling Hu lambs with [...] Read more.
This study systematically compared the effects of dietary supplementation with glutamine (Gln) and its precursors, including glutamic acid (GA) and α-ketoglutarate (AKG), on growth performance, serum antioxidant and immune parameters, and multi-region gastrointestinal microbiota in suckling lambs. Forty healthy suckling Hu lambs with similar body weight (7.37 ± 1.18 kg) and age (7 ± 0.8 d) were selected and randomly allocated into four groups (n = 10 per group): a control group (CON, without additive), and three treatment groups (GA, AKG, and Gln), each receiving 2 g per animal per day of the corresponding additive. The experimental period lasted for 42 d. All three additives showed a tendency to increase the final body weight (p = 0.056) and significantly increased the average daily gain (ADG) of lambs (p < 0.05). GA supplementation increased the dry matter intake throughout the entire trial (p < 0.05), whereas the addition of AKG and Gln increased the dry matter intake only during the later period (d 21–42) (p < 0.05). The feed-to-gain ratios did not differ among all groups (p > 0.05). Compared with the CON group, all three treatment groups showed elevated serum activities of catalase, glutathione peroxidase, and total antioxidant capacity, as well as increased IgA and IgG contents (p < 0.05). In addition, malondialdehyde concentration was decreased in all three treatment groups (p < 0.05). Moreover, GA supplementation reduced the ruminal alpha diversity while increasing the abundance of butyrate-producing bacteria (Ruminococcaceae UCG-014) (p < 0.05). All three interventions consistently decreased the abundance of the intestinal pathogen Escherichia-Shigella in the ileum (p < 0.05). Correlation analyses showed that ruminal Treponema 2 abundance was negatively correlated with ADG, whereas jejunal Methylobacterium and ileal [Eubacterium] coprostanoligenes group were positively correlated with final body weight or ADG. In conclusion, glutamine and its precursors play an important role in modulating gastrointestinal bacterial diversity and composition, enhancing antioxidant and immune functions, and improving the growth performance of suckling lambs. Full article
(This article belongs to the Special Issue Gut Health and Nutritional Strategies in Animals)
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34 pages, 5775 KB  
Article
Taxonomic and Phylogenetic Resolution of Novel Endophytic Arthrinium-like Fungi with an Updated Checklist of Nigrospora Species
by Jutamart Monkai, Rungtiwa Phookamsak, Darbhe Jayarama Bhat, Danushka S. Tennakoon, Sinang Hongsanan, Toe Swe Zin Ei, Jianchu Xu and Saisamorn Lumyong
Life 2026, 16(6), 1011; https://doi.org/10.3390/life16061011 - 16 Jun 2026
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Abstract
Arthrinium-like fungi in the family Apiosporaceae are taxonomically complex and still require a thorough characterization despite recent phylogenetic reassessments. This study aimed to investigate the diversity and taxonomic position of endophytic Arthrinium-like fungi associated with Itea japonica and I. riparia in Thailand. Two [...] Read more.
Arthrinium-like fungi in the family Apiosporaceae are taxonomically complex and still require a thorough characterization despite recent phylogenetic reassessments. This study aimed to investigate the diversity and taxonomic position of endophytic Arthrinium-like fungi associated with Itea japonica and I. riparia in Thailand. Two fungal strains discovered from healthy stems of these hosts were characterized by integrative approaches including morphology, multi-locus phylogenetic analyses based on ITS, LSU, TEF1-α, TUB2 sequence data, and nucleotide base–pair comparisons. One isolate from I. japonica is introduced as Nigrospora iteae sp. nov. supported by distinct morphological traits, a well-resolved phylogenetic placement, and significant nucleotide difference from its closest relatives. The second isolate was identified as Apiospora vietnamensis and is reported herein as a new host record for I. riparia based on morphological congruence, a close phylogenetic relationship, and TUB2 nucleotide similarity with the type strain. In addition, a new species, Apiospora fici, originally described from dead leaves of Ficus septica in Taiwan, is reclassified based on updated phylogenetic analyses to clarify its taxonomic placement within Apiosporaceae. Furthermore, Nigrospora wurfbainiae nom. nov. is proposed as a replacement name for the later homonym N. guangdongensis. A summary of important morphological characteristics, host relationships, current distribution, and biological activities of Nigrospora species is provided. This study emphasizes the previously unrecognized fungal diversity within Itea hosts and offers new insights into species diversity and phylogenetic relationships within the Apiosporaceae. Full article
(This article belongs to the Special Issue New Developments in Mycology)
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Article
Gynecomastia: Etiological Analysis Beyond Hormonal Imbalance
by Jae Heon Kim, Miho Song, Kisoo Lee, Min Hyuk Lee and Yun Seob Song
Life 2026, 16(6), 1010; https://doi.org/10.3390/life16061010 - 16 Jun 2026
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Abstract
Background: Gynecomastia is a benign enlargement of the male breast with multiple causes. This retrospective study evaluated whether serum estradiol (E2), testosterone (T), or the E2/T ratio differed between patients and controls, while explicitly accounting for the limited hormonal subset and lack of [...] Read more.
Background: Gynecomastia is a benign enlargement of the male breast with multiple causes. This retrospective study evaluated whether serum estradiol (E2), testosterone (T), or the E2/T ratio differed between patients and controls, while explicitly accounting for the limited hormonal subset and lack of statistical significance. Methods: We retrospectively reviewed 68 men with benign gynecomastia (1996–2000) and 10 healthy controls. Analyses were conducted in two predefined populations: a full etiologic cohort (n = 68) and a hormonal-analysis subset (37 patients and 10 controls). Serum E2 and T were measured in 37 patients and all controls, and the E2/T ratio was calculated. The E2/T ratio was analyzed primarily as a continuous variable rather than relying solely on a control-derived threshold. Results: Gynecomastia was most frequent in adult and middle-aged men. Idiopathic cases were most common, followed by drug-related, hormonal, and disease-related causes. The mean E2/T ratio was higher in patients (12.0 ± 1.8) than controls (7.1 ± 0.5), but this difference did not reach statistical significance (E2: p = 0.21; T: p = 0.34; E2/T: p = 0.07). Among tested patients, 13.5% had low T, 24.3% high E2, and 43.2% elevated E2/T ratios. Liver disease and drugs such as H2 blockers and psychoactive agents contributed in some cases, while 50% were idiopathic. Conclusions: Because hormone comparisons were non-significant and based on a limited subset, these data do not support an independent association between gynecomastia and circulating E2, T, or the E2/T ratio. Clinical evaluation should consider age, comorbidities, and medications in addition to hormonal factors. Full article
(This article belongs to the Section Reproductive and Developmental Biology)
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