Life

29 pages, 3009 KB

Open AccessArticle

The Heart of Fetal Growth Restriction: Congenital Heart Defects—An Analysis of Risk Factors and Morbidity Outcomes

by Anca Adam-Raileanu, Delia Lidia Salaru, Ancuta Lupu, Elena Jechel, Mitica Ciorpac, Emil Anton, Laura Iulia Bozomitu, Stefana Maria Moisa, Oana Raluca Temneanu, Alice Grudnicki, Manuel Florin Rosu, Sorana Caterina Anton, Alin Horatiu Nedelcu, Magdalena Cuciureanu and Vasile Valeriu Lupu

Life 2026, 16(9), 1568; https://doi.org/10.3390/life16091568 (registering DOI) - 19 Sep 2026

Abstract

Background: Congenital heart disease (CHD) co-occurring with fetal growth restriction (FGR) is clinically important but incompletely characterized. We assessed the proportion and subtype spectrum of CHD in term-born children with FGR, and factors associated with its presence and complexity. Methods: Retrospective analysis of [...] Read more.

Background: Congenital heart disease (CHD) co-occurring with fetal growth restriction (FGR) is clinically important but incompletely characterized. We assessed the proportion and subtype spectrum of CHD in term-born children with FGR, and factors associated with its presence and complexity. Methods: Retrospective analysis of 375 term singleton children with documented FGR at a tertiary pediatric center. CHD required echocardiographic confirmation; isolated patent foramen ovale was excluded. Patients with multiple lesions were hierarchically classified as simple or complex. Multivariable logistic regression was restricted to characteristics available at or before birth. Results: CHD was confirmed in 96/375 children (25.6%): 71 (74.0%) simple, 25 (26.0%) complex. Atrial septal defect and patent ductus arteriosus were most frequent (each 45.8%), followed by patent foramen ovale (44.8%) and ventricular septal defect (32.3%). Severe FGR (aOR 2.012, 95% CI 1.222–3.313; p = 0.006) and genetic syndrome (aOR 5.969, 95% CI 2.565–13.889; p < 0.001) were independently associated with CHD presence. Within the CHD subgroup, genetic syndrome was also associated with complex disease (aOR 5.156, 95% CI 1.651–16.104; p = 0.005). Diagnosis occurred before six months in 95.8%. Hospitalization outcomes and comorbidity burden did not differ by complexity. Conclusions: FGR severity and genetic syndrome were both independently associated with the presence of a cardiac defect, and genetic syndrome was further associated with its complexity. These findings support targeted rather than universal echocardiographic assessment. Directionality cannot be established from postnatal data. Full article

(This article belongs to the Special Issue Pediatric Cardiology Frontiers: Innovations in Diagnosis and Treatment)

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15 pages, 1010 KB

Open AccessArticle

Baseline-Referenced Longitudinal Point-of-Care Ultrasound for Fluid Management After Kidney Transplantation: A Retrospective Comparison with Central Venous Pressure-Guided Care

by Adam Varga, Zoltan Sandor, Dorottya Katics, Karoly Kalmar Nagy and Peter Szakaly

Life 2026, 16(9), 1567; https://doi.org/10.3390/life16091567 (registering DOI) - 18 Sep 2026

Abstract

Fluid management after kidney transplantation requires balancing adequate graft perfusion against fluid overload. We compared central venous pressure (CVP)-guided and point-of-care ultrasound (POCUS)-guided postoperative management and explored whether longitudinal changes in inferior vena cava (IVC) diameter relative to an individual postoperative reference provided [...] Read more.

Fluid management after kidney transplantation requires balancing adequate graft perfusion against fluid overload. We compared central venous pressure (CVP)-guided and point-of-care ultrasound (POCUS)-guided postoperative management and explored whether longitudinal changes in inferior vena cava (IVC) diameter relative to an individual postoperative reference provided information beyond absolute IVC diameter. This single-center retrospective comparative study included 60 adult kidney transplant recipients (30 per group) with standardized assessments on postoperative days 1–5 and 10. POCUS-guided management was associated with more active therapeutic adjustments during days 1–5 (48.0% vs. 25.3%; OR 2.80, 95% CI 1.45–5.42; p = 0.002), without a significant difference in cumulative fluid balance. Reference IVC diameter ranged from 7 to 21 mm and showed substantial interindividual variability. Within-patient IVC variation was associated with daily fluid balance (p = 0.002) and weight change (p = 0.003). In a post hoc exploratory ROC analysis, peak baseline-referenced ΔIVC showed an AUC of 0.749 (95% CI 0.574–0.924) for >1 kg postoperative weight gain, compared with 0.518 (95% CI 0.300–0.737) for peak absolute IVC; the two AUCs were not formally compared. No statistically significant between-group differences in early graft outcomes were observed, although the study was not powered for these outcomes. POCUS-guided monitoring was associated with greater treatment actionability; whether this translates into clinical benefit requires prospective evaluation. Full article

(This article belongs to the Special Issue Point-of-Care Ultrasound (POCUS) in Nephrology)

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21 pages, 684 KB

Open AccessSystematic Review

High-Recall Biomedical Language Models for Radiation Oncology Evidence Synthesis: An Integrated Systematic Review of Prediction Models for Radiotherapy-Induced Complications in Nasopharyngeal Carcinoma

by Guang-Zhi Lin, Yang-Wei Hsieh, Chih-Yu Cheng, Chen-Cheng Wang, Liyun Chang, Chao-Hong Liu, Wen-Ping Yun, Shyh-An Yeh, Cheng-Shie Wuu, Chien-Liang Chiu, Pei-Ju Chao and Tsair-Fwu Lee

Life 2026, 16(9), 1566; https://doi.org/10.3390/life16091566 (registering DOI) - 18 Sep 2026

Abstract

Background: Radiotherapy-related complications can impair long-term outcomes in nasopharyngeal carcinoma (NPC), while high-volume literature screening remains a bottleneck in evidence synthesis. Methods: Four databases were searched through January 2026. After deduplication, 4916 records underwent two-stage manual screening, yielding 38 studies. Three Bidirectional Encoder [...] Read more.

Background: Radiotherapy-related complications can impair long-term outcomes in nasopharyngeal carcinoma (NPC), while high-volume literature screening remains a bottleneck in evidence synthesis. Methods: Four databases were searched through January 2026. After deduplication, 4916 records underwent two-stage manual screening, yielding 38 studies. Three Bidirectional Encoder Representations from Transformers (BERT) models, BERT-base, BioBERT, and PubMedBERT, were fine-tuned using stratified five-fold cross-validation, and screening performance was assessed using the area under the receiver operating characteristic curve (ROC-AUC), the area under the precision-recall curve (PR-AUC), and work saved over sampling (WSS) at the 100% and 85% recall thresholds (WSS@100% and WSS@85%).The clinical evidence was evaluated using the Prediction Model Risk of Bias Assessment Tool (PROBAST) and synthesized narratively according to endpoint, discrimination metric, time horizon, unit of analysis, validation level, and uncertainty reporting. Results: At complete recall, BioBERT and PubMedBERT achieved mean WSS values of 97.8% and 97.5%, respectively, compared with 89.7% for BERT-base. Separately, the clinical evidence review identified 39 discrimination estimates: 33 conventional binary ROC-AUCs, three Harrell’s C-indices, and three time-dependent AUCs. Only two studies contributed external-validation estimates and one contributed a temporal-validation estimate. Sixteen estimates lacked a usable measure of uncertainty, and PROBAST rated all studies as having a high overall risk of bias, driven by the analysis domain. Conclusions: Within the retrieved and manually annotated corpus, biomedical pretrained language models showed the potential to reduce the title-and-abstract screening burden while maintaining complete recall. Independently, the clinical evidence map identified promising discrimination but insufficiently robust and transportable evidence for routine clinical implementation. Full article

(This article belongs to the Special Issue Advanced Technologies and Clinical Practice of Cancer Radiotherapy)

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26 pages, 1578 KB

Open AccessArticle

Acute Salivary Biomarker, Cognitive, and Tennis Performance Responses to Tennis-Specific Exercise Versus HIIT: A Randomized Crossover Study

by Harun Genç, Mustafa Türkmen, Mehmet Şerif Ökmen, İsmail Polatcan, İsmail Kirkpinar, Muhammed Şahin, Ramazan Baltaci, Hasan Şahin, Furkan İdgö and Alperen Erkin

Life 2026, 16(9), 1565; https://doi.org/10.3390/life16091565 (registering DOI) - 18 Sep 2026

Abstract

Tennis requires the integration of physiological, technical, and cognitive abilities during intermittent high-intensity exercise; however, it remains unclear whether tennis-specific exercise induces different acute responses from duration-matched high-intensity interval training (HIIT). This randomized crossover study compared the acute effects of a tennis-specific exercise [...] Read more.

Tennis requires the integration of physiological, technical, and cognitive abilities during intermittent high-intensity exercise; however, it remains unclear whether tennis-specific exercise induces different acute responses from duration-matched high-intensity interval training (HIIT). This randomized crossover study compared the acute effects of a tennis-specific exercise protocol (TSEP) and duration-matched HIIT on salivary biomarkers, working memory-related cognitive performance, and tennis-specific performance in 12 amateur competitive male tennis players (22.1 ± 1.6 years). Participants completed both protocols separated by a 7-day washout period. Salivary alpha-amylase (sAA) and secretory immunoglobulin A (sIgA) were assessed before, immediately after, and 30 min after exercise, whereas salivary creatine kinase (CK) was assessed before and 24 h after exercise. Tennis-specific accuracy, auditory 2-back target detection accuracy, and separated and combined dual-task performance were evaluated before and immediately after each protocol. Dual-task costs (DTCs) were also calculated separately for the motor and cognitive components. Both protocols produced significant time-dependent changes in sAA and sIgA (both p < 0.001), without significant condition or Condition × Time interaction effects. Salivary CK increased following both protocols, with a significantly greater Pre-to-Post-24 h increase following HIIT (Condition × Time, p = 0.032). The binomial generalized linear mixed-effects models showed significant overall time effects for single-task forehand and backhand accuracy and single-task 2-back target detection accuracy, whereas the time effect for serve accuracy was not statistically significant. However, none of the single-task performance outcomes showed a significant Condition × Time interaction. Among the separated dual-task outcomes, significant overall time effects were observed for backhand and cognitive accuracy, whereas forehand and serve accuracy showed no significant time effects. Combined dual-task accuracy also showed a significant overall time effect. None of the separated or combined dual-task outcomes showed a significant Condition × Time interaction. Relative motor and cognitive DTC outcomes were summarized descriptively and treated as exploratory because of non-normality, denominator instability, and one undefined value. Overall, both exercise protocols were followed by changes in selected salivary biomarkers and declines in selected technical and cognitive performance outcomes, but the analyses provided insufficient evidence that the magnitude of technical, cognitive, or dual-task performance change differed between TSEP and HIIT. In contrast, HIIT elicited a greater delayed salivary CK response. A multidimensional assessment combining physiological, biochemical, technical, cognitive, perceptual, and external-load measures may therefore provide a more comprehensive approach to monitoring acute fatigue in tennis. Full article

(This article belongs to the Special Issue Advances and Applications of Sport Physiology: 2nd Edition)

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21 pages, 745 KB

Open AccessArticle

Dynamic Assessment of the C-Reactive Protein-to-Albumin Ratio Improves Early Prediction of Severe Acute Pancreatitis: A Retrospective Cohort Study

by Crina Fofiu, Laura Nat, Andrei Constantin Ioanovici and Alina Boeriu

Life 2026, 16(9), 1564; https://doi.org/10.3390/life16091564 (registering DOI) - 17 Sep 2026

Abstract

Background/Objectives: Previous studies have demonstrated the prognostic value of the C-reactive protein-to-albumin ratio (CAR) in acute pancreatitis, but the incremental value of serial measurements remains unclear. We evaluated whether CAR measured at 24 and 48 h provides additional prognostic information beyond admission [...] Read more.

Background/Objectives: Previous studies have demonstrated the prognostic value of the C-reactive protein-to-albumin ratio (CAR) in acute pancreatitis, but the incremental value of serial measurements remains unclear. We evaluated whether CAR measured at 24 and 48 h provides additional prognostic information beyond admission CAR for predicting severe acute pancreatitis (SAP). Methods: In this retrospective cohort study, 150 consecutive patients with acute pancreatitis were included. CAR was calculated at admission (CAR-T0), 24 h (CAR-T24), and 48 h (CAR-T48). Univariable and multivariable logistic regression, receiver operating characteristic (ROC) analysis, and DeLong’s test were used to evaluate prognostic performance. Secondary analyses explored associations with pancreatic pseudocyst, pancreatic ascites, and splanchnic venous thrombosis. Results: Forty-four patients (29.3%) developed SAP. CAR was significantly associated with SAP at all three time points, with CAR-T24 demonstrating the highest predictive performance (AUC 0.874), followed by CAR-T48 (AUC 0.857) and CAR-T0 (AUC 0.829). CAR-T24 showed the highest individual discriminative performance, although its AUC was not significantly higher than that of CAR-T0 (DeLong p = 0.067). In contrast, adding CAR-T24 to the prespecified multivariable model significantly improved discrimination compared with the admission model (AUC 0.890 vs. 0.841; p = 0.016). Dynamic changes in CAR (ΔCAR) were not independently associated with SAP. Admission NLR showed poor predictive performance (AUC 0.578) and was significantly inferior to all CAR time points. Exploratory analyses suggested a potential association between CAR-T24 and splanchnic venous thrombosis; however, given the small number of thrombotic events (n = 10), this finding should be considered preliminary and hypothesis-generating. Conclusions: Serial CAR assessment, particularly at 24 h after admission, provides incremental prognostic value beyond admission CAR alone and may provide additional prognostic information during early clinical reassessment in acute pancreatitis. Full article

(This article belongs to the Special Issue From Physiology and Pathology Research to Clinical Insights in Gastrointestinal Disorders)

17 pages, 4504 KB

Open AccessArticle

Distinct Associations of PTEN and TMPRSS4 Expression with Clinical Outcomes and Fudan Immunohistochemistry-Based Subtypes in Triple-Negative Breast Cancer

by Wei Hou, Sheng Zhang, Xianbin Wei, Lixin Zhou, Xinting Diao, Yiqiang Liu and Xiuli Ma

Life 2026, 16(9), 1563; https://doi.org/10.3390/life16091563 (registering DOI) - 17 Sep 2026

Abstract

Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive subtype with limited therapeutic targets. We retrospectively evaluated the expression of phosphatase and tensin homolog (PTEN) and transmembrane serine protease 4 (TMPRSS4) by immunohistochemistry in formalin-fixed, paraffin-embedded tumor tissues from 145 patients with histologically [...] Read more.

Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive subtype with limited therapeutic targets. We retrospectively evaluated the expression of phosphatase and tensin homolog (PTEN) and transmembrane serine protease 4 (TMPRSS4) by immunohistochemistry in formalin-fixed, paraffin-embedded tumor tissues from 145 patients with histologically confirmed TNBC, and we analyzed associations with clinicopathological features, Fudan immunohistochemistry-based subtypes, and clinical outcomes. Clinicopathological analyses included all 145 cases. Exploratory survival analyses included 59 patients with complete, verifiable follow-up and outcome data (median follow-up, 46 months), during which three deaths and eight progression events occurred. PTEN-retained expression was associated with worse overall survival (OS; log-rank p = 0.030), whereas TMPRSS4-positive expression was associated with worse progression-free survival (PFS; log-rank p = 0.034). TMPRSS4 expression showed a nominal association with Fudan subtype in the unadjusted omnibus analysis (p = 0.025), which was considered exploratory after Benjamini–Hochberg correction (q = 0.379). The PTEN and TMPRSS4 staining categories were not significantly associated. In an exploratory four-group survival analysis, patients with concurrent PTEN-retained and TMPRSS4-positive expression (PTEN⁺/TMPRSS4⁺) showed the lowest OS and PFS estimates, patients with PTEN loss and TMPRSS4 negativity (PTEN⁻/TMPRSS4⁻) showed the highest estimates, and the two single-positive groups showed intermediate estimates. Independent transcript-level validation restricted to TNBC in The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) did not reproduce these protein-level associations. These protein-level findings should therefore be considered exploratory and hypothesis-generating and warrant confirmation in larger, adequately powered cohorts using standardized immunohistochemistry with complete treatment data. Full article

(This article belongs to the Special Issue Advances in Computational and Spatial Pathology)

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Graphical abstract

12 pages, 1507 KB

Open AccessArticle

Effects of Zinc Toxicity on Chlorophyll Fluorescence and Translocation Factor of Potentilla chinensis

by Yue Wang, Yu Qiao, Sen Yang, Weizhou Xu, Yaojun Bo and Xia Han

Life 2026, 16(9), 1562; https://doi.org/10.3390/life16091562 - 17 Sep 2026

Abstract

Zinc (Zn) is essential for plant metabolism but becomes toxic at high concentrations. In this study, we investigated the effects of Zn concentrations (40, 80, 160, 240, 320, 400 mg L⁻¹) on plant growth, root morphology, chlorophyll fluorescence, and Zn accumulation [...] Read more.

Zinc (Zn) is essential for plant metabolism but becomes toxic at high concentrations. In this study, we investigated the effects of Zn concentrations (40, 80, 160, 240, 320, 400 mg L⁻¹) on plant growth, root morphology, chlorophyll fluorescence, and Zn accumulation in Potentilla chinensis grown in soil for 21 days. The results showed that total root length, root surface area, root volume, qP, qL, ETR, and SPAD values responded at ≤240 mg L⁻¹, whereas plant height was affected at 400 mg L⁻¹, indicating that SPAD, some fluorescence, and root traits responded before major biomass effects became statistically significant. At 400 mg L⁻¹, shoot and root Zn concentrations reached 1353.75 and 187.16 mg kg⁻¹ DW, respectively, and the translocation factor was 7.24. F_m, F_v, F_v/F_m, and ΦPSII remained stable, whereas F₀ decreased and NPQ increased, indicating that PSII function was largely maintained, with partial reaction center damage offset by enhanced protective thermal dissipation. Shoot Zn concentrations exceeded root Zn concentrations across all treatments, indicating efficient root-to-shoot Zn translocation. These findings show that P. chinensis exhibits Zn accumulation and efficient root-to-shoot translocation under the tested conditions and warrants further investigation as a candidate species for Zn phytoextraction. Full article

(This article belongs to the Section Plant Science)

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25 pages, 2232 KB

Open AccessArticle

Neurobehavioral Consequences of the 5′-AMP-Induced Torpor-like Hypothermic State

by Alessandro Stronati, Giorgia Macchioni, Arianna Racca, Daniela Santucci and Matteo Cerri

Life 2026, 16(9), 1561; https://doi.org/10.3390/life16091561 - 17 Sep 2026

Abstract

Torpor is a hypometabolic and hypothermic state that enables survival under extreme energetic constraints. Pharmacological induction with 5′-AMP produces a controllable torpor-like hypothermic state with hypometabolic features documented for this model, relevant to long-duration spaceflight. Such a state could mitigate the physiological hazards [...] Read more.

Torpor is a hypometabolic and hypothermic state that enables survival under extreme energetic constraints. Pharmacological induction with 5′-AMP produces a controllable torpor-like hypothermic state with hypometabolic features documented for this model, relevant to long-duration spaceflight. Such a state could mitigate the physiological hazards of deep-space missions, including cosmic radiation exposure and muscle wasting, and, by minimizing oxygen demand, preserve neural integrity and enhance radiation tolerance. However, translational application requires confirmation that induced hypometabolism does not impair cognitive or behavioral function; this is especially pressing given evidence that the state causes reversible tau hyperphosphorylation at phospho-sites also altered in Alzheimer’s disease, but without tau aggregation. We subjected C57BL/6 mice to 5′-AMP combined with a mildly reduced ambient temperature (15–18 °C) and compared them with cold-exposed and room-temperature vehicle controls using systematic neurobehavioral testing. Despite the deep hypothermia (and the hypometabolism documented for this model), Y-maze spontaneous alternation performance was unaffected. Locomotor activity fell transiently during post-arousal recovery, with concurrent increases in self-directed behaviors. These results support further evaluation of this reversible metabolic intervention for critical care medicine and future human space missions. Full article

(This article belongs to the Section Physiology and Pathology)

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26 pages, 9387 KB

Open AccessArticle

Targeted Cepharanthine-Mediated Dual-Pathway Inhibition Sensitizes Pancreatic Cancer to Gemcitabine

by Tongshan Zhu, Shumei Zhang, Mengxin Hao, Ling Wan, Fulei Nie, Guowei Zhang, Bingrui Liu, Chunyu Tian, Xinyue Wang, Haibin Liu, Yijia Li, Yuhan Feng, Di Guo, Nan Li, Yingchao Zhang, Pengcai Liu, Fan Shi, Shuoqian Ma, Rui Cao, Liangdan Sun and Xiaoming Song Show full author list Hide full author list

Life 2026, 16(9), 1560; https://doi.org/10.3390/life16091560 - 17 Sep 2026

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy, and gemcitabine (GEM) resistance is a major contributor to its poor clinical outcomes, generating an urgent need for novel therapeutic strategies targeting tumor proliferation and tumor-cell-intrinsic malignant signaling. This study aimed to investigate the [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy, and gemcitabine (GEM) resistance is a major contributor to its poor clinical outcomes, generating an urgent need for novel therapeutic strategies targeting tumor proliferation and tumor-cell-intrinsic malignant signaling. This study aimed to investigate the synergistic anti-PDAC efficacy and underlying mechanism of cepharanthine (CEP) combined with GEM. A series of in vitro and in vivo experiments were performed to evaluate the antitumor activity, synergistic effect and preliminary in vivo safety of the CEP-GEM combination. Bioinformatics analysis coupled with experimental validation was applied to dissect the underlying mechanisms. The results demonstrated that CEP produced marked synergistic effects with GEM to suppress PDAC growth both in vitro and in vivo. Mechanistic investigations revealed that CEP blocked the PI3K/AKT/mTOR pathway and reduced tumor-cell-intrinsic PD-1/PD-L1 levels, thereby facilitating tumor-cell apoptosis, restraining cell migration and invasion, and sensitizing GEM-relatively insensitive AsPC-1 cells to GEM. Under our experimental conditions, no obvious histopathological injury or prominent systemic toxicity was observed. In conclusion, this work provides preclinical evidence showing that the CEP-GEM combination exerts anti-tumor activity via dual-pathway suppression in PDAC cells, and supports further translational research for PDAC. Full article

(This article belongs to the Special Issue From Physiology and Pathology Research to Clinical Insights in Gastrointestinal Disorders)

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19 pages, 10073 KB

Open AccessArticle

Genetic Variation and Haplotype Structure of CFAP299 and PRDM8 Associated with Fiber Yield and Hair Length Traits in Tianzhu White Yak

by Yicheng Liu, Xuedong Qi, Yongfu La, Xiaoming Ma, Wenxue Luo, Wenwen Ren, Guowu Yang, Zhenyu Zhang, Min Chu, Xiaoyun Wu, Xian Guo, Shaobin Li, Wanzhen Qi and Chunnian Liang

Life 2026, 16(9), 1559; https://doi.org/10.3390/life16091559 - 17 Sep 2026

Abstract

Fiber yield and hair length are important economic traits in Tianzhu White Yak. However, the genetic variants associated with fiber production performance in this breed remain insufficiently characterized. This study aimed to investigate the associations of single nucleotide polymorphisms (SNPs) in the CFAP299 [...] Read more.

Fiber yield and hair length are important economic traits in Tianzhu White Yak. However, the genetic variants associated with fiber production performance in this breed remain insufficiently characterized. This study aimed to investigate the associations of single nucleotide polymorphisms (SNPs) in the CFAP299 and PRDM8 genes with fiber yield and hair length traits in Tianzhu White Yak and to identify potential molecular markers for marker-assisted selection. A total of 759 Tianzhu White Yaks were included in this study. Genomic DNA was extracted from blood samples, SNP detection and genotyping were performed using GATK (v. 4.2.6.1), and candidate SNPs were validated by PCR amplification and Sanger sequencing. Five SNPs in CFAP299 and three SNPs in PRDM8 were selected for analyses of genetic diversity, Hardy–Weinberg equilibrium, linkage disequilibrium, haplotype structure, and associations with phenotypic traits. All eight loci displayed three genotypes. No significant departure from Hardy–Weinberg equilibrium was detected at any locus (p > 0.05), and PIC values of 0.25–0.50 indicated moderate polymorphism. After adjustment for sex and age and FDR correction, all eight SNPs remained significantly associated with head hair length (HL) and fiber yield (FY), while several loci were also significantly associated with body-side hair length (BSL) and back hair length (BL) (q < 0.05). Individuals carrying mutant homozygous genotypes generally exhibited higher phenotypic values for the corresponding traits, whereas heterozygous genotypes generally showed intermediate values between the two homozygous genotypes. Linkage disequilibrium and haplotype analyses revealed that the eight SNPs formed three haplotype blocks. Haplotype combinations in Blocks 1 and 3 were significantly associated with variation in HL, FY, and SL, whereas no significant associations were detected for Block 2. Overall, SNPs and haplotype combinations in CFAP299 and PRDM8 were associated with variation in fiber yield and hair length traits in Tianzhu White Yak. These findings support CFAP299 and PRDM8 as candidate genes associated with fiber-related traits and provide potential molecular markers for further validation and marker-assisted selection. Full article

(This article belongs to the Special Issue Advances in Livestock Breeding, Nutrition and Metabolism)

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24 pages, 2173 KB

Open AccessArticle

A Bacillus pretiosus Biofertilizer Enhances Early Growth, Nutritional Profile, and Rhizospheric Dynamics in Quercus Species for Forest Restoration

by Marina Robas-Mora, Daniel González-Reguero, Vanesa M. Fernández-Pastrana, Diana Penalba-Iglesias, Agustín Probanza and Pedro A. Jiménez-Gómez

Life 2026, 16(9), 1558; https://doi.org/10.3390/life16091558 - 17 Sep 2026

Abstract

Plant growth-promoting bacteria (PGPBs) have emerged as essential biological inputs to improve the establishment, physiological performance and survival of forest species used in ecological restoration programs. The decline of Quercus forests throughout the Mediterranean basin requires innovative and sustainable strategies to improve early [...] Read more.

Plant growth-promoting bacteria (PGPBs) have emerged as essential biological inputs to improve the establishment, physiological performance and survival of forest species used in ecological restoration programs. The decline of Quercus forests throughout the Mediterranean basin requires innovative and sustainable strategies to improve early seedling establishment. Among possible PGBs, Bacillus pretiosus has attracted significant interest due to its ability to promote plant growth, modulate the nutrient status of the host, and safely interact with native rhizosphere microbiota. At the same time, evaluating urban wastewater waste using PGPB offers a promising circular economy approach. To provide an integrated functional and ecological assessment of B. pretiosus C1, this in silico study harmonizes and reinterprets experimental datasets through contrasting fertigation regimes—water (W), wastewater treatment plant effluent (EDAR) and electrochemically treated effluent (EDARST)—evaluating inoculation (C1) versus uninoculated controls (C0). Inoculation resulted in a consistent positive biometric response, significantly promoting outbreak length (up to +16.2% in EDARST). In addition, B. pretiosus C1 improved nitrogen leaf metabolism, raising crude protein levels (+11.8%), soluble protein and total amino acids (+15.4%). Sequencing and functional profiling of the high-yield 16S rRNA gene revealed that the introduction of strains did not significantly alter the alpha-diversity or overall beta structure of the native rhizosphere microbiome, demonstrating high ecological compatibility. Phenotypic profiling of the resistome by cenoantibiogram did not confirm an increase in resistance to antibiotics at the community level, instead showing a significant reduction in the minimum inhibitory concentration (MIC) for imipenem and amoxicillin/clavulanic acid under the fertigation of effluents. Together, these findings demonstrate that combining effluents valued with p > 0.05 B. pretiosus C1 shows a consistent functional profile with a high-value biotechnological agent, improving the biometric and nutritional status of seedlings without altering the stability of the soil microbial community. This supports its potential application as a safe biofertilizer candidate within forest restoration strategies and One Health, although more prospective field trials will be needed to validate each site. Full article

(This article belongs to the Special Issue Trends and Outlooks in Microbial Degradation and Environmental Bioremediation Technology)

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12 pages, 464 KB

Open AccessArticle

Manometric and Sonographic Examination of Anal Sphincter Complex, Fecal Incontinence and Quality of Life Outcomes in Fournier’s Gangrene Survivors

by Özgen Işık, İrem Zehra Acar, Murat Şen, Abdullah Boğa, Ahmet Ali Aktaş, Levent Tezcan, Ersin Öztürk and Tuncay Yılmazlar

Life 2026, 16(9), 1557; https://doi.org/10.3390/life16091557 - 16 Sep 2026

Abstract

Fournier’s gangrene (FG) often requires repeated aggressive debridement. Its long-term effects on continence, anal sphincter integrity, and quality of life remain insufficiently defined. Among 188 patients treated for FG between 2000 and 2021 and assessed for eligibility, 21 survivors who had perianal debridement [...] Read more.

Fournier’s gangrene (FG) often requires repeated aggressive debridement. Its long-term effects on continence, anal sphincter integrity, and quality of life remain insufficiently defined. Among 188 patients treated for FG between 2000 and 2021 and assessed for eligibility, 21 survivors who had perianal debridement within 5 cm of the anal verge, healed without permanent stoma, and completed the study protocol were included. Participants underwent standardized physical examination, anorectal manometry, endoanal ultrasonography, and questionnaire-based assessment of fecal incontinence and quality of life. Majority of patients were male (66.7%) with a median age of 59 years (39–74). The median follow-up time was 83 months (27–211). On anorectal examination, 3 patients had anal fistula, 1 had anal fissure, 1 had external rectal prolapse, and 11 had decreased anal tone on digital examination. Endoanal ultrasonography demonstrated isolated external sphincter defects in 2 patients and combined external and internal sphincter defects in 2. Anorectal manometry showed decreased resting pressure in 2 patients and decreased squeeze pressure in 11. Questionnaire-based assessment demonstrated that fecal incontinence and reduced quality of life were common among long-term survivors. Long-term survivors of Fournier’s gangrene frequently report fecal incontinence and reduced quality of life, although overt sphincter defects are uncommon. Full article

(This article belongs to the Section Medical Research)

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16 pages, 2095 KB

Open AccessArticle

A New Electrophysiological Approach to Sleep Microstructure: The Gülhane Classification of K-Complex Subtypes in Narcolepsy Type 1 and Type 2

by Volkan Tekin, Mehmet Koçer, Esra Ünverdi-Bıçakçı, Fulya Şahin, Bülent Devrim Akçay and Sinan Yetkin

Life 2026, 16(9), 1556; https://doi.org/10.3390/life16091556 - 16 Sep 2026

Abstract

Study Objectives: While the pathophysiology of Narcolepsy Type 1 (NT1) involves hypocretin deficiency, the microstructural electrophysiological features that distinguish NT1 from Narcolepsy Type 2 (NT2) remain incompletely defined. This study evaluated sleep microstructure with a six-subtype K-complex (KC) categorization (Gülhane Classification). Methods: Retrospective [...] Read more.

Study Objectives: While the pathophysiology of Narcolepsy Type 1 (NT1) involves hypocretin deficiency, the microstructural electrophysiological features that distinguish NT1 from Narcolepsy Type 2 (NT2) remain incompletely defined. This study evaluated sleep microstructure with a six-subtype K-complex (KC) categorization (Gülhane Classification). Methods: Retrospective polysomnography from the December 2016–January 2026 clinical archive was reviewed. K-complex scoring defined the analyzed sample: NT1 n = 18, NT2 n = 13, and simple-snoring controls with AHI < 5 (n = 15). Complete overnight PSG summaries were available for NT1 n = 16 and NT2 n = 13. Six visually defined KC subtypes (Isolated-KC, KC-Burst, KC-Sigma, KC-Delta, Polyphasic-KC, and Polyphasic-KC-Sigma) were compared across Descendant, Intermediate, and Ascendant portions of the NREM cycle. Results: Compared with controls, NT1 showed lower Isolated-KC and KC-Sigma counts across cycle periods (p < 0.05). NT1 also had higher wake after sleep onset (WASO; 34.7 ± 21.1 min) and lower sleep efficiency (90.7 ± 5.4%) than NT2. NT1–NT2 differences that reached p < 0.05 were KC-Delta in the Intermediate (p = 0.015) and Descendant (p = 0.030) periods, Isolated-KC in the Intermediate period (p = 0.039), and KC-Sigma in the Descendant period (p = 0.041). Conclusions: In this retrospective cohort, morphological KC subtyping showed a coherent reduction in Isolated-KC and KC-Sigma in NT1. The findings are descriptive and require prospective validation; they do not constitute a standalone diagnostic test. Full article

(This article belongs to the Section Physiology and Pathology)

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20 pages, 977 KB

Open AccessSystematic Review

Clinical Spectrum and Organ Involvement in Pediatric Melioidosis: A Systematic Review and Meta-Analysis

by Jongkonnee Thanasai, Anchalee Chittamma, Supphachoke Khemla, Atthaphong Phongphithakchai, Moragot Chatatikun, Jitbanjong Tangpong, Sa-ngob Laklaeng, Jirarat Songsri and Wiyada Kwanhian Klangbud

Life 2026, 16(9), 1555; https://doi.org/10.3390/life16091555 - 16 Sep 2026

Abstract

Background: Pediatric melioidosis causes substantial morbidity and mortality in tropical regions, yet its clinical spectrum has not been comprehensively quantified. We conducted a systematic review and meta-analysis to characterize clinical manifestations, organ involvement, and mortality among children with melioidosis. Methods: PubMed, Embase, and [...] Read more.

Background: Pediatric melioidosis causes substantial morbidity and mortality in tropical regions, yet its clinical spectrum has not been comprehensively quantified. We conducted a systematic review and meta-analysis to characterize clinical manifestations, organ involvement, and mortality among children with melioidosis. Methods: PubMed, Embase, and Scopus were searched from inception to 31 May 2026 for observational studies reporting clinical manifestations or outcomes in children (<18 years) with melioidosis. Pooled prevalence estimates and case-fatality rates were calculated using random-effects generalized linear mixed models with logit transformation. Heterogeneity was assessed using Cochran’s Q, I², and τ². Country subgroup analyses were performed, and small-study effects were assessed for outcomes with at least ten studies. Results: Twenty-five studies involving 6874 children from 10 countries were included. Localized infection predominated (69%; 95% CI, 52–82%), whereas disseminated infection occurred in 30% (95% CI, 18–46%). Skin and soft tissue infection was the most frequent manifestation (31%; 95% CI, 23–41%), followed by lymphadenitis (24%; 95% CI, 3–76%), pneumonia (18%; 95% CI, 17–19%), and parotitis (13%; 95% CI, 5–28%). Bacteremia occurred in 23% (95% CI, 11–43%), septic shock in 6% (95% CI, 0–53%), and the pooled case-fatality rate was 12% (95% CI, 7–20%). Significant geographic variation was observed for localized infection, disseminated infection, pneumonia, bacteremia, and mortality (all p < 0.01). Small-study effects were detected for several outcomes. Conclusions: Pediatric melioidosis predominantly presents as localized disease, but disseminated infection, bacteremia, and mortality remain clinically important. Geographic variation and substantial heterogeneity highlight differences in disease presentation across settings. These findings provide quantitative evidence to support earlier recognition, diagnostic evaluation, and timely management of pediatric melioidosis in endemic regions. Full article

(This article belongs to the Section Microbiology)

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28 pages, 16741 KB

Open AccessArticle

Comparative Analysis of Plasma Biomarkers of Alzheimer’s Disease and Frontotemporal Dementia: The Dual Role of Soluble Fractalkine as a Biomarker of Frontotemporal Dementia and Its Neuroprotective Effects in Cortical Neurons “In Vitro”

by José Joaquín Merino, José Julio Rodríguez-Arellano, Xavier Busquets, Ana I. Flores and Adolfo Toledano

Life 2026, 16(9), 1554; https://doi.org/10.3390/life16091554 - 16 Sep 2026

Abstract

Frontotemporal lobar degeneration (FTD) and Alzheimer’s disease (AD) are proteinopathies characterized by the abnormal accumulation and aggregation of specific proteins like Aβ-42 deposits, p-tau accumulation, and abnormal cytosolic aggregation of TAR DNA-binding protein 43 (TDP-43) in FTD patients. Recently, the identification of neuroinflammatory [...] Read more.

Frontotemporal lobar degeneration (FTD) and Alzheimer’s disease (AD) are proteinopathies characterized by the abnormal accumulation and aggregation of specific proteins like Aβ-42 deposits, p-tau accumulation, and abnormal cytosolic aggregation of TAR DNA-binding protein 43 (TDP-43) in FTD patients. Recently, the identification of neuroinflammatory mediators as predictors of cognitive decline has gained attention. We have compared several plasma biomarkers of cognitive impairment between AD and FTD patients using Enzyme-Linked Immunosorbent Assay (ELISA) (pg/mL), including CX3CR1 and soluble fractalkine (sFK, also termed CX3CL1), TDP-43, neurofilament light chain M (NfL M), p-tau217, and GFAP (glial fibrillary acidic protein). Chemokines are HIV-1 co-receptors that facilitate the spread of HIV-1 infection and induce apoptosis in the brain. Whilst these chemokines promote neuronal survival and regulate neuron-glia interactions, they also contribute to neurodegeneration. Fractalkine, also known as CX3CL1, is a delta chemokine that binds to its CX3CR1 chemokine receptor. As a membrane isoform, fractalkine can be released in a soluble form by damaged neurons under either inflammatory and/or excitotoxic conditions; since neuroinflammation contributes to neurodegeneration and dementia, we compared these CX3CR1/sFK delta chemokine levels in seropositive patients (with suppressed viral loads) and without neurodegeneration to age-matched controls. This was done in order to study whether inflammation could upregulate these chemokines in the absence of cognitive impairment. To our knowledge, this is the first study showing that increased plasma levels of CX3CR1 and soluble fractalkine could be associated with FTD pathology as compared to control subjects (without neurodegeneration). However, peripheral NfL M, GFAP, and p-tau217 levels did not differ between AD and FTD patients. Post-mortem analysis of human FTD brains revealed anatomical changes, including hippocampal involution and tau deposits. Given that soluble fractalkine can contribute to cognitive impairment while also exerting protective effects against brain insults, we did an additional (independent experiment) in cortical neurons in vitro under LPS-induced neurotoxicity. We confirmed that adding recombinant fractalkine for 24 h prevented lipopolysaccharide (LPS)-induced apoptosis in cortical neurons at 7 days in vitro (DIV); moreover, twenty-four hours after LPS treatment, sFK prevented neuronal apoptosis by decreasing caspase-3 activity and exerted neuroprotective effects against inflammation. Our findings suggest that fractalkine mitigates LPS-induced neuronal injury by limiting apoptosis and inflammatory responses. Furthermore, our findings suggest for the first time that elevated circulating sFK levels may indirectly be associated with FTD pathology as compared to healthy controls. However, sFK could also reflect compensatory protective responses to neuronal injury. Full article

(This article belongs to the Section Medical Research)

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20 pages, 8165 KB

Open AccessArticle

Individual Patterns of Heart Rate Variability During Prolonged Cognitive Load with Mental Fatigue Induction

by Ekaterina I. Borovkova, Anton R. Kiselev, Vladimir A. Shvartz, Mikhail D. Prokhorov, Aleksey N. Hramkov, Anna M. Vakhlaeva, Sergey E. Burmistrov, Ekaterina M. Zinchenko, Svetlana V. Frolova, Ekaterina A. Lazunina, Elena N. Shvartz, Aleksandr V. Kurbako, Boris P. Bezruchko and Anatoly S. Karavaev

Life 2026, 16(9), 1553; https://doi.org/10.3390/life16091553 - 16 Sep 2026

Abstract

We investigated individual dynamics of cognitive performance and heart rate variability (HRV) measures during prolonged mental load. The aim of this study was to identify characteristic phases of cognitive performance and individual patterns of physiological responses induced by prolonged mentally fatiguing tasks. In [...] Read more.

We investigated individual dynamics of cognitive performance and heart rate variability (HRV) measures during prolonged mental load. The aim of this study was to identify characteristic phases of cognitive performance and individual patterns of physiological responses induced by prolonged mentally fatiguing tasks. In prolonged experiments with two cognitive tasks of different structure, cognitive performance, HRV measures, and subjective fatigue were analyzed. The proposed integrated index of relative performance made it possible to identify individual phases of cognitive performance: the adaptation phase (AP), the optimal performance phase (OP), and the fatigue phase (FP). The OP was observed in all subjects, the FP in most subjects, whereas the AP was observed in fewer than half of the subjects, indicating pronounced inter-individual variability in cognitive performance dynamics. Two patterns of the initial heart rate (HR) response were identified, ΔHR ≥ 0 and ΔHR < 0, which were associated with differences in the subsequent dynamics of HR and individual HRV measures. The nature of these differences depended on the phase of cognitive performance and the type of task. Among subjects who performed both tasks, approximately half showed the same direction of the initial HR response in the Serial Subtraction Task (SST) and the Working Memory Task (WMT), whereas the remaining subjects showed different directions, indicating limited reproducibility across tasks. The obtained results demonstrate pronounced inter-individual variability in cognitive performance and physiological responses during prolonged mental load and support the need to account for individual dynamics when developing personalized approaches to monitoring mental fatigue. Full article

(This article belongs to the Section Medical Research)

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19 pages, 8285 KB

Open AccessArticle

Aloe-Emodin Modifies Adipogenic Genes and the Expression of miR-143 and miR-155 in 3T3-L1 Cells

by Carlos Uriel Torres-Estrella, Jose Luis Acosta-Rodríguez, Julio Jesús Garcia-Coste, Fausto Sánchez-Muñoz, Rodrigo Romero-Nava and Karla Aidee Aguayo-Cerón

Life 2026, 16(9), 1552; https://doi.org/10.3390/life16091552 - 16 Sep 2026

Abstract

Adipogenesis is crucial for maintaining energy homeostasis, as it facilitates the differentiation of mesenchymal stem cells into adipocytes. This process is transcriptionally regulated by key factors including PPARγ and C/EBPβ, alongside FABP4 during lipogenesis. However, it is now well established that a significant [...] Read more.

Adipogenesis is crucial for maintaining energy homeostasis, as it facilitates the differentiation of mesenchymal stem cells into adipocytes. This process is transcriptionally regulated by key factors including PPARγ and C/EBPβ, alongside FABP4 during lipogenesis. However, it is now well established that a significant portion of this regulation is also mediated by small non-coding RNAs (miRNAs) and long non-coding RNAs (lncRNAs), which post-transcriptionally modulate gene expression. This study aimed to identify key miRNAs involved in adipogenesis and to determine how Aloe-emodin, a molecule with potent anti-inflammatory properties known to modulate adipocyte differentiation, alters their expression. Using an integrative approach combining 3T3-L1 cell culture, RNA-seq, and qPCR analyses, this study demonstrates that Aloe-emodin can upregulate transcription factors (PPARγ and C/EBPβ) as well as miR-143 and miR-155, suggesting its potential as a modulator of adipogenic gene or miRNA expression in this exploratory setting. Full article

(This article belongs to the Special Issue New Updates in Adipocytes and Adipose Tissue—3rd Edition)

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16 pages, 997 KB

Open AccessArticle

Low-Supervision Asynchronously Monitored Home Rehabilitation for Adhesive Capsulitis: A Pilot Randomized Study

by Hsin-Wei Lin, Chia-Chen Hu, Hui-Min Yen and Jiunn-Horng Kang

Life 2026, 16(9), 1551; https://doi.org/10.3390/life16091551 - 16 Sep 2026

Abstract

Background: Adhesive capsulitis often requires prolonged rehabilitation, and home exercise performed without supervision is difficult to document objectively. This pilot randomized trial evaluated the preliminary clinical effects and system-recorded engagement of a low-supervision, asynchronously monitored home rehabilitation system used as an adjunct to [...] Read more.

Background: Adhesive capsulitis often requires prolonged rehabilitation, and home exercise performed without supervision is difficult to document objectively. This pilot randomized trial evaluated the preliminary clinical effects and system-recorded engagement of a low-supervision, asynchronously monitored home rehabilitation system used as an adjunct to conventional outpatient rehabilitation. Methods: Thirty adults with adhesive capsulitis were randomly assigned 1:1 at a university-affiliated outpatient rehabilitation department. Both groups received conventional outpatient rehabilitation twice weekly for 4 weeks; the intervention group additionally used a gamified, smartphone-based home program (HappyGoGo) with asynchronous system monitoring, and the control group received standard home exercise instructions. Because the outcome hierarchy was assigned at retrospective registration, after data collection and analysis had been completed, all outcomes are reported as exploratory. Fourteen clinical outcomes were analyzed by analysis of covariance adjusting for the corresponding baseline value, with Benjamini–Hochberg correction; unadjusted change scores were compared as a sensitivity analysis. Results: Substantial baseline imbalance was present, with the intervention group more restricted in range of motion and reporting higher pain. After adjustment, no outcome reached nominal significance and the 95% confidence interval included the null for all 14 outcomes. The largest estimate was for pain (adjusted mean difference −1.30 points, 95% CI −2.64 to 0.04; p = 0.057). In the unadjusted analysis, pain and internal rotation reached nominal significance but neither survived correction for multiple comparisons. All 30 participants completed the protocol, no adverse events were reported, and engagement was retrieved for 14 of 15 intervention participants (mean 61.0%, range 7.1–96.4%). Conclusions: This trial found no detectable between-group difference on any clinical outcome, with confidence intervals too wide to determine whether a clinically meaningful effect exists. The system could be implemented alongside routine care without adverse events, and participation could be documented automatically, though it varied widely between individuals. Full article

(This article belongs to the Section Epidemiology)

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18 pages, 25557 KB

Open AccessArticle

Combined Mesenchymal Stem Cells and Low-Energy Shock Wave Therapy Significantly Reduced Inflammation, Oxidative Stress and Preserved Podocytes in Diabetic Nephropathy

by Chang-Chun Hsiao, Hsien-Wei Hsiao, Yu-Hsuan Liu and Chien-Te Lee

Life 2026, 16(9), 1550; https://doi.org/10.3390/life16091550 - 16 Sep 2026

Abstract

Diabetic nephropathy (DN) is among the leading microvascular complications of diabetes mellitus and a major cause of end-stage renal disease. Current treatments slow disease progression but do not restore lost podocytes. We tested whether Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) combined with low-energy [...] Read more.

Diabetic nephropathy (DN) is among the leading microvascular complications of diabetes mellitus and a major cause of end-stage renal disease. Current treatments slow disease progression but do not restore lost podocytes. We tested whether Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) combined with low-energy shock wave (SW) therapy could be a safe and effective therapy in a streptozotocin-induced rat model of DN. Diabetic rats received 107 WJ-MSCs together with SW (0.13 mJ/mm², 200 shocks) once a week for five weeks. The combined regimen lowered urinary microalbumin and the albumin-to-creatinine ratio, attenuated glomerular hypertrophy, and reduced fibronectin and collagen I deposition. Podocyte markers (WT-1, synaptopodin, nephrin) recovered toward normal levels. WJ + SW therapy suppressed NF-κB and IL-6 while raising IL-4 and IL-10, lowered NOX4 expression, and increased the antioxidant enzyme HO-1. Renal macrophages also shifted from the pro-inflammatory M1 phenotype to the reparative M2 phenotype. Together, these findings indicate that combining WJ-MSCs with low-energy SW therapy acts on multiple pathogenic axes of DN and may offer a potential interventional strategy for this inescapable and progressive complication. Full article

(This article belongs to the Special Issue An Update on Diabetic Kidney Disease: Epidemiology, Diagnosis, Treatment)

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