Journal Description
Life
Life
is an international, peer-reviewed, open access journal related to fundamental themes in life sciences from basic to applied research, published monthly online by MDPI. The Spanish Association for Cancer Research (ASEICA) is affiliated with Life and its members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q1 (Biology) / CiteScore - Q1 (Paleontology)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 15.3 days after submission; acceptance to publication is undertaken in 2.9 days (median values for papers published in this journal in the first half of 2026).
- Recognition of Reviewers: Reviewers whose reports are timely and of high quality receive an APC discount voucher for a future publication in an MDPI journal. Become a reviewer.
Impact Factor:
3.9 (2025);
5-Year Impact Factor:
3.9 (2025)
Latest Articles
Dynamic Assessment of the C-Reactive Protein-to-Albumin Ratio Improves Early Prediction of Severe Acute Pancreatitis: A Retrospective Cohort Study
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
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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.
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(This article belongs to the Special Issue From Physiology and Pathology Research to Clinical Insights in Gastrointestinal Disorders)
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
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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.
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(This article belongs to the Special Issue Advances in Computational and Spatial Pathology)
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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
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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. Fm, Fv, Fv/Fm, 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.
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(This article belongs to the Section Plant Science)
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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
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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.
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(This article belongs to the Section Physiology and Pathology)
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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 Songadd
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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
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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.
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(This article belongs to the Special Issue From Physiology and Pathology Research to Clinical Insights in Gastrointestinal Disorders)
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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
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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.
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(This article belongs to the Special Issue Advances in Livestock Breeding, Nutrition and Metabolism)
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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
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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.
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(This article belongs to the Special Issue Trends and Outlooks in Microbial Degradation and Environmental Bioremediation Technology)
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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
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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.
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(This article belongs to the Section Medical Research)
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A New Electrophysiological Approach to Sleep Microstructure: The Gülhane Classification of K-Complex Subtypes in Narcolepsy Type 1 and Type 2
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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
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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.
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(This article belongs to the Section Physiology and Pathology)
Open AccessSystematic Review
Clinical Spectrum and Organ Involvement in Pediatric Melioidosis: A Systematic Review and Meta-Analysis
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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
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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.
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(This article belongs to the Section Microbiology)
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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
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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.
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(This article belongs to the Section Medical Research)
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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
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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.
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(This article belongs to the Section Medical Research)
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
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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.
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(This article belongs to the Special Issue New Updates in Adipocytes and Adipose Tissue—3rd Edition)
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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
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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.
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(This article belongs to the Section Epidemiology)
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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
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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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Open AccessArticle
Characterization of Escherichia Phage ND-4 Against Avian Pathogenic Escherichia coli IMT5155 and Its Preliminary Application in Chicks
by
Leping Wang, Jiahe Zhou, Guotai Liu, Qinting Dong, Huili Bai, Changting Li, Yongcui Feng, Dongyan Deng, Yangyan Yin, Chunxia Ma, Ling Teng, Honggan Wei, Ruofu Qin, Xian Li, Yanwen Zhang and Hao Peng
Life 2026, 16(9), 1549; https://doi.org/10.3390/life16091549 - 16 Sep 2026
Abstract
Colibacillosis caused by avian pathogenic Escherichia coli (APEC) remains an important bacterial disease in poultry production and is increasingly difficult to control because of antimicrobial resistance. In this study, a lytic phage, ND-4, was isolated from poultry-farm sewage using the O2:K1 APEC strain
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Colibacillosis caused by avian pathogenic Escherichia coli (APEC) remains an important bacterial disease in poultry production and is increasingly difficult to control because of antimicrobial resistance. In this study, a lytic phage, ND-4, was isolated from poultry-farm sewage using the O2:K1 APEC strain IMT5155 as the host, and its biological characteristics, genome features and preliminary application potential were evaluated. ND-4 formed clear plaques on IMT5155 and showed a tailed morphology, with an elliptical head of 110 ± 5 nm by 82 ± 5 nm and a tail of 97 ± 5 nm by 18 ± 2 nm, giving a total virion length of approximately 204 ± 10 nm. The phage had an optimal multiplicity of infection of 0.01, a latent period of 20 min, a 50 min burst period and a burst size of 231 PFU/cell. ND-4 remained active across pH 4–9 and at temperatures up to 60 °C, and it retained titers above 108 PFU/mL after exposure to chloroform concentrations up to 15%. Whole-genome sequencing revealed a 154,669 bp double-stranded DNA genome with 184 predicted open reading frames and a G + C content of 48.98%. No virulence or antimicrobial resistance genes were detected. ND-4 reduced biofilm biomass in vitro and decreased tissue bacterial loads and alleviated hepatic inflammation and vacuolar degeneration in IMT5155-challenged chicks. These results indicate that ND-4 is a promising candidate for further development as a phage-based control agent against APEC infection, although larger in vivo studies are needed to define its efficacy, dosing window and biosafety profile.
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(This article belongs to the Special Issue Microorganisms as Animal Health Promoters)
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Open AccessArticle
Admission Liver Injury Is an Independent Predictor of Early and Overall Mortality in Hospitalized Patients with Moderate-to-Critical COVID-19: A Retrospective Cohort Study
by
Delia-Ionela Negru-Vodă, Ana Stemate and Lucian Negreanu
Life 2026, 16(9), 1548; https://doi.org/10.3390/life16091548 - 16 Sep 2026
Abstract
Background: Liver injury (LI) is frequently observed in patients with COVID-19, particularly in severe forms of disease. However, its prognostic significance remains incompletely defined. Aim: To evaluate the association between LI at admission and clinical outcomes in hospitalized patients with moderate,
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Background: Liver injury (LI) is frequently observed in patients with COVID-19, particularly in severe forms of disease. However, its prognostic significance remains incompletely defined. Aim: To evaluate the association between LI at admission and clinical outcomes in hospitalized patients with moderate, severe, and critical COVID-19. Methods: This single-centre retrospective cohort study included 816 adults hospitalized with moderate-to-critical COVID-19 at a tertiary care hospital in Romania. LI was defined as elevations ≥ 2× the upper limit of normal (ULN) in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), or total bilirubin (TB) at admission. Clinical, laboratory, imaging, and outcome data, including intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and mortality, were analysed. Results: LI was present in 34.9% of patients. Compared with patients without LI, affected patients more frequently exhibited inflammatory syndrome (98.7% vs. 95.2%, p = 0.017), elevated interleukin-6 (IL-6) levels (65.3% vs. 44.3%, p = 0.007), and extensive pulmonary involvement (>75% on chest computed tomography; 38.2% vs. 27.3%, p = 0.003). They were also more likely to require ICU admission (44.2% vs. 36.2%, p = 0.025) and IMV (30.9% vs. 23.5%, p = 0.011). Seven-day mortality (25.9% vs. 16.1%, p = 0.001) and overall mortality (49.8% vs. 36.8%, p < 0.001) were significantly higher among patients with LI. In multivariable analysis, LI remained independently associated with both 7-day and overall mortality. The association between admission LI and mortality remained consistent across pandemic waves, with no significant interaction between liver injury and wave (p = 0.731). Conclusions: LI at admission may help identify patients with COVID-19 at increased risk of adverse outcomes and represents a simple and widely available tool for early risk stratification and clinical management.
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(This article belongs to the Section Medical Research)
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Open AccessArticle
Discriminative Performance of Routine Inflammation- and Nutrition-Based Indices for Histopathologically Confirmed Gastric Malignancy: A Retrospective Case–Control Study
by
Muammer Bilici, Dilek Ayvaz, Didem Güney, Ünzile Işıl Yüce and Selim Aydemir
Life 2026, 16(9), 1547; https://doi.org/10.3390/life16091547 - 16 Sep 2026
Abstract
Background/Objectives: This study aimed to evaluate the discriminative performance of routine systemic inflammation- and nutrition-based indices for distinguishing histopathologically confirmed gastric malignancy from non-malignant endoscopic findings. Methods: This retrospective case–control study included 211 patients who underwent upper gastrointestinal endoscopy with histopathological evaluation: 139
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Background/Objectives: This study aimed to evaluate the discriminative performance of routine systemic inflammation- and nutrition-based indices for distinguishing histopathologically confirmed gastric malignancy from non-malignant endoscopic findings. Methods: This retrospective case–control study included 211 patients who underwent upper gastrointestinal endoscopy with histopathological evaluation: 139 non-malignant endoscopic controls (129 benign/non-neoplastic and 10 premalignant findings) and 72 gastric malignancy cases. Premalignant lesions were not considered malignant outcomes. Discrimination was evaluated using univariable ROC analyses and multivariable logistic models. The fixed predictor set was assessed using 10-fold out-of-fold validation and 500-resample bootstrap optimism correction; a separate fully nested selection-inclusive audit was used to quantify uncertainty arising from variable selection. Results: NLR (AUC = 0.792), INR (AUC = 0.791), and SIRI (AUC = 0.783) showed the highest univariable discrimination. Among the variables retained in Model 1, higher ESR and RDW, lower MPV and HDL, higher INR values, and male sex showed statistically significant multivariable associations. Model 1 had an apparent AUC of 0.928 (95% CI, 0.890–0.959), a fixed-set 10-fold out-of-fold AUC of 0.890, and a bootstrap optimism-corrected AUC of 0.901. A fully nested selection-inclusive audit yielded an out-of-fold AUC of 0.873 and a bootstrap-corrected AUC of 0.869. Conclusions: Routine inflammation- and nutrition-related laboratory measures discriminated gastric malignancy from non-malignant endoscopic findings in this endoscopy-selected cohort. The model remains exploratory and requires prospective external validation. These data do not establish screening performance or diagnostic accuracy for early or asymptomatic gastric cancer.
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(This article belongs to the Section Medical Research)
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Open AccessArticle
Postoperative Quadriceps Symmetry, Knee Laxity, and Single-Leg Hop Performance in Association with 24-Month Ipsilateral Graft Retear After Anterior Cruciate Ligament Reconstruction: A Cohort Study
by
Georgios Kakavas, Nikolaos Malliaropoulos and Florian Forelli
Life 2026, 16(9), 1546; https://doi.org/10.3390/life16091546 - 16 Sep 2026
Abstract
Background: Ipsilateral graft retear after anterior cruciate ligament reconstruction (ACLR) remains a major concern in athletes, while the relationship between postoperative mechanical and functional measures and retear remains uncertain. Methods: This cohort study included 48 athletes after primary unilateral ACLR with hamstring-tendon autograft.
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Background: Ipsilateral graft retear after anterior cruciate ligament reconstruction (ACLR) remains a major concern in athletes, while the relationship between postoperative mechanical and functional measures and retear remains uncertain. Methods: This cohort study included 48 athletes after primary unilateral ACLR with hamstring-tendon autograft. Follow-up was scheduled at 6, 9, and 12 months (184 ± 13, 276 ± 17, and 368 ± 22 days), and the analytic export retained one postoperative value per athlete for GNRB side-to-side laxity at 250 N, concentric isokinetic quadriceps limb symmetry index (LSI) at 60°/s, single-leg hop-for-distance LSI, and patient-reported outcomes, without preserving the originating visit. MRI-confirmed ipsilateral graft retear was recorded within 24 months after clinically suspected reinjury; retear dates were not retained. Results: Fourteen athletes (29.2%) sustained a retear. Quadriceps LSI was lower in the retear group than in the no-retear group (81.3 ± 7.5% vs. 88.1 ± 9.0%; p = 0.011), and each 1-SD higher quadriceps LSI was associated with lower retear odds (OR 0.43, 95% CI 0.21–0.89). In an exploratory threshold analysis, quadriceps LSI < 85% was associated with a higher retear proportion (RR 3.21, 95% CI 1.17–8.82). Associations for knee laxity, hop performance, and patient-reported outcomes were not statistically robust. Conclusions: Postoperative quadriceps symmetry showed the clearest association with 24-month graft-retear status. However, because the originating measurement visit and retear dates were unavailable, temporal precedence could not be established, and the exploratory <85% LSI finding should not be interpreted as a validated return-to-sport threshold.
Full article
(This article belongs to the Special Issue Advances in Knee Biomechanics—2nd Edition)
Open AccessReview
Equivocal Dopamine Transporter Imaging: Integrating Visual Assessment, Quantification, and Clinical Follow-Up
by
So Young Kim
Life 2026, 16(9), 1545; https://doi.org/10.3390/life16091545 - 16 Sep 2026
Abstract
Dopamine transporter (DAT) imaging is widely used to determine whether parkinsonian symptoms reflect presynaptic nigrostriatal degeneration. Although most examinations can be confidently classified as normal or abnormal, a clinically important subset remains equivocal. Such scans may show subtle posterior putaminal reduction, mild asymmetry,
[...] Read more.
Dopamine transporter (DAT) imaging is widely used to determine whether parkinsonian symptoms reflect presynaptic nigrostriatal degeneration. Although most examinations can be confidently classified as normal or abnormal, a clinically important subset remains equivocal. Such scans may show subtle posterior putaminal reduction, mild asymmetry, preserved comma-shaped morphology despite low quantitative values, or disagreement between visual and semiquantitative assessments. These findings may result from early neurodegeneration, physiological variation, medication effects, structural lesions, technical artifacts, or limitations of image processing and normative databases. This narrative review examines visual criteria, the complementary role and limitations of quantification, longitudinal outcomes of scans without evidence of dopaminergic deficit (SWEDD), common interpretive pitfalls, and the roles of clinical follow-up and repeat imaging. No universal quantitative cutoff can be applied across scanners, reconstruction methods, tracers, and software platforms. Expert visual interpretation remains the primary basis for assessment, while age- and platform-matched quantification is most useful as an adjunct in borderline cases. Integrating image quality, regional uptake pattern, quantitative findings, structural imaging, medication history, and clinical evolution may reduce diagnostic error and premature labeling of neurodegenerative parkinsonism.
Full article
(This article belongs to the Special Issue Innovations in Nuclear Medicine and Molecular Imaging)
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