Life

15 pages, 1766 KB

Open AccessPerspective

The Compartmental and Fibrillar Polyhedral Architecture of Fascia: An Assessment of Connective Tissue Anatomy Without Its Abstract Classifications

by Graham Scarr

Life 2025, 15(9), 1479; https://doi.org/10.3390/life15091479 (registering DOI) - 20 Sep 2025

Abstract

The process of dissection is essential to the study of anatomy, with the variety of colours, shapes, patterns and textures revealing the distinctive features of each anatomical system, but it can also be misleading, because while the body’s constituent ‘parts’ have traditionally been [...] Read more.

The process of dissection is essential to the study of anatomy, with the variety of colours, shapes, patterns and textures revealing the distinctive features of each anatomical system, but it can also be misleading, because while the body’s constituent ‘parts’ have traditionally been classified according to their appearance, assumed functions and perceived importance, this basic information can be interpreted in different ways. Living organisms are intrinsically indeterminate, which implies that the conclusions arrived at through the study of anatomy are not necessarily congruent with the anatomical reality, and the abstract classifications of the connective tissues (CTs) are a case in point. This paper highlights a seventeenth-century interpretation of CT anatomy that was pushed aside as the musculoskeletal duality assumed functional dominance and relegated the fascial tissues to mere ancillary roles. In other words, an architectural framework of tensioned fibrous tissues that encompasses a complex body-wide heterarchy of space-filling compartments under compression and reasserts the structural significance of the soft CTs. The problems with orthodox classifications are then discussed alongside a mechano-structural role for the ‘loose’ fibrillar network: a closed-chain kinematic system that guides changes in the relative positions of adjacent compartments and refutes the notion of fascial ‘layers’. Full article

(This article belongs to the Special Issue Advances in Ubiquitous Connective Tissue Architecture: Fascia, Dynamic movements and Perception in Living Structures)

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17 pages, 1116 KB

Open AccessArticle

Minimally-Invasive Imaging of Sublingual Vessels—A New Method to Study Microvascular Changes in Mice

by Ellen Dyminski Parente Ribeiro, Maryam Dastan, Ursula Bellut-Staeck, Juan Zhou and Christian Lehmann

Life 2025, 15(9), 1478; https://doi.org/10.3390/life15091478 (registering DOI) - 20 Sep 2025

Abstract

Sepsis causes profound microcirculatory dysfunction, where heterogeneous capillary perfusion and abnormal vasomotion contribute to tissue hypoxia and organ failure. Sublingual videomicroscopy is established in large animals and humans to monitor these alterations, but this approach has not been applied in murine models. We [...] Read more.

Sepsis causes profound microcirculatory dysfunction, where heterogeneous capillary perfusion and abnormal vasomotion contribute to tissue hypoxia and organ failure. Sublingual videomicroscopy is established in large animals and humans to monitor these alterations, but this approach has not been applied in murine models. We developed a method to assess sublingual perfusion and vasomotion in mice using sidestream dark field (SDF) videomicroscopy. Male C57BL/6 mice were anesthetized, and sublingual vessels were imaged for 90 min. Perfusion and vasomotion parameters were assessed, and a Fast Fourier Transform was performed on vasomotion data to characterize the frequency components of rhythmic microvessel diameter changes. Another group of animals was administered lipopolysaccharide (LPS) intraperitoneally as a model of systemic inflammation in sepsis. LPS-treated mice exhibited a significant decline in the proportion of perfused vessels at 90 min and in the microvascular flow index. Very low-frequency vasomotion (0.005–0.15 Hz) declined in controls but was preserved during endotoxemia, suggesting an active microvascular tone response to inflammatory stress. This study establishes the first murine protocol for sublingual SDF imaging, allowing early detection of perfusion deficits and vasomotor changes in experimental sepsis. The minimal-invasive approach offers a translational platform for mechanistic and therapeutic studies in sepsis. Full article

(This article belongs to the Special Issue Advances in Medical Imaging of Animal Models for Human Diseases)

15 pages, 1666 KB

Open AccessArticle

Physiological and Biochemical Responses of Nostoc linckia to Metal Oxide Nanoparticles

by Liliana Cepoi, Vera Potopová, Ludmila Rudi, Tatiana Chiriac, Svetlana Codreanu, Ana Valuta and Valeriu Rudic

Life 2025, 15(9), 1477; https://doi.org/10.3390/life15091477 (registering DOI) - 20 Sep 2025

Abstract

Metal oxide nanoparticles, such as ZnONPs and TiO₂NPs, are increasingly applied in various industries. However, their effects on photosynthetic microorganisms at environmentally relevant concentrations remain poorly understood. This study evaluated the impact of ZnONPs and TiO₂NPs, at concentrations ranging [...] Read more.

Metal oxide nanoparticles, such as ZnONPs and TiO₂NPs, are increasingly applied in various industries. However, their effects on photosynthetic microorganisms at environmentally relevant concentrations remain poorly understood. This study evaluated the impact of ZnONPs and TiO₂NPs, at concentrations ranging from 0.1 to 30 mg/L, on the cyanobacterium Nostoc linckia (strain CNMN-CB-03), a species recognized for its adaptability and biotechnological potential. The nanoparticles were added to controlled cultures, and changes in biomass composition and pigment content were assessed using spectrophotometric assays. Both nanoparticle types significantly affected the physiological and biochemical profile of Nostoc linckia. Low concentrations of ZnONPs stimulated the accumulation of biomass, chlorophyll, carotenoids, and lipids, while higher doses caused a reduction in phycocyanin and in total phycobiliproteins content. TiO₂NPs consistently promoted biomass growth across all tested concentrations, with decrease in carotenoids and total phycobiliproteins observed at the highest concentrations. For both nanoparticle types, malondialdehyde (MDA) levels decreased compared to the control, indicating reduced oxidative stress and effective cellular adaptation. The results highlight the remarkable resilience and metabolic flexibility of Nostoc linckia in the presence of nanoparticles, supporting its potential as a biotechnological platform for the sustainable production of valuable metabolites under controlled stress conditions. Full article

(This article belongs to the Section Microbiology)

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22 pages, 16181 KB

Open AccessArticle

Genome-Wide Identification of the CBL-CIPK Gene Family in the Ice Plant and Functional Analysis of Salt Stress Tolerance

by Can Wang, Nan Li, Haifeng Sun, Tianyue Xu, Jinghua He, Chenhao Zhang, Zipeng Meng, Xinyao Zhang, Rong Zhou, Yingchao Zhang and Xiaoming Song

Life 2025, 15(9), 1476; https://doi.org/10.3390/life15091476 - 19 Sep 2025

Abstract

Background: The ice plant (Mesembryanthemum crystallinum L.) is a typical halophyte with remarkable stress resistance traits, including salinity and alkalinity tolerance. As a crucial signaling transduction pathway for plant responses to environmental stress, the CBL-CIPK signaling system plays a key role [...] Read more.

Background: The ice plant (Mesembryanthemum crystallinum L.) is a typical halophyte with remarkable stress resistance traits, including salinity and alkalinity tolerance. As a crucial signaling transduction pathway for plant responses to environmental stress, the CBL-CIPK signaling system plays a key role in regulating plant stress resistance. Methods: This study systematically analyzed the composition characteristics of the CBL and CIPK gene families across 24 plant species, including the ice plant, using comparative genomics approaches. Results: A total of 297 CBL and 561 CIPK gene family members were identified across the 24 species. Within the ice plant genome, 9 CBL and 18 CIPK genes were identified. Compared to model plants like Arabidopsis thaliana, the ice plant possesses a relatively higher number of CIPK genes, which may be related to its specific adaptation to saline–alkaline environments. Phylogenetic analysis indicated that the ice plant CBL and CIPK genes could be classified into three and four subfamilies, respectively. Expression analysis revealed that several genes (e.g., McCBL1, McCBL4, McCIPK1, McCIPK2) were significantly upregulated under salt stress, suggesting their important roles in the salt stress response. Notably, ice plant CBL and CIPK genes exhibit significant structural diversity. For instance, McCBL3 contains significantly more CDS regions than other members, while CIPK genes can be divided into two types: single-CDS type and multi-CDS type. This structural variation may be associated with functional divergence during the evolution of the gene family. Furthermore, three-dimensional (3D) structure prediction showed that CBL proteins primarily consist of EF-hand domains and α-helices, whereas CIPK proteins additionally contain β-sheet domains, implying that this structural difference may be related to their distinct regulatory mechanisms. Conclusions: This study provides an important theoretical basis for a deeper understanding of the molecular mechanisms underlying the CBL-CIPK signaling pathway in the saline–alkaline stress response of the ice plant. Full article

(This article belongs to the Section Plant Science)

18 pages, 2389 KB

Open AccessArticle

Multigene Identification of a Giant Wild Strain of Ganoderma mutabile (ZHM1939) and Screening of Its Culture Substrates

by Huiming Zhou, Longqian Bao, Zeqin Peng, Yuying Bai, Qiqian Su, Longfeng Yu, Chunlian Ma, Jun He and Wanzhong Tan

Life 2025, 15(9), 1475; https://doi.org/10.3390/life15091475 - 19 Sep 2025

Abstract

In the present study, a new Ganoderma sp. (ZHM1939) was collected from Lincang, Yunnan, China, and described on the basis of morphological characters and multigene phylogenetic analysis of rDNA-ITS, TEF1α and RPB2 sequences. This fungus is characterized by the exceptionally large basidiomata, [...] Read more.

In the present study, a new Ganoderma sp. (ZHM1939) was collected from Lincang, Yunnan, China, and described on the basis of morphological characters and multigene phylogenetic analysis of rDNA-ITS, TEF1α and RPB2 sequences. This fungus is characterized by the exceptionally large basidiomata, oval shape, a pileus measuring 63.86 cm long, 52.35 cm wide, and 21.63 cm thick, and a fresh weight of 80.51 kg. The skeleton hyphae from the basidiocarp are grayish to grayish-red in color, septate, and 1.41–2.75 μm in diameter, with frequently dichotomous branched and broadly ellipsoid basidiospores. The basidiospores are monocellular, ellipsoid, with round ends or one slightly pointed end, brown–gray in color, and measured 6.52–10.26 μm × 4.68–7.17 μm (n = 30). When cultured for 9 days at 25 ± 2 °C on PDA, the colony was white, ellipsoid or oval, with slightly ragged edges, measured Φ58.26 ± 3.05 mm (n = 5), and the growth rate = 6.47 mm/day; prosperous blast-spores formed after culturing for 21 days, making the colony surface powdery-white. The mycelia were septate, hyaline, branching at near-right angles, measured Φ1.28–3.32 μm (n = 30), and had some connections. The blast-spores were one-celled, elliptic or barley-seed shaped, and measured 6.52–10.26 μm × 4.68–7.17 μm (n = 30). Its rDNA-ITS, TEF1α and RPB2 sequences amplified through PCR were 602 bp, 550 bp and 729 bp, respectively. Blast-n comparison with these sequences showed that ZHM1939 was 99.67–100% identical to related strains of Ganoderma mutabile. A maximum likelihood phylogenic tree using the concatenated sequence of rDNA-ITS, TEF1α and RPB2 was constructed and it showed that ZHM1939 clustered on the same terminal branch of the phylogenic tree with the strains Cui1718 and YUAN 2289 of G. mutabile (Bootstrap support = 100%). ZHM1939 could grow on all the 15 original inoculum substrates tested, among which the best growth was shown on substrate 2 (cornmeal 40 g, sucrose 10 g, agar 20 g), with the fastest colony growth rate (6.79 mm/day). Of the five propagation substrates tested, substrate 1 (wheat grains 500 g, gypsum powder 6.5 g and calcium carbonate 2 g) resulted in the highest mycelium growth rate (7.78 mm/day). Among the six cultivation substrates tested, ZHM1939 grew best in substrate 2 (cottonseed hulls 75 g, rice bran 12 g, tree leaves 5 g, cornmeal 5 g, lime powder 1 g, sucrose 1 g and red soil 1 g) with a mycelium growth rate of 7.64 mm/day. In conclusion, ZHM1939 was identified as Ganoderma mutabile, which is a huge mushroom and rare medicinal macrofungus resource. The original inoculum substrate 9, propagation substrate 1 and cultivation substrate 2 were the most optimal substrates for producing the original propagation and cultivation inocula of this macrofungus. This is the first report on successful growing conditions for mycelial production, but basidiocarp production could not be achieved. The results of the present work establish a scientific foundation for further studies, resource protection and application development of G. mutabile. Full article

(This article belongs to the Special Issue New Developments in Mycology)

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13 pages, 1428 KB

Open AccessArticle

Risk Factors for Endoscopic Gastric Mucosal Lesions: Analysis of Lifestyle, Dietary, and Clinical Determinants in 361 Patients

by Patrick-Lazăr-Dominik Chiciudean, Ana-Maria Filip, Sabrina-Nicoleta Munteanu, Cristian-Ioan Cîmpian, Simona Mocan, Monica Pantea and Anca Elena Negovan

Life 2025, 15(9), 1474; https://doi.org/10.3390/life15091474 - 19 Sep 2025

Abstract

Background/Objectives: Gastric mucosal lesions represent a significant health burden, with Helicobacter pylori infection being the primary cause of chronic gastritis worldwide. However, the role of modifiable lifestyle factors in modulating the severity of gastric lesions remains incompletely characterized, particularly in Eastern European populations. [...] Read more.

Background/Objectives: Gastric mucosal lesions represent a significant health burden, with Helicobacter pylori infection being the primary cause of chronic gastritis worldwide. However, the role of modifiable lifestyle factors in modulating the severity of gastric lesions remains incompletely characterized, particularly in Eastern European populations. This study aimed to analyze the relationship between dietary behaviors, smoking, alcohol consumption, and the severity of endoscopic gastric lesions in Romanian patients. Methods: We conducted a cross-sectional study including 361 patients who underwent upper gastrointestinal endoscopy at Târgu Mureș County Clinical Emergency Hospital between 2019 and 2025. Endoscopic lesion severity was classified on an ordinal scale (0 = normal; 1 = edema/erythema; 2 = erosions; 3 = ulcer/bleeding). Dietary intake was assessed using a validated food frequency questionnaire, with foods classified as pro-inflammatory or protective. Ordinal logistic regression models were used to examine associations between lifestyle factors and the severity of gastric lesions, adjusted for age, sex, and H. pylori status. Results: Among participants (median age 65 years, 46.5% male), 45.2% had clinically significant lesions (≥2). H. pylori infection was present in 31.6% of participants. Current smoking (15.2% of participants) showed a trend toward increased severity of gastric lesions (fully adjusted OR 1.59, 95% CI 0.93–2.71, p = 0.092), though not statistically significant. Among current smokers, 52.7% had clinically significant lesions versus 43.8% among non/former smokers. The smoking–alcohol interaction was not statistically significant (interaction OR = 1.19, 95% CI: 0.34–4.17, p = 0.780). Dietary balance score showed no association with the severity of gastric lesions (OR = 1.061 per 10-unit increase, p = 0.355). NSAID use emerged as the strongest predictor (OR = 1.68, 95% CI 1.01–2.78, p = 0.044). The number of cumulative risk factors correlated significantly with clinically significant lesions (Spearman r = 0.107, p = 0.042), with prevalence increasing from 34.5% in patients with 0–1 factors to 83.3% with 6+ factors. Conclusions: Current smoking showed a trend toward increased severity of gastric lesions in this Romanian cohort, though not reaching statistical significance. NSAID use was the only significant independent predictor. The dose–response relationship between cumulative risk factors and the severity of lesions emphasizes the importance of comprehensive risk assessment and multi-factorial interventions in gastric disease prevention. However, as a cross-sectional study, these associations cannot establish causality and should be confirmed in prospective cohorts. Full article

(This article belongs to the Special Issue Helicobacter pylori: 2nd Edition)

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25 pages, 7213 KB

Open AccessArticle

Interpreting Deep Neural Networks in Diabetic Retinopathy Grading: A Comparison with Human Decision Criteria

by Sangeeta Biswas, Md. Ahanaf Arif Khan, Md. Hasnain Ali, Johan Rohdin, Subrata Pramanik, Md. Iqbal Aziz Khan, Sanjoy Kumar Chakravarty and Bimal Kumar Pramanik

Life 2025, 15(9), 1473; https://doi.org/10.3390/life15091473 - 19 Sep 2025

Abstract

Diabetic retinopathy (DR) causes visual impairment and blindness in millions of diabetic patients globally. Fundus image-based Automatic Diabetic Retinopathy Classifiers (ADRCs) can ensure regular retina checkups for many diabetic patients and reduce the burden on the limited number of retina experts by referring [...] Read more.

Diabetic retinopathy (DR) causes visual impairment and blindness in millions of diabetic patients globally. Fundus image-based Automatic Diabetic Retinopathy Classifiers (ADRCs) can ensure regular retina checkups for many diabetic patients and reduce the burden on the limited number of retina experts by referring only those patients who require their attention. Over the last decade, numerous deep neural network-based algorithms have been proposed for ADRCs to distinguish the severity levels of DR. However, it has not been investigated whether DNN-based ADRCs consider the same criteria as human retina professionals (HRPs), i.e., whether they follow the same grading scale when making decisions about the severity level of DR, which may put the reliability of ADRCs into question. In this study, we investigated this issue by experimenting on publicly available datasets using MobileNet-based ADRCs and analyzing the output of the ADRCs using two eXplainable artificial intelligence (XAI) techniques named Gradient-weighted Class Activation Map (Grad-CAM) and Integrated Gradients (IG). Full article

(This article belongs to the Special Issue Retinal Diseases: From Molecular Mechanisms to Therapeutics)

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18 pages, 3386 KB

Open AccessArticle

Expression of a Tuberculosis-Associated Immunogenic Protein in Escherichia coli

by Gizem Kılıç, Burcu Saygıner, Muhammed Yusuf Yılmaz, Bilge Suyolcu Albayrak, Neda Tatlıoğlu, Ayça Tan, Tanil Kocagoz, Nihan Ünübol and Erkan Mozioğlu

Life 2025, 15(9), 1472; https://doi.org/10.3390/life15091472 - 19 Sep 2025

Abstract

It is estimated that one in four people worldwide carries Mycobacterium tuberculosis bacteria. MPT64 is a protein exclusively secreted by Mycobacterium tuberculosis complex (MTC) bacteria. It serves as a crucial diagnostic marker and plays a role in the bacterium’s survival by modulating the [...] Read more.

It is estimated that one in four people worldwide carries Mycobacterium tuberculosis bacteria. MPT64 is a protein exclusively secreted by Mycobacterium tuberculosis complex (MTC) bacteria. It serves as a crucial diagnostic marker and plays a role in the bacterium’s survival by modulating the host immune response. Consequently, the development of innovative diagnostic tools based on MPT64, as well as the production of high-purity MPT64 protein to support research on tuberculosis pathogenesis and the advancement of novel therapeutic strategies, is of great importance. In this study, optimization experiments were conducted to produce this protein in E. coli with high yield and purity. First, a gBlock was designed by codon optimization and then cloned into a plasmid vector using the LIC method. For more efficient production, E. coli BL21(DE3)-R3-pRARE2 strain, which carries rare tRNAs for rare codons, was used as the host. Five different culture media were tested to maximize protein production, with the highest yield obtained in eBHI medium. The resulting protein yield was 4.9 mg/L. To the best of our knowledge, this study provides the most detailed information on the recombinant production and characterization of MPT64 to date. Therefore, these results contribute important data for future studies on the MPT64 protein. Full article

(This article belongs to the Special Issue Trends in Microbiology 2025)

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18 pages, 2626 KB

Open AccessArticle

Seasonal Dynamics of Macroinvertebrate Communities in Offshore Mussel Aquaculture in the Southern Black Sea: Implications for Diversity

by Eylem Aydemir Çil

Life 2025, 15(9), 1471; https://doi.org/10.3390/life15091471 - 19 Sep 2025

Abstract

This study investigates the taxon composition, seasonal variations, and diversity dynamics of macroinvertebrate communities associated with Mytilus galloprovincialis cultivated in mussel longline systems in the central Black Sea. Monthly sampling conducted between September 2023 and August 2024 yielded a total of 99,719 individuals [...] Read more.

This study investigates the taxon composition, seasonal variations, and diversity dynamics of macroinvertebrate communities associated with Mytilus galloprovincialis cultivated in mussel longline systems in the central Black Sea. Monthly sampling conducted between September 2023 and August 2024 yielded a total of 99,719 individuals representing 20 taxa. The communities were predominantly dominated by amphipods, particularly Jassa marmorata (71%) and Stenothoe monoculoides (28%). Individual abundance peaked in autumn, whereas taxon richness reached its highest levels in summer. ANOVA results revealed significant seasonal differences in diversity indices (p < 0.05). Multivariate analyses, including NMDS and RDA (PCA proxy), indicated distinct seasonal clustering, with pH (41%) and salinity (35 g/kg) identified as the primary environmental drivers of community composition. These findings demonstrate that offshore mussel longline systems function not only as aquaculture infrastructure but also as reef-like artificial habitats that support benthic diversity. The dominance of opportunistic and detritivorous amphipods, along with their sensitivity to environmental gradients, suggests their potential utility as bioindicators for ecological monitoring. Full article

(This article belongs to the Section Animal Science)

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23 pages, 1010 KB

Open AccessReview

Cerebral Vascular Disturbances Following Traumatic Brain Injury: Pathophysiology, Diagnosis, and Therapeutic Perspectives—A Narrative Review

by Nicoleta-Larisa Serban, Gheorghe Ungureanu, Ioan Stefan Florian and Daniela Ionescu

Life 2025, 15(9), 1470; https://doi.org/10.3390/life15091470 - 18 Sep 2025

Abstract

Traumatic brain injury (TBI) is a major global health concern and a leading cause of long-term disability and mortality. While the primary mechanical insult is often the focus of acute care, secondary injury mechanisms—particularly cerebrovascular dysfunction—play a critical role in ongoing neural damage [...] Read more.

Traumatic brain injury (TBI) is a major global health concern and a leading cause of long-term disability and mortality. While the primary mechanical insult is often the focus of acute care, secondary injury mechanisms—particularly cerebrovascular dysfunction—play a critical role in ongoing neural damage and poor outcomes. Increasing research highlights the role of neurovascular changes in TBI pathophysiology. This narrative review compiles evidence from the past decade on mechanisms, diagnostic methods, and treatments related to cerebrovascular dysfunction after TBI. A structured search of PubMed and Embase identified relevant clinical and preclinical studies. Key mechanisms include blood–brain barrier disruption, impaired cerebral autoregulation, microthrombosis, and oxidative stress. Diagnostic tools discussed include perfusion imaging, cerebrovascular reactivity testing, and blood-based biomarkers of vascular injury. Therapeutic strategies targeting the neurovascular unit are categorized by mechanism: anti-inflammatory agents (e.g., celecoxib, minocycline), mitochondrial protectors (e.g., Tanshinone IIA), and vasomodulators (e.g., sildenafil). We propose an integrated therapeutic approach for a multimodal treatment plan that integrates these interventions. The findings emphasize the importance of patient-specific vascular therapies to reduce secondary ischemic injury and enhance neurological recovery. Although promising preclinical data exist, clinical application remains limited. More well-designed trials are needed to confirm the safety and effectiveness of emerging therapies. Full article

(This article belongs to the Special Issue Regulation of Cerebrovascular Resistance in Health and Disease: From Molecules to Humans)

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11 pages, 468 KB

Open AccessArticle

Association Between Physical Performance, Gait Variability, and Fall Risk in Community-Dwelling Older Adults: Predictive Validity of Step-Width Variability for Screening of Fall Risk

by Yongnam Park and Youngsook Bae

Life 2025, 15(9), 1469; https://doi.org/10.3390/life15091469 - 18 Sep 2025

Abstract

Objective: This cross-sectional study aimed to investigate the associations between physical performance, gait variability, and fall risk in community-dwelling older adults. Methods: A total of 446 participants were divided into fall-risk and non-fall-risk groups. Physical performance was assessed using hand grip [...] Read more.

Objective: This cross-sectional study aimed to investigate the associations between physical performance, gait variability, and fall risk in community-dwelling older adults. Methods: A total of 446 participants were divided into fall-risk and non-fall-risk groups. Physical performance was assessed using hand grip strength (HGS), the Timed Up-and-Go (TUG) test, and the Five Times Sit-to-Stand test (5TSTS). Spatiotemporal gait parameters and their coefficients of variation (CV) were measured on a treadmill. Results: Logistic regression revealed that TUG, HGS, step-width CV, and velocity CV were significantly associated with fall risk, whereas age was not. Among these, TUG and step-width CV demonstrated the highest discriminative ability (AUC = 0.708 and 0.715, respectively). Conclusions: Step-width CV was a particularly sensitive indicator of gait stability. These findings suggest that a combination of TUG and step-width CV may help identify older adults at risk of falls, underscoring the importance of gait variability in fall risk screening. Full article

(This article belongs to the Special Issue Physical Medicine and Rehabilitation: Trends and Applications—4th Edition)

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18 pages, 2073 KB

Open AccessArticle

Comparative Efficacy of Reused Medium Cut-Off Dialyzers on Uremic Toxin and Cytokine Clearance: A Randomized Controlled Trial

by Eakalak Lukkanalikitkul, Nichnan Jirayuphat and Sirirat Anutrakulchai

Life 2025, 15(9), 1468; https://doi.org/10.3390/life15091468 - 18 Sep 2025

Abstract

Introduction: Expanded hemodialysis using medium cut-off (MCO) dialyzers effectively removes middle-molecule uremic toxins, comparable to hemodiafiltration, but their single-use designation increases the dialysis costs. This study evaluated the efficacy and safety of reusing two MCO dialyzers available in Thailand. Methods: In this randomized [...] Read more.

Introduction: Expanded hemodialysis using medium cut-off (MCO) dialyzers effectively removes middle-molecule uremic toxins, comparable to hemodiafiltration, but their single-use designation increases the dialysis costs. This study evaluated the efficacy and safety of reusing two MCO dialyzers available in Thailand. Methods: In this randomized controlled trial, hemodialysis patients were assigned to receive treatment with either Theranova^® 500 or Elisio^® 21HX dialyzers. Each dialyzer was reprocessed using peracetic acid and reused for up to 15 sessions. Dialyzer performance was assessed by the reduction ratios (RRs) of solutes, including β2-microglobulin (β2-MG), kappa and lambda free light chains (κ-FLC, λ-FLC), and interleukin-6 (IL-6), at baseline and the 2nd, 5th, 10th, and 15th sessions. Results: Forty-eight patients were enrolled (mean age 63.6 ± 13.7 years; 62.5% male) and randomized into 2 groups with comparable baseline characteristics. RRs for β2-MG, κ-FLC, and λ-FLC were similar between the groups and declined modestly over time after dialyzer reused (β2-MG: 78.2% to 72.5% vs. 77.2% to 74.5%, κ-FLC: 64.6% to 51.3% vs. 58.9% to 49.5%, and λ-FLC: 51.2% to 46.4% vs. 49.4% to 39.2% in the Theranova^® 500 and Elisio^® 21HX groups, respectively). Theranova^® 500 demonstrated significantly higher IL-6 clearance in the 2nd (29.9% vs. 16.0%; p = 0.018) and 5th (23.8% vs. 7.7%, p = 0.031) sessions. It also showed a non-significant trend toward lower dialyzer survival (HR 3.98; p = 0.085) and higher, though clinically acceptable, albumin loss (mean difference 0.56 g/session; p < 0.001), which decreased with reuse. Conclusions: Both MCO dialyzers demonstrated comparable overall performance during reuse. Theranova^® 500 provided better IL-6 clearance with manageable albumin loss. Implementation of high-quality dialyzer reuse protocols may optimize clinical efficacy and patient outcomes while balancing cost, accessibility, and environmental considerations. Full article

(This article belongs to the Section Medical Research)

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18 pages, 1131 KB

Open AccessArticle

Examining the Relationships Between Blood Cadmium, DNA Methylation Biomarker, Telomere Length, and Their Associations with Mortality in U.S. Adults

by Chien-Yu Lin, Ching-Way Chen and Pei-Lun Chu

Life 2025, 15(9), 1467; https://doi.org/10.3390/life15091467 - 18 Sep 2025

Abstract

Cadmium exposure has been associated with shortened telomeres, alterations in DNA methylation patterns, and increased mortality. However, the role of DNA methylation in mediating the relationship between cadmium and telomere dynamics is still unclear. Additionally, it is unknow how telomere dynamics and DNA [...] Read more.

Cadmium exposure has been associated with shortened telomeres, alterations in DNA methylation patterns, and increased mortality. However, the role of DNA methylation in mediating the relationship between cadmium and telomere dynamics is still unclear. Additionally, it is unknow how telomere dynamics and DNA methylation alterations may affect the association between cadmium exposure and mortality outcomes. We utilized data from 8716 National Health and Nutrition Examination Survey (NHANES) participants aged 18 and above, collected between 1999 and 2002, and linked these to mortality outcomes from the National Center for Health Statistics (NCHS) through 2019. In the final model, ln-blood cadmium was significantly and inversely associated with ln-T/S ratio (β = −0.043, 95% CI: −0.059 to −0.027, p < 0.001), while ln-Horvath DNAmTL was strongly and positively associated with ln-T/S ratio (β = 1.782, 95% CI: 1.467 to 2.097, p < 0.001). Moreover, ln-blood cadmium also showed a significant inverse association with ln-Horvath DNAmTL (β = −0.010, 95% CI: −0.014 to −0.006, p < 0.001). Structural equation modeling showed that the association between cadmium and T/S ratio was mediated by Horvath DNAmTL, with a total effect of −0.044, a direct effect of −0.027, and an indirect effect of −0.017. Furthermore, stratified analyses revealed that a 1-unit increase in ln-blood cadmium was associated with higher all-cause mortality, with hazard ratios (HR) of 1.47 for participants with T/S ratio below the median and 1.41 for those above. Similar patterns were observed for cardiovascular (HR = 1.68 vs. 1.30) and cancer mortality (HR = 1.75 vs. 1.42). For Horvath DNAmTL, the association was significant only for all-cause mortality (HR = 1.36 vs. 1.31). However, no significant interactions were detected. In conclusion, our findings suggest that Horvath DNAmTL is associated with the relationship between cadmium and telomere length, suggesting a potential DNA methylation pathway that warrants further longitudinal investigation. Individuals with lower T/S ratios or Horvath DNAmTL appear to be more susceptible to cadmium-related mortality. Further research is necessary to confirm these results. Full article

(This article belongs to the Section Epidemiology)

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22 pages, 6893 KB

Open AccessArticle

Comprehensive Pharmacobotanical and Phytochemical Profiling of Glechoma hederacea L. from Bihor County, North-West Romania

by Manuela Bianca Pasca, Alicia-Denisa Costa, Daniela Gitea, Corina Moisa, Tunde Jurca, Cristina Burlou-Nagy (Fati), Neli Kinga Olah, Annamaria Pallag and Manuel Alexandru Gitea

Life 2025, 15(9), 1466; https://doi.org/10.3390/life15091466 - 18 Sep 2025

Abstract

Glechoma hederacea L. (GH) is an understudied species with significant phytotherapeutic potential, whose botanical characteristics and phytochemical profile have not previously been investigated from Bihor County, North-West Romania, namely Săldăbagiu de Munte (261 m a.s.l.) and Beiuș (553 m a.s.l.). In this study, [...] Read more.

Glechoma hederacea L. (GH) is an understudied species with significant phytotherapeutic potential, whose botanical characteristics and phytochemical profile have not previously been investigated from Bihor County, North-West Romania, namely Săldăbagiu de Munte (261 m a.s.l.) and Beiuș (553 m a.s.l.). In this study, we aimed to examine the species from both pharmacobotanical and phytochemical perspectives focusing on two populations originating from areas with different altitudes, which were selected as representative sites for collecting GH populations. The morphological analysis included both macroscopic and microscopic examinations performed with optical microscopy, complemented by phytochemical profiling and antioxidant activity evaluation. The phenolic profile was analyzed by high-performance liquid chromatography. Total phenolic content was determined using the Folin–Ciocalteu method, while total flavonoid content was assessed by the aluminum chloride colorimetric assay. In addition, the total anthocyanin content was determined, too. The antioxidant properties of the samples were evaluated using cupric ion reducing antioxidant capacity (CUPRAC) and ferric reducing antioxidant power (FRAP) assays. Our results indicate that GH from the higher-altitude area is a rich source of phenolics and exhibits notable antioxidant activity. Among the identified active compounds, apigenin and caffeic acid were found in the highest concentrations. These findings support the potential use of this species in phytopharmaceutical formulations. Full article

(This article belongs to the Special Issue Therapeutic Innovations from Plants and Their Bioactive Extracts)

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13 pages, 1682 KB

Open AccessArticle

Antifatigue Effects of 5-Aminolevulinic Acid Chronic Treatment on Mice

by Chinatsu Ohmori, Eiko Kumamoto, Satoka Kasai, Kotaro Okano, Urara Ota, Atsuko Kamiya, Mitsugu Yamauchi, Kiwamu Takahashi, Masahiro Ishizuka, Kazumi Yoshizawa, Daisuke Yamada and Akiyoshi Saitoh

Life 2025, 15(9), 1465; https://doi.org/10.3390/life15091465 - 18 Sep 2025

Abstract

5-aminolevulinic acid (5-ALA) is a heme precursor involved in mitochondrial activation. A clinical study suggested that 5-ALA supplementation alleviates fatigue in healthy individuals who experience chronic physical tiredness. However, the detailed mechanisms are unknown. Therefore, we investigated the mechanism underlying the antifatigue effect [...] Read more.

5-aminolevulinic acid (5-ALA) is a heme precursor involved in mitochondrial activation. A clinical study suggested that 5-ALA supplementation alleviates fatigue in healthy individuals who experience chronic physical tiredness. However, the detailed mechanisms are unknown. Therefore, we investigated the mechanism underlying the antifatigue effect of 5-ALA using fatigue mouse models. C57BL/6N mice were orally administered 5-ALA hydrochloride or distilled water for 8 weeks. Fatigue mouse models were developed by housing the mice in a cage filled with water for 4 days. Fatigue was evaluated through running distance via a treadmill test. The decrease in the running distance in female mice significantly recovered after 5-ALA administration. 5-ALA administration ameliorated the decreased blood glucose levels in fatigue mouse models. These results suggest that 5-ALA improves fatigue-induced hypoglycemia by promoting the use of fatty acids. PpIX’s concentration in the FCX of the fatigue mouse models significantly increased after 5-ALA treatment. Decreased levels of 3-methoxy-4-hydroxyphenylglycol and noradrenaline (NA) turnover ratio in the FCX recovered to non-fatigue levels after 5-ALA treatment. Therefore, the antifatigue effect of 5-ALA in mice could be related to the activation of the NA neuronal systems in the FCX and the increase in energy production via glycogenesis activation from peripheral adipose tissue. Full article

(This article belongs to the Special Issue Advances in 5-Aminolevulinic Acid Applications in Medical and Healthcare)

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16 pages, 6289 KB

Open AccessArticle

The Clinical Value of the Ferning Test in Monitoring Dry Eye Syndrome in Patients with Sarcoidosis

by Călina Anda Sandu, Cosmin Victor Ganea, Vlad Constantin Donica, Anisia Iuliana Alexa, Ioana Alexandra Sandu, Madalina Ioana Bilha and Camelia Margareta Bogdănici

Life 2025, 15(9), 1464; https://doi.org/10.3390/life15091464 - 18 Sep 2025

Abstract

Background: Sarcoidosis is a systemic inflammatory disease characterized by the formation of non-caseating granulomas, predominantly affecting the lungs and lymph nodes. However, the disease can affect any organ, including the eye, where it most commonly manifests as uveitis and dry eye disease (DED). [...] Read more.

Background: Sarcoidosis is a systemic inflammatory disease characterized by the formation of non-caseating granulomas, predominantly affecting the lungs and lymph nodes. However, the disease can affect any organ, including the eye, where it most commonly manifests as uveitis and dry eye disease (DED). The Ferning Test (FT), a non-invasive method for tear film analysis, offers insight into tear quality. Through this study, we aimed to evaluate the ability of the FT to diagnose and differentiate DED in patients with sarcoidosis. Methods: The study included a sample of 30 patients, divided into three groups, each consisting of 10 patients: one group of patients with sarcoidosis and dry eye disease (S-DED), one group of patients with DED without other systemic pathologies, and a control group of healthy individuals. Tear film samples were collected from the right eye of each participant, without stimulation, by microcapillarity. A drop of tear was spread on a microscope slide, allowed to dry, and then examined under a microscope to analyze the crystallization pattern. Results: Microscopic analysis revealed a significant difference in the structure and morphology of crystallization, as well as in the number of formed branchings, in sarcoidosis patients compared to patients in the other two groups. This finding suggests a distinct alteration in tear film composition in patients with sarcoidosis. Conclusions: Based on these results, the FT represents a valuable and promising tool for the diagnosis of DED associated with sarcoidosis. Being a non-invasive, easy-to-perform, and inexpensive test, it can be widely implemented in any ophthalmology department, opening perspectives for the test to become an important component among the diagnostic elements of dry eye syndrome in patients with sarcoidosis. Full article

(This article belongs to the Special Issue Prognosis and Management of Dry Eye Disease)

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16 pages, 234 KB

Open AccessArticle

Diagnosis and Risk Factors in Retinopathy of Prematurity: A Five-Year Single-Center Descriptive Study

by Fatma Sumer, Mehmet Kenan Kanburoglu, Ozgur Altuntas, Fatma Erbatur Uzun, Isil Uslubas, Feyzahan Uzun and Aytac Kanar

Life 2025, 15(9), 1463; https://doi.org/10.3390/life15091463 - 18 Sep 2025

Abstract

Objective: We aimed to determine the incidence and screening outcomes of retinopathy of prematurity (ROP) in preterm infants managed at a tertiary neonatal intensive care unit (NICU) and to identify associated risk factors. Material and Methods: Medical records of 454 premature infants who [...] Read more.

Objective: We aimed to determine the incidence and screening outcomes of retinopathy of prematurity (ROP) in preterm infants managed at a tertiary neonatal intensive care unit (NICU) and to identify associated risk factors. Material and Methods: Medical records of 454 premature infants who underwent ROP screening between April 2016 and August 2021 were retrospectively analyzed. Infants with birth weight (BW) ≤ 1500 g or ≤32 weeks of gestational age and those with BW > 1500 g or GA > 32 weeks who had an unstable clinical course were included. All of them were born in the same center. Demographic characteristics, potential risk factors for ROP, ocular examination findings, and treatment requirement were recorded. Results: During the five-year study period, ROP was observed in 75 (16.6%) of a total of 454 premature infants with a mean gestational age (GA) of 30.19 ± 2.49 weeks and a mean BW of 2025.15 ± 614.46 g in the NICU. Of these patients, 67 (14.8%) had stage I disease and 8 (1.8%) had stage II disease. Advanced-stage ROP was not detected in any of the cases. The median GA of patients diagnosed with ROP was 29 weeks (22–35) and the median BW was 2100 g (500–3750), which were significantly lower than those without ROP (p < 0.001). When multivariate logistic regression analysis was evaluated with the Wald method, the accuracy rate of the model examining the combined effect of GA, intraventricular hemorrhage (IVH), respiratory distress syndrome (RDS), patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), and surfactant treatment was 85.9%. In this model, gestational age (OR: 0.712, p < 0.001), IVH (OR: 2.915, p = 0.010), RDS (OR: 2.129, p = 0.004), NEC (OR: 3.679, p < 0.001), PDA (OR: 2.434, p = 0.021), and surfactant treatment (OR: 2.271, p = 0.002) were found to be independent risk factors for ROP development. Conclusions: Small GA and low BW are the main risk factors for the development of ROP. The incidence of ROP was found to be lower than similar studies conducted in our country. While severe ROP cases have been reported in more mature infants in Turkey, our study found no treatment-requiring ROP cases, likely reflecting the higher mean GA and BW characteristics of our cohort. Full article

(This article belongs to the Special Issue Pediatric Ophthalmic Pathology—Integrating Clinical and Basic Research)

12 pages, 243 KB

Open AccessArticle

The Role of Microbiology at the 1-Month Surveillance Bronchoalveolar Lavage in the Identification of Complications in the First Year After Lung-Transplantation—A Retrospective Single-Center Experience

by Rocco Francesco Rinaldo, Antonio Curtoni, Mattia Verardo, Silvia Zaffina, Nour Shbaklo, Francesca Sidoti, Francesco Giuseppe De Rosa, Silvia Corcione, Massimo Boffini, Matteo Marro, Cristina Costa and Paolo Solidoro

Life 2025, 15(9), 1462; https://doi.org/10.3390/life15091462 - 17 Sep 2025

Abstract

Acute rejection and infections are the most frequent complications in the first year after lung transplantation, often representing relevant causes of death. There is still no consensus on the ideal strategy for preventing these events, with a still open debate on active bronchoscopic [...] Read more.

Acute rejection and infections are the most frequent complications in the first year after lung transplantation, often representing relevant causes of death. There is still no consensus on the ideal strategy for preventing these events, with a still open debate on active bronchoscopic surveillance protocols vs. clinically mandated ones. The aim of our single-center exploratory study was to evaluate retrospectively the role of microbiology at bronchoalveolar lavage (BAL) at the first month from transplantation in asymptomatic patients in relation to the development of complications up to 12 months from surgery. We collected data from 28 patients who underwent surveillance bronchoscopies according to our center protocol (transbronchial biopsies and BAL at months 1, 4, 8, 12, 18, and 24 post-transplantation) who had a 12-month follow-up. The inclusion criterion was the absence of infiltrates at 1-month post-transplantation chest CT. We excluded patients transplanted due to suppurative diseases of the lung to minimize the pre-transplantation risk factors for infection. We also assessed differences in complications according to the underlying disease. We enrolled 15 patients with interstitial lung diseases (ILDs) and 13 with chronic obstructive pulmonary disease (COPD). Of the 28 patients, 11 had a positive BAL for bacteria. Patients with a positive BAL developed a higher number of pulmonary infectious complications (odds ratio of 18.33, p-value = 0.013 at regression model), with a near significance for moderate–severe pulmonary infections (odds ratio 4.8, p-value = 0.061). We did not find a significant correlation with rejection, cytomegalovirus reactivation, or pseudomembranes. We did not find differences in the rates of complications when grouping subjects according to pre-transplantation disease. Our results suggest a possible role for BAL positivity for bacteria in asymptomatic patients at surveillance bronchoscopy in predicting the development of future infections, warranting a tailored follow-up of patients that considers this data. Larger, multicentric studies are needed to explore and confirm the utility of our findings. Full article

(This article belongs to the Section Medical Research)

22 pages, 588 KB

Open AccessReview

Chloride Homeostasis in Neuronal Disorders: Bridging Measurement to Therapy

by Daniele Arosio and Carlo Musio

Life 2025, 15(9), 1461; https://doi.org/10.3390/life15091461 - 17 Sep 2025

Abstract

Neuronal chloride (Cl⁻) homeostasis is fundamental for brain function, with disruptions increasingly recognized as pathogenic across neurological disorders. This review synthesizes evidence from preclinical models and clinical studies, integrating electrophysiological measurements, molecular analyses, imaging with genetically encoded sensors like ClopHensor, and [...] Read more.

Neuronal chloride (Cl⁻) homeostasis is fundamental for brain function, with disruptions increasingly recognized as pathogenic across neurological disorders. This review synthesizes evidence from preclinical models and clinical studies, integrating electrophysiological measurements, molecular analyses, imaging with genetically encoded sensors like ClopHensor, and behavioral assays. Key findings demonstrate that Cl⁻ dysregulation follows distinct patterns: (1) in epilepsy, KCC2 downregulation converts GABAergic inhibition to excitation, promoting seizures; (2) in Alzheimer’s disease (AD) models, pre-symptomatic KCC2 loss in hippocampus is observed, with KCC2 restoration reversing aspects of cognitive decline; (3) in autism spectrum disorders (ASD), developmental delays in GABA polarity shifts feature due to altered NKCC1/KCC2 ratios; and (4) in Huntington’s disease (HD), striatal neuron-specific Cl⁻ imbalances are linked to motor dysfunction. Methodologically, advanced tools—including subcellular Cl⁻ imaging and high-throughput drug screening—have enabled precise dissection of these mechanisms. Therapeutic strategies targeting Cl⁻ transporters (NKCC1 inhibitors like bumetanide, KCC2 enhancers like CLP290) show preclinical promise but require improved central nervous system (CNS) delivery and selectivity. These findings establish Cl⁻ homeostasis as both a biomarker and therapeutic target, necessitating precision medicine approaches to address heterogeneity in neurological disorders. Full article

(This article belongs to the Special Issue The Contribution of Neurogenetics in Disentangling the Pathophysiology of Neurodegenerative Diseases)

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