Life | September 2025 - Browse Articles

14 pages, 524 KB

Open AccessArticle

Diabetic Kidney Disease: Evidence from Two Selected Cohorts of Patients from Low–Middle and High Income Countries

by Maria Mattiotti, Matteo Righini, Daniele Vetrano, Danilo Ribichini, Valentina Vicennati, Valeria Aiello, Ermanno Notaro, Paolo Belardi, Noemi Bazzanini, Katunzi Mutalemwa, Emmanuel Ndile, Rehema Itambu, Uberto Pagotto, Gaetano Azzimonti, Giuseppe Cianciolo, Irene Capelli and Gaetano La Manna

Life 2025, 15(9), 1429; https://doi.org/10.3390/life15091429 (registering DOI) - 11 Sep 2025

Abstract

Objectives: Diabetic kidney disease (DKD) is the leading cause of kidney failure worldwide. Different phenotypes of DKD are emerging, partially attributable to a better glycemic control, partially to concomitant risk factors for kidney disease. Diabetes belongs to Non-Communicable Diseases (NCDs), but poor data [...] Read more.

Objectives: Diabetic kidney disease (DKD) is the leading cause of kidney failure worldwide. Different phenotypes of DKD are emerging, partially attributable to a better glycemic control, partially to concomitant risk factors for kidney disease. Diabetes belongs to Non-Communicable Diseases (NCDs), but poor data about DKD in Low–Middle Income Countries are currently available. In the present paper we compare two cohorts of patients affected by DKD from Tanzania and from Italy. Study design: Retrospective observational study conducted by NCDs Clinic of Tosamaganga Regional Referral Hospital (Tanzania) and from the Multidisciplinary Diabetological-Nephrological Clinic of Bologna (Italy). Methods: Included patients’ data were analyzed for demographical features, diabetes complications, laboratory findings, and pharmacological therapy at the time of enrollment and after 6-month follow-up. Results: Tanzanian patients were younger (56.65 vs. 67.66 years, p < 0.001), with a higher prevalence of women (66.9% vs. 25.5%, p < 0.001), and showed lower level of BMI (26.39 vs. 30.18 kg/m², p < 0.001). Worsened glycemic control could be observed in the Tanzanian cohort (HbA1c 83.71 vs. 56.92 mmol/mol, p < 0.001) and higher eGFR (70.13 ± 31.93 vs. 52.31 ± 23.37 mL/min, p < 0.001). A sharp reduction in albuminuria was observed in both cohorts with an increase in nephroprotective drugs and better glycemic control. Conclusions: Two phenotypes of diabetic patients have emerged from comparison between two cohorts. Tanzanian patients are mostly female, younger, and with a normal BMI, whereas Italian patients are mainly male, older, and affected by metabolic syndrome and vascular complications. Therapy implementation is associated with a delayed decline of eGFR and downgrading of albuminuria at 6-month follow-up. Full article

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

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18 pages, 2690 KB

Open AccessArticle

Ferreting Out the Effects of Neonatal Hypoxia–Ischemia and Sex on Ferret Cortical Gyrification

by Olivia C. Brandon, Olivia R. White, Kylie A. Corry, Andreea Stanescu, Arian Ariaye, Daniel H. Moralejo, Janessa B. Law, Sarah E. Kolnik, Sandra E. Juul and Thomas R. Wood

Life 2025, 15(9), 1428; https://doi.org/10.3390/life15091428 - 11 Sep 2025

Abstract

Gyrification, the folding of the cerebral cortex, plays a crucial role in brain development and function. Perinatal hypoxia–ischemia (HI) is a leading cause of neonatal brain injury, affecting cortical folding that can be measured by the gyrification index (GI). Using a late-preterm ferret [...] Read more.

Gyrification, the folding of the cerebral cortex, plays a crucial role in brain development and function. Perinatal hypoxia–ischemia (HI) is a leading cause of neonatal brain injury, affecting cortical folding that can be measured by the gyrification index (GI). Using a late-preterm ferret model, our objective was to explore the relationships between HI injury, GI changes, and behavior, as well as the potential moderating effects of sex and treatment. Animals received 3 mg/kg E. coli lipopolysaccharide and underwent bilateral carotid artery ligation followed by alternating hypoxia and hyperoxia (HIH) and were randomized to saline vehicle (n = 25), erythropoietin (n = 20), therapeutic hypothermia (6 h at 33.5 °C, n = 20), and uridine monophosphate (n = 6), with n = 20 unexposed littermates serving as controls. Early reflex testing, CatWalk gait analysis, open-field behavior, and an open-water swim test were performed. Average, peak, motor, and somatosensory strip GIs were then assessed using ex vivo MRI. In control animals, males had lower GI than females; however, HIH exposure resulted in male GI being more similar to females, where HIH animals had significantly higher average GI than controls (p = 0.02). Adjusting for brain volume and injury, GIs in motor and somatosensory areas were associated with faster reflex outcomes in males but not females. In female controls, motor and somatosensory GIs were associated with increased anxiety-like behaviors, such as spending less time in open water during the swim test. By comparison, in male controls, higher GI was associated with decreased anxiety-like behaviors, including higher exploration index in the swim test. These sex-specific relationships between GI and behavior were lost with HIH injury. Treatment did not meaningfully restore the relationship between GI and behavior after HIH, but targeting this outcome may be an important measure for use in future neuroprotection studies in the ferret. Full article

(This article belongs to the Section Medical Research)

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31 pages, 1179 KB

Open AccessArticle

Metabolic Responses of Newly Isolated Microalgal Strains Cultured in an Open Pond Simulating Reactor Under Balanced Conditions and Nutrient Limitation

by Panagiotis Dritsas and George Aggelis

Life 2025, 15(9), 1427; https://doi.org/10.3390/life15091427 - 11 Sep 2025

Abstract

Microalgal strains—Picochlorum costavermella VAS2.5, Picochlorum oklahomense PAT3.2B and SAG4.4, Microchloropsis gaditana VON5.3, and Nephroselmis pyriformis PAT2.7—were evaluated in an Open Pond Simulating Reactor (OPSR) under varied conditions to assess their biomass yield and high-value metabolite production. Overall, the strains produced 269.1–523.0 mg/L [...] Read more.

Microalgal strains—Picochlorum costavermella VAS2.5, Picochlorum oklahomense PAT3.2B and SAG4.4, Microchloropsis gaditana VON5.3, and Nephroselmis pyriformis PAT2.7—were evaluated in an Open Pond Simulating Reactor (OPSR) under varied conditions to assess their biomass yield and high-value metabolite production. Overall, the strains produced 269.1–523.0 mg/L of biomass under balanced growth conditions in modified Artificial Seawater, continuous illumination, and pH 8.5. Phosphorus limitation notably enhanced yields for SAG4.4 and PAT2.7 (529.0 ± 52.2 mg/L and 452.2 ± 21.0 mg/L, respectively). Conversely, nitrogen limitation reduced productivity. In most strains the glycolipid plus sphingolipid fraction was dominant. Significant quantities of 20:5(n-3) were traced in the cultures of VAS2.5 and VON5.3, while the PAT3.2B and SAG4.4 strains produced considerable amounts of 18:3(n-3). In contrast, the most interesting fatty acid synthesized by PAT2.7 was 16:1(n-7), which was also detected in significant quantities in VAS2.5 and VON5.3. Polysaccharide content remained stable across conditions (10–15%), and protein levels reached 45–50% under control and phosphorus-limited environments. Pigment synthesis peaked at control conditions. Overall, the biochemical profiles of these strains revealed their potential for use primarily as feed additives in the aquaculture sector. Full article

(This article belongs to the Section Microbiology)

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Graphical abstract

28 pages, 1161 KB

Open AccessReview

Arrhythmias in Rheumatoid Arthritis: A Call for a Multidisciplinary Team

by Veronica Ungurean, Diana Elena Costan, Monica Claudia Dobos, Anca Ouatu, Paula Cristina Morariu, Alexandru Florinel Oancea, Maria Mihaela Godun, Diana-Elena Floria, Dragos Traian Marcu, Genoveva Livia Baroi, Silviu Marcel Stanciu, Anton Knieling, Daniela Maria Tanase, Codrina Ancuta and Mariana Floria

Life 2025, 15(9), 1426; https://doi.org/10.3390/life15091426 - 11 Sep 2025

Abstract

Background: Rheumatoid arthritis is the most prevalent systemic inflammatory disease, mainly affecting the synovial tissue of small and large joints, also associated with significant extra-articular manifestations. Throughout the progression of the disease, cardiac structures may be affected, including the conducting system, myocardium, endocardium, [...] Read more.

Background: Rheumatoid arthritis is the most prevalent systemic inflammatory disease, mainly affecting the synovial tissue of small and large joints, also associated with significant extra-articular manifestations. Throughout the progression of the disease, cardiac structures may be affected, including the conducting system, myocardium, endocardium, coronary arteries, and valves, potentially resulting in a higher incidence of cardiac arrhythmias. Methods: We performed a narrative review of the most recent studies that highlight the epidemiology, pathophysiology, diagnosis, and management of arrhythmias occurring in patients with rheumatoid arthritis. Furthermore, we examined the impact of disease-modifying antirheumatic drugs (DMARDs)—including conventional synthetic (csDMARDs), biologic (bDMARDs), and targeted synthetic agents (tsDMARDs)—on cardiac electrophysiology. Results: Cardiac immune cells may influence arrhythmogenesis through non-canonical and inflammatory mechanisms by modifying myocardial tissue architecture or by interacting with cardiomyocytes, potentially altering their electrical function. Conclusions: This review emphasizes the essential role of a multidisciplinary approach integrating rheumatology and cardiology expertise in the screening and management of arrhythmias in patients with rheumatoid arthritis. Full article

(This article belongs to the Special Issue Interdisciplinarity in Cardiovascular Diseases: From Pathophysiology to Diagnosis and Treatment—4th Edition)

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18 pages, 1758 KB

Open AccessSystematic Review

Does Nitrate Supplementation Improve Muscle Strength, Power, and Sprint Performance in Females? A Systematic Review and Meta-Analysis

by Fanhao Meng, Yuhang Liu, Bopeng Qiu and Juan Li

Life 2025, 15(9), 1425; https://doi.org/10.3390/life15091425 - 11 Sep 2025

Abstract

Background: Inorganic nitrate (NO₃⁻) may enhance muscle contractility and blood flow via nitric oxide production, offering potential ergogenic benefits. However, most studies have focused on males, and its effects in females during high-intensity, short-duration exercise remain unclear. Objective: This review [...] Read more.

Background: Inorganic nitrate (NO₃⁻) may enhance muscle contractility and blood flow via nitric oxide production, offering potential ergogenic benefits. However, most studies have focused on males, and its effects in females during high-intensity, short-duration exercise remain unclear. Objective: This review assessed the acute effects of nitrate supplementation on muscle strength, power, and sprint performance in healthy females. Methods: A comprehensive literature search was conducted in PubMed, Web of Science, Scopus, SPORTDiscus, and Cochrane CENTRAL, from inception to July 2025. Randomized controlled trials (RCTs) that examined the effects of oral inorganic nitrate (e.g., beetroot juice or nitrate salts) in healthy females were included. Eligible studies involved (i) healthy women aged 18–30, (ii) nitrate supplementation vs. placebo, and (iii) outcome measures of muscle strength (e.g., MVC), power (e.g., countermovement jump height, peak power), or sprint performance (e.g., sprint time or repeated sprint ability). Studies were excluded if they did not report sex-specific results or lacked relevant physical performance outcomes. Random-effects meta-analyses were conducted for each outcome. Results: Nitrate supplementation had small, non-significant effects on muscle strength (SMD = 0.10, 95% CI: −0.10 to 0.30, p > 0.05) and sprint performance (SMD = 0.14, 95% CI: −0.13 to 0.41, p > 0.05). A statistically significant, small-to-moderate improvement was observed in power (SMD = 0.38, 95% CI: 0.06 to 0.69, p < 0.05). Sensitivity analyses confirmed robustness of the power result. The certainty of evidence ranged from low to moderate based on the GRADE assessment. Conclusions: Inorganic nitrate supplementation may modestly enhance power in healthy females but does not appear to significantly improve muscle strength or sprint performance. These findings highlight the importance of sex-specific research in sports nutrition to guide targeted supplementation strategies for female athletes. Full article

(This article belongs to the Special Issue Focus on Exercise Physiology and Sports Performance: 2nd Edition)

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14 pages, 2000 KB

Open AccessArticle

Following-Up Micro-Rheological and Microcirculatory Alterations During the Early Wound Healing Phase of Local and Rotated Musculocutaneous Flaps in Rats

by Gergo Kincses, Laszlo Adam Fazekas, Adam Varga, Adam Attila Matrai, Nguyen Xuan Loc, Kincso Barabasi, Anna Orsolya Flasko, Tamas Juhasz, Abel Molnar and Norbert Nemeth

Life 2025, 15(9), 1424; https://doi.org/10.3390/life15091424 - 11 Sep 2025

Abstract

In reconstructive surgery, usage of different flaps is essential to cover tissue defects. Twisting, stretching or damaging the vascular pedicle may jeopardize the flaps’ viability. The aim of our experiment was to monitor tissue perfusion parameters of local versus rotated musculocutaneous flaps. In [...] Read more.

In reconstructive surgery, usage of different flaps is essential to cover tissue defects. Twisting, stretching or damaging the vascular pedicle may jeopardize the flaps’ viability. The aim of our experiment was to monitor tissue perfusion parameters of local versus rotated musculocutaneous flaps. In rats, musculus cutaneus maximus-based muscle–skin flaps were prepared bilaterally: one was sutured back to its original position, while the other flap was rotated to the ventral chest region (Flap group). In the Control group, flaps were not prepared. Tissue microcirculation was monitored intraoperatively, and on the 7th and 14th postoperative days. Blood samples were taken for testing hematological and hemorheological parameters. At the end of the observation period, biopsies were taken for biomechanical (tensile strengths) and histological investigations. We found that leukocyte and platelet counts significantly increased in the Flap group, while erythrocyte deformability decreased and aggregation increased. Although both local and rotated flaps survived and wound healing progressed well, in microcirculatory recordings, hypoperfusion and visible red blood cell aggregates were seen mostly in the rotated flaps. The rotated flaps were biomechanically weaker compared to local flaps or intact skin regions. This new model seems to be suitable for studying further flap pathophysiology focusing on tissue perfusion. Full article

(This article belongs to the Special Issue Blood Rheology: Insights & Innovations)

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16 pages, 1652 KB

Open AccessArticle

Evaluation of Dry Eye Disease Signs, Symptoms, and Vision-Related Quality of Life in Patients with Systemic Lupus Erythematosus

by Wojciech Luboń, Anna Agaś-Lange, Ewa Mrukwa-Kominek, Adrian Smędowski and Dorota Wyględowska-Promieńska

Life 2025, 15(9), 1423; https://doi.org/10.3390/life15091423 - 10 Sep 2025

Abstract

Dry eye disease (DED) represents one of the most prevalent ocular manifestations associated with systemic lupus erythematosus (SLE), with reported incidence rates ranging from 15% to 35%. DED constitutes a multifactorial condition that significantly impairs both visual function and health-related quality of life. [...] Read more.

Dry eye disease (DED) represents one of the most prevalent ocular manifestations associated with systemic lupus erythematosus (SLE), with reported incidence rates ranging from 15% to 35%. DED constitutes a multifactorial condition that significantly impairs both visual function and health-related quality of life. The objective of this study was to assess the impact of DED symptoms on vision-related quality of life in patients diagnosed with SLE, employing the Ocular Surface Disease Index (OSDI) as a disease-specific instrument. Additionally, the study aimed to evaluate correlations between clinical diagnostic tests and OSDI scores, and to determine the frequency of abnormalities affecting individual ocular structures. This study included 35 SLE patients, identifying DED in 37.1%. Common ophthalmic abnormalities included lens opacification (22.9%) and hyaloid degeneration (34.3%). Astigmatism (>0.50 D cyl) was prevalent (60.0%), being significantly higher in DED patients. While visual acuity and intraocular pressure were comparable, DED patients showed significantly lower Schirmer I test values, reduced tear break-up time, and higher van Bijsterveld scores, indicating impaired tear film and surface integrity. OSDI scores were significantly elevated in the DED group, with 51.4% reporting moderate to severe dysfunction. Strong, statistically significant correlations between the OSDI and objective tear film parameters confirmed a robust association between subjective symptoms and clinical signs. These findings highlight the significant impact of DED on visual function in SLE patients, underscoring the importance of routine ophthalmological evaluation and timely intervention. Full article

(This article belongs to the Section Medical Research)

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18 pages, 632 KB

Open AccessReview

GLP-1 Receptor Agonists in Mood Disorders: A Psychiatric Perspective

by Pietro Carmellini, Alessandro Cuomo, Maria Beatrice Rescalli and Andrea Fagiolini

Life 2025, 15(9), 1422; https://doi.org/10.3390/life15091422 - 10 Sep 2025

Abstract

Mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD), are among the leading causes of disability worldwide and are frequently associated with treatment resistance, functional impairment, and high comorbidity with metabolic dysfunction. Increasing evidence implicates insulin resistance (IR) as a key [...] Read more.

Mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD), are among the leading causes of disability worldwide and are frequently associated with treatment resistance, functional impairment, and high comorbidity with metabolic dysfunction. Increasing evidence implicates insulin resistance (IR) as a key pathophysiological factor linking metabolic and psychiatric illness. IR is associated with chronic low-grade inflammation, hypothalamic–pituitary–adrenal (HPA) axis dysregulation, impaired neuroplasticity, mitochondrial dysfunction, and altered reward processing mechanisms that may contribute to core depressive features such as anhedonia, cognitive slowing, and emotional dysregulation. These processes are further exacerbated by the metabolic side effects of many psychotropic medications, creating a self-perpetuating cycle that worsens both psychiatric and physical health outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed for type 2 diabetes and obesity, have emerged as promising candidates to address this metabolic–psychiatric interface. Beyond improving glycemic control and promoting weight loss, GLP-1 RAs exert central actions relevant to mood disorders, including modulation of dopaminergic reward pathways, enhancement of hippocampal neurogenesis, attenuation of neuroinflammation, and regulation of appetite and energy balance. Preclinical studies demonstrate that GLP-1 RAs reduce microglial activation, promote hippocampal neurogenesis, and normalize stress-induced behavioral changes. Early clinical trials in patients with metabolic disorders suggest improvements in depressive symptoms, quality of life, and cognitive function, with some effects independent of weight loss or glycemic outcomes. Observational evidence also indicates reduced antidepressant use and psychological distress in diabetic and obese populations receiving GLP-1 RAs. While these findings are promising, large randomized controlled trials in primary psychiatric populations are lacking. Key challenges include clarifying dose–response relationships, disentangling central from peripheral effects, and addressing safety and adherence concerns in individuals with comorbid psychiatric conditions. Future research should focus on biomarker-informed stratification, comparative trials with standard treatments, and integration of GLP-1 RAs into multimodal care frameworks. Overall, GLP-1 RAs represent a biologically plausible and clinically relevant approach to bridging metabolic and psychiatric care, with the potential to improve outcomes in patients with mood disorders who carry a high metabolic burden. Full article

(This article belongs to the Special Issue Pharmacology, Diagnosis and Treatments of Psychiatric Diseases)

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22 pages, 3274 KB

Open AccessArticle

Non-Union Treatment in the Shoulder, Arm, Wrist, and Fingers: A Multicentre Retrospective Study Comparing Conventional Treatment with the Human Allogeneic Cortical Bone Screw (Shark Screw^®)

by Elisabeth Huber, Gerd Jakob, Wolfgang Palle, Gudrun H. Borchert and Klaus Pastl

Life 2025, 15(9), 1421; https://doi.org/10.3390/life15091421 - 10 Sep 2025

Abstract

Successful non-union therapy consists of a combination of optimizing mechanical stability and activating biological factors. The conventional method for treating non-union is debridement and stabilization with metal hardware. The human allogeneic cortical bone screw (Shark Screw^®) merges human cortical bone properties [...] Read more.

Successful non-union therapy consists of a combination of optimizing mechanical stability and activating biological factors. The conventional method for treating non-union is debridement and stabilization with metal hardware. The human allogeneic cortical bone screw (Shark Screw^®) merges human cortical bone properties with screw stability, addressing non-union surgery principles by integrating mechanical and biological aspects. The objective of this retrospective study was to compare the clinical and radiological outcomes of the conventional method with those of the new method using the Shark Screw^®. This retrospective, multicentre, level III study included 41 patients with non-unions in upper extremities, 11 treated with the conventional method (metal hardware ± graft), and 30 patients with the Shark Screw^® (±graft). Patient demographics, non-union location, autograft and/or allograft use, follow-up time, complications, union rate, time to union, and time to return to work were recorded. Follow-up was 18 months in the conventional group and 10 months in the Shark Screw^® group. The union rate was 72.7% in the conventional group and 96.7% in the Shark Screw^® group. Time to union was significantly shorter in the Shark Screw^® group. In the conventional group, the complication rate was 36%, and it was 3.4% in the Shark Screw^® group. Hardware removal in the conventional group was 64%, and it was 0% in the Shark Screw^® group. The Shark Screw^® presents a reliable option for treating non-unions in the shoulder, forearm, hand, and fingers. Full article

(This article belongs to the Special Issue Advanced Strategies in Fracture Treatments)

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15 pages, 2693 KB

Open AccessReview

Conservation of Domestic Animal Genetic Resources in China: Overview of the Status, Activities, Policies, and Challenges

by Xiao Chen, Jian Lu, Wenqiang Cheng, Ming Xue and Fuqing Yu

Life 2025, 15(9), 1420; https://doi.org/10.3390/life15091420 - 10 Sep 2025

Abstract

Livestock and poultry biodiversity constitutes an essential element of global biological diversity, playing a pivotal role in sustaining human livelihood and socioeconomic development. Domestic animal genetic resources in China are abundant and various. Especially, local breeds have strong adaptability to the environment and [...] Read more.

Livestock and poultry biodiversity constitutes an essential element of global biological diversity, playing a pivotal role in sustaining human livelihood and socioeconomic development. Domestic animal genetic resources in China are abundant and various. Especially, local breeds have strong adaptability to the environment and exhibit excellent traits. They are the material foundation for both the original innovation in agricultural technology and the development of modern animal husbandry. Conservation of animal genetic resources is the primary action for sustainable use and development of domestic animals. Globally, many national and international institutions have initiated a variety of conservation measures, legislation, and technical strategies. China has likewise undertaken relevant initiatives. In this paper, we summarize the current situation of domestic animal resources in China, including the current status of domestic animals, the conservation measurements, the sustainable utilization, the management policies, challenges, and suggestions for the conservation of domestic animal resources. The sustainable use and protection work on domestic animals can be incorporated with the issues of food security and sustainability, the protection of the environment and climatic change, concepts in which societal interest is continuously increasing. Full article

(This article belongs to the Section Animal Science)

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15 pages, 4131 KB

Open AccessArticle

Deciphering the Complex Intertwining Between Cytopenia and Transfusion Needs After CAR-T-Cell Therapy for B-Cell Malignancies

by Claudio Pellegrino, Eugenio Galli, Patrizia Chiusolo, Rossella Ladiana, Caterina Giovanna Valentini, Marcello Viscovo, Federica Sorà, Simona Sica and Luciana Teofili

Life 2025, 15(9), 1419; https://doi.org/10.3390/life15091419 - 9 Sep 2025

Abstract

Immune-effector-cell-associated hematotoxicity has emerged as the most common CAR-T-cell-related complication in the real-world setting. Therefore, transfusion of blood components remains unavoidable in many patients treated with CAR-T cells to alleviate symptomatic anemia and prevent major bleeding events. This study investigates predictive factors associated [...] Read more.

Immune-effector-cell-associated hematotoxicity has emerged as the most common CAR-T-cell-related complication in the real-world setting. Therefore, transfusion of blood components remains unavoidable in many patients treated with CAR-T cells to alleviate symptomatic anemia and prevent major bleeding events. This study investigates predictive factors associated with the transfusion requirement in patients receiving anti-CD19 CAR-T-cell therapy for B-cell malignancies in a real-world setting and the potential correlation between transfusion needs, ICAHT, and long-term survival outcomes. Among 90 investigated patients, 51 (56.7%) received at least one transfusion in the three months post-infusion (33.4% received only RBC concentrates, and 23.4% received both RBC and platelet transfusions). The highest transfusion needs occurred in the first month post-infusion, with 50 transfused patients (55.5%). Early transfusion-requiring cytopenia was associated with pre-infusion altered bone marrow function, patients-related factors, including female sex, and acute inflammatory toxicities. The incidence of late cytopenia was mainly predicted by the need for pre-infusion transfusion support. Patients receiving platelet transfusions were characterized by an inferior progression-free (p = 0.013) and overall survival (p = 0.005). CAR-T-cell-treated patients can experience a high transfusion burden, impairing their quality of life, potentially affecting survival outcomes, and resulting in overutilization of clinical resources Full article

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27 pages, 5458 KB

Open AccessArticle

Therapeutic Potential of Astrocyte-Derived Extracellular Vesicles in Post-Stroke Recovery: Behavioral and MRI-Based Insights from a Rat Model

by Yessica Heras-Romero, Axayácatl Morales-Guadarrama, Luis B. Tovar-y-Romo, Diana Osorio Londoño, Roberto Olayo-González and Ernesto Roldan-Valadez

Life 2025, 15(9), 1418; https://doi.org/10.3390/life15091418 - 9 Sep 2025

Abstract

Astrocyte-derived extracellular vesicles (ADEVs) have emerged as promising neuroprotective agents for ischemic stroke. In this study, we evaluated the therapeutic potential of hypoxia-conditioned ADEVs (HxEVs) administered intracerebroventricularly in a rat model of transient middle cerebral artery occlusion (tMCAO). Serial magnetic resonance imaging (MRI) [...] Read more.

Astrocyte-derived extracellular vesicles (ADEVs) have emerged as promising neuroprotective agents for ischemic stroke. In this study, we evaluated the therapeutic potential of hypoxia-conditioned ADEVs (HxEVs) administered intracerebroventricularly in a rat model of transient middle cerebral artery occlusion (tMCAO). Serial magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) was performed at 1, 7, 14, and 21 days post-stroke. HxEV treatment produced a significant reduction in infarct volume from day 1, sustained through day 21, and was accompanied by improvements in motor and sensory recovery. DTI analyses showed progressive normalization of fractional anisotropy (FA) and radial diffusivity (RD), particularly in the corpus callosum and striatum, reflecting microstructural repair. In contrast, mean diffusivity (MD) was less sensitive to these treatment effects. Regional differences in therapeutic response were evident, with earlier and more sustained recovery in the corpus callosum than in other brain regions. Histological findings confirmed greater preservation of dendrites and axons in HxEV-treated animals, supporting the role of these vesicles in accelerating post-stroke neurorepair. Together, these results demonstrate that hypoxia-conditioned ADEVs promote both structural and functional recovery after ischemic stroke. They also highlight the value of DTI-derived biomarkers as non-invasive tools to monitor neurorepair. The identification of region-specific therapeutic effects and the validation of reliable imaging markers provide a strong foundation for future research and development. Full article

(This article belongs to the Special Issue Innovative Applications of Extracellular Vesicles: From Diagnostics to Drug Delivery)

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15 pages, 2988 KB

Open AccessArticle

Prophage Activation: An In Silico Platform for Identifying Prophage Regulatory Elements to Inform Phage Engineering Against Drug-Resistant Bacteria

by Saher Musrrat, Zequan Han, Kai Wang, Yunhai Huang, Yanhui Xiang, Sen Liu and Wen Yin

Life 2025, 15(9), 1417; https://doi.org/10.3390/life15091417 - 9 Sep 2025

Abstract

Multidrug-resistant bacterial infections pose a severe global health threat, highlighting the urgent need for innovative therapeutic options beyond traditional antibiotics. Phage therapy, which employs bacteriophages to infect and eradicate pathogenic bacteria, specifically offers a promising solution. However, the lack of well-characterized therapeutic phages [...] Read more.

Multidrug-resistant bacterial infections pose a severe global health threat, highlighting the urgent need for innovative therapeutic options beyond traditional antibiotics. Phage therapy, which employs bacteriophages to infect and eradicate pathogenic bacteria, specifically offers a promising solution. However, the lack of well-characterized therapeutic phages has limited their broader clinical use. A critical aspect of activating the lytic potential of dormant prophages involves the strategic manipulation of transcription factor binding sites (TFBS), which function as pivotal regulatory nodes governing the transition between lysogenic dormancy and lytic activation. Our platform utilizes advanced bioinformatics tools to accurately identify and analyze TFBS, facilitating the targeted redesign or replacement of these sites to disrupt host-mediated repression. By systematically simulating modifications of these regulatory ‘switches,’ our platform computationally predicts reduced repressor activity, suggesting the potential for prophage activation and bacterial cell lysis. This novel methodology not only broadens the spectrum of therapeutic bacteriophages but also establishes a basis for individualized phage-based therapies, presenting a robust strategy to address the escalating challenge of antibiotic-resistant infections. By enabling the precise identification and engineering of TFBS, our platform signifies a transformative advancement in phage biology, effectively bridging the divide between computational analysis and therapeutic application. Full article

(This article belongs to the Special Issue Synthetic Genetic Elements, Devices, and Systems: 2nd Edition)

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11 pages, 539 KB

Open AccessArticle

Risk Factors for Hypertension in Polycystic Ovary Syndrome: Evidence from a Retrospective Study

by Ralitsa Robeva, Atanaska Elenkova, Georgi Kirilov, Krassimir Kalinov and Sabina Zacharieva

Life 2025, 15(9), 1416; https://doi.org/10.3390/life15091416 - 8 Sep 2025

Abstract

Background: Polycystic ovarian syndrome (PCOS) is a common female endocrinopathy, but its interrelations with arterial hypertension (AH) are still debatable. Therefore, the present study aims to explore the risk factors for hypertension in a large group of well-phenotyped women with PCOS. Methods [...] Read more.

Background: Polycystic ovarian syndrome (PCOS) is a common female endocrinopathy, but its interrelations with arterial hypertension (AH) are still debatable. Therefore, the present study aims to explore the risk factors for hypertension in a large group of well-phenotyped women with PCOS. Methods: The data of 1047 Bulgarian PCOS patients diagnosed according to Rotterdam criteria in the period 2005–2022 were studied retrospectively. The risk factors for hypertension were estimated in the PCOS women with different phenotypes. Results: The prevalence of AH was 17.6% among the PCOS women, with 4.2% of them being on antihypertensive treatment. The AH prevalence was increased in women with the “classic” phenotype compared to others (18.9% vs. 12.9%, p = 0.037). The most important risk factors associated with hypertension were the presence of diabetes mellitus type 2 (DMT2), obesity, family history of AH, and age ≥ 30 years (p < 0.001). The prevalence of impaired glucose tolerance (IGT) but not impaired fasting glucose was also related to the development of AH. Conclusions: The leading independent factors associated with hypertension in PCOS patients are the presence of DMT2, IGT, obesity, family history of hypertension, and age, but not the degree of hyperandrogenism. Population-based studies, including distinct ethnic groups, are needed to reveal the pathophysiology and the optimal clinical management of AH in PCOS. Full article

(This article belongs to the Special Issue Gynecological Endocrinology: From Physiological Mechanisms to Clinical Practice)

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15 pages, 305 KB

Open AccessReview

The Role of Spectacle Lenses in the Control and Management of Myopia Progression: A Narrative Review

by Livio Vitiello, Filippo Lixi, Valerio Calabresi, Mario Troisi, Ilaria De Pascale, Alfonso Pellegrino, Giulia Coco, Aldo Vagge and Giuseppe Giannaccare

Life 2025, 15(9), 1415; https://doi.org/10.3390/life15091415 - 8 Sep 2025

Abstract

The number of people affected by myopia worldwide is estimated to reach two billion and to further grow. Therefore, numerous treatment approaches (pharmacological, behavioral, environmental, and optical) have been put forth to slow the progression of myopia, especially in children. Among these, spectacle [...] Read more.

The number of people affected by myopia worldwide is estimated to reach two billion and to further grow. Therefore, numerous treatment approaches (pharmacological, behavioral, environmental, and optical) have been put forth to slow the progression of myopia, especially in children. Among these, spectacle lenses represent a straightforward and less intrusive therapeutic approach for children and their parents. For this reason, in recent years, several spectacle lenses with different technologies have been developed to slow myopia progression and enhance the quality of life for myopic children, thus trying to reduce the related health care burden. According to the published scientific literature, three different types of spectacle lenses are currently the most validated optical options for myopia management: (i) Defocus Incorporated Multiple Segments lenses (DIMS), (ii) Highly Aspherical Lenslet Target lenses (HALT) and (iii) Cylindrical Annular Refractive Elements (CARE) lenses. The aim of this narrative review is to exclusively discuss the scientific evidence of these three different spectacles lenses, and to point out the potential benefits and drawbacks in their use for myopia control and management. Full article

(This article belongs to the Section Medical Research)

17 pages, 1281 KB

Open AccessArticle

Jinyuan 601 a Novel High-Protein Soybean Variety with Improved Agronomic Traits and Nutritional Quality

by Xinyu Wei, Xiaoguang Yu, Xiangjin Chen, Shaobin Cui, Jieyin Cui, Ran Wei, Henan Diao, Honglei Ren, Wencheng Lu and Xiaodong Tang

Life 2025, 15(9), 1414; https://doi.org/10.3390/life15091414 - 8 Sep 2025

Abstract

The global demand for high-protein soybeans is rapidly increasing, driven by the growing popularity of healthy foods and plant-based protein products. To address this demand, a novel high-protein soybean variety, Jinyuan 601, was developed through a systematic breeding program. This study details the [...] Read more.

The global demand for high-protein soybeans is rapidly increasing, driven by the growing popularity of healthy foods and plant-based protein products. To address this demand, a novel high-protein soybean variety, Jinyuan 601, was developed through a systematic breeding program. This study details the breeding process, agronomic characteristics, and performance evaluation of Jinyuan 601, which was derived from a cross between Heihe YX10-534 (female parent) and Heihe No. 45 (male parent). The variety was selected over multiple generations (F₂–F₇) and stabilized as Heihe 18-250, demonstrating excellent quality, upright stalks, and resistance to diseases and pests. Jinyuan 601 exhibits a protein content of 43.66% and a fat content of 17.21%, meeting the standard for high-protein soybeans (≥43% protein). It has a growth period of 111 days, with a plant height of 93.2 cm, and shows moderate resistance to soybean mosaic virus (SMV). Yield trials conducted over two years (2021–2022) produced an average of 2292 kg ha⁻¹, representing a 3.0% increase over the control variety (Huajiang No. 2). This variety holds significant potential for applications in health foods, plant-based products, and sustainable agriculture, contributing to food security and reducing reliance on soybean imports. Full article

(This article belongs to the Section Plant Science)

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14 pages, 989 KB

Open AccessSystematic Review

The Effect of Physical Exercise on Non-Oncological Musculoskeletal Chronic Pain and Its Associated Biomarkers: Systematic Review on Randomized Controlled Trials

by Israel Castillo-Bellot, Ana María Peiró and Thomas Zandonai

Life 2025, 15(9), 1413; https://doi.org/10.3390/life15091413 - 8 Sep 2025

Viewed by 87

Abstract

Objective: Non-oncological musculoskeletal chronic pain has a high prevalence and is a cause of disability, reduced quality of life, and significant economic impact. Physical exercise is presented as a treatment option; however, pain measurement remains a challenge, and various biomarkers are potential candidates [...] Read more.

Objective: Non-oncological musculoskeletal chronic pain has a high prevalence and is a cause of disability, reduced quality of life, and significant economic impact. Physical exercise is presented as a treatment option; however, pain measurement remains a challenge, and various biomarkers are potential candidates to objectify this process. This systematic review aims to study the effect of physical exercise on non-oncological musculoskeletal chronic pain and its associated biomarkers based on randomized controlled trials. Methods: A search for randomized controlled trials was conducted in the PubMed, Web of Science, and Scopus databases based on the established inclusion and exclusion criteria, along with a risk of bias assessment following the recommendations of the Cochrane Collaboration. Results: Five studies investigated various physical exercise interventions and their effects on biomarkers linked to chronic pain. Exercise consistently reduced self-reported pain, though no clear overall correlation with biomarker changes was found. However, significant associations emerged for specific biomarkers, particularly inflammatory markers and those identified through structural and functional brain imaging, suggesting potential mechanisms underlying pain modulation. Conclusions: The findings suggest that identifying chronic pain variations through biomarkers requires selecting markers linked to immune activity or brain processes. More randomized controlled trials with sufficient sample sizes and rigorous methodologies are needed. Despite this, physical exercise remains a valuable intervention for managing non-oncological musculoskeletal chronic pain. Additionally, it holds potential as a tool for uncovering novel biomarkers that may contribute to the objectification and understanding of chronic pain mechanisms. Full article

(This article belongs to the Special Issue Pain: New Insights into Mechanisms, Diagnosis, Therapy, and Management)

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18 pages, 995 KB

Open AccessArticle

Microbiota and Gut Inflammatory Markers (Zonulin and Fecal Calprotectin) Exhibit Age-Dependent Variation in Patients with Ulcerative Colitis

by José Joaquín Merino, Nuría Bastande Rey and Rubén Fernández-García

Life 2025, 15(9), 1412; https://doi.org/10.3390/life15091412 - 8 Sep 2025

Viewed by 170

Abstract

Patients with bowel diseases (inflammatory bowel disease (IBD) in general) tend to seek medical, nursing, and/or physiotherapeutic consultations. Physiotherapists specialized in gastrointestinal (visceral) therapy can help reduce inflammation in patients with ulcerative colitis (UC). In this study, we divided UC patients into three [...] Read more.

Patients with bowel diseases (inflammatory bowel disease (IBD) in general) tend to seek medical, nursing, and/or physiotherapeutic consultations. Physiotherapists specialized in gastrointestinal (visceral) therapy can help reduce inflammation in patients with ulcerative colitis (UC). In this study, we divided UC patients into three groups according to their age: the youngest (18–35 years old), middle-aged (36–49 years old), and oldest (50–70 years old). Our hypothesis was that gut inflammatory markers (zonulin and fecal calprotectin levels) and microbiota strains would exhibit age-dependent variations in UC patients. We compared differences in zonulin, calprotectin, and vitamin D levels, together with a plethora of microbiota strains, based on age. Calprotectin is a marker of intestinal inflammation and zonulin identifies gut permeability; as IBD is characterized by gastrointestinal inflammation, these are useful markers for diagnosing and monitoring treatment/s in IBD patients, including ulcerative colitis (UC). Dysbiosis can alter the normal balance of intestinal function, and thus, several microbiota strains were compared between different age ranges in UC patients. The results indicated that the middle-aged UC (36–49) patients had the highest endogenous vitamin D levels, as well as lower zonulin and calprotectin levels than the youngest (18–35) and oldest (50–70) UC participants, respectively. The middle-aged group also had lower Enterococcus, E. Coli biovare, and Pseudomonas spp. levels than the youngest UC participants. Meanwhile, the most LPS microbiota producers were found in middle-aged patients. Finally, a higher number of Candida albicans and elevated LPS were found in the oldest UC participants than in the middle-aged (36–49) group. This study was, however, limited by uneven age-group sizes, which may have may limited the power in the youngest cohort. Although altered gut microbiota levels can increase gut inflammation in rodent models of UC, a definitive cause–effect relationship between UC and intestinal microbiota alteration is difficult to demonstrate in humans. Full article

(This article belongs to the Section Physiology and Pathology)

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31 pages, 8445 KB

Open AccessArticle

HIRD-Net: An Explainable CNN-Based Framework with Attention Mechanism for Diabetic Retinopathy Diagnosis Using CLAHE-D-DoG Enhanced Fundus Images

by Muhammad Hassaan Ashraf, Muhammad Nabeel Mehmood, Musharif Ahmed, Dildar Hussain, Jawad Khan, Younhyun Jung, Mohammed Zakariah and Deema Mohammed AlSekait

Life 2025, 15(9), 1411; https://doi.org/10.3390/life15091411 - 8 Sep 2025

Viewed by 255

Abstract

Diabetic Retinopathy (DR) is a leading cause of vision impairment globally, underscoring the need for accurate and early diagnosis to prevent disease progression. Although fundus imaging serves as a cornerstone of Computer-Aided Diagnosis (CAD) systems, several challenges persist, including lesion scale variability, blurry [...] Read more.

Diabetic Retinopathy (DR) is a leading cause of vision impairment globally, underscoring the need for accurate and early diagnosis to prevent disease progression. Although fundus imaging serves as a cornerstone of Computer-Aided Diagnosis (CAD) systems, several challenges persist, including lesion scale variability, blurry morphological patterns, inter-class imbalance, limited labeled datasets, and computational inefficiencies. To address these issues, this study proposes an end-to-end diagnostic framework that integrates an enhanced preprocessing pipeline with a novel deep learning architecture, Hierarchical-Inception-Residual-Dense Network (HIRD-Net). The preprocessing stage combines Contrast Limited Adaptive Histogram Equalization (CLAHE) with Dilated Difference of Gaussian (D-DoG) filtering to improve image contrast and highlight fine-grained retinal structures. HIRD-Net features a hierarchical feature fusion stem alongside multiscale, multilevel inception-residual-dense blocks for robust representation learning. The Squeeze-and-Excitation Channel Attention (SECA) is introduced before each Global Average Pooling (GAP) layer to refine the Feature Maps (FMs). It further incorporates four GAP layers for multi-scale semantic aggregation, employs the Hard-Swish activation to enhance gradient flow, and utilizes the Focal Loss function to mitigate class imbalance issues. Experimental results on the IDRiD-APTOS2019, DDR, and EyePACS datasets demonstrate that the proposed framework achieves 93.46%, 82.45% and 79.94% overall classification accuracy using only 4.8 million parameters, highlighting its strong generalization capability and computational efficiency. Furthermore, to ensure transparent predictions, an Explainable AI (XAI) approach known as Gradient-weighted Class Activation Mapping (Grad-CAM) is employed to visualize HIRD-Net’s decision-making process. Full article

(This article belongs to the Special Issue Advanced Machine Learning for Disease Prediction and Prevention)

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13 pages, 1650 KB

Open AccessArticle

Safety, Pharmacokinetics, and Food Effect of the RORα Agonist TB-840, a Novel Candidate for Metabolic Dysfunction-Associated Steatohepatitis (MASH): A Randomized First-in-Human Study in Healthy Volunteers

by Inyoung Hwang, Shi-Ra Lee, Heung Jae Kim, Yun Kim and Sang Won Lee

Life 2025, 15(9), 1410; https://doi.org/10.3390/life15091410 - 7 Sep 2025

Viewed by 165

Abstract

TB-840 is a novel RORα agonist being developed by Therasid Bioscience Inc. for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). This first-in-human study evaluated the safety, tolerability, pharmacokinetics, and food effect of single ascending doses of TB-840 in healthy adult volunteers. In the [...] Read more.

TB-840 is a novel RORα agonist being developed by Therasid Bioscience Inc. for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). This first-in-human study evaluated the safety, tolerability, pharmacokinetics, and food effect of single ascending doses of TB-840 in healthy adult volunteers. In the single ascending dose part, 64 participants were randomized to receive TB-840 (12.5–200 mg) or placebo. In the food effect part, 6 participants received a single 200 mg dose under fasted and fed conditions in a crossover design. TB-840 was rapidly absorbed (median T_max 1.7–2.5 h) with a mean half-life of 4.8–9.7 h. Systemic exposure increased dose-proportionally across the studied dose range. A high-fat meal delayed absorption and increased the systemic exposure. TB-840 was well-tolerated, with no serious adverse events reported. These results support the continued development of TB-840 as a potential treatment for MASH. Further studies are warranted to evaluate its efficacy and safety in the target patient population (ClinicalTrials.gov identifier: NCT05045534). Full article

(This article belongs to the Special Issue Update on Clinical Pharmacology)

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14 pages, 428 KB

Open AccessArticle

Instrumented Functional Mobility Assessment in Elderly Patients Following Total Knee Arthroplasty: A Retrospective Longitudinal Study Using the Timed Up and Go Test

by Andrei Machado Viegas da Trindade, Leonardo Pinheiro Rezende, Helder Rocha da Silva Araújo, Rodolfo Borges Parreira and Claudia Santos Oliveira

Life 2025, 15(9), 1409; https://doi.org/10.3390/life15091409 - 7 Sep 2025

Viewed by 205

Abstract

In the context of the rising demand for total knee arthroplasty (TKA) in older adults and persistent uncertainty about the quality of long-term functional recovery, this study evaluated elderly patients’ mobility after unilateral TKA via a transquadriceps approach using instrumented Timed Up and [...] Read more.

In the context of the rising demand for total knee arthroplasty (TKA) in older adults and persistent uncertainty about the quality of long-term functional recovery, this study evaluated elderly patients’ mobility after unilateral TKA via a transquadriceps approach using instrumented Timed Up and Go (TUG) tests. A total of 20 patients treated between 2022 and 2024 at a tertiary hospital were invited to participate in this observational, retrospective, descriptive study, and 19 met the inclusion criteria (age 50–80 and Kellgren–Lawrence ≥ 4). The participants performed two TUG trials at two postoperative time points (18 and 53 months), with an inertial measurement unit (G-sensor) capturing 15 kinematic variables. When comparing the postoperative time points, it was found that the total TUG duration remained stable (14.97 ± 3.48 vs. 15.47 ± 2.93 s; p = 0.58), while the mid-turning peak velocity increased significantly (106.44 ± 30.96 vs. 132.77 ± 30.82°/s; p = 0.0039; r = 0.88). The end-turning velocity and sit-to-stand parameters showed small-to-moderate effect size gains without statistical significance. These findings suggest that, in the first year following surgery, patients continue to experience difficulties with movement fluidity and motor control—especially during turning—underscoring the value of segmented, sensor-based assessments and the need for extended rehabilitation protocols that emphasize rotational control and balance. These findings provide clinically relevant parameters that can support future interventional studies and help guide rehabilitation planning after TKA. Full article

(This article belongs to the Special Issue Knee Bracing in Human Movement: Biomechanics, Artificial Intelligence, and Optimization)

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20 pages, 1710 KB

Open AccessArticle

Predictive Model for Estimating the Length of Stay in Hip Arthroplasty Patients by Machine Learning—H.I.P.P.O Score

by Andrei Danet, Razvan Spiridonica, Georgian Iacobescu, Adrian Cursaru, Bogdan Cretu, Bogdan Serban, Sergiu Iordache, Antonio-Daniel Corlatescu and Catalin Cirstoiu

Life 2025, 15(9), 1408; https://doi.org/10.3390/life15091408 - 7 Sep 2025

Viewed by 229

Abstract

Introduction: Total hip arthroplasty is a major orthopedic intervention, which is increasingly performed, and involves a variable duration of postoperative hospitalization. Estimating this duration is essential for optimizing resources and improving perioperative planning. Materials and Methods: The retrospective study included 85 patients admitted [...] Read more.

Introduction: Total hip arthroplasty is a major orthopedic intervention, which is increasingly performed, and involves a variable duration of postoperative hospitalization. Estimating this duration is essential for optimizing resources and improving perioperative planning. Materials and Methods: The retrospective study included 85 patients admitted to an orthopedic clinic between 2020 and 2025, undergoing primary hip arthroplasty. Pre- and postoperative clinical, biological, and surgical data were collected. Based on these variables, the H.I.P.P.O. (Hip Intervention Patient Prognostic Outcome) score was developed, using a Random Forest algorithm to predict the length of stay (short, medium, long). Results: The model achieved an overall accuracy of 80%. The most important predictors were as follows: day of surgery, type of prosthesis, preoperative fibrinogen, INR, APTT, preoperative hemoglobin, age, and presence of liver cirrhosis. The H.I.P.P.O. score allowed efficient stratification of patients and showed a high capacity to identify cases at risk of prolonged hospitalization (F1 score = 0.857). Conclusions: The H.I.P.P.O. score is a practical, interpretable, and clinically applicable tool that integrates biological and organizational factors to predict the length of stay after hip arthroplasty. It can support surgical decision making and optimize perioperative management. Full article

(This article belongs to the Special Issue Orthopedic Disease Treatment and Management: Innovations, Challenges, and Future Directions)

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10 pages, 326 KB

Open AccessArticle

Influence of Specialization from Intensive Care Physicians on Outcome in Multiply Injured Patients—A Matched-Pair Analysis at a Level I Trauma Center

by Gökmen Aktas, Larissa Rolfes, Maximilian Koblenzer, Vesta Brauckmann, Jorge Mayor, Jan Clausen, Jonas Ajouri, Tarek Omar Pacha, Stephan Sehmisch and Philipp Mommsen

Life 2025, 15(9), 1407; https://doi.org/10.3390/life15091407 - 6 Sep 2025

Viewed by 209

Abstract

The specialty background of intensive physicians managing severely injured patients varies internationally, with trauma ICUs often led by either trauma surgeons or anesthesiologists, both of whom receive additional intensive care training. Whether physician specialty affects outcomes remains uncertain. We conducted a retrospective single-center [...] Read more.

The specialty background of intensive physicians managing severely injured patients varies internationally, with trauma ICUs often led by either trauma surgeons or anesthesiologists, both of whom receive additional intensive care training. Whether physician specialty affects outcomes remains uncertain. We conducted a retrospective single-center cohort study of patients aged ≥ 16 years with an Injury Severity Score (ISS) ≥ 16 admitted to a level I trauma center between January 2005 and December 2022. Patients were treated either in a trauma surgery ICU (T-ICU) or an anesthesiology ICU (A-ICU). Briefly, 1:1 matching was conducted based on demographic and injury-related variables, with the primary outcome being in-hospital mortality and secondary outcomes including transfusion requirements, duration of mechanical ventilation, ICU and hospital length of stay, and Glasgow Outcome Scale (GOS) at discharge. Among the 1015 eligible patients (T-ICU: n = 920; A-ICU: n = 95), 52 patients (26 per group) were successfully matched with comparable baseline characteristics. No significant differences were observed in mortality, GOS, transfusion requirements, ventilation duration, or ICU/hospital length of stay. These findings suggest that, when both are led by certified intensive care specialists, trauma surgery- and anesthesiology-based ICUs achieve comparable outcomes, supporting multidisciplinary models while highlighting the need for larger multicenter studies. Full article

(This article belongs to the Special Issue Emergency and Trauma Management)

14 pages, 234 KB

Open AccessArticle

Therapeutic Plasma Exchange in Intensive Care Units—A 5-Year Multicenter Retrospective Study

by Daria Syguła, Paulina Kluszczyk, Wiktor Wagner, Michał Krawiec, Szymon Bialka, Ewa Trejnowska, Grzegorz Brozek, Magdalena Latos, Paweł Dubik, Piotr Palaczynski, Piotr Knapik and Szymon Skoczyński

Life 2025, 15(9), 1406; https://doi.org/10.3390/life15091406 - 6 Sep 2025

Viewed by 245

Abstract

(1). Background: Therapeutic plasma exchange (TPE) is a method of extracorporeal plasma filtration designed to remove immunoglobulins and pro-inflammatory factors as pathogenesis of numerous diseases. Procedures are performed in intensive care units (ICUs); however, the complications and treatment outcomes remain unclear. The aim [...] Read more.

(1). Background: Therapeutic plasma exchange (TPE) is a method of extracorporeal plasma filtration designed to remove immunoglobulins and pro-inflammatory factors as pathogenesis of numerous diseases. Procedures are performed in intensive care units (ICUs); however, the complications and treatment outcomes remain unclear. The aim of the study was to evaluate clinical outcomes and identify risk factors of complications associated with TPE. (2). Methods: In this multi-center, retrospective, 5-year cohort study, we analyzed a database of 56 adult ICU patients who had undergone TPE at two academic hospitals and one regional hospital. (3). Results: In our study, the median APACHE II was 7.5 IQR 12.5 (4–16.5) and SOFA score was 2 IQR 4 (1–5). In the multivariate analysis, the APACHE II (p = 0.043) and SOFA score (p = 0.046) were the predictors of prolonged length of stay. The SOFA score was a predictor of hospital-acquired infection (HAI) (p = 0.011). Multivariate logistic regression revealed age (p = 0.011), SOFA (p = 0.011), and APACHE II score (p = 0.032) as independent predictors of the development of shock as a TPE complication. (4). Conclusions: Our results suggest that the SOFA and APACHE II scores are significant predictors of the length of hospitalization and the occurrence of shock. In addition, the SOFA score was a predictor of HAI in patients treated TPE in ICU. Full article

(This article belongs to the Special Issue Updates on Respiratory Pathologies)

14 pages, 1105 KB

Open AccessArticle

Effect of Carboxymethylcellulose Hyaluronan (SEPRAFİLM^®) on an Arthrofibrosis Model Created in Rabbit Knees

by Ismail Tugay Yagci, Ovunc Akdemir, Atilla Eyuboglu, Murat Sezak and Semih Aydogdu

Life 2025, 15(9), 1405; https://doi.org/10.3390/life15091405 - 5 Sep 2025

Viewed by 281

Abstract

Purpose: This study aimed to evaluate the efficacy of carboxymethylcellulose (Seprafilm^®) for the prevention and treatment of arthrofibrosis in rabbit knees, as well as to investigate its underlying mechanisms of action against fibrosis and adhesion formation. Methods: Sixteen male New Zealand [...] Read more.

Purpose: This study aimed to evaluate the efficacy of carboxymethylcellulose (Seprafilm^®) for the prevention and treatment of arthrofibrosis in rabbit knees, as well as to investigate its underlying mechanisms of action against fibrosis and adhesion formation. Methods: Sixteen male New Zealand white rabbits were randomly divided into two groups: a control group and a treatment group that received Seprafilm^® following surgically induced arthrofibrosis in the knee joint. Macroscopic and histological assessments were performed to evaluate adhesion, fibrosis, inflammation, and edema. Results: In the control group, macroscopic adhesion was severe in five rabbits (62.5%), moderate in two (25%), and minimal in one (12.5%). No macroscopic adhesion was observed in the Seprafilm^® group. The mean adhesion score was 2.5 ± 0.75 in the control group versus 0 in the treatment group (p < 0.001). Histologically, five rabbits (62.5%) in the control group showed significant fibrosis, and three (37.5%) showed moderate fibrosis, whereas all rabbits in the Seprafilm^® group exhibited only minimal fibrosis (p < 0.001). Conclusions: Seprafilm^® was effective in reducing both macroscopic and histological signs of adhesion and fibrosis in a rabbit arthrofibrosis model. These findings suggest its potential as a preventive and therapeutic agent in managing arthrofibrosis. Full article

(This article belongs to the Special Issue Advancements in Postoperative Management of Patients After Surgery)

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22 pages, 5685 KB

Open AccessReview

Ultrasound-Guided Interventions for Neuropathic Pain: A Narrative Pictorial Review

by Ting-Yu Lin, Ke-Vin Chang, Wei-Ting Wu, Kamal Mezian, Vincenzo Ricci and Levent Özçakar

Life 2025, 15(9), 1404; https://doi.org/10.3390/life15091404 - 5 Sep 2025

Viewed by 323

Abstract

Neuropathic pain presents a persistent therapeutic challenge, arising from diverse etiologies such as trigeminal neuralgia, postherpetic neuralgia, post-amputation pain, painful polyneuropathy, peripheral nerve injury pain, and painful radiculopathy. Given the limitations and side effects associated with pharmacologic treatments, interest in interventional therapies has [...] Read more.

Neuropathic pain presents a persistent therapeutic challenge, arising from diverse etiologies such as trigeminal neuralgia, postherpetic neuralgia, post-amputation pain, painful polyneuropathy, peripheral nerve injury pain, and painful radiculopathy. Given the limitations and side effects associated with pharmacologic treatments, interest in interventional therapies has surged. Herein, ultrasound guidance provides real-time, radiation-free visualization that enhances procedural accuracy and safety. This narrative review synthesizes current evidence on ultrasound-guided techniques—including nerve blocks, pulsed radiofrequency, hydrodissection, and peripheral nerve stimulation—in the management of neuropathic pain. These minimally invasive approaches demonstrate potential in providing significant and durable pain relief, enhancing functional outcomes, and reducing reliance on systemic medications. Notably, much of the existing literature comprises small-scale or observational studies and larger randomized controlled trials are therefore essential to confirm efficacy, define optimal treatment parameters, and inform clinical guidelines for broader adoption. Full article

(This article belongs to the Special Issue A Paradigm Shift in Airway and Pain Management—2nd Edition)

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18 pages, 1527 KB

Open AccessArticle

Gene-Level Shift in Response to Synthetic Nitrogen Addition Promotes Larix olgensis (Ussurian Larch) Growth in a Short-Term Field Trial

by Muhammad Jamal Ameer, Yushan Liu, Siyu Yan and Tongbao Qu

Life 2025, 15(9), 1403; https://doi.org/10.3390/life15091403 - 4 Sep 2025

Viewed by 264

Abstract

Climate change and injudicious nitrogen addition alter the soil physico-chemical properties and microbial activity in oligotrophic forest soil, which disrupts the nitrogen cycle balance. Nevertheless, recommended fertilizer forms and levels are considered to be crucial for stable nitrogen application. We established a short-term [...] Read more.

Climate change and injudicious nitrogen addition alter the soil physico-chemical properties and microbial activity in oligotrophic forest soil, which disrupts the nitrogen cycle balance. Nevertheless, recommended fertilizer forms and levels are considered to be crucial for stable nitrogen application. We established a short-term field trial for the first time using a randomized complete block design under the yellow larch forest, with six treatments applied, including urea CO(NH₂)₂, ammonium chloride NH₄Cl, and sodium nitrate NaNO₃ at concentrations of 10 and 20 kg N hm⁻² yr⁻¹, each extended by three replicates. The gene abundances were measured using quantitative PCR (qPCR), in which the abundance levels of AOA (amoA) and nirS were higher under high CO(NH₂)₂ 2.87 × 10¹⁰ copies g⁻¹ dry soil and low NO₃⁻ 8.82 × 10⁹ copies g⁻¹ dry soil, compared to CK, representing 2.8-fold and 1.5-fold increases, respectively. We found niche partitioning as revealed despite AOA (amoA) increasing in number, AOB (amoA) contributing more to ammonia oxidation while nirS proved opportunistic under stress conditions. This was supported by distinct significant correlations among factors, in which soil urease enzymatic activity (S-UE) was associated with AOA (amoA) and nirK, while AOB (amoA) and nirS positively correlated with NH₄⁺ content and soil potential of hydrogen (pH), respectively. Among the applied treatments, high-level NO₃⁻ increased total nitrogen content and had a significant effect on soil N-acetyl-β-d-glucosaminidase (S-NAG) and soil acid protease (S-ACPT) activity. In summary, we observed an increase in Larix olgensis growth with high nitrogen retention. Full article

(This article belongs to the Special Issue Carbon and Nitrogen Cycles in Terrestrial Ecosystems)

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14 pages, 2332 KB

Open AccessArticle

Preconditioning with Low-Dose Radiation Improves Antitumor Immunity and Survival in DC-Vaccinated Mice

by Eric Kwon, Shelby Namen, Colin J. Willoughby, Solomon Kang, Gaurav Pandey, Alexander B. Kim and Carl J. DeSelm

Life 2025, 15(9), 1402; https://doi.org/10.3390/life15091402 - 4 Sep 2025

Viewed by 307

Abstract

Preconditioning regimens are essential for the immunologic success of cell therapies like CAR T cells. Nevertheless, their effect on cancer vaccines is underexplored, and preconditioning regimens are generally absent from cancer vaccine clinical trials. To address this knowledge gap, we evaluated the impact [...] Read more.

Preconditioning regimens are essential for the immunologic success of cell therapies like CAR T cells. Nevertheless, their effect on cancer vaccines is underexplored, and preconditioning regimens are generally absent from cancer vaccine clinical trials. To address this knowledge gap, we evaluated the impact of various preconditioning strategies on dendritic cell (DC) vaccine efficacy in a murine tumor model. Mice bearing syngeneic tumors received preconditioning with 2 Gy low-dose radiation therapy (LD RT; whole-body or tumor-only), cyclophosphamide, paclitaxel, LD RT plus cyclophosphamide, or no preconditioning, followed by administration of antigen-loaded DCs. Whether whole-body or tumor-directed, LD RT preconditioning significantly enhanced vaccine-induced antitumor CD8⁺ T cell responses and improved survival compared to DC vaccine alone and all other preconditioning groups. Cyclophosphamide preconditioning reduced vaccine efficacy and negated the benefits of LD RT, while paclitaxel had no significant effect. Notably, whole-body LD RT induced the strongest tumor antigen-specific T cell response. These findings suggest that preconditioning regimens can significantly influence cancer vaccine outcomes, as in CAR T cell therapy. Rational selection of preconditioning agents may either maximize or minimize the therapeutic potential of DC cancer vaccines and should be considered carefully in clinical trials. Full article

(This article belongs to the Section Physiology and Pathology)

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18 pages, 992 KB

Open AccessArticle

Effects of Exercise Snack Program on Quality of Life, Cardiorespiratory Fitness, and Metabolic Flexibility in Elderly Cancer Survivors: A Preliminary Study

by Peng Zhou, Zimei Hu, Taesung Kim, Yonghwan Kim, Zhengqing Leng and Moonyoung Choi

Life 2025, 15(9), 1401; https://doi.org/10.3390/life15091401 - 4 Sep 2025

Viewed by 289

Abstract

Background: Cancer has a high mortality rate and leaves physical and mental difficulties even after treatment. When it afflicts frail elderly people, it poses a greater burden to them and society. Regular exercise helps to restore the deteriorated health of cancer survivors. The [...] Read more.

Background: Cancer has a high mortality rate and leaves physical and mental difficulties even after treatment. When it afflicts frail elderly people, it poses a greater burden to them and society. Regular exercise helps to restore the deteriorated health of cancer survivors. The purpose of this study was to compare the effects of a short-term, high-repetition, home-based “exercise snack” program with those of a traditional, continuous, moderate-intensity exercise format on key health outcomes in elderly cancer survivors, including quality of life, cardiorespiratory fitness, and metabolic flexibility. Methods: A short-duration, high-repetition exercise snack group (ESG, n = 17) and a traditional exercise group (TEG, n = 17) were compared after 12 weeks of training. The effects of exercise on quality of life, cardiorespiratory fitness, metabolic flexibility, and blood lipids were measured. Results: Quality-of-life vitality, social functioning, cardiorespiratory fitness VO₂ peak, and high-density lipoprotein cholesterol were improved more in ESG than in TEG (p < 0.05). Metabolic flexibility showed that fat utilization increased and carbohydrate utilization decreased post-training compared to pre-training at VO₂ peak 20 and 40% in both groups (p < 0.05). Conclusions: In both groups, cardiorespiratory fitness was shown along with physical and psychological improvements in quality of life, and the efficiency of metabolic flexibility was also improved. Therefore, short-term, frequent exercise may be an appropriate exercise alternative for elderly people with difficulties. Full article

(This article belongs to the Section Physiology and Pathology)

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18 pages, 3539 KB

Open AccessArticle

Neuro-Genomic Mapping of Cardiac Neurons with Systemic Analysis Reveals Cognitive and Neurodevelopmental Impacts in Congenital Heart Disease

by Abhimanyu Thakur and Raj Kishore

Life 2025, 15(9), 1400; https://doi.org/10.3390/life15091400 - 4 Sep 2025

Viewed by 301

Abstract

Congenital heart disease (CHD) is associated with neurodevelopmental and cognitive impairments, but the underlying molecular mechanisms remain unclear. This study investigated cardiac neuronal genomics in CHD using single-nucleus RNA-sequencing data (GSE203274) from 157,273 cardiac nuclei of healthy donors and patients with hypoplastic left [...] Read more.

Congenital heart disease (CHD) is associated with neurodevelopmental and cognitive impairments, but the underlying molecular mechanisms remain unclear. This study investigated cardiac neuronal genomics in CHD using single-nucleus RNA-sequencing data (GSE203274) from 157,273 cardiac nuclei of healthy donors and patients with hypoplastic left heart syndrome (HLHS), Tetralogy of Fallot (TOF), dilated (DCM), and hypertrophic (HCM) cardiomyopathies. The Uniform Manifold Approximation and Projection (UMAP) clustering identified major cardiac cell types, revealing neuron-specific transcriptional programmes. Neuronal populations showed enriched expression of neurodevelopmental disorder-linked genes (NRXN3, CADM2, ZNF536) and synaptic signalling pathways. CHD cardiac neurons exhibited upregulated markers of cognitive dysfunction (APP, SNCA, BDNF) and neurodevelopment regulators (DNMT1, HCFC1) across subtypes. Cardiomyocyte troponin elevation correlated with neuronal exosome receptor expression (TLR2, LRP1), suggesting intercellular communication. Gene ontology analysis highlighted overlaps between cardiovascular disease pathways and neurodevelopmental disorder signatures in CHD neurons. These findings provide the first neuro-genomic map of cardiac neurons in CHD, linking cardiac pathology to neural outcomes through transcriptional dysregulation. Further, the systemic analysis of clinical findings in CHD further supports the risk of neurodevelopmental impacts. In summary, this study identifies transcriptional dysregulation within cardiac neurons in CHD and, together with a systemic analysis of clinical data, provides molecular evidence linking cardiac pathology to neurodevelopmental and cognitive impairments. Full article

(This article belongs to the Section Genetics and Genomics)

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Life, Volume 15, Issue 9 (September 2025) – 96 articles

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