Leaf phenology in Tropical Dry Forests (TDF) is strongly influenced by environmental factors; however, responses may vary according to edaphic, structural, and floristic differences. The Caatinga, one of the largest continuous TDF in the Americas, exhibits pronounced hydric seasonality and encompasses distinct physiognomies such as the carrasco (deciduous shrubland) and crystalline caatinga (xeric shrubland). Studies addressing phenological variation among these two vegetation types remain limited and largely based on direct human observation. Our study aimed to advance the understanding of phenological dynamics in Caatinga TDF by investigating the climatic factors influencing leaf production and fall in woody communities of carrasco and crystalline vegetations using repeated digital photographs. Daily monitoring (2020-2024) provided green chromatic coordinate time series. Climatic drivers of Caatinga phenology (photoperiod, precipitation, temperature, and atmospheric moisture) were analyzed using principal component analysis and temporally structured generalized additive models. Woody communities of crystalline caatinga and carrasco exhibited distinct phenological strategies reflecting different responses to climatic variability. Leaf phenology in both areas was mainly driven by precipitation but was also associated with temperature. Carrasco showed more stable and predictable dynamics, with lower interannual variation in start of growing season (SOS), end of growing season (EOS), and length of growing season (LOS), retaining leaves about 20 days longer and responding to relief of hydrothermal stress at the end of the dry season. Crystalline caatinga was highly sensitive to rainfall irregularity and precipitation pulses. These results suggest that crystalline caatinga is more vulnerable to increasing climatic variability, whereas carrasco appears more resilient.
Coccidiosis is a major avian enteropathy caused by Eimeria spp., and mixed infections can hinder diagnosis due to overlapping lesions. This study aimed to evaluate the occurrence of coccidiosis in broiler chickens through characterization of gross and histopathologic lesions, parasitologic identification, and investigation of potentially associated bacterial infections. A cross-sectional study was conducted on 28 flocks housed in positive-pressure ventilated poultry houses, with a sample of 280 broilers collected at two time points: sampling 1 (21 to 28 days of age) and sampling 2 (35 to 42 days of age). Analyses included scoring of gross and histopathologic lesions, morphometric and morphologic assessment of Eimeria oocysts, Salmonella testing in feces and litter, and aerobic bacterial culture of organs with lesions. Eimeria spp. positivity was 82.14% in sampling 1 and 100% in sampling 2. Oocysts morphologically consistent with Eimeria acervulina predominated initially, while Eimeria tenella was most frequent later. Due to morphometric overlap among species, identification was based solely on morphology and not confirmed molecularly. Mixed infections were frequent. Histopathology showed higher diagnostic sensitivity, with a 28.5% increase in positive case detection compared to gross evaluation. Grade 1 lesions were predominant at both time points, except in sampling 2, where E. tenella was responsible for a higher frequency of grade 3 lesions. No flocks tested positive for Salmonella. Opportunistic bacteria (Escherichia coli, coagulase-negative Staphylococcus) were isolated in broilers with septic extraintestinal lesions, including airsacculitis, perihepatitis, pericarditis, hepatitis, and splenitis, with no significant association with coccidiosis. The results reinforce the importance of integrating diagnostic methods to increase the accuracy of disease detection and suggest that the low incidence of bacterial infections may reflect appropriate biosecurity practices on the evaluated farms. Asociación de diferentes métodos diagnósticos para identificar la coccidiosis en pollos de engorde y las lesiones bacterianas potencialmente asociadas. La coccidiosis es una enteropatía aviar importante causada por Eimeria spp., y las infecciones mixtas pueden dificultar el diagnóstico debido a la superposición de lesiones. Este estudio tuvo como objetivo evaluar la incidencia de coccidiosis en pollos de engorde mediante la caracterización de lesiones macroscópicas e histopatológicas, la identificación parasitológica y la investigación de infecciones bacterianas potencialmente asociadas. Se realizó un estudio transversal en 28 parvadas alojadas en gallineros con ventilación a presión positiva, con una muestra de 280 pollos de engorde recolectada en dos momentos: muestreo 1 (21 a 28 días de edad) y muestreo 2 (35 a 42 días de edad). Los análisis incluyeron la puntuación de las lesiones macroscópicas e histopatológicas, la evaluación morfométrica y morfológica de los ooquistes de Eimeria, las pruebas de Salmonella en heces y cama, y el cultivo bacteriano aeróbico de los órganos con lesiones. La positividad de Eimeria spp. fue del 82.14% en el muestreo 1 y del 100% en el muestreo 2. Los ooquistes morfológicamente consistentes con Eimeria acervulina predominaron inicialmente, mientras que Eimeria tenella fue la más frecuente posteriormente. Debido a la superposición morfométrica entre las especies, la identificación se basó únicamente en la morfología y no se confirmó molecularmente. Las infecciones mixtas fueron frecuentes. La histopatología mostró una mayor sensibilidad diagnóstica, con un aumento del 28.5% en la detección de casos positivos en comparación con la evaluación macroscópica. Las lesiones de grado 1 fueron predominantes en ambos puntos temporales, excepto en el muestreo 2, donde E. tenella fue responsable de una mayor frecuencia de lesiones de grado 3. Ninguna parvada dio positivo para Salmonella. Se aislaron bacterias oportunistas (Escherichia coli, Staphylococcus coagulasa-negativo) en pollos de engorde con lesiones sépticas extraintestinales, como aerosaculitis, perihepatitis, pericarditis, hepatitis y esplenitis, sin asociación significativa con la coccidiosis. Los resultados refuerzan la importancia de integrar métodos de diagnóstico para aumentar la precisión en la detección de enfermedades y sugieren que la baja incidencia de infecciones bacterianas podría reflejar prácticas adecuadas de bioseguridad en las granjas evaluadas.
Metabolic dysfunction-associated steatotic liver disease (MASLD) frequently coexists with type 2 diabetes mellitus (T2DM), complicating its management. In this population, we aimed to compare the effectiveness of subcutaneous GLP-1 receptor agonists (scGLP-1RA) to SGLT2 inhibitors (SGLT2i) on metabolic and hepatic parameters, while investigating the influence of GLP1R and PNPLA3 genetic variants on treatment response. This retrospective study included patients with T2DM starting scGLP-1RA or SGLT2i, balanced through Propensity Score Matching (PSM) to account for baseline clinical differences. Clinical and biochemical data were compared at baseline and after one year of treatment. Genotyping was performed for PNPLA3 (rs738409) and GLP1R (rs761387, rs6923761) polymorphisms. Multivariable linear regression was used to identify independent predictors of HbA1c, BMI, and transaminase reduction. Both drug classes significantly improved glycemic control and BMI. However, scGLP-1RA demonstrated superior efficacy in HbA1c and BMI reduction compared to SGLT2i (β = -0.349, p = 0.001; β = -0.711, p = 0.045). In MASLD subgroups (baseline ALT > 35 U/L or hepatic steatosis), only scGLP-1RA led to a significant reduction in ALT levels (p = 0.02). Multivariable analysis identified the GLP1R rs761387 G allele as an independent predictor of a blunted glycemic response (β = -0.277, p = 0.018). In a real-world setting, scGLP-1RA showed higher potency than SGLT2i on metabolic and hepatic parameters. These findings support the preferential use of scGLP-1RA in patients with T2DM and MASLD and are consistent with current international recommendations. The association between GLP1R rs761387 variant and HbA1c reduction sheds light on the impact of this variant on treatment response. Further studies are needed to validate this genetic predictor in broader populations.
Type 1 diabetes mellitus (T1DM) alters microRNA (miRNA) expression in key metabolic tissues. The effects of different exercise modalities on miRNA expression in white adipose tissue (WAT) of the T1DM rat model remain largely unexplored. This exploratory preclinical study investigated the effects of eight weeks of moderate-intensity endurance training (MIET) and high-intensity interval training (HIIT) on the expression of miR-29a and miR-126 in the WAT of the T1DM rat model. Fifty-four male Wistar rats were randomly assigned to six groups (n = 7 in healthy and n = 11 in diabetic groups): Control, MIET, HIIT, T1DM, T1DM + MIET, and T1DM + HIIT. Diabetes was induced by a single injection of STZ (60 mg/kg). T1DM upregulated miR-29a (15-fold, p < 0.001) and miR-126 (fourfold, p < 0.001) compared to the control. Both MIET and HIIT completely normalized miR-29a expression in diabetic rats (p < 0.001). Furthermore, both exercise interventions profoundly suppressed miR-126 expression to levels significantly below those of the T1DM group (p < 0.001). Both interventions reduced fasting blood glucose, with MIET showing a greater effect (p < 0.001). Both MIET and HIIT normalized diabetes-induced dysregulation of miR-29a and miR-126 in WAT. These changes were associated with improved glycemic control, identifying these miRNAs as candidate responders to exercise modality in T1DM. The observed association between exercise intensity and glucose-lowering effects generates hypotheses for future mechanistic studies but does not establish causality. This exploratory study provides a candidate-based foundation for further research.
It is crucial to conduct strict surveillance on the diversity of HIV-1 to aid the generation of evidence-based biomedical and behavioral prevention programs to HIV/AIDS. In the current study, the social demographic characteristics, HIV-1 viral diversity among migration populations between 2017 and 2021 were investigated comprehensively and were compared with those in the previous five-year, between 2012 and 2016. Epidemiological investigation indicated that the male-to-female ratio decreased from 10.34:1 to 5.12:1, indicating significantly more female were infected when compared to the previous five years (p = 0.004). Moreover, an inversion on both the gender and nationality was found when comparison between study participants from southeastern ports and northwestern ports (p < 0.05) during the ten-year study period. Molecular epidemiology study revealed that two subtypes C/BC and CRF01_AE dominated, with the emerging of novel unique recombinant forms, including CRF01_AE/C/BC, CRF03_AB/C/BC, A/D, CRF01_AE/C, CRF08_BC/B, CRF01_AE/B, and B/CRF01_AE/C between 2017 and 2021. In addition, a significant higher proportion of drug-resistant viruses was found among this population when compared with the previous five-year (p < 0.001). In conclusion, the altered social demographic characteristics, co-circulation of CRF01_AE, C/BC recombinants, multiple URFs, and increasing amount of multiple drug-resistant viruses, indicated a new trend of the HIV-1 molecular epidemic in this population, which called for enhanced public health responses and prioritization of resources.
Titanium fastener technology is increasingly adopted for use in minimally invasive valve surgery and open procedures to facilitate faster operative times and reproducible fastening of sutures. The objective of this study was to evaluate the technical feasibility and short-term safety of automated titanium fastener technology for securing sutures in heart valve repair and/or heart valve replacement procedures. The CRIMP study is a multicenter, prospective study that enrolled patients undergoing heart valve repair or replacement via open or minimally invasive approaches at three centers (n = 120). The primary endpoints were device success and prosthesis implantation time. Mean age was 62.5 (SD 11.1) years, 33.3% of patients was female and the cohort was characterized as low surgical risk (EuroSCORE II 1.6%; SD 2.3%). Predominant valve disease was mitral regurgitation. Median procedure time was 178 (IQR 145-210) min. Median aortic cross-clamp time was 82 (IQR 59-107) min. The majority of procedures was minimally invasive (76.7%). In aortic valve procedures, median prosthesis implantation time (first stitch until last COR-KNOT placement) was 25 (IQR 18-46) min and in mitral valve procedures median implantation time was 50 (IQR 48-52) min. Device success was 100%, since no automated titanium fastener failed to grip or crimp appropriately. Median number of COR-KNOTS used was 14 (IQR 12-16) per valve. In-hospital mortality was 0.8%. All observed adverse events were considered unrelated to the device and there was no valve prosthesis dehiscence at 30-days of follow-up. The use of automated titanium fastener technology for suture fixation in heart valve surgery was technically feasible and showed short-term safety in all patients, with no obvious device-related adverse events observed. Graphical abstract available for this article.  Clinical trial registration number: DRKS00038956. Heart valve surgery often requires surgeons to tie many small sutures to secure repaired or replaced valves. Automated titanium fastener devices can replace manual knot tying and may help surgeons work faster and more consistently. This study evaluated whether this technology is safe during short-term observation and technically feasible when used in heart valve repair or replacement surgery. The CRIMP study was a prospective study conducted at three hospitals and included 120 patients undergoing heart valve surgery. Procedures included mitral, tricuspid, and aortic valve repair or replacement. The average patient age was about 63 years, one-third were women, and overall surgical risk was low. Researchers measured if the fastener device worked and how long it took to implant the valve prostheses. The automated titanium fasteners functioned successfully in all cases, meaning every fastener properly secured the sutures. In aortic valve procedures, placing and fastening the sutures took about 25 min, while in mitral valve procedures it took about 50 min. Around 14 fasteners were used per valve. In-hospital mortality was low (0.8%), and no complications were related to the fastener device. At 30 days after surgery, no patients experienced loosening of the implanted valve. However, the study only had one group, which was observed without a comparative group of patients undergoing manual knot tying, and the follow-up period was relatively short, which are important limitations. Overall, the results suggest that automated titanium fastener technology show short-term safety and are technically feasible for securing sutures in heart valve surgery.
This study investigated the effects of proline on intestinal injury in piglets infected with porcine epidemic diarrhea virus (PEDV). Twenty-eight 7-day-old piglets were assigned to four groups: control (CON), proline (Pro), PEDV, and Pro + PEDV. Piglets in the Pro and Pro + PEDV groups received oral proline (500 mg/kg body weight) for 7 days. During the last 3 days, piglets in the PEDV and Pro + PEDV groups were inoculated with PEDV. Under PEDV infection, proline administration increased villus height and the villus height/crypt depth ratio in both the jejunum and ileum, and villus width and villus surface area in the ileum. Proline increased PEDV N protein abundance and interferon β (IFN-β) mRNA level in both intestinal segments, suppressed downstream antiviral genes in infected piglets, but upregulated these genes in the jejunum of uninfected piglets. Proline further increased interleukin 1β (IL-1β) concentrations and the expression of inflammation-related genes in the jejunum of infected piglets. Under PEDV infection, proline increased superoxide dismutase (SOD) activity in serum and jejunum, while reducing jejunal H2O2 concentration. Furthermore, proline downregulated genes related to lipid synthesis and ion transport in the jejunum of infected piglets. Transcriptomic and RT-qPCR analyses supported these findings, indicating that proline enhanced immune defense while suppressing lipid metabolism. In conclusion, proline alleviated PEDV-induced intestinal injury by improving villus morphology and enhancing antiviral and antioxidant defenses. However, it promoted viral replication and inflammation, while suppressing lipid metabolism. The multifaceted effects of proline on PEDV infection indicate its practical use warrants careful consideration.
Unlike the pattern-reversal visual evoked potential, the flash visual evoked potential (FVEP) has had limited clinical use because of lower reproducibility and higher inter- and intra-individual variability. One potential explanation involves the time-locked nature of FVEP recordings, where activity such as unintentional suppression of eyes-closed alpha can lead to overlapping potentials that might obscure the FVEP-P2. The present investigation evaluated the reliability of the FVEP-P2 in young healthy controls across five sessions after applying narrow-band filtering (1-7 Hz) and additional notch filtering to remove alpha and beta activity. It was hypothesized that spectral entrainment would occur within the alpha and that correction for this entrainment would significantly improve the reliability of FVEP-P2. 27 younger, healthy participants aged 18-39 years (M = 24.48, SD = 5.26; 17 females) took part in the study, all reporting no history of photosensitivity or seizures, neurological disorders, or color deficiency. Each participant experienced five sessions of 100 strobe flashes with their eyes closed. The FVEP-P2 associated with each trial was identified using an automated algorithm. Narrow-band filtering (1-7 Hz) significantly improved FVEP-P2 latency reliability compared to the uncorrected condition. Notch filters targeting alpha and beta separately did not produce significant improvements, suggesting additive or overlapping contributions. FVEP-P2 amplitude reliability also improved with filtering, primarily because of attenuating alpha-band interference. Narrow-band and notch filtering mitigated alpha- and beta-band interference, enhancing the test-retest reliability of the FVEP-P2. These findings establish a clearer physiological basis for FVEP unreliability and demonstrate that spectral correction can elevate the FVEP-P2 to clinically acceptable reliability levels, supporting the continued clinical utility of the FVEP, particularly in patients for whom pattern-reversal stimuli are unsuitable (e.g., infants, comatose, or uncooperative individuals) and as a candidate biomarker in mild cognitive impairment and Alzheimer's disease (Arruda et al., 2020; Fix et al., 2014).
Renal cell carcinoma (RCC) is characterized by a complex and highly heterogeneous tumor microenvironment (TME), the regulation of which remains incompletely understood. This study systematically investigated the role of protein tyrosine phosphatase non-receptor type 6 (PTPN6) in RCC. Through integrated bioinformatics analysis of TCGA and GEO datasets, we found PTPN6 was consistently overexpressed in multiple cancers, including clear cell (KIRC) and papillary (KIRP) RCC subtypes, where it served as a robust diagnostic marker. Elevated PTPN6 specifically correlated with advanced stage, metastasis, and poor survival exclusively in KIRC. Functional assays in renal carcinoma cells revealed that PTPN6 knockdown minimally affected short-term migration but modestly reduced long-term clonogenic potential. Critically, PTPN6 expression strongly correlated with an immunosuppressive TME signature, enriched stromal/immune scores, and infiltration of M2 macrophages and Tregs. In vitro co-culture experiments and transcriptome sequencing established a mechanistic axis whereby PTPN6 in tumor cells promotes M2 macrophage polarization via upregulation of thrombospondin 1 (THBS1). Furthermore, high PTPN6 expression defined a coherent immunosuppressive landscape and identified a patient subgroup (high PTPN6/low cytolytic activity) with the worst prognosis. Finally, PTPN6 expression was linked to distinct drug sensitivity profiles, and in silico docking supported its potential as a direct pharmacological target. In conclusion, our work establishes PTPN6 as a multifaceted promoter of immunosuppressive microenvironment remodeling and a pivotal regulator of the TME in RCC, positioning it as a promising prognostic marker and a new therapeutic target.
Accelerated cellular perturbations such as cellular senescence, neuroinflammation and oxidative stress are hallmarks of Alzheimer's disease, a neurodegenerative disease associated with memory decline. However, the senolytic effects of silymarin, a flavonolignan with known antioxidant and anti-inflammatory properties, on memory decline remain unknown. Hence, we investigated the effect of silymarin on doxycycline-mediated senescence and exacerbated neuroinflammation in lipopolysaccharide-induced memory-impaired mice. Five groups of adult Swiss female mice (n = 10) were exposed to doxycycline-induced accelerated senescence for 21 days, followed by lipopolysaccharide-induced neuroinflammation from days 15-21, and silymarin (50 and 100 mg/kg, p.o.) or donepezil (1 mg/kg, p.o.) treatments. Spatial and non-spatial memory, and social and motor function tests in mice were assessed. Biochemical assays were performed on the prefrontal cortex and hippocampus to assess senescence-associated secretory phenotypes (SASPs), including SA-β-galactosidase activity, cytokines (TNF-α, IL-6, IL-10), amyloid-beta levels, acetylcholinesterase activity, oxidative stress markers, and molybdoenzymes. Doxycycline-lipopolysaccharide-exacerbated memory impairments were reversed by silymarin, accompanied by reduced molybdoenzymes, malondialdehyde, nitrite, and elevated antioxidants (glutathione, superoxide-dismutase, catalase) in the prefrontal cortex and hippocampus. Additionally, silymarin reverses doxycycline-exacerbated lipopolysaccharide-induced increases in IL-6 and TNF-α release and myeloperoxidase activity while also reducing IL-10 levels. Similar to donepezil, silymarin reduced heightened acetylcholinesterase activity associated with doxycycline-enhanced lipopolysaccharide-induced accumulation of cortical SA-β-galactosidase and amyloid-β levels, relative to the doxycycline-lipopolysaccharide group. These findings suggest that silymarin ameliorates doxycycline-lipopolysaccharide-exacerbated memory impairment and modulates senescence and neuroinflammation by reducing oxidative stress, SASP marker levels, and amyloid-beta concentrations in the prefrontal cortex and hippocampus of mouse brains.
Resistance to Imatinib hinders the long-term management of gastrointestinal stromal tumors (GISTs). We examined the potential of combining Imatinib with immune checkpoint inhibitors (ICIs) to augment anti-tumor efficacy and alter stress responses in GIST models. GIST cells were assessed in 2D monolayer and 3D co-culture spheroid models utilizing donor peripheral blood mononuclear cells. The treatments consisted of Imatinib administered alone and in combination with Ipilimumab and Nivolumab. MTT assays were used to evaluate cell viability, total oxidant status/reactive oxygen species (ROS), and advanced glycation end products (AGEs) assays, and mitochondrial superoxide (MitoSox) imaging to assess oxidative and glycation stress. Immunoassay and confocal microscopy were employed to measure cell proliferation (Kiel antigen 67 (Ki-67)). Western immunoblotting was performed to explore proteins involved in stress and autophagy (p62, Beclin-1). Data were expressed as mean ± SD from independent experiments (N ≥ 3); statistical significance was assessed using one-way ANOVA with Dunnett's T3 (p < 0.05). Imatinib significantly diminished GIST cell viability in both 2D and 3D models (p < 0.001), decreased intracellular ROS and AGEs, lowered Ki-67 expression, and reduced MitoSox levels. Combination therapies (Ipilimumab, Nivolumab, and combinations with Imatinib) resulted in greater reductions in 3D cell culture viability and further diminished ROS/AGEs levels compared to single agents (p < 0.001). Western immunoblotting showed that Imatinib activated autophagy (↑Beclin‑1, ↓p62). Imatinib demonstrates cytotoxic and antioxidative properties in GIST models and induces autophagy. Combining Imatinib with ICIs enhances anti-tumor effects and further reduces oxidative/glycation stress in 3D tumor-immune co-cultures. These results endorse additional preclinical and translational investigations of tyrosine kinase inhibitor immunotherapy combinations in GIST.
Biological ageing is a heterogeneous process that shapes susceptibility to chronic disease. However, whether ageing patterns diverge within clinically defined type 2 diabetes (T2D) subgroups remains unclear. We investigated whether epigenetic age acceleration (EAA) differs across T2D phenotypes and whether these patterns relate to subsequent renal vulnerability. We included 607 multi-ethnic Asians with recent-onset T2D previously classified into three clinically distinct subgroups: mild obesity-related diabetes (MOD), mild age-related diabetes with insulin insufficiency (MARD-II), and severe insulin-resistant diabetes with relative insulin insufficiency (SIRD-RII). EAA was quantified using multiple epigenetic clocks. Kidney function was assessed longitudinally using eGFR slope over a median follow-up of 7.3 years, serving as a maker of cumulative systemic ageing burden. SIRD-RII, despite being chronologically younger, showed accelerated ageing across multiple second-generation clocks, whereas MARD-II, despite being chronologically older, showed comparatively lower levels of EAA. Among all epigenic clocks examined, GrimAge2logA1c was both highest in SIRD-RII and the only clock associated with kidney function decline (eGFR slope, β [SE] = -0.113 [0.040], p = 4.77 × 10-3). Epigenome-wide analyses identified subgroup-specific, glucose-responsive loci associated with accelerated ageing. Hypomethylation at TXNIP (cg19693031) characterised the SIRD-RII subgroup and was associated with both faster ageing pace and kidney function decline. Exploratory longitudinal within-person changes in glucose-linked epigenetic ageing were correlated with changes in TXNIP methylation within SIRD-RII (r = -0.901, p = 1.93 × 10-6). These findings suggest that T2D subgroups represent distinct epigenetic ageing phenotypes that may be associated with renal vulnerability. Integrating epigenetic ageing metrics with clinical stratification may enhance identification of individuals at risk for accelerated systemic ageing, informing geroscience-guided intervention strategies early in disease development.
Bisphenol A (BPA), a xenoestrogen and endocrine disruptor, is widely used in plastic and polycarbonate products, contributing to metabolic disorders such as dyslipidemia and obesity. Algae, like Chlorella vulgaris (CV), contain highly active compounds that act as natural reducing agents, converting inorganic selenium into nanoparticle form. In this study, we developed novel biologically synthesized selenium nanoparticles using CV (SeNPs-CV) and investigated their protective properties in comparison to physically synthesized selenium nanoparticles (SeNPs) against BPA-induced metabolic disturbances in rats. 40 male albino rats were allocated into four groups (n = 10) and received different oral treatments for 45 days: a control group, a BPA group (150 mg/kg/day), a SeNPs group (2 mg/kg/day alongside BPA), and a SeNPs-CV group (2 mg/kg/day alongside BPA). BPA exposure caused oxidative stress and various metabolic disturbances, evidenced by changes in redox biomarkers, upregulation of fatty acid synthesis-related genes (SREBP1, FAS, ACC1, miRNA-122), and altered lipid profiles. Levels of leptin, adiponectin, NF-κB, TNF-α, and liver function markers were also affected. However, co-treatment with SeNPs and SeNPs-CV significantly alleviated these alterations caused by BPA. Histopathological analysis corroborated these biochemical findings, showing improved hepatic tissue structures with SeNPs and SeNPs-CV. Overall, SeNPs-CV exhibit hypolipidemic, anti-inflammatory, and antioxidant properties that are on par with those of their physically synthesized equivalent, demonstrating their therapeutic potential and acting as an eco-friendly agent that promotes green innovation and environmental sustainability.
Cellular senescence has emerged as an important mechanism linking renal ageing, acute kidney injury, diabetic kidney disease, chronic kidney disease, renal fibrosis, and kidney transplantation-related injury. This study aimed to map the global research landscape, knowledge bases, and emerging frontiers of cellular senescence-related kidney disease research. Publications were retrieved from the Science Citation Index Expanded of the Web of Science Core Collection. After screening by language and document type, 775 English-language articles and reviews were included. CiteSpace and VOSviewer were used to analyze publication trends, citation impact, collaboration networks, productive countries, institutions, authors, journals, highly cited documents, co-cited references, keyword co-occurrence, and citation bursts. The field expanded rapidly after 2016 and reached its highest annual output in 2025. China and the United States were the leading contributors by publication volume. Co-cited reference clustering identified major knowledge bases related to renal ageing, chronic kidney disease-associated premature ageing, maladaptive repair, renal fibrosis, diabetic kidney disease, tubular epithelial injury, SASP, uremic toxicity, transplantation-related injury, and senescence-targeted interventions. Recent hotspots centered on diabetic kidney disease, acute kidney injury, kidney fibrosis, tubular epithelial cells, DNA damage, mitochondrial dysfunction, inflammaging, immunosenescence, extracellular vesicles, and senolytic therapy. Research on cellular senescence-related kidney diseases has shifted from descriptive studies of renal ageing and chronic kidney disease complications toward disease-specific, cell-type-specific, and translational investigations. Future studies should integrate single-cell and spatial multi-omics, establish reliable renal senescence biomarkers, and develop safer kidney-targeted senotherapeutic strategies.
Rare cases of myocarditis and pericarditis following mRNA coronavirus disease-19 (COVID-19) vaccination have been reported, primarily among males under 30 years of age. Although the underlying mechanisms remain unclear, cardiovascular risk factors such as hypertension, diabetes, dyslipidemia, and obesity have been hypothesized as potential contributors. Using the Vaccine Adverse Event Reporting System (VAERS), this study investigated whether these comorbidities were disproportionately reported among young adult males with myocarditis or pericarditis following mRNA COVID-19 vaccination compared with vaccinated and general populations. Additionally, this study represents a novel application of disproportionality principles in spontaneous reporting databases to explore, beyond signal detection, the factors that might be associated with the occurrence of an adverse event. An observed-versus-expected analysis was conducted using reports of myocarditis or pericarditis following mRNA COVID-19 vaccination among males aged 18-30 recorded in VAERS between 2021 and 2022. The prevalence of hypertension, diabetes, dyslipidemia, and obesity among reported cases was compared with prevalence estimates derived from epidemiological studies of vaccinated populations and national population statistics. In addition, disproportionality analyses were performed using comparator groups consisting of reports associated with other vaccines and other adverse events following immunization (AEFIs) within VAERS. A total of 859 eligible reports of myocarditis/pericarditis following mRNA COVID-19 vaccination were identified among males aged 18-30. The prevalence of hypertension, diabetes, dyslipidemia, and obesity was 0.35%, 0.58%, 0.81%, and 1.75%, respectively and was significantly lower than those reported in vaccinated and prepandemic general populations. In disproportionality analyses, myocarditis/pericarditis reports following mRNA vaccination showed higher prevalence of dyslipidemia and obesity, but lower prevalence of hypertension, compared with selected VAERS comparator groups. However, absolute comorbidity prevalence remained low across all groups. No evidence of a modifying role for hypertension, diabetes, dyslipidemia, or obesity was observed for the increased reporting of myocarditis/pericarditis among young adult males following mRNA COVID-19 vaccination. Despite the limitations inherent to spontaneous reporting systems, this study highlights a novel application of disproportionality-based approaches within VAERS to explore potential risk modifiers of vaccine-related adverse events in a hypothesis-generating manner. Rare cases of inflammation of the heart muscle (myocarditis) or of the protective layer around the heart (pericarditis), have been reported after mRNA COVID-19 vaccination, especially in young adult males. This study examined whether common conditions with cardiovascular burden—high blood pressure, diabetes, high cholesterol, and obesity—were more common among males aged 18–30 years who developed myocarditis or pericarditis after mRNA COVID-19 vaccination, which could explain the reason for an increased risk. The study used information from a US vaccine safety monitoring database (VAERS) that collects reports of health problems occurring after vaccination. Researchers compared how often these cardiovascular conditions were reported in young males with myocarditis/pericarditis after mRNA COVID-19 vaccination with how common these conditions are in vaccinated and general US populations. The study found that these conditions were reported less often than expected among myocarditis/pericarditis cases. Additional analyses also showed low reporting of these conditions across other vaccine-related adverse event reports. Overall, the findings do not suggest that high blood pressure, diabetes, high cholesterol, or obesity play a major role in the increased reporting of myocarditis/pericarditis among young adult males following mRNA-based COVID-19 vaccination. The study also highlights a new way of using vaccine safety databases to explore factors that may influence vaccine-related adverse events.
The role of environmental factors in college students' learning adaptation has been widely examined. However, few studies have adopted a more micro-level perspective by focusing on the dormitory context to investigate the relationship between dormitory exclusion and learning adaptation, and its underlying mechanisms. This study investigates the chain mediating roles of loneliness and psychological distress in the relationship between dormitory exclusion and college students' learning adaptation, as well as the gender differences in these mediating pathways based on the Temporal Need-threat Model of Social Exclusion, Social Support Theory and Gender Role Theory. Using a convenience sampling method, 940 college students were surveyed using the dormitory exclusion scale, the loneliness scale, the depression-anxiety-stress scale, and the learning adaptation scale. The results showed that: (1) Dormitory exclusion significantly negatively predicted learning adaptation; (2) Dormitory exclusion predicted college students' learning adaptation through the single and chain mediation of loneliness and psychological distress; and (3) The chain mediation model exhibits gender differences. Specifically, for males, loneliness mediated the relationship between dormitory exclusion and learning adaptation; for females, loneliness and psychological distress serve as both independent mediators and sequential mediators in the relationship between dormitory exclusion and learning adaptation. The findings revealed the underlying mechanism of college students' dormitory exclusion and learning adaptation, providing valuable insights for interventions.
A phase 2 trial (NCT04818346) of the oral Janus kinase 1 inhibitor povorcitinib demonstrated substantial total body and facial repigmentation over 52 weeks in adults with extensive nonsegmental vitiligo (NSV). Here, post hoc analyses evaluated povorcitinib efficacy in patients based on demographic and clinical characteristic subgroups, as well as affected body regions. Data were pooled for 103 patients in the extension-evaluable population who received povorcitinib (15, 45, or 75 mg once daily) throughout the 52-week study. Efficacy among subgroups was evaluated using achievement of ≥ 50% reduction from baseline in total Vitiligo Area Scoring Index (T-VASI50) and ≥ 50%/≥ 75% reduction from baseline in facial VASI (F-VASI50/F-VASI75). Efficacy in the affected body regions was evaluated using VASI50 responses. Data were analyzed using descriptive statistics, and missing values were imputed as nonresponders. At Week 52, 34.0% (35/103) of patients achieved T-VASI50, 61.2% (63/103) achieved F-VASI50, and 45.6% (47/103) achieved F-VASI75. Repigmentation occurred across subgroups regardless of patient age, sex, race, Fitzpatrick skin type, affected body surface area, other autoimmune comorbidities, disease duration, or prior NSV treatment. In addition, VASI50 response rates increased consistently and, in most cases, without plateauing for each body region, ranging from 25.8% for the feet to 57.3% for the head and neck (excluding the face). Decreased rates of disease activity were also evident across body regions. In this exploratory post hoc analysis of adults with extensive NSV, oral povorcitinib produced clinically meaningful repigmentation (as measured by achievement of T-VASI50 and F-VASI75) across patient characteristic subgroups and body regions through 1 year of treatment. Response rates varied by body region, reinforcing the lengthy repigmentation process, especially in nonfacial areas, and highlighting the need to manage patient expectations and encourage adherence to long-term therapy. ClinicalTrials.gov identifier, NCT04818346. Vitiligo is a condition that causes the skin to form white patches. These patches can develop anywhere on the body. In a recent study, people with widespread vitiligo took povorcitinib tablets daily for 1 year. Many saw color return to the white patches of skin on their face and body. The analysis described here examined data from this study and assessed how well the treatment worked in different groups of people based on factors such as age, skin tone, duration of vitiligo, prior treatments, and affected body parts. The analysis included 103 patients who took povorcitinib for 1 year. After a year of treatment, one in three patients had at least half of the lost color return across their body. The face responded even better—nearly half the patients had at least three-quarters of their color return. Importantly, povorcitinib improved skin coloring across different groups of people, regardless of their age, sex (men/women), race, skin tone (fairer/darker), or how much of the body was affected with vitiligo. It also helped people whether they had other autoimmune health problems or not, had vitiligo for a short or long time, or had tried other medicines before. Povorcitinib also worked on different parts of the body, although results were best on the face and the head and neck. Since treatment takes many months and results may appear slowly in some body areas (e.g., the hands and feet), patients should be encouraged to continue treatment long term for the best outcomes.
Ileostomy formation requires major dietary adjustments to prevent complications and maintain nutritional status, yet dietary advice is often inconsistent, and evidence guiding best practice remains limited. This study explored how people living with an ileostomy (ileostomates) and healthcare professionals (HCPs) experience and support dietary management, uniquely comparing UK and Australian perspectives. Fifty semi-structured interviews were conducted with ileostomates (n = 26) and HCPs (n = 12 stoma care nurses, n = 12 dietitians) across the UK and Australia. Interviews were recorded, transcribed and analysed using thematic content analysis guided by the Social Ecological Model (SEM). Seven main categories emerged, spanning intrapersonal, interpersonal, community, institutional and public policy factors. Ileostomates reported persistent dietary restriction, fear of food bolus blockages, and reliance on online forums when HCP follow up was limited. HCP transcripts highlighted variations in practice, constrained caseloads, and gaps in evidence underpinning dietary guidance. Country-specific differences were observed, with Australian ileostomates emphasising hydration and geographical barriers. HCPs in the UK highlighted reinforcement of advice from a stoma nurse or dietitian as being central to dietary reintroduction, whereas their Australian counterparts prioritised a patient-led approach. Findings reveal systemic gaps in dietary support across both countries and highlight the need for individualised support, improved professional training, and integration of digital or telehealth solutions to enhance accessibility and continuity of care.
Huachansu, derived from the dried skin glands of the Chinese toad (Bufo bufo gargarizans), has been used in traditional Chinese medicine for its anti-tumor properties, particularly in hepatocellular carcinoma (HCC). However, its molecular mechanisms remain unclear. This study investigates Huachansu's therapeutic potential by focusing on mitochondrial apoptosis and endoplasmic reticulum (ER) stress pathways. In vitro studies on HepG2 cells revealed that Huachansu (48-96 mg/mL for 24 h) disrupted mitochondrial function by elevating reactive oxygen species (ROS) generation (~ 83% and ~ 208% increase at 48 and 96 mg/mL, respectively) and reducing membrane potential. Molecular analyses showed upregulated pro-apoptotic Bax and ER stress effector CHOP alongside downregulated anti-apoptotic Bcl-2 and caspase family proteins, indicating PERK-ATF4 pathway activation. In vivo investigations using orthotopic and xenograft HCC mouse models demonstrated significant tumor volume (~ 25% at 2 g/kg and ~ 39% at 4 g/kg) and weight reduction with Huachansu treatment (2-4 g/kg/day, oral gavage for 18-21 days). Hepatic function improvements were evidenced by decreased serum ALT, AST, and LDH levels alongside increased superoxide dismutase (SOD) activity. Histopathological analyses confirmed reduced tumor progression and organ toxicity, while inflammatory cytokine profiling revealed diminished pro-inflammatory mediators. Mechanistically, Huachansu activated ER stress markers (PERK, ATF4) in tumor tissues without inducing systemic toxicity. These findings demonstrate that Huachansu exerts potent anticancer effects in HCC through concurrent induction of mitochondrial damage and ER stress activation. This study provides a mechanistic basis for Huachansu's traditional use and highlights its potential as a promising therapeutic agent for HCC treatment.
The present study aimed to investigate MR-based evidence for potential causal relationships between circulating leukocytes, immune cell traits, and multiple sclerosis (MS) using a two-sample, bidirectional Mendelian randomisation (MR) approach. We analysed summary-level data from large-scale genome-wide association studies conducted by the International Multiple Sclerosis Genetics Consortium, the Blood Cell Consortium, and Immune Cell traits. Using inverse variance weighted (IVW), weighted mode, weighted median, simple mode, and MR-Egger methods, we estimated genetically predicted associations. The MR-Egger intercept assessed horizontal pleiotropy, Cochran's Q test examined genetic heterogeneity, and leave-one-out procedures evaluated the sensitivity of the results. We adjusted for multiple comparisons using the false discovery rate (FDR). Forward MR analysis using IVW as the primary method revealed associations between increased white blood cell count (OR = 1.16, 95% CI = 1.05-1.29, P = 0.004, PFDR = 0.031) and lymphocyte count (OR = 1.18, 95% CI = 1.06-1.31, P = 0.003, PFDR = 0.035) with a higher risk of developing MS. Conversely, the CD25hi CD45RA-CD4 not Treg %CD4+ (OR = 0.87, 95% CI = 0.808-0.942, P = 0.0005, PFDR = 0.075) and the CD16-CD56 on HLA DR+ NK (OR = 0.85, 95% CI = 0.780-0.935, P = 0.0007, PFDR = 0.093) were associated with a reduced risk of MS. In reverse MR analyses, MS showed no robust evidence of a causal effect on white blood cell or lymphocyte counts. Although an FDR-significant reverse association was observed for the IgD+ CD38 + B-cell absolute count subtype, leave-one-out sensitivity analysis indicated instability. Therefore, this finding was not considered reliable evidence of reverse causality. Genetic predisposition to increased white blood cell and lymphocyte counts elevates the risk of MS, while certain immune cell traits may reduce this risk.