Search Results (176)

Tri-o-cresyl phosphate (TOCP) is widely used as a plasticizer, flame retardant, and lubricant additive, but has been reported to impair spermatogenesis. However, how TOCP affects spermatogenesis remains unclear. Therefore, the objective of this study is to investigate the underlying mechanism by which TOCP disrupts spermatogenesis. In order to achieve this, adult male mice were orally administered TOCP at doses of 0, 200, or 400 mg/kg for two weeks, and we found that TOCP exposure reduced the number of germ cells and decreased sperm density. Moreover, the numbers of PCNA-positive cells and phospho-histone H3 (Ser10)-positive cells in mouse testicular tissues were significantly decreased following TOCP treatment, indicating that germ cell proliferation may be impaired. In addition, TOCP did not affect the protein expression of neuropathy target esterase (NTE) in testicular tissues but markedly inhibited its enzymatic activity (by approximately 30% relative to the control level). In vitro experiments further demonstrate that TOCP suppressed cell proliferation and mitotic progression in mouse GC-1 spg cells and excessively activated endoplasmic reticulum (ER) stress. Treatment with 4-phenylbutyric acid (4-PBA), an ER stress inhibitor, partially reversed the TOCP-induced inhibition of cell proliferation and mitosis. Furthermore, TOCP inhibited NTE activity in GC-1 spg cells, and NTE knockdown produced a phenotype similar to that observed after TOCP exposure, characterized by suppressed cell proliferation and mitotic progression. Surprisingly, ER stress was not activated in GC-1 spg cells following NTE knockdown. Collectively, these findings suggest that TOCP may impair spermatogenesis by inhibiting the proliferation and mitotic progression of mouse germ cells, potentially through mechanisms involving excessive activation of ER stress or suppression of NTE activity. Full article

Forward osmosis (FO) membranes face challenges in balancing high water permeability, low reverse salt flux (RSF), and mechanical durability. Although nanopores in graphene have great theoretical potential, the existing methods make it difficult to independently optimize the nanopores of the graphene layer and the microstructure of the substrate without damaging each other. Here, we propose a defect engineering strategy based on oxygen plasma etching to address this collaborative optimization challenge. Monolayer porous graphene (PG) was integrated with polysulfone (Psf) substrates, followed by oxygen plasma etching to introduce nanopores and oxygen-containing functional groups (e.g., carboxyl, hydroxyl). By controlling the etching time to 10 s, the resulting membrane (S-PG10) exhibited a water flux of 0.24 LMH in 0.5 M NaCl, representing an order-of-magnitude increase compared to the pristine graphene membrane (S-G). Remarkably, S-PG10 maintained a high salt rejection (>96%) and a low J_s/J_w (<0.35 g·L⁻¹). Substrate modification via short-term plasma etching (5 min) further doubled the water flux of S*5-PG10 (0.47 LMH in 0.5 M NaCl) by increasing porosity (81.8%→85.6%) and hydrophilicity. However, prolonged etching (>15 min) degraded mechanical strength and increased RSF due to pore structure disruption. To enhance robustness, Poly(D,L-lactic acid) (PDLLA)-doped substrates (S^#-PG) were engineered, with 0.1 wt.% PDLLA optimizing mechanical properties while maintaining low RSF and high flux. Excessive PDLLA (10 wt.%) induced hydrophobicity and crystalline structures, reducing permeability. The study demonstrates that synergistic optimization of plasma etching duration on the graphene selective layer (5~10 s) and substrates (5 min) as well as PDLLA doping (0.1 wt.%) balances pore architecture, surface chemistry, and substrate integrity, achieving FO membranes with superior water-salt selectivity and mechanical stability. These findings provide critical insights into designing high-performance graphene-based membranes for sustainable desalination and water purification. Full article

Social media has become a vital source for humanitarian organizations to gather information during crises. However, existing multimodal classification methods operate primarily as isolated systems, while neglecting external references crucial for accurate judgment. Furthermore, while user comments can provide valuable context, they are often scarce during the early stages of a crisis. To address these limitations, we propose a framework named Mix-Persona Comment Generation with Geographically Enhanced Context Retrieval for LLM Instruction Fine-tuning (MPCG-GECR). To mitigate comment scarcity, we employ a Synthetic Persona Generator (SPG) that prompts LLMs to adopt diverse mix-personas, generating synthetic comments that simulate multi-perspective public discourse. To incorporate external references, we introduce a Geographically Enhanced Context Retrieval (GECR) module. Unlike standard retrieval approaches, GECR utilizes a hybrid re-ranking strategy to identify samples that are both multimodally similar and geographically consistent, serving as reliable reference anchors for the LLM. By integrating these social perspectives and geographic references into a unified instruction-tuning format, we transform the classification task into a context-aware text generation problem and fine-tune the LLM using Low-Rank Adaptation (LoRA). Extensive experiments on the CrisisMMD and DMD datasets demonstrate that MPCG-GECR effectively overcomes data scarcity and context isolation, significantly outperforming existing methods. Full article

Male infertility, a global health issue marked by spermatogenic failure, hinges on selenium (Se) as a key element for normal spermatogenesis. Among different Se species, Se-methylselenocysteine (MeSeCys) has been developed as a natural organic Se supplement with potent antioxidant and anti-inflammatory properties, but its direct effects on male reproduction need to be further explored. This study investigated the effect of MeSeCys on GC-1 spg (GC-1) and GC-2 spd (ts) (GC-2) cell lines, which mimic early stages. Treatment with 75 μmol/L MeSeCys for 24 h markedly enhanced the viability of both cell lines, with a more pronounced effect observed in GC-1 than in GC-2 cells. Moreover, this study demonstrated that MeSeCys enters cells through SLC7A11 or LRP8 channels and elevates intracellular Se levels in both GC-1 and GC-2 cells, with higher levels observed in GC-1 cells. RNA sequencing (RNA-seq) and bioinformatics analysis revealed that MeSeCys may regulate selenocompound metabolism and the glutathione metabolism pathway in both cell lines, increasing their intracellular glutathione (GSH) levels. Importantly, in GC-1 cells, MeSeCys specifically modulates the mTOR pathway, which further modulates glutathione metabolism and intracellular redox balance. This finding provides novel insights into the beneficial effects of MeSeCys on male reproductive cells, highlighting its potential as a nutritional supplement for male reproductive health. Full article

Glutamate metabotropic receptors (mGluRs) and their molecular partners at the postsynaptic density (PSD) represent a highly dynamic molecular hub that integrates multiple neurotransmitter signals and regulates synaptic plasticity and metaplasticity, which are putatively involved in the pathophysiology of psychiatric illnesses, including schizophrenia. Group I mGluRs (mGluR1 and mGluR5) interact with PSD adaptor and scaffolding proteins, such as Homer, Shank, Norbin, and PICK1, as well as intracellular downstream effectors, creating a molecular network that resembles a Lego-like structure, where modular protein interactions fine-tune glutamatergic transmission. Evidence from preclinical research indicates that dysregulation of mGluR expression and function, along with disrupted PSD protein expression, may contribute to the pathophysiology of schizophrenia by altering glutamatergic neurotransmission and synaptic stability. Antipsychotic mechanisms of action may involve, at least in part, the modulation of mGluR activity mediated through PSD proteins. Notably, novel agents that enhance spinogenesis by acting at the level of PSD proteins, such as SPG302, may open promising avenues for therapeutics aimed at restoring synaptic integrity. While Group I mGluRs dominate postsynaptic regulation, Group II (mGluR2/3) and III (mGluR4/6/7/8) receptors -primarily presynaptic- inhibit neurotransmitter release and plasticity, offering complementary therapeutic avenues. Emerging strategies, such as allosteric modulators of mGluRs, aim to rebalance synaptic signaling in treatment-resistant schizophrenia. This review synthesizes how PSD proteins and mGluRs interact in schizophrenia, exploring their potential as druggable targets for novel therapies. Full article

Aluminum chloride (AlCl₃), a widely used inorganic polymeric coagulant in everyday products and industrial materials, has been associated with male reproductive toxicity, though its molecular mechanisms remain poorly understood. To investigate the complex molecular mechanisms underlying GC-1spg cells’ responses to AlCl₃ exposure, transcriptome and small RNA (sRNA) sequencing analyses were performed. Transcriptome sequencing identified 1168 differentially expressed genes (DEGs), while sRNA sequencing detected 65 differentially expressed microRNAs (DEMs). An mRNA–miRNA regulatory network was established, and functional enrichment analysis showed that its target genes were significantly associated with multiple signaling pathways, particularly the p53 pathway. Further validation via Western blot and Hoechst 33342 staining assays confirmed that GC-1spg cells underwent apoptosis upon AlCl₃ exposure via the p53 signaling pathway. Among the identified DEMs, mmu-miR-503-5p was found to enhance GC-1spg cells’ tolerance to AlCl₃-induced stress. Moreover, dual-luciferase reporter assays and RT-qPCR confirmed that mmu-miR-503-5p directly binds to the Islr gene, which plays a role in modulating GC-1spg cell tolerance to AlCl₃-induced stress. These findings provide critical insights into the molecular mechanisms governing GC-1spg cells’ responses to AlCl₃ exposure. Full article

Skin aging could lead to dermal collagen loss and elastic fiber degradation, ultimately manifesting as skin laxity. We aimed to counteract this by using poly-L-lactic acid (PLLA) microsphere (MS)-based fillers to facilitate long-term volume restoration through collagen regeneration. However, conventional MSs exhibit limitations such as broad size distribution and surface irregularities, which are frequently associated with significant adverse reactions. This study employed shirasu porous glass (SPG) membrane emulsification to fabricate uniform and well-shaped polyethylene glycol-block-poly (L-lactic acid) (PEG-PLLA) MSs. A single-factor experiment was employed to optimize the parameters. The optimal preparation conditions for PEG-PLLA MSs were as follows: PEG-PLLA concentration of 40 mg/mL, polyvinyl alcohol (PVA) concentration of 0.5%, and magnetic stirring speed of 200 rpm. Under the optimal conditions, the average particle size of PEG-PLLA MSs was 58.982 μm, and the span value (SPAN) was 1.367. In addition, a cytotoxicity assay was performed, and the results revealed no significant toxicity of the MSs toward L929 mouse fibroblasts at concentrations below 500 μg/mL. Furthermore, PEG-PLLA MSs significantly enhanced the production of key extracellular matrix (ECM) components—type I collagen (Col-I), type III collagen (Col-III), and hyaluronic acid (HA)—while simultaneously alleviating cellular oxidative stress responses. This work offers a reliable and reproducible fabrication strategy for developing biocompatible MS fillers with controllable particle sizes. Full article

Hereditary ataxias are a heterogeneous group of disorders with overlapping clinical presentations but diverse genetic and molecular etiologies. Biomarkers are increasingly essential to improve diagnosis, refine prognosis, and accelerate the development of targeted therapies. Following PRISMA-ScR guidelines, we conducted a scoping review of PubMed and complementary sources (2010–2025) to map and describe the current landscape of genetic, imaging, fluid, electrophysiological, and digital biomarkers across the most prevalent hereditary ataxias, including SCA1, SCA2, SCA3, SCA6, SCA7, SCA17, SCA27B, dentatorubral–pallidoluysian atrophy (DRPLA), Friedreich’s ataxia (FRDA), RFC1-related ataxia (CANVAS), SPG7, and fragile X-associated tremor/ataxia syndrome (FXTAS). Eligible evidence encompassed observational cohorts, clinical trials, case series, and case reports providing primary biomarker data, with the objective of characterizing evidence breadth and identifying knowledge gaps rather than assessing comparative effectiveness. Across modalities, converging evidence highlights subtype-specific biomarker signatures. MRI volumetry, DTI, and FDG-PET map characteristic neurodegeneration patterns. Fluid biomarkers such as neurofilament light chain are informative across several SCAs and FRDA, while frataxin levels constitute robust endpoints in FRDA trials. Pathology-specific biomarkers such as ataxin-3 are advancing as tools for target engagement and may generalize to future gene-lowering strategies. Electrophysiological and oculographic measures show sensitivity for early disease detection, and wearable technologies are emerging as scalable tools for longitudinal monitoring. This scoping review synthesizes the heterogeneous evidence on hereditary ataxia biomarkers, highlighting multimodal frameworks that link molecular mechanisms with clinical endpoints. Mapping current approaches also reveals substantial variability and gaps across diseases and modalities, underscoring the need for harmonized validation in international multicenter cohorts and systematic integration into future clinical trials to advance precision medicine in hereditary ataxias. Full article

Background/Objectives: Osteoarthritis (OA) is a pervasive chronic joint disease characterized by the triad of persistent articular cartilage degeneration, debilitating synovial inflammation, and sustained chronic pain. Although salmon nasal cartilage proteoglycan (SPG) is recognized for supporting joint health, the precise molecular mechanism underlying its effects during OA progression remains to be fully elucidated. This study evaluated the therapeutic efficacy of SPG using a monosodium iodoacetate (MIA)-induced mouse model. Methods: A total of 180 male C57BL/6J mice (six-week-old) were utilized, organized into three independent cohorts to analyze distinct analytical endpoints: (1) pain assessment, histology, and immunohistochemistry; (2) mRNA expression analysis for early-stage OA (Day 3); and (3) mRNA expression analysis for the late-stage OA (Day 28). All subjects received daily oral treatment via gavage, commencing 5 days prior to OA induction and continuing until the designated experimental termination points (either Day 3 or Day 28). Each cohort comprised five experimental groups (n = 10–12 per group): a saline-injected Sham group, an MIA-induced Control group, a positive comparator receiving celecoxib (CLX, 20 mg/kg/day), and two groups administered SPG at a dose of 50 or 100 mg/kg/day. Results: Our findings demonstrated that SPG, particularly at the 100 mg/kg dose, significantly mitigated joint pain symptoms, performing comparably to CLX. Histopathological assessments confirmed that SPG effectively preserved the structural integrity of the cartilage matrix and substantially reduced pathological damage, as evidenced by lower Mankin scores. Mechanistically, SPG treatment led to a marked downregulation of degradative enzymes, including matrix metalloproteinase-3 (MMP-3) and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), while concurrently normalizing the levels of tissue inhibitors of metalloproteinases (TIMPs). Furthermore, SPG prevented the aberrant, over-compensatory expression of anabolic markers such as SRY-box transcription factor 9 (SOX-9), type II collagen alpha 1 chain (COL2A1), and aggrecan (ACAN) typically observed in the disease’s later stages. While SPG demonstrated a limited impact on broadly pro-inflammatory cytokine profiles, it specifically and significantly reduced interleukin-6 (IL-6) gene expression during the chronic phase. Conclusions: These results suggest that SPG serves as a promising natural agent that maintains articular homeostasis by balancing matrix metabolic pathways, positioning it as a scientifically validated functional food candidate for the management of joint health. Full article

Aims: Structural lower limb-length discrepancies (LLLD) have been classically associated with the etiology of low back pain. However, their biomechanical effects on lower-limb muscle activity during running remain unclear. This pilot crossover study aimed to evaluate the influence of orthotic interventions—designed to compensate for LLLD and modify foot biomechanics—on the electromyographic (EMG) activity of the contralateral tensor fasciae latae (TFL) in healthy runners. Methods: A total of 41 recreational male and female runners (mean age 32.27 ± 6.09) with structural LLLD were recruited and classified as neutral (Ng), supinated (SPg), or pronated (PRg) based on their foot posture. Surface EMG activity of the TFL in the longer leg was recorded with specific surface electrodes while participants ran on a treadmill at a constant speed of 9 km/h for 3 min. Each subject randomly wore standard orthoses with 5 mm pronating (PRO), supinating (SUP) wedges or orthoses with a heel lift (TAL) to compensate for the shorter leg, alongside the baseline condition (SIN). Results: Perfect reliability (close to 1) was obtained for all measurements. A statistically significant reduction in TFL EMG activity was recorded in the Ng group: SIN 105.64 ± 50.6%MVC vs. PRO 100.16 ± 48.61%MVC (p < 0.05), and SIN vs. TAL 93.49 ± 15.88%MVC (p < 0.001). A significant reduction was also observed in the PRg group: SIN 91.82 ± 40.75%MVC vs. TAL 80.08 ± 31.75%MVC (p < 0.05). Conclusion: Orthotic compensation for LLLD and foot pronation modifications produced measurable changes in TFL EMG activity during running. These findings provide mechanistic insight into the interaction between limb-length asymmetry, foot biomechanics, and proximal muscle activation in runners, and may inform future studies on overuse injuries such as iliotibial band syndrome. Full article

Mutations in the human patatin-like lysophospholipase domain containing the 6 gene PNPLA6 encode an evolutionarily conserved (lyso)phospholipase, leading to the development of a complex hereditary spastic paraplegia 39 (SPG 39) and a number of rare severe syndromes in humans. Diseases disrupt the functioning of the nervous and reproductive systems and the gastrointestinal tract. The study aims to investigate the role of the Drosophila melanogaster swiss cheese gene, an ortholog of the human PNPLA6 gene, in gut function. We showed that the swiss cheese gene knockout leads to changes in the morphology of the midgut, disruption of the septate junction structure and the intestinal barrier permeability, and a decrease in the lipid droplet number in enterocytes. As a result of such disturbances, intestinal stem cells (ISCs) proliferation is activated, and the gut microbiome is altered. Ectopic expression of human PNPLA6 leads to the recovery of the intestinal barrier in the fly gut. The example of Drosophila demonstrates the important role of evolutionarily conserved (lyso)phospholipase in intestinal homeostasis. Full article

Background: Neurodegenerative diseases, including spastic paraplegia type 11 (SPG11), are complex disorders characterized by progressive neurological decline and significant metabolic disturbances. Spatacsin, the protein encoded by the SPG11 gene, plays a critical role in autophagy and lysosomal homeostasis, which are essential for neuronal health. Its impairment leads to defective cellular clearance and neurodegeneration. Recently, personalized and precision nutrition have emerged as promising approaches to enhance clinical outcomes by tailoring dietary interventions to individual genetic, metabolic, and phenotypic profiles. Objectives: This mini scoping review aimed to synthesize current evidence on the application of personalized and precision nutrition in SPG11 and to explore how insights from related neurodegenerative diseases could inform the development of future dietary and metabolic interventions for this rare disorder. Methods: Following PRISMA-ScR guidelines, a scoping review was conducted using PubMed, Scopus, and Web of Science databases (2020–2024). Eligible studies included investigations addressing nutritional, genomic, or metabolic interventions in neurodegenerative diseases. Of 30 screened papers, nine met the inclusion criteria, primarily focusing on nutritional and metabolic interventions related to neurodegenerative and neuromuscular conditions. Results: To date, no dietary intervention trials have been conducted specifically for SPG11. However, evidence from studies on related neurodegenerative diseases suggests that antioxidant, mitochondrial-supportive, and microbiota-targeted dietary approaches may beneficially influence key pathological processes such as oxidative stress, lipid dysregulation, and autophagy—core mechanisms that are also central to SPG11 pathophysiology. Conclusions: Although current evidence remains preliminary, personalized nutrition is a promising supplementary strategy for managing neurodegenerative diseases, including SPG11. Future research should incorporate systems-based approaches that combine dietary, metabolic, and neuroimaging assessments, with sex and comorbidity-stratified analyses, multi-omics profiling, and predictive modeling. These frameworks could help design safe, effective, and personalized nutritional interventions aimed at enhancing metabolic resilience and slowing disease progression in SPG11. Full article

Propiconazole (PRO), a triazole fungicide, controls fungal diseases by disrupting ergosterol production in fungal cells. It is used in crops such as cereals and fruits. However, there are concerns regarding its potential to disrupt the endocrine system and cause reproductive toxicity. This study examined the effects of PRO on mouse testes, germ cells, and GC-1 spermatogonia. After eight weeks, PRO reduced testicular diameter and downregulated key germ cell genes (Sall4, Piwil, Nanos2, and Dazl). A histological examination revealed smaller seminiferous tubules and fewer SALL4+ cells. PRO also impaired steroidogenesis by downregulating genes (StAR, Cyp11a1, 3β-HSD1) and reducing sperm motility, with a decline in Velocity Straight Line (VSL), Linearity (LIN), Straightness (STR), and motile sperm. PRO caused dose-dependent cytotoxicity in GC-1 spermatogonia, decreased proliferation, and increased apoptosis, marked by cleaved caspase-3 and BAX. PRO also induced autophagy, as presented by elevated levels of autophagy-related genes (LC3 and ATG12) and proteins (ATG5 and LC3A/B). 3-Methyladenine (3-MA), an autophagy inhibitor, downregulates levels of autophagy- and apoptosis-related proteins when 3-MA and PRO are simultaneously treated in vitro. This suggests that both apoptosis and autophagy contribute to PRO-induced testicular cytotoxicity. This study is the first to detail that PRO affects sperm motility in mice and induces autophagy-mediated apoptosis in GC-1 spg. Full article

Deoxynivalenol (DON) is a trichothecene mycotoxin produced by Fusarium species that frequently contaminates cereal crops, representing a major threat to food safety, public health, and agricultural productivity. Its remarkable chemical stability during food processing presents significant challenges for effective detoxification. Among the available mitigation strategies, biological approaches have emerged as particularly promising, as they exploit enzymatic systems capable of converting DON into metabolites with substantially reduced toxicity. In this study, we provide a comprehensive analysis of the structural and evolutionary mechanisms underlying DON detoxification across three kingdoms of life. We investigated the fungal glutathione S-transferase Fhb7, the bacterial DepA/DepB epimerization pathway, and the plant SPG glyoxalase using integrative bioinformatics, phylogenetics, molecular modeling, and docking simulations. The selected enzymatic systems employ distinct yet complementary strategies: Fhb7 conjugates DON with glutathione and disrupts its epoxide ring, DepA/DepB converts it into the less toxic 3-epi-DON through stereospecific epimerization, and SPG glyoxalase mediates DON isomerization. Despite their mechanistic differences, these enzymes share key adaptive features that enable efficient DON recognition and detoxification. This work provides an integrative view of cross-kingdom enzymatic strategies for DON degradation, offering insights into their evolution and functional diversity. These findings open avenues for biotechnological applications, including the development of DON-resistant crops and innovative solutions to reduce mycotoxin contamination in the food chain. Full article

The gene SPG7 codes for the protein paraplegin, a subunit of the m-AAA protease in the inner mitochondrial membrane involved in protein quality control. SPG7 was initially identified as causing autosomal recessive hereditary spastic paraplegia (HSP), with a pure (insidiously progressive bilateral leg weakness and spasticity) and complex (with additional neurologic features including cerebellar signs and optic atrophy) forms. Now identified as one of the most common causes of HSP, SPG7-associated disease has been linked to additional neuro-ophthalmologic features, including isolated dominant optic atrophy, cerebellar eye signs (various forms of nystagmus, dysmetric saccades), progressive external ophthalmoplegia (PEO), and supranuclear vertical palsy. This review describes in detail the various neuro-ophthalmologic presentations of SPG7-associated disease, illustrating the role of mitochondrial dysfunction in the pathophysiology of these different entities. Knowledge of the different manifestations of SPG7-associated disease is crucial for both neurologists and ophthalmologists, and SPG7 should be considered in the work-up of patients presenting with entities such as optic atrophy, PEO, and cerebellar eye signs. Full article