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Remotely supervised home-based transcranial direct current stimulation (HB-tDCS) may expand access to neuromodulation for treatment-resistant depression (TRD), but real-world evidence on candidate biomarkers remains limited. In this single-arm pre-post study, 40 adults with major depressive disorder and inadequate response to ≥2 treatments were enrolled. After MRI/clinical screening, 2 were excluded for potential stimulation contraindications and 5 did not start or discontinued within the first sessions for personal reasons unrelated to stimulation. 33 participants completed a 6-week semi-supervised HB-tDCS protocol (42 sessions, 30min, 2mA; anode F3/cathode F4). Baseline and post-treatment assessments included clinician-rated and self-rated depression (MADRS, QIDS-SR16, BDI-II), global cognition (MoCA), quality of life (Q-LES-Q-SF), and neurophysiological markers (resting-state EEG and TMS-EEG). Feasibility, technical incidents, and adverse effects were recorded after each session. Feasibility and safety constituted the primary outcomes; clinical and neurophysiological outcomes were treated as secondary and exploratory endpoints respectively, with biomarker analyses uncorrected for multiple comparisons. Completers delivered 1,219/1,386 scheduled sessions (88%). Depressive symptoms decreased from baseline to post-treatment (MADRS -24%, QIDS-SR16 -15%, BDI-II -12%; all p≤.002). Sixteen of 33 (48.5%) achieved ≥25% MADRS reduction (partial response), including 5 (15.2%) with ≥50% reduction. MoCA improved modestly, whereas Q-LES-Q-SF did not change significantly. Adverse effects were mostly mild/moderate (e.g., tingling, headache, scalp dryness), and no stimulation-related serious adverse events occurred. Exploratory analyses suggested higher baseline left-frontal alpha (F3) relative power and candidate TMS-EEG evoked potentials in the left DLPFC (P30, P180) may differentiate responders from non-responders. An intensive, semi-supervised HB-tDCS program was feasible and well tolerated in TRD and was associated with significant symptom reductions. Candidate EEG/TMS-EEG markers warrant replication in controlled trials.

Percutaneous endoscopic gastrostomy (PEG) is widely used to provide long-term enteral nutrition; however, mortality remains substantial, particularly among frail and multimorbid patients. Data on how specific metabolic and inflammatory phenotypes influence both early and long-term survival after PEG are limited. This study aimed to identify predictors of 30-day and long-term mortality following PEG, with a particular focus on nutritional and inflammatory biomarkers. This single-center retrospective cohort study included 495 adult patients who underwent PEG insertion between December 2013 and May 2024. Predictors of 30-day mortality were assessed using multivariable logistic regression. Long-term survival, with follow-up of up to 10 years, was evaluated using Kaplan-Meier analysis and multivariable Cox proportional hazards regression. The mean age of the cohort was 72.5 &#xb1; 15.5 years, and 30-day all-cause mortality occurred in 97 patients (19.6%). In multivariable logistic regression analysis, low serum creatinine (<0.40 mg/dL; OR=2.64), elevated neutrophil-to-lymphocyte ratio (NLR > 5; OR=2.31), hypoalbuminemia, and a higher Age-Adjusted Charlson Comorbidity Index were independently associated with early mortality. Long-term survival analysis demonstrated a pronounced gradient according to metabolic status. Patients with severe hypoalbuminemia (<2.0 g/dL) had a median survival of only 40 days, compared with 776 days in the highest albumin category (&#x2265;3.2 g/dL) (p < 0.001). Marked systemic inflammation (CRP > 150 mg/L) was associated with a median survival of 46 days. Notably, very low serum creatinine (<0.40 mg/dL), interpreted as an indirect marker of reduced creatinine generation and potentially reduced muscle reserve, was independently associated with long-term mortality (HR= 1.77, 95% CI 1.15-2.71) and in contrast, elevated creatinine was not independently associated with mortality in the adjusted model. In this retrospective cohort, markers of metabolic depletion and systemic inflammation, particularly hypoalbuminemia, elevated CRP/NLR, and low serum creatinine, were independently associated with short- and long-term mortality after PEG insertion. These associations remained clinically relevant after considering procedural indication, although the heterogeneity of PEG candidates and the retrospective nature of the study preclude causal inference. Low serum creatinine may reflect a high-risk phenotype characterized by reduced muscle reserve, but it should be interpreted as an indirect surrogate rather than a diagnostic marker of sarcopenia. Incorporating routinely available pre-procedural markers such as albumin, CRP, NLR, and creatinine into the clinical assessment may support more individualized PEG candidate evaluation and shared decision-making.

Apolygus lucorum has become an economically damaging pest due to the lack of efficacy in currently used Bacillus thuringiensis (Bt) cotton varieties and the reduced application of broad-spectrum insecticides. Mpp51Aa (Cry51Aa) proteins are promising insecticidal candidates with specific activity against hemipteran pests, including A. lucorum. However, the molecular mechanisms of their toxicity and the host cellular response remain poorly understood. This study aimed to characterize the temporal transcriptomic response of the A. lucorum gut to Mpp51Aa1 and Mpp51Aa2 toxins and to elucidate the functional roles of MAPK signaling and downstream targets in mediating toxicity. Our findings showed that Mpp51Aa1 triggered a more robust transcriptomic response than Mpp51Aa2, correlating with its higher potency. Analysis of MAPK signaling revealed that Mpp51Aa toxins increased p38 and ERK expression but decreased JNK expression at both the transcript and protein levels. Silencing these pathways reduced nymph mortality, indicating that p38 and ERK activation facilitates toxin-induced damage rather than protective roles observed in other species. Analysis of candidate gut proteins identified ALP2 as an essential susceptibility factor for both Mpp51Aa toxins. Furthermore, silencing p38 and ERK significantly reduced the expression of this downstream target. In conclusion, Mpp51Aa toxins utilize a unique mechanism by manipulating the MAPK signaling network of A. lucorum to trans-regulate ALP2 expression, thereby enhancing toxin susceptibility and pathogenicity. These findings provide critical insights into the molecular basis of hemipteran susceptibility to Bt Mpp51Aa toxins.

Oxidative stress drove neuronal damage by disrupting redox homeostasis and played a crucial role in the progression of neurological disorders. Natural antioxidants garnered significant interest as potential therapeutics. Morroniside exhibited promising antioxidant activity but had low bioavailability and poor lipid solubility, limiting its therapeutic application. To address these limitations, a series of alkyl and benzenesulfonate ester derivatives were designed and synthesized. Their antioxidant activities were evaluated using multiple in vitro assays. Structure-activity relationship (SAR) analysis indicated that both the type and position of substituents influenced antioxidant activity. Subsequently, the six most active derivatives were selected and evaluated for cytotoxicity and antioxidant capacity in hydrogen peroxide (H2O2)-induced PC12 cells. The results identified derivative 4b as the most promising candidate, demonstrating acceptable cytotoxicity and strong protective effects. Furthermore, 4b significantly increased superoxide dismutase (SOD) activity while reducing intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Mechanistic studies suggested that 4b exerted antioxidant effects through modulation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. These findings demonstrated that sulfonate ester modification was an effective strategy to improve the antioxidant activity of morroniside, and derivative 4b was identified as a promising antioxidant and neuroprotective candidate.

Chronic obstructive pulmonary disease (COPD) progression may be influenced by non-smoking environmental exposures, especially among never-smokers and environmentally exposed populations. Semi-volatile organic compounds (SVOCs) are relevant because they persist in air, particles, dust, surfaces and biological matrices and can enter the body through inhalation, dust ingestion, diet and dermal uptake. This review aimed to synthesize evidence on SVOC exposure assessment, respiratory and COPD-related outcomes, and candidate metabolomic pathways related to COPD progression. We conducted a critical narrative review with structured evidence mapping. PubMed and Web of Science searches identified 4535 records; 3087 remained after DOI- and title-based deduplication, and 1251 unique studies were included in the primary evidence map after screening and manual classification. Polycyclic aromatic hydrocarbons (PAHs) and phthalates showed the most developed evidence across respiratory and lung-function outcomes and the closest, although still limited, evidence related to COPD progression. Evidence from asthma, airway inflammation, general lung function and cross-sectional COPD occurrence was interpreted as supportive but indirect. Direct progression evidence in diagnosed COPD cohorts remains sparse. Metabolomic evidence suggested candidate pathways involving glycerophospholipid-sphingolipid remodeling, amino-acid metabolism, arginine-nitric oxide signaling, acylcarnitine-tricarboxylic acid cycle activity and redox balance, but these pathways have not been validated as mediators. Current evidence supports respiratory relevance of several SVOC classes but is insufficient to establish SVOCs as causal drivers of COPD progression. Future longitudinal COPD cohorts should integrate repeated environmental sampling, human biomonitoring, source attribution, mixture modeling and targeted metabolomics to clarify preventable exposure-progression pathways.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with a 5-year survival rate below 20 % for advanced-stage patients. Fuzheng Xiaozheng Prescription (FZXZP), a traditional Chinese medicine compound, has demonstrated promising anti-HCC activity in preliminary studies, but its key bioactive components and molecular targets remain undefined. To systematically elucidate the active constituents and mechanistic targets of FZXZP against HCC using an integrated bulk RNA, single cell RNA sequencing (scRNA-seq), network pharmacology and experimental validation approach. The anti-tumor efficacy of FZXZP was evaluated in a murine HCC model and in human HCC cell lines. Untargeted metabolomics (LC-MS/MS) was performed to identify bioactive components in FZXZP aqueous extract and drug-containing serum. Network pharmacology analyses were then conducted to predict potential molecular targets associated with these bioactive constituents. Transcriptomic analyses integrated bulk RNA-seq data from TCGA-LIHC and GEO (GSE87630, GSE149614) with scRNA-seq data (GSE149614). Differential expression analysis, weighted gene co-expression network analysis, univariate Cox regression and network pharmacology were integrated to identify candidate genes. Three machine-learning algorithms (XGBoost, maximal clique centrality, and Eccentricity) were used to refine key genes. Key findings were rigorously validated in independent cohorts at the single-cell level, and confirmed through in vitro and in vivo experiments, including flow cytometry, Western blot, and quantitative real-time PCR (qRT-PCR). Loss- and gain-of-function experiments were performed via cell transfection to validate key targets and mechanisms. Finally, molecular docking, molecular dynamics (MD) simulations and surface plasmon resonance (SPR) assay assessed compound-target binding. FZXZP treatment markedly inhibited HCC progression in murine models, significantly improving liver histopathology and serum ALT/AST levels. In vitro, FZXZP effectively suppressed HCC cell proliferation, migration, and invasion. A total of 134 bioactive components were identified in FZXZP aqueous extract and drug-containing serum, corresponding to 1181 predicted targets. Integration of 1208 differentially expressed genes, 297 hub genes, 9999 risk-associated genes, and 1181 drug targets yielded 17 candidate genes, significantly enriched in cell cycle regulation signaling pathways. Machine-learning algorithms consistently selected CCNB1 as the core regulatory gene. scRNA-seq analysis demonstrated that fibrotic cells exhibited the most pronounced intercellular communication with other cell types, and CCNB1 expression was significantly elevated within the fibrotic cell population in HCC. CCNB1 showed robust diagnostic performance (AUC of 0.971 in TCGA, 0.784 in GSE87630). Mechanistically, FZXZP induced G2/M phase arrest and downregulated CCNB1 and CDK1 expression at both the mRNA and protein levels. In cell models involving gene knockdown and overexpression, CCNB1 has been validated as an oncogene and identified as a key target for FZXZP against HCC. Molecular docking, MD simulations and SPR assay further confirmed stable binding between 7-Methoxyflavone, a principal active component, and CCNB1(binding energy:-83.218 kJ/mol; KD=1.72 &#xb5;M). 7-Methoxyflavone alone recapitulated the anti-HCC effects, supporting its role as a representative bioactive compound of FZXZP. FZXZP exerts its anti-HCC effects primarily through its representative component, 7-Methoxyflavone, by suppressing CCNB1/CDK1 and consequently triggering G2/M cell cycle arrest. These findings establish CCNB1 as a therapeutic target and provide a mechanistic rationale for FZXZP in HCC treatment.

Pain is a highly prevalent and disabling non-motor symptom of Parkinson's disease (PD), yet it remains underrecognized and frequently undertreated in clinical practice. Although long considered a secondary consequence of motor dysfunction, pain in PD is now increasingly understood as a manifestation of disease-related alterations in nociceptive processing. These changes extend beyond dopaminergic deficiency and involve broader neurotransmitter imbalances and impaired descending inhibitory control across different neuroanatomical regions, providing a framework for understanding pain as an intrinsic feature of PD rather than a purely peripheral or motor-related phenomenon. We also summarize the main categories of pain experienced in PD, each with distinct clinical features and underlying pathophysiological mechanisms, and link them with current management strategies. A multimodal, mechanism-informed approach that integrates optimization of dopaminergic therapy with non-dopaminergic pharmacological treatments, neuromodulation, rehabilitation, and complementary interventions is key to a personalized treatment plan for pain in patients with PD. Finally, we highlight emerging translational directions, including candidate biomarkers that may help objectify pain and its related dysfunction in the PD population. Focusing on the neurobiological basis of pain in PD, this review aims to support a shift toward mechanism-based assessment and management, with an ultimate goal of improving pain outcomes and quality of life for individuals living with the disease.

Hepatitis A is a viral infection of the liver that can cause mild to severe illness. Currently, two types of HAV vaccines are used worldwide, inactivated hepatitis A vaccines, which are used in most countries, and live attenuated vaccines (H2 and L-A-1 strain), which are mainly used in China. the major disadvantage of live attenuated virus to cause secondary infections among contacts and mutation shifts of the live vaccine strain. The H2 strain was selected for the development of an inactivated hepatitis A vaccine to further reduce biosafety risks. Rhesus macaques high genomic homology with humans and the incubation period after hepatitis A vaccination and human natural infections are similar. We use rhesus macaques to assess immunogenicity and safety of the H2 strain Hepatitis A Inactivated Vaccine. The vaccine was assessed in rhesus macaques, divided into four groups (n=10 per group): the control group (adjuvant buffer; aluminum content 0.35mg/mL; 2mL per dose), the low-dose group (320EU, 0.5mL of 640EU/mL with aluminum content 0.35mg/mL), the medium-dose group (640EU, 1mL of 640EU/mL with aluminum content 0.35mg/mL), and the high-dose group(1280EU, 2mL of 640EU/mL with aluminum content 0.35mg/mL). Animals were injected intramuscularly at multiple sites in the hind limbs and received four inoculations at 4-week intervals. Test items including Clinical indicators, immunogenicity indicators and Histopathological examination. No abnormalities were observed in any group in terms of general clinical condition throughout the study period except for slight decreases in body temperature after immunization. Hematological parameters, serum biochemistry indices, and histopathological findings showed fluctuated to different degrees of fluctuation after immunization across all groups. Immunogenicity assessments showed that the inactivated hepatitis A vaccine (H2) induced both humoral and cellular immune responses effectively, and the levels of neutralizing antibodies increased with certain dose- and time-response trends. The inactivated hepatitis A vaccine (H2 strain, human diploid cell) was safe and immunogenic in non-human primates. The results provide strong preclinical support for the further clinical development of this vaccine candidate.

Progressive pulmonary fibrosis (PPF) is a severe lung disease characterized by persistent tissue damage and scarring, with no curative therapies currently available. The multifactorial and poorly understood pathogenesis complicates drug development, highlighting the need for novel multi-targeted anti-fibrotic therapeutics. Our previous study established a phenotypic screening platform identifying inhibitors of radiation-induced endothelial-to-mesenchymal transition. The screening revealed that 2-methoxyestradiol (2-ME), a hypoxia-inducible factor (HIF)-1&#x3b1; inhibitor, altered morphology and ultrastructure with abrogation of actin stress fibers in radiation-treated human umbilical vein endothelial cells (HUVECs). In this study, we synthesized 15 novel 2-ME derivatives to enhance anti-fibrotic efficacy. Among them, ABRL8301 showed the greatest potency, promoting mesenchymal-to-endothelial transition (MEndT) and reducing mesenchymal markers. ABRL8301 reduced 11&#x3b2;-hydroxysteroid dehydrogenase type 1 (11&#x3b2;-HSD1) expression and concomitantly increased heme oxygenase-1 (HO-1) levels in fibrosis-relevant cell types, which we interpret as pathway-level evidence consistent with 11&#x3b2;-HSD1 engagement rather than direct pharmacodynamic target validation. This leads to decreased NF-&#x3ba;B nuclear translocation, HIF-1&#x3b1;, and extracellular matrix protein levels, enhancing MEndT/mesenchymal-to-epithelial transition (MET) and suppressing fibrotic progression. In macrophages, ABRL8301 inhibits NF-&#x3ba;B signaling, promotes polarization toward the M2 anti-inflammatory phenotype, and suppresses interleukin-6 expression, contributing to its anti-fibrotic and immunomodulatory effects. Furthermore, ABRL8301 significantly attenuated PPF in both bleomycin- and radiation-induced mouse models, showing more pronounced histological and radiological improvement in lung consolidation and collagen deposition compared with nintedanib at the tested doses. ABRL8301 also mitigated radiation-induced skin vascular injury and collagen accumulation. Collectively, these findings identify ABRL8301 as a promising therapeutic candidate for PPF via the 11&#x3b2;-HSD1/HO-1/HIF-1&#x3b1; axis.

Foeniculum vulgare Mill. is an important medicinal and edible plant, whose volatile constituents are predominantly composed of monoterpenes and sesquiterpenes. However, studies on genes involved in terpenoid biosynthesis and their functional characterization in this species remain relatively limited. In this study, integrated metabolomic and transcriptomic analyses were conducted to systematically elucidate terpenoid metabolites and their associated biosynthetic genes in F. vulgare. A total of 53 terpenoid metabolites and 109 putative terpene biosynthetic genes were identified. Five candidate terpene synthase (TPS) genes were identified from full-length transcriptome sequencing and functionally characterized using an Escherichia coli heterologous expression system. FvTPS1 exhibited limonene synthase activity, whereas FvTPS2 primarily produced &#x3b1;-pinene together with minor amounts of &#x3b2;-pinene. Shake-flask fermentation experiments showed that the titer of limonene reached 295.75&#x202f;&#xb1;&#x202f;35.63&#x202f;mg/L, while &#x3b1;-pinene production reached 254.01&#x202f;&#xb1;&#x202f;12.72&#x202f;mg/L. Overall, this study provides a comprehensive overview of the terpenoid metabolome and transcriptome of F. vulgare, and reports for the first time the identification of limonene synthase and pinene synthase in this species. These findings offer valuable functional gene resources for the metabolic engineering and industrial production of high-value monoterpenes derived from F. vulgare.

Improving nitrogen use efficiency (NUE) is essential for sustainable agriculture, yet conventionally measured plant characteristics have limited value as NUE proxies. Here we show that artificial intelligence (AI) can uncover previously unrecognized phenotypic variation associated with NUE, revealing genetic variation that is largely missed by conventional phenotypes. We trained a convolutional neural network (CNN) on 25,080 maize images to learn features that distinguish how plants respond to low- and high-N conditions, achieving 96.7% accuracy. The learned features were defined as deep phenotypes. Compared with conventional phenotypes, deep phenotypes showed greater phenotypic variation and higher heritability, enabling the identification of 523 significant loci compared with 21 for conventional phenotypes. We next investigated candidate genes underlying these loci and used these findings to interpret the learned features. Lower CNN layers primarily reflected visual patterns overlapping with conventional phenotypes, whereas deeper layers encoded additional features associated with N-responsive genetic variation. To validate candidate genes identified by the AI framework, we functionally characterized Liguleless2 (LG2), a basic-leucine zipper (bZIP) transcription factor, and demonstrated that lg2 mutants exhibit enhanced root architecture and increased N uptake efficiency. Field trials of 200 hybrids across diverse N environments further supported the AI findings, with each beneficial allele increasing ear weight by an average of 18 g per plot under low-N conditions. These results show how integrating AI and biology can uncover biologically relevant variation underlying complex traits such as NUE and enhance the interpretability of AI models.

Tobacco is a model plant as well as an important economic crop. Black shank disease, caused by Phytophthora nicotianae, severely undermines tobacco yield and quality, yet the molecular basis of differential cultivar resistance remains incompletely understood. Here, we compared the resistant cultivar, 'Xiangyan 7' (X7) and the susceptible cultivar 'Honghuadajinyuan' (HD), after inoculation with P. nicotianae race 0. Disease evaluation showed that X7 had a significantly lower disease index than HD. Transcriptomic and metabolomic analyses were performed on leaves collected at 0, 1, 2, 4, 8, and 12 days post-inoculation (dpi). RNA-seq identified extensive transcriptional responses in both cultivars; the inter-cultivar differentially expressed gene (DEG) number peaked at 8 dpi with 14,160 DEGs (7057 up-regulated and 7103 down-regulated). Widely targeted metabolomics detected 1092 metabolites, and the inter-cultivar differentially accumulated metabolite (DAM) number peaked at 12 dpi with 355 DAMs (95 up-regulated and 260 down-regulated). Weighted Gene Co-expression Network Analysis (WGCNA) identified 593 hub genes from three resistance-associated modules (Coral3, Lightblue3, and Lavender). Integrated Kyoto Encyclopedia of Genes and Genomes (KEGG) co-enrichment analysis revealed that phenylpropanoid biosynthesis, biosynthesis of secondary metabolites, and plant hormone signal transduction were common transcriptional-metabolic pathways enriched in X7, together with early calcium-related signaling in the plant-pathogen interaction pathway. These results suggest that the stronger resistance to P. nicotianae by X7 is associated with rapid coordination of defense-related transcription, phenylpropanoid and flavonoid metabolism, hormone signaling, and suppression of photosynthesis and primary metabolism. Our study provides multi-omics resources and candidate genes, including Nitab4.5_0000101g0110, Nitab4.5_0000101g0120, Nitab4.5_0001915g0140, and Nitab4.5_0002942g0040, for improving tobacco resistance to black shank disease.

Bacterial epididymo-orchitis, primarily driven by uropathogenic Escherichia coli (UPEC), is a major cause of inflammatory testicular injury and male infertility. While our previous study indicates that neutrophils are rapidly recruited to the immune-privileged testis to contain the infection, their excessive activation can paradoxically exacerbate tissue destruction. However, the specific cellular states and molecular mediators driving this injurious inflammatory response remain poorly defined. To address this gap, we utilized single-cell transcriptomics in a murine orchitis model to map the dynamic remodeling of the testicular neutrophil compartment. We identified a dominant pathogenic subpopulation (Cluster 0) that rapidly expands during acute infection and is characterized by robust S100a8 expression (accompanied by concomitant induction of its heterodimeric partner, S100a9). Flow cytometric and spatial analyses confirmed the marked accumulation of CD11b+Ly6G+S100A8+ neutrophils within damaged reproductive niches. Notably, pharmacological inhibition of the S100A8/S100A9 complex with paquinimod reduced this pathogenic neutrophil infiltration and preserved testicular architecture. Together, these findings identify S100A8 as a key marker and candidate contributor to neutrophil-mediated tissue injury, and suggest that this axis warrants further investigation as a targeted immunomodulatory strategy that may help preserve fertility during bacterial infections.

Diagnostic errors are a substantial source of patient harm. As artificial intelligence (AI) integrates into clinical workflows, opportunities are emerging to assess their impacts on diagnostic excellence (DxEx). The Coordinating Center for Diagnostic Excellence (CODEX) at the University of California San Francisco established the Action Incubator to translate research advances in DxEx into tangible strategies for improving diagnosis. The September 2025&#xa0;in-person inaugural Action Incubator convened 30 multidisciplinary stakeholders representing health systems, patient advocacy, industry, and policy groups. Through structured discussions and breakout sessions, participants identified AI scribes as a near-term, scalable use case for evaluating AI's impact on diagnosis not only because of their widespread adoption, but&#xa0;-&#xa0;as supported by cognitive load theory&#xa0;-&#xa0;because of their potential to reduce cognitive burden and allow clinicians to focus more on diagnosis. A modified Delphi process was used to prioritize candidate measures based on feasibility, and impact. Participants generated 17 candidate measures of AI scribe impact on DxEx. Consensus was reached on two priority metrics as functions of AI scribe usage rates by primary care physicians: (1) Timely follow-up of abnormal test results related to breast and colorectal cancer screening and (2) Patient-reported diagnostic experience. Participating health systems will pilot these measures using electronic health record audit logs and patient surveys. The first CODEX Action Incubator developed a pragmatic, consensus-driven framework for measuring the impact of AI on DxEx. Future annual Action Incubators will take up timely, actionable topics related to&#xa0;DxEx.

Male fertility is declining, and synthetic chemicals are a major candidate for causing it. This study investigated the effect of oral consumption of perfluorooctanoic acid on sperm quality and in vitro fertilization and the therapeutic role of alpha-lipoic acid in improving its possible effects. Twenty adults male NMRI mice weighing 24-20 g were used. The male mice were divided into four groups. The control group received no drug. The sham group received only DMSO. The model group received PFOA (10 mg/kg), and the treatment group received PFOA (10 mg/kg) and ALA (dissolved in distilled water, 100 mg /kg). After the treatment period, blood, sperm and testicular tissue samples were collected from male mice. Serum testosterone level, testicular weight and histology, sperm analysis and sperm DFI were assayed. Then, using the IVF technique, fertilization rates at the 2PN, two-cell and cleavage stages were recorded. Exposure of male mice to PFOA significantly reduced sperm parameters (concentration, motility, morphology, viability), testicular weight, testosterone levels, IVF rates at the 2PN, two-cell and cleavage stages and increased sperm DFI. Simultaneous administration of ALA significantly reduced these adverse effects. P < 0.05 was considered significant. Our findings showed that ALA can improve the harmful effects of PFOA on sperm and fertilization rate. Therefore, the use of ALA to improve IVF outcomes deserves further attention. Given the persistent presence of PFOA in the environment and its associative (not causal) link with reduced sperm quality, further research and larger studies in this area seem necessary.

Fungi are major phytopathogens that have a strong impact on agricultural productivity. Recently, biological control has gained attention for managing plant pathogenic fungi due to its eco-friendly characteristics. Hence, using biological agents to replace chemical fungicides is a viable alternative approach in sustainable agriculture systems. In this study, we demonstrated the potentiality of Streptomyces sp. VNUA24 as a promising biocontrol agent. The strain strongly inhibited mycelial growth of several common pathogenic fungi. Its culture filtrate also altered fungal morphology, restricted hyphal elongation, inhibited spore germination, and suppressed fungal virulence. Biochemical assays and genomic analysis revealed the productions and encoding genes for several hydrolytic enzymes. The antiSMASH analysis identified 38 biosynthetic gene clusters in the genome. Interestingly, many of these exhibited strong homologies to clusters responsible for producing established antifungal metabolites such as &#x3b5;-poly-L-lysine, concanamycin A, informatipeptin, and humidimycin. These findings highlight the strong antifungal potential of Streptomyces sp. VNUA24 and suggest that it is a promising candidate for developing microbial control agents in sustainable fungal disease management.

With increasing emphasis on extending healthy lifespan, aging research requires vertebrate models that permit efficient mechanistic investigation and intervention testing within practical time and cost constraints. The African turquoise killifish (Nothobranchius furzeri) has attracted growing attention because it combines an exceptionally short life cycle with an intact vertebrate physiological context and an expanding genetic toolkit, enabling relatively rapid evaluation of candidate aging interventions and mechanistic analysis across molecular, tissue, and organismal levels. This review assesses N. furzeri from an integrative-physiology perspective, focusing on germline-soma interactions, gut microbiota-host crosstalk, nutrient sensing and metabolic remodeling, temperature responsiveness, and AMPK-mTOR-linked programs. It also examines expanding genome-engineering and reporter approaches that support mechanistic and tissue-resolved investigation of these physiological processes. Building on recent reviews of killifish biology, disease modeling, regeneration, and the hallmarks of aging, we synthesize evidence across major intervention domains, distinguish established phenotypic effects from incompletely resolved mechanisms, and highlight functional endpoints, methodological standardization, and the appropriate interpretation of the model's translational relevance. Together, these features position N. furzeri as a strategically useful vertebrate platform for rapid mechanistic testing, intervention evaluation, and prioritization of aging-related pathways. Future progress will require improved methodological standardization, tissue-resolved causal studies, and question-driven cross-species validation where appropriate.