搜索结果：Candidate

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.

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.

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.

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.

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 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 - as supported by cognitive load theory - 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 DxEx.

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.

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.

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.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, irreversible interstitial lung disease that severely impairs patients' quality of life and overall survival, yet few therapeutic drugs are available for this disease. Cordyceps militaris (L.) Link. is an edible and medicinal fungus renowned for its lung- and kidney-nourishing properties. Decoctions containing C. militaris and other traditional Chinese medicines have been used clinically to treat elderly patients with IPF. Nevertheless, whether C. militaris or its derived products can suppress the progression of pulmonary fibrosis remains unclear. This study aimed to evaluate the effect of a granule formulation prepared from the aqueous extract of C. militaris (CC) on pulmonary fibrosis. An HPLC-UV method was used for the quantification of five major nucleosides in CC and its ethanol extract (CCE, with maltodextrin removed). Two pulmonary fibrosis cellular models were utilized to evaluate the bioactivity of CCE, including TGF-&#x3b2;1-stimulated BEAS-2B human bronchial epithelial cells and A549 human lung adenocarcinoma epithelial cells. A bleomycin-induced mouse model of pulmonary fibrosis was established to evaluate in vivo efficacy of CC. Western blot and RT-qPCR were performed to quantify the protein and mRNA expression levels of key biomarkers associated with epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) deposition in pulmonary fibrosis, including E-cadherin, N-cadherin, vimentin, &#x3b1;-SMA, fibronectin, collagen I and collagen III. Non-invasive whole-body plethysmography (WBP) was used to measure pulmonary function parameters in mice. The contents of uridine, guanosine, adenosine, cordycepin, and N6-(2-hydroxyethyl)adenosine were 0.84, 0.56, 0.93, 1.56 and 1.15 mg/g in CC and 4.49, 1.71, 3.96, 5.57 and 4.79 mg/g in CCE, respectively, with the total nucleoside content being 5.04 and 20.52 mg/g. CCE (200-800 &#x3bc;g/mL) dose-dependently inhibited the mRNA and protein expression of fibronectin, collagen I, and collagen III (ECM-related markers) in TGF-&#x3b2;1-stimulated BEAS-2B cells, whereas CCE upregulated E-cadherin mRNA and protein expression (EMT-related marker) in TGF-&#x3b2;1-treated A549 cells. In bleomycin-challenged mice, intragastric administration of CC at 600 mg/kg reduced lung hydroxyproline level, mitigated elevated enhanced pause (Penh), and markedly downregulated the protein expression of fibronectin, collagen I and collagen III. In vitro and in vivo studies indicated that CC and CCE alleviated pulmonary fibrosis, which associated with reduced EMT/ECM marker expression, in particular inhibiting overproduction of ECM components (fibronectin, collagen I, and collagen III). C. militaris granules represent a potential anti-fibrotic candidate that merits further preclinical investigation.

Electric cues (ECs) permeate microbial habitats, yet electrosensing, the ability of microorganisms to detect and respond to these cues, remains largely overlooked. We distinguish four principal EC types [electric fields (EFs), electrode potentials, redox signals, and electromagnetic induction] and map each to its biological sensing mechanism. Recent findings reveal that cable bacteria respond to dynamic EFs through electromagnetic induction, a candidate sensing mechanism that is absent from existing models. We synthesize conserved sensing strategies primarily in bacteria, with emerging evidence in eukaryotes, and assess applications in bioenergy, bioremediation, and electroceutical therapy. Realizing this potential requires moving beyond static-field models toward experimental frameworks that capture the full temporal complexity of natural electric landscapes.

Cardiac contractility modulation (CCM) is a novel therapeutic approach for heart failure patients, which utilizes nonexcitatory electrical myocardial stimulation in the absolute refractory period of the cardiac cycle. This stimulation has been shown to increase contractility, leading to improved heart failure symptoms, functional status, and quality of life. CCM is FDA approved for heart failure patients with an LVEF between 25% and 45% who remained symptomatic despite optimal medical therapy and not candidate of cardiac resynchronization therapy. CCM offers expanded treatment options for heart failure patients who have continued symptoms while on optimal medical therapy.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra, leading to debilitating motor and non-motor symptoms. Current therapeutic strategies, including levodopa, dopamine agonists, monoamine oxidase-B inhibitors, and surgical interventions primarily offer symptomatic relief without halting disease progression. Long-term use of these treatments is often associated with complications such as motor fluctuations, dyskinesia, and systemic side effects, underscoring the urgent need for safer and disease-modifying approaches. In recent years, increasing attention has been directed toward natural products as potential therapeutic agents for PD due to their multi-targeted mechanisms and favourable safety profiles. Among these, plant-derived saponins have emerged as promising candidates owing to their diverse pharmacological properties. Saponins exhibit potent antioxidant, anti-inflammatory, anti-apoptotic, and anti-aggregation activities, enabling them to modulate key pathological pathways involved in PD, including oxidative stress, mitochondrial dysfunction, neuroinflammation, and &#x3b1;-synuclein aggregation. Experimental studies have demonstrated the neuroprotective effects of various saponins such as astragaloside IV, ginsenosides, bacosides, dioscin, and notoginsenosides in animal models of PD. These compounds have been shown to preserve dopaminergic neuronal integrity, enhance mitochondrial function, regulate apoptotic signalling, and promote autophagy. Despite these promising findings, challenges such as poor bioavailability in natural sources and limited access to brain remain significant barriers to clinical translation. This review provides a comprehensive overview of current PD therapies and their limitations, while highlighting the therapeutic potential of plant-derived saponins as multi-target agents. It also discusses recent advances in drug delivery strategies that may enhance their clinical applicability. Overall, saponins represent a promising avenue for the development of novel neuroprotective and disease-modifying therapies for PD.

Platelets have been increasingly recognized as versatile regulators of ageing, immunity, and cancer, yet their functional heterogeneity has remained poorly defined. We performed the first large-scale single-cell RNA sequencing of 28,192 platelets from healthy, aged, metastatic, and treated mice using the BD Rhapsody platform. Our analysis revealed four conserved and functionally distinct platelet transcriptional states: haemostatic platelet (HP), neural gene-enriched platelet (NEP), platelet-leukocyte aggregate (PLA) and platelet-erythrocyte aggregate (PEA). Among these states, Tpm2-high HP is linked to ageing-associated lung metastasis and is characterized by cytoskeletal remodelling gene signatures. The PLA state was predicted to be a signalling hub for immunothrombosis, with a PLA-Bridge subpopulation coordinating immune-adherent platelets via the Ppbp-Cxcl2 and Thbs1-Cd47 checkpoint axes. Strikingly, AAV-mPf4 gene therapy was associated with a neural gene-enriched platelet-associated transcriptional program, which mitigates age-related functional decline. This study provides a single-cell transcriptomic atlas of murine platelets under ageing and metastasis conditions and reveals transcriptional state-specific heterogeneity. This study also proposes PF4-based interventions and cytoskeletal candidates for diagnosis and therapy.

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.

Recurrent respiratory papillomatosis (RRP) is an HPV-associated airway disease with incompletely defined inflammatory and tissue-remodeling programs. All seven public 10x matrices in GSE261589 (four RRP and three HC donors) were reanalysed. After uniform quality control and unsupervised clustering, raw counts were aggregated by donor within coarse cellular strata. edgeR quasi-likelihood models and Benjamini-Hochberg correction were used to screen inflammation-, stress-, innate-defense-, chemokine-, and remodeling-related genes. A total of 64,044 cells passed quality control and formed 30 Leiden clusters. Donor composition and embedding structure were documented across the integrated dataset. FN1 in the myeloid stratum was the only transcript passing the within-stratum FDR threshold (log2 fold change 6.91, FDR 0.027), while DEFB4A, CXCL3, CXCL8, CXCL1, CXCL2, and SERPINE1 formed a prioritized candidate set. External paired LSCC analyses showed higher tumor expression of the CXCL1/CXCL2 co-annotated transcript cluster, CXCL8, and SERPINE1 and identified coordinated matrix-remodeling and squamous epithelial tumor-associated features. The seven-donor analysis provides a donor-aware single-cell framework for inflammatory and remodeling feature prioritization in RRP. The integrated framework additionally provides a malignant-laryngeal transcriptomic context for inflammatory, chemokine, and extracellular-matrix remodeling features.

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.

Migraine frequently co-occurs with psychiatric disorders, yet the immunogenetic mechanisms linking these conditions remain largely unexplored. Using cis-eQTL data from 28 immune cell subtypes (1,925 donors) and GWAS summary statistics for migraine and five psychiatric disorders, we performed single-cell transcriptome-wide Mendelian randomization, Bayesian colocalization, genetic correlation, and cross-disease pleiotropy analyses. Independent replication was performed using external datasets. Migraine and its subtypes showed significant positive genetic correlations with all five psychiatric disorders (rg&#x2009;=&#x2009;0.39-0.73). We identified 83 immune cell gene targets for migraine, 13 for migraine with aura, and 19 for migraine without aura. Among these, 6 targets showed shared associations with anxiety and 1 with depression. Three prioritized genes-HLA-A, CDK2AP1, and TTC24-demonstrated cross-disease pleiotropic effects. Notably, HLA-A in cDC1 exhibited discordant pleiotropy (protective for migraine with aura, risk for depression), with known drug-gene interactions involving antiepileptics and tricyclic antidepressants. These findings suggest that immune cell-specific genes, particularly HLA-A, CDK2AP1, and TTC24, may bridge migraine and psychiatric disorders, offering potential candidates for further investigation into shared immunogenetic mechanisms. Not applicable.