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Myocarditis and valvulitis are inflammatory diseases affecting myocardium and heart valves. Myocarditis, a viral-induced disease of myocardium, may lead to dilated cardiomyopathy and loss of heart function, and valvulitis leads to deformed heart valves and altered blood flow in rheumatic heart disease. Animal models recapitulating these diseases are important for understanding the human conditions. Cardiac myosin is a major autoantigen in heart tissue, and antibodies and T cells to cardiac myosin are evident in inflammatory heart diseases. This article is a practical guide to the induction and evaluation of experimental autoimmune myocarditis (EAM) in several mouse strains and the Lewis rat. Purification protocols for cardiac myosin and protocols for the induction of EAM by cardiac myosin and its myocarditis-producing peptides, as well as coxsackievirus B3 (CVB3), are defined. Protocols for assessment of myocarditis and valvulitis in humans and animal models provide methods to define functional autoantibodies targeting cardiac myosin, β-adrenergic, and muscarinic receptors, and their deposition in tissues. © 2026 Wiley Periodicals LLC. Basic Protocol 1: Induction of EAM in mice by active immunization with cardiac myosin Alternate Protocol: Induction of EAM in mice by adoptive transfer of cardiac-myosin-stimulated T cells Basic Protocol 2: Induction of EAM in rats by active immunization with cardiac myosin Support Protocol 1: Purification of cardiac myosin Support Protocol 2: Preparation of antigen/adjuvant emulsion by agitation for EAM induction in mice and rats Support Protocol 3: Collection and histopathological assessment of mouse or rat hearts Support Protocol 4: Immunostaining of rat heart tissue or cells for deposited antibody Basic Protocol 3: Induction of myocarditis in mice by inoculation with coxsackievirus B3 (CVB3) from infectious cDNA clones Basic Protocol 4: Induction of myocarditis and dilated cardiomyopathy in mice by inoculation with heart-passaged coxsackievirus B3 (CVB3) Basic Protocol 5: Induction of autoimmune valvular heart disease by inoculation with recombinant streptococcal M protein Basic Protocol 6: Protein kinase A (PKA) assay of serum antibody signaling of the β-adrenergic receptor with subsequent activation of PKA Basic Protocol 7: Measurement of serum antibody titers against human cardiac myosin, human adrenergic β1 and β2 receptors, and muscarinic 2 receptor Basic Protocol 8: Detection of antibodies against human cardiac myosin peptides in human serum.

The firmest evidence in favor of models that posit early high-level influences of cognition on perception comes from electroencephalography (EEG). Enhanced early, preattentive processing of light and dark blue feature changes compared to light and dark green changes was reported in Greek speakers, who have two basic terms for "blue" (ghalazio/ble). In the present three-experiment study, we systematically reevaluate this evidence and test an alternative model that the early difference waves in the human EEG instead mainly reflect contrast adaptation phenomena. We use the same classical oddball paradigm presenting alternating standards and deviants that systematically differ in color and/or luminance and chromatic contrast. We then calculate the visual mismatch negativity (vMMN), a putative index of preattentive feature change processing and predictive coding derived from EEG data, by subtracting the activity elicited by standards from that elicited by task-irrelevant deviants. Our experiments demonstrate the following: 1) vMMN is driven by contrast adaptation, being observable only in the presence of contrast differences between the stimuli and not reliably observed for categorically different hues equated in contrast; 2) there is no reliable difference between green- and blue-related difference waves in speakers (Russian) with two basic blue color categories, the difference waves, again, being driven by contrast rather than their categorical content. Our findings are highly significant for the debate concerning the interface between perception and cognition, as the absence of early categorical effects speaks against models that predict Whorfian-type preattentive cognitive influences on perception.

BackgroundWomen's futsal has experienced significant growth, highlighting the importance of understanding psychological need satisfaction and burnout as key determinants of athlete well-being. Basic psychological needs satisfaction, according to Self-Determination Theory, and athlete burnout are key constructs in promoting healthy and sustainable sports environments. Foot injuries are also prevalent in high-intensity sports such as Futsal and may be related to psychological outcomes in athletes.ObjectivesThis study aimed to examine the relationship between psychological need satisfaction and burnout in female futsal players, and to explore associations between foot and ankle injuries (podiatric pathology), age, and sport experience with these psychological variables.DesignObservational, cross-sectional, descriptive study.MethodsNinety-four adult female futsal players from first and second national divisions participated. Participants completed a sociodemographic and injury questionnaire, the Athlete Burnout Questionnaire (ABQ), and the Psychological Needs in Sport Questionnaire (PNSQ-15). Injury history included ankle sprains, plantar fasciitis, Achilles tendinopathy, fifth metatarsal fractures, and anterior cruciate ligament ruptures. Data were analyzed using descriptive and correlational statistics.ResultsThe majority of players (85%) reported previous injuries, with ankle sprains (73.4%) and plantar fasciitis (35.1%) being most common. PNSQ-15 scores indicated high activation and concentration, with moderate confidence and motivation. Greater age and sport experience were associated with higher concentration and motivation. ABQ scores were moderate overall; more weekly training hours were associated with lower burnout in the dimensions of reduced sense of accomplishment and sport devaluation. Players with plantar fasciitis showed higher burnout scores, particularly in reduced sense of accomplishment (p=0.036).ConclusionFemale futsal players showed favorable psychological skills and moderate levels of burnout. Age, sport experience, and training load were associated with some psychological dimensions, while the presence of certain foot injuries was related to higher burnout scores. These findings suggest that psychological need satisfaction, training load, and injury history are interrelated factors influencing burnout and psychological well-being in female futsal players. Female futsal is growing rapidly, making it important to understand the psychological and physical factors that affect players’ well-being and performance. This study looked at how satisfaction of basic psychological needs such as feeling competent, connected, and autonomous relates to burnout, a state of emotional and physical exhaustion caused by prolonged stress. We also examined whether foot and ankle injuries influence burnout or psychological well-being. Ninety-four adult female futsal players completed questionnaires about their psychological skills, burnout levels, and previous injuries. Most players (85%) had experienced injuries, with ankle sprains and plantar fasciitis being the most common. Overall, players reported good psychological skills, especially in concentration and motivation. More experienced players showed better psychological outcomes. Players who trained more hours per week tended to have lower burnout, suggesting that regular engagement in sport can be protective. However, players with chronic foot injuries, like plantar fasciitis, showed higher burnout levels, indicating that persistent pain may negatively affect well-being. These findings highlight the importance of supporting both the psychological and physical health of female futsal players. Coaches and sports organizations should consider strategies that promote psychological skills, prevent injuries, and provide support for players dealing with chronic pain to maintain well-being and enhance performance.

Orthodontic residency programs increasingly expect residents to present research and publish in peer-reviewed journals, yet resident satisfaction with research opportunities remains low. Historical data indicate declining research productivity, but comprehensive current assessments are lacking. This study aims to quantify and characterize research productivity among orthodontic residents and fellows across training programs in the United States. Using ADEA Pass, we identified orthodontic residency and fellowship programs and compiled rosters for graduating classes 2025-2028. For each trainee, we recorded demographics and training details and conducted systematic PubMed searches to identify publications. Publications were analyzed for authorship position, article type, timing relative to residency, dental relevance, journal impact factor, and citation counts. Statistical analyses compared productivity by sex and post-graduate year (PGY) status. Among 686 residents and fellows from 42 programs, only 157/686 (23%) had at least one publication, with an average of 0.5 ± 1.8 total publications per trainee. The cohort produced 369 publications, predominantly basic science (152/369, 41%), and published pre-residency (298/369, 81%). Only 73/369 (20%) were first-author publications. PGY 2 residents consistently outperformed residents in other years across all metrics. Males had a higher proportion of dental-related publications than females (114/158 males, 72% vs 135/211 females, 64%; χ²(1, 369) = 3.96, P = 0.029). Comparing final-year residents, longer program duration (3 vs 2 years) did not significantly increase publication output. Most orthodontic trainees have minimal research involvement, with publications concentrated among a few high-output individuals. Despite expectations for scholarly activity, current research productivity suggests inadequate mentorship, resources, or time dedicated to research. Programs must enhance research infrastructure to ensure trainees can critically evaluate and contribute to evolving orthodontic literature.

Student navigation through a PhD Program is marked by intellectual challenges, emotional fluctuations, and personal growth. Students develop excellence by absorbing and adjusting, recovering, and improving in response to challenges. The ability to bounce back is termed elasticity, an engineering principle where systems are designed to withstand stress, recover from disruptions, and maintain functionality. Students can proceed from elasticity (resilience) to then develop antifragility, the ability to become better from an experience. It occurred to the first author (a PhD graduate student in biomedical sciences) that developing antifragility is conceptually easier to understand by applying basic engineering concepts. We examine five thematic categories that connect engineering concepts with practical realities of graduate study: (1) load and stress management; (2) redundancy and backup systems; (3) setback modes and recovery; (4) adaptive capacity and flexibility; and (5) sustainability and long-term performance. By understanding how to gain antifragility, one can navigate demands more effectively.

Human metapneumovirus (HMPV) is a leading cause of acute respiratory infection worldwide, and most people over the age of 10 have been infected. Despite its high prevalence, its pathogenesis is not yet fully elucidated. Many cell types, including stem cells, are susceptible to HMPV infection. Our previous results suggested that mesenchymal stem cells (MSCs) are susceptible and permissive to HMPV infection. This study aimed to understand the effects of HMPV on stem cell biology. Specifically, we focused on the expression and localization of cytoskeletal proteins and their role during syncytium formation. To this end, we evaluated the surface markers CD90, CD73, and CD105 in infected and non-infected cells using flow cytometry; assessed infection-induced modifications in cytoskeletal proteins using immunofluorescence, and analyzed changes in the secretion pattern of the growth factors including Ang-2, EGF, EPO, FGF-basic, G-CSF, GM-CSF, HGF, M-CSF, PDGF-AA, PDGF-BB, SCF, TGF-α, and VEGF. We observed changes in the distribution of tubulin and actin. Annexin V levels were also increased following HMPV infection, likely due to membrane modifications associated with viral fusion during entry and/or viral exit by budding. HMPV infection induced a significant decrease in EGF and VEGF secretion compared with mock-infected cultures. In contrast, Ang-2 and PDGF-AA levels were significantly elevated in infected MSCs. HMPV infection alters the structure and surface marker expression of PL-MSCs; however, these cells retain their ability to differentiate into various tissue types. Nevertheless, the virus disrupts growth factor production, creating a complex balance between cellular damage and the remaining potential for tissue repair.

Soybean root rot, a soil-borne fungal disease, severely impacts soybean production. Limited research has specifically addressed this disease during the mid-to-late growth stages, which represent a critical yield-limiting period for soybean. In the autumn of 2024, a total of 478 pathogenic isolates were obtained and validated following Koch's postulates. These isolates were classified into eight fungal species, among which Diaporthe longicolla was the predominant species, accounting for 72.0% of the total isolates. Notably, Nigrospora oryzae, an unreported causal agent of soybean root rot in China, was first isolated from field samples collected in Jiamusi City, constituting 2.1% of all obtained isolates. Pathogenicity assays revealed that most isolates exhibited high or moderate virulence. Host range assays confirmed that N. oryzae had a broad host spectrum, infecting green pea, snow pea, lentils, flower-faced cowpea, and mung bean, but not kidney beans, red beans, corn, or peanut. Fungicide sensitivity tests indicated N. oryzae was highly sensitive to difenoconazole and prochloraz, which exhibited excellent field control efficacies of 87.50% and 69.58%, respectively, with prochloraz being more suitable for field application. This study provides basic data for the integrated management of N. oryzae-induced soybean root rot via non-host crop rotation and prochloraz.

Subarachnoid hemorrhage (SAH) often leads to cognitive impairment, in which neuroinflammation plays a pivotal role. While remote ischemic postconditioning (RIPostC) has demonstrated neuroprotective potential, its clinical efficacy and underlying mechanisms remain incompletely defined. This study identified interleukin-9 (IL-9) as a key mediator of RIPostC's effects through an integrated clinical and basic research approach. In a prospective proof-of-concept clinical trial, RIPostC was associated with improved early neurological recovery and significantly upregulated serum IL-9 levels in SAH patients. It suggests a potential clinical benefit that warrants further validation. Using a murine SAH model, results showed RIPostC improved cognitive function, suppressed pro-inflammatory cytokines (IL-1β, IL-6), and elevated anti-inflammatory cytokines (IL-9, IL-10). Mechanistically, RIPostC activated the JAK2/STAT5 signaling pathway. Immunofluorescence revealed specific expression of the IL-9 receptor (IL-9R) on microglia. In vitro experiments using BV2 microglial cells confirmed that IL-9 directly promotes microglial polarization towards an anti-inflammatory M2 phenotype and enhances IL-10 production via the JAK2/STAT5 pathway. Collectively, these preliminary findings suggest that RIPostC alleviates neuroinflammation and cognitive impairment after SAH, a process mechanistically linked to the upregulation of IL-9 and subsequent activation of the JAK2/STAT5 pathway in microglia. This study positions IL-9 as a promising therapeutic target for SAH.

Alkaloids are nitrogen-containing basic compounds derived from plants, characterized by complex cyclic structures. They serve as key active components in most traditional Chinese medicines (TCM) and demonstrate significant clinical value in colorectal cancer therapy. In recent years, TCM-derived alkaloids represented by berberine, matrine, and camptothecin have attracted widespread attention due to their remarkable anti-tumor activity. Research indicates that these compounds exert synergistic effects across multiple pathways and targets by modulating key signaling pathways, including Wnt/β-catenin, PI3K/Akt, etc. They play important roles in regulating tumor cell proliferation, apoptosis, invasion, and reversal of drug resistance. However, despite the significant multi-pathway and multi-target effects demonstrated by alkaloid compounds, current research has yet to provide a comprehensive and systematic review of their intervention effects on colorectal cancer. To address this gap, this review systematically examines the mechanisms of action of TCM-derived alkaloids and their nano-formulations in colorectal cancer treatment. It summarizes the molecular pathway networks regulated by these representative alkaloids and discusses their potential clinical benefits and current limitations.Building on this foundation, this paper further outlines future research directions, including structure optimization based on molecular structure considerations, targeted drug design strategies, and the prospects of alkaloid nanodelivery systems in clinical translation. The aim is to establish a systematic research framework for alkaloid-based colorectal cancer therapy and provide a theoretical basis for developing novel high-efficiency, low-toxicity treatment strategies.

Stress fractures affect military personnel at higher rates than the general population. They can lead to serious injury and negatively impact military force readiness. Most prior studies have focused on recruits undergoing basic training. Our goal was to characterize stress fractures over the full spectrum of military career stages to identify whether fracture locations varied by career length. A retrospective chart review was conducted of a 3-year period (January 1, 2017-December 31, 2019) to identify active duty military patients in the National Capital Region diagnosed with a new stress fracture. Patients were stratified by career length: New Recruit (<12 months of service), Early-Career (1-5 years of service), Mid-Career (5-14 years of service), and Late-Career (>14 years of service). The percentage of fractures at each anatomic location was reported and compared by binary career length (New Recruit vs. others) with Chi-square or Fisher's exact tests performed among the full cohort. The total cohort was stratified by sex, and the analysis was repeated separately in males and females. The percentage of patients who presented with multiple fractures was similarly reported and compared by career length, among the full cohort and by sex strata. The study was approved by the Walter Reed National Military Medical Center Institutional Review Board, protocol # WRNMMC-2018-0162. The study population included 446 military members with 537 total fractures. Percentages of femoral neck (11.1% vs. 3.6%, P&#x2009;=&#x2009;.001), femoral shaft (8.1% vs. 1.8%, P&#x2009;=&#x2009;.001) and pelvis fractures (3.8% vs. 0.7%, P&#x2009;=&#x2009;.031) were greater in the New Recruit group compared to the other career-length groups. Percentage of foot fractures was lower (19.2% vs. 34.3%, P&#x2009;<&#x2009;.001) in the New Recruit group vs. the other career-length groups. Percentage of patients presenting with multiple stress fractures (23.7% vs. 10.1%, P&#x2009;<&#x2009;.001) was greater in the New Recruit group vs. the other career-length groups. The significant differences in femoral shaft and foot fractures persisted when males and females were analyzed separately. Our findings support that the distribution of the anatomic locations of stress fractures differs between military members in the New Recruit period versus later in their careers. Specifically, New Recruits had a higher percentage of femoral neck, femoral shaft, and pelvic fractures. Providers may consider having a lower threshold for imaging new recruits with hip pain as this could identify a stress reaction before it becomes a stress fracture. Potential explanations for the findings include sex, training intensity, and force attrition. Some of the significant findings persisted when males and females were analyzed separately, which supports that there are contributions from other factors than patient's sex. Additional studies are needed to build upon these findings. Limitations included the use of ICD-10 codes and physician reporting to identify stress fractures, the lower numbers of patients once the total study population was stratified by sex, unavailability of bone density data, and unclear generalizability of the findings.

Digital public health services (DPHS) succeed when three elements align: dependable operations, clear public-value benefits, and credible institutional trust. How these elements jointly shape user satisfaction across cultures remains unclear. Identify which user-voiced themes relate most to satisfaction, whether legitimacy and civic messages change how complaints affect ratings, and how these relationships vary across cultures. We analyzed app-store reviews for two DPHS apps (Indian/UK) using structural topic modeling aligned with Public Value Theory dimensions, public-value outcomes (PVO), operational capacity (OC), and the authorizing environment (AE). Ordered logit models estimated main effects of theme salience on ratings; interaction models tested whether AE cues (institutional legitimacy, prosocial messaging) moderate OC and PVO complaints; a cross-country sensitivity analysis compared India and the UK. OC problems, access, verification, updates, stability, are the most consistent drivers of dissatisfaction. PVO features lift satisfaction only when they deliver end-to-end in real conditions (reliable booking, trustworthy exposure logic, seamless results integration); ambiguous signals or broken data flows quickly erode confidence. Legitimacy and civic cues matter, but not as substitutes for reliability: pairing "trust in government" or solidarity appeals with unresolved core faults typically worsens perceptions; the same cues help when problems are peripheral or visibly being fixed. Cultural differences reshape these effects. In more collectivist, higher power-distance settings, stewardship and shared-purpose framing contribute more to satisfaction once basics work. In more individualist, egalitarian settings, users weigh demonstrable privacy safeguards, transparent evidence, and precise remediation over patriotic messaging. Make reliability non-negotiable, verify public-value features in live conditions before promotion, and tailor legitimacy strategies to culture. Use civic appeals to amplify, not replace, operational excellence; lead with privacy, transparency, and proof where autonomy expectations are higher. This framework turns Public Value Theory into an actionable playbook for DPHS design, communication, and rollout.

Abnormal accumulation of reactive oxygen species (ROS) induces oxidative stress, a central pathological factor in many human diseases. Traditionally, antioxidants are suggested to relieve oxidative stress in the body; however, their efficacy is limited by poor stability in vivo and inadequate tissue targeting in clinical practice. Therefore, there is a great need for an effective, safe, biocompatible, and environmentally friendly antioxidant strategy to reduce damage caused by oxidative stress. Previous work has demonstrated that nanobubbles (NBs) can regulate hydroxyl radical (&#x2022;OH)-mediated redox reactions. However, it remains unclear whether NBs can exert similar regulatory control on singlet oxygen (1O2), and the molecular mechanisms that control this interaction need to be elucidated. In this work, we employed photodynamic reactions to generate 1O2 and systematically investigated the effects of NBs of different particle sizes and different encapsulated gas compositions (N2 or O2) on 1O2-mediated oxidation of selective fluorescent probes. Our findings indicate that ultrasmall NBs exhibit remarkable antioxidant activity across all test systems and that even NBs prepared with O2, a gas that typically enhances ROS-driven oxidation, inhibit 1O2-mediated substrate oxidation. These insights establish a basic framework for the rational design of NB-based antioxidant platforms, which hold significant promise for applications in biomedical antioxidant therapy, material protection, and food preservation.

Urogenital schistosomiasis remains a major public health problem in irrigated areas of Sudan. We conducted a cross-sectional descriptive survey to determine the prevalence and intensity of Schistosoma haematobium infection and associated risk factors among basic schoolchildren in Althawra Mobi Village, Wad Madani Alkobra Locality, Gezira State. A total of 261 children aged 5-16 years were examined using urine centrifugation and microscopy. The overall prevalence was 44% (115/261), with most infections classified as light intensity (102/115). Infection was markedly higher among boys (96.5%) than among girls (3.5%). Frequent contact with irrigation canals for swimming, bathing, washing, and watering animals was significantly associated with infection, despite tap water being the main source of drinking water. These findings confirm ongoing transmission of urogenital schistosomiasis in irrigated communities of Gezira and highlight the need for sustained preventive chemotherapy, health education, and improved sanitation to reduce exposure among school-age children.

Fuzzy knowledge graph embedding (KGE) aims to represent uncertain facts for reliable reasoning and decision-making. While recent studies have begun to explore fine-grained fuzzy KGs that associate uncertainty with individual elements, existing approaches remain limited by (i) unreliable neighborhood aggregation that may amplify low-confidence noise, (ii) entangled semantic and reliability signals that obscure where uncertainty originates and hinder interpretability, and (iii) restricted generality due to task- or metadata-specific designs. To address these issues, we propose FGF-GAT, a general encoder-decoder framework for fine-grained fuzzy KGE. On the encoder side, FGF-GAT employs a learnable neuro-fuzzy reasoning module for fine-grained fuzziness modeling, where fixed element-level memberships are transformed into reliability-aware signals through an ANFIS-inspired fuzzy parameterization and a lightweight TSK-style rule reasoning layer. These memberships are then injected into a rule-constrained fuzzy graph attention encoder for reliability-modulated neighborhood aggregation, thereby suppressing uncertainty-induced noise accumulation. On the decoder side, we develop a pluggable membership injection strategy and demonstrate that the framework is decoder-agnostic by instantiating a basic Fuzzy-TransE scorer and two stronger variants with DistMult and RotatE. Extensive experiments on four benchmarks under both entity prediction and relation prediction, together with ablation and sensitivity studies, consistently verify the effectiveness, robustness, and adaptability of the proposed framework.

The precise activation of the cGAS-STING pathway for effective tumor immunotherapy remains a significant challenge due to the complexity of immune responses and tumor microenvironment (TME) limitations. Here, a multifunctional nanoagonist, cRGD-PDA/ZIF8@ICG/TPT (cDZ@IP), was developed to realize nano-metabolite-driven multimodal synergistic activation of the STING pathway and enhanced immune recognition. The agonist combines cRGD peptide-targeted polydopamine-coated zeolitic imidazolate framework-8 with the photosensitizer indocyanine green and the chemotherapeutic drug topotecan. Upon near-infrared laser irradiation, cDZ@IP degrades within the TME, generating high levels of reactive oxygen species, inducing mitochondrial stress, and releasing endogenous mitochondrial DNA. Additionally, topotecan enhances DNA damage accumulation by inhibiting nuclear DNA repair. Zn2 + released from the agonist further amplifies cGAS-STING pathway activation, thereby ensuring a robust immune response. The mild photothermal therapy-induced immunogenic cell death promotes the initiation of antitumor immunity, while also enhancing the effectiveness of immune checkpoint blockade. In vivo studies show that cDZ@IP significantly inhibits primary and distant tumor growth and prevents lung metastasis, providing a promising strategy for STING pathway-targeted cancer immunotherapy.

Single prolonged stress (SPS) is a validated PTSD-like paradigm that causes cognitive and affective dysfunction and corticolimbic injuries due to the dysregulation of the HPA-axis and neurotrophic, redox, and neuroimmune pathways. Berberine is a bioactive isoquinoline alkaloid that demonstrates neuroprotective effects, although its effect on corticolimbic-pathology caused by SPS is yet to be fully characterized. To ascertain whether berberine attenuates SPS-induced neurobehavioral impairments and corticolimbic neuronal damage in Wistar rats. Adult male Wistar rats were exposed to SPS (restraint, forced swim, and anesthetic-induced loss of consciousness) and left undisturbed for 7 days to allow stress consolidation. Then, rats were given oral berberine (50 or 200&#x2005;mg/kg) or fluoxetine (10&#x2005;mg/kg) in a single daily dose. Behavioral measures were Y-maze spontaneous alternation, Morris water maze, novel object recognition and sucrose preference. ELISA was used to quantify serum corticosterone. BDNF, SOD, catalase, MDA, and IL-1b/IL-6/TNF-a were assayed in the hippocampus and mPFC. CFV and NeuN immunohistochemistry were used to assess neuronal integrity and astrocytic reactivity was assessed using GFAP-immunoreactivity. SPS induced severe deficits in working memory, spatial and recognition memories and reward sensitivity, and high basal corticosterone. It increased lipid peroxidation and pro-inflammatory cytokines while reducing antioxidant enzyme activities in brain tissue homogenates (hippocampus and medial prefrontal cortex). Berberine improved behavioral outcomes and attenuated endocrine, biochemical, and histopathological abnormalities in a dose-dependent manner. Berberine attenuates SPS-induced-cognitive/affective dysfunction and corticolimbic-lesion and establishes normalization of basal corticosterone, BDNF recovery, antioxidant defense, lipid peroxidation, cytokine elevations, and astrocytic activation. These findings support berberine as a multi-target candidate for mitigating stress-related-neurotoxicity.

CD4 cytotoxic T lymphocytes (CTLs) are a distinct subset of CD4+ T cells that can mediate antigen-specific cytotoxicity. However, their specific surface markers have yet to be defined. In this study, we used gene-plasticity-based mutual exclusion analysis to identify negative biomarkers for CD4 CTLs, using granzyme B (GZMB) expression as the pivotal reference. We analyzed bulk RNA-seq data from 768 human CD4+ T cell samples, calculated gene plasticity scores, and applied cosine similarity to detect genes that are anti-correlated with GZMB. Several genes encoding cell surface membrane proteins were identified as important candidates. ITGA6 (CD49f) and IL6R (CD126) were validated by flow cytometry in healthy individuals and primary Sj&#xf6;gren's syndrome (pSS) patients. The expression profile confirmed mutually exclusive between GZMB and both CD49f and CD126, with CD49f-CD126-GPR56+ CD4+ T cells exhibiting the highest GZMB levels. In pSS patients, CD49f-CD126-GPR56+ cells in CD8+ T cells were significantly negatively correlated with clinical parameters (IgA, anti-SSB). ROC analysis revealed the percentages of GZMB in CD4+ T cells (AUC = 0.766) and GPR56/GZMB in CD8+ T cells (AUC = 0.76) as diagnostic biomarkers.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor strongly associated with Epstein-Barr virus (EBV) infection. EBV-mediated dysregulation of host microRNAs (miRNAs) contributes to NPC pathogenesis, but the functions of many EBV-regulated host miRNAs remain incompletely defined. miR-10b-3p is markedly downregulated in EBV-positive NPC, yet its biological significance and downstream mechanism remain unclear. Here, we found that miR-10b-3p was reduced in EBV-positive NPC tissues and was further suppressed following EBV infection of non-malignant nasopharyngeal epithelial cells and EBV-negative NPC cell lines. Restoration of miR-10b-3p expression markedly inhibited cell proliferation, colony formation, migration, invasion, and epithelial-mesenchymal transition (EMT) in EBV-positive NPC cells, whereas inhibition of miR-10b-3p in EBV-negative NPC cells produced the opposite effects. In nude mouse xenograft and lung metastasis models, overexpression of miR-10b-3p significantly reduced tumor growth and pulmonary metastasis. Mechanistically, miR-10b-3p directly targeted the 3'-UTR of integrin subunit alpha V (ITGAV), leading to decreased ITGAV expression and subsequent attenuation of STAT5 and ERK1/2 signaling. Forced ITGAV expression partially reversed the suppressive effects of miR-10b-3p on tumor cell proliferation, migration, invasion, and EMT. Moreover, miR-10b-3p levels were inversely correlated with ITGAV expression in NPC tissues. Collectively, these findings identify an EBV-regulated miR-10b-3p/ITGAV/STAT5-ERK1/2 axis in NPC and show that loss of miR-10b-3p promotes tumor growth and metastasis by relieving ITGAV repression, suggesting potential therapeutic targets for EBV-associated NPC.

Conventional platinum-based drugs are always constrained by their limited therapeutic efficacy due to sole chemotherapy without diagnostic guidance. This makes the development of multifunctional theranostic platinum complexes an appealing goal in medicinal chemistry. Herein, we designed a multifunctional bidentate platinum(II) complex, namely, BSeTPE-Pt-ac, featuring near-infrared (NIR) emission, an aggregation-induced emission (AIE) effect, and a photothermal effect, and achieved tumor-specific imaging and efficient gene-regulation synergized chemo-photothermal therapy (chemo-PTT). The introduction of 6/6 metallocycles linked to the benzoselenadiazole acceptor of the AIEgen expanded the electron conjugation effect, achieving NIR emission by leveraging a strong intramolecular metal-to-ligand charge transfer. The incorporation of benzoselenadiazole and tetraphenylethylene units modulated the photophysical property and increased molecular steric hindrance, endowing BSeTPE-Pt-ac with AIE and photothermal effects. To further optimize its therapeutic regimen, we executed a systematic bioinformatics-driven mapping to decode the cellular response to BSeTPE-Pt-ac, identifying thermal-resistance-related antiapoptotic gene B-cell lymphoma 2 (BCL2) as the key and direct intervention target. Synergistic gene regulation was introduced by co-delivering BCL2 antisense oligonucleotide and BSeTPE-Pt-ac with amphiphilic tumor-targeting polymers, which effectively silenced BCL2 expression, overcame thermal resistance, and thus maximized the chemo-PTT efficacy of BSeTPE-Pt-ac. Our work elucidates the rational design of a multifunctional platinum(II) agent by effectively integrating key anticancer functionalities, offering valuable insights into the development of advanced multifunctional agents.