<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d13133733e150">The tumor vasculature, characterized by pathological angiogenesis and structural abnormalities, drives the progression of solid tumors by inducing hypoxia-acidosis microenvironments and therapeutic resistance. Targeting the tumor vasculature has emerged as a critical therapeutic strategy. Although conventional approaches such as anti-angiogenic drugs, vascular disrupting agents, and embolization have shown efficacy, their single-target focus hinders addressing tumor heterogeneity and evolving stage-specific needs. For example, rapid vascular disruption is effective for debulking advanced tumors, whereas vascular normalization enhances early- to mid-stage therapy by improving postoperative chemo-radiotherapy outcomes. Unlike single-mechanism interventions, ultrasound modulates acoustic parameters to achieve diverse effects including angiogenesis suppression, vessel disruption, and vasodilation, thus addressing multi-stage vascular needs. Ultrasound-based monitoring systems provide precise, dynamic vascular assessments to guide intervention strategies. Compared with traditional static imaging ultrasound offers real-time angiogenesis visualization and therapeutic response evaluation, thus enabling treatment optimization. This review synthesizes recent advances in ultrasound-based vascular targeting, emphasizing its dual role in spatiotemporally adaptive therapy and angiogenesis monitoring. We critically examine clinical translation challenges and future directions, highlighting how ultrasound-driven strategies, by bridging mechanistic precision with clinical scalability, might enable personalized, multi-effect therapeutic paradigms in oncology.</p>

<div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"><a class="named-anchor" id="d20205636e178"><!-- named anchor --></a><h5 class="section-title" id="d20205636e179">Background:</h5><p dir="auto" id="d20205636e181">Accurate localization of anatomical landmarks is crucial for clinical diagnosis and treatment assessment. However, existing Convolutional Neural Network (CNN)-based methods may result in global spatial information loss and consequent localization failures in the presence of complex anatomical structures or parenchymal abnormalities. Therefore, a method capable of modeling global context while preserving local information is needed.</p></div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"><a class="named-anchor" id="d20205636e183"><!-- named anchor --></a><h5 class="section-title" id="d20205636e184">Methods:</h5><p dir="auto" id="d20205636e186">Leveraging the Transformer’s ability to capture long-range dependencies, we propose a novel landmark localization framework, Res-SwinFusion, which integrates a Swin Transformer and a classical CNN backbone in parallel. To effectively merge their complementary features, we designed a feature interactive aggregation module that fuses semantic representations from both branches. Additionally, we introduced a discrimination feature guidance module to provide pixel-level cues and disambiguate landmark locations. We further analyzed the effects of various Gaussian heatmap settings on convergence.</p></div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"><a class="named-anchor" id="d20205636e188"><!-- named anchor --></a><h5 class="section-title" id="d20205636e189">Results:</h5><p dir="auto" id="d20205636e191">Res-SwinFusion achieved strong performance across three anatomical landmark localization datasets. The mean radial errors were 1.04 mm and 1.37 mm on two public cephalogram test sets, 0.63 mm on a public hand X-ray dataset, and 1.44 mm on an internal pelvic X-ray dataset. Ablation studies indicated that Transformer-based global modeling, feature interactive aggregation, and discrimination feature guidance each contributed to improved localization accuracy.</p></div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"><a class="named-anchor" id="d20205636e193"><!-- named anchor --></a><h5 class="section-title" id="d20205636e194">Conclusion:</h5><p dir="auto" id="d20205636e196">The proposed Res-SwinFusion framework offers a solution for anatomical landmark localization with enhanced robustness and precision by combining global contextual modeling and local feature preservation. Code is publicly available at <a data-untrusted="" href="https://github.com/JZK00/Res-SwinFusion" id="d20205636e198" target="xrefwindow">https://github.com/JZK00/Res-SwinFusion</a>.</p></div>

<div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"><a class="named-anchor" id="d18401348e189"><!-- named anchor --></a><h5 class="section-title" id="d18401348e190">Background:</h5><p dir="auto" id="d18401348e192">Cell death pathways have crucial roles in cancer development, immune responses, and disease progression. With the discovery of 14 distinct types of regulated cell death, there is a critical need for integrated analytical tools that can simultaneously evaluate multiple cell death pathways in transcriptomic data.</p></div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"><a class="named-anchor" id="d18401348e194"><!-- named anchor --></a><h5 class="section-title" id="d18401348e195">Methods:</h5><p dir="auto" id="d18401348e197">We developed CellDeathAnalysis (v0.4.0), an R package providing a unified framework for analyzing 14 cell death pathways in bulk RNA-seq data. The package introduces two novel algorithms: Crosstalk-Aware Pathway Scoring, which uses gene specificity weighting (inverse document frequency-inspired) and residual debiasing to reduce redundancy from inter-pathway gene overlap; and Cell Death Subtype Classification, which uses consensus clustering on pathway score profiles to identify biologically meaningful patient subtypes. The package integrates curated gene sets from FerrDb, MSigDB, KEGG, and the primary literature, and implements multiple scoring methods (z-score, ssGSEA, GSVA, and AUCell, and the novel crosstalk-aware method), survival analysis, enrichment analysis, and publication-ready visualizations.</p></div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"><a class="named-anchor" id="d18401348e199"><!-- named anchor --></a><h5 class="section-title" id="d18401348e200">Results:</h5><p dir="auto" id="d18401348e202">By applying CellDeathAnalysis to 2704 The Cancer Genome Atlas (TCGA) samples across four cancer types (BRCA, LUAD, LIHC, and STAD), the crosstalk-aware method reduced inter-pathway correlation (mean reduction = 0.69) compared to z-score scoring. The disulfidptosis score in LUAD exhibited a significant survival association (HR = 2.19, <i>P</i>_adj = 0.037). Consensus clustering identified clinically meaningful subtypes in LIHC (<i>P</i> = 0.017) and STAD (<i>P</i> = 0.028).</p></div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"><a class="named-anchor" id="d18401348e213"><!-- named anchor --></a><h5 class="section-title" id="d18401348e214">Conclusions:</h5><p dir="auto" id="d18401348e216">CellDeathAnalysis provides the first dedicated toolkit for multi-pathway cell death analysis with novel crosstalk-aware scoring and subtype classification capabilities. The package addresses the critical challenge of gene overlap between cell death pathways and enables discovery of clinically meaningful patient subtypes.</p></div>

Platinum Open Access with no APCs.

Platinum Open Access with no APCs.

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d20943211e108">Cardiovascular diseases (CVDs), a leading global cause of mortality, are characterized by complex pathogenesis involving multifactorial molecular and cellular processes. Pannexin-1 (Panx1), a transmembrane channel protein, facilitates intercellular signaling through regulated release of small molecules such as adenosine triphosphate (ATP), thereby modulating diverse physiological and pathological pathways. This review explores the structural and functional landscape of Panx1, including its physiological roles, post-translational modifications and activation mechanisms. Its contributions to the pathophysiology of myocardial ischemia-reperfusion injury, cardiac remodeling, electrophysiological abnormalities, and diabetic cardiomyopathy are emphasized. Current evidence highlights the dual pathophysiological roles of Panx1 channels in CVDs: whereas ATP-mediated activation initiates cytoprotective signaling cascades, channel hyperactivation exacerbates pathological progression. Future research should prioritize mechanistic elucidation of Panx1’s molecular biology, and the development of targeted inhibitors with enhanced specificity and therapeutic efficacy, to advance novel therapeutic strategies for cardiovascular disorders. </p>

<div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d1742410e160"> <!-- named anchor --> </a> <h5 class="section-title" id="d1742410e161">Background:</h5> <p dir="auto" id="d1742410e163">In northeastern China, tick-borne diseases pose a major public health challenge, which is exacerbated by environmental and anthropogenic changes. This study was aimed at assessing the risk of tick bites and the effectiveness of protective measures in an endemic region, and investigating the influences of socio-demographic, behavioral, and landscape factors. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d1742410e165"> <!-- named anchor --> </a> <h5 class="section-title" id="d1742410e166">Methods:</h5> <p dir="auto" id="d1742410e168">A comprehensive online survey was conducted among 3000 participants from Heilongjiang, Liaoning, and Jilin provinces between July and August 2022. Data on self-reported tick bites, protective measures, and associated socio-demographic characteristics were gathered. Landscape analysis was conducted with satellite imagery, and the Shannon diversity index (SHDI) and forest patch density (PD) were selected to quantify landscape factors. Factors influencing tick bite incidence were identified with a logistic regression model, and linkages between landscape characteristics and exposure risk were assessed with spatial statistics. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d1742410e170"> <!-- named anchor --> </a> <h5 class="section-title" id="d1742410e171">Results:</h5> <p dir="auto" id="d1742410e173">Twenty-one percent of respondents reported experiencing tick bites, primarily during the active tick season (May to October). The self-reported incidence of tick-borne diseases (e.g., tick-borne encephalitis (TBE), Lyme disease (LD), and severe fever with thrombocytopenia syndrome (SFTS)) varied across provinces, and notable socio-demographic factors (e.g., age, gender, occupation, and lifestyle) associated with tick exposure were identified. Adoption of protective measures was high (80.3%) among the surveyed population, particularly among those who had previously experienced tick bites. Landscape analysis revealed an inverse relationship between land use diversity and tick bite incidence, thus suggesting that areas with lower land use diversity might have higher tick bite risk. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d1742410e175"> <!-- named anchor --> </a> <h5 class="section-title" id="d1742410e176">Conclusions:</h5> <p dir="auto" id="d1742410e178">The study highlights the multifaceted nature of tick-borne disease risk in northeastern China and the importance of integrated strategies encompassing awareness, behavioral change, and environmental management to decrease tick exposure and prevent disease transmission. These insights might assist public health authorities in developing targeted interventions to combat the spread of tick-borne diseases in the region. </p> </div>

Platinum Open Access with no APCs & Fast peer review/Fast publication online after article acceptance

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d49440192e127">Tuberculosis (TB) is among the main infectious diseases responsible for global mortality worldwide. Cases in India, markedly contribute to the global TB burden. Despite substantial progress in diagnosis and treatment, challenges such as drug-resistant TB (DR-TB), HIV co-infection, and major gaps in private sector regulation hinder effective disease control. In India, TB control efforts have evolved from the Revised National Tuberculosis Control Program (RNTCP) to the current National Tuberculosis Elimination Program (NTEP), reflecting a strategic shift from disease control to elimination. Although these initiatives have improved case detection and treatment outcomes, operational, infrastructural, and socioeconomic challenges persist. This narrative review presents an updated overview of the development of, and progress in, TB control strategies in India. Key achievements, challenges, and future directions necessary to achieve TB elimination goals in India are highlighted. In addition, global TB control programs, and the effects of the COVID-19 pandemic on TB notification and treatment, are evaluated. </p>

<div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d8221145e220"> <!-- named anchor --> </a> <h5 class="section-title" id="d8221145e221">Background:</h5> <p dir="auto" id="d8221145e223">Hypertensive disorders of pregnancy (HDP), the third leading cause of maternal mortality worldwide, account for approximately 16% of all maternal deaths. The incidence and mortality rates of HDP vary across regions. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d8221145e225"> <!-- named anchor --> </a> <h5 class="section-title" id="d8221145e226">Objective:</h5> <p dir="auto" id="d8221145e228">This study was aimed at examining global trends in HDP prevalence from 1990 to 2021, identifying major risk factors associated with HDP-related mortality, and assessing the influence of dietary habits on HDP risk. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d8221145e230"> <!-- named anchor --> </a> <h5 class="section-title" id="d8221145e231">Methods:</h5> <p dir="auto" id="d8221145e233">Using data from the 2021 global burden of disease (GBD) study, we conducted a cross-sectional analysis across 204 countries and 21 regions. The estimated annual percentage change was used to evaluate trends in incidence, disability-adjusted life years (DALYs), and mortality associated with HDP. Mendelian randomization analysis was applied to investigate the causal relationships between dietary habits and HDP risk. In addition, projections of HDP prevalence were made through 2035 according to GBD data. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d8221145e235"> <!-- named anchor --> </a> <h5 class="section-title" id="d8221145e236">Results:</h5> <p dir="auto" id="d8221145e238">Although the absolute number of HDP cases has risen, HDP incidence, DALYs, and mortality rates have declined globally. Regional, age-related, and socioeconomic disparities persist, and low-income countries are disproportionately affected because of limited healthcare resources. Behavioral risks, maternal and child malnutrition, and iron deficiency were identified as risk factors for HDP-related mortality. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d8221145e240"> <!-- named anchor --> </a> <h5 class="section-title" id="d8221145e241">Conclusions:</h5> <p dir="auto" id="d8221145e243">Despite the overall decline in HDP incidence, DALYs, and mortality rates over the past 3 decades, the persistent high burden in low socio-demographic index regions highlights the urgent need for targeted health interventions. Addressing broader socioeconomic determinants is essential to sustainably decrease the global effects of HDP. </p> </div>

<div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d6809144e159"> <!-- named anchor --> </a> <h5 class="section-title" id="d6809144e160">Background:</h5> <p dir="auto" id="d6809144e162">Transglutaminase 2 (TGM2) has been implicated in various health conditions, yet its role in acute coronary syndrome (ACS) remains poorly characterized in clinical settings. This study investigated the association between circulating TGM2 levels and the severity of coronary stenosis in ACS. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d6809144e164"> <!-- named anchor --> </a> <h5 class="section-title" id="d6809144e165">Methods:</h5> <p dir="auto" id="d6809144e167">A total of 242 individuals with ACS were included in this study. Clinical data were collected, and the severity of coronary stenosis was evaluated with the Gensini and Syntax scoring systems. Kaplan-Meier analysis, logistic regression, and receiver operating characteristic (ROC) curve analysis were performed. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d6809144e169"> <!-- named anchor --> </a> <h5 class="section-title" id="d6809144e170">Results:</h5> <p dir="auto" id="d6809144e172">Circulating TGM2 levels were significantly higher in the STEMI group (176.3 pg/mL) and the non-STEMI group (181 pg/mL) than the UA group (64 pg/mL) and the stable CAD group (50.95 pg/mL) (P < 0.001). Multivariate analysis, after adjustment for confounding factors, identified TGM2 as an independent risk factor for acute myocardial infarction (odds ratio: 44.292 per 100 pg/mL increase in TGM2; 95% CI: 2.491–7.398; P < 0.001). During a median follow-up of 477 days, Kaplan-Meier survival analysis demonstrated that patients with higher TGM2 levels (≥91.9 pg/mL) exhibited a significantly lower MACE-free survival rate (P = 0.0142). ROC curve analysis further revealed that combining TGM2 and Gensini scores yielded superior predictive performance for MACE to that of either parameter alone. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d6809144e174"> <!-- named anchor --> </a> <h5 class="section-title" id="d6809144e175">Conclusion:</h5> <p dir="auto" id="d6809144e177">Circulating TGM2 is elevated in ACS and is strongly associated with the presence of AMI. Furthermore, it provides prognostic information for MACE, particularly when it is used in combination with established anatomical risk scores. </p> </div>

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d1752539e142">Osteoprotegerin (OPG), a glycoprotein in the tumor necrosis factor superfamily, regulates bone metabolism by suppressing the formation and activation of osteoclasts. Nonetheless, increasing evidence underscores its physiological importance, particularly in cardiovascular diseases (CVDs). Elevated OPG levels are associated with atherosclerosis, arterial calcification, and heart failure, thus indicating their involvement in cardiac remodeling and vascular pathology. OPG regulates calcification and vascular homeostasis by restricting the transdifferentiation of vascular smooth muscle cells into osteogenic phenotypes. OPG expression is aberrant in illnesses posing cardiovascular risk, such as aortic valve stenosis, chronic renal disease, and diabetes. Beyond structural regulation, OPG interacts with inflammatory and apoptotic mediators, including RANKL and TRAIL, in signaling pathways linking bone metabolism, inflammation, and vascular dysfunction. Myocardial infarction, left ventricular remodeling, and mortality are associated with elevated circulating OPG and altered OPG/TRAIL ratios. This review discusses molecular and clinical insights regarding OPG’s multifaceted role in CVDs, highlighting its potential as a regulator of disease etiology and a predictive biomarker. In cardiovascular medicine, understanding the OPG/RANKL/TRAIL axis has potential to facilitate targeted therapy and risk stratification. </p>

<div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d7657008e226"> <!-- named anchor --> </a> <h5 class="section-title" id="d7657008e227">Objective:</h5> <p dir="auto" id="d7657008e229">Hepatitis E virus (HEV) is an emerging zoonosis circulating in multiple wild and domestic mammals. In Argentina, genotype 3 has been detected in humans, pigs, and environmental water, but the role of feral swine (Sus scrofa) in HEV ecology and transmission dynamics remains underexplored. This study was aimed at investigating HEV exposure in feral swine from Bahía Samborombón, a high-density coastal population. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d7657008e231"> <!-- named anchor --> </a> <h5 class="section-title" id="d7657008e232">Methods:</h5> <p dir="auto" id="d7657008e234">Serum samples from 44 feral swine culled during population control activities in Campos del Tuyú National Park (Bahía Samborombón, Buenos Aires Province, Argentina) between 2021 and 2022 were opportunistically collected and tested with a commercial multispecies ELISA detecting anti-HEV antibodies (genotypes 1–4). </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d7657008e236"> <!-- named anchor --> </a> <h5 class="section-title" id="d7657008e237">Results:</h5> <p dir="auto" id="d7657008e239">Overall, 54.5% (24/44; 95% CI: 38.8–69.6) of the animals were seropositive for HEV, and no significant differences were found between males and females (p = 0.077). </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d7657008e241"> <!-- named anchor --> </a> <h5 class="section-title" id="d7657008e242">Conclusions:</h5> <p dir="auto" id="d7657008e244">The observed high seropositivity exceeding previously reported levels in Argentina indicated widespread exposure in this high-density coastal wetland. These findings underscore the need for integrated One Health and multi-species surveillance to better understand transmission dynamics and inform risk mitigation at the wildlife-livestock-human interface. </p> </div>

<div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d48061961e276"> <!-- named anchor --> </a> <h5 class="section-title" id="d48061961e277">Background:</h5> <p dir="auto" id="d48061961e279">Varicella-zoster virus (VZV) is a clinically important human neurotropic herpesvirus that causes varicella (chickenpox) as primary infection, typically in children. After primary infection, VZV establishes lifelong latency in sensory ganglia and can later reactivate and cause herpes zoster (shingles). Globally, varicella and shingles affect a substantial number of individuals each year. Although people with shingles can recover without specific antiviral treatment, the persistent, often severe pain associated with the disease can lead to depression and significantly decrease quality of life. Currently, acyclovir and its derivatives or similar compounds are the primary FDA-approved treatments for VZV infection. However, resistance to acyclovir, often because of mutations in the viral thymidine kinase, is increasingly observed in clinical settings. Therefore, alternative antiviral strategies against VZV are needed. Propolis (also known as “bee glue”), a resin-like substance produced by bees, has well-documented antibacterial and anti-inflammatory properties. Herein, we investigated the antiviral potential of propolis against VZV in in vitro systems including a cell culture model, human skin, and human dorsal root ganglia (DRG) tissue. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d48061961e281"> <!-- named anchor --> </a> <h5 class="section-title" id="d48061961e282">Methods:</h5> <p dir="auto" id="d48061961e284">ARPE-19 cells, human fetal skin, DRG tissues, and the VZV pOka-Luc-GFP strain (expressing luciferase and GFP for viral monitoring) were used. Propolis (Brazilian green propolis in DMSO) cytotoxicity was assessed with MTT assays. Viral replication was quantified with time-dependent luciferase assays. RNA sequencing (RNA-seq) was performed to analyze differential gene expression in propolis-treated (0.0625% and 0.125%) and control cells (with/without VZV), and was followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Additionally, an acyclovir-resistant VZV mutant (VZV-delTK, lacking the thymidine kinase gene ORF36) was generated with BAC technology for a mechanistic comparison of propolis and acyclovir. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d48061961e286"> <!-- named anchor --> </a> <h5 class="section-title" id="d48061961e287">Results:</h5> <p dir="auto" id="d48061961e289">MTT assays indicated that propolis at ≤0.125% had low cytotoxicity to ARPE-19 cells. Luciferase assays demonstrated that propolis inhibited VZV replication in a concentration-dependent manner. This efficacy was consistent in skin and DRG tissues, in which 0.1% propolis approached acyclovir’s antiviral activity. RNA-seq revealed that propolis altered host gene expression. Among the 207–1035 differentially expressed genes identified across concentrations, the enriched pathways included glycolysis/gluconeogenesis, calcium signaling, and ferroptosis. Propolis also inhibited VZV RNA transcription and splicing. Notably, propolis effectively inhibited the acyclovir-resistant strain VZV-delTK, whereas acyclovir did not, thus confirming the treatments’ distinct mechanisms. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d48061961e291"> <!-- named anchor --> </a> <h5 class="section-title" id="d48061961e292">Conclusions:</h5> <p dir="auto" id="d48061961e294">Propolis exhibited significant antiviral activity against VZV in both cellular and tissue models, through a mechanism distinct from that of acyclovir. These results support further investigation of propolis as a potential anti-VZV agent with a novel mechanism of action. </p> </div>

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d18398939e117">Skeletal healing is constrained by a long-standing paradox. Specifically, analgesia is clinically essential, yet neural signaling is biologically required for effective repair. Recent evidence showed that bone-innervating sensory neurons are temporally plastic rather than functionally fixed. After injury, these neurons transition from an early nociceptive state to a later pro-regenerative secretory program, including trophic factors that are required for periosteal progenitor expansion and successful callus formation. Importantly, this switch is better interpreted as stage-linked than clock-like, broadly tracking the evolution from inflammatory injury signaling toward reparative callus formation with timing varying by skeletal site, age, and injury context. This dynamic framework helps explain why broad neural inhibition can relieve pain, while inadvertently compromising osteogenesis. The translational implication is not to reduce analgesia but to redesign analgesia. Future strategies should decouple nociceptive suppression from the loss of regenerative neural output. Defining therapeutic time windows and modality-specific effects on neurotrophic signaling as well as pain and developing biomarker-guided rescue strategies will be essential for next-generation skeletal management that preserves pain control and biological healing.</p>

<div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"><a class="named-anchor" id="d18401078e264"><!-- named anchor --></a><h5 class="section-title" id="d18401078e265">Background:</h5><p dir="auto" id="d18401078e267">Inflammatory bowel disease (IBD) and Alzheimer’s disease (AD) are major global health burdens that are rising in prevalence but are typically studied as distinct disorders. This study systematically characterizes the convergent risk architecture between IBD and AD using integrated epidemiological, causal, and molecular approaches.</p></div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"><a class="named-anchor" id="d18401078e269"><!-- named anchor --></a><h5 class="section-title" id="d18401078e270">Methods:</h5><p dir="auto" id="d18401078e272">Global epidemiology, Mendelian randomization (MR), and <i>in silico</i> transcriptomic cross-validation were integrated. Global Burden of Disease 2021 data from 204 countries (1990–2021) were analyzed. Two-sample MR was conducted using inverse-variance weighted (IVW) as the primary method, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses to assess causal effects of genetically proxied lifestyle and socio-environmental factors on IBD and AD. Cross-disease transcriptomic analyses were performed to identify shared pathways.</p></div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"><a class="named-anchor" id="d18401078e277"><!-- named anchor --></a><h5 class="section-title" id="d18401078e278">Results:</h5><p dir="auto" id="d18401078e280">Parallel increases in IBD and AD burden were observed, with pronounced sociodemographic disparities and a steep rise in AD in aging, high-sociodemographic index (SDI) populations. Higher genetically proxied educational attainment was associated with reduced risk of IBD (odds ratio [OR] = 0.87, 95% confidence interval [CI] = 0.80–0.94) and AD (OR = 0.82, 95% CI = 0.74–0.91). Higher coffee consumption increased IBD (OR = 1.20, 95% CI = 1.09–1.33) and AD risk (OR = 1.19, 95% CI = 1.05–1.35). Higher beef intake had an inverse association with IBD (OR = 0.48, 95% CI = 0.27–0.88) and AD (OR = 0.0012, 95% CI = 0.0006–0.0025). Transcriptomic analyses demonstrated concordant dysregulation of inflammatory and immune pathways, including TNF/NF-κB signaling. Projections indicated a continued escalation of AD burden to 2050.</p></div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"><a class="named-anchor" id="d18401078e282"><!-- named anchor --></a><h5 class="section-title" id="d18401078e283">Conclusions:</h5><p dir="auto" id="d18401078e285">Convergent epidemiologic, causal, and molecular evidence indicates that IBD and AD share modifiable determinants along the gut–brain axis. These findings highlight opportunities for coordinated prevention strategies targeting chronic inflammatory disease trajectories.</p></div>

<div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"><a class="named-anchor" id="d18399804e171"><!-- named anchor --></a><h5 class="section-title" id="d18399804e172">Background:</h5><p dir="auto" id="d18399804e174">Bone marrow mesenchymal stem cell (BMSC) therapy holds great promise for regenerative medicine, but its clinical translation is hindered by the lack of non-invasive, real-time methods to track transplanted cell fate <i>in vivo</i>. Although photoacoustic (PA) imaging offers deep-tissue penetration and high sensitivity, existing cell-labeling strategies relying on endocytosis of contrast agents have drawbacks of prolonged incubation times and variable efficiency, thus potentially compromising cell viability and function.</p></div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"><a class="named-anchor" id="d18399804e179"><!-- named anchor --></a><h5 class="section-title" id="d18399804e180">Methods:</h5><p dir="auto" id="d18399804e182">To address these limitations, we developed a rapid, bioorthogonal pre-labeling strategy. Azide (N₃) groups were first metabolically engineered onto BMSC surfaces. Subsequently, dibenzocyclooctyne (DBCO)-functionalized gold nanostars (Au-star-DBCO) were conjugated to the cells via a highly efficient, copper-free click reaction, thereby enabling covalent membrane anchoring.</p></div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"><a class="named-anchor" id="d18399804e187"><!-- named anchor --></a><h5 class="section-title" id="d18399804e188">Results:</h5><p dir="auto" id="d18399804e190">This approach achieved rapid and specific stem cell labeling within 3 h, with an efficiency of 83.1% ± 0.67. The labeling process did not impair BMSC viability or multilineage differentiation potential. The Au-star-DBCO-labeled BMSCs generated strong, concentration-dependent PA signals both <i>in vitro</i> and in a rat subcutaneous model, and enabled dynamic monitoring for at least 72 h post-transplantation. The specificity of the bioorthogonal reaction provided a significantly higher signal-to-noise ratio than passive uptake methods.</p></div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"><a class="named-anchor" id="d18399804e195"><!-- named anchor --></a><h5 class="section-title" id="d18399804e196">Conclusions:</h5><p dir="auto" id="d18399804e198">We successfully established a biocompatible and efficient platform for stem cell tracking by integrating metabolic glycoengineering, bioorthogonal chemistry, and nanostar-enhanced PA imaging. This strategy overcomes key limitations of traditional endocytosis-based labeling, and offers a rapid, specific, and functional cell-compatible tool for sensitive, longitudinal <i>in vivo</i> monitoring. This platform may advance precise assessment of cell therapies and facilitate their clinical application.</p></div>

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d18405250e217">Pulmonary fibrosis (PF) is a progressive and irreversible interstitial lung disease that is characterized by destruction of alveolar architecture, excessive proliferation of fibroblasts, and aberrant deposition of extracellular matrix (ECM) but the precise pathogenesis has yet to be fully elucidated. Although traditionally regarded as the terminal metabolite of glycolysis, lactate has been reappreciated, especially following the rise of metabolic reprogramming concepts after the Warburg effect, as an important signaling molecule capable of actively regulating diverse cellular functions. Among these cellular functions, the lactate-induced post-translational modification (PTM), known as lactylation, offers a new perspective for understanding the broad biological actions of lactate beyond metabolism. Notably, the pathologic microenvironment of PF is characterized by widespread metabolic reprogramming and lactate accumulation, suggesting that lactate and lactate-mediated lactylation may serve key roles in disease progression by regulating pro-fibrotic gene expression and influencing fibroblast activation and differentiation. Therefore, this review focuses on how lactylation functions as a bridge linking metabolic reprogramming to fibrotic phenotypes in PF and the translational potential as a novel therapeutic target is discussed.</p>

<div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"><a class="named-anchor" id="d18399809e201"><!-- named anchor --></a><h5 class="section-title" id="d18399809e202">Background:</h5><p dir="auto" id="d18399809e204">Marker-based motion capture remains the gold standard for deriving lower-limb kinematics and kinetics, but its high cost, lengthy setup time, and large space requirements limit its widespread use. Markerless technologies, such as depth camera systems (e.g., Azure Kinect) and emerging smartphone-based pipelines (e.g., OpenCap), promise laboratory-grade motion capture without markers. However, the effects of their capture data on musculoskeletal multibody dynamics simulation outcomes remain insufficiently understood.</p></div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"><a class="named-anchor" id="d18399809e206"><!-- named anchor --></a><h5 class="section-title" id="d18399809e207">Methods:</h5><p dir="auto" id="d18399809e209">This study was aimed at developing a single lower-limb musculoskeletal model simultaneously driven by two markerless motion capture inputs (Azure Kinect and OpenCap), and benchmarking the resulting joint angles, ground-reaction forces, and joint contact forces against synchronous Vicon recordings. In gait trials, movements were simultaneously recorded with Azure Kinect, OpenCap, and a Vicon motion capture system. The collected data were processed and used as inputs to construct the musculoskeletal model, which was then combined with a foot-ground contact model to compute lower-limb joint angles, ground reaction forces (GRFs), and joint contact forces.</p></div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"><a class="named-anchor" id="d18399809e211"><!-- named anchor --></a><h5 class="section-title" id="d18399809e212">Results:</h5><p dir="auto" id="d18399809e214">The OpenCap-based model showed strong agreement with the Vicon-referenced model (<i>ρ</i> > 0.73) in hip flexion-extension (FE), knee FE, and ankle FE, with a root mean square error (RMSE) of 4.04° to 7.66°, Sprague and Geers magnitude error (<i>M</i>) of −0.25 to −0.10, phase error (<i>P</i>) of 0.08 to 0.25, and composite error (<i>C</i>) of 0.16 to 0.39. Additionally, strong correlations (<i>ρ</i> > 0.77) in hip contact force, knee contact force, medial knee contact force, and ankle contact force were observed between OpenCap and Vicon, with an RMSE of 0.26 to 0.90 Body Weight (BW), <i>M</i> of −0.03 to 0.13, <i>P</i> of 0.05 to 0.08, and <i>C</i> of 0.08 to 0.17.</p></div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"><a class="named-anchor" id="d18399809e241"><!-- named anchor --></a><h5 class="section-title" id="d18399809e242">Conclusions:</h5><p dir="auto" id="d18399809e244">Overall, under the study conditions, the smartphone-based OpenCap preliminarily showed accuracy as a potential alternative to marker-based systems for estimating lower-limb biomechanics. However, given the small sample size and tasks restricted to walking, it is currently primarily suited for research settings or initial screening, rather than high-precision clinical diagnosis. Further studies in larger, more diverse cohorts and validation across dynamic activities are required to confirm and extend its applicability.</p></div>

Platinum Open Access with no APCs.

<p xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="first" dir="auto" id="d13391869e221">In normal cardiac energy metabolism, 95% of the heart’s energy is provided by mitochondria, and preferences for energy-providing substrates vary at different times (Nguyen BY, Ruiz-Velasco A, Bui T, Collins L, Wang X, Liu W. Mitochondrial function in the heart: the insight into mechanisms and therapeutic potentials. Br J Pharmacol 2019;176(22):4302–4318). However, prolonged metabolic alterations impair cardiac function (Hu L, Tang D, Qi B, Guo D, Wang Y, Geng J, et al. Mfn2/Hsc70 complex mediates the formation of mitochondria-lipid droplets membrane contact and regulates myocardial lipid metabolism. Adv Sci (Weinh) 2024;11(14):e2307749). Therefore, this study primarily focuses on the relationship between amino acid metabolism and diabetic cardiomyopathy and atherosclerosis. Changes in metabolic processes also promote the development and worsening of these two diseases. Lipid and glucose metabolism in such diseases have been extensively studied, and emerging evidence suggests that amino acid metabolism also plays major roles in diabetic cardiomyopathy and atherosclerosis. Specific amino acid intake or catabolism might influence oxidative stress, inflammation, and fibrosis, among related processes, thus indirectly highlighting their potential as novel targets for metabolic interventions. However, the mechanisms and clinical relevance of amino acid metabolism in these diseases remain incompletely understood and warrant further investigation. </p>

Platinum Open Access with no APCs.