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关键词： Monkeypox virus   Mpox   Cambodia   lineage C.1   Bayesian phylodynamics  

摘要： Mpox is an infectious disease caused by the Monkeypox virus, which is divided into two main genetic clades: Clade I and Clade II. A large-scale outbreak linked to Clade IIb emerged in 2022 and rapidly spread to more than 100 countries worldwide. Here, we describe the first and only documented Mpox outbreak in Cambodia (2023-2024 the public health outbreak response efforts and analysis, and integrating epidemiological and genomic approaches.To investigate the outbreak, samples from suspect cases were confirmed using qPCR before virus whole genome sequences were obtained for phylogenomic analyses.Epidemiological investigation revealed transmission primarily through intimate contact within socially connected networks, exclusively among men who have sex with men. None of the confirmed cases reported recent international travel or zoonotic exposure. Phylogenomic analysis showed that all Cambodian Mpox genomes belonged to lineage C.1, nested within Clade IIb. Bayesian analysis of publicly available C.1 genomes indicated that the most closely related sequence was from Thailand. Monophyletic clustering of Cambodian sequences, alongside a high proportion of APOBEC3 mutations, indicates localized human-to-human transmission after introduction.Altogether, these results illustrate the risk of regional lineages like C.1 introducing Mpox into previously unaffected countries, where socially connected human networks can sustain outbreaks despite control efforts.

关键词： Synthetic aperture radar  

摘要： Rice production in the Vietnamese Mekong Delta (VMD) faces rising climate and ecological challenges, prompting national policies to reduce cropping intensity and restore floodplain functions. Synthetic Aperture Radar (SAR) is an effective tool for continuous rice production monitoring, as it is less affected by cloud cover. As such, it can capture complete phenological cycles of rice growth and enable differentiation of rice typologies. This research developed an object-based classification framework using SAR backscatter time series data and Dynamic Time Warping (DTW) to map the Triple Rice and Double Rice production typologies. Landscape segmentation was implemented to delineate homogeneous units for object-based analysis. Sentinel-1 backscatter time series were generated for each unit to capture annual temporal dynamics. Using t-SNE and HDBSCAN clustering, the predominant temporal patterns within the VMD were identified. By associating these with field survey labels, reference temporal profiles for Double and Triple Rice were defined. Finally, landscape units were assigned to rice typologies with the most similar temporal profiles, and the similarity was measured using DTW. This framework was implemented for two years (2019 and 2022). Its accuracy exceeded 83% for 2022. A comparison between 2019 and 2022 indicates a clear transition toward lower cropping intensity. La production rizicole dans le delta du M & eacute;kong vietnamien (DMV) est confront & eacute;e & agrave;des d & eacute;fis climatiques et & eacute;cologiques croissants, ce qui a incit & eacute;les autorit & eacute;s nationales & agrave;mettre en oe uvre des politiques visant & agrave;r & eacute;duire l'intensit & eacute;des cultures et & agrave;restaurer les fonctions des plaines inondables. Le radar & agrave;synth & egrave;se d'ouverture (RSO) est un outil efficace pour le suivi continu de la production rizicole, car il est moins sensible & agrave;la couverture nuageuse. Il permet ainsi de saisir l

关键词： COVID-19   influenza   combination vaccine   immunogenicity   safety   Matrix-M adjuvant  

摘要： Based on viral evolution, increases in seasonal infections, and facilitation of delivery, an annual combination vaccine simultaneously targeting influenza and SARS-CoV-2 would benefit public health. The safety and immunogenicity of a COVID-19-Influenza Combination nanoparticle vaccine (CIC) containing SARS-CoV-2 recombinant spike (rS) to the ancestral strain (Wuhan) and quadrivalent influenza hemagglutinin with a Matrix-M (R) saponin-based adjuvant were evaluated in a phase 1/2 blinded, randomized trial. The safety, tolerability, and immunogenicity of a CIC two-dose series were assessed and compared with standalone quadrivalent influenza (qNIV) and monovalent COVID-19 (NVX-CoV2373) vaccines. Reactogenicity events, unsolicited adverse events (AEs antiviral microneutralization responses, hemagglutination-inhibition antibody titers, anti-rS protein immunoglobulin G, and human angiotensin-converting enzyme 2 receptor binding inhibition antibody responses for SARS-CoV-2 were measured. All participants had been previously vaccinated against ancestral SARS-CoV-2. From September 8, 2021, to April 22, 2022, 642 participants were enrolled and randomized into the study;637 received at least one vaccination. After each dose, CIC formulations induced antibody responses against homologous and heterologous influenza and SARS-CoV-2 strains that were comparable with the references. The CIC vaccine group had similar incidence of solicited and unsolicited AEs as the qNIV and NVX-CoV2373 reference groups. Severe unsolicited AEs only occurred in the CIC group but were infrequent and not considered related to the study vaccine. Overall, CIC formulations displayed reference-comparable safety and immunogenicity and provided data for statistical modeling analyses to optimize influenza hemagglutinin and SARS-CoV-2 rS antigen concentrations for use in phase 2 clinical trials investigating CIC.

关键词： Salvianolic acid B   benzoylpaeoniflorin   ischemic stroke   angiogenesis   Nrf2/HO-1/VEGFA signaling axis  

摘要： ContextAngiogenesis is one of the essential protective mechanisms that promote neural repair and regeneration after ischemic stroke (IS). Salvianolic Acid B (SAB) and Benzoyl paeoniflorin (BP) are compounds extracted from the Chinese medicines Salvia miltiorrhiza Bunge and Paeonia suffruticosa Andrews, respectively.ObjectiveWe investigated whether SAB combined with BP alleviated IS by promoting micrangium angiogenesis and determined the potential molecular mechanisms.Materials and methodsThe impact of SAB-BP on angiogenesis after IS was investigated in middle cerebral artery occlusion (MCAO) rat model, ponatinib-induced ischemic stroke in zebrafish, and human umbilical vein endothelial cells (HUVECs). The neuroprotective effect of SAB-BP in rats was assessed using behavior tests and histopathological staining. The cerebral thrombosis assessment and angiogenesis assay were performed in the zebrafish model. Cell proliferation and angiogenesis in oxygen-glucose deprivation and reperfusion (OGD/R) HUVECs were assessed through cell viability, tube formation, migration, and invasion assays. Western blot analysis and immunofluorescence staining were used to determine the protein expression levels of Nrf2, HO-1, and VEGFA.ResultsThe findings indicated that SAB-BP significantly reduced neurological impairment following IS and promoted the formation of functional vessels in the cerebral ischemic penumbra. Furthermore, SAB-BP up-regulated the protein expression of Nrf2, HO-1, HIF-1 alpha, and VEGFA. Intriguingly, the pro-angiogenic effect of SAB-BP markedly restrained by adding the inhibitor of Nrf2 (ML385).Discussion and conclusionOur study demonstrates that SAB-BP enhances angiogenesis following IS by modulating the Nrf2/HO-1/VEGFA signaling axis both in vivo and in vitro. SAB-BP could serve as a promising therapeutic agent for IS recovery.

关键词： Angiotensin II type 1 receptor A1166C gene polymorphism   essential hypertension   susceptibility   association  

摘要： PurposeThis study aims to explore the association between the angiotensin II type 1 receptor (AT1R) A1166C gene polymorphism and susceptibility to essential hypertension (EH) within the Chinese population.Materials and MethodsRelevant literature published domestically and internationally was systematically retrieved from database inception to 31 December 2024. A total of 17 eligible studies involving 9,213 patients with EH and 4,494 healthy controls were included. Meta-analysis, subgroup analysis (by ethnicity and region sensitivity analysis and publication bias assessment were performed.ResultsMeta-analysis showed that the AC/CC genotype (odds ratio [OR] = 1.34, 95% confidence interval [CI 1.07-1.69, p = 0.01) and C allele (OR = 1.44, 95% CI: 1.14-1.82, p = 0.002) were modestly associated with an increased EH risk. Subgroup analysis revealed significant associations in the Han (AC/CC: OR = 1.56;C allele: OR = 1.58) and Yi (AC/CC: OR = 1.80;C allele: OR = 1.84) populations, as well as a significant association between the C allele and EH in northern/northwestern regions (OR = 1.37, p = 0.04). However, these subgroup findings should be interpreted cautiously. Funnel plots indicated low publication bias.ConclusionThe AT1R A1166C polymorphism may modestly contribute to EH susceptibility in the Chinese population, with ethnic and regional factors partly influencing this association. Large-scale prospective studies with more balanced subgroup representations and standardised blood pressure assessment methods are needed to validate these findings.

关键词： Non-National Immunization Program   PCV   Hib   rotavirus   varicella   vaccination coverage   Beijing  

摘要： The pneumococcal conjugate vaccine (PCV Haemophilus influenzae type b (Hib) vaccine, rotavirus vaccine (RV and varicella vaccine (VarV) have been recommended by WHO for inclusion in National Immunization Program (NIP). However, their vaccination rate is low in China as self-funded vaccines. This study aimed to investigate the coverage of these four vaccines and to identify their influencing factors. Selected via multi-stage stratified sampling, 4,182 guardians participated in a February-March 2025 study. Guardians completed an online questionnaire capturing sociodemographic characteristics, attitudes toward vaccination, and indicators of immunization service accessibility. Individual-level vaccination histories for children were extracted from the Beijing Immunization Information System and linked to survey responses. The vaccination coverage of PCV, Hib vaccine, RV and VarV were 48.5%, 47.4%, 43.5% and 89.3%, respectively. Older age, residence outside urban areas (suburban, outer suburban and greater number of children in the household were associated with lower coverage of PCV, Hib vaccine, and RV, with adjusted ORs ranging from 0.160 to 0.929 (all p values < .05). Conversely, higher household income (200,000-499,999 CNY and >= 500,000 CNY guardians' perceived vaccination necessity, and receipt of vaccination notifications were associated with higher coverage of PCV, Hib vaccine, and RV, with adjusted ORs ranging from 1.018 to 6.521 (all p values < .05). The results indicated the vaccination coverage of PCV, Hib vaccine, and RV remains suboptimal in Beijing, with evident regional disparities. Free vaccination policies for PCV, Hib vaccine, RV, and VarV, together with strengthened reminder systems and targeted health education interventions, may help improve vaccine coverage among children.

关键词： Earthquake sequence   rupture propagation   interferometric synthetic aperture radar   Sentinel-1   ALOS-2  

摘要： Rupture propagation in the August 2018 Kaktovik earthquake sequence, which included Mw 6.4, Mw 5.3, and Mw 6.0 events near the Sadlerochit Mountains in northeastern Alaska, was constrained using three Sentinel-1 C-band interferometric synthetic aperture radar (InSAR) datasets acquired from different viewing geometries and one ALOS-2 L-band InSAR dataset. Line-of-sight (LOS) displacements measured from these datasets were used to derive east-west and vertical displacement components. The maximum displacements observed were 27.6 cm of westward motion near the Mw 5.3 epicenter and 20.9 cm of subsidence near the Mw 6.0 epicenter. The LOS displacements derived from all interferograms except one low-coherence descending Sentinel-1 interferogram were then jointly inverted to estimate the source parameters and distributed slip of the three faults responsible for the observed displacement. By integrating the distributed-slip models with Coulomb stress change analysis and aftershock patterns, we identified a fault network in which two intersecting faults interact with a main fault. In particular, the L-band InSAR observation clearly resolved a symmetric displacement pattern around the Mw 5.3 epicenter, and its integration with multi-track Sentinel-1 data in a joint inversion enabled estimation of a physically plausible geometry for the intersecting fault. These results are consistent with a rupture propagation scenario in which rupture may have initiated on the main fault and propagated eastward in a stepwise manner through interactions with the intersecting faults.

关键词： AKK   LKLKLL peptide   incretins   obesity   type 2 diabetes mellitus  

摘要： The ability of Akkermansia muciniphila (AKK) to ameliorate metabolic dysfunction has attracted increasing attention as a potential strategy for obesity and diabetes management. Moving beyond the use of live bacteria toward the identification of defined bioactive components may facilitate translational development. In this study, we found that the metabolic supernatant of AKK promoted GLP-1 and GIP secretion in STC-1 cells. Metabolomic profiling identified 54 small molecules in the AKK supernatant, among which a bioactive hexapeptide, LKLKLL, was identified. LKLKLL reduced body weight in high-fat diet-induced obese mice, improved glucose tolerance in diabetic models, enhanced GLP-1 secretion, and reduced GIP levels. Mechanistically, our data suggest that LKLKLL may interact with GPR119 and activate the G alpha s/adenylate cyclase/cAMP signaling pathway, leading to increased intracellular Ca & sup2;(+) levels. Together, these findings identify an AKK-derived peptide with GLP-1/GIP regulatory activity and provide a foundation for further investigation of its potential role in metabolic diseases modulation.

关键词： Preeclampsia   second trimester   sFlt-1/PlGF ratio   composite adverse neonatal outcome   neonatal risk prediction  

摘要： Objectives To investigate the predictive performance of the second-trimester soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio for composite adverse neonatal outcome (CANO) in preeclampsia (PE). Methods This retrospective cohort study enrolled 253 PE women during June 2022-June 2024. Maternal serum levels of sFlt-1 and PlGF were assessed, and their ratio was determined at 13-27 gestational weeks. Subjects were stratified into CANO (n = 80) and non-CANO (n = 173) groups. Baseline characteristics and the sFlt-1/PlGF ratio were compared. Univariate and multivariate logistic regression analyses were employed to identify independent risk factors for CANO. Predictive value was assessed using ROC curve analysis, and a nomogram prediction model was constructed. Results The sFlt-1/PlGF ratio was markedly higher in the CANO group than the non-CANO group (p < 0.001). Multivariate analysis identified the sFlt-1/PlGF ratio (OR = 1.040, 95% CI: 1.020-1.060, p < 0.001 serum uric acid level (OR = 1.007, 95% CI: 1.000-1.013, p = 0.043 and history of pre-pregnancy hypertension (OR = 13.51, 95% CI: 2.065-88.36, p = 0.007) as independent risk factors for CANO. Conversely, gestational age at delivery (OR = 0.727, 95% CI: 0.621-0.852, p < 0.001) was a protective factor. The sFlt-1/PlGF ratio predicted CANO with an AUC of 0.799 (95% CI: 0.743-0.855). The integrated nomogram model achieved a C-index of 0.880 (95% CI: 0.836-0.923 indicating excellent discrimination. Conclusion The second-trimester sFlt-1/PlGF ratio is an independent predictor for CANO in PE. A model incorporating this biomarker facilitates the early identification of high-risk neonates, informing personalized perinatal management.

关键词： TREK-1   arrhythmia   depression   heart failure   therapeutic target  

摘要： TREK-1 (KCNK2) is a polymodal two-pore domain potassium (K2P) channel that functions as a background K+ conductance and integrator of mechanical, chemical, and thermal stimuli across diverse cell types. Its unique structure enables sensitivity to membrane stretch, lipid composition, pH, temperature, pharmacologic agents, and intracellular signaling pathways. Beyond shaping resting membrane potential and excitability, TREK-1 engages in noncanonical signaling roles involving protein-protein interactions, trafficking, and modulation of intracellular signaling cascades such as MAPK and calcineurin pathways. TREK-1 is widely expressed in the nervous system, where it regulates neuronal firing, pain sensitivity, mood, and neuroprotection. In the heart, TREK-1 influences action potential duration, mechano-electric feedback, sinoatrial node function, and stress-induced remodeling, with mutations linked to arrhythmogenesis. In fibroblasts and fibroblast-like cells, TREK-1 acts as a mechanotransducer driving differentiation and fibrosis through MAPK signaling. TREK-1 also modulates immune activation, inflammasome signaling, adipogenesis, epithelial injury responses, vascular tone, and cancer cell proliferation. Across tissues, dysregulation of TREK-1 contributes to pathological excitability, fibrosis, inflammation, and degeneration. Given its multimodal regulation and broad impact on cellular function, TREK-1 represents a compelling therapeutic target, though challenges remain due to limited subtype-selective pharmacology and incomplete understanding of its nonionic signaling roles.