Background and Objectives: SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms. Methods: Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes. Results: The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes. Conclusions This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.

Background and Objectives: SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms. Methods: Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes. Results: The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes. Conclusions This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.

Objective On the basis of systematically summarizing and organizing the existing standards of mineral drugs in traditional Chinese medicine,this study aims to construct the top-level framework of the mineral drug standard system and promote the standardization process of the mineral drug industry.Methods A comprehensive search and analysis of the standards for 87 kinds of mineral drugs were conducted on authoritative platforms such as the National Standard Information Public Service Platform,China Standard Service Network,and Traditional Chinese Medicine Standard and Guideline Information Service.By delving into the theoretical foundation and scientific methods,combined with practical research,this study uses analogy reference,systematic decomposition,and process analysis to design the top-level framework of the mineral drug standard system.Results Through comprehensive analysis and scientific design,this study summarizes the construction process and methods of the mineral drug standard system,clarifies the hierarchical structure and classification principles of the system,proposes the compilation path,and forms a standard system covering the entire industry chain of mineral drugs,including raw minerals,product categories,and circulation categories.Conclusion This study constructs a full industry chain process framework for the standard system of mineral drugs,providing a clear perspective for the research of mineral drugs.It can more comprehensively display the current state of development of mineral drug standards in our country,laying a foundation for the research on the standardization of mineral drugs.

Autophagy is a cellular self-degradation process that maintains homeostasis and has been shown to promote tumor progression in advanced stages.Pancreatic cancer cells and the surrounding stromal cells exhibit high levels of autophagy.Therefore,targeting au-tophagy has emerged as a promising therapeutic strategy for pancreatic cancer.This review focuses on research targeting autophagy in pancreatic cancer treatment,elaborating on the roles and underlying mechanisms of autophagy in pancreatic cancer cell proliferation,metas-tasis,modulation of the tumor immune microenvironment,and drug resistance.Additional-ly,we summarize preclinical and clinical studies investigating autophagy-targeted therapies both as monotherapy and in combination with other treatments,aiming to provide new theo-retical rationale and therapeutic strategies for pancreatic cancer management.

Objective:To explore the molecular epidemiological characteristics of human metapneumovirus (HMPV) in children with acute respiratory infection (ARI) in Beijing from 2023 to 2024.Methods:In the longitudinal study, 9 834 children with ARI were enrolled from August 2023 to December 2024, including the influenza-like illness (ILI) group from emergency and outpatient department receiving influenza virus (Flu) and HMPV test and the ARI inpatient group for 13 common respiratory pathogen screening test including HMPV, Flu, respiratory syncytial virus, and so on. All respiratory samples positive with HMPV were genotyped by amplifying and sequencing of G gene and further phylogenetic analysis. The χ2 test and Wilcoxon rank-sum test were used to compare the positive rate and basic clinical data of the 2 groups. Results:Among 9 834 enrolled patient, there were 5 276 male and 4 558 female children, with age 5.4 (1.9, 8.2) years. In ILI group of 1 460 patients, there were 83 cases (5.7%) positive for HMPV, with the age 4.9 (3.6, 6.6) years and children under 6.0 years old 59 cases (71.1%). Among 8 374 ARI inpatients, there were 256 cases (3.1%) positive for HMPV, with age 3.5 (1.3, 6.4) years and children under 6.0 years old 188 cases (73.4%). The HMPV positive rate and the age of children positive for HMPV in ARI inpatient group were significantly lower than that in ILI group (both P<0.001). In December, 2024, the HMPV positive rates of ILI and ARI inpatient group (21.3% (17/80), 15.0% (47/314)) were significantly higher than the total positive rates of each group (both P<0.001). Among 279 subtyped specimens, there were 155 cases (55.6%) belonging to genotype A and 124 cases (44.4%) belonging to genotype B. Sub-lineage A2.2.2 containing 111nt-insertions was predominate one in 2023 with positive ratio 89.2% (91/102), and B2 was predominate in 2024 with positive ratio 64.4% (114/177). Conclusions:From 2023 to 2024, the positive rate of HMPV in the ILI group was higher than that in the ARI inpatient group, suggesting a common epidemic of HMPV infection. Children positive for HMPV in the ARI inpatient group were younger than that in the ILI group. A severe epidemic of HMPV was observed in the winter of 2024, which requires attention. Sub-lineage A2.2.2 with 111nt-duplicate insertions and B2 were the predominant epidemic strains in 2023 and 2024, respectively.

Objective To assess the clinical value of a novel surgical technique—Tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device in the resection of anterior mediastinal masses. Methods Patients who underwent tubeless subxiphoid uniportal video-assisted thoracoscopic surgery via balance-shaped sternal elevation device in anterior mediastinal masses process at the Department of Thoracic Surgery, West China Hospital, Sichuan University from March to April 2025 were included, and their clinical data were analyzed. Results A total of 4 patients were included, with 2 males and 2 females, aged 58-75 years. The diameter of the tumor was 2.5-3.0 cm. The operation time was 60.0-150.0 min, intraoperative blood loss was 5-10 mL, pain score on the 3rd day after surgery was 0 points, and postoperative hospital stay was 2-3 days. All patients achieved complete resection of the masses and thymus without perioperative complications. Conclusion The tubeless subxiphoid uniportal video-assisted thoracoscopic surgery with percutaneous suspension technique via balance-shaped sternal elevation device technique optimizes surgical visualization and instrument maneuverability while avoiding complications related to conventional anesthesia and tubing, thereby markedly enhancing the minimally invasive profile of anterior mediastinal masses resections. In addition to maintaining procedural safety, this approach effectively reduces postoperative pain and accelerates patient recovery, highlighting its potential for widespread clinical adoption.

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

OBJECTIVE: Recombination events are common and serve as the primary driving force of diverse human adenovirus (HAdV), particularly in children with acute respiratory tract infections (ARIs). Therefore, continual monitoring of these events is essential for effective viral surveillance and control. METHODS: Respiratory specimens were collected from children with ARIs between January 2022 and December 2023. The penton base, hexon, and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type. In cases with inconsistent typing results, genes were cloned into the pGEM-T vector to detect recombination events. Metagenomic next-generation sequencing (mNGS) was performed to characterize the recombinant HAdV genomes. RESULTS: Among 6,771 specimens, 277 (4.09%, 277/6,771) were positvie for HAdV, of which 157 (56.68%, 157/277) were successfully typed, with HAdV-B3 being the dominant type (91.08%, 143/157), and 14 (5.05%, 14/277) exhibited inconsistent typing results, six of which belonged to species B. The penton base genes of these six specimens were classified as HAdV-B7, whereas their hexon and fiber genes were classified as HAdV-B3, resulting in a recombinant genotype designated P7H3F3, which closely resembled HAdV-B114. Additionally, a partial gene encoding L1 52/55 kD was identified, which originated from HAdV-B16. CONCLUSION A novel recombinant, P7H3F3, was identified, containing sequences derived from HAdV-B3 and HAdV-B7, which is similar to HAdV-B114, along with additional sequences from HAdV-B16.
Humans ; Adenoviruses, Human/isolation & purification* ; Respiratory Tract Infections/epidemiology* ; Child, Preschool ; Child ; Recombination, Genetic ; Male ; Beijing/epidemiology* ; Infant ; Female ; Phylogeny ; Adenovirus Infections, Human/epidemiology* ; Acute Disease ; Genome, Viral

Viruses constitute a significant group of pathogens that have caused numerous fatalities and substantial economic losses in recent years, particularly with the emergence of coronaviruses. While the impact of SARS-CoV-2 appears to be diminishing in daily life, only a limited number of drugs have received approval or emergency use authorization for its treatment. Given the high mutation rate of viral genomes, host-directed agents (HDAs) have emerged as a preferred choice due to their broad applicability and lasting effectiveness. In contrast to direct-acting antivirals (DAAs), HDAs offer several advantages, including broad-spectrum antiviral activities, potential efficacy against future emerging viruses, and a lower likelihood of inducing drug resistance. In our review article, we have synthesized known host-directed antiviral targets that span diverse cellular pathways and mechanisms, shedding light on the intricate interplay between host cells and viruses. Additionally, we have provided a brief overview of the development of HDAs based on these targets. We aim for this comprehensive analysis to offer valuable perspectives and insights that can guide future antiviral research and drug development efforts.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.