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The outbreak of emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) in China has been brought to global attention and declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Scientific advancements since the pandemic of severe acute respiratory syndrome (SARS) in 2002~2003 and Middle East respiratory syndrome (MERS) in 2012 have accelerated our understanding of the epidemiology and pathogenesis of SARS-CoV-2 and the development of therapeutics to treat viral infection. As no specific therapeutics and vaccines are available for disease control, the epidemic of COVID-19 is posing a great threat for global public health. To provide a comprehensive summary to public health authorities and potential readers worldwide, we detail the present understanding of COVID-19 and introduce the current state of development of measures in this review.

The collaboration of healthcare systems in Hong Kong, Macao, and the mainland of China is a critical issue for addressing the medical needs of internal migrants in China, who often face disparities in coverage and access to services when moving across these three regions. These migrants are particularly disadvantaged by the structural differences between the universal public healthcare systems of Hong Kong and Macao and the combined social medical insurance and universal health insurance system in the mainland of China. This paper examines these distinct healthcare models and finds that significant differences in coverage, funding, and service delivery pose key challenges to the portability of benefits for cross-region migrants and the collaboration of regional healthcare systems. To advance healthcare collaboration and ensure that migrant populations receive equitable healthcare, the paper proposes establishing a fiscal compensation mechanism to address the financial imbalances caused by cross-region service usage. It also advocates for adopting principles for the portability of healthcare benefits and regulating cross-region medical services to create a more cohesive and integrated regional healthcare system.

The rapid and sensitive detection of the important biomarker C-reactive protein (CRP) is of great significance for monitoring inflammation and tissue damage. In this work, an electrochemiluminescence (ECL) aptasensor was fabricated based on dual signal amplification for the sensitive detection of CRP in serum samples. The sensor was constructed by modifying a silica nanochannel array film (SNF) on a cost-effective indium tin oxide (ITO) electrode using the Stöber solution growth method. Gold nanoparticles (AuNPs) were grown in situ within the nanochannels using a simple electrodeposition method as a nanocatalyst to enhance the active electrode area as well as the ECL signal. The negatively charged nanochannels also significantly enriched the positively charged ECL emitters, further amplifying the signal. The recognition aptamer was covalently immobilized on the outer surface of SNF after modification with epoxy groups, constructing the aptasensor. In the presence of CRP, the formation of complexes on the recognitive interface led to a decrease in the diffusion of ECL emitters and co-reactants to the supporting electrode, resulting in a reduction in the ECL signal. Based on this mechanism, ECL detection of CRP was achieved with a linear range of 10 pg/mL to 1 μg/mL and a low limit of detection (7.4 pg/mL). The ECL aptasensor developed in this study offers advantages such as simple fabrication and high sensitivity, making promising applications in biomarker detection.

Photothermoelectric materials have important applications in many fields. Here, we joined a silver nanostructure film and a carbon nanotube film by van der Waals force to form a heterojunction, which shows excellent photothermal and photoelectric conversion properties. The local temperature difference and the output photovoltage increase rapidly when the heterojunction is irradiated by lasers with wavelengths ranging from ultraviolet to terahertz. The maximum temperature difference reaches 215.9 K, which is significantly higher than that of other photothermoelectric materials reported in the literature. The photothermal and photoelectric responsivity depend on the wavelength of lasers, which are 175~601 K W -1 and 9.35~40.4 mV W -1 , respectively. We demonstrate that light absorption of the carbon nanotube is enhanced by local surface plasmons, and the output photovoltage is dominated by Seebeck effect. The proposed heterostructure can be used as high-efficiency sensitive photothermal materials or as ultra-wideband fast-response photoelectric materials. Finding efficient photothermoelectric materials remains critical to the development of clean and renewable energy conversion technologies. Here, authors prepare a silver nanostructure film/carbon nanotube film heterojunction with excellent photothermal and photoelectric conversion performance.

Osimertinib is the standard first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for EGFR-mutant non-small-cell lung cancer (NSCLC), yet acquired resistance remains inevitable. While metabolic adaptation and proteostasis rewiring have emerged as key contributors to EGFR-TKI resistance, the actionable regulators that integrate these processes are incompletely defined. FKBP4 expression was assessed in public NSCLC cohorts and institutional specimens and examined in acquired osimertinib-resistant cell models. Gain- and loss-of-function studies were performed to evaluate osimertinib sensitivity, proliferation, clonogenicity, migration/invasion, and epithelial–mesenchymal transition (EMT). Glycolytic remodeling was characterized by untargeted metabolomics, glucose uptake and lactate production assays, and Seahorse extracellular flux analysis. PI3K–AKT signaling was analyzed by immunoblotting and pharmacological inhibition using MK2206. Candidate deubiquitinases were prioritized in silico and validated by molecular modeling, co-immunoprecipitation, ubiquitination assays, and cycloheximide chase. Therapeutic relevance was further examined in xenograft models. FKBP4 was upregulated in NSCLC tissues and further increased in acquired osimertinib-resistant cells. FKBP4 overexpression enhanced cell viability and clonogenic survival under osimertinib and shifted dose–response curves toward higher IC50 values, whereas FKBP4 depletion partially restored drug sensitivity in resistant cells. FKBP4 also promoted migration/invasion and was associated with EMT-related changes, marked by E-cadherin downregulation and increased N-cadherin, vimentin, and Snail. Mechanistically, FKBP4 promoted glucose metabolism toward a Warburg-like phenotype, as evidenced by increased glucose uptake and lactate output, upregulation of GLUT1 (SLC2A1) and LDHA, elevated ECAR, and reduced oxidative respiration. FKBP4 further activated PI3K–AKT signaling, and MK2206 attenuated FKBP4-driven resistance. Upstream, USP7 physically interacted with FKBP4 and maintained FKBP4 protein stability through deubiquitination: USP7 depletion reduced FKBP4 protein abundance without affecting its mRNA, accelerated FKBP4 turnover, and increased FKBP4 polyubiquitination, whereas wild-type USP7—but not a catalytically inactive mutant—suppressed FKBP4 ubiquitination. In vivo, FKBP4 silencing enhanced the antitumor effect of osimertinib in resistant xenografts and mitigated EMT features. These findings support a role for the USP7–FKBP4 axis in acquired osimertinib resistance in NSCLC and suggest that FKBP4 stabilization is associated with glycolytic remodeling and pro-survival signaling in resistant cells. Our study extends current understanding of resistance-associated metabolic adaptation and identifies the USP7–FKBP4 pathway as a potential therapeutic vulnerability that warrants further investigation.

The relationship between physical activity (PA) and the risk of frailty has not reached a conclusive result. This systematic review with meta-analysis aimed to evaluate the effect of PA on the onset of frailty in the community-dwelling middle and older age adults by pooling data from cohort studies. A systematic literature search was performed via PubMed, Embase, and Web of Science up to June 01, 2021. Pooled adjusted effect estimates (ES) with 95% confidence interval (CI) were calculated by using the random-effect model and by comparing the highest with lowest levels of PA. Heterogeneity was tested using the I2 statistic and Q-test. The quality of evidence was evaluated by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A total of ten cohort studies with 14 records were selected, and the GRADE approach classified the quality of evidence as low. In comparison with the lowest level of PA, the highest level of PA was associated with 41% decreased odds of frailty (ES: 0.59, 95% CI: 0.51-0.67; I2 = 70.0%, P-heterogeneity < 0.001) after pooling results from included studies. In stratified analysis by frailty assessment approach, the highest level of PA was significantly associated with 37% (ES 0.63, 95% CI: 0.52-0.77, 49% (ES: 0.51, 95% CI: 0.41-0.63), and 30% (ES: 0.70, 95% CI: 0.65-0.75) reduced odds of frailty when pooling studies using criteria of physical frailty, multidimensional model, and accumulation of disability, respectively. Stratified analyses further by PA indicators and PA assessment tools yielded similar protective effects in any subgroups. This study with moderate-certainty evidence shows that a higher level of PA was associated with lower odds of frailty, and the benefits of PA for frailty prevention were independent of frailty assessment tools, PA indicators, and PA assessment methods. Findings from this study may help implement active exercise strategies to prevent frailty.

Retinal fundus photography provides a non-invasive approach for identifying early microcirculatory alterations of chronic diseases prior to the onset of overt clinical complications. Here, we developed neural network models to predict hypertension, hyperglycemia, dyslipidemia, and a range of risk factors from retinal fundus images obtained from a cross-sectional study of chronic diseases in rural areas of Xinxiang County, Henan, in central China. 1222 high-quality retinal images and over 50 measurements of anthropometry and biochemical parameters were generated from 625 subjects. The models in this study achieved an area under the ROC curve (AUC) of 0.880 in predicting hyperglycemia, of 0.766 in predicting hypertension, and of 0.703 in predicting dyslipidemia. In addition, these models can predict with AUC>0.7 several blood test erythrocyte parameters, including hematocrit (HCT), mean corpuscular hemoglobin concentration (MCHC), and a cluster of cardiovascular disease (CVD) risk factors. Taken together, deep learning approaches are feasible for predicting hypertension, dyslipidemia, diabetes, and risks of other chronic diseases.

Background Overall survival (OS) is a key endpoint measure in the management of patients with cancer. Immunotherapy has become a dominant strategy in cancer therapy. To investigate the relationship between OS and the immune system, we assessed the role of immune genes in OS in 8648 patients across 22 cancer types. Methods Gene expression data and clinical information were collected from The Cancer Genome Atlas (TCGA) and cBioPortal. Survival analysis was performed with a Cox proportional hazards regression model. Results (1) The number of prognostic genes, prognostic immune genes (PIGs) and the hazard ratio (HR) of PIGs in different cancer types all varied greatly; (2) KEGG pathway enrichment analyses indicated that the prognostic genes of 6 cancer types were significantly enriched in multiple (≥5) immune system-related pathways. Of the PIGs in these 6 cancer types, we screened 48 common PIGs in at least 5 cancer types. Eleven out of the 48 PIGs were found to participate in the T cell receptor (TCR) signaling pathway according to the STRING database. Among these genes, ZAP70, CD3E, CD3G, CD3D, and CD247 were part of the TCR ‘signal-triggering module’; (3) High expression of the PIGs involved in the TCR signaling pathway was associated with improved OS in 5 cancer types (breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), head and neck squamous cell carcinoma (HNSC), lung adenocarcinoma (LUAD), and sarcoma (SARC)), but was associated with decreased OS in brain lower-grade glioma (LGG). Conclusions The TCR signaling pathway played a distinct role in the OS of these 6 cancer types.

Background Exosomes have emerged as critical mediators of intercellular communication. Hypoxia is widely recognized as a key regulator of tumor aggressiveness, and significantly affects exosome release by tumor cells. However, the effects of exosomes derived from hypoxic lung adenocarcinoma (LUAD) cells are poorly understood. Methods Samples of miRNA isolated from hypoxic LUAD cell-derived exosomes (HExo) and normoxic LUAD cell-derived exosomes (NExo) were sequenced to identify miRNAs that might mediate tumor progression. Exosomal miRNA was co-cultured with LUAD cells to assess its biological effects on cell migration and metastasis both in vitro and in vivo . The cellular target of exosomal miRNA was confirmed by dual-luciferase assays. Western blot studies showed that exosomal miRNA regulated the related pathway. The availability of circulating exosomal miRNA derived from plasma was also evaluated. Results We found that HExo could significantly enhance the migration and invasion of normoxic LUAD cells. MiRNA sequencing results suggested that miR-31-5p was largely internalized within HExo and could be taken up by normoxic LUAD cells. Exosomal miR-31-5p was found to directly target Special AT-Rich Sequence-Binding Protein 2 (SATB2)-revered epithelial mesenchymal transition and significantly increase activation of MEK/ERK signaling, thereby contributing to tumor progression both in vitro and in vivo . Furthermore, higher levels of circulating exosomal miR-31-5p were detected in LUAD patients, especially in patients with metastatic disease. Conclusions Our findings demonstrate that exosomal miR-31-5p exerts a crucial role in LUAD progression, and could serve as a diagnostic biomarker for LUAD.