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Multidimensional capital is crucial for improving the quality of life of older adults. This study aimed to analyze the relationship between Internet use and the multidimensional capital among older adults in China. We also examined whether rural-urban status moderates this relationship. A total of 8,038 older adults (Mage = 71.06, SDage = 7.17) were included in this study, including 3937 (48.98%) urban and 4,101 (51.02%) rural samples. Using the ordinary least square (OLS) model and propensity score matching (PSM) methods with the 2018 wave of the China Longitudinal Aging Social Survey (CLASS), our results showed that the digital divide and multidimensional capital inequality existed between rural and urban older adults. The digital divide may further accelerate the rural-urban multidimensional capital inequality. Rural-urban status moderated the relationship between Internet use and multidimensional capital among older adults. To narrow the digital divide and further reduce the multidimensional capital inequality among older adults, strategies could be considered by promoting Internet popularization, providing convenient Internet access, and conducting fraud prevention education for older adults. [ABSTRACT FROM AUTHOR]

Background: Left–right (LR) asymmetry disorders present a complex etiology, with genetic factors emerging as a primary contributor. This study aims to explore the genetic underpinnings of chromosomal variants and individual genes in fetuses afflicted with prenatal LR asymmetry disorder. Methods: Through a retrospective analysis conducted between 2020 and 2023 at Tongji Hospital, Huazhong University of Science and Technology, genetic outcomes of LR asymmetric disorder were scrutinized utilizing copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) methodologies. Results: With a combination of CNV-seq and WES, 5 fetuses in 17 patients with LR asymmetry had chromosomal or genetic variants. CNV-seq revealed a 16p11.2 microdeletion syndrome in a situs inversus fetus presenting pathogenic and a 2q36.3 microduplication syndrome in a fetus with Heterotaxy presenting a variant of uncertain significance (VUS). WES identified NM_198075.4:c.755del in the LRRC56 gene and NM_001454.4:c.865_868dup in the FOXJ1 gene in two situs inversus cases, along with two variants in DNAH5 in two other fetuses. Further bioinformatics scrutiny was conducted to assess the protein structure and function prediction of these variants, ultimately indicating their potential pathogenicity. Conclusion: The study highlights that fetuses with LR asymmetric disorders may have copy number variants, underscoring the significance of mutations in LRRC56 and FOXJ1 in the development of LR asymmetry disorders. [ABSTRACT FROM AUTHOR]

Coxsackievirus A6 (CVA6) has emerged as a major pathogen causing hand, foot and mouth disease (HFMD) outbreaks worldwide. The CVA6 epidemic poses a new challenge in HFMD control since there is currently no vaccine available against CVA6 infections. The Vero cell line has been widely used in vaccine production, particularly in the preparation of viral vaccines, including poliovirus vaccines and EV71 vaccines. Unfortunately, most CVA6 strains failed to propagate effectively on Vero cells. The expression level of virus-specific receptors on the cell membrane significantly influences viral infection. Here, a Vero cell line with stable over-expressing of KREMEN1 (KRM1), a crucial receptor for CVA6, was constructed using the lentivirus system. The cloned cell line, called Vero-KRM1_#11, could efficiently support most CVA6 infections. The propagation of CVA6-TW00141 strain on Vero-KRM1_#11 was equal to that on RD cells. After four passages, the virus batch was obtained with a titer of about 107 TCID50/mL. Moreover, the purified CVA6 particles produced from Vero-KRM1_#11 or RD cells both could induce high and comparable levels of IgG and neutralizing antibodies. Importantly, passive transfer of the antisera from CVA6-vaccined mice showed 100% preventive efficacy against CVA6 infection in mice. Therefore, KRM1-expressing cells have the potential to serve as a valuable tool for the development and production of CVA6 or polyvalent HFMD vaccines. [ABSTRACT FROM AUTHOR]

Summary: 1. Kindlin-3 but not talin-1 contributes to integrin inside-out signaling induced β2 integrin clustering. 2. The Pleckstrin homology domain of kindlin-3 was critical for its mediated β2 integrin clustering. Background: Neutrophils are the most abundant leukocytes in human blood, and their recruitment is essential for innate immunity and inflammatory responses. The initial and critical step of neutrophil recruitment is their adhesion to vascular endothelium, which depends on G protein-coupled receptor (GPCR) triggered integrin inside-out signaling that induces β2 integrin activation and clustering on neutrophils. Kindlin-3 and talin-1 are essential regulators for the inside-out signaling induced β2 integrin activation. However, their contribution in the inside-out signaling induced β2 integrin clustering is unclear because conventional assays on integrin clustering are usually performed on adhered cells, where integrin–ligand binding concomitantly induces integrin outside-in signaling. Methods: We used flow cytometry and quantitative super-resolution stochastic optical reconstruction microscopy (STORM) to quantify β2 integrin activation and clustering, respectively, in kindlin-3 and talin-1 knockout leukocytes. We also tested whether wildtype or Pleckstrin homology (PH) domain deleted kindlin-3 can rescue the kindlin-3 knockout phenotypes. Results: GPCR-triggered inside-out signaling alone can induce β2 integrin clustering. As expected, both kindlin-3 and talin-1 knockout decreases integrin activation. Interestingly, only kindlin-3 but not talin-1 contributes to integrin clustering in the scenario of inside-out-signaling, wherein a critical role of the PH domain of kindlin-3 was highlighted. Conclusions: Since talin was known to facilitate integrin clustering in outside-in-signaling-involved cells, our finding provides a paradigm shift by suggesting that the molecular mechanisms of integrin clustering upon inside-out signaling and outside-in signaling are different. Our data also contradict the conventional assumption that integrin activation and clustering are tightly inter-connected by showing separated regulation of the two during inside-out signaling. Our study provides a new mechanism that shows kindlin-3 regulates β2 integrin clustering and suggests that integrin clustering should be assessed independently, aside from integrin activation, when studying leukocyte adhesion in inflammatory diseases. [ABSTRACT FROM AUTHOR]

Currently, with the gradual development of corrosion-resistant materials, coatings often exhibit ultra-high hydrophobic properties while possessing corrosion resistance, complicating the preparation of corrosion-resistant coatings. To explore a novel coating that combines high corrosion resistance with simplified preparation methods, mullite/kaolin powder was stirred using ball milling, and polyvinyl butyral was added to serve as a binder, thereby preparing a hydrophilic and highly corrosion-resistant coating. The coating was characterized using SEM, IR, XRD, and other testing methods. The results revealed that the components of the coating are connected through physical crosslinking, avoiding chemical reactions. Regarding the coating's performance, electrochemical and salt spray tests were conducted to characterize the prepared coating. According to electrochemical impedance spectroscopy tests, after immersion for 7 days, the electrochemical impedance spectroscopy impedance value of the A4C6EP coating reached 1.13 × 108 Ω·cm2, several times higher than that of other coatings, demonstrating its superior corrosion resistance. After a salt spray test for 2000 h, the coating surface showed neither bubbles, further validating the excellent corrosion resistance of the A4C6EP coating. The A4C6EP coating underwent an abrasion test using sandpaper and, after 100 cycles, the contact angle decreased by only 2.3°, with only slight scratches appearing on the surface, indicating very high mechanical abrasion resistance. This research demonstrates the successful preparation of a hydrophilic coating with excellent corrosion resistance and ultra-high mechanical abrasion resistance through a simple method, providing new insights for the development of hydrophilic corrosion-resistant coatings and reducing the cost of such coatings. [ABSTRACT FROM AUTHOR]

Objective: We aimed to screen and construct a predictive model for pregnancy loss in polycystic ovary syndrome (PCOS) patients through machine learning methods. Methods: We obtained the endometrial samples from 33 PCOS patients and 7 healthy controls at the Reproductive Center of the Second Hospital of Lanzhou University from September 2019 to September 2020. Liquid chromatography tandem mass spectrometry (LCMS/MS) was conducted to identify the differentially expressed proteins (DEPs) of the two groups. Gene Ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to analyze the related pathways and functions of the DEPs. Then, we used machine learning methods to screen the feature proteins. Multivariate Cox regression analysis was also conducted to establish the prognostic models. The performance of the prognostic model was then evaluated by the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). In addition, the Bootstrap method was conducted to verify the generalization ability of the model. Finally, linear correlation analysis was performed to figure out the correlation between the feature proteins and clinical data. Results: Four hundred and fifty DEPs in PCOS and controls were screened out, and we obtained some pathways and functions. A prognostic model for the pregnancy loss of PCOS was established, which has good discrimination and generalization ability based on two feature proteins (TIA1, COL5A1). Strong correlation between clinical data and proteins were identified to predict the reproductive outcome in PCOS. Conclusion: The model based on the TIA1 and COL5A1 protein could effectively predict the occurrence of pregnancy loss in PCOS patients and provide a good theoretical foundation for subsequent research. [ABSTRACT FROM AUTHOR]

A series of bis(thiosemicarbazide)gallium (III) complexes were synthesized and characterized by infrared spectroscopy, mass spectrometry, nuclear magnetic resonance, single‐crystal x‐ray crystallography, and density functional theory (DFT) calculation. The cytotoxicity of these gallium(III) complexes (CP 1–4) was subsequently evaluated against HCT‐116, HeLa, MDA‐MB‐231, and A549 cancer cell lines, as well as the normal cell line LO2, by MTT assays. The results indicated that CP‐1 displayed potent inhibitory effects against human colorectal cancer cells (HCT‐116) (IC50 = 0.03 ± 0.01) and human breast cancer cells (MDA‐MB‐231) (IC50 = 0.02 ± 0.01), significantly outperforming cisplatin. Moreover, CP‐2 exhibited notable selectivity towards MDA‐MB‐231 cells (IC50 = 5.01 ± 0.40) with minimal toxicity towards normal cells. Mechanistic studies revealed that treatment with CP 1–2 led to elevated intracellular reactive oxygen species (ROS) levels, resulting in cell cycle arrest at different phases. Specifically, CP‐1 induced G2/M phase arrest, inhibiting cancer cell proliferation, whereas CP‐2 hindered DNA synthesis (S phase) to impede cell proliferation. Furthermore, both CP‐1 and CP‐2 caused a reduction in mitochondrial membrane potential, activating the mitochondrial apoptotic pathway and inducing apoptosis in cancer cells. Molecular docking experiments demonstrated strong interactions between CP 1–2 and protein disulfide isomerase (PDI) at the molecular level. These findings suggest that CP‐1 and CP‐2 serve as potential anticancer agents, particularly showing promising potential in the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

The tunable electrocyclic reactions for the synthesis of a series of mono‐ and disulfonyl‐substituted pyrazoles from sulfonyl hydrazines and 1,3‐diketones were investigated by utilizing inexpensive electrolytes under electrochemical conditions in an undivided cell. When nBu4NBF4 was used as an electrolyte, it afforded monosulfonyl‐substituted pyrazoles. By contrast, when NH4I was used as an electrolyte, it gave disulfonyl‐substituted pyrazoles. The mechanistic investigation shows that they all underwent a free radical process but formed N‐centered sulfonyl hydrazine radical and S‐centered sulfonyl radical in the synthesis of mono‐ and disulfonyl‐substituted pyrazoles, respectively. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a risk factor of chronic kidney disease, without specific treatment. This study investigated the effect of co‐treatment using erythropoietin‐derived helix B surface peptide (HBSP) and caspase‐3 small interfering RNA (CASP3siRNA) on preventing fibrosis post AKI in order to achieve better efficacy by different action mechanisms. Ischemia–reperfusion (IR) in mice was induced by clamping bilateral renal pedicles for 30 min followed by 2‐week reperfusion, with HBSP and/or CASP3siRNA administered at the onset of IR. Serum creatinine, apoptosis, active caspase‐3 and high mobility group protein B1 (HMGB1) in kidneys were decreased by HBSP, CASP3siRNA or both, with increased PCNA. α‐SMA expression and collagen I deposition were also reduced by CASP3siRNA and both. Most interestingly, the co‐treatment further reduced tubulointerstitial damage and fibrosis, but raised PCNA compared to CASP3siRNA. EPOR/βcR was reduced by HBSP, and positively correlated with Sirius red staining, whereas EPOR was unchanged. In TCMK‐1 cells, H2O2 raised apoptosis and α‐SMA were reduced by HBSP, while the same was occurred to HMGB1. However, HMGB1 was further increased by EPOR siRNA under H2O2 stimulation with/without HBSP treatment. In conclusion, this study demonstrated synergistic long‐term renoprotection post IR‐AKI by HBSP and CASP3siRNA, which may be due to co‐inhibiting inflammation and stimulating repair at early stage, and subsequently preventing fibrosis. [ABSTRACT FROM AUTHOR]