Simulation study on functional group-modified Ni-MOF-74 for CH4/N2 adsorption separation.

This study employs grand canonical Monte Carlo (GCMC) simulations to investigate the impact of functional group modifications (CH3, OH, NH2, and OLi) on the adsorption performance of CH4/N2 on Ni-MOF-74. The results revealed that functional group modifications significantly increased the adsorption capacity of Ni-MOF-74 for both CH4 and N2. The packed methyl groups in CH3-Ni-MOF-74 create an environment conducive to CH4, leading to the highest CH4 adsorption capacity. The electrostatic potential distribution indicates that the strong electron-donating effect introduced by the alkali metal Li results in the highest electrostatic potential gradient in Li-O-Ni-MOF-74, leading to the strongest adsorption of N2, this is unfavorable for CH4/N2 separation. At 1500 kPa the selectivity order of adsorbents for mixed gases was as follows: CH3-Ni-MOF-74 > NH2-Ni-MOF-74 > OH-Ni-MOF-74 > Ni-MOF-74 > Li-O-Ni-MOF-74. This study highlights that CH3-Ni-MOF-74 possesses optimal CH4 selectivity and adsorption performance. Given the current lack of research on functionalized MOF-74 for the separation of CH4 and N2, the findings of this study will serve as a theoretical guide and provide references for the applications of CH4 adsorption and CH4/N2 separation.

Design, Synthesis, and Antimicrobial Activity of Amide Derivatives Containing Cyclopropane.

As an important small organic molecule, cyclopropane is widely used in drug design. In this paper, fifty-three amide derivatives containing cyclopropane were designed and synthesized by introducing amide groups and aryl groups into cyclopropane through the active splicing method, and their antibacterial and antifungal activities were evaluated in vitro. Among them, thirty-five compounds were new compounds, and eighteen compounds were known compounds (F14, F15, F18, F20-F26, F36, and F38-F44). Bioassay results disclosed that four, three, and nine of the compounds showed moderate activity against Staphylococcus aureus, Escherichia coli, and Candida albicans, respectively. Three compounds were sensitive to Candida albicans, with excellent antifungal activity (MIC80 = 16 µg/mL). The molecular docking results show that compounds F8, F24, and F42 have good affinity with the potential antifungal drug target CYP51 protein.

Nucleoporin 50 mediates Kcna4 transcription to regulate cardiac electrical activity.

Emerging evidence has demonstrated that nucleoporins (Nups) play a pivotal role in cell-type-specific gene regulation, but how they control the expression and activity of ion channel genes in the heart remains unclear. Here, we show that Nup50, which is localized in the nucleus of cardiomyocytes, selectively induces an increase in the transcription and translation of Kcna4. The Kcna4 gene encodes a K+ voltage-gated channel of shaker-related subfamily member 4 and is essential for regulating the action potential in cardiac membranes. Using immunofluorescence imaging, luciferase assays and chromatin immunoprecipitation assays, we identified that the direct binding of the FG-repeat domain within Nup50 to the proximity of the Kcna4 promoter was required to activate the transcription and subsequent translation of Kcna4. Functionally, Nup50 overexpression increased the currents of KCNA4-encoded Ito,s channels, and reverse knockdown of Nup50 resulted in a remarkable decrease in the amplitude of Ito,s currents in cardiomyocytes. Moreover, a positive correlation between Nup50 and Kcna4 mRNA and protein expression was observed in heart tissues subjected to ischemic insults. These findings provide insights into the homeostatic control of cardiac electrophysiology through Nup-mediated regulation.

Associations of Chinese visceral adiposity index and new-onset stroke in middle-aged and older Chinese adults: an observational study.

BACKGROUND: Stroke represents the second most prevalent contributor to global mortality. The Chinese Visceral Adiposity Index (CVAI) serves as an established metric for assessing visceral adiposity in the Chinese population, exhibiting prognostic capabilities. This investigation aimed to explore the association of CVAI and new-onset stroke among middle-aged and older Chinese populations. METHODS: The study employed data from the 2011 and 2018 China Health and Retirement Longitudinal Study (CHARLS) to assess the association of CVAI and the incidence of new-onset stroke. Utilizing a directed acyclic graph (DAG), 10 potential confounders were identified. Moreover, to explore the association between CVAI and new-onset stroke, three multifactor logistic regression models were constructed, accounting for the identified confounders and mitigating their influence on the findings. RESULTS: The study comprised 7070 participants, among whom 417 (5.9%) experienced new-onset strokes. After controlling for confounding variables, regression analysis suggested that the new-onset stroke's highest risk was linked to the fourth quartile (Q4) of the CVAI, with an odds ratio (OR) of 2.33 and a 95% confidence interval (CI) of 1.67-3.28. The decision tree analysis demonstrated a heightened probability of new-onset stroke among hypertensive individuals with a CVAI equal to or greater than 83, coupled with a C-reactive protein level no less than 1.1 mg/l. Age seemed to have a moderating influence on the CVAI and new-onset stroke association, exhibiting a more prominent interaction effect in participants under 60 years. CONCLUSIONS: In middle-aged and older Chinese populations, a linear relationship was discerned between CVAI and the probability of new-onset stroke. CVAI provides a predictive framework for stroke incidence in this demographic, laying the groundwork for more sophisticated risk prediction models that improve the precision and specificity of stroke risk evaluations.

Toll-like receptor 3 controls QT interval on the electrocardiogram by targeting the degradation of Kv4.2/4.3 channels in the endoplasmic reticulum.

TLRs have been proven to be essential mediators for the early innate immune response. Overactivation of TLR-mediated immune signaling promotes deterioration of cardiovascular diseases; however, the role of TLRs in the heart under physiologic conditions remains neglected. Here, we show that Tlr3 deficiency induced the endoplasmic reticulum (ER) retention of Kv4.2/4.3 proteins and consequent degradation via the ubiquitin-proteasome pathway. Knockout of Tlr3 resulted in a prolonged QT interval (the space between the start of the Q wave and the end of the T wave) in mice with no significant signs of inflammation and tissue abnormality in cardiac muscles. Prolongation of action potential duration resulted from the depression of transient outward potassium channel (Ito) currents in Tlr3-deficient ventricular myocytes mirrored the change in QT interval. Mechanistically, we found that Tlr3 was exclusively localized in the ER of cardiomyocytes where it interacted with Kv4.2/4.3 subunits of Ito channel. Thus, our data indicated that TLR3 directly regulates Ito channel protein dynamics to maintain cardiac repolarization, which may implicate a new molecular surveillance system for cardiac electrophysiological homeostasis.-Gao, X., Gao, S., Guan, Y., Huang, L., Huang, J., Lin, L., Liu, Y., Zhao, H., Huang, B., Yuan, T., Liu, Y., Liang, D., Zhang, Y., Ma, X., Li, L., Li, J., Zhou, D., Shi, D., Xu, L., Chen, Y.-H. Toll-like receptor 3 controls QT interval on the electrocardiogram by targeting the degradation of Kv4.2/4.3 channels in the endoplasmic reticulum.

Nucleoporin 107 facilitates the nuclear export of Scn5a mRNA to regulate cardiac bioelectricity.

Nucleoporins (Nups) are known to be functional in nucleo-cytoplasmic transport, but the roles of nucleoporins in nonproliferating cells, such as cardiac myocytes, are still poorly understood. In this study, we report that Nup107 regulates cardiac bioelectricity by controlling the nucleo-cytoplasmic trafficking of Scn5a mRNA. Overexpression of Nup107 induced the protein expression of Scn5a rather than that of other ion channels, with no effects of their mRNA levels. The analysis for the protein production demonstrated Nup107-facilitated transport of Scn5a mRNA. Using RIP-PCR and luciferase assay, we found that the 5'-UTR of Scn5a mRNA was not involved in the interaction, whereas the spatial interaction between Nup107 protein and Scn5a mRNA was formed when Scn5a mRNA passing through the nuclear pore. Functionally, Nup107 overexpression in neonatal rat ventricle myocytes significantly increased the currents of Scn5a-encoded INa channel. Moreover, the close correlation between Nup107 and Nav1.5 protein expression was observed in cardiomycytes and heart tissues subjected to hypoxia and ischaemic insults, suggesting a fast regulation of Nup107 on Nav1.5 channel in cardiac myocytes in a posttranscriptional manner. These findings may provide insights into the emergent control of cardiac electrophysiology through Nup-mediated modulation of ion channels.

Using epidemiological data to identify needs for child-rearing support among Chinese parents: a cross-sectional survey of parents of children aged 6 to 35 months in 15 Chinese cities.

BACKGROUND: The quality of the family environment-in particular, the kind of parenting children receive in their early years-plays a critical role in influencing children's growth and development. To facilitate the development and delivery of appropriate parenting and family interventions for Chinese parents, this study explores the prevalence of the difficulties that may arise in the course of child-rearing, the associated sociodemographic factors and parents' help-seeking behavior. METHODS: A cross-sectional self-reporting survey was conducted with a sample of 2229 parents of children between 6 and 35 months of age. Using a stratified random-digit design, parents from 15 Chinese cities were surveyed to determine their child-rearing difficulties, support-seeking behavior and their preferences for service delivery. The sociodemographic factors that influenced major child-rearing difficulties were analyzed using bivariate and logistic analyses. RESULTS: The majority (87.5%) of Chinese parents of children aged 6-35 months reported experiencing child-rearing difficulties. Nearly one third (31.5%) of parents reported experiencing major difficulties. Feeding and sleep problems were most often reported. Regression analysis revealed that major child-rearing difficulties most often involved male children (OR = 1.35, 95% CI 1.11-1.64), single-child households (OR = 1.38, 95% CI 1.07-1.77), and households with financial problems (OR = 1.40, 95% CI 1.06-1.85). Just over one third of parents (33.44%) sought professional support, while 21.37% had attended a parenting course in the past year. Prefer ways of sourcing parental support included professional online platform (69.24%), self-help books (43.70%), face-to-face consultation (24.99%), and attending lectures (36.57%). CONCLUSIONS: Child-rearing difficulties are common among parents of children between 6 and 35 months of age in Chinese cities. The family with boys, single-child, financial problems, and father not joining in child-rearing may face the high risk to major child-rearing difficulties. The national initiative to provide more guidance and support for child-rearing difficulties is worthwhile, as is the development of online parenting programs.

Clinical study on the treatment of primary trigeminal neuralgia by robot-assisted percutaneous balloon compression.

Background: C-arm-guided percutaneous puncture balloon compression alone has risk factors of puncture failure, complications, and poor prognosis. Robot-assisted PBC can effectively increase the one-time puncture success rate and improve the safety of the procedure. However, evidence on the superiority of robot-assisted PBC over C-arm-guided PBC alone remains relatively limited. Methods: Retrospective analysis The clinical data of 60 patients with trigeminal neuralgia aged 60 years or older in the Department of Neurosurgery of the Fourth Hospital of Harbin Medical University from January 2021 to October 2021. There were 29 males and 31 females, and the patients' ages ranged from 60 to 79 years, with an average of 71.63 ± 5.12 years. Two groups were divided according to the surgical method, the C-arm guidance-only group (30 cases, n = 30) and the robot-assisted group (30 cases, n = 30). The success rate of first puncture, total operation time, number of "pear-shaped" balloons, number of C-arm x-ray scans, and immediate postoperative relief rate were recorded in both groups, and follow-up was performed to evaluate the postoperative results and complications. The overall evaluation of postoperative results and complications was performed. Results: Intraoperative balloon compression was successfully completed in all 60 patients, and the first puncture success rate was higher in the robot-assisted group than in the simple C-arm group, with a significant difference between the two groups (P < 0.001). In terms of intraoperative balloon morphology, the number of "pear-shaped" balloons was higher in the PBC than in the C-arm-only PBC group, with a significant difference between the two groups (P < 0.005). The degree of immediate postoperative remission in the robotic group was 0 VAS score, which was not statistically significant in both groups (P > 0.05). By the final follow-up, the mean VAS score of the robot-assisted group was lower than that of the simple C-arm group, and both were statistically significant (P < 0.05); complications of masticatory muscle weakness or abnormal facial sensation occurred in both groups after surgery, but the number of cases in the robot-assisted group was less than that of the simple C-arm group. Conclusion: Robot-assisted PBC is better than PBC with a C-arm x-ray machine in terms of first puncture success rate, number of intraoperative balloon "pear-shaped" cases, number of C-arm x-ray scans and short-term efficacy.

Identification of an endogenous glutamatergic transmitter system controlling excitability and conductivity of atrial cardiomyocytes.

As an excitatory transmitter system, the glutamatergic transmitter system controls excitability and conductivity of neurons. Since both cardiomyocytes and neurons are excitable cells, we hypothesized that cardiomyocytes may also be regulated by a similar system. Here, we have demonstrated that atrial cardiomyocytes have an intrinsic glutamatergic transmitter system, which regulates the generation and propagation of action potentials. First, there are abundant vesicles containing glutamate beneath the plasma membrane of rat atrial cardiomyocytes. Second, rat atrial cardiomyocytes express key elements of the glutamatergic transmitter system, such as the glutamate metabolic enzyme, ionotropic glutamate receptors (iGluRs), and glutamate transporters. Third, iGluR agonists evoke iGluR-gated currents and decrease the threshold of electrical excitability in rat atrial cardiomyocytes. Fourth, iGluR antagonists strikingly attenuate the conduction velocity of electrical impulses in rat atrial myocardium both in vitro and in vivo. Knockdown of GRIA3 or GRIN1, two highly expressed iGluR subtypes in atria, drastically decreased the excitatory firing rate and slowed down the electrical conduction velocity in cultured human induced pluripotent stem cell (iPSC)-derived atrial cardiomyocyte monolayers. Finally, iGluR antagonists effectively prevent and terminate atrial fibrillation in a rat isolated heart model. In addition, the key elements of the glutamatergic transmitter system are also present and show electrophysiological functions in human atrial cardiomyocytes. In conclusion, our data reveal an intrinsic glutamatergic transmitter system directly modulating excitability and conductivity of atrial cardiomyocytes through controlling iGluR-gated currents. Manipulation of this system may open potential new avenues for therapeutic intervention of cardiac arrhythmias.