Search

Objectives Household consumption significantly affects the quality of life and successful aging of older adults. However, prior research has often overlooked the connection between household consumption and long-term care insurance (LTCI). This study aims to investigate the influence of LTCI on consumption patterns within older Chinese households. Methods We used harmonized data from the China Health and Retirement Longitudinal Study and merged it with data from cities that implemented LTCI in China. We analyzed a total of 6,494 households consisting of individuals who were 60 years of age or older. To ensure accurate and stable research findings, we employed a series of difference-in-differences models. Results We found that LTCI has a significant impact on consumption levels, including total and per capita consumption within older households. Furthermore, our research demonstrates that LTCI significantly enhances enjoyable consumption across the consumption types. Through a heterogeneous analysis, it is shown that LTCI has a unique effect on both the total and enjoyable consumption of urban older households and also promotes comprehensive consumption improvements in older rural and disabled households. Discussion These findings highlight the crucial role of LTCI in improving the financial security and well-being of older households. They also have considerable policy implications for dealing with the challenges of an aging population. [ABSTRACT FROM AUTHOR]

In order to cope with the grid fluctuation caused by large‐scale wind power connected to the grid, the wind thermal power generation system has been proposed and extensively studied. The wind thermal power generation system uses a wind turbine to drive a heat generation device to heat the heat storage medium, which is further exchanged to drive a turbine to generate electricity. A superconducting magnetic eddy current heater (SMH) is proposed for the characteristics of wind thermal power generation system, which uses non‐resistive, large current‐carrying superconducting coils for excitation, and has high output efficiency and power density. The working principle of magnetic eddy current heating is analysed, and the structure of SMH with no ferromagnetic material and two heating screens inside and outside is proposed according to the characteristics of SMH. An analytical model of the SMH is established, and the influence of the structure and materials of the SMH on the magnetic field distribution is analysed. Based on this, a 22‐pole SMH was designed and analysed for output power at 10–20 rpm. A three‐dimensional magnetism‐stress combined analysis model of SMH is established, and the strain and stress characteristics of SMH are simulated under the condition of maximum output power, which verifies the feasibility of the mechanical properties of existing superconducting materials for application in SMH. [ABSTRACT FROM AUTHOR]

Background: Dilated cardiomyopathy (DCM) is a severe heterogeneous cardiomyopathy characterized by cardiac enlargement and declining heart function, often leading to refractory heart failure and life-threatening outcomes, particularly prevalent in China. The challenge lies in the scarcity of targeted therapies with substantial efficacy for DCM. Additionally, traditional anti-heart failure drugs are constrained due to hypotension propensity or limited symptom improvement. Kuoxin Formula (KXF), internally endorsed at Longhua Hospital, demonstrates clear biological evidence for enhancing cardiac function and myocardial remodeling. Previous clinical studies suggest its potential to enhance patients' quality of life. This trial aims to further evaluate KXF's safety and efficacy in managing DCM-related heart failure. Methods: This prospective, randomized, double-blind, placebo-controlled, multicenter trial aims to recruit 230 DCM patients from five centers. Participants will be randomly assigned to either KXF or placebo for 12 weeks, with careful monitoring of key indicators and adverse events. The primary outcome measures the proportion of patients with NT-proBNP reduction exceeding 30%. Secondary outcomes include New York Heart Association functional classification, Traditional Chinese Medicine syndrome scores, 6-minute walk test, Lee's heart failure score, and Minnesota Heart Failure Quality of Life Scale score. Ventricular remodeling will be assessed using cardiac ultrasound and ELISA. Safety metrics and adverse events will be meticulously recorded. Discussion: This study will be the first multicentered research conducted in China that utilizes a randomized, double-blind, placebo-controlled design to investigate the use of TCM in the treatment of DCM. It seeks to develop new theoretical frameworks and provide solid clinical data to support the integration of TCM and modern medicine in treating heart failure in DCM patients. Trial Registration: China Clinical Trial Registry, ChiCTR2300068937. Registered on March 1, 2023. https://www.chictr.org.cn/bin/project/edit?pid=190926. [ABSTRACT FROM AUTHOR]

Pyroptosis, an inflammatory form of programmed cell death, is linked to the pathology of rheumatoid arthritis (RA). Here, we investigated the molecular mechanism underlying pyroptosis in T cells isolated from patients with RA. Compared with healthy individuals, patients with RA had more pyroptotic CD4+ T cells in blood and synovia, which correlated with clinical measures of disease activity. Moreover, the mRNA expression and protein abundance of arachidonate 5-lipoxygenase (ALOX5), which converts arachidonic acid to leukotriene A4 (LTA4), were increased in CD4+ T cells from patients with RA and, among patients with RA, were lowest in those in clinical remission. Knockdown or pharmacological inhibition of ALOX5 suppressed CD4+ T cell pyroptosis and improved symptoms in two rodent models of RA. Mechanistically, the increase in ALOX5 activity in RA CD4+ T cells enhanced the production of the LTA4 derivative LTB4, which stimulated Ca2+ influx through ORAI3 channels, leading to the activation of NLRP3 inflammasomes and pyroptosis. Our findings reveal a role for ALOX5 in RA and provide a molecular basis for further exploring the clinical utility of ALOX5 inhibition in RA and for using ALOX5 as a biomarker to distinguish active disease and remission in RA. Editor's summary: Pyroptosis of CD4+ T cells is associated with synovial inflammation in rheumatoid arthritis (RA). Cai et al. found that increased abundance of the leukotriene biosynthetic enzyme ALOX5 in circulating and synovium-infiltrating CD4+ T cells drove pyroptosis in these cells, which correlated with the clinical severity of RA. Leukotrienes generated by ALOX5 stimulated Ca2+ influx through ORAI3 channels that led to inflammasome activation and pyroptosis. The FDA-approved ALOX5 inhibitor zileuton suppressed CD4+ T cell pyroptosis and reduced joint inflammation in rodent models of RA, suggesting ALOX5 as a potential therapeutic target in RA. —Annalisa M. VanHook [ABSTRACT FROM AUTHOR]

Pulmonary hypertension is a progressive disease of the pulmonary arteries that begins with increased pulmonary artery pressure, driven by progressive remodeling of the small pulmonary arteries, and ultimately leads to right heart failure and death. Vascular remodeling is the main pathological feature of pulmonary hypertension, but treatments for pulmonary hypertension are lacking. Determining the process of vascular proliferation and dysfunction may be a way to decipher the pathogenesis of pulmonary hypertension. In this review, we summarize the important pathways of pulmonary hypertension pathogenesis. We show how these processes are integrated and emphasize the benign role of aerobic exercise, which, as an adjunctive therapy, may be able to modify vascular remodeling in pulmonary hypertension., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Song, Jia, Ma, Zhang, Lai and Wang.)

Aims: Adaptive changes in the heart by exercise have been shown to reduce the risk of cardiovascular disease, and M 2 Acetylcholine receptor (M 2 AChR), a receptor abundantly present on cardiac parasympathetic nerves, is closely associated with the development of cardiovascular disease. The present study intends to investigate whether exercise can regulate endoplasmic reticulum stress (ERS) and mitophagy through M 2 AChR to resist myocardial ischemia-reperfusion (I/R) injury and to elucidate its mechanism of action. Results: Exercise enhanced parasympathetic nerve function and increased myocardial M 2 AChR protein expression in I/R rats. In addition, it promoted the protein expression of MFN2 and inhibited the expression of Drp1, Chop, PINK1/Parkin, and PERK/eIF2α/ATF4 signaling pathways, effectively reducing mitophagy, ERS, and apoptosis. At the cellular level, 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) reduced hypoxia/reoxygenation (H/R)-induced ERS through the downregulated expression of PERK/eIF2α/ATF4 pathway proteins in H9C2 cardiomyocytes. When intervened with M 2 AChR inhibitors, the levels of ERS and phosphorylation levels of the PERK/eIF2α/ATF4 pathway were increased in H/R cells. Innovation and Conclusion: Exercise intervention activated the parasympathetic state in rats. It inhibited myocardial mitophagy and ERS levels, and reduced myocardial apoptosis through M 2 AChR, thereby resisting I/R-induced myocardial injury and improving cardiac function. Antioxid. Redox Signal. 40, 209-221.

Objective: Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease with a complex pathogenesis that has not yet been fully elucidated, and T-cell pyroptosis is an important pathogenetic factor in RA. This study aimed to investigate the role of endoplasmic reticulum aminopeptidase 2 (ERAP2) in the pyroptosis of CD4 + T cells in RA and the specific molecular mechanism., Methods: Peripheral venous blood was collected from human subjects, and CD4 + T cells were isolated and activated to measure the level of pyroptosis and ERAP2 expression. Pyroptosis levels were assessed using immunofluorescence, flow cytometry, qRT-PCR, and Western blotting. Changes in pyroptosis levels were observed upon knockdown or overexpression of ERAP2. To detect activated Caspase-1 in tissues, chimeric mice were engrafted with human synovial tissue and reconstituted with human CD4 + T cells. CD4 + T cells were treated with GLI1 antagonists and SMO receptor agonists to detect changes in pyroptosis levels., Results: CD4 + T cell levels undergoing pyroptosis were found to be elevated in the blood and synovium of RA patients. The gene and protein expression of ERAP2 were significantly higher in CD4 + T cells from RA patients. Deletion of ERAP2 suppressed pyroptosis of these cells, attenuated the activation of Caspase-1 in tissue T cells, and reduced tissue inflammatory responses. Reciprocally, overexpression of ERAP2 triggered inflammasome assembly, activated Caspase-1, and induced pyroptosis in CD4 + T cells. Mechanistically, ERAP2 inhibits the Hedgehog signaling pathway and upregulates the expression of nucleotide-binding oligomerization segment-like receptor family 3(NLRP3), cleaved Caspase-1, and Gasdermin D to promote pyroptosis in CD4 + T cells., Conclusions: Taken together, our results identify a novel mechanism by which ERAP2 regulates RA development and document the effect of the ERAP2/Hedgehog signaling axis on pyroptosis of CD4 + T cells from RA patients., (© 2024. The Author(s).)

Efflux pumps play a crucial role in the development of antibiotic resistance. The aim of this study was to investigate the relationship between efflux pump gene expression and resistance gene mutations in Helicobacter pylori . Twenty-six clinical strains with varying resistance characteristics were selected for further experiment. Seven susceptible strains were induced to become resistant, and the expression of efflux pump genes and point mutations were recorded. Four susceptible strains were selected to undergo candidate mutation construction, and changes in efflux pump gene expression were detected. Efflux pump knockout strains were constructed, and their effects on preventing and reversing antibiotic resistance gene mutations were assessed. Results showed that the expression of efflux pump genes hefA and hefD was significantly higher in the multidrug-resistant group compared to other groups. During the process of antibiotic-induced resistance, efflux pump gene expression did not exhibit a steady increase or decrease. Strains with the A2143G or A2142G point mutations in 23S rRNA exhibited lower hefA gene expression. Strains with mutations at 87K/91N, 87N/91 G, 87K/91D, or 87N/91Y in gyrA and the 194insertA mutation in rdxA showed higher hefA gene expression compared to the wild-type strain. During the process of antibiotic-induced resistance, the strain with the knockout of the efflux pump gene hefA developed mutations in the 23S rRNA, gyrA, or rdxA genes later compared to the wild-type strain. Knockout of the efflux pump gene could reverse the phenotypic resistance to clarithromycin or metronidazole in some strains but had no effect on reverse resistance gene mutation. This study suggested that different resistance gene point mutations may have varying effects on efflux pump gene expression. Knockout of the efflux pump gene can delay or prevent antibiotic resistance gene mutations to some extent and can reverse phenotypic resistance to clarithromycin and metronidazole in certain strains.