Efficacy and safety of Qixue Tongzhi Granule in improving the exercise capacity of stable coronary artery disease: study protocol for a multicenter, randomized, double-blind, placebo-controlled trial

BackgroundDespite optimal medical therapy, patients with stable coronary artery disease (SCAD) still have a high risk of recurrent cardiovascular events. Exercise capacity measured by cardiopulmonary exercise testing (CPET) is a good surrogate marker for the long-term prognosis of SCAD. Qixue Tongzhi Granule (QTG) is created by academician Chen Keji and has the function of tonifying qi, promoting blood circulation, and regulating qi-flowing. This trial aims to investigate the efficacy and safety of QTG in improving exercise tolerance, alleviating angina pectoris and anxiety/depression symptoms, promoting health-related quality of life, and reducing the risk of adverse cardiovascular events in subjects with SCAD.MethodsThis is a randomized, double-blind, placebo-controlled trial. 150 SCAD patients with qi deficiency, blood stasis, and liver qi stagnation syndrome are enrolled. Patients will be randomly allocated to the QTG or placebo groups at a 1:1 ratio. QTG and placebo will be added to the modern guideline-directed medical therapy for 12 weeks and patients will be followed up for another 24 weeks. The primary outcome is the improvement of metabolic equivalents measured by CPET. The secondary outcomes are cumulative incidence of composite endpoint events, other indicators in CPET, changes in the Seattle Angina Questionnaire, traditional Chinese medicine syndrome scale, 12 items of Short Form Health Survey Questionnaire, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7, changes of ST-T segment in the electrocardiogram, improvement of left ventricular ejection fraction and left ventricular end-diastolic diameter in echocardiography. In addition, metabolomics analysis will be performed based on blood samples. Adverse events and safety evaluations will also be documented. A full analysis set, per protocol set, and safety analysis set will be conducted.DiscussionThis clinical trial can enrich treatment options for CHD patients with low cardiorespiratory fitness and psychological imbalance, and it may also create a new situation for promoting the application of traditional Chinese medicine in cardiac rehabilitation.Clinical Trial Registration: [http://www.chictr.org.cn], identifier: [ChiCTR2200058988]

Human adenovirus type 7 subunit vaccine induces dendritic cell maturation through the TLR4/NF-κB pathway is highly immunogenic

IntroductionHuman adenovirus type 7 (HAdv-7) infection is the main cause of upper respiratory tract infection, bronchitis and pneumonia in children. At present, there are no anti- adenovirus drugs or preventive vaccines in the market. Therefore, it is necessary to develop a safe and effective anti-adenovirus type 7 vaccine.MethodsIn this study, In this study, we used the baculovirus-insect cell expression system to design a recombinant subunit vaccine expressing adenovirus type 7 hexon protein (rBV-hexon) to induce high-level humoral and cellular immune responses. To evaluate the effectiveness of the vaccine, we first detected the expression of molecular markers on the surface of antigen presenting cells and the secretion of proinflammatory cytokines in vitro. We then measured the levels of neutralizing antibodies and T cell activation in vivo.ResultsThe results showed that the rBV-hexon recombinant subunit vaccine could promote DC maturation and improve its antigen uptake capability, including the TLR4/NF-κB pathway which upregulated the expression of MHCI, CD80, CD86 and cytokines. The vaccine also triggered a strong neutralizing antibody and cellular immune response, and activated T lymphocytes.DiscussionTherefore, the recombinant subunit vaccine rBV-hexon promoted promotes humoral and cellular immune responses, thereby has the potential to become a vaccine against HAdv-7

Single-Cell Transcriptome Analyses Reveal Signals to Activate Dormant Neural Stem Cells

SummaryThe scarcity of tissue-specific stem cells and the complexity of their surrounding environment have made molecular characterization of these cells particularly challenging. Through single-cell transcriptome and weighted gene co-expression network analysis (WGCNA), we uncovered molecular properties of CD133+/GFAP− ependymal (E) cells in the adult mouse forebrain neurogenic zone. Surprisingly, prominent hub genes of the gene network unique to ependymal CD133+/GFAP− quiescent cells were enriched for immune-responsive genes, as well as genes encoding receptors for angiogenic factors. Administration of vascular endothelial growth factor (VEGF) activated CD133+ ependymal neural stem cells (NSCs), lining not only the lateral but also the fourth ventricles and, together with basic fibroblast growth factor (bFGF), elicited subsequent neural lineage differentiation and migration. This study revealed the existence of dormant ependymal NSCs throughout the ventricular surface of the CNS, as well as signals abundant after injury for their activation

sj-pdf-2-inq-10.1177_00469580241235755 – Supplemental material for Lifestyle and ADL Are Prioritized Factors Influencing All-Cause Mortality Risk Among Oldest Old: A Population-Based Cohort Study

Supplemental material, sj-pdf-2-inq-10.1177_00469580241235755 for Lifestyle and ADL Are Prioritized Factors Influencing All-Cause Mortality Risk Among Oldest Old: A Population-Based Cohort Study by Zhiwen Ge, Cheng Li, Yaru Li, Nan Wang and Zhongxin Hong in INQUIRY: The Journal of Health Care Organization, Provision, and Financing</p

sj-pdf-1-inq-10.1177_00469580241235755 – Supplemental material for Lifestyle and ADL Are Prioritized Factors Influencing All-Cause Mortality Risk Among Oldest Old: A Population-Based Cohort Study

Supplemental material, sj-pdf-1-inq-10.1177_00469580241235755 for Lifestyle and ADL Are Prioritized Factors Influencing All-Cause Mortality Risk Among Oldest Old: A Population-Based Cohort Study by Zhiwen Ge, Cheng Li, Yaru Li, Nan Wang and Zhongxin Hong in INQUIRY: The Journal of Health Care Organization, Provision, and Financing</p

Transcriptomic analyses show that 24-epibrassinolide (EBR) promotes cold tolerance in cotton seedlings.

In plants, brassinosteroids (BRs) are a class of steroidal hormones that are involved in numerous physiological responses. However, the function of BRs in cold tolerance in cotton has not been explored. In this study, cotton seedlings were treated with five concentrations (0, 0.05, 0.1, 0.2, 0.5 and 1.0 mg/L) of 24-Epibrassinolide (EBR) at 4°C. We measured the electrolyte leakage, malondialdehyde (MDA) content, proline content, and net photosynthesis rate (Pn) of the seedlings, which showed that EBR treatment increased cold tolerance in cotton in a dose-dependent manner, and that 0.2 mg/L is an optimum concentration for enhancing cold tolerance. The function of EBR in cotton cotyledons was investigated in the control 0 mg/L (Cold+water) and 0.2 mg/L (Cold+EBR) treatments using RNA-Seq. A total of 4,001 differentially expressed genes (DEGs), including 2,591 up-regulated genes and 1,409 down-regulated genes were identified. Gene Ontology (GO) and biochemical pathway enrichment analyses showed that EBR is involved in the genetic information process, secondary metabolism, and also inhibits abscisic acid (ABA) and ethylene (ETH) signal transduction. In this study, physiological experiments showed that EBR can increase cold tolerance in cotton seedlings, and the comprehensive RNA-seq data shed light on the mechanisms through which EBR increases cold tolerance in cotton seedlings

Intestinal Permeability Associated with the Loss of Skeletal Muscle Strength in Middle-Aged and Older Adults in Rural Area of Beijing, China

The association between intestinal permeability and sarcopenia remains unclear, and few studies have mentioned the relationship between intestinal permeability and skeletal muscle strength. The present cross-sectional community study was conducted in a rural area of Beijing to explore the association between intestinal permeability and handgrip strength (HGS) in middle-aged and older adults. Serum lipopolysaccharide (LPS), diamine oxidase (DAO) and D-lactate were detected to evaluate intestinal permeability. Gut microbiota (GM) and its potential interaction were also analyzed in the decision tree model. HGS was negatively correlated with DAO (r = &minus;0.396, p &lt; 0.01) in males. The negative association between HGS and DAO remained significant with the adjustment of covariates (&beta; = &minus;1.401, p &lt; 0.05). Serum DAO and LPS were both negatively associated with HGS in middle-aged and older males, with the significant interactions of GM in the decision tree model, and D-lactate showed a negative association with HGS in females. Therefore, intestinal permeability was associated with the loss of skeletal muscle strength in middle-aged and older adults, and serum DAO may be a novel predictor for the loss of skeletal muscle strength in middle-aged and older males

Altered brassinolide sensitivity1 Regulates Fruit Size in Association with Phytohormones Modulation in Tomato

BRs (Brassinosteroids) regulate many essential pathways related to growth, cell elongation, cell expansion, plant architecture, and fruit development. The potential exogenous application of BR-derivatives has been proven to stimulate plant growth and development, including quality attributes of fruits, whereas its biosynthesis inhibition has shown the opposite effect. In this study, BR-insensitive tomato mutants were used to reveal the potential function of BR signaling in the regulation of fruit development to elaborate the regulatory mechanism of BR signaling in tomato fruits. The BR-signaling mutant exhibited a typical dwarf phenotype and reduced vegetative growth, fruit size, and weight. Microscopic and transcriptional evaluation of the abs1 mutant fruits implies that reduced cell size and number are responsible for the phenotypic variations. Additionally, we also found that the altered content of phytohormones, such as auxin, gibberellin, cytokinin, and ethylene levels, contributed to altered fruit development. Moreover, fruit growth and cell development-specific gene expression levels were downregulated in BR-insensitive plants; culminating in reduced cell size, cell number, and cell layers. These findings provide insight into physio-chemical changes during fruit development in response to BR-insensitivity

<i>Altered brassinolide sensitivity1</i> Regulates Fruit Size in Association with Phytohormones Modulation in Tomato

BRs (Brassinosteroids) regulate many essential pathways related to growth, cell elongation, cell expansion, plant architecture, and fruit development. The potential exogenous application of BR-derivatives has been proven to stimulate plant growth and development, including quality attributes of fruits, whereas its biosynthesis inhibition has shown the opposite effect. In this study, BR-insensitive tomato mutants were used to reveal the potential function of BR signaling in the regulation of fruit development to elaborate the regulatory mechanism of BR signaling in tomato fruits. The BR-signaling mutant exhibited a typical dwarf phenotype and reduced vegetative growth, fruit size, and weight. Microscopic and transcriptional evaluation of the abs1 mutant fruits implies that reduced cell size and number are responsible for the phenotypic variations. Additionally, we also found that the altered content of phytohormones, such as auxin, gibberellin, cytokinin, and ethylene levels, contributed to altered fruit development. Moreover, fruit growth and cell development-specific gene expression levels were downregulated in BR-insensitive plants; culminating in reduced cell size, cell number, and cell layers. These findings provide insight into physio-chemical changes during fruit development in response to BR-insensitivity

The Increased Risk of Hypertension Caused by Irrational Dietary Pattern May Be Associated with Th17 Cell in the Middle-Aged and Elderly Rural Residents of Beijing City, Northern China: A 1:1 Matched Case-Control Study

An irrational diet has been widely considered as one of the vital risk factors of hypertension. Previous studies have indicated that immune dysfunction may be involved in the pathogenic process of hypertension, while fewer studies have mentioned whether CD4+ T cells are involved in the association between dietary pattern and hypertension. This present 1:1 matched case-control study was conducted to analyze the association among dietary pattern, CD4+ T cells and hypertension. A total of 56 patients with diagnosed hypertension and 56 subjects without diagnosed hypertension in the rural area of Beijing City, northern China, were matched by age and gender, and then classified into a case group and a control group, respectively. Compared with the control group, higher frequencies of pro-inflammatory CD4+ T cells, such as Th1, Th1(IFN-γ), Th17(IL-17A), and Th1/17 (IFN-γ/IL-17A), were found in the case group (p p β = 5.38, 95%CI = 0.73~10.03, p < 0.05) in the multiple linear regression model with the adjustment of potential covariates. The other dietary patterns showed no significant association with blood pressure. Furthermore, meat, processed meat, and animal viscera were positively correlated with the peripheral Th17 or Th1/17. In conclusion, the irrational dietary pattern characterized by refined wheat, meat, poultry, and alcoholic beverage, was positively correlated with blood pressure, and may increase the risk of hypertension in the rural area of Beijing, northern China. Th17, a subset of the CD4+ T helper cells, may be involved in the association between irrational dietary pattern and hypertension