Protocol for evaluating the effects of the Reducing Cardiometabolic Diseases Risk dietary pattern in the Chinese population with dyslipidaemia: a single-centre, open-label, dietary intervention study.

INTRODUCTION: Cardiometabolic disease (CMD) is the leading cause of mortality in China. A healthy diet plays an essential role in the occurrence and development of CMD. Although the Chinese heart-healthy diet is the first diet with cardiovascular benefits, a healthy dietary pattern that fits Chinese food culture that can effectively reduce the risk of CMD has not been found. METHODS/DESIGN: The study is a single-centre, open-label, randomised controlled trial aimed at evaluating the effect of the Reducing Cardiometabolic Diseases Risk (RCMDR) dietary pattern in reducing the risk of CMDs in people with dyslipidaemia and providing a reference basis for constructing a dietary pattern suitable for the prevention of CMDs in the Chinese population. Participants are men and women aged 35-45 years with dyslipidaemia in Tianjin. The target sample size is 100. After the run-in period, the participants will be randomised to the RCMDR dietary pattern intervention group or the general health education control group with a 1:1 ratio. The intervention phases will last 12 weeks, with a dietary intervention of 5 working days per week for participants in the intervention group. The primary outcome variable is the cardiometabolic risk score. The secondary outcome variables are blood lipid, blood pressure, blood glucose, body composition indices, insulin resistance and 10-year risk of cardiovascular diseases. ETHICS AND DISSEMINATION: The study complies with the Measures for Ethical Review of Life Sciences and Medical Research Involving Human Beings and the Declaration of Helsinki. Signed informed consent will be obtained from all participants. The study has been approved by the Medical Ethics Committee of the Second Hospital of Tianjin Medical University (approval number: KY2023020). The results from the study will be disseminated through publications in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2300072472).

Rice HEAT SHOCK PROTEIN60-3B maintains male fertility under high temperature by starch granule biogenesis.

Heat stress has a deleterious effect on male fertility in rice (Oryza sativa), but mechanisms to protect against heat stress in rice male gametophytes are poorly understood. Here, we have isolated and characterized a heat-sensitive male-sterile rice mutant, heat shock protein60-3b (oshsp60-3b), that shows normal fertility at optimal temperatures but decreasing fertility as temperatures increase. High temperatures interfered with pollen starch granule formation and reactive oxygen species (ROS) scavenging in oshsp60-3b anthers, leading to cell death and pollen abortion. In line with the mutant phenotypes, OsHSP60-3B was rapidly upregulated in response to heat shock and its protein products were localized to the plastid. Critically, overexpression of OsHSP60-3B enhanced the heat tolerance of pollen in transgenic plants. We demonstrated that OsHSP60-3B interacted with FLOURY ENDOSPERM6(FLO6) in plastids, a key component involved in the starch granule formation in the rice pollen. Western blot results showed that FLO6 level was substantially decreased in oshsp60-3b anthers at high temperature, indicating that OsHSP60-3B is required to stabilize FLO6 when temperatures exceed optimal conditions. We suggest that in response to high temperature, OsHSP60-3B interacts with FLO6 to regulate starch granule biogenesis in rice pollen and attenuates ROS levels in anthers to ensure normal male gametophyte development in rice.

Moderating Role of TSHR and PTPN22 Gene Polymorphisms in Effects of Excessive Fluoride on Thyroid: a School-Based Cross-Sectional Study.

We aimed to investigate the relationship between the effects excessive of fluoride on thyroid health in children and the moderating role of thyroid stimulating hormone receptor (TSHR) or protein tyrosine phosphatase nonreceptor-22 (PTPN22) gene polymorphisms. Four hundred thirteen children (141 with dental fluorosis and 198 boys) were enrolled from both historical endemic and non-endemic areas of fluorosis in Tianjin, China. The fluoride exposure levels, thyroid health indicators, and TSHR (rs2268458) and PTPN22 (rs3765598) polymorphisms were examined. Multiple logistic models were applied to evaluate the relationship between dental fluorosis and thyroid abnormalities. Children over 9 year old with dental fluorosis have lower FT4 and TGAb levels and thyroid volume and higher TPOAb levels (all P < 0.05). In overall participants, children with dental fluorosis were more likely to have thyroid antibody single positive issues (adjusted P = 0.039) and less likely to have a goiter according to age or body surface area (age or BSA) (adjusted P = 0.003); In the TSHR (rs2268458) SNP = CC/CT or PTPN22 (rs3765598) SNP = CC subgroup, dental fluorosis may cause thyroid antibody single positive (adjusted P = 0.036; adjusted P = 0.002); in the TSHR (rs2268458) SNP = TT or PTPN22 (rs3765598) SNP = CC subgroup, dental fluorosis may protect children from goiter (age or BSA) (adjusted P = 0.018; adjusted P = 0.013). Excessive fluoride may induce thyroid antibody single positive and reduce goiter in children. Heterogeneity exists in the relationship between excessive fluoride and thyroid antibody single positive or goiter issues across children carrying different TSHR (rs2268458) or PTPN22 (rs3765598) genotypes.

Ectopic expression of OsJAZ6, which interacts with OsJAZ1, alters JA signaling and spikelet development in rice.

Jasmonates (JAs) are key phytohormones that regulate plant responses and development. JASMONATE-ZIM DOMAIN (JAZ) proteins safeguard JA signaling by repressing JA-responsive gene expression in the absence of JA. However, the interaction and cooperative roles of JAZ repressors remain unclear during plant development. Here, we found that OsJAZ6 interacts with OsJAZ1 depending on a single amino acid in the so-called ZIM domain of OsJAZ6 in rice JA signaling transduction and JA-regulated rice spikelet development. In vivo protein distribution analysis revealed that the OsJAZ6 content is efficiently regulated during spikelet development, and biochemical and genetic evidence showed that OsJAZ6 is more sensitive to JA-mediated degradation than OsJAZ1. Through over- and mis-expression experiments, we further showed that the protein stability and levels of OsJAZ6 orchestrate the output of JA signaling during rice spikelet development. A possible mechanism, which outlines how OsJAZ repressors interact and function synergistically in specifying JA signaling output through degradation titration, is also discussed.

microRNA-139-5p alleviates neurological deficit in hypoxic-ischemic brain damage via HDAC4 depletion and BCL-2 activation.

AIM: Studies paid much attention to the role of microRNAs (miRNAs) in hypoxic-ischemic brain damage (HIBD) but not much to miR-139-5p. Thus, this study is to uncover the potential role of miR-139-5p in HIBD and its mechanisms. METHODS: Rat HIBD models were established by Rice-Vannucci method. Rats were injected with miR-139-5p agomir and si-histone deacetylase 4 (HDAC4) to explore their roles in HIBD. For further verification, growth and development assessments, and neurological behavior test were conducted. Oxidative stress-related factors, miR-139-5p, HDAC4 and B-cell lymphoma 2 (Bcl-2) expression in brain tissues and serum inflammatory response were detected. RESULTS: MiR-139-5p and Bcl-2 were decreased while HDAC4 was elevated in brain tissues of rats with HIBD. Growth and neurological behaviors were restrained in rats with HIBD. MiR-139-5p up-regulation or HDAC4 down-regulation alleviated pathological status, impaired oxidative stress, increased NGF and BDNF expression and inhibited neurons apoptosis of brain tissues in rats with HIBD. Increased miR-139-5p or decreased HDAC4 impaired inflammation in serum of rats with HIBD. CONCLUSION: Our study highlights that miR-139-5p elevation or HDAC4 knockdown alleviated neurological deficit and induced neurons growth via Bcl-2 elevation.

The OsJAZ1 degron modulates jasmonate signaling sensitivity during rice development.

Jasmonates (JAs) are crucial to the coordination of plant stress responses and development. JA signaling depends on JASMONATE-ZIM DOMAIN (JAZ) proteins that are destroyed by the SCFCOI1-mediated 26S proteasome when the JAZ co-receptor COI1 binds active JA or the JA-mimicking phytotoxin coronatine (COR). JAZ degradation releases JAZ-interacting transcription factors that can execute stress and growth responses. The JAZ proteins typically contain Jas motifs that undergo conformational changes during JA signal transduction and that are important for the JAZ-COI1 interaction and JAZ protein degradation. However, how alterations in the Jas motif and, in particular, the JAZ degron part of the motif, influence protein stability and plant development have not been well explored. To clarify this issue, we performed bioassays and genetic experiments to uncover the function of the OsJAZ1 degron in rice JA signaling. We found that substitution or deletion of core segments of the degron altered the OsJAZ1-OsCOI1b interaction in a COR-dependent manner. We show that these altered interactions function as a regulator for JA signaling during flower and root development. Our study therefore expands our understanding of how the JAZ degron functions, and provides the means to change the sensitivity and specificity of JA signaling in rice.

microRNA­3941 targets IGF2 to control LPS­induced acute pneumonia in A549 cells.

The present study aimed to investigate the potential roles and regulatory mechanism of microRNA (miR)-3941 in lipopolysaccharides (LPS)­induced acute pneumonia. The expression of miR­3941 in child patients with acute pneumonia was detected and A549 cells were treated with LPS to establish the cellular model of acute pneumonia. The effects of miR­3941 in LPS­induced cell injury were investigated by assessing cell viability, apoptosis and inflammation. In addition, the regulatory relationship between miR­3941 and insulin­like growth factor 2 (IGF2) was explored, as well as the association between miR­3941 and the phosphatidylinositol­4,5­bisphosphate 3­kinase/protein kinase B (PI3K/AKT) pathway. miR­3941 was significantly down­regulated in patients with acute pneumonia (P<0.01). In the cell model of acute pneumonia, LPS treatment significantly induced cell injury via inhibiting cell viability (P<0.05 or P<0.01), inducing cell apoptosis (P<0.01) and enhancing the production of cytokines [interleukin (IL)­6, IL­8 and tumor necrosis factor­α; P<0.01 or P<0.001]. LPS treatment also resulted in a significantly decreased expression of miR­3941 in A549 cells (P<0.01) and the overexpression of miR­3941 significantly alleviated LPS­induced cell injury (P<0.05). In addition, IGF2 was confirmed as a direct target gene of miR­3941. Knockdown of IGF2 significantly alleviated LPS­induced cell injury (P<0.05, P<0.01 or P<0.001), which was significantly reversed by suppression of miR­3941 (P<0.05, P<0.01 or P<0.001). Furthermore, inhibition of miR­3941 was demonstrated to activate the PI3K/AKT pathway, which was inhibited following knockdown of IGF2. The present study indicates that miR­3941 is downregulated in child patients with acute pneumonia and that downregulation of miR­3941 may promote LPS­induced cell injury in A549 cells via targeting IGF2 to regulate the activation of the PI3K/AKT pathway. Therefore, miR­3941 may be a potential therapeutic target for the treatment of acute pneumonia in child patients.