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The impact of pediatric body mass index (BMI) trajectories on the risk of adolescent hypertension (HTN) determined by three separate visits remains unclear. This longitudinal study aims to identify potential pediatric sex-specific BMI trajectories and to assess their associations with HTN and HTN subtypes.Based on the Health Promotion Program for Children and Adolescents (HPPCA) in Suzhou, China, a total of 24,426 participants who had initial normal blood pressure (BP) and had at least four BMI measurements during 2012-2020 were included. HTN was defined as simultaneously having three separate visits of elevated BP in 2020. Latent class growth models were used to explore sex-specific BMI trajectories, whose associations with HTN and HTN subtypes were further examined by logistic regression.The incidence of HTN determined through three separate visits was 3.34%. Four trajectories were identified for both sexes: low BMI increasing, medium BMI increasing, high BMI increasing, and highest BMI increasing. Compared to the medium BMI increasing group, the odds ratio (95% confidential interval) for developing adolescent HTN of the low, high, and highest BMI increasing groups among boys were 0.54 (0.39, 0.75), 1.90 (1.44, 2.51), and 2.89 (1.90, 4.39), respectively; and the corresponding values for girls were 0.66 (0.48, 0.90), 2.30 (1.72, 3.09), and 4.71 (3.06, 7.26). Similar gradually elevated associations between different trajectories with isolated systolic hypertension, systolic and diastolic hypertension were observed.Current results emphasized the adverse effects of stable high BMI on HTN and the benefits of maintaining normal weight throughout childhood.

The first-cured tobacco contains macromolecular substances with negative impacts on tobacco products quality, and must be aged and fermented to mitigate their effects on the tobacco products quality. However, the natural fermentation takes a longer cycle with large coverage area and low economic efficiency. Microbial fermentation is a method to improve tobacco quality. The change of chemical composition of tobacco during the fermentation is often correlated with shapes of tobacco. This study aimed to investigate the effects of tobacco microorganisms on the quality of different shapes of tobacco. Specifically, Bacillus subtilis B1 and Cytobacillus oceanisediminis C4 with high protease, amylase, and cellulase were isolated from the first-cured tobacco, followed by using them for solid-state fermentation of tobacco powder (TP) and tobacco leaves (TL). Results showed that strains B1 and C4 could significantly improve the sensory quality of TP, enabling it to outperform TL in overall texture and skeleton of tobacco products during cigarette smoking. Compared with the control, microbial fermentation could increase reducing sugar; regulate protein, starch, and cellulose, reduce nicotine, improve total aroma substances, and enable the surface of fermented TP and TL to be more loose, wrinkled, and porous. Microbial community analysis indicated that strains B1 and C4 could change the native structure of microbial community in TP and TL. LEfSe analysis revealed that the potential key biomarkers in TP and TL were Bacilli, Pseudonocardia, Pantoea, and Jeotgalicoccus, which may have cooperative effects with other microbial taxa in improving tobacco quality. This study provides a theoretical basis for improving tobacco fermentation process for better cigarettes quality. Graphical Abstract

Atherosclerosis is a chronic inflammatory disease. The triggering receptor expressed on myeloid cells-1 (TREM-1) plays a crucial role in inflammatory diseases; recently, it was identified as a major upstream proatherogenic receptor, but its mechanism is still unclear. In this study, we explore the role of TREM-1 on dendritic cells maturation and inflammatory responses induced by ox-LDL and its possible mechanism. Human dendritic cells were differentiated from blood monocytes and treated with ox-LDL. Naive autologous T cells were cocultured with pretreated DCs or treated directly. The expression of TREM-1 and inflammatory factors were evaluated by real-time PCR, western blot, and ELISA methods. And the expression of immune factors to evaluate the DCs maturation and T-cell activation were determined by the FACS. Our study showed that ox-LDL induced TREM-1 expression, DC maturation, and T-cell activation. T cells exposed to ox-LDL-treated DCs produced interferon-γ and interleukin-17 (IL-17). Blocking TREM-1 suppressed the DC maturation, showing lower expression of CD1a, CD40, CD86, CD83, and HLA-DR, and limited their production of tumor necrosis factor-alpha (TNF-α), IL-1β, IL-6, and monocyte chemoattractant protein-1 (MCP-1), meanwhile increased transforming growth factor-β(TGF-β) and IL-10 production. Ox-LDL induced miR-155, miR-27, Let-7c, and miR-185 expression; however, TREM-1 inhibiting decreased miRNA-155 expression. Furthermore, silencing miRNA-155 restores SOCS1 repression induced by ox-LDL. Experiments with T cells derived from carotid atherosclerotic plaques or healthy individuals showed similar results. Our results uncover a new link between ox-LDL and TREM-1 and may provide insight into this interaction in the context of atherosclerosis.

The purpose of this study was to (i) identify the level of posttraumatic growth among nurses suffering from workplace violence, (ii) clarify the relationship between nurses' posttraumatic growth and compassion satisfaction, burnout, secondary traumatic stress, and (iii) determine the influencing factors for posttraumatic growth among nurses suffering from workplace violence. A cross-sectional study was conducted to investigate 726 nurses suffering from workplace violence in 10 tertiary hospitals by using demographic, work-related information, lifestyle questionnaire, simplified Chinese version of the Posttraumatic Growth Inventory, and professional quality of life scale. In the findings, (i) the participants' posttraumatic growth scores were 57.29 ± 21.56, while the compassion satisfaction, burnout, and secondary traumatic stress scores were 32.82 ± 6.80, 27.17 ± 5.53, and 26.67 ± 5.29, respectively, (ii) posttraumatic growth was positively correlated with compassion satisfaction and secondary traumatic stress, and negatively correlated with burnout, and (iii) compassion satisfaction, sleep hours per day, department, scheduling, alcohol, secondary traumatic stress, children, and work hours per day were influencing factors of posttraumatic growth, which explained 36.3% of the total variance. Our study indicates that Chinese nurses may experience moderate levels of compassionate satisfaction, burnout, secondary traumatic stress, and low levels of posttraumatic growth after suffering from workplace violence, while the posttraumatic growth of nurses suffering from workplace violence is more affected by work-related variables and lifestyle-related variables, but less affected by other sociodemographic variables. Therefore, it is necessary to strengthen the psychological evaluation of nurses and adopt targeted strategies to promote nurses' posttraumatic growth.

There is no consensus on whether triplet regimen is better than doublet regimen in the first-line treatment of advanced gastric cancer (AGC). We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine (XELOX) and epirubicin, oxaliplatin, plus capecitabine (EOX) regimens in treating AGC.This phase III trial enrolled previously untreated patients with AGC who were randomly assigned to receive the XELOX or EOX regimen. The primary endpoint was non-inferiority in progression-free survival (PFS) for XELOX as compared with EOX on an intention-to-treat basis.Between April 10, 2015 and August 20, 2020, 448 AGC patients were randomized to receive XELOX (n = 222) or EOX (n = 226). The median PFS (mPFS) was 5.0 months (95% confidence interval [CI] = 4.5-6.0 months) in the XELOX arm and 5.5 months (95% CI = 5.0-6.0 months) in the EOX arm (hazard ratio [HR] = 0.989, 95% CI = 0.812-1.203; PThis non-inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first-line treatment for AGC patients. However, the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.

This work introduces vinyl boronic acid and its pinacol ester derivative as suitable monomers in radical polymerization to prepare well-defined polyolefins with boron-containing groups that show sol–gel transition properties.

MgO nanoparticles (NPs) are widely used in bactericides, fuel cells and electronic materials and are frequently detected in aquatic environments.

The use of mild pretreatment conditions can significantly lower the cost of the biorefining process. This study evaluated a mild pretreatment approach for tobacco stem waste using a combination of dilute acid and dilute alkali. By optimizing the pretreatment conditions, we obtained a high reducing sugar concentration at a pretreatment temperature

Background Cancer stem cell (CSC) and ferroptosis play critical roles in cancer development, but the underlying mechanisms remain unclear. Cervical cancer induces a great mortality and an increased incidence globally. Zinc oxide nanoparticle is the nanomaterial that has been applied in industrial products and targets multiple cancer cell types and cancer stem cells. Here, we aimed to explore the effect of ZON on CSC and ferroptosis of cervical cancer. Methods In the present study, we identified that the treatment of ZON in vitro inhibited the proliferation of cervical cancer cells. Results The ZON stimulated the apoptosis of cervical cancer cells. The tumor growth of cervical cancer cells was attenuated by ZON in the xenograft mouse model in vivo. Meanwhile, ZON represses cell invasion and migration of cervical cancer. Crucially, the sphere formation numbers were repressed by ZON. Meanwhile, the SP ratio of cervical cancer cells was inhibited by ZON. The expression of CSC markers, including Sox-2, Oct3/4, and Nanog, was suppressed by circFoxo3 inhibition. Moreover, the ferroptosis was enhanced by ZON in cervical cancer cells. About the mechanism, we observed that ZON enhanced miR-506-3p expression and CD164 was a target of miR-506-3p, in which ZON inhibited CD164 expression by promoting miR-506-3p in cervical cancer cells. We validated that CD164 reversed miR-506-3p-mediated stemness and ferroptosis in cervical cancer cells. ZON repressed stemness and reduced ferroptosis of cervical cancer cells by targeting CD164. ZON inhibits cell growth of cervical cancer in vivo by targeting CD164. Conclusions In brief, we concluded that ZON regulated the ferroptosis, proliferation, invasion, and steaminess of cervical cancer by miR-506-3p/CD164 signaling. Our finding provides new insights into the mechanism by which ZON regulates ferroptosis and steaminess of cervical cancer by a miR-506-3p/CD164 axis.

Grain weight and size, mostly determined by grain length, width and thickness, are crucial traits affecting grain quality and yield in rice. A quantitative trait locus controlling grain length and width in rice, qGS1-35.2, was previously fine-mapped in a 57.7-kb region on the long arm of chromosome 1. In this study, OsPUB3, a gene encoding a U-box E3 ubiquitin ligase, was validated as the causal gene for qGS1-35.2. The effects were confirmed firstly by using CRISPR/Cas9-based mutagenesis and then through transgenic complementation of a Cas9-free knock-out (KO) mutant. Two homozygous KO lines were produced, each having a 1-bp insertion in OsPUB3 which caused frameshift mutation and premature termination. Compared with the recipient and a transgenic-negative control, both mutants showed significant decreases in grain weight and size. In transgenic complementation populations derived from four independent T0 plants, grain weight of transgenic-positive plants was significantly higher than transgenic-negative plants, coming with increased grain length and a less significant decrease in grain width. Based on data documented in RiceVarMap V2.0, eight haplotypes were classified according to six single-nucleotide polymorphisms (SNPs) found in the OsPUB3 coding region of 4695 rice accessions. Significant differences on grain size traits were detected between the three major haplotypes, Hap1, Hap2 and Hap3 that jointly occupy 98.6% of the accessions. Hap3 having the largest grain weight and grain length but intermediate grain width exhibits a potential for simultaneously improving grain yield and quality. In another set of 257 indica rice cultivars tested in our study, Hap1 and Hap2 remained to be the two largest groups. Their differences on grain weight and size were significant in the background of non-functional gse5, but non-significant in the background of functional GSE5, indicating a genetic interaction between OsPUB3 and GSE5. Cloning of OsPUB3 provides a new gene resource for investigating the regulation of grain weight and size.

Grain shape and size are key determinants of grain appearance quality and yield in rice. In our previous study, a grain shape QTL

We conducted an umbrella review to consolidate the evidence of adopting plant-based diets on anthropometric and cardiometabolic outcomes. Six electronic databases (CINAHL, EMBASE, PubMed, Scopus, the Cochrane Library, and Web of Science) were searched for systematic reviews with meta-analysis (SRMAs) published from each journal’s inception until 1 October 2022. Effect sizes from SRMAs and primary studies were pooled separately using random effects models. Overlapping primary studies were removed for primary studies’ analyses. Seven SRMAs representing 51 primary studies were included, suggesting significant benefits of plant-based diets on weight (−2.09 kg, 95% CI: −3.56, −0.62 kg, p = 0.01, I2 = 95.6%), body mass index (−0.95 kg/m2, 95% CI: −1.26, −0.63 kg/m2, p = 0.002; I2 = 45.1%), waist circumference (−2.20 cm, 95% CI: −0.08, 0.00 cm, p = 0.04; I2 = 88.4%), fasting blood glucose (−0.11 mmol/L, 95% CI: −0.13, −0.09 mmol/L, p < 0.001, I2 = 18.2%), and low-density lipoprotein cholesterol (−0.31 mmol/L, 95% CI: −0.41, −0.20 mmol/L, p < 0.001, I2 = 65.6%). Changes in high-density lipoprotein cholesterol, triglycerides, and blood pressure were not statistically significant. Generally, plant-based diets were recommended to improve anthropometry, lipid profile, and glucose metabolism. However, findings should be interpreted with caution, because most of the reviews were rated to be of low credibility of evidence and were largely based on Western eating habits and traditions, which may limit the generalizability of findings.

Two new cycloartane triterpenoids, (24 R)-cycloartane-3β,24,25,30-tetrol (1) and (24 R)-24,25,30-trihydroxy-9,19-cycloartane-3-one (2), along with three known compounds (3-5) were isolated from leaves and twigs of Aphanamixis polystachya. The new compounds were elucidated based on comprehensive spectroscopic analysis, including 1 D, 2 D NMR and HREIMS. The in vitro cytotoxic activities evaluation of five human cancer cell lines revealed that compound 1 exhibited cytotoxic activity on all of tested human cancer cell lines, while compound 2 only had specific activity on SMMC-7721 cell line.

We propose and demonstrate a cost-effective liquid refractive index (RI) sensor in polymer materials by employing a Mach-Zehnder interferometer (MZI) formed with the conventional strip waveguide. The proposed sensor can attain high sensitivity by choosing a suitable reference arm length to reduce optical path difference (OPD) between the two arms of the employed MZI. Our fabricated devices, which have the same sensing arm length of 7900 μm but different reference arm lengths of 7900.0, 7942.5, 7950.9, 7962.2, and 7969.5 μm, respectively, exhibit the maximum RI sensitivities of 33662.8 nm/RIU, and almost the same detection range (DR) of 0.0041 ± 0.0002 RIU.

An intrinsic topological metal (TM) state is found in the T-graphene, a monolayer with both the time-reversal symmetry and the four-fold symmetry. The state distinguishes itself by the nontrivial electric polarization from the ordinary metals and features with two local edge states in the corresponding nanoribbons. The TM state is confirmed as a transition state bridging the ordinary metal state and the topological insulator state when the relative neighboring hoppings change in the lattice. The topological nature is further verified by checking the robustness of transport property against randomly-introduced strong disorders. The fact that the multiple topological states indexed by different parameters coexist in such a practical system shows a broad prospect in versatile topological transport devices.

Diabetic wound, a common complication in patients with diabetes, is difficult to treat because of the long-term consequences of accumulating advanced glycation end products and high glucose levels. Moreover, wound infections occur frequently in diabetes; therefore, developing effective treatments is of great significance for healing diabetic wounds. Electrospun nanofibers have played a favorable role in wound healing, but the efficacy in diabetes is yet to be investigated. This study used mouse models of DW in order to determine the effect of electrospun nanofibers on wound healing. It turned out that electrospun nanofibers increased the healing rate in mice and inhibited levels of inflammatory cytokines, as well as activated epidermal growth factor (EGF). In vitro experiments revealed that the migration and proliferation of human umbilical vein endothelial cells (HUVECs) were enhanced after the intervention. Overall, electrospun nanofibers can improve the healing of diabetic wounds significantly.

The cover image is based on the Original Article XELOX doublet regimen versus EOX triplet regimen as first‐line treatment for advanced gastric cancer: An open‐labeled, multicenter, randomized, prospective phase III trial (EXELOX) by Wei‐Jian Guo et al., https://doi.org/10.1002/cac2.12278. [Image: see text]

Background: Genome-wide association studies (GWASs) have consistently identified MAP2K5 as an obesity susceptibility gene. To deepen our understanding of the potential causal genetic variants of this region, a fine-mapping study of MAP2K5 was conducted.Methods and Results: SNPs rs7175517 (G > A) and rs4776970 (T > A) were identified as the leading SNPs associated with BMI in both Chinese and the United Kingdom populations. Second, colocalization of GWAS and expression quantitative trait loci (eQTL) analyses and bioinformatic analyses indicated that rs7175517 is the functionally leading variant in the MAP2K5 gene region. Dual-luciferase assays indicated that the G allele of rs7175517 reduced the mRNA expression of MAP2K5 in HEK293T cells. The possible mechanism was that the G allele interacted with more RNA repressors from nuclei extracts, which was evidenced by electrophoretic mobility shift assays (EMSAs). Furthermore, the pathway enrichment analyses of the products from DNA pull-down and protein mass spectrometry demonstrated that the G allele of rs7175517 might interact with RNA catabolic or splicing transcription factors, which consequentially increased adiposity deposition.Conclusion: SNP rs7175517 of the MAP2K5 gene was the putative causal variant associated with BMI. More precisely designed in vitro or animal experiments are warranted to further delineate the function of MAP2K5 in adipogenesis.

Body mass index (BMI) and waist-to-hip ratio (WHR) have been reported to be causally associated with cardiometabolic diseases in adults in European populations. However, this causality was less explored in East Asian populations and in children. Our study aimed to explore and compare the causal associations of general obesity (measured by BMI) and central obesity (measured by WHR) with cardiometabolic traits.We performed a Mendelian randomization (MR) analysis in 2030 unrelated children from two independent case-control studies in Beijing, China. BMI-associated single nucleotide polymorphisms (SNPs) and WHR-SNPs identified by previous genome-wide association studies were used as genetic instruments to examine the casual associations of BMI and WHR with cardiometabolic traits, including glycemic traits, blood lipids, and blood pressure. Each 1-SD increase in BMI and WHR were significantly associated with 0.111 mmol/L and 0.110 mmol/L increase in log-transformed fasting insulin (FINS), 0.049 and 0.060 increase in log-transformed HOMA-β, 0.112 and 0.108 increase in log-transformed HOMA-IR, 0.009 mmol/L and 0.015 mmol/L increase in log-transformed triglyceride, and 15.527 mmHg and 7.277 mmHg increase in systolic blood pressure, respectively (all P 0.05). The receiver operating characteristic curves showed that WHR had a stronger effect on FINS, HOMA-β, HOMA-IR, and triglyceride than BMI (all P 0.05).Using the MR method, we found that the genetic predisposition to higher BMI or WHR was associated with altered cardiometabolic traits in Chinese children. When compared with general obesity, central obesity might have stronger effects on glycemic traits and blood lipids among children.

Since the outbreak of novel coronavirus pneumonia (coronavirus disease 2019, COVID-19), it has rapidly spread to 187 countries, causing serious harm to the health of people and a huge social burden. However, currently, drugs specifically approved for clinical use are not available, except for vaccines against COVID-19 that are being evaluated. Traditional Chinese medicine (TCM) is capable of performing syndrome differentiation and treatment according to the clinical manifestations of patients, and has a better ability of epidemic prevention and control. The authors comprehensively analyzed the etiology and pathogenesis of COVID-19 based on the theory of TCM, and discussed its syndrome differentiation, treatment and prevention measures so as to provide strategies and reference for the prevention and treatment with TCM.

Aphananoid A, a limonoid which features a rare C24 appendage and new 5/6/5 fused-ring framework, was obtained from Aphanamixis polystachya. The planar structure as well as the absolute configuration was identified based on extensive spectroscopic analysis and electronic circular dichroism calculations. The biogenetic pathway of aphananoid A was also speculated, which arises from the triterpene by the 3,4-seco-7,8-seco-6,8 cyclo-7,30-decarbon key pattern. In addition, bioassays indicated that aphananoid A inhibited NO production in the RAW264.7 cell line (46.80 ± 1.93%).

Background Previous studies have related FAM3C gene with childhood bone health, and the regulation of lipid metabolism in hepatocytes. The present case-control study aimed to analyze the association of FAM3C genetic variants with overweight/obesity and lipid traits among Chinese children. Methods Two genetic variants (rs7776725 and rs7793554) within the FAM3C gene were genotyped in 3305 Chinese children aged 6-18 years. Results In the whole study population, the T-allele of rs7776725 and A-allele of rs7793554 within the FAM3C gene were associated with 40.2% (95% CI: 11.6-76.1%; P = 0.004) and 29.1% (6.9-56.0%; P = 0.008) increased risk of dyslipidemia, higher triglyceride (P = 0.014 and P = 0.001) and lower HDL-C (P = 0.015 and P = 0.003). In addition, we found that rs7776725 interacted with sex on dyslipidemia (Pfor interaction = 0.004), and sex-stratified analyses showed that it was significantly associated with dyslipidemia only in girls (P = 8.78 × 10-5). The variant also showed nominally significant interactions with sex on total cholesterol and LDL-C (Pfor interaction = 0.012 and 0.008). Conclusion We found that FAM3C genetic variants were associated with dyslipidemia and lipid traits among Chinese children. In addition, we found significant gene-by-sex interactions. Our findings provided evidence supporting the role of FAM3C gene in regulating lipid metabolism in humans. Impact FAM3C genetic variants were associated with dyslipidemia and lipid traits among Chinese children. In addition, we found significant gene-by-sex interactions.FAM3C/rs7776725 was associated with dyslipidemia and lipid traits only in girls.Our findings provided evidence supporting the role of FAM3C gene in regulating lipid metabolism in humans.

The one-pot synthesis of dibenzo[a,f]azulen-12-ones has been established starting from o-propargyl alcohol benzaldehydes and alkynes. The key azulenone bicyclic skeletons were formed through the intramolecular tandem cyclization and intermolecular [5 + 2]-cycloaddition sequence. This annulation process showed high atom and step economy, regioselectivity and stereoselectivity by creating three C–C and one C–O bonds.

Additional file 1. Figure S1. Characterization of the cells in the outer glume epidermal of CK and KO-1 for OsPUB3. A Comparison of cell length in the outer glume epidermal. B Comparison of cell width in the outer glume epidermal. C Comparison of cell numbers in the longitudinal direction. D Comparison of cell numbers in the transverse direction. E Scanning electron microscopic images of the cells. Scale bars=100 μm. Values are given as the mean ± SD (n = 20). Differences between CK and KO-1 were tested by student’s t-test. *, p < 0.05; ns: not significant. Figure S2. The effects of OsPUB3 knock-out on grain width, grain length and head rice recovery. A Comparisons of grain width among the knock-out mutants and the two controls. B Comparisons of grain length among the knock-out mutants and the two controls. C Comparisons of head rice recovery among the knock-out mutants and the two controls. Scale bars = 10 mm. Figure S3. Phenotypic differences among three haplotypes of OsPUB3. A 1,000-grain weight. B Grain length. C Grain width. D Ratio of grain length to width. Values are given as the mean ± SD (n = 338 for Hap1, n = 122 for Hap2, n = 50 for Hap3). Values with different letters are significantly different at p < 0.05 based on the Duncan’s multiple range test. Figure S4. Phenotypic differences between ZS97-type and MY46-type of OsPUB3. A-C Three traits measured in Lingshui trial. D-F Three traits measured in Hangzhou trial. Values are given as the mean ± SD ( n = 19 for ZS97-type; n = 230 for MY46-type). *, p < 0.05; **, p < 0.01; ns: not significant. Figure S5. Protein variations of the eight haplotypes. Difference in amino acid is shown in green.

Additional file 2. Table S1. Phenotypic change due to OsPUB3 knockout. Table S2. Haplotypes of OsPUB3 in rice germplasms. Table S3. Rice germplasms used in this study. Table S4. Primers used in this study.

Additional file 1: Figure S1 Characterization of ZON. A, B ZON was synthesized and the actual size and surface charge were observed by TEM and zeta potential analyzer. Figure S2 Effect of ZON on HcerEpic cells. A HcerEpic cells were treated with ZON. The cell growth was analyzed by colony formation assays. Ns no significant. Figure S3 ZON inhibits cell growth of cervical cancer in vivo by targeting CD164. A–D Tumor growth of Hela cell was analyzed by xenograft mouse model in vivo (n=5). The tumor images (A), tumor weight (B), Ki-67 levels (C), and CD164 expression (D) were shown. The experiments were repeated 3 times, **P < 0.01.

Rice is a major dietary source of essential mineral nutrients and toxic elements (aka ionome) for humans. However, the genetic basis underlying the variation in ionome is still largely unknown. Here, we mapped 51 and 61 quantitative trait loci (QTLs) controlling the concentrations of 13 and 15 elements in rice (Oryza sativa L.) grain and straw, respectively, using a recombinant inbred lines (RILs) that were grown at three different field sites in 3 years. Several QTLs were repeatedly detected in both grain and straw or in multiple years; the resulting 87 unique QTLs with 17 of them (20%) were co-localized with previously reported corresponding QTLs and 70 were novel ionomic QTLs. At least, 14 genomic clusters that controlled the concentrations of multiple elements were identified. Furthermore, we identified a molybdate transporter gene OsMOT1;1 as the putative causal gene for a QTL controlling molybdenum concentration in both straw and grain. QTL analyses based on the concentrations of multiple elements in both grain and straw of RIL population grown in three field sites in 3 years allow us to identify tissue common QTLs and reproducible QTLs that were validated in multiple years. The identification of ionomic QTLs will be useful in revealing the molecular mechanisms underlying the accumulation of elements in rice and providing the opportunity to reduce the accumulation of toxic elements and enrich the accumulation of beneficial elements in rice grain.

Grain weight and size are important traits determining grain yield and influencing grain quality in rice. In a previous study, a quantitative trait locus controlling thousand-grain weight (TGW) in rice, qTGW10-20.8, was mapped in a 70.7 kb region on chromosome 10. Validation of the candidate gene for qTGW10-20.8, OsMADS56 encoding a MADS-box transcription factor, was performed in this study. In a near-isogenic line (NIL) population segregated only at the OsMADS56 locus, NILs carrying the OsMADS56 allele of IRBB52 were 1.9% and 2.9% lower in TGW than NILs carrying the OsMADS56 allele of Teqing in 2018 and 2020, respectively. Using OsMADS56 knock-out mutants and overexpression transgenic plants, OsMADS56 was validated as the causal gene for qTGW10-20.8. Compared with the recipients, the TGW of the knock-out mutants was reduced by 6.0–15.0%. In these populations, decreased grain weight and size were associated with a reduction in the expression of OsMADS56. In transgenic populations of OsMADS56 driven by a strong constitutive promoter, grain weight and size of the positive plants were significantly higher than those of the negative plants. Haplotype analysis showed that the Teqing-type allele of OsMADS56 is the major type presented in cultivated rice and used in variety improvement. Cloning of OsMADS56 provides a new gene resource to improve grain weight and size through molecular design breeding.

Background: Genome-wide association studies (GWASs) have consistently identified MAP2K5 as the obesity susceptible gene. To deepen our understanding of the potential causal genetic variants of this region, a fine-mapping study of MAP2K5 was conducted. Results: First, a target single nucleotide polymorphisms (SNPs) sequencing of MAP2K5 was carried out in 2030 Chinese children and followed by a fine mapping with the UK biobank GWAS data in 264,838 adults to identify the leading SNPs within the MAP2K5 gene region. SNP rs7175517 (G>A) and rs4776970(T>A) were identified as the leading SNPs associated with BMI in both Chinese and the UK population. Second, colocalization of GWAS and expression quantitative trait loci (eQTL) analyses and bioinformatic functional annotations indicated that rs7175517 is the leading variants in MAP2K5 gene region functionally. Additionally, dual luciferase assay indicated that the G allele of rs7175517 reduced the mRNA expression of MAP2K5 in HEK293T cells. The possible mechanism was that the G allele of rs7175517 interacted with more RNA repressors from nuclei extracts, which was evidenced by electrophoretic mobility shift assays (EMSAs). Furthermore, the pathway enrichment analyses of the products from DNA pull-down and protein mass spectrometry demonstrated that the G allele of rs7175517 might interact with RNA catabolic or splicing transcription factors, which consequentially increased the adiposity deposition. Conclusions: SNP rs7175517 of MAP2K5 gene was the putative causal variant associated with BMI. More precisely designed in vitro or animal experiments are warranted to further delineate the function of MAP2K5 in the adipogenesis.

Based on literature research and Delphi expert consensus method, the important acupoints for cancer pain was summarized to provide evidence basis for the formulation of采用文献调研和德尔菲专家共识，总结针刺治疗癌痛的重要穴位，为制订《针刺治疗癌痛临床实践指南》提供证据基础。通过系统检索中、英文数据库，纳入针刺治疗癌痛的临床研究28项，归纳分析选穴方法和高频使用的穴位，据此设计德尔菲调查问卷，对30名国内外针灸、肿瘤相关领域专家进行两轮问卷调查。认为针刺治疗癌痛应采用个性化取穴方案，取穴以足三里、合谷、太冲、三阴交、阳陵泉和阿是穴为主。结合临床研究证据与专家调研结果得出针刺治疗癌痛的重要穴位，然而临证选穴仍有待进一步研究和细化。.

Humans have been suffering from vitiligo for a long time. Target vitiligo drugs have yet been approved. Activation of Wnt/β-catenin signalling has potential in the therapeutic use of vitiligo, so exploring new drugs that specifically directly activate Wnt is worthwhile to obtain new anti-vitiligo agents. In this work, two portions design and synthesis were put into effect. firstly, 17 phenanthridine derivatives with C-4 substitutes were designed and synthesized, which compounds 4, 6, 12, 13 served as H-acceptor with protein showed enhance melanogenesis activity; Secondly, 7 hybrid new scaffolds of compounds were designed and synthesized, scaffold hopping compound 36 that aromatic benzene was replaced pyrazole on ring C showed enhance melanogenesis and tyrosinase activity; The last and most important, a comprehensive optimization and SARs of compound 36 were carried out, compounds 41 and 43 shared phenolic hydroxyl or 3-methyl-pyridine substitutes at C-7 position remarkably improved the capacity of melanogenesis and tyrosinase activity. Compound 43 were identified as new anti-vitiligo agents that specifically activate the Wnt/β-catenin signalling pathway by targeting Axin. Structure-activity relationship analysis implied that H-acceptor substitutions at the C-4 position and phenolic hydroxyl or pyridine substitutions at the C-7 position would improve the activities of the compounds. These findings reveal a new therapeutic strategy for vitiligo, and compounds 41 and 43 may represent potential compounds for vitiligo treatment.

Grain size, shape and weight are important factors influencing grain yield and quality of rice. They are mostly determined by grain length (GL) and grain width (GW). A 13.2 Mb interval, RM167–RM287 on chromosome 11 of rice, was previously found to be associated with variations in 1000-grain weight (TGW). In this study, three populations derived from the indica rice cross Teqing/IRBB52 were used to identify and validate quantitative trait loci (QTLs) controlling GL, GW, TGW and the ratio of GL to GW (RLW) in the RM167–RM287 region. First, two QTL clusters associated with these traits were detected using two populations, segregating the RM167–RM287 interval only. One controlled GL, GW and TGW and was designated as qGS11. The other controlled GL and RLW. The allelic directions of the two QTL clusters on GL were opposite. Then, qGS11 was further mapped in a 1.4 Mb interval using near-isogenic lines, showing a small effect on GL and a relatively large effect on TGW, GW and RLW. Meanwhile, a stable and small effect on the heading date was detected. The allelic direction for the heading date was the opposite for TGW and GW but the same for GL and RLW. The results suggest that qGS11 has the potential for application in rice breeding.

Background Circular RNAs (circRNAs) have been considered as pivotal biomarkers in Diabetic nephropathy (DN). CircRNA ARP2 actin-related protein 2 homolog (circ-ACTR2) could promote the HG-induced cell injury in DN. However, how circ-ACTR2 acts in DN is still unclear. This study aimed to explore the molecular mechanism of circ-ACTR2 in DN progression, intending to provide support for the diagnostic and therapeutic potentials of circ-ACTR2 in DN. Methods RNA expression analysis was conducted by the quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Cell growth was measured via Cell Counting Kit-8 and EdU assays. Inflammatory response was assessed by Enzyme-linked immunosorbent assay. The protein detection was performed via western blot. Oxidative stress was evaluated by the commercial kits. The molecular interaction was affirmed through dual-luciferase reporter and RNA immunoprecipitation assays. Results Circ-ACTR2 level was upregulated in DN samples and high glucose (HG)-treated human renal mesangial cells (HRMCs). Silencing the circ-ACTR2 expression partly abolished the HG-induced cell proliferation, inflammation and extracellular matrix accumulation and oxidative stress in HRMCs. Circ-ACTR2 was confirmed as a sponge for miR-205-5p. Circ-ACTR2 regulated the effects of HG on HRMCs by targeting miR-205-5p. MiR-205-5p directly targeted high-mobility group AT-hook 2 (HMGA2), and HMGA2 downregulation also protected against cell injury in HG-treated HRMCs. HG-mediated cell dysfunction was repressed by miR-205-5p/HMGA2 axis. Moreover, circ-ACTR2 increased the expression of HMGA2 through the sponge effect on miR-205-5p in HG-treated HRMCs. Conclusion All data have manifested that circ-ACTR2 contributed to the HG-induced DN progression in HRMCs by the mediation of miR-205-5p/HMGA2 axis.

To examine whether sex-specific associations between baseline PA level and follow up cognitive performance in Chinese subjects exist from the China Health and Retirement Longitudinal study (CHARLS).A total of 3395 adults aged 45 or old from the CHARLS were used for analysis. The combined scores of measurements of mental status and verbal episodic memory were utilized for assessing cognitive function at baseline in 2011 and the follow-up survey in 2015. Baseline PA level was quantified as the total PA score. Multiple linear regression and logistic regression models were used to examine the association between baseline PA status and global cognitive function and cognitive domains.In the female subjects (In the female subjects, higher PA level was associated with reduced risk of cognitive decline within 4 years, this might be associated with reduced decline of verbal episodic memory. Our findings confirmed that female sex would positively affect the association between PA levels and cognitive decline.

A metal-free intramolecular [3+2] cycloaddtion has been achieved by treating benzene-linked propynol-ynes with AcOH/H

ObjectiveThe purpose of this systematic review and meta-analysis is to evaluate the efficacy and safety of carbon ion radiotherapy (CI-RT) in improving meningioma by comparing photon and protons radiotherapy.MethodsA comprehensive search for relevant studies published until March 17, 2021, was conducted in PubMed, the Cochrane Library, Chinese Biomedical Literature Database and EMBASE. Statistical analyses were performed with R 4.0.3.ResultsWe identified 396 studies, of which 18 studies involving 985 participants were included. Except for one low quality study, the quality of the included studies was found to be either moderate or high quality. The analyses conducted according random effects model indicated that the 1-year overall survival rate (OS) of benign and non-benign meningiomas after the CI-RT treatment was 99% (95%CL=.91-1.00, I2 = 0%). The overall average 5-year OS for meningiomas was 72% (95%CL=0.52-0.86, I2 = 35%), not as effective as proton radiotherapy (PR-RT) 85% (95%CL=.72-.93, I2 = 73, Q=4.17, df=2, p=.12). Additionally, 5-year OS of atypical meningiomas (81%) was found to be significantly higher than anaplastic meningiomas (52%). The 10-year OS after CI-RT of patients with mixed grade meningioma was 91% (95%CL=.75-.97, I2 = 73%). The 15-year OS after CI-RT 87% (95%CL=.11-1.00) or PR-RT 87% (95%CL=.23-.99, I2 = 79%) were the same (Q=0, df=1, p=.99). After undergoing CI-RT for 3 and 5 years, the LC for benign meningioma was 100% and 88%, respectively, while the 2-year LC of non-benign meningiomas (atypical/anaplastic) was 33%. Headache, sensory impairment, cognitive impairment, and hearing impairment were found to be the most common adverse reactions, with individual incidences of 19.4%, 23.7%, 9.1%, and 9.1%, respectively.ConclusionCI-RT is a rapidly developing technique that has been proven to be an effective treatment against meningioma. The efficacy and safety of CI-RT for meningiomas were similar to those of PR-RT, better than photon radiotherapy (PH-RT). However, there is a need for more prospective trials in the future that can help provide more supportive evidence.

Background: Staphylococcus aureus (S. aureus) is the leading cause of various infective diseases including topical soft tissue infections. Due to an increasing prevalence of the methicillin-resistant Staphylococcus aureus (MRSA), S. aureus infection become more challenging to being treated over recent years. The goals of this study were to investigate the roles of antisense yycF/G RNAs in the regulation of the biofilm formation and pathogenicity. Methods: MRSA ASyycF/G overexpression mutants were constructed. The biofilm biomass was determined by crystal violet microtiter assay and scanning electron mi-ceroscopy (SEM). Quantitative RT-PCR and western blotting analysis were used to detect the transcripts and translations of biofilm-related genes. The effects of the antisense RNAs (ASyycF/G) strategy on the susceptibility of biofilm-producing S. aureus to hydrogen peroxide were also investigated. Result: The ASyycF/G transcript leaded to reduction in the biofilm formation. Overexpression of ASyycF/G inhibited the transcripts and translations of biofilm-related genes. The sensibility to vancomycin was improved in ASyycF/G overexpression MRSA. Conclusions: The biofilm biomass and the transcripts of the pathogenicity associated genes decreased in the ASyycF/G overexpression mutant. Thus, the current evidence may provide a supplementary strategy for managing MRSA infections.