Novel trans-Resveratrol Derivatives: Design, Synthesis, Antibacterial Activity, and Mechanisms.

Rice bacterial leaf blight and rice bacterial leaf streak have induced tremendous damage to production of rice worldwide. To discover an effective novel antibacterial agent, a series of novel trans-resveratrol (RSV) derivatives containing 1,3,4-oxadiazole and amide moieties were designed and synthesized for the first time. Most of them showed excellent antibacterial activities against Xanthomonas oryzae pv oryzicola and Xanthomonas oryzae pv oryzae. Especially, compound J12 had the best inhibitory with the half-maximal effective concentration values of 4.2 and 5.0 mg/L, respectively, which were better than that of RSV (63.7 and 75.4 mg/L), bismerthiazol (79.5 and 89.6 mg/L), and thiodiazole copper (105.4 and 112.8 mg/L). Furthermore, compound J12 had an excellent control effect against rice bacterial leaf streak and rice bacterial leaf blight, with protective activities of 46.2 and 42.1% and curative activities of 44.5 and 41.7%, respectively. Preliminary mechanisms indicated that compound J12 could not only remarkably decrease biofilm formation, extracellular polysaccharide production, and the synthesis of extracellular enzymes but also destroy bacterial cell surface morphology, thereby reducing the pathogenicity of bacteria. In addition, compound J12 could increase the activity of defense-related enzymes and affect the expression of multiple pathogenic-related genes including plant-pathogen interaction, the MAPK signaling pathway, and phenylpropanoid biosynthesis, and this could improve the defense of rice against rice bacterial leaf streak infection. The present work indicates that the RSV derivatives can be used as promising candidates for the development of antibacterial agents.

New advances of NG2-expressing cell subset in marrow mesenchymal stem cells as novel therapeutic tools for liver fibrosis/cirrhosis.

BACKGROUND: Bone marrow-derived mesenchymal stem cell (BMMSC)-based therapy has become a major focus for treating liver fibrosis/cirrhosis. However, although these cell therapies promote the treatment of this disease, the heterogeneity of BMMSCs, which causes insufficient efficacy during clinical trials, has not been addressed. In this study, we describe a novel Percoll-Plate-Wait procedure (PPWP) for the isolation of an active cell subset from BMMSC cultures that was characterized by the expression of neuroglial antigen 2 (NG2/BMMSCs). METHODS: By using the key method of PPWP and other classical biological techniques we compared NG2/BMMSCs with parental BMMSCs in biological and functional characteristics within a well-defined diethylnitrosamine (DEN)-induced liver fibrosis/cirrhosis injury male C57BL/6 mouse model also in a culture system. Of note, the pathological alterations in the model is quite similar to humans'. RESULTS: The NG2/BMMSCs revealed more advantages compared to parentalBMMSCs. They exhibited greater proliferation potential than parental BMMSCs, as indicated by Ki-67 immunofluorescence (IF) staining. Moreover, higher expression of SSEA-3 (a marker specific for embryonic stem cells) was detected in NG2/BMMSCs than in parental BMMSCs, which suggested that the "stemness" of NG2/BMMSCs was greater than that of parental BMMSCs. In vivo studies revealed that an injection of NG2/BMMSCs into mice with ongoing DEN-induced liver fibrotic/cirrhotic injury enhanced repair and functional recovery to a greater extent than in mice treated with parental BMMSCs. These effects were associated with the ability of NG2/BMMSCs to differentiate into bile duct cells (BDCs). In particular, we discovered for the first time that NG2/BMMSCs exhibit unique characteristics that differ from those of parental BMMSCs in terms of producing liver sinusoidal endothelial cells (LSECs) to reconstruct injured blood vessels and sinusoidal structures in the diseased livers, which are important for initiating hepatocyte regeneration. This unique potential may also suggest that NG2/BMMSCs could be an novel off-liver progenitor of LSECs. Ex vivo studies revealed that the NG2/BMMSCs exhibited a similar trend to that of their in vivo in terms of functional differentiation responding to the DEN-diseased injured liver cues. Additionally, the obvious core role of NG2/BMMSCs in supporting the functions of BMMSCs in bile duct repair and BDC-mediated hepatocyte regeneration might also be a novel finding. CONCLUSIONS: Overall, the PPWP-isolated NG2/BMMSCs could be a novel effective cell subset with increased purity to serve as a new therapeutic tool for enhancing treatment efficacy of BMMSCs and special seed cell source (BDCs, LSECs) also for bioliver engineering.

Chiral Herbicide 2,4-D Ethylhexyl Ester: Absolute Configuration, Stereoselective Herbicidal Activity, Crop Safety, and Metabolic Behavior on Maize and Flixweed.

This study represents the initial examination of the herbicidal efficacy, crop safety, and degradation patterns of 2,4-D ethylhexyl ester (2,4-D EHE) at the enantiomeric level. Baseline separation of 2,4-D EHE enantiomers was achieved using a superchiral R-AD column, with their absolute configurations determined through chemical reaction techniques. Evaluation of weed control efficacy against sensitive species such as sun spurge and flixweed demonstrated significantly higher inhibition rates for S-2,4-D EHE compared to R-2,4-D EHE. Conversely, no stereoselectivity was observed in the fresh-weight inhibition rates of both enantiomers on crops or nonsensitive weeds. A sensitive HPLC-MS/MS method was developed to simultaneously detect two enantiomers and the metabolite 2,4-D in plants. Investigation into degradation kinetics revealed no substantial difference in the half-lives of R- and S-2,4-D EHE in maize and flixweed. Notably, the metabolite 2,4-D exhibited prolonged persistence at elevated levels on flixweed, while it degraded rapidly on maize.

Novel aurone-derived piperazine sulfonamides: Development and mechanisms of action as immunostimulants against plant bacterial diseases.

Bacterial diseases pose a significant threat to the sustainable production of crops. Given the unsatisfactory performance and poor eco-compatibility of conventional bactericides, here we present a series of newly structured bactericides that are inspiringly designed by aurone found in plants of the Asteraceae family. These aurone-derived compounds contain piperazine sulfonamide motifs and have shown promising in vitro performance against Xanthomonas oryzae pv. oryzae, Xanthomonas oryzae pv. oryzicola and Xanthomonas axonopodis pv. citri, in particular, compound II23 achieved minimum half-maximal effective concentrations of 1.06, 0.89, and 1.78 µg/mL, respectively. In vivo experiments conducted in a greenhouse environment further revealed that II23 offers substantial protective and curative effects ranging between 68.93 and 70.29% for rice bacterial leaf streak and 53.17-64.43% for citrus bacterial canker, which stands in activity compared with lead compound aurone and commercial thiodiazole copper. Additional physiological and biochemical analyses, coupled with transcriptomics, have verified that II23 enhances defense enzyme activities and chlorophyll levels in rice. Significantly, it also stimulates the accumulation of abscisic acid (ABA) and upregulates the expression of key genes OsPYL/RCAR5, OsBIPP2C1, and OsABF1, thereby activating the ABA signaling pathway in rice plants under biological stress from bacterial infections.

Discovery of Pyrido[1,2-α] Pyrimidinone Mesoionic Compounds as Potential Control Agents Against Potato Virus Y.

Potato virus Y (PVY) relies on aphids and tubers to spread in the field and causes serious economic losses in the potato industry. Here, we found that pyrido[1,2-α] pyrimidinone mesoionic compounds with insecticidal activity against aphids possessed a good inhibitory effect on PVY. Among them, compound 35 had the best inhibitory activity against PVY (EC50 = 104 µg/mL), even superior to that of ningnanmycin (125 µg/mL). The fluorescence and qPCR results confirmed that compound 35 could inhibit the proliferation of PVY in Nicotiana benthamiana. Preliminary experiments on the mechanism of action indicated that compound 35 had good binding affinity with the coat protein (CP), which plays an essential role in aphid-PVY interactions. Molecular docking revealed that compound 35 could bind to the pocket of CP formed by Ser52, Glu204, and Arg208. Compound 35 had substantially lower binding affinity (Kd) values with CPS52A (219 µM), CPE204A (231 µM), and CPR208A (189 µM) than those with CPWT (5.80 µM). A luciferase assay confirmed that mutating Ser52, Glu204, and Arg208 significantly affected the expression level of CP and further reduced virus proliferation. Therefore, the broad-spectrum activity of compound 35 provides a unique strategy for the prevention and treatment of PVY.

Decomposing Socioeconomic Inequality in Early Childhood Caries Among 3 to 5-Year-Old Children in China.

INTRODUCTION AND AIMS: Early childhood caries (ECC) is a widespread oral disease that harms children's health in China. Although previous studies have linked ECC prevalence to socioeconomic status, few have measured the degree of socioeconomic inequality. This study aimed to evaluate the socioeconomic inequality of ECC in children aged 3 to 5 years in China and identify the contributor to the inequality. METHODS: We extracted data on 3 to 5-year-old children from the fourth National Oral Health Survey. We measured the inequality of ECC by the average household income per capita. We used the average household income per capita to measure the inequality of ECC. To describe inequality both qualitatively and quantitatively, we used the following methods: concentration curve, Erreygers-corrected concentration index, relative index of inequality and slope index of inequality. We also applied a decomposition based on the probit model to identify the factors that contributed to inequality. RESULTS: The prevalence of ECC in Chinese preschool children was 63.11% (95% CIs: 60.54%, 65.61%). The negative value of the Erreygers-corrected concentration index (-0.0459; 95% CIs: -0.0594, -0.0324), slope index of inequality (-0.0674; 95% CIs: -0.0876, -0.0471) and the positive value of relative index of inequality (0.7484; 95% CIs: 0.6856, 0.8169) all indicated that ECC prevalence was higher among children from low-income families. The main factors contributing to inequality were average household income, parents' educational level and living areas. CONCLUSION: There is a pro-poor inequality in ECC among 3 to 5-year-old children in China. CLINICAL RELEVANCE: To improve oral health equality, policymakers should focus more on children from low-income families, with less educated parents and living in rural areas.

Evaluation of serum CA125, HE4 and CA724 and the risk of ovarian malignancy algorithm score in the diagnosis of high-grade serous ovarian cancer.

AIM: To develop a new algorithm for the detection of high-grade serous ovarian cancer (HGSOC). METHODS: Patients diagnosed with HGSOC, borderline ovarian tumours (BOTs) or benign ovarian masses (BOMs) were enrolled between February 2019 and December 2020. Patients with BOTs or BOMs were grouped as non-HGSOC. The cases were divided randomly into a training cohort (two-thirds of cases) and a validation cohort (one-third of cases). Logistic regression was used to find risk factors for HGSOC and to create a new algorithm in the training cohort. Receiver operating characteristic curves were used to compare the diagnostic value of tumour biomarkers. Sensitivity and specificity of tumour markers and the new algorithm were calculated in the training cohort and validation cohort. RESULTS: This study found significant differences in age; BRCA1/2 mutation status; CA125, CA724 and HE4 levels; and Risk of Ovarian Malignancy Algorithm score between the two groups.Logistic regression analysis showed that CA125 and BRCA1/2 were risk factors for HGSOC. A new algorithm combining CA125 and BRCA1/2 increased the specificity of CA125 for diagnosis of HGSOC. The new algorithm had sensitivity of 81.08% and specificity of 93.10% in the training cohort. CONCLUSION: The new algorithm using CA125 and BRCA1/2 helped to distinguish between patients with HGSOC and patients with non-HGSOC.

Long-term exposure to ambient fine particulate matter and periodontitis: An observational study using nationally representative survey data.

AIM: The rising prevalence of periodontitis imposes substantial burdens on individuals and society. Identifying environmental risk factors for periodontitis may contribute to tackling the global public health burden of it. This study aimed to assess the association between long-term exposure to PM2.5 and periodontitis in a nationally representative population from China. MATERIALS AND METHODS: In this multi-centre cross-sectional study of 372 communities in 31 provinces of Mainland China, we used data from the Fourth National Oral Health Survey of China in 2015-2016, in combination with high-resolution gridded concentrations of fine particulate matter (PM2.5). Logistic regression was applied to assess the relationship between long-term PM2.5 exposure and the risk of periodontitis. In addition, we examined whether the association varied by individual characteristics, and estimated the exposure-response relationship and the risk of damaged tooth in each tooth quadrant. RESULTS: A total of 8391 participants from 96 cities were diagnosed with periodontitis, accounting for 60.04% (8391/13,459) of the participants. For each 10 µg/m3 increment in 1-, 3- and 5-year average concentrations of PM2.5, the risk of total periodontitis increased by 9.0% (95% confidence interval: 6.0%, 12.0%), 8.0% (6.0, 11·0) and 7.0% (5.0, 10.0), respectively. Mild periodontitis was more strongly associated with PM2.5 exposure than moderate and severe periodontitis. The teeth in the lower anterior, lower posterior or upper anterior are more susceptible to the effect of PM2.5 on the periodontal pocket, calculus and bleeding gums. CONCLUSIONS: Long-term exposure to PM2.5 is significantly associated with an increased risk of periodontitis in the nationally representative Chinese population. Considering the rising prevalence of periodontitis, considerable costs of treatment, and substantially adverse effects on individuals and society, these findings suggest that stricter air quality regulations may help ease the burden of periodontal disease.

Manipulating HGF signaling reshapes the cirrhotic liver niche and fills a therapeutic gap in regeneration mediated by transplanted stem cells.

Long-term stem cell survival in the cirrhotic liver niche to maintain therapeutic efficacy has not been achieved. In a well-defined diethylnitrosamine (DEN)-induced liver fibrosis/cirrhosis animal model, we previously showed that liver-resident stem/progenitor cells (MLpvNG2+ cells) or immune cells have improved survival in the fibrotic liver environment but died via apoptosis in the cirrhotic liver environment, and increased levels of hepatocyte growth factor (HGF) mediated this cell death. We tested the hypothesis that inhibiting HGF signaling during the cirrhotic phase could keep the cells alive. We used adeno-associated virus (AAV) vectors designed to silence the c-Met (HGF-only receptor) gene or a neutralizing antibody (anti-cMet-Ab) to block the c-Met protein in the DEN-induced liver cirrhosis mouse model transplanted with MLpvNG2+ cells between weeks 6 and 7 after DEN administration, which is the junction of liver fibrosis and cirrhosis at the site where most intrahepatic stem cells move toward apoptosis. After 4 weeks of treatment, the transplanted MLpvNG2+ cells survived better in c-Met-deficient mice than in wild-type mice, and cell activity was similar to that of the mice that received MLpvNG2+ cells at 5 weeks after DEN administration (liver fibrosis phase when most of these cells proliferated). Mechanistically, a lack of c-Met signaling remodeled the cirrhotic environment, which favored transplanted MLpvNG2+ cell expansion to differentiation into mature hepatocytes and initiate endogenous regeneration by promoting mature host hepatocyte generation and mediating functional improvements. Therapeutically, c-Met-mediated regeneration can be mimicked by anti-cMet-Ab to interfere functions, which is a potential drug for cell-based treatment of liver fibrosis/cirrhosis.

Degradation dynamics, residues, processing factors, and dietary risk assessment of bisultap in citrus by LC-MS/MS.

BACKGROUND: Citrus leaf miners are a common pest harming citrus production and quality during citrus planting. During the citrus plant's growth phase, bisultap formulation was frequently used to boost yield and produce fruit of high quality. However, research on citrus's dietary risk assessment for bisultap residues, dissipation and residues is lacking. RESULTS: Liquid chromatography-tandem mass spectrometry was used to develop an accurate and sensitive analytical method for derivatizing bisultap into nereistoxin in whole fruit, pulp and peel. At various levels of addition, the mean recovery of bisultap ranged from 84.64% to 111.09% with a reasonable relative RSD (< 20%). The half-lives in Guangxi and Guizhou were 3.96 and 6.03 days, respectively. After 14-21 days of bisultap application, total residues (bisultap and its metabolite nereistoxin) in the whole fruit were from < 0.02 to 0.228 mg kg-1 in the four experiment sites. Total residue (bisultap and nereistoxin, expressed by bisultap) in whole fruit was approximately 1.05-7.23 times that of pulp. The washing process with tap water removed 85.71% to 98.78% of the bisultap residue in the whole fruit. Bisultap's risk assessment value in citrus was in the range 0.16-1.28%. CONCLUSION: In the whole citrus fruit, bisultap degrades rapidly. Bisultap residues primarily accumulate on citrus peels, and so washing and peeling citrus may effectively remove bisultap residues. For various age groups, the chronic dietary risk of bisultap was acceptable. © 2023 Society of Chemical Industry.

Epidemiology of plaque-induced gingivitis among 12-15-year-old Chinese schoolchildren: A study based on the 2018 case definition.

AIM: To explore the epidemiology of plaque-induced gingivitis and related factors among Chinese adolescents. MATERIALS AND METHODS: This cross-sectional survey comprised 118,601 schoolchildren in the 12-15-year age group. Data came from the National Oral Health Survey in mainland China. The field investigation was conducted according to the World Health Organization guidelines. The new 2018 case definition for plaque-induced gingivitis was used. Participants underwent clinical examinations and completed a structured questionnaire. Bleeding on probing (BOP) was performed on all teeth. Multinomial logistic regression was used to explore the factors related to the extent of gingivitis. RESULTS: Nearly half of the study population (47.3%) had plaque-induced gingivitis; 23.9% and 23.3% presented with localised and generalised gingivitis, respectively. The first molars were the most affected by BOP. Well-established factors, such as demographic characteristics, socioeconomic status, local factors and smoking habits, were significantly associated with the extent of gingivitis. Odds ratios for localised and generalised gingivitis increased with the decrease in frequency of toothbrushing with a fluoride dentifrice. CONCLUSIONS: The study population had high plaque-induced gingivitis prevalence. The extent of gingivitis appeared to have a dose-response relationship with the frequency of toothbrushing with a fluoride dentifrice.

Development and Mechanism Investigation of Novel Thioacetalized Indoles as Antiphytoviral Agents.

Potato virus Y (PVY) is a highly destructive pathogen that infects Solanum tuberosumvL., commonly known as potato, a crop that produces one of the most crucial food staples of the world. The PVY viral infection can considerably reduce the yield and quality of potatoes, thereby causing significant economic ramifications. Given the unsatisfactory performance of commercially available antiviral agents against PVY, we synthesized a series of novel indole-derived compounds followed by their bioevaluation and investigation of the mechanisms governing their anti-PVY activity. These indole-based derivatives contain dithioacetal as a key chemical moiety, and most of them exhibit promising anti-PVY activities. In particular, compound B2 displays remarkable in vivo protective and inactivating properties, with half-maximal effective concentration (EC50) values of 209.3 and 113.0 µg/mL, respectively, in stark contrast to commercial agents such as ningnanmycin (EC50 = 281.4 and 136.3 µg/mL, respectively) and ribavirin (EC50 = 744.8 and 655.4 µg/mL, respectively). The mechanism using which B2 enhances plant immune response to protect plants from PVY is elucidated using enzyme activity tests, real-time quantitative polymerase chain reaction (RT-qPCR), and proteomics techniques. This study aims to pave the way for developing candidate pesticides and related molecules using antiphytoviral activity.

Tooth brushing with fluoridated toothpaste and associated factors among Chinese adolescents: a nationwide cross-sectional study.

BACKGROUND: Tooth brushing with fluoridated toothpaste has become the most important way to provide the anti-caries effect of fluoride around the world. China has promoted the use of fluoridated toothpaste since 1989. However, there are few studies on the national profile of use of fluoridated toothpaste and related factors in Chinese adolescents. We carried out this study to investigate oral hygiene behaviours, especially the status of tooth brushing with fluoridated toothpaste and its correlates among adolescents, based on data from the latest Nation Oral Health Survey in mainland China. METHODS: This cross-sectional study recruited 118,601 participants aged 12-15 years using multistage stratified sampling. Questionnaires were completed by students at school. Data employed in analyses were extracted from the questionnaire, including information on tooth brushing, fluoridated toothpaste, dental floss, sociodemographic factors, fluoride knowledge and attitude towards regular dental check-ups. A binary logistic regression was performed to compute the odds ratios (OR). Tooth brushing twice daily with fluoridated toothpaste was the dependent variable. Sociodemographic factors, fluoride knowledge, attitude towards regular dental check-ups, dental visit experience and perceived oral health were the independent variables. P < 0.05 was considered statistically significant. RESULTS: A total of 32.6% of participants brushed their teeth twice daily, 7.4% used fluoridated toothpaste, and 3.9% cleaned their teeth twice daily with fluoridated toothpaste. The logistic regression showed the probability of twice-a-day tooth brushing with fluoridated toothpaste was higher among these groups: females (OR: 1.141; 95%CI: 1.072-1.214), 15-year-olds (OR: 1.786; 95%CI: 1.634-1.952), from urban areas (OR: 1.389; 95%CI: 1.288-1.497), without siblings (OR: 1.351; 95%CI: 1.259-1.450), with an educated father (OR: 1. 605; 95%CI: 1.442-1.788) and mother (OR: 1.706; 95%CI: 1.530-1.903), having dental visit experiences (OR: 1.702; 95%CI: 1.589-1.823), rating one's oral health as good (OR: 2.341; 95%CI: 2.083-2.631), having fluoride knowledge (OR: 4.345; 95%CI: 4.034-4.678) and having a positive attitude towards regular dental check-ups (OR: 1.589; 95%CI: 1.460-1.729). CONCLUSIONS: The oral hygiene behaviours of Chinese adolescents were undesirable. Twice daily tooth brushing with fluoridated toothpaste was significantly associated with sociodemographic factors, fluoride knowledge, and attitudes towards regular dental check-ups.

Heavy metals in drinking water and periodontitis: evidence from the national oral health survey from China.

BACKGROUND: Periodontitis has become an increasingly important public health issue, coupled with a high economic burden for prevention and treatment. Exposure to essential trace heavy metals has been associated with various diseases; however, the relationships between essential trace heavy metals and periodontitis remain inconclusive. OBJECTIVES: To investigate the association between essential trace heavy metals in tap water and periodontitis in a nationally representative sample in China. METHODS: We conducted a nationwide study including 1348 participants from the Fourth National Oral Health Survey in the 2015-2016 period. The trace heavy metals concentration was measured in the local pipeline terminal tap water. Periodontitis was diagnosed according to the classification scheme proposed at the 2018 world workshop on the classification of periodontal and peri-implant diseases and conditions. We used weighted multivariable logistic regression to estimate the association between essential trace heavy metals and the risk of periodontitis. We additionally used spline analysis to explore the possible nonlinear dose-response associations. RESULTS: Periodontitis patients were exposed to higher concentrations of essential trace heavy metals. In adjusted models, for 1 SD increase in the concentration of iron, manganese, and copper in tap water, the risk of periodontitis increased by 30% (OR: 1.30, 95%CI: 1.12-1.50), 20% (OR: 1.20, 95%CI: 1.03-1.41), and 20% (OR: 1.20, 95%CI: 1.04-1.39), respectively. Stratified analyses demonstrated that the associations between essential trace heavy metals and periodontitis were higher in females, elders, and rural residents. Spline analysis revealed nonlinear exposure-response relationships between periodontitis and exposure to iron, manganese, and copper in tap water. CONCLUSIONS: Exposures to essential trace heavy metals in drinking water were associated with greater odds of periodontitis. Given the growing burden of periodontitis, our study sheds light on tailored public health policies for improving drinking water standards to alleviate periodontitis impairment.

Comparative effects of hepatocyte growth factor and tacrolimus on acute liver allograft early tolerance.

Allostimulated CD8+ T cells (aCD8+ T cells), as the main mediators of acute liver rejection (ARJ), are hyposensitive to apoptosis due to the inactivation of death receptor FAS-mediated pathways and fail to allow tolerance induction, eventually leading to acute graft rejection. Although tacrolimus (FK506), the most commonly used immunosuppressant (IS) in the clinic, allows tolerance induction, its use is limited because its target immune cells are unknown and it is associated with increased incidences of malignancy, infection, and nephrotoxicity, which substantially impact long-term liver transplantation (LTx) outcomes. The dark agouti (DA)-to-Lewis rat LTx model is a well-known ARJ model and was hence chosen for the present study. We show that both hepatocyte growth factor (HGF) (cHGF, containing the main form of promoting HGF production) and recombinant HGF (h-rHGF) exert immunoregulatory effects mainly on allogeneic aCD8+ T cell suppression through FAS-mediated apoptotic pathways by inhibiting cMet to FAS antagonism and Fas trimerization, leading to acute tolerance induction. We also showed that such inhibition can be abrogated by treatment with neutralizing antibodies against cMet (HGF-only receptor). In contrast, we did not observe these effects in rats treated with FK506. However, we observed that the effect of anti-rejection by FK506 was mainly on allostimulated CD4+ T cell (aCD4+ T cell) suppression and regulatory T cell (Treg) promotion, in contrast to the mechanism of HGF. In addition, the protective mechanism of HGF in FK506-mediated nephrotoxicity was addressed. Therefore, HGF as a tolerance inducer, whether used in combination with FK506 or as monotherapy, may have good clinical value. Additional roles of these T-cell subpopulations in other biological systems and studies in these fields will also be meaningful.

Comparative analysis of toxicity and metabolomic profiling of rac-glufosinate and L-glufosinate in zebrafish.

Glufosinate is a chiral pesticide, with commercial formulations such as racemic glufosinate (rac-glufosinate) and pure L-glufosinate enantiomer (L-glufosinate) on the market. There has been little research on the difference in toxicity to non-target organisms between these two main ingredients. The effects of rac-glufosinate and L-glufosinate on glutathione reductase (GR), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) levels in zebrafish were investigated in this study. The effect of two glufosinate agents at low concentrations (0.01 and 0.1 mg/L) on these four oxidative indicators was found to be significantly lower than that of high concentrations (1 and 10 mg/L). L-glufosinate had a stronger enhancing effect on CAT, GR, and MDA content than rac-glufosinate and a stronger inhibitory effect on SOD activity than rac-glufosinate. The researchers used ultra-high-performance liquid chromatography coupled with high-resolution mass spectroscopy metabolomics to compare rac-glufosinate and L-glufosinate for metabolic disorders in adult zebrafish. Stable and obvious metabolic maps of the two agents were obtained using multivariate statistical results, such as principal component analysis and orthogonal partial minimum discriminant analysis. Compared to the control group, the rac-glufosinate and L-glufosinate treatment groups shared 151 differential metabolites, which primarily affected zebrafish energy metabolism, amino acid metabolism, and other metabolic pathways. Caffeine metabolism and biotin metabolism were among the unique pathways disrupted in rac-glufosinate-exposed zebrafish. Contrarily, L-glufosinate treatment primarily affected eight metabolic pathways, including arginine biosynthesis, melanogenesis, and glutathione metabolism. These findings may provide more detailed information on the toxicity of rac-glufosinate and L-glufosinate in zebrafish, as well as some context for assessing the environmental risk of the two glufosinate agents to aquatic organisms.

Design, Synthesis, Antibacterial Activity, and Mechanism of Novel Mesoionic Compounds Based on Natural Pyrazole Isolated from an Endophytic Fungus Colletotrichum gloeosporioides.

Xanthomonas oryzae pv. oryzicola (Xoo) is a type of bacteria that causes bacterial leaf blight disease in rice plants. This disease is substantially harmful, and the current prevention and control measures are facing challenges. This study has investigated the effectiveness of the control activity that the endophytic fungus NS7 fermented from Dendrobium candidum possessed against Xoo. Twenty-eight novel mesoionic compounds were designed and synthesized based on the natural compound D. These compounds displayed moderate to excellent anti-Xoo activity in vitro. Notably, compound 24 exhibited prominent anti-Xoo activity in vitro with an EC50 value of 40.3 mg/L, which was better than that of the positive control thiodiazole copper (TC)(71.2 mg/L) and the lead compound D (108.1 mg/L). In vivo pot experiments on Xoo showed that compound 24 exhibited protective and curative activities of 39.4 and 30.4%, respectively, which were better than those of TC (35.7 and 28.8%, respectively). Further, a preliminary mechanism study indicated that compound 24 could enhance the activity of defense enzymes to improve the ability for anti-Xoo. Meanwhile, compound 24 could also regulate the carbon fixation in photosynthetic organisms, which might be related to the enhanced immune function of rice. This study offers a new strategy for discovering antibacterial agents based on natural products.

Degradation Dynamics and Residue Analysis of Four Propiconazole Stereoisomers in "Fengtang" Plum during Storage by LC-MS/MS.

Herein, an accurate and sensitive method was developed for detecting four stereoisomers of propiconazole in "Fengtang" plum by LC-MS/MS. The mean recovery of four propiconazole stereoisomers ranged from 79.42 to 104.10% at three adding levels with reasonable RSD of 1.54-11.68%, and the LOD and LOQ of the four stereoisomers was 0.0005 mg/kg and 0.004 mg/kg, respectively. In addition, the residue and selective degradation of propiconazole stereoisomers in plums were investigated by storage at 20 °C and 4 °C. The half-lives of propiconazole stereoisomeric during storage were 9.49-15.40 d at 20 °C, and 21.00-28.88 d at 4 °C. The degradation of (2R,4R)-propiconazole and (2R,4S)-propiconazole in stored plums was slightly slower than that of the corresponding enantiomers (2S,4S)-propiconazole and (2S,4R)-propiconazole. The total residues of propiconazole were 0.026-0.487 mg/kg in the plum storage period, and the water washing could remove 49.35% to 54.65% of the propiconazole residue in plum. The hardness of plums treated with propiconazole was generally higher than that of control in the middle and late stages of storage. The effects of propiconazole on the total soluble solid content of plums were different at 20 °C and 4 °C. This study provides a scientific reference for the food safety evaluation of the "Fengtang" plum after the application of propiconazole during the storage period.

Absolute Configuration, Enantioselective Bioactivity, and Mechanism Study of the Novel Chiral Fungicide Benzovindiflupyr.

Benzovindiflupyr has gained increasing attention as a new chiral succinate dehydrogenase inhibitor fungicide; however, its determination, bioactivity, and mechanism at the enantiomeric level are very limited. In the present study, optical rotation determination and X-ray single-crystal diffraction results identified that the absolute configurations were (+)-(1R,4S)-benzovindiflupyr and (-)-(1S,4R)-benzovindiflupyr. A quantitative determination method for enantiomers was established using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) for pesticide detection. The stereoselective bioactivity assay indicated that (-)-(1S,4R)-benzovindiflupyr exhibited greater potency than (+)-(1R,4S)-benzovindiflupyr against seven phytopathogenic fungi. Molecular docking analysis showed that (-)-(1S,4R)-benzovindiflupyr possessed a stronger binding affinity to succinate dehydrogenase than (+)-(1R,4S)-benzovindiflupyr. The binding modes between enantiomers and the mutant with H272(B) predicted that the phytopathogenic fungi with H272(B) of succinate dehydrogenase mutation would not be resistant to benzovindiflupyr enantiomers. This study provides a basis for residue evaluation, risk assessment, and the safe application of benzovindiflupyr at the enantiomer level.

Decomposing socioeconomic inequalities in dental caries among Chinese adults: findings from the 4th national oral health survey.

OBJECTIVE: This cross-sectional study aimed to investigate socioeconomic inequalities in dental caries among adults (35 years and older) in China and explore the contributions of various factors to these inequalities. METHODS: This study included 10,983 adults (3,674 aged 35-44 years, 3,769 aged 55-64 years and 3,540 aged 65-74 years) who participated in the 4th National Oral Health Survey (2015-2016) in China. Dental caries status was evaluated by the decayed, missing and filled teeth (DMFT) index. Concentration indices (CIs) were applied to quantify the different degrees of socioeconomic-related inequality in DMFT, decayed teeth with crown or root caries (DT), missing teeth due to caries or other reasons (MT), and filled teeth without any primary or secondary caries (FT) among adults of different age groups. Decomposition analyses were conducted to identify the determinants and their associations with inequalities in DMFT. RESULTS: The significant negative CI indicated that DMFT for the total sample were concentrated among socioeconomically disadvantaged adults (CI = - 0.06; 95% confidence interval [CI], - 0.073 to - 0.047). The CIs for DMFT for adults aged 55-64 and 65-74 years were - 0.038 (95% CI, - 0.057 to - 0.018) and - 0.039 (95% CI, - 0.056 to - 0.023), respectively, while the CI for DMFT for adults aged 35-44 years was not statistically significant (CI = - 0.002; 95% CI, - 0.022 to 0.018). The concentration indices of DT were negative and concentrated in disadvantaged populations, while FT showed pro-rich inequalities in all age groups. Decomposition analyses showed that age, education level, toothbrushing frequency, income and type of insurance contributed substantially to socioeconomic inequalities, accounting for 47.9%, 29.9%, 24.5%,19.1%, and 15.3%, respectively. CONCLUSION: Dental caries was disproportionately concentrated among socioeconomically disadvantaged adults in China. The results of these decomposition analyses are informative for policy-makers attempting to develop targeted health policy recommendations to reduce dental caries inequalities in China.