Association of the external environmental exposome and obesity: A comprehensive nationwide study in 2019 among Chinese children and adolescents.

OBJECTIVE: Children and adolescents are particularly vulnerable to the effects of various environmental factors, which could disrupt growth processes and potentially lead to obesity. Currently, comprehensive and systematic assessments of these environmental exposures during developmental periods are lacking. Therefore, this study aims to evaluate the association between external environmental exposures and the incidence of obesity in children and adolescents. METHODS: Data was collected from the 2019 Chinese National Survey on Students' Constitution and Health, including 214,659 Han children aged 7 to 19. Body Mass Index (BMI) and BMI-for-age z-score (zBMI) were the metrics used to assess overweight and obesity prevalence. The study assessed 18 environmental factors, including air pollutants, natural space, land cover, meteorological conditions, built environment, road conditions, and artificial light at night. Exposome-wide association study (ExWAS) to analyze individual exposures' associations with health outcomes, and Weighted Quantile Sum (WQS) to assess cumulative exposure effects. RESULTS: Among the children and adolescents, there were 24.2 % participants classified as overweight or obesity. Notably, 17 out of 18 environmental factors exhibited significant associations with zBMI and overweight/obesity. Seven air pollutants, road conditions, and built density were positively correlated with higher zBMI and obesity risk, while NDVI, forests, and meteorological factors showed negative correlations. Co-exposure analysis highlighted that SO2, ALAN, PM10, and trunk road density significantly increased zBMI, whereas rainfall, grassland, and forest exposure reduced it. Theoretically reduction in the number and prevalence of cases was calculated, indicating potential reductions in prevalence of up to 4.51 % for positive exposures and 5.09 % for negative exposures. Notably, substantial reductions were observed in regions with high pollution levels. CONCLUSION: This large-scale investigation, encompassing various environmental exposures in schools, highlights the significant impact of air pollution, road characteristics, rainfall, and forest coverage on childhood obesity.

Differentiated impacts of short-term exposure to fine particulate constituents on infectious diseases in 507 cities of Chinese children and adolescents: A nationwide time-stratified case-crossover study from 2008 to 2021.

This study assesses the association of short-term exposure to PM2.5 (particles ≤2.5 µm) on infectious diseases among Chinese children and adolescents. Analyzing data from 507 cities (2008-2021) on 42 diseases, it focuses on PM2.5 components (black carbon (BC), ammonium (NH4+), inorganic nitrate (NO3-), organic matter (OM), and sulfate (SO42-)). PM2.5 constituents significantly associated with incidence. Sulfate showed the most substantial effect, increasing all-cause infectious disease risk by 2.72 % per interquartile range (IQR) increase. It was followed by BC (2.04 % increase), OM (1.70 %), NO3- (1.67 %), and NH4+ (0.79 %). Specifically, sulfate and BC had pronounced impacts on respiratory diseases, with sulfate linked to a 10.73 % increase in seasonal influenza risk and NO3- to a 16.39 % rise in tuberculosis. Exposure to PM2.5 also marginally increased risks for gastrointestinal, enterovirus, and vectorborne diseases like dengue (7.46 % increase with SO42-). Sexually transmitted and bloodborne diseases saw an approximate 6.26 % increase in incidence, with specific constituents linked to diseases like hepatitis C and syphilis. The study concludes that managing PM2.5 levels could substantially reduce infectious disease incidence, particularly in China's middle-northern regions. It highlights the necessity of stringent air quality standards and targeted disease prevention, aligning PM2.5 management with international guidelines for public health protection.

Abscisic-acid-responsive StlncRNA13558 induces StPRL expression to increase potato resistance to Phytophthora infestans infection.

Late blight, caused by Phytophthora infestans, is one of the most serious diseases affecting potatoes (Solanum tuberosum L.). Long non-coding RNAs (lncRNAs) are transcripts with a length of more than 200 nucleotides that have no protein-coding potential. Few studies have been conducted on lncRNAs related to plant immune regulation in plants, and the molecular mechanisms involved in this regulation require further investigation. We identified and screened an lncRNA that specifically responds to P. infestans infection, namely, StlncRNA13558. P. infestans infection activates the abscisic acid (ABA) pathway, and ABA induces StlncRNA13558 to enhance potato resistance to P. infestans. StlncRNA13558 positively regulates the expression of its co-expressed PR-related gene StPRL. StPRL promotes the accumulation of reactive oxygen species and transmits a resistance response by affecting the salicylic acid hormone pathway, thereby enhancing potato resistance to P. infestans. In summary, we identified the potato late blight resistance lncRNA StlncRNA13558 and revealed its upstream and downstream regulatory relationship of StlncRNA13558. These results improve our understanding of plant-pathogen interactions' immune mechanism and elucidate the response mechanism of lncRNA-target genes regulating potato resistance to P. infestans infection.

Cytokinin oxidase gene CKX5 is modulated in the immunity of Arabidopsis to Botrytis cinerea.

In our previous work, cytokinin (CK) signaling and biosynthesis were found to be modulated during Arabidopsis defense against infection by the necrotrophic pathogen Botrytis cinerea. Notably, the expression level of CYTOKININ OXIDASE/DEHYDROGENASE 5 (CKX5) was significantly induced in B. cinerea-infected leaves and later in distant B. cinerea-untreated leaves of the same plant. To confirm and determine how CKX5 is involved in the response to B. cinerea infection, transcript levels of CKX family genes were analyzed in B. cinerea-inoculated leaves, and only CKX5 was remarkably induced by B. cinerea infection. Furthermore, CKX5-overexpressing Arabidopsis plants were more resistant to B. cinerea than wild-type plants. Transcription factors (TFs) binding to the CKX5 promoter were then screened by yeast one-hybrid assays. Quantitative Real-Time Reverse Transcription PCR (qRT-PCR) analysis further showed that genes encoding TFs, including WRKY40, WRKY33, ERF6, AHL15, AHL17, ANAC003, TCP13 and ANAC019, were also strongly induced in infected leaves, similar to CKX5. Analysis of ERF6-overexpressing plants and ERF6-and AHL15-knockout mutants indicated that ERF6 and AHL15 are involved in plant immunity to B. cinerea. Furthermore, CKX5 upregulation by B. cinerea infection was affected when ERF6 or AHL15 levels were altered. Our work suggests that CKX5 levels are controlled by the plant defense system to defend against attack by the pathogen B. cinerea.

The Natural Products as Novel Anti-obesity Agents: Mechanisms Based on Adipose Tissue.

Obesity presently stands as a formidable global public health concern, exerting a profound impact on human life and well-being. Despite the plethora of pharmacological interventions targeting obesity, their extensive use in clinical settings is hindered by the emergence of numerous adverse reactions during drug interventions. Naturally occurring compounds or extracts found in traditional Chinese medicine, fruits, and vegetables, possessing various attributes, such as metabolic modulation, thermogenic induction, appetite alteration, and inhibition of lipase activity and fat synthesis, have positioned themselves as potential anti-obesity pharmaceutical candidates. Promoting thermogenesis through the browning of adipose tissue, reducing fat tissue generation and ectopic deposition, along with the regulation of adipose factors, has emerged as a primary focus in the treatment of obesity. This shift underscores the pivotal role of adipose tissue as a critical target in obesity management. This study delves into various approaches based on adipose tissue, providing an overview of the efficacy of bioactive components derived from medicinal plants and fruits for treating obesity through adipose tissue modulation. Insights are drawn from both animal experiments and clinical applications, with a discussion of potential mechanisms underlying these effects. In conclusion, we have determined that natural compounds are significant candidates for the treatment of obesity, and adipose tissue represents a crucial target in the therapeutic process. We hope that our research will contribute novel perspectives for the development of future pharmaceuticals and dietary supplements, as well as provide innovative directions for clinical trials in the field.

High-throughput and genome-scale targeted mutagenesis using CRISPR in a nonmodel multicellular organism, Bombyx mori.

Large-scale genetic mutant libraries are powerful approaches to interrogating genotype-phenotype correlations and identifying genes responsible for certain environmental stimuli, both of which are the central goal of life science study. We produced the first large-scale CRISPR-Cas9-induced library in a nonmodel multicellular organism, Bombyx mori We developed a piggyBac-delivered binary genome editing strategy, which can simultaneously meet the requirements of mixed microinjection, efficient multipurpose genetic operation, and preservation of growth-defect lines. We constructed a single-guide RNA (sgRNA) plasmid library containing 92,917 sgRNAs targeting promoters and exons of 14,645 protein-coding genes, established 1726 transgenic sgRNA lines following microinjection of 66,650 embryos, and generated 300 mutant lines with diverse phenotypic changes. Phenomic characterization of mutant lines identified a large set of genes responsible for visual phenotypic or economically valuable trait changes. Next, we performed pooled context-specific positive screens for tolerance to environmental pollutant cadmium exposure, and identified KWMTBOMO12902 as a strong candidate gene for breeding applications in sericulture industry. Collectively, our results provide a novel and versatile approach for functional B. mori genomics, as well as a powerful resource for identifying the potential of key candidate genes for improving various economic traits. This study also shows the effectiveness, practicality, and convenience of large-scale mutant libraries in other nonmodel organisms.

Deep learning-based identification of eyes at risk for glaucoma surgery.

To develop and evaluate the performance of a deep learning model (DLM) that predicts eyes at high risk of surgical intervention for uncontrolled glaucoma based on multimodal data from an initial ophthalmology visit. Longitudinal, observational, retrospective study. 4898 unique eyes from 4038 adult glaucoma or glaucoma-suspect patients who underwent surgery for uncontrolled glaucoma (trabeculectomy, tube shunt, xen, or diode surgery) between 2013 and 2021, or did not undergo glaucoma surgery but had 3 or more ophthalmology visits. We constructed a DLM to predict the occurrence of glaucoma surgery within various time horizons from a baseline visit. Model inputs included spatially oriented visual field (VF) and optical coherence tomography (OCT) data as well as clinical and demographic features. Separate DLMs with the same architecture were trained to predict the occurrence of surgery within 3 months, within 3-6 months, within 6 months-1 year, within 1-2 years, within 2-3 years, within 3-4 years, and within 4-5 years from the baseline visit. Included eyes were randomly split into 60%, 20%, and 20% for training, validation, and testing. DLM performance was measured using area under the receiver operating characteristic curve (AUC) and precision-recall curve (PRC). Shapley additive explanations (SHAP) were utilized to assess the importance of different features. Model prediction of surgery for uncontrolled glaucoma within 3 months had the best AUC of 0.92 (95% CI 0.88, 0.96). DLMs achieved clinically useful AUC values (> 0.8) for all models that predicted the occurrence of surgery within 3 years. According to SHAP analysis, all 7 models placed intraocular pressure (IOP) within the five most important features in predicting the occurrence of glaucoma surgery. Mean deviation (MD) and average retinal nerve fiber layer (RNFL) thickness were listed among the top 5 most important features by 6 of the 7 models. DLMs can successfully identify eyes requiring surgery for uncontrolled glaucoma within specific time horizons. Predictive performance decreases as the time horizon for forecasting surgery increases. Implementing prediction models in a clinical setting may help identify patients that should be referred to a glaucoma specialist for surgical evaluation.

Functional analysis of a rice 12-oxo-phytodienoic acid reductase gene (OsOPR1) involved in Cd stress tolerance.

BACKGROUND: The accumulation of cadmium (Cd) in plants may compromise the growth and development of plants, thereby endangering human health through the food chain. Understanding how plants respond to Cd is important for breeding low-Cd rice cultivars. METHODS: In this study, the functions of 12-oxo-phytodienoic acid reductase 1 (OsOPR1) were predicted through bioinformatics analysis. The expression levels of OsOPR1 under Cd stress were analyzed by using qRT-PCR. Then, the role that OsOPR1 gene plays in Cd tolerance was studied in Cd-sensitive yeast strain (ycf1), and the Cd concentration of transgenic yeast was analyzed using inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Bioinformatics analysis revealed that OsOPR1 was a protein with an Old yellow enzyme-like FMN (OYE_like_FMN) domain, and the cis-acting elements which regulate hormone synthesis or responding abiotic stress were abundant in the promoter region, which suggested that OsOPR1 may exhibit multifaceted biological functions. The expression pattern analysis showed that the expression levels of OsOPR1 were induced by Cd stress both in roots and roots of rice plants. However, the induced expression of OsOPR1 by Cd was more significant in the roots compared to that in roots. In addition, the overexpression of OsOPR1 improved the Cd tolerance of yeast cells by affecting the expression of antioxidant enzyme related genes and reducing Cd content in yeast cells. CONCLUSION: Overall, these results suggested that OsOPR1 is a Cd-responsive gene and may has a potential for breeding low-Cd or Cd-tolerant rice cultivars and for phytoremediation of Cd-contaminated in farmland.

Opportunities for Improving Glaucoma Clinical Trials via Deep Learning-Based Identification of Patients with Low Visual Field Variability.

PURPOSE: Develop and evaluate the performance of a deep learning model (DLM) that forecasts eyes with low future visual field (VF) variability, and study the impact of using this DLM on sample size requirements for neuroprotective trials. DESIGN: Retrospective cohort and simulation study. METHODS: We included 1 eye per patient with baseline reliable VFs, OCT, clinical measures (demographics, intraocular pressure, and visual acuity), and 5 subsequent reliable VFs to forecast VF variability using DLMs and perform sample size estimates. We estimated sample size for 3 groups of eyes: all eyes (AE), low variability eyes (LVE: the subset of AE with a standard deviation of mean deviation [MD] slope residuals in the bottom 25th percentile), and DLM-predicted low variability eyes (DLPE: the subset of AE predicted to be low variability by the DLM). Deep learning models using only baseline VF/OCT/clinical data as input (DLM1), or also using a second VF (DLM2) were constructed to predict low VF variability (DLPE1 and DLPE2, respectively). Data were split 60/10/30 into train/val/test. Clinical trial simulations were performed only on the test set. We estimated the sample size necessary to detect treatment effects of 20% to 50% in MD slope with 80% power. Power was defined as the percentage of simulated clinical trials where the MD slope was significantly worse from the control. Clinical trials were simulated with visits every 3 months with a total of 10 visits. RESULTS: A total of 2817 eyes were included in the analysis. Deep learning models 1 and 2 achieved an area under the receiver operating characteristic curve of 0.73 (95% confidence interval [CI]: 0.68, 0.76) and 0.82 (95% CI: 0.78, 0.85) in forecasting low VF variability. When compared with including AE, using DLPE1 and DLPE2 reduced sample size to achieve 80% power by 30% and 38% for 30% treatment effect, and 31% and 38% for 50% treatment effect. CONCLUSIONS: Deep learning models can forecast eyes with low VF variability using data from a single baseline clinical visit. This can reduce sample size requirements, and potentially reduce the burden of future glaucoma clinical trials. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Responses of plant immune system and rhizosphere soil microbiome to the elicitor BAR11 in Arabidopsis thaliana.

Microbial elicitors have been shown to boost plant immunity by inducing defense responses to reduce plant disease. However, little is known about the changes in plant microbiome and metabolism in the process of enhancing plant immunity with elicitors. The protein elicitor BAR11, from Saccharothrix yanglingensis Hhs.015, induces defense responses in Arabidopsis thaliana that enhances resistance to pathogens. In this study, bar11 was inserted into Col-0 A. thaliana to obtain BAR11-Trans plant by Agrobacterium-mediated immersion transformation. BAR11-Trans exhibited an elevated defense level against Pseudomonas syringae pv. tomato DC3000 while experiencing a decline in biomass production of above-ground parts. In the process, BAR11-Trans increased the activity of phenylalanine ammonia lyase (PAL) and catalase (CAT), and up-regulated genes related to plant defense pathways. Furthermore, BAR11-Trans decreased root tip reactive oxygen species (ROS) levels while increasing ROS burst in the leaves. Soil transplantation experiments showed that soil planted with BAR11-Trans could enhance the resistance of Col-0 A. thaliana to DC3000. Analysis of A. thaliana rhizosphere soil through 16S rRNA amplified sequencing revealed that BAR11-Trans increased the relative abundance and diversity of the rhizosphere microbial community, leading to the recruitment of more plant probiotics. Additionally, the accumulation of kaempferitrin and robinin in BAR11-Trans influenced the physicochemical properties of rhizosphere soil and the composition of the bacterial community. In summary, BAR11-Trans exhibited heightened defense levels compared to Col-0, leading to increased secretion of secondary metabolites and the recruitment of a greater number of microorganisms to adapt to the environment. These findings offer novel insights for the potential application of elicitors in agricultural disease control.

Genome-wide CRISPR screening reveals key genes and pathways associated with 20-hydroxyecdysone signal transduction in the silkworm (Bombyx mori).

Metamorphosis is a complex developmental process involving multiple pathways and a large number of genes that are regulated by juvenile hormone (JH) and 20-hydroxyecdysone (20E). Despite important progress in understanding various aspects of silkworm biology, the hormone signaling pathway in the silkworm remains poorly understood. Genome-wide screening using clustered regularly interspaced short palindromic repeats (CRISPR) / CRISPR-associated protein 9 (Cas9)-based libraries has recently emerged as a novel method for analyzing genome function, enabling further research into essential genes, drug targets, and virus-host interaction. Previously, we constructed a genome-wide CRISPR/Cas9-based library of the silkworm (Bombyx mori) and successfully revealed the genes involved in biotic or abiotic stress factor responses. In this study, we used our silkworm CRISPR library and large-scale genome-wide screening to analyze the key genes in the silkworm 20E signaling pathway and their mechanisms of action. Functional annotation showed that 20E regulates key proteins in processes that mainly occur in the cytoplasm and nucleus. Pathway enrichment analysis showed that 20E can activate phosphorylation and may affect innate immunity, interfere with intracellular nutrition and energy metabolism, and eventually cause cell apoptosis. The screening results were experimentally validated by generating cells with knockout alleles of the relevant genes, which had increased tolerance to 20E. Our findings provide a panoramic overview of signaling in response to 20E in the silkworm, underscoring the utility of genome-wide CRISPR mutant libraries in deciphering hormone signaling pathways and the mechanisms that regulate metamorphosis in insects.

Significant enhancement in antioxidant and antimicrobial activity of tragacanth gum through chemical modification using amino acids.

Herein, glutamic acid, lysine, arginine and glycine grafted tragacanth gum (TG) were synthesized and designated as TG-Glu, TG-Lys, TG-Arg, and TG-Gly, respectively. The corresponding degrees of substitution (DS) were 0.212, 0.255, 0.394, and 0.169. Thermal, antioxidant, and antibacterial properties of synthesized amino acid-grafted tragacanth gum (ATG) were investigated. The results suggested that the grafting of amino acids onto TG has the potential to alter its thermal properties. When compared with TG and amino acid alone, ATG exhibited significantly enhanced antioxidant and antibacterial properties, with these properties being concentration-dependent. At a concentration of 2 mg/mL for TG-Glu and 3 mg/mL for TG-Arg, TG-Gly, and TG-Lys, the scavenging rate for 2,2'-hypoazido-3-ethylbenzothiazoline sulfonate (ABTS) radical reached 100 %. On the other hand, the scavenging rate of TG-Glu for hydroxyl radical achieved 100 % even at a concentration as low as 1 mg/mL. These properties were accompanied by an increase in reducing force and a notable improvement in the ability to scavenge superoxide anion (O2-). Moreover, the combination of amino acids and TG represents a promising approach to enhance the antimicrobial activities of TG, with the bacteriostatic rate reaching 100 %. Consequently, ATG shows promise as a novel agent for both antioxidation and antimicrobial applications.

Target-site and non-target-site based resistance to clodinafop-propargyl in wild oats (Avena fatua L.).

Wild oat (Avena fatua L.) is a common and problematic weed in wheat fields in China. In recent years, farmers found it increasingly difficult to control A. fatua using acetyl-CoA carboxylase (ACCase)-inhibiting herbicides. The purpose of this study was to identify the molecular basis of clodinafop-propargyl resistance in A. fatua. In comparison to the S1496 population, whole dose response studies revealed that the R1623 and R1625 populations were 71.71- and 67.76-fold resistant to clodinafop-propargyl, respectively. The two resistant A. fatua populations displayed high resistance to fenoxaprop-p-ethyl (APP) and low resistance to clethodim (CHD) and pinoxaden (PPZ), but they were still sensitive to the ALS inhibitors mesosulfuron-methyl and pyroxsulam. An Ile-2041-Asn mutation was identified in both resistant individual plants. The copy number and relative expression of the ACCase gene in the resistant population were not significantly different from those in the S1496 population. Under the application of 2160 g ai ha -1 of clodinafop-propargyl, the fresh weight of the R1623 population was reduced to 74.9%; however, pretreatment with the application of the cytochrome P450 inhibitor malathion and the GST inhibitor NBD-Cl reduced the fresh weight to 50.91% and 47.16%, respectively, which proved the presence of metabolic resistance. This is the first report of an Ile-2041-Asn mutation and probable metabolic resistance in A. fatua, resulting in resistance to clodinafop-propargyl.

ALS gene overexpression and enhanced metabolism conferring Digitaria sanguinalis resistance to nicosulfuron in China.

Crabgrass (Digitaria sanguinalis) is a common malignant weed in corn fields in China. Recently, the acetolactate synthase (ALS) inhibitor, nicosulfuron, has shown decreasing efficacy against crabgrass. In order to elucidate the molecular basis of resistance to nicosulfuron in crabgrass, we conducted bioassays, combined with gene sequence analysis, relative expression and relative copy number analysis, to characterize resistance in crabgrass populations collected from Beijing, Heilongjiang, Jilin and Anhui provinces. Whole-plant dose-response results indicated that only population collected in Heilongjiang province (HLJ) had developed low level of resistance to nicosulfuron compared with the sensitive population (SD22). No known resistant mutation of ALS gene was found in HLJ population. The real-time fluorescence quantitative PCR results showed that the ALS gene copy number did not differ significantly between the HLJ and SD22 populations. However, the ALS gene expression in the HLJ was 2.07-fold higher than that of the SD22 population at 24 h after treatment with nicosulfuron. Pretreatment with the cytochrome P450 (CYP450) inhibitor malathion, piperonyl butoxide (PBO), and the glutathione S-transferase (GST) inhibitor 4-Chloro-7-nitro-1,2,3-benzoxadiazole (NBD-Cl) all partially reversed HLJ resistance. Among them, the synergistic effect of PBO and nicosulfuron is the most significant. This is the first report of resistance to nicosulfuron in crabgrass through ALS gene overexpression and possible metabolic resistance.

Traditional Chinese Medicine in the treatment of hemorrhoids-a review of preparations used and their mechanism of action.

Hemorrhoids are a proctological disease primarily characterized by bleeding, prolapse, edema, and pain, severely affecting the quality of life. Surgery is an effective treatment for hemorrhoids, but the cost is relatively high, and complications such as difficulty in defecation, persistent pain, and heavy bleeding may occur postoperatively. Traditional Chinese Medicine (TCM) has a distinctive advantage in alleviating the clinical symptoms of hemorrhoid patients, reducing pain, and improving the quality of life. However, there are few summary literature about the mechanism of TCM in the prevention and treatment of hemorrhoids. Based on the etiology of hemorrhoids in both traditional Chinese and Western medicine, this paper reviews the recent research on the mechanism of TCM in the treatment of hemorrhoids, hoping to provide a basis for the better application of TCM in clinical and experimental research.

Identification of an Acinetobacter pittii acyltransferase involved in transformation of deoxynivalenol to 3-acetyl-deoxynivalenol by transcriptomic analysis.

Deoxynivalenol (DON), a mycotoxin primarily produced by Fusarium graminearum (F. graminearum), is widely present in food and feed, posing great hazards to human and livestock health. In this study, a strain of Acinetobacter pittii (A. pittii) S12 capable of degrading DON was isolated from soil samples and identified through morphological characterization, biochemistry analysis, and 16 S rRNA gene sequencing. The results of HPLC-MS indicated that the degradation products underwent a conversion from [M-H]- to [M+CH3CO], with concomitant transformation of the hydroxyl group into an acetyl moiety. Based on transcriptome sequencing analysis, the acyltransferase encoded by DLK06_RS13370 was predicted to be the pivotal gene responsible for DON biotransformation. The result of molecular docking analysis suggest a high affinity between the enzyme and DON. The recombinant protein encoded by DLK06_RS13370 was expressed in Escherichia coli (E. coli) and demonstrated the capacity to catalyze the conversion of DON into 3-Acetyl-deoxynivalenol (3-ADON), as confirmed by HPLC analysis. In conclusion, our findings confirm that the acyltransferase encoded by DLK06-RS13370 is responsible for the acetylation of DON. This sheds light on the co-occurrence of DON and its acetyl-derivatives in wheat-based products. DATA AVAILABILITY: Not applicable.

Advances in sulfonated modification and bioactivity of polysaccharides.

Polysaccharides, as biological macromolecules, are widely found in plants, animals, fungi, and bacteria and exhibit various biological activities. However, many natural polysaccharides exhibit low or non-existent biological activities because of their high molecular weights and poor water solubility, limiting their application in many fields. Sulfonation is one of the most effective chemical modification methods to improve physicochemical properties and biological activities of natural polysaccharides or even impart natural polysaccharides with new biological activities. Therefore, sulfonated polysaccharides have attracted increasing attention because of their antioxidant, anticoagulant, antiviral, and immunomodulatory properties. This paper reviews the recent advances in the sulfonation of polysaccharides, including preparation, characterization, and biological activities of sulfonated polysaccharides, and provides a theoretical basis for wide applications of sulfonated polysaccharides.

Comparison of CT Values between Thrombus and Postmortem Clot Based on Cadaveric Pulmonary Angiography.

OBJECTIVES: To explore the difference in CT values between pulmonary thromboembolism and postmortem clot in postmortem CT pulmonary angiography (CTPA) to further improve the application value of virtual autopsy. METHODS: Postmortem CTPA data with the definite cause of death from 2016 to 2019 were collected and divided into pulmonary thromboembolism group (n=4), postmortem clot group (n=5), and control group (n=5). CT values of pulmonary trunk and left and right pulmonary artery contents in each group were measured and analyzed statistically. RESULTS: The average CT value in the pulmonary thromboembolism group and postmortem clot group were (168.4±53.8) Hu and (282.7±78.0) Hu, respectively, which were lower than those of the control group (1 193.0±82.9) Hu (P<0.05). The average CT value of the postmortem clot group was higher than that of the pulmonary thromboembolism group (P<0.05). CONCLUSIONS: CT value is reliable and feasible as a relatively objective quantitative index to distinguish pulmonary thromboembolism and postmortem clot in postmortem CTPA. At the same time, it can provide a scientific basis to a certain extent for ruling out pulmonary thromboembolism deaths.

Molecular Characterization of Resistance to Nicosulfuron in Setaria viridis.

The green foxtail, Setaria viridis (L.) P. Beauv. (Poales: Poaceae), is a troublesome and widespread grass weed in China. The acetolactate synthase (ALS)-inhibiting herbicide nicosulfuron has been intensively used to manage S. viridis, and this has substantially increased the selection pressure. Here we confirmed a 35.8-fold resistance to nicosulfuron in an S. viridis population (R376 population) from China and characterized the resistance mechanism. Molecular analyses revealed an Asp-376-Glu mutation of the ALS gene in the R376 population. The participation of metabolic resistance in the R376 population was proved by cytochrome P450 monooxygenases (P450) inhibitor pre-treatment and metabolism experiments. To further elucidate the mechanism of metabolic resistance, eighteen genes that could be related to the metabolism of nicosulfuron were obtained bythe RNA sequencing. The results of quantitative real-time PCR validation indicated that three ATP-binding cassette (ABC) transporters (ABE2, ABC15, and ABC15-2), four P450 (C76C2, CYOS, C78A5, and C81Q32), and two UDP-glucosyltransferase (UGT) (UGT13248 and UGT73C3), and one glutathione S-transferases (GST) (GST3) were the major candidates that contributed to metabolic nicosulfuron resistance in S. viridis. However, the specific role of these ten genes in metabolic resistance requires more research. Collectively, ALS gene mutations and enhanced metabolism may be responsible for the resistance of R376 to nicosulfuron.

The roles of AMPK/mTOR autophagy pathway in the acute kidney injury-induced acute lung injury.

Acute kidney injury (AKI) is one of the most challenging clinical problems in kidney disease due to serious complications and high mortality rate, which can lead to acute lung injury (ALI) through inflammatory reactions and oxidative stress. Adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway has been reported to be involved in the development of renal ischemia-reperfusion through autophagy and it remains unclear whether AMPK/mTOR pathway has an effect on the AKI-induced ALI. In this study, we aimed to investigate the effects of autophagy-related AMPK/mTOR signaling pathway on inflammatory factors and oxidative stress in an AKI-induced ALI model. The 48 male Sprague-Dawley rats were divided into four groups randomly: (i) sham, (ii) ischemia/reperfusion injury (IRI), (iii) IRI + rapamycin (RA), and (iv) IRI + 3-methyladenine (3-MA). Unilateral flank incisions were made and right kidneys were excised. The left kidney was subjected to 60 min of ischemia followed by 12, 24, 48, and 72 h of reperfusion. The levels of Scr, blood urea nitrogen (BUN), Wet/Dry ratio, indexes of inflammation, and oxidative stress were assayed. Histological examinations were performed. The protein expression of AMPK, mTOR, LC3-II/LC3-I ratio, and Beclin-1, ULK1 was evaluated by western blotting and immunohistochemistry. Compared to the rats from the sham group, IRI rats showed significantly pulmonary damage after AKI with increased Scr, BUN, Wet/Dry ratio, indexes of inflammation, and oxidative stress. The expression of AMPK, LC3-II/LC3-I ratio, Beclin-1, and ULK1 and were increased, while p62 and mTOR were decreased. In addition, RA treatment significantly attenuated lung injury by promoting autophagy through the activation of the AMPK/mTOR pathway, and 3-MA treatment exhibited adverse effects inversely. Therefore, the activation of the AMPK/mTOR pathway after renal IRI induction could significantly attenuate kidney injury and following AKI-induced ALI by inducing autophagy, which alienates inflammation, oxidative stress, and apoptosis.