ObjectiveTo investigate the migration and distribution characteristics of chemical constituents in blood and hippocampal tissues before and after vinegar processing of Citri Reticulatae Pericarpium Viride（CRPV）， and to explore the potential material basis and mechanisms underlying their regulatory effects on emotional disorders by comparing the effects of raw and vinegar-processed products of CRPV. MethodsUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was employed to characterize and identify the chemical constituents of raw and vinegar-processed products of CRPV extracts， as well as their migrating components in blood and hippocampal tissues after oral administration. Reference standards， databases， and relevant literature were utilized for compound annotation， with data processing performed using PeakView 1.2 software. Seventy male C57BL/6 mice were randomly divided into seven groups， including the blank group， model group， diazepam group（2.5 mg·kg^-1）， raw CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， and vinegar-processed CRPV low/high dose groups（0.6， 1.2 g·kg^-1）， with 10 mice per group. Except for the blank group， all other groups underwent chronic restraint stress（2 h·d^-1） for 20 d. Each drug-treated group received oral administration at the predetermined dose starting 10 d after modeling， with a total treatment duration of 10 d. Following model-based drug administration， mice underwent open-field， forced swimming， and elevated plus maze tests. After anesthesia with isoflurane， whole brains were collected from each group of mice， and hippocampi were dissected. Reactive oxygen species（ROS） level in hippocampal tissues was quantified by enzyme-linked immunosorbent assay（ELISA）. Hematoxylin-eosin（HE） staining was used to observe hippocampal tissue morphology. Immunofluorescence was performed to detect neuronal nuclei（NeuN） and peroxisome proliferator-activated receptor alpha（PPARα） expressions in hippocampal tissue. Then， pharmacodynamic evaluations were conducted to assess the effects of raw and vinegar-processed CRPV on mood disorders， exploring the potential mechanisms. ResultsVinegar processing caused significant changes in the chemical composition of CRPV， with 18 components showing increased relative content and 35 components showing decreased relative content. The primary changes occurred in flavonoid compounds， including 20 flavonoids， 20 flavonoid glycosides， 3 triterpenes， 3 phenolic acids， 1 alkaloid， and 6 other compounds. Twenty-one components were detected in blood（15 methoxyflavones， 4 flavonoid glycosides， and 2 phenolic acids）， with 17 shared between raw and vinegar-processed CRPV. Seven components reached hippocampal tissues（all common to both forms）. In regulating emotional disorders， Vinegar-processed CRPV exhibited superior antidepressant-like effects compared to raw products. HE staining revealed that both treatments improved hippocampal neuronal morphology， particularly in the damaged CA1 and CA3 regions. Immunofluorescence and ELISA analyses demonstrated that both raw and vinegar-processed CRPV significantly modulated NeuN and PPARα expressions in hippocampal tissue while alleviating oxidative stress induced by excessive ROS（P<0.05）. ConclusionThe chemical composition of CRPV undergoes changes after vinegar processing， but the migrating components in blood and hippocampus are primarily methoxyflavonoids. These components may serve as the potential material basis for activating the PPARα pathway， thereby negatively regulating ROS generation in the hippocampus， reducing oxidative stress， and promoting the development of NeuN-positive neurons. These findings provide experimental evidence for enhancing quality standards， pharmacodynamic material research， and active drug development of raw and vinegar-processed CRPV.

ObjectiveTo explore the spatial distribution patterns of flavonoid glycosides in Epimedium sagittatum and the influences of environmental factors on the accumulation of these components. MethodsThe spatial statistical analysis and GeoDetector model were used to analyze the distribution patterns of epimedin A，epimedin B，epimedin C，icariin，and total flavonoid glycosides in E. sagittatum samples from 92 different production areas in 36 cities of 13 provinces/municipalities/autonomous regions of China，as well as the effects of 28 environmental factors on the accumulation of each component. ResultsThe average content of flavonoid glycosides 64 （69.56%） producing areas and 30 （83.33%） cities met the quality standard of no less than 1.50% of total flavonoid glycosides in the 2020 edition of Chinese Pharmacopoeia.Epimedin A，epimedin B，epimedin C，icariin，and their sum showed significantly high accumulation.The hot spots regions of epimedin A and epimedin B were similar with each other，mainly located in western Hunan，eastern Hubei，eastern Guizhou，and northern Guangxi.The common hot spot areas of epimedin C and total flavonoid glycosides were in western and southwestern Hunan，southern Henan，northern Anhui，eastern Guizhou，and southern Chongqing.The hot spots areas of icariin were in southern Chongqing，western Hunan，and eastern and northeastern Guizhou.The interactions between environmental factors had stronger explanatory power for the accumulation of components than single factors.The strongest single factor and interactive factor affecting the accumulation of epimedin C were precipitation of wettest quarter （q=0.16） and its interaction with temperature seasonality （q=0.35），respectively.The strongest single factor influencing both the accumulation of icariin and total flavonoid glycosides was the precipitation of coldest quarter （q equals 0.15 and 0.22，respectively）.The strongest interactions were observed between precipitation of coldest quarter and gravel content （q=0.34），as well as between precipitation of coldest quarter and aspect （q=0.35）. ConclusionThirteen cities，including Zhumadian and Nanyang in Henan，Huaihua，Shaoyang，and Zhangjiajie in Hunan，and Zunyi，Qiandongnan，and Tongren in Guizhou，were hot spots of total flavonoid glycosides in E.sagittatum.Precipitation，gravel content，temperature seasonality，and aspect significantly influence the accumulation of flavonoid glycosides in E.sagittatum.This study provides reference for the utilization and production zoning of E.sagittatum.

Bombesin receptor subtype-3 (BRS3) is an orphan G protein-coupled receptor (GPCR) that plays critical roles in energy homeostasis, glucose metabolism, and insulin secretion. Recent structural studies have elucidated BRS3 signaling mechanisms using synthetic ligands, including BA1 and MK-5046. However, the molecular basis of BRS3 activation by bioactive natural compounds and their derivatives, particularly those derived from traditional Chinese medicine, remains unclear. Here, we present high-resolution cryogenic electron microscopy (cryo-EM) structures of the human BRS3-G_q complex in both unliganded and active states bound by two herb-derived compounds (DSO-5a and oridonin), at resolutions of 2.9, 2.8, and 2.9 Å, respectively. These structures display distinct ligand recognition patterns between DSO-5a and oridonin. Although both compounds bind to the orthosteric pocket, they differentially engage the interaction network of BRS3, as demonstrated by mutagenesis studies assessing calcium mobilization and inositol phosphate 1 (IP1) accumulation. These findings enhance our understanding of BRS3 activation and provide valuable insights into the development of small-molecule BRS3 modulators with therapeutic potential.

Rice (Oryza sativa L.) is an important food crop. The appearance of lesion mimics in rice leads to phytohormone disorders, which affects rice adaptation to environmental stresses and ultimately reduces the yield and quality. To explore whether the changes in the adaptability of rice lesion-mimic mutants to stressful environments are caused by the disorder of phytohormone metabolism in plants. In this study, we screened an ethyl methane sulfonate-treated population of the japonica cultivar 'Taipei 309' for a mutant with rust-like spots on leaves at the early tillering stage and brown-red spots at maturity and named it rsl1 (rust spotted leaf 1). Compared with the wild type, rsl1 showed decreases in plant height, panicle length, primary branch number, secondary branch number, filled grains per panicle, seed-setting rate, and 1 000-grain weight, and an increase in number of effective panicles. Genetic analysis indicated that rsl1 was controlled by a single recessive nuclear gene. RSL1 was localized between two molecular markers, B7-7 and B7-9, on rice chromosome 7 by map-based cloning. PCR sequencing of the annotated genes in this interval revealed a mutation of C1683A on the eighth exon of SPL5 (LOC_Os07g10390) in rsl1, which resulted in premature termination of protein translation. Exogenous phytohormone treatments showed that rsl1 was less sensitive to salicylic acid (SA), abscisic acid (ABA), and indo-3-acetic acid (IAA) and more sensitive to methyl jasmonate (MeJA) and gibberellin acid (GA) than the wild type. In addition, the survival rate of rsl1 was lower than that of the wild type under salt, alkali, drought, and high temperature stresses, and it was higher than that of the wild type under cold stress. Quantitative real-time polymerase chain reaction (qRT-PCR) results showed that RSL1 was involved in the regulation of ABA, SA, MeJA, IAA, and GA-related genes under abiotic stresses. The present study showed that the RSL1 mutation led to the appearance of lesion mimics and affected the growth, development, and stress resistance of rsl1 under abiotic stresses. The study of the functional mechanism of this gene can provide theoretical guidance for the research on rice stress resistance.
Oryza/microbiology* ; Stress, Physiological/genetics* ; Plant Diseases/genetics* ; Cloning, Molecular ; Chromosome Mapping ; Plant Growth Regulators/metabolism* ; Plant Proteins/genetics* ; Mutation ; Cyclopentanes ; Genes, Plant ; Plant Leaves/genetics* ; Oxylipins

Synthetic biology, recognized as one of the most revolutionary interdisciplinary fields in the 21st century, has established innovative strategies for the genetic improvement of rice through the integration of multidisciplinary technologies including genome editing, genetic circuit design, metabolic engineering, and artificial intelligence. This review systematically summarizes recent research advancements and breakthrough achievements in the application of synthetic biology in the genetic improvement of rice, focusing on three critical domains: yield improvement, nutritional quality fortification, and reinforcement of disease resistance and abiotic stress tolerance. It elucidates that synthetic biology enables precise genomic and metabolic pathway engineering through modular, standard, and systematic approaches, effectively overcoming the limitations of conventional breeding methods characterized by prolonged cycles and restricted trait modification capabilities. The implementation of synthetic biology has facilitated synergistic improvement of multi-traits, thereby providing critical technical references for developing elite rice cultivars with superior productivity and nutritional value. These technological breakthroughs hold significant implications for ensuring global food security and promoting green and sustainable development of agriculture.
Oryza/growth & development* ; Synthetic Biology/methods* ; Metabolic Engineering ; Plant Breeding/methods* ; Gene Editing ; Genetic Engineering/methods* ; Plants, Genetically Modified/genetics* ; Disease Resistance/genetics*

Objective:To clarify the potential correlation between biological changes of meninges in periodontitis mice and cognitive impairment by analyzing the biological changes of meninges in periodontitis mice using single-cell RNA sequencing.Methods:Thirty C57BL/6 mice were divided into two groups by using random number table method (15 mice in each group). Mice in the control group were locally administered 2% carboxyl methyl cellulose (CMC) without Porphyromonas gingivalis (Pg) on both buccal sides. A mixture of Pg W83 and 2% CMC was applied on both buccal sides in the experimental group mice three times a week, lasting for 16 weeks in total. The absorption of alveolar bone, locomotor activity and cognitive function, the activation of microglia and astrocytes in the cortex were observed and assessed. The mRNA expression levels of Occludin in meninges and brain were detected in two groups. Single-cell RNA sequencing data of meninges were processed by uniform manifold approximation and projection (UMAP). Differential genes expressions of endothelial cells were processed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In addition, real-time fluorescence quantitative PCR (RT-qPCR) was used to verify the expressions of transcription activating factor 3 (Atf3) and apolpoprotein L domain-containing 1 (Apold 1). Results:Methylene blue staining found the distances of buccal and palatal cement-enamel junction-alveolar bone crest in experimental mice [(185.60±17.60), (206.90±13.37) μm] increased significantly compared with the control group [(135.33±9.57), (163.05±14.98) μm] ( t=5.02, P=0.002; t=4.37, P=0.005). Open field experiment showed the total distance and average speed of mice in the experimental group [(971.88±164.57) cm, (3.25±0.55) cm/s] were not statistically significant compared with the control group [(914.24±278.81) cm, (3.05±0.93) cm/s] ( t=0.65, P=0.525; t=0.65, P=0.520). The recognition index of the experimental group [(48.02±16.92) %] was lower than the control group [(66.27±17.90) %] ( t=2.40, P=0.027) by novel object recognition tests. Compared with the control group [(63.56±11.88) %], the alternation of experimental group [(50.99±14.17) %] was significantly decreased in Y maze tests ( t=2.33, P=0.030). Immunohistochemistry results showed microglia and astrocytes were activated in the cortex of experimental mice. Compared with the control group (1.02±0.25, 1.04±0.31), the relative mRNA expressions of Occludin decreased significantly in the meninges and brain of periodontitis mice, respectively (0.61±0.10, 0.64±0.20) ( t=3.47, P=0.010; t=2.66, P=0.024). By single-cell RNA sequencing, meninges cells were divided into 11 types, such as endothelial cells, fibroblasts, immune cells and so on. Endothelial cells were the main cell types in meninges [the control group: 26.47% (1 589/6 004), the experimental group: 26.26% (807/3 073)]. Compared with the control group [5.56% (334/6 004)], the percentage of granulocytes increased in the periodontitis mice [11.65% (358/3 073)]. Using clustering analysis to further focus on endothelial cells, GO enrichment analysis revealed differential genes were mainly related to angiogenesis, cell adhesion, apoptosis and so on. KEGG enrichment analysis revealed that differential genes were related to signaling pathways of interleukin-17, relaxin and so on. The relative mRNA expressions of Atf3 and Apold1 in meninges of periodontitis mice (0.42±0.24, 0.54±0.27) were significantly lower than the control group (1.03±0.26, 1.02±0.23) ( t=3.88, P=0.005; t=3.02, P=0.017). Conclusions:The mice chronically infected with Pg W83 occurred memory impairment, neuroinflammation and changes of barrier function. In the meninges of periodontitis mice, there were infiltration of immune cells and down-regulation expressions of Atf3 and Apold1 by single-cell RNA sequencing. Meningeal immunity and changes of barrier function may play an important role in the cognitive impairment caused by periodontitis.

Background::Substantial progress in air pollution control has brought considerable health benefits in China, but little is known about the spatio-temporal trends of economic burden from air pollution. This study aimed to explore their spatio-temporal features of disease burden from air pollution in China to provide policy recommendations for efficiently reducing the air pollution and related disease burden in an era of a growing economy.Methods::Using the Global Burden of Disease method and willingness to pay method, we estimated fine particulate matter (PM 2.5) and/or ozone (O 3) related premature mortality and its economic burden across China, and explored their spatio-temporal trends between 2005 and 2017. Results::In 2017, we estimated that the premature mortality and economic burden related to the two pollutants were RMB 0.94 million (68.49 per 100,000) and 1170.31 billion yuan (1.41% of the national gross domestic product [GDP]), respectively. From 2005 to 2017, the total premature mortality was decreasing with the air quality improvement, but the economic burden was increasing along with the economic growth. And the economic growth has contributed more to the growth of economic costs than the economic burden decrease brought by the air quality improvement. The premature mortality and economic burden from O 3 in the total loss from the two pollutants was substantially lower than that of PM 2.5, but it was rapidly growing. The O 3-contribution was highest in the Yangtze River Delta region, the Fen-Wei Plain region, and some western regions. The proportion of economic burden from PM 2.5 and O 3 to GDP significantly declined from 2005 to 2017 and showed a decreasing trend pattern from northeast to southwest. Conclusion::The disease burden from O 3 is lower than that of PM 2.5, the O 3-contribution has a significantly increasing trend with the growth of economy and O 3 concentration.

Objective:To evaluate the clinical efficacy and safety of endoscopic ultrasound (EUS)-guided coil implantation combined with glue injection for preventing rebleeding of tumorous gastric fundal varices.Methods:A retrospective analysis was performed on the clinical data of patients who underwent EUS-guided coil implantation combined with glue injection due to tumorous gastric fundal variceal bleeding from September 2017 to December 2020 in the First Affiliated Hospital, Zhejiang University School of Medicine. The basic characteristics and endoscopic manifestations of patients treated with this technique were analyzed, and the success rate of this technique, the usage of tissue glue and coil, the variceal obliteration rate and the incidence of complications such as pulmonary embolism were analyzed. Patients were followed up over a long period of time to obtain data on rebleeding. At the same time, patients were divided into complete obliteration group and incomplete obliteration group according to the endoscopic performance after the treatment, and the rebleeding rate in the two groups was compared.Results:Among the 41 patients included in this study, 18 cases (43.90%) had single isolated gastric varices type 1, and 23 cases (56.10%) had gastroesophageal varices combined. Fourteen cases had signs of recent bleeding such as thrombi and ulcers under endoscopy, and 13 cases had combined portal hypertensive gastropathy. All patients successfully completed the operation of EUS-guided coil implantation combined with glue injection. The technical success rate for the first attempt was 92.68% (38/41). The one-time pre-installation success rate of coils was 95.12% (39/41). The success rate of target vessel aspiration under EUS guidance was 100.00% (41/41). The release success rate of coil was 97.56% (40/41). The number of coils used was 1.12±0.33, and the amount of tissue glue used after inserting the coils was 1.54±0.46 mL. The target vessel obliteration rate after operation was 97.56% (40/41), and the complete gastric fundal variceal obliteration rate was 51.22% (21/41). There were 2 cases (4.88%) of intraoperative bleeding, 1 case stopped spontaneously, and 1 case successfully stopped bleeding after additional injection of tissue glue under direct endoscopic vision. No patient had symptoms of pulmonary embolism such as decreased oxygen saturation during the operation. Postoperative computed tomography angiography of pulmonary artery or lung computed tomography was performed in 24 cases, of which 1 case (4.17%) showed distal pulmonary artery embolism, but there were no relevant clinical manifestations. The patients were followed up for 21.64±16.86 months (1-50 months) after the surgery. There were 13 cases (31.71%) of recurrent gastrointestinal bleeding after the surgery, no rebleeding within 5 days, 2 cases of rebleeding within 3 months, 5 cases from 3 to 12 months, and 6 cases more than 1 year. Among the 13 cases of recurrent bleeding after the surgery, the recurrence rate of bleeding after operation in the complete obliteration group was 23.81% (5/21), which was lower than that in the incomplete obliteration group with 40.00% (8/20), but there was no statistically significant difference ( χ2=1.240, P=0.265). Conclusion:EUS-guided coil implantation combined with glue injection has good secondary prevention value and safety for tumorous gastric fundal variceal bleeding, and is worthy of clinical promotion and application.

Objective:To understand the status quo and influencing factors of evidence-based nursing competencies among oncology nurses and provide a reference for enhancing this competency among oncology nurses.Methods:From September 2022 to January 2023, totally 300 practicing nurses from Zhejiang Cancer Hospital were selected by convenience sampling and surveyed with the Chinese version of the Evidence-Based Practice Belief-Knowledge-Practice Scale. Univariate analysis and multiple linear regression were employed to analyze factors affecting the evidence-based nursing competencies of these nurses.Results:The evidence-based nursing competency scores of the 300 oncology nurses were (44.50±10.78) . Among the three dimensions, the belief dimension had the highest average item score, while the practice dimension had the lowest. Multiple linear regression analysis revealed that gender, age, evidence-based training, participation in evidence-based projects, reading professional literature, publication of papers within the last five years and medical statistical level were influencing factors of their evidence-based nursing competencies (all P<0.05) . Conclusions:The evidence-based nursing competencies of oncology nurses are at a relatively low level. Nursing managers and educators should focus on female nurses, older nurses, intensify evidence-based nursing training efforts, and thus enhance the evidence-based nursing competencies and overall research quality of the nursing team.

Objective To investigate the correlation between interleukin 1β gene-511C/T polymorphism of and essential hypertension in the Yi ethnic group of Yunnan province.Methods-511C/T polymorphism of interleukin 1β gene was detected by PCR-RFLP in 85 Yi patients with essential hypertension(EH group)and 106 Yi healthy people(control group)in Shuanghe Township,Jinning County,Yunnan Province.Genotype and allele frequencies were analyzed by SPSS 27.0 software,and association analysis was performed.Results The frequency distribution of CC,CT and TT genotypes at the mutation site 511 of the IL-1βgene in EH group was 18.82%,44.71%and 36.47%,respectively,and it was 5.66%,26.42%and 67.92%in the control group.The difference in genotype frequency between the two groups was statistically significant(P＜0.05).The allele frequency of C and T in EH group was 41.18%and 58.82%,respectively,and the allele frequency of C and T in control group was 18.87%and 81.13%.The frequency difference of alleles between the two groups was statistically significant(P＜0.05).Both genotype frequency and allele frequency found in males and females had statistical differences(P＜0.05).Conclusions The distribution of IL-1β gene-511C/T polymorphism is related to the incident of essential hyper-tension among the Yi ethnic group Yunnan Province,and is the susceptibility gene of the Yi ethnic group to essen-tial hypertension.