Ten novel xanthones, garpedunxanthones A-G (1-5, 6a/6b, 7a/7b) and nujiangxanthone Q (8), along with sixteen known analogs (9-24), were isolated from Garcinia pedunculata and G. nujiangensis. Their structures were elucidated through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) data, comprehensive nuclear magnetic resonance (NMR) spectroscopic analyses, and electronic circular dichroism (ECD) calculations. All compounds without cytotoxicity were assessed for anti-inflammatory properties by measuring the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 cells. Structure-activity relationships are also discussed. Compounds 7b, 19, and 21 exhibited significant anti-inflammatory activity with IC₅₀ values of 16.44 ± 0.69, 14.28 ± 0.78, and 10.67 ± 3.28 μmol·L^-1, respectively. Enzyme-linked immunosorbent assay (ELISA) demonstrated that compounds 7b, 19, and 21 inhibited the expression of pro-inflammatory cytokines TNF-α and IL-6 in a dose-dependent manner. The inhibitory effect of compound 21 on IL-6 at 20 μmol·L^-1 was comparable to that of the positive control. In network pharmacology studies, potential targets of compounds and inflammation were identified from PharmMapper and GeneCards databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the overlapped targets were intricately associated with major pathogenic processes linked to inflammation, including positive regulation of mitogen-activated protein kinase (MAPK) cascade, protein kinase activity, NO synthase regulator activity, MAPK signaling pathway, and EGFR tyrosine kinase inhibitor resistance.
Xanthones/therapeutic use* ; Garcinia ; Anti-Inflammatory Agents/therapeutic use* ; Plant Preparations/therapeutic use* ; Structure-Activity Relationship ; Nitric Oxide/metabolism* ; RAW 264.7 Cells ; Animals ; Mice ; Enzyme-Linked Immunosorbent Assay ; Mitogen-Activated Protein Kinase Kinases/metabolism* ; Circular Dichroism

Objective:To understand the genetic characteristics of varicella-zoster virus（VZV）prevalent in Qinghai province，China since 2020.Methods:A total of 54 pharyngeal swab specimens were collected from sporadic suspected varicella cases in Qinghai province in 2020，2023，and 2024. Real-time fluorescence quantitative polymerase chain reaction was used for etiological screening of the specimens. Sequencing of three genes，namely ORF22，ORF38，and ORF62，and single-nucleotide polymorphism（SNP）analysis were performed on VZV nucleic acid-positive specimens.Results:All 54 suspected varicella cases were diagnosed with VZV infection，and three gene sequences were successfully obtained from 53 specimens. The results of genotype identification showed that all VZV infection case specimens obtained in this study in Qinghai province were wild strains. Among them，4 specimens in 2020 were of clade 2 type；among 14 specimens in 2023，7 were of clade 2 type and the remaining 7 were of clade 5 type；among 35 specimens in 2024，27 were of clade5 type，5 were of clade 2 type，and 3 were of clade 4 type. The SNP results showed that in 2023 and 2024，one specimen each had an A→G base mutation at position 37 990，and in 2024，3 specimens had a T→C base mutation at position 37946. Among them，the sequences containing the former mutation have been prevalent and spread in multiple regions of China，and the latter has not been reported in other regions of China.Conclusion:From 2020 to 2024 in Qinghai province，at least three genotypes of VZV，namely clade 2 type，clade 5 type，and clade 4 type，co-prevailed，and the clade 5 genotype of VZV may become the dominant prevalent strain.

Objective:To understand the genetic characteristics of varicella-zoster virus（VZV）prevalent in Qinghai province，China since 2020.Methods:A total of 54 pharyngeal swab specimens were collected from sporadic suspected varicella cases in Qinghai province in 2020，2023，and 2024. Real-time fluorescence quantitative polymerase chain reaction was used for etiological screening of the specimens. Sequencing of three genes，namely ORF22，ORF38，and ORF62，and single-nucleotide polymorphism（SNP）analysis were performed on VZV nucleic acid-positive specimens.Results:All 54 suspected varicella cases were diagnosed with VZV infection，and three gene sequences were successfully obtained from 53 specimens. The results of genotype identification showed that all VZV infection case specimens obtained in this study in Qinghai province were wild strains. Among them，4 specimens in 2020 were of clade 2 type；among 14 specimens in 2023，7 were of clade 2 type and the remaining 7 were of clade 5 type；among 35 specimens in 2024，27 were of clade5 type，5 were of clade 2 type，and 3 were of clade 4 type. The SNP results showed that in 2023 and 2024，one specimen each had an A→G base mutation at position 37 990，and in 2024，3 specimens had a T→C base mutation at position 37946. Among them，the sequences containing the former mutation have been prevalent and spread in multiple regions of China，and the latter has not been reported in other regions of China.Conclusion:From 2020 to 2024 in Qinghai province，at least three genotypes of VZV，namely clade 2 type，clade 5 type，and clade 4 type，co-prevailed，and the clade 5 genotype of VZV may become the dominant prevalent strain.

Objective To investigate the neurobehavioral development of young children aged 24 to 60 months in Shunde and explore the factors influencing the development of young children and provide reference for the interven-tion of neurobehavioral development delays in young children.Methods A retrospective cohort study was used to enroll the young children who were initially screened by the Pediatric Neuropsychological Developmental Scale(Pe-diatric Heart Scale)with a score of ≤85 was included in the study.With a score of ≤85,the young children might be at risk of developmental delays,and needed to be further diagnosed by the GESELL Developmental Diagnostic Scale,the basic information of the young children and their mothers at the time of birth were investigated,as well as basic information about the young children at the time of completing the GESELL Developmental Diagnostic Scale was collected.Results A total of 271 young children were included,196 males and 75 females.Young children had the lowest developmental quotient(DQ)in the language domain among the five domains(P＜0.001).Multiple lin-ear regression models showed:compared with girls,the language domain DQ of boys decreased by 5.321 points(P=0.049,95％CI:-10.620--0.021),and the personal-social domain DQ decreased by 4.474 points(P=0.023,95％CI:-8.316--0.631).Compared with young children via natural vaginal delivery(NVD),the gross motor domain DQ of young children via caesarean section(CS)decreased by 4.890 points(P=0.008,95％CI:-8.499--1.281),the fine motor domain DQ decreased by 3.373 points(P=0.037,95％CI:-6.532--0.213),the language domain DQ decreased by 7.621 points(P=0.004,95％CI:-12.826--2.416),per-sonal-social domain DQ decreased by 6.232 points(P=0.001,95％CI:-10.006--2.457).The results of bi-nary logistic regression models showed,compared with young children via NVD,the risk of gross motor domain retar-dation in young children increased(OR=1.763,95％CI:1.003-3.100),the risk of fine motor domain retardation increased(OR=2.217,95％CI:1.235-3.980),the risk of language domain retardation increased(OR=3.306,95％CI:1.080-10.124).Conclusion Young children with suspected neurobehavioral delays were more likely to have delayed development in language domain than in other domains,boys had lower DQ in language domain and personal-social domain than girls,and the development of young children via CS was slower than that via NVD.Fo-cus should be on the language development of young children especially on the language and personal-social devel-opment of boys.Carefully chose delivery way.Focus should be placed on assessment of young children's comprehen-sive neurobehavioral development in early time.

Objective:To analyze the gene sequence of varicella-zoster virus (VZV) in Liaoning Province, and determine the prevailing dominant genotypes and nucleotide and amino acid variations.Methods:The open reading frames (ORFs) of 31 VZV strains from 2017 to 2020 in Liaoning Province were analyzed by PCR, including 1, 6, 12, 16, 17, 21, 22, 35, 37, 38, 50, 54, 55, 56, 60 and 66. The amplified products were sequenced, combined with single nucleotide polymorphism (SNP) and phylogenetic tree to determine the virus genotype, and the variation of nucleotides and amino acids at different sites was analyzed.Results:All 31 VZV strains in Liaoning Province were Clade 2 genotype. Compared with Clade 2 genotype reference strains, the 31 strains had nucleotide and amino acid homology of 99.6%-100.0% and 98.7%-100.0%, respectively, and the genetic distance was 0-0.002. Compared with V-Oka vaccine strain, the 31 strains all had site mutation, which led to amino acid changes, including one strain with ACCTCCCAA deletion at 541-549 sites of ORF1 and two strains with inserted CGG at the 780-781 site of ORF1; the 31 VZV strains had point mutations at 24 sites, including 15 synonymous mutations, 9 missense mutations, 20 mutations in the coding region, 4 mutations outside the coding region, 13 synonymous mutations in the coding region and 7 missense mutations in the coding region. The missense mutations in the coding region included a base mutation of C→T at site 731, a base mutation of C→T at site 790, a base mutation of C→T at site 791, a base mutation of A→G at site 17829, a base mutation of G→A at site 24567, a base mutation of T→C at site 98261, a base mutation of A→C at site 101579, which leaded to the amino acid changes of Arginine→Lysine, Arginine→Glutamine, Arginine→Glutamine, Histidine→Arginine, Arginine→Glutamine, Tyrosine→Histidine, Leucine→Arginine.Conclusions:Clade 2 genotype is the dominant genotype of VZV in Liaoning Province in recent years, and the gene sequences of VZV strains in Liaoning Province is highly conserved. Studying the characteristics of VZV gene is of great significance for studying the molecular epidemiology of VZV in Liaoning Province, and provides important scientific basis for varicella control and vaccination plan.

AIM:This study aims to investigate the impact of nobiletin(NOB)on the gut microbiota and short-chain fatty acids(SCFAs)in high-fat diet-induced obese rats.METHODS:A total of 22 SD rats were randomly di-vided into the control(CON)group and high-fat diet(HFD)group.The HFD induced obesity,upon successful modeling,the rats were further divided into the HFD and NOB group,each group consisting of 6 rats.The NOB group received nobi-letin solution(100 mg·kg-1·d-1)via gavage for 21 consecutive days.Body weight was measured bi-daily,and hematoxylin-eosin(HE)staining was employed to observe pathological changes in adipose tissue and liver.Serum lipid levels were as-sessed using an auto-biochemical analyzer.Analysis of the gut microbiota was performed using 16S ribosomal RNA(rRNA)sequencing,while high-performance liquid chromatography mass spectrometry(LC-MS)was used to determine SCFAs levels in rat feces.RESULTS:Compared with CON group,HFD-fed demonstrated a substantial increase in body weight(P<0.01),accompanied by an augmentation in adipocyte diameter and the presence of hepatic cell vacuolization,indicative of cellular steatosis and inflammation.Moreover,there was a notable elevation in TG and TC levels(P<0.05).At the phylum level,the HFD rats exhibited an altered composition,characterized by an increase in Firmicutes and a con-current decrease in Bacteroidetes.At the genus level,Bacteroides,Lactobacillus and Blautia experienced a significant de-crease,while Colidextribacter showed an increase.Notably,there was a substantial reduction in the expression of propion-ic acid and butyric acid.In comparison to the HFD group,rats administered with NOB demonstrated a marked decrease in body weight(P<0.05),a reduction in adipocyte diameter,and an amelioration in hepatic cell vacuolization and cellular steatosis.Furthermore,TG and TC levels exhibited a significant decrease(P<0.05).At the phylum level,Firmicutes de-creased,and Bacteroidetes increased.At the genus level,Bacteroides,Lactobacillus and Blautia exhibited a significant in-crease,while Colidextribacter displayed a decrease.Additionally,there was an up-regulation of propionic acid and butyric acid levels in the NOB group.CONCLUSION:Nobiletin,through its multifaceted actions,demonstrates a potential anti-obesity effect by effectively reducing body weight in obese rats.This includes the regulation of gut microbiota structure,modulation of SCFAs content,and enhancement of lipid metabolism.

Objective:To analyze the gene sequence of varicella-zoster virus (VZV) in Liaoning Province, and determine the prevailing dominant genotypes and nucleotide and amino acid variations.Methods:The open reading frames (ORFs) of 31 VZV strains from 2017 to 2020 in Liaoning Province were analyzed by PCR, including 1, 6, 12, 16, 17, 21, 22, 35, 37, 38, 50, 54, 55, 56, 60 and 66. The amplified products were sequenced, combined with single nucleotide polymorphism (SNP) and phylogenetic tree to determine the virus genotype, and the variation of nucleotides and amino acids at different sites was analyzed.Results:All 31 VZV strains in Liaoning Province were Clade 2 genotype. Compared with Clade 2 genotype reference strains, the 31 strains had nucleotide and amino acid homology of 99.6%-100.0% and 98.7%-100.0%, respectively, and the genetic distance was 0-0.002. Compared with V-Oka vaccine strain, the 31 strains all had site mutation, which led to amino acid changes, including one strain with ACCTCCCAA deletion at 541-549 sites of ORF1 and two strains with inserted CGG at the 780-781 site of ORF1; the 31 VZV strains had point mutations at 24 sites, including 15 synonymous mutations, 9 missense mutations, 20 mutations in the coding region, 4 mutations outside the coding region, 13 synonymous mutations in the coding region and 7 missense mutations in the coding region. The missense mutations in the coding region included a base mutation of C→T at site 731, a base mutation of C→T at site 790, a base mutation of C→T at site 791, a base mutation of A→G at site 17829, a base mutation of G→A at site 24567, a base mutation of T→C at site 98261, a base mutation of A→C at site 101579, which leaded to the amino acid changes of Arginine→Lysine, Arginine→Glutamine, Arginine→Glutamine, Histidine→Arginine, Arginine→Glutamine, Tyrosine→Histidine, Leucine→Arginine.Conclusions:Clade 2 genotype is the dominant genotype of VZV in Liaoning Province in recent years, and the gene sequences of VZV strains in Liaoning Province is highly conserved. Studying the characteristics of VZV gene is of great significance for studying the molecular epidemiology of VZV in Liaoning Province, and provides important scientific basis for varicella control and vaccination plan.

l-Heptopyranoses are important components of bacterial polysaccharides and biological active secondary metabolites like septacidin (SEP), which represents a group of nucleoside antibiotics with antitumor, antifungal, and pain-relief activities. However, little is known about the formation mechanisms of those l-heptose moieties. In this study, we deciphered the biosynthetic pathway of the l,l-gluco-heptosamine moiety in SEPs by functional characterizing four genes and proposed that SepI initiates the process by oxidizing the 4'-hydroxyl of l-glycero-α-d-manno-heptose moiety of SEP-328 ( 2) to a keto group. Subsequently, SepJ (C5 epimerase) and SepA (C3 epimerase) shape the 4'-keto-l-heptopyranose moiety by sequential epimerization reactions. At the last step, an aminotransferase SepG installs the 4'-amino group of the l,l-gluco-heptosamine moiety to generate SEP-327 ( 3). An interesting phenomenon is that the SEP intermediates with 4'-keto-l-heptopyranose moieties exist as special bicyclic sugars with hemiacetal-hemiketal structures. Notably, l-pyranose is usually converted from d-pyranose by bifunctional C3/C5 epimerase. SepA is an unprecedented monofunctional l-pyranose C3 epimerase. Further in silico and experimental studies revealed that it represents an overlooked metal dependent-sugar epimerase family bearing vicinal oxygen chelate (VOC) architecture.

Acute pancreatitis often progresses rapidly, and if it is not controlled in time, it may lead to multiple organ injury and even death due to organ failure. At present, there is still a high proportion of patients with acute pancreatitis who died due to liver failure. The liver and the pancreas are interrelated physiologically and affect each other pathologically. This article elaborates on the molecular mechanism of liver injury in acute pancreatitis from the six aspects of the physiological relationship between the pancreas and the liver, cytokines, inflammatory response, oxidative stress, microcirculation disturbance, and intestinal flora translocation.

Metabolic disorders are observed in women after menopause, and the postmenopausal women suffering from chronic liver diseases have an increased risk of progression to liver fibrosis, with a higher risk than male patients of the same age, which may be associated with the decline of ovarian function and the reduction of estrogen level after menopause. This article summarizes the research advances in the molecular mechanism of progression to liver fibrosis from the aspects of estrogen and oxidative stress, activation of hepatic stellate cells, accumulation of extracellular matrix, and immune regulation. It is pointed out supplementation with an appropriate amount of estrogen in the perimenopausal period and the early menopausal period can reduce the risk of liver fibrosis and delay or even reverse the process of liver fibrosis, thereby improving quality of life and prolonging survival time in elderly female patients.