Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

With the increasing prevalence of overweight and obesity among children and adolescents in China, pediatric metabolic syndrome has emerged as a significant public health challenge. The Developmental Origins of Health and Disease (DOHaD) theory underscores the critical influence of early environmental factors on lifelong metabolic health. Consequently, maternal nutritional status and physical activity during pregnancy have become key modifiable factors that have attracted considerable attention in recent years. Research indicates exposure to a maternal high-fat diet (HFD) during pregnancy has long-term effects on offspring health, which may be transmitted through placental transit disorder, inflammation, and oxidative stress. Similarly, a high-protein diet (HPD) during pregnancy exhibits a dose- and time-dependent biphasic effect: excessive intake may lead to fetal growth restriction and an increased risk of preterm birth, whereas moderate supplementation may instead reduce the susceptibility of offspring to obesity. Interestingly, caloric restriction (CR) during pregnancy presents a double-edged sword: while it may impair the development of metabolic organs in offspring, moderate CR in metabolically compromised mothers can ameliorate maternal metabolic dysfunction and reprogram oocyte DNA methylation, significantly lowering the risk of metabolic disorders in offspring. Notably, metabolic abnormalities induced by a low-protein diet (LPD) during pregnancy demonstrate lifecycle-accumulative effects and transgenerational inheritance, with offspring exhibiting obesity phenotypes during weaning, insulin resistance in adulthood, and hepatic decompensation in old age, mediated through oocyte epigenetic reprogramming. Additionally, maintaining an optimal micronutrient balance is crucial for the metabolic homeostasis of offspring, as both deficiency and excess can lead to detrimental outcomes. Maternal exercise has been established as a safe and effective non-pharmacological intervention that confers multigenerational metabolic benefits through diverse biological pathways. Maternal metabolic dysregulation represents a critical determinant of offspring metabolic disorders. Regular exercise during gestation exerts protective effects by attenuating maternal systemic inflammation and reducing the incidence of pregnancy-related complications, thereby effectively mitigating fetal overgrowth and metabolic dysfunction. This dual benefit for both mother and offspring underscores the pivotal role of gestational physical activity in promoting long-term metabolic health. The placenta, serving as the exclusive interface for maternal-fetal communication, mediates exercise-induced metabolic programming through enhanced secretion of key regulatory factors (including SOD3, Apelin, ADPN, and Irisin) and promotes the development of vascular networks, collectively optimizing nutrient transport efficiency. The intrauterine period represents a crucial window for epigenetic reprogramming, during which maternal exercise modulates DNA methylation patterns of critical metabolic genes (e.g., Ppargc-1α, Prdm16, Klf4, and Slc23a2) in offspring, thereby enhancing their capacity to resist metabolic disorders. Notably, the regulatory effects of maternal exercise extend beyond the gestational period. Postnatally, exercise-induced modifications in the bioactive components of breast milk and gut microbiota composition contribute to the sustained maintenance of metabolic homeostasis in offspring, establishing a continuum of metabolic protection from prenatal to postnatal stages. This review explores the potential of maternal combined nutrition-exercise interventions, suggesting that such strategies may synergistically enhance transgenerational health benefits through interactions within the metabolic-epigenetic network, thereby outperforming single interventions. Additionally, it examines current research limitations, including controversies surrounding transgenerational mechanisms, sex-specific responses, and undefined dynamic thresholds, while providing directions for future investigations. These findings pave the way for a theoretical foundation for early-life health interventions, potentially offering a more effective strategy for combatting intergenerational metabolic disorders.

A prokaryotic expression vector for the mutant diphtheria toxin CRM197 was constructed and expressed in Esch-erichia coli cells.Anti-CRM197 antibody concentrations were detected in serum samples of healthy volunteers.The crm 197 gene was codon-optimized in E.coli and cloned into the plasmid pET28a(+)under optimized expression conditions.CRM197 was purified using Ni-NTA spin columns and ion exchange chromatography,and confirmed by western blot analysis.The puri-fied CRM197 was used to detect specific anti-CRM197 antibody levels in serum samples of different age groups.The results showed that soluble codon-optimized CRM197 was successfully expressed under optimized expression conditions.The purity of CRM197 was more than 95％,as determined with Ni-NTA spin columns and ion exchange chromatography,consistent with the single specific bands obtained by western blot analysis and detection of serum levels of the anti-CRM197 antibody.Collec-tively,these results confirmed that the proposed expression strategy achieved high-yield production of soluble CRM197,al-though high levels in human serum may affect evaluation of immune interactions with glycan-CRM197 conjugates for applica-tion as a diagnostic antigen.The diphtheria mutant toxin CRM197 is used in many conjugate vaccines.The synthetic crm 197 gene with codon optimization in pET28a was transformed into E.coli Origami B(DE3)cells.CRM197 was induced by isopro-pyl β-d-1-thiogalactopyranoside and high level accumulation of soluble CRM197 was purified using Ni-NTA spin columns and ion exchange chromatography.The purity of the final prepara-tion reached 95％.CRM197 was used to detect the concentra-tions of the anti-CRM197 antibody in serum samples of healthy volunteers of different ages.The proposed expression strategy yielded high production of CRM197,which could interfere with evaluations of induced immune interactions by glycan-CRM197 conjugates and prohibit application as a diagnostic antigen.

This study was aimed at investigating the pathogenic and molecular characteristics of Klebsiella pneumoniae(KP)in fecal samples of diarrhea cases in a district of Beijing.Fecal samples from diarrhea cases in an outpatient department in a district of Beijing from 2018 to 2021 were collected,and used for isolation and culture of KP.The KP strains isolated strains were subjected to drug resistance phenotype testing and whole-genome sequencing.Multilocus sequence typing and whole-genome phyletic evolution analysis were performed on the sequencing results.The cases'epidemiological and clinical characteristics were analyzed.From 2018 to 2021,1 103 fecal samples were collected and detected.The total detection rate of KP was 10.43％(115/1 103),and the infection rate of KP mixed with other diarrhea-causing pathogens was 42.61％(49/115).The positivity rate was slightly high(12.47％,61/489)a-mong females and was highest in young adults 16-45 years of age.Small peaks were observed in January,April to May,and August to September.The gastrointestinal symptoms in cases were mainly nausea and watery stool,and the suspicious food was unknown.Ampicillin,tetracycline,and sulfafurazole were the top three antibiotics to which these 115 KP strains showed resistance,and 29 strains were resistant to multiple antibiotics.The strains were divided into 72 sequence types,among which ST23 was dominant.According to the phylogenetic tree,the strains were divided into four main branches,among which 14 ST23 strains had a very close genetic relationship with the highly virulent NTUH-K2044 reference strain.KP infection persisted in fecal samples from diarrhea cases in the district of Beijing.Women and young adults were particularly susceptible.The drug resistance of KP strains in this region was very serious,and the ST types were diverse.Moreover,the ST23 pathogenic strains were closely related to high virulence strains.

Objective:To analyze the clinical and genetic characteristics of acute myeloid leukemia,myelodysplasia-related(AML-MR)patients and evaluate their prognostic risk stratification,to guide clinical treatment decisions and improve understanding of the biological characteristics and disease progression.Methods:The study analyzed cellular and molecular genetic information of 307 AML-MR patients,diagnosed based on clinical history,bone marrow morphology,cytogenetics,and molecular genetic abnormalities.The risk stratification followed the 2022 ELN guidelines.Results:57 cases(18.6％)met the AML-MR diagnostic criteria based on morphology and clinical history,110 cases(37.2％)met the AML-MR diagnostic criteria based on cytogenetic results,and 210 cases(74.5％)met the AML-MR diagnostic criteria based on molecular testing results.Among different type of mutations,ASXL1 mutation was the most frequent,followed by SRSF2 and BCOR mutations.Except for 2 cases with incomplete data that could not be classified.263(86.2％)of the 305 patients were classified as poor prognosis,20(6.6％)were classified as good prognosis group,and 22(7.2％)were classified as intermediate prognosis group.Conclusion:Molecular genetic information plays a crucial role in diagnosing AML-MR,highlighting the importance of genetics in diagnosis and prognosis.Most AML-MR patients fall into poor prognosis categories,necessitating early intensive and targeted therapy for better survival outcomes.

Objective:To investigate the causal correlation between depression and stress urinary incontinence(SUI)using Mendelian randomization(MR)analysis.Methods:We searched the FinnGen Consortium database for genome-wide association studies(GWAS)on depression and obtained 23 424 case samples and 192 220 control samples,with the GWAS data on SUI provided by the UK Biobank,including 4 340 case samples and 458 670 control samples.We investigated the correlation between depression and SUI based on the depression data collected from the Psychiatric Genomics Consortium(PGC).We employed inverse-variance weighting as the main method for the MR study,and performed sensitivity analysis to verify the accuracy and stability of the findings.Results:Analysis of the data from the UK Biobank and FinnGen Consortium showed that depression was significantly correlated with an increased risk of SUI(P=0.005),but not SUI with the risk of depression(P=0.927).And analysis of the PGC data verified the correlation of depression with the increased risk of SUI(P=0.043).Conclusion:Depression is associated with an increased risk of SUI,while SUI does not increase the risk of depression.

Guillain-Barre syndrome rarely develops after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and only a few reports exist in China. Guillain-Barre syndrome is an acute and life-threatening condition that requires early diagnosis and treatment. A patient with acute myeloid leukemia underwent allogeneic HSCT for >5 months and gradually developed limb muscle weakness and limited eye movement after coexisting with delayed acute intestinal graft-versus-host disease. After the examination of cerebrospinal fluid and electromyography, the diagnosis of Guillain–Barre syndrome was confirmed. After a high-dose intravenous immunoglobulin (IVIg) treatment, muscle strength gradually recovered, and the prognosis was good.

Objective To study the pharmacokinetic characteristics of buspirone hydrochloride tablets in healthy adult populations under conditions of fasting and postprandial administration.Methods A single-center,randomized,three-cycle partially repeated crossover trial design was adopted,and 36 subjects were enrolled on fasting/postprandial,one tablet of the test preparation was taken in one cycle,one tablet of reference preparation(5 mg of buspirone tablets)was taken once in each of 2 cycles,the drug concentration of buspirone in plasma was determined by liquid chromatography-tandem mass spectrometry,and the pharmacokinetic parameters were calculated by WinNonlin software.Results Main pharmacokinetics of buspirone after oral administration of test and reference preparations in fasting group,the Cmax was(285.72±286.08)and(308.94±341.03)pg·mL-1;AUC0-t were(577.09±491.10)and(618.62±642.56)pg·mL-1·h;AUC0-∞ were(586.85±510.04)and(655.92±687.95)pg·mL-1·h;tmax was 0.75(0.33-4.00)and 0.75(0.33-1.75)h.Main pharmacokinetics of buspirone after oral administration of test and reference preparations in the postprandial group,the Cmax were(676.36±603.64)and(760.33±610.27)pg·mL-1;AUC0-t were(1 755.58±1 001.69)and(1 743.00±1 073.33)pg·h·mL-1;AUC0-∞ were(1 839.97±1 044.60)and(1 818.00±1 106.95)pg·mL-1·h;tmax was 1.25(0.25-4.50)and 1.00(0.25-3.50)h.The 90％confidence intervals of the AUC0-t and AUC0-∞ geometric mean ratios of the test preparation and the reference preparation in the fasting test and the postprandial test all fell between 80.00％and 125.00％,and the 95％upper confidence limit of of Cmax was ≤0 and geometric mean ratios point estimates fall between 80.00％and 125.00％.Conclusion Two kinds of buspirone hydrochloride are bioequivalent in Chinese healthy adult subject.

ObjectiveCoronavirus is a class of long-standing pathogens, which are enveloped single-stranded positive-sense RNA viruses. The genome all encodes 4 structural proteins: spike protein (S), nucleocapsid protein (N), membrane protein (M), and envelope protein (E). The nucleocapsid protein (NP) serves as a key structural component of coronaviruses, playing a vital function in the viral life cycle. NP acts as an RNA-binding protein, with a critical role in identifying specific sequences within the viral genome RNA, facilitating the formation of ribonucleoprotein (RNP) complexes with viral RNA to stabilize the viral genome and contribute to viral particles assembly. The NP consists of two primary structural domains, the N-terminal domain (NTD) and the C-terminal domain (CTD). The NTD is primarily responsible for RNA binding, whereas the CTD is involved in polymerization. The N protein demonstrated to trigger the host immune response and to modulate the cell cycle of infected cells by interacting with host proteins. The NP, one of the most abundant protein in coronaviruses, is essential in understanding the pathogenic mechanism of coronaviruses through its interaction with host factors, which response for determining the virus pathogenicity. HCoV-229E is a widely distributed coronavirus that typically causes mild upper respiratory tract diseases, accounting for a significant portion of common cold cases. However, its pathogenicity is notably lower compared to other coronaviruses like MERS-CoV, SARS-CoV, and SARS-CoV-2. The exact molecular mechanism behind remains unexplained, and how HCoV-229E N protein influences virus replication, host antiviral immunity, and pathogenesis need to be further explored. MethodsProximity labeling-mass spectrometry technique and bioinformatics analysis were used to screen for potential host factors interacting with the NP of human coronavirus 229E (HCoV-229E). In this study, a recombinant adenovirus Ad-V5-NP^HCoV-229E-TurboID was constructed to express the fusion protein of HCoV-229E NP and biotin ligase (TurboID). A549 cells were infected with the Ad-V5-NP^HCoV-229E-TurboID. After 30 min biotin treatment, NP interacting proteins were labeled with biotin by biotin ligase, and subsequently isolated with streptavidin cross-linked magnetic beads. The potential interacting proteins were identified using label-free proteomic mass spectrometry and further validated through immunoprecipitation and immunofluorescence assays. ResultsWe identified a total of 584 potential interacting proteins. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted the enrichment of glycogen synthase kinase (GSK)3A and GSK3B in the glycolysis/gluconeogenesis pathway, indicating HCoV-229E NP connection to diabetes through aberrant activity. Moreover, SARS-CoV-2 infection can exacerbate hyperglycemia and metabolic dysregulation in diabetic individuals by activating the ACE2 receptor. Moreover, SARS-CoV-2 was observed to cause potentially harm to pancreatic β‑cells and leading to insulin deficiency, which not only worsens the condition of diabetic patients but also raises the possibility of new-onset diabetes in non-diabetic individuals. We demonstrated that GSK3A and GSK3B interacted with NP of HCoV-229E, suggesting that the NP may engage in various coronavirus pathogenic processes by interacting with GSK3. ConclusionThese findings suggest that proximity labeling-mass spectrometry technique is a valuable tool for identifying virus-host interaction factors, and lay the foundation for future investigations into the mechanisms underlying coronavirus replication, proliferation, and pathogenesis.

The compound (E)-1-(4-(3-(5-chloro-6-oxo-3,6-dihydropyridin-1(2H)-yl)-3-oxo-propyl-1-ene-1-yl) phenyl)-3-(4-fluorophenyl) urea (C12), a novel derivative of piperlongumine previously synthesized by our research group, was investigated in this study to examine its effects on human non-small cell lung cancer cell line H1299 in vitro and elucidate its potential mechanism of action. The impact of C12 on the proliferation, migration, and invasion abilities of H1299 cells were assessed using methyl thiazolyl tetrazolium (MTT) assay, wound healing assay, cloning formation assay, and Transwell assay. Flow cytometry was employed to evaluate the influence of C12 on cell cycle progression, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and apoptosis induction in H1299 cells. Western blot analysis was conducted to investigate the expression levels of p21, Cyclin B1, CDK1, Bax, Bcl-2, JNK, p-JNK, Erk1/2, p-Erk1/2, p38 and p-p38 proteins for exploring the anti-tumor mechanism underlying C12's actions. The results demonstrated that C12 exerted inhibitory effects on the proliferation, migration, and invasion capacities of H1299 cells in a time-dependent and concentration-dependent manner. Moreover, C12 induced G2/M phase arrest in the cell cycle, reduced MMP levels, elevated ROS production, and triggered apoptotic processes. Flow cytometry analysis revealed that C12 downregulated Cyclin B1 and CDK1 protein expressions, resulting in G2/M phase arrest. C12 also upregulated Bax/Bcl-2 ratio, promoting apoptosis. Furthermore, C12 activated MAPK signaling pathway by enhancing phosphorylation levels of JNK, Erk1/2, and p38 proteins. In conclusion, C12 significantly suppressed proliferation, migration, and invasion capabilities while inducing cell cycle arrest and apoptosis in H1299 cells. These effects may be attributed to activation of the MAPK signaling pathway.