Merkel cell polyomavirus (MCV) was named thus because it is the causative agent of Merkel cell carcinoma (MCC), with 80% of MCC cases being MCV-positive. MCV has been classified as a 2A carcinogen. It promotes carcinogenesis by integrating T antigens into the cell genome. The anti-MCV seroprevalence in the general population is as high as 90%. Usually, MCV is latent after infection in immunocompetent patients, and the incidence of MCC in immunosuppressive or defective patients, such as those with organ transplants, chronic lymphocytic leukemia, and HIV infection, is remarkably high. Patients with HIV/AIDS are a typical population with acquired immunodeficiency. At present, the research on patients with HIV/AIDS and MCV infection, activation, and pathogenesis is limited. In this paper, the progress of previous research is reviewed and the relationship between HIV infection and MCV activation is systematically investigated to provide a reference for the prevention and treatment of MCC in key populations, such as patients with HIV/AIDS.

Objective To investigate the prevalence of Cryptosporidium infection and the distribution of parasite species and genotypes among HIV-positive individuals in Jiangxi Province. Methods HIV-positive individuals' sociodemographic and clinical data were collected from three AIDS designated hospitals in Jiangxi Province from January 2022 to March 2023. Subjects' stool samples were collected, and genomic DNA was extracted from stool samples. Nested PCR assay was performed based on the small subunit ribosomal RNA (SSU rRNA) gene of Cryptosporidium, and Cryptosporidium gp60 gene was amplified in stool samples positive for the SSU rRNA gene. The second-round PCR amplification product was checked with 1.5% agarose gel electrophoresis, and the products of suspected positive amplifications were sequenced, followed by sequence alignment. The phylogenetic tree was created using the Neighbor-Joining method with the software MEGA 11.0, to characterize the species, genotypes and sub-genotypes of Cryptosporidium. Results A total of 382 HIV-positive individuals were enrolled, with two cases identified with Cryptosporidium infection (0.52% prevalence), and both cases had no abdominal pain or diarrhea. Following sequencing and sequence alignment, the gene sequences of these two Cryptosporidium isolates shared 99.76% and 99.88% similarity with the gene sequence of C. meleagridis isolates. Phylogenetic analysis based on the Cryptosporidium SSU rRNA gene sequence identified the species of these two Cryptosporidium-positive stool samples as C. meleagridis. Following nested PCR amplification of the Cryptosporidium gp60 gene, sequencing and sequence alignment, the two C. meleagridis isolates were characterized as III eA17G2R1 and III bA25G1R1a sub-genotypes, and the sub-genotype III bA25G1R1a was firstly described in humans. Conclusion The prevalence of Cryptosporidium is low among HIV-positive individuals in Jiangxi Province. The likelihood of Cryptosporidium infection cannot be neglected among HIV-positive individuals without diarrhea.

Objective:To identify diagnostic markers related to oxidative stress in chronic rhinosinusitis with nasal polyps (CRSwNP) by analyzing transcriptome sequencing data, and to investigate their roles in CRSwNP.Methods:Utilizing four CRSwNP sequencing datasets, differentially expressed genes (DEGs) analysis, weighted gene co-expression network analysis (WGCNA), and three machine learning methods for Hub gene selection were performed in this study. Subsequent validation was carried out using external datasets, as well as real-time quantitative polymerase chain reaction (Real-time qPCR), and immunofluorescence staining of clinical samples. Moreover, the diagnostic efficacy of the genes was assessed by receiver operating characteristic (ROC) curve, followed by functional and pathway enrichment analysis, immune-related analysis, and cell population localization. Additionally, a competing endogenous RNA (CeRNA) network was constructed to predict potential drug targets. Statistical analysis and plotting were conducted using SPSS 26.0 and Graphpad Prism9 software.Results:Through data analysis and clinical validation, CP, SERPINF1 and GSTO2 were identified among 4 138 DEGs as oxidative stress markers related to CRSwNP. Specifically, the expression of CP and SERPINF1 increased in CRSwNP, whereas that of GSTO2 decreased, with statistically significant differences ( P<0.05). Additionally, an area under the curve (AUC)>0.7 indicated their effectiveness as diagnostic indicators. Importantly, functional analysis indicated that these genes were mainly related to lipid metabolism, cell adhesion migration, and immunity. Single-cell data analysis revealed that SERPINF1 was mainly distributed in epithelial cells, stromal cells, and fibroblasts, while CP was primarily located in epithelial cells, and GSTO2 was minimally present in the epithelial cells and fibroblasts of nasal polyps. Consequently, a CeRNA regulatory network was constructed for the genes CP and GSTO2. This construction allowed for the prediction of potential drugs that could target CP. Conclusion:This study successfully identifies CP, SERPINF1 and GSTO2 as diagnostic and therapeutic markers related to oxidative stress in CRSwNP.

Objective To investigate the ameliorative effects and potential mechanism of Lithocarpus litseifoliu on renal function and inflammation in mice with hyperuricemic nephropathy(HN).Methods The HN model was established by the combined administration of adenine and potassium oxyzate.The mice were randomly divided into normal control group,model control group,benzbromarone group,and high,medium and low dose groups of Lithocarpus litseifoliu.Different drugs were given to the mice,and their body mass was recorded once a week.The levels of uric acid(UA),creatinine(Cr),urine protein(UP),blood urea nitrogen(BUN)and urine urea nitrogen(UUN)as well as the levels of tumor necrosis factor α(TNF-α)and interleukin 6(IL-6)in serum or urine of each group were collected and measured on the 21st day.Hematoxylin-eosin(HE)staining was performed to observe kidney tissue injury in mice;real-time PCR(RT-PCR)was performed to determine ATP-binding cassette subfamily G member 2(ABCG2),urate transporter protein(URAT1),glucose transporter protein 9(GLUT9),and cytosolic factor NF-κB p50(κB p50)in kidney tissues.Results Compared with the normal control group,the body mass of mice in the model control group was significantly lower after the second weeks of modeling(P＜0.05),and the levels of UA,Cr,UP,BUN,UUN,TNF-α,IL-6 contents and GLUT9 mRNA and κB p50 mRNA expression contents of kidney tissues were significantly higher(P＜0.01,P＜0.05).Compared with the model control group,the levels of Cr,UP,BUN and UUN contents and renal tissue nuclear cytokine κB p50 mRNA expression were significantly lower in the high,medium and low dose groups of Lithocarpus litseifoliu(P＜0.01,P＜0.05).The UA levels were significantly lower in the high dose group of Lithocarpus litseifoliu(P＜0.05),and renal ABCG2 mRNA expression was significantly higher in the medium dose group(P＜0.01).The renal URAT1 mRNA expression was significantly decreased in the low dose group(P＜0.01).Conclusion Lithocarpus litseifoliu has shown ameliorative effects on HN mice,and the mechanism may be related to the modulation of renal uric acid transporters,improvement of renal function and anti-inflammation effects.

OBJECT IVE To study the effects and potential mechanism of saltwater stir-baked Eucommia ulmoides on kidney-yang deficiency in rats. METHODS Ninety SD rats were randomly divided into normal control group （15 rats） and modeling group （75 rats）. Modeling group was given adenine intragastrically to establish kidney-yang deficiency model. After modeling，modeling group were randomly divided into model group ，positive control group （Guifu dihuang tablet 2.5 g/kg）， low-dose，medium-dose and high-dose groups of saltwater stir-baked E. ulmoides （1.5，3，6 g/kg），with 15 rats in each group. Administration groups were given relevant medicine intragastrically ，normal control group and model group were given normal saline intragastrically ，once a day ，for consecutive 8 weeks. The body weight of rats was measured before modeling and after medication. The score of kidney-yang deficiency syndrome was performed after medication. The levels of blood urea nitrogen （BUN），serum creatinine （SCR），testosterone（T）and cortisol （COR）in serum and superoxide dismutase （SOD）activity， malondialdehyde（MDA）level in renal tissue were detected. The pathological changes of renal tissue were observed after HE staining. Relative expressions of hypoxia-inducible factor- 1 α（HIF-1 α）and signal transducer and activator of transcription 5 （STAT5） mRNA in renal tissue were detected by RT-PCR. The relative expressions of HIF- 1α，STAT5 and phosphorylated STAT 5 （p-STAT5）protein and the ratio of gray values of p-STAT 5 and STAT 5（p-STAT5/STAT5）in renal tissue were detected by Western blot. RESULTS Before modeling ，there was no statistical significance in body weight of rats in each group （P＞0.05）. After medication， compared with model group ， pathological changes of renal tissue were all recovered in saltwater stir-baked E. ulmoides groups and positive control group ， while body weight ，the level of T in serum and SOD activity qq.com in renal tissue were all increase d significantly （P＜0.05）. The scores of kidney-yang deficiency syndrome ，levels of BUN ， SCR and COR in serum ，MDA level in renal tissue ，the relative expressions of HIF- 1α and STAT5 mRNA，the relative expressions of HIF- 1α，STAT5 and p-STAT 5 protein as well as p-STAT5/STAT5 were all significantly decre ased （P＜0.05）. The above effects of saltwater stir-baked E. ulmoides were in dose-dependent manner （P＜0.05）. CONCLUSIONS Saltwater stir-baked E. ulmoides can significantly relieve renal tissue damage in rats with kidney-yang deficiency ，decrease the levels of BUN ，SCR and COR in serum ，increase the level of T in serum ，the mechanism of which may be associated with anti-oxidative stress and inhibition of the expression of HIF- 1α and STAT5 protein.

It has been demonstrated that APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) is involved in the regulation of several growth-related signaling pathways and thus closely associated with the development and progression of some cancers. Diallyl trisulfide (DAT), a garlic-derived bioactive compound, exerts selective cytotoxicity to various human cancer cells through interfering with pro-survival signaling pathways. However, whether and how DAT affects survival of human hepatocellular carcinoma (HCC) cells remain unclear. Herein, we tested the hypothesis of the involvement of APPL1 in DAT-induced cytotoxicity in HCC HepG2 cells. We found that Lys 63 (K63)-linked polyubiquitination of APPL1 was significantly decreased whereas phosphorylation of APPL1 at serine residues remained unchanged in DAT-treated HepG2 cells. Compared with wild-type APPL1, overexpression of APPL1 K63R mutant dramatically increased cell apoptosis and mitigated cell survival, along with a reduction of phosphorylation of STAT3, Akt, and Erk1/2. In addition, DAT administration markedly reduced protein levels of intracellular TNF receptor-associated factor 6 (TRAF6). Genetic inhibition of TRAF6 decreased K63-linked polyubiquitination of APPL1. Moreover, the cytotoxicity impacts of DAT on HepG2 cells were greatly attenuated by overexpression of wild-type APPL1. Taken together, these results suggest that APPL1 polyubiquitination probably mediates the inhibitory effects of DAT on survival of HepG2 cells by modulating STAT3, Akt, and Erk1/2 pathways.

Fungal polyketides display complex structures and variously biological activities. Their biosynthetic pathways generally contain novel enzyme-catalyzed reactions. This review provides a summary of recent research advances in molecular mechanism of the biosynthesis of fungal polyketides including highly-reducing polyketide synthases (HR-PKSs), non-reducing polyketide synthases (NR-PKSs), as well as polyketide-nonribosomal peptide synthase (PKS-NRPSs) and reducingnon- reducing polyketide synthase (HR-NR PKSs) hybrids. The elucidation of biosynthetic mechanism of many fungal polyketides provides guidance on the discovery of new biosynthetic gene cluster of fungal polyketide natural products and compounds with novel structures as well as their analogue.

Objective To establish a sensitive and specific LC-MS/MS method for measurement of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, ginsenoside Rd, tanshinone Ⅰ, astragaloside Ⅳ and harpagosidein of Fufang Xueshuantong Capsule in rat plasma. Methods The HPLC separation was performed on Thermo Hypersil GOLD column (2.1 mm× 100mm, 5 μm) at 30 ℃, injecting 10 μL and using acetonitrile-water (0.1% formic acid) as the mobile phrase (B was acetonitrile, A was 0.1%formic acid;0-10 min, 25%-55%B;10-20 min, 55%-70%B) with the flow rate of 0.2 mL/min. Detection was performed on a tandem quadrapole mass spectrometer using positive electrospray ionization, SRM scan mode. Results The eight compounds showed good linearity in wide ranges (notoginsenoside R1 1.00-800 ng/mL, ginsenoside Rg1 0.950-760 ng/mL, ginsenoside Re 1.44-1440 ng/mL, ginsenoside Rb1 1.33-1330 ng/mL, ginsenoside Rd 9.90-990 ng/mL, harpagosidein 1.01-1010 ng/mL, astragaloside Ⅳ 1.16-928 ng/mL, tanshinone Ⅰ 10.0-800 ng/mL). In addition, the accuracy and recovery were around 85%-115%and 50%-70%. The RSD of intra and inter day precision were lower than 15%. Conclusion The method is specific, rapid and sensitive. Therefore, it can be applied to pharmacokinetic study of eight effective compounds in Fufang Xueshuantong Capsule.

Sixty male SD rats were separately fed by normal diet or high-fat diet.After eight weeks of highfat diet,these rats were injected low dose streptozotocin (30 mg/kg).Diazoxide or glipizide was administered to the diabetic rats for 4 weeks.The results showed that body weight,serum insulin,and insulin sensitive index were decreased in the obese diabetic rats while the fasting blood glucose,total cholesterol,and triglyceride levels were increased compared with the high-fat diet group ( all P＜0.01 ).Consistent with the results of glipizide,diazoxide treatment lowered blood glucose,improved glucose tolerance,and decreased islet cell apoptosis compared with the diabetes mellitus group ( all P＜0.05 ).The results suggest that diazoxide can improve islet function of obese type 2 diabetic rats via decreasing insulin secretion and thus lessening the load on islet cells.

OBJECTIVETo investigate the inhibitory activities of norcantharidin (NCTD), a demethylated analogue of cantharidin, on Hep3B cells (a human hepatoma cell line) with deficiency of p53.

METHODSThe survival rate of the Hep3B cells after treating with NCTD was measured by MTT assay. Cell cycle of treated cells was analyzed by flow cytometry, and DNA fragmentation was observed by electrophoresis. The influence of inhibitors for various caspases and anti-death receptors antibodies on the NCTD-induced apoptosis in the cells was determined.

RESULTSNCTD treatment resulted in growth inhibition of Hep3B cells in a dose- and time-dependent manner. Cell cycle analysis of the cells after treatment with NCTD for 48 h shows that NCTD induced G(2)M phase arrest occurs at low concentration ([Symbol: see text] 25 μmol/L) but G(0)G(1) phase arrest at high concentration (50 μmol/L). The addition of both caspase-3 and caspase-10 inhibitors completely inhibited DNA fragmentation. Addition of anti-TRAIL/DR5 antibody significantly inhibited DNA fragmentation.

CONCLUSIONNCTD may inhibit the proliferation of Hep3B cells by arresting cell cycle at G(2)M or G(0)G(1) phase, and induce cells apoptosis via TRAIL/DR5 signal transduction through activation of caspase-3 and caspase-10 by a p53-independent pathway.

Antibodies, Neoplasm ; pharmacology ; Antibodies, Neutralizing ; pharmacology ; Apoptosis ; drug effects ; Bridged Bicyclo Compounds, Heterocyclic ; pharmacology ; Carcinoma, Hepatocellular ; enzymology ; pathology ; Caspase 10 ; metabolism ; Caspase 3 ; metabolism ; Caspase Inhibitors ; pharmacology ; Cell Cycle Checkpoints ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; DNA Fragmentation ; drug effects ; Humans ; Immunohistochemistry ; Liver Neoplasms ; enzymology ; pathology ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; metabolism ; Signal Transduction ; drug effects ; TNF-Related Apoptosis-Inducing Ligand ; metabolism ; Tumor Suppressor Protein p53 ; metabolism