Using the release and collection method, it is confirmed that cotton leaf roller, Syllepte derogata overwinters as mature diapausing larvae. To elucidate the species’ cold resistance mechanism, body water content, biochemical substance levels and the supercooling point of diapausing and non-diapausing larvae were evaluated during the winter. The maximum and minimum supercooling points of diapausing larvae were –18.23°C and −22.33°C, respectively, which were significantly lower. The free body water content of diapausing and non-diapausing larvae was 74.72% and 78.00%, respectively. However, the combined water, glycogen and fat contents were significantly higher in diapausing larvae. In the early overwintering stage, the supercooling point and body free water content steadily declined while glycogen content decreased rapidly. On the other hand, the fat and combined water contents increased slightly. In the late overwintering stage, glycogen content changed minimally, fat content declined rapidly and free water content increased slightly. These demonstrate that S. derogata utilises glycogen in the early stage and fat in the late stage of its overwintering.
The persistence of latent viral reservoirs remains the major obstacle to eradicating human immunodeficiency virus (HIV). We herein found that ICP34.5 can act as an antagonistic factor for the reactivation of HIV latency by herpes simplex virus type I (HSV-1), and thus recombinant HSV-1 with ICP34.5 deletion could more effectively reactivate HIV latency than its wild-type counterpart. Mechanistically, HSV-ΔICP34.5 promoted the phosphorylation of HSF1 by decreasing the recruitment of protein phosphatase 1 (PP1α), thus effectively binding to the HIV LTR to reactivate the latent reservoirs. In addition, HSV-ΔICP34.5 enhanced the phosphorylation of IKKα/β through the degradation of IκBα, leading to p65 accumulation in the nucleus to elicit NF-κB pathway-dependent reactivation of HIV latency. Then, we constructed the recombinant HSV-ΔICP34.5 expressing simian immunodeficiency virus (SIV) env, gag, or the fusion antigen sPD1-SIVgag as a therapeutic vaccine, aiming to achieve a functional cure by simultaneously reactivating viral latency and eliciting antigen-specific immune responses. Results showed that these constructs effectively elicited SIV-specific immune responses, reactivated SIV latency, and delayed viral rebound after the interruption of antiretroviral therapy (ART) in chronically SIV-infected rhesus macaques. Collectively, these findings provide insights into the rational design of HSV-vectored therapeutic strategies for pursuing an HIV functional cure.
The persistence of latent viral reservoirs remains the major obstacle to eradicating human immunodeficiency virus (HIV). We herein reported that recombinant herpes simplex virus type I (HSV-1) with ICP34.5 deletion could more effectively reactivate HIV latency than its wild-type counterpart. Mechanistically, HSV-ΔICP34.5 promoted the phosphorylation of HSF1 by decreasing the recruitment of protein phosphatase 1 (PP1α), thus effectively binding to the HIV LTR to reactivate the latent reservoirs. In addition, HSV-ΔICP34.5 enhanced the phosphorylation of IKKα/β through the degradation of IκBα, leading to p65 accumulation in the nucleus to elicit NF-κB pathway-dependent reactivation of HIV latency. Then, we constructed the recombinant HSV-ΔICP34.5 expressing simian immunodeficiency virus (SIV) env, gag, or the fusion antigen sPD1-SIVgag as an HIV therapeutic vaccine, aiming to achieve a functional cure by simultaneously reactivating viral latency and eliciting antigen-specific immune responses. Results showed that these constructs effectively elicited SIV-specific immune responses, reactivated SIV latency, and delayed viral rebound after the interruption of antiretroviral therapy (ART) in chronically SIV-infected rhesus macaques. Collectively, these findings provide insights into the rational design of HSV-vectored therapeutic strategies for pursuing an HIV functional cure.
OBJECTIVE:To investigate the mechanism of the prevention and treatment effects of dongbaogantai tablet(DT)on rats with alcoholic fatty liver(AFL).METHODS:SD rats were randomly divided into normal control group,model group and DT group.The model group and DT group were administered intragastrically with alcohol and fed with high fat diet for 8 weeks to replicate AFL model,meanwhile the model group were administered intragastrically with normal saline and DT group with DT synchronously for 8 weeks.Levels of TG,CHO,LDL-C,HDL-C,AST and ALT in serum,and MDA,NEFA,SOD and GSH-PX in hepatic tissue were detected and the pathological changes of liver were observed under light microscope.RESULTS:In DT group compared with model group,serum levels of TG,CHO,LDL-C,AST,ALT,MDA and NEFA were significantly down-regulated(P0.05),but levels of HDL-C,SOD and GSH-PX were significantly up-regulated(P0.05);however,the pathological changes of liver were similar to those in normal control group.CONCLUSION:DT can effectively prevent and treat AFL by reducing the lipid peroxidation.
AbstractBackground HIV/AIDS has emerged as a nationwide epidemic and has taken the forefront position as the primary infectious killer of adults in China. The control and prevention of the disease have been hampered by a weak link in the form of heterosexual transmission. However, conventional intervention measures have demonstrated suboptimal efficacy in reducing the incidence of new HIV infections. In light of the current epidemiological characteristics, we have developed and executed an innovative intervention model known as the Joint Prevention and Control Mechanism of the ‘CDC-Public Security Bureau-NGO’. The purpose of this research is to assess the impact of this model on the AIDS awareness, HIV infection rates, sexual behavior, and associated factors among female sex workers and elderly clients. Through the provision of robust evidence of the efficacy of this innovative model, we seek to advocate for its implementation in future interventions. Methods An 8-year consecutive cross-sectional survey, including a 4-year traditional intervention (2014-2017) and the 4-year ‘CDC-Public Security Bureau-NGO’ innovative intervention (2018-2021), was conducted to evaluate the effects of the new intervention. Compared to the traditional intervention, the ‘CDC-Public Security Bureau-NGO’ intervention achieved positive effects by decreasing risky behaviours. The GM(1, 1) model was performed to predict the proportion of HIV infection without implementing the innovative intervention in 2018–2021; P and C values were used to evaluate the performance of the model. Results The most recent condom use rate among female sex workers and elderly clients has increased from 81.1% to 95.3% (P < 0.05), newly reported cases of HIV have decreased by 15.56% yearly and the HIV infection rate among middle-aged and elderly people has dropped by 19.91% yearly. The innovative intervention model has significantly reduced the HIV infection rates. Conclusions The ‘CDC-Public Security Bureau-NGO’ innovative intervention has achieved beneficial effects on HIV/AIDS prevention and control and provides a good reference for Guangxi, China.
The persistence of latent viral reservoirs remains the major obstacle to eradicating human immunodeficiency virus (HIV). We herein reported that recombinant herpes simplex virus type I (HSV-1) with ICP34.5 deletion could more effectively reactivate HIV latency than its wild-type counterpart. Mechanistically, HSV-ΔICP34.5 promoted the phosphorylation of HSF1 by decreasing the recruitment of protein phosphatase 1 (PP1α), thus effectively binding to the HIV LTR to reactivate the latent reservoirs. In addition, HSV-ΔICP34.5 enhanced the phosphorylation of IKKα/β through the degradation of IκBα, leading to p65 accumulation in the nucleus to elicit NF-κB pathway-dependent reactivation of HIV latency. Then, we constructed the recombinant HSV-ΔICP34.5 expressing simian immunodeficiency virus (SIV) env, gag, or the fusion antigen sPD1-SIVgag as a therapeutic vaccine, aiming to achieve a functional cure by simultaneously reactivating viral latency and eliciting antigen-specific immune responses. Results showed that these constructs effectively elicited SIV-specific immune responses, reactivated SIV latency, and delayed viral rebound after the interruption of antiretroviral therapy (ART) in chronically SIV-infected rhesus macaques. Collectively, these findings provide insights into the rational design of HSV-vectored therapeutic strategies for pursuing an HIV functional cure.
Abstract Background Aortic dissection (AD) is an acute critical disease of the cardiovascular system characterized by high mortality and morbidity. According to reports, immune cell infiltration is associated to AD. However, the intrinsic molecular mechanisms underlying the pathogenesis of AD still need to be clarified. Methods Four datasets (GSE52093, GSE98770, GSE153434 and GSE190635) were download through the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) of each dataset were screened by robust rank aggregation (RRA) algorithms. Gene ontology (GO) functional enrichment analysis and Kyto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to DEGs. Using the Search Tool for Retrieval of Interacting Genes/Proteins (STRING) database, a protein–protein interaction (PPI) network was constructed, and the hub genes were identified by Cytoscape. And, after correcting for nonbiological effects between four datasets by Rank-In algorithm, we obtained a merged matrix. Furthermore, we adopted this merged matrix to evaluate immune infiltration by using CIBERSORT and single sample gene set enrichment analysis (ssGSEA). Finally, we calculated the correlation between hub genes and immune cells. Results Sixty-two integrated DEGs were identified. These DEGs were mainly enriched in 69 biological process (BP) terms and the ATP-binding cassette (ABC) transporters pathways. By applying 12 methods from Cytoscape plugin CytoHubba respectively, we selected final hub genes. The final hub genes consist of angiotensin Ⅰ converting enzyme (ACE), angiotensin converting enzyme 2 (ACE2), calsequestrin 2 (CASQ2) and TIMP metallopeptidase inhibitor 1 (TIMP1). CIBERSORT showed that monocytes ( P < 0.001) and activated mast cells ( P < 0.05) were higher fraction in AD group. ssGSEA showed that regulatory T cell ( P < 0.05), CD56 bright natural killer (NK) cell ( P < 0.01), central memory CD4 T cell ( P < 0.01), T follicular helper cell ( P < 0.01), activated dendritic cell ( P < 0.001), myeloid derived suppressor cells (MDSC) ( P < 0.001), monocytes ( P < 0.001), NK T cell ( P < 0.001), type 1 T helper cell (Th1) ( P < 0.001) and Th17 cell ( P < 0.001) were higher fraction in AD group. Conclusion ACE, ACE2, CASQ2 and TIMP1 are engaged in the process of AD, which can be used as molecular biomarkers for the screening and diagnosis of AD. Immune cell infiltration plays a major role in the development of AD.
Objective Talaromycosis is a serious regional disease endemic in Southeast Asia. In China, Talaromyces marneffei (T. marneffei) infections is mainly concentrated in the southern region, especially in Guangxi, and cause considerable in-hospital mortality in HIV-infected individuals. Currently, the factors that influence in-hospital death of HIV/AIDS patients with T . marneffei infection are not completely clear. Existing machine learning techniques can be used to develop a predictive model to identify relevant prognostic factors to predict death and appears to be essential to reducing in-hospital mortality. Methods We prospectively enrolled HIV/AIDS patients with talaromycosis in the Fourth People’s Hospital of Nanning, Guangxi, from January 2012 to June 2019. Clinical features were selected and used to train four different machine learning models (logistic regression, XGBoost, KNN, and SVM) to predict the treatment outcome of hospitalized patients, and 30% internal validation was used to evaluate the performance of models. Machine learning model performance was assessed according to a range of learning metrics, including area under the receiver operating characteristic curve (AUC). The SHapley Additive exPlanations (SHAP) tool was used to explain the model. Results A total of 1927 HIV/AIDS patients with T . marneffei infection were included. The average in-hospital mortality rate was 13.3% (256/1927) from 2012 to 2019. The most common complications/coinfections were pneumonia (68.9%), followed by oral candida (47.5%), and tuberculosis (40.6%). Deceased patients showed higher CD4/CD8 ratios, aspartate aminotransferase (AST) levels, creatinine levels, urea levels, uric acid (UA) levels, lactate dehydrogenase (LDH) levels, total bilirubin levels, creatine kinase levels, white blood-cell counts (WBC) counts, neutrophil counts, procaicltonin levels and C-reactive protein (CRP) levels and lower CD3 + T-cell count, CD8 + T-cell count, and lymphocyte counts, platelet (PLT), high-density lipoprotein cholesterol (HDL), hemoglobin (Hb) levels than those of surviving patients. The predictive XGBoost model exhibited 0.71 sensitivity, 0.99 specificity, and 0.97 AUC in the training dataset, and our outcome prediction model provided robust discrimination in the testing dataset, showing an AUC of 0.90 with 0.69 sensitivity and 0.96 specificity. The other three models were ruled out due to poor performance. Septic shock and respiratory failure were the most important predictive features, followed by uric acid, urea, platelets, and the AST/ALT ratios. Conclusion The XGBoost machine learning model is a good predictor in the hospitalization outcome of HIV/AIDS patients with T . marneffei infection. The model may have potential application in mortality prediction and high-risk factor identification in the talaromycosis population.
The persistence of latent viral reservoirs remains the major obstacle to eradicating human immunodeficiency virus (HIV). We herein reported that recombinant herpes simplex virus type I (HSV-1) with ICP34.5 deletion could more effectively reactivate HIV latency than its wild-type counterpart. Mechanistically, HSV-ΔICP34.5 promoted the phosphorylation of HSF1 by decreasing the recruitment of protein phosphatase 1 (PP1α), thus effectively binding to the HIV LTR to reactivate the latent reservoirs. In addition, HSV-ΔICP34.5 enhanced the phosphorylation of IKKα/β through the degradation of IκBα, leading to p65 accumulation in the nucleus to elicit NF-κB pathway-dependent reactivation of HIV latency. Then, we constructed the recombinant HSV-ΔICP34.5 expressing simian immunodeficiency virus (SIV) env, gag, or the fusion antigen sPD1-SIVgag as an HIV therapeutic vaccine, aiming to achieve a functional cure by simultaneously reactivating viral latency and eliciting antigen-specific immune responses. Results showed that these constructs effectively elicited SIV-specific immune responses, reactivated SIV latency, and delayed viral rebound after the interruption of antiretroviral therapy (ART) in chronically SIV-infected rhesus macaques. Collectively, these findings provide insights into the rational design of HSV-vectored therapeutic strategies for pursuing an HIV functional cure.
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