Distinct Determinants in HIV-1 Vif and Human APOBEC3 Proteins Are Required for the Suppression of Diverse Host Anti-Viral Proteins

APOBEC3G (A3G) and related cytidine deaminases of the APOBEC3 family of proteins are potent inhibitors of many retroviruses, including HIV-1. Formation of infectious HIV-1 requires the suppression of multiple cytidine deaminases by Vif. HIV-1 Vif suppresses various APOBEC3 proteins through the common mechanism of recruiting the Cullin5-ElonginB-ElonginC E3 ubiquitin ligase to induce target protein polyubiquitination and proteasome-mediated degradation. The domains in Vif and various APOBEC3 proteins required for APOBEC3 recognition and degradation have not been fully characterized.In the present study, we have demonstrated that the regions of APOBEC3F (A3F) that are required for its HIV-1-mediated binding and degradation are distinct from those reported for A3G. We found that the C-terminal cytidine deaminase domain (C-CDD) of A3F alone is sufficient for its interaction with HIV-1 Vif and its Vif-mediated degradation. We also observed that the domains of HIV-1 Vif that are uniquely required for its functional interaction with full-length A3F are also required for the degradation of the C-CDD of A3F; in contrast, those Vif domains that are uniquely required for functional interaction with A3G are not required for the degradation of the C-CDD of A3F. Interestingly, the HIV-1 Vif domains required for the degradation of A3F are also required for the degradation of A3C and A3DE. On the other hand, the Vif domains uniquely required for the degradation of A3G are dispensable for the degradation of cytidine deaminases A3C and A3DE.Our data suggest that distinct regions of A3F and A3G are targeted by HIV-1 Vif molecules. However, HIV-1 Vif suppresses A3F, A3C, and A3DE through similar recognition determinants, which are conserved among Vif molecules from diverse HIV-1 strains. Mapping these determinants may be useful for the design of novel anti-HIV inhibitors

Herbal Compound “Jiedu Huayu” Reduces Liver Injury in Rats via Regulation of IL-2, TLR4, and PCNA Expression Levels

Aim of the Study. To investigate the preventative effects of Jiedu Huayu (JDHY) on D-galactosamine (D-GalN) and lipopolysaccharide-induced acute liver failure (ALF) and to evaluate the possible mechanisms of action. Materials and Methods. ALF was induced in Wistar rats by administrating D-GalN (900 mg/kg) and lipopolysaccharide (10 μg/kg). After treatment with JDHY granules, the levels of blood alanine aminotransferase, aspartate aminotransferase, total bilirubin, and prothrombin time were determined. Proliferating cell nuclear antigen was detected by immunohistochemistry staining. The expression of interleukin-2 (IL-2) and toll-like receptor 4 (TLR4) was examined by fluorescence quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. Results. JDHY treatment dramatically improved liver function and increased survival rates in an ALF model in rats. We observed a decrease in IL-2 and TLR4 expression following treatment with JDHY in liver cells from ALF rats using qRT-PCR and Western blot analysis. Conclusion. We hypothesize that the therapeutic potential of JDHY for treating ALF is due to its modulatory effect on the suppression of inflammation and by promoting hepatocyte regeneration. Our results contribute towards validation of the traditional use of JDHY in the treatment of liver disease

Can LLMs like GPT-4 outperform traditional AI tools in dementia diagnosis? Maybe, but not today

Recent investigations show that large language models (LLMs), specifically GPT-4, not only have remarkable capabilities in common Natural Language Processing (NLP) tasks but also exhibit human-level performance on various professional and academic benchmarks. However, whether GPT-4 can be directly used in practical applications and replace traditional artificial intelligence (AI) tools in specialized domains requires further experimental validation. In this paper, we explore the potential of LLMs such as GPT-4 to outperform traditional AI tools in dementia diagnosis. Comprehensive comparisons between GPT-4 and traditional AI tools are conducted to examine their diagnostic accuracy in a clinical setting. Experimental results on two real clinical datasets show that, although LLMs like GPT-4 demonstrate potential for future advancements in dementia diagnosis, they currently do not surpass the performance of traditional AI tools. The interpretability and faithfulness of GPT-4 are also evaluated by comparison with real doctors. We discuss the limitations of GPT-4 in its current state and propose future research directions to enhance GPT-4 in dementia diagnosis.Comment: 16 pages, 6 figure

High Prevalence and Genetic Diversity of HCV among HIV-1 Infected People from Various High-Risk Groups in China

BACKGROUND: Co-infection with HIV-1 and HCV is a significant global public health problem and a major consideration for anti-HIV-1 treatment. HCV infection among HIV-1 positive people who are eligible for the newly launched nationwide anti-HIV-1 treatment program in China has not been well characterized. METHODOLOGY: A nationwide survey of HIV-1 positive injection drug uses (IDU), former paid blood donors (FBD), and sexually transmitted cases from multiple provinces including the four most affected provinces in China was conducted. HCV prevalence and genetic diversity were determined. We found that IDU and FBD have extremely high rates of HCV infection (97% and 93%, respectively). Surprisingly, people who acquired HIV-1 through sexual contact also had a higher rate of HCV infection (20%) than the general population. HIV-1 subtype and HCV genotypes were amazingly similar among FBD from multiple provinces stretching from Central to Northeast China. However, although patterns of overland trafficking of heroin and distinct HIV-1 subtypes could be detected among IDU, HCV genotypes of IDU were more diverse and exhibited significant regional differences. CONCLUSION: Emerging HIV-1 and HCV co-infection and possible sexual transmission of HCV in China require urgent prevention measures and should be taken into consideration in the nationwide antiretroviral treatment program

Land use/cover change dynamics of the Heihe river basin revealed by Knowledge-based classification with landsat TM.DEM and other information

Radiometric correction was difficult to perform on imageries of mountainous areas where atmospheric and climatic data were difficult to obtain, because of the absence of weather station. It was a general knowledge that the classification of the non-radiometrically corrected imagery resulted to misclassifications, low accuracy and inconsistencies. From these problems，the objective of this study were drawn, namely to utilize a knowledge-based decision land cover and land use data. The study site was the heihe watershed, Province of Gansu, China. Two sets of Landsat TM taken form 1989 and 2002 were used as inputs to the project. The raw imageries were geometrically rectified, and atmospheric correction was done by the software of 6S. classified image using knowledge-based decision rule criteria created by the software of ERDAS Imagine. Result of the cross-tabulation showed that the classified imageries refined by the computer program had no incidence of invalid change result unlike the classified imageries produced without the assistance of the knowledge-based computer program. Also, its classification accuracy was higher than that of the imageries produced without the assistance of the computer program. We therefore conclude that the use of knowledge-based decision rule computer program to assist the standard classification procedures improved the accuracy of the land cover and land use data and the consistency of the land cover and land use change results

RESEARCH ON DYNAMIC CHARACTERISTICS OF WIND TURBINE MAIN SHAFT BEARING UNDER DIFFERENT WORKING CONDITIONS

In order to get the dynamic characteristics of wind turbinemain shaft bearing under different working conditions,tooka 1. 5 MW wind turbine manufactured by one turbine factoryas an example,the main shaftwassimplifiedabstractly and the axial and radial loadon main shaft bearingwere given by blade element theory. The 3 D model of main shaft bearingwasdrawn in UG and imported into ADAMS toestablish the multi rigid kinetic model of main shaft bearing,the interactionsbetween the balls of main shaft bearing and inner ring,outer ring and separator wereanalyzed under threedifferent working conditions. The analysis resultsindicate that the interaction forces between the balls of main shaft bearing and inner ring,outer ring and separator aremaximal during theemergency brake period of wind turbine,it is second during thesuddenvariation periodof the wind turbine revolving speedand it is minimalfrom starting until running steadily