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Based on the inhibitory effect of CA-4 analogues and indoles on tubulin polymerization, we designed and synthesized a series of N-((1-methyl-1H-indol-3-yl)methyl)-2-(1H-pyrazol-1-yl or triazolyl)-N-(3,4,5-trimethoxyphenyl)acetamides.

Job exhaustion is not uncommon among Chinese middle school teachers, but the key antecedents of job exhaustion and the underlying mechanisms in this historically underrepresented population remain poorly understood. This study examined the association between job demand and exhaustion, and tested the mediating role of job satisfaction and the moderating role of teachers' role (i.e., homeroom versus subject) in this association. The two-wave, China Education Panel Survey data from 701 Chinese junior middle school teachers (

Staphylococcus and Streptococcus , two groups of major human pathogens, are equipped with a fatty acid kinase (Fak) machinery to scavenge host fatty acids. The Fak complex is contains an ATP-binding subunit FakA, which interacts with varied FakB isoforms, and synthesizes acyl-phosphate from extracellular fatty acids. However, how FakA recognizes its FakB partners and then activates different fatty acids is poorly understood. Here, we systematically describe the Fak system from the zoonotic pathogen, Streptococcus suis . The crystal structure of SsFakA complexed with SsFakB2 was determined at 2.6 Å resolution. An in vitro system of Fak-PlsX (phosphate: acyl-ACP transacylase) was developed to track acyl-phosphate intermediate and its final product acyl-ACP. Structure-guided mutagenesis enabled us to characterize a mechanism for streptococcal FakA working with FakB partners engaged in host fatty acid scavenging. These findings offer a comprehensive description of the Fak kinase machinery, thus advancing the discovery of attractive targets against deadly infections with Streptococcus .

The heterotrimeric Replication protein A (RPA) is the ubiquitous eukaryotic single-stranded DNA (ssDNA) binding protein and participates in nearly all aspects of DNA metabolism, especially DNA damage response. The N-terminal OB domain of the RPA70 subunit (RPA70N) is a major protein-protein interaction element for RPA. Previous crystallography studies of RPA70N with p53, DNA2 and PrimPol fragments revealed that RPA70N binds to amphipathic peptides that mimics ssDNA. NMR chemical-shift studies also provided valuable information of RPA70N residues interacting with target sequences. However, it is still not clear how RPA70N recognizes and distinguishes such a diverse group of proteins. Here we present high resolution crystal structures of RPA70N in complex with peptides from HelB, ATRIP, RMI1, WRN and BLM. The structures showed that in addition to the ssDNA mimicry mode of interaction, RPA70N employs multiple ways to bind its partners, some of which may serve to increase the avidity of RPA70N binding.

While the role of flipped teaching in students’ language performance is well documented, English teachers’ perspective about flipped teaching remains underexplored. Informed by the self-determinati...

To better understand scene images in the field of remote sensing, multi-label annotation of scene images is necessary. Moreover, to enhance the performance of deep learning models for dealing with semantic scene understanding tasks, it is vital to train them on large-scale annotated data. However, most existing datasets are annotated by a single label, which cannot describe the complex remote sensing images well because scene images might have multiple land cover classes. Few multi-label high spatial resolution remote sensing datasets have been developed to train deep learning models for multi-label based tasks, such as scene classification and image retrieval. To address this issue, in this paper, we construct a multi-label high spatial resolution remote sensing dataset named MLRSNet for semantic scene understanding with deep learning from the overhead perspective. It is composed of high-resolution optical satellite or aerial images. MLRSNet contains a total of 109,161 samples within 46 scene categories, and each image has at least one of 60 predefined labels. We have designed visual recognition tasks, including multi-label based image classification and image retrieval, in which a wide variety of deep learning approaches are evaluated with MLRSNet. The experimental results demonstrate that MLRSNet is a significant benchmark for future research, and it complements the current widely used datasets such as ImageNet, which fills gaps in multi-label image research. Furthermore, we will continue to expand the MLRSNet. MLRSNet and all related materials have been made publicly available at https://data.mendeley.com/datasets/7j9bv9vwsx/1 and https://github.com/cugbrs/MLRSNet.git .

Based on 4 annual waves of data from a large sample of Chinese college students (N = 2,329, Mage = 18.40 years old, SD = .85; 63.10% females), this study examines the within-person and between-person effects in the association between problematic Internet use (PIU) and mental health issues. Results of analyses using the developmental equilibrium model (i.e., an autoregressive, cross-lagged panel model) demonstrate a reciprocal positive association between PIU and mental health issues consistently across waves. In contrast, results of analyses utilizing the random intercept, cross-lagged panel model (i.e., a model that can disaggregate within-person and between-person effects) indicate a unidirectional positive within-person effect from PIU to mental health issues (rather than the reverse) consistently over time, while controlling for the between-person effects that exist when comparing different individuals. Such findings highlight the importance of disaggregating within-person and between-person effects in understanding the nature of the temporal dynamics of the association between PIU and mental health. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background. Coronavirus disease 2019 (COVID-19) is a potentially fatal pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially those of novel SARS-CoV-2 variants and infection has affected over 700 million people globally. Methods. This retrospective, descriptive study included 118 patients admitted with SARS-CoV-2 infection as confirmed by real-time reverse transcription polymerase chain reaction. Results. The median duration of detectable SARS-CoV-2 infection in patients with high ALT, AST, and PLT/LYMPH, or low CD4+, CD8+, and PLT/MONO was considerably longer. In the risk factor model, multivariate analysis was performed for the estimation of ALT (HR, 0.54; 95% CI, 0.36-0.81), AST (HR, 0.56; 95% CI, 0.34-0.93), CD4+ (HR,0.77; 95% CI, 0.48-1.24), CD8+ (HR,0.64; 95% CI, 0.37-1.11), PLT/LYMPH (HR, 1.16; 95% CI, 0.76-1.77), and PLT/MONO (HR, 0.64; 95% CI, 0.43-0.94). Conclusions. The longer viral RNA duration was associated with a higher International Prognostic Index score ( p = 0.0013 ), demonstrating for the first time that multivariate features of the bioindicators closely associated with SARS-CoV-2-infected patients clear the virus.

Qiu- Yue Ning,1,&ast; Na Liu,2,&ast; Ji-Zhou Wu,1 Die-Fei Hu,1 Qi Wei,1 Jin-Ai Zhou,3 Jun Zou,4 Ning Zang,5,6 Guo-Jian Li1 1Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Life Sciences Institute, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3Youjiang Medical University for Nationalities, Baise, Guangxi, People’s Republic of China; 4The Fourth People’s Hospital of Nanning, Nanning, Guangxi, People’s Republic of China; 5School of Basic Medicine, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 6Key Laboratory of AIDS Prevention and Treatment, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guo-Jian Li; Ning Zang Tel +86 771-5356531Email liguojian2016@yeah.net; zangning@gxmu.edu.cnIntroduction: In order to find the early diagnostic markers of AIDS combined with TM infection, we detected and analyzed the serum exosomal miRNAs of AIDS patients with or without TM infection.Materials and Methods: We profiled the expression levels of miRNAs via RNA sequencing in serum exosomes from the pooled samples of 17 AIDS patients combined without TM infection and 15 AIDS combined with TM infection patients. For external validation, we validated these results using real-time quantification polymerase chain reaction (qRT-PCR) in an independent cohort of 35 AIDS patients combined without TM infection and 33 AIDS combined with TM infection patients. Finally, bioinformatics was used to predict the target genes and pathways of meaningful miRNAs.Results: A total of 131 serum exosomal miRNAs including 73 up-regulated and 59 down-regulated miRNAs were found to be differentially expressed (log2FC≥ 1 and FDR < 0.01) in the two groups. A validation analysis revealed that three miRNAs (miR-192-5p, miR-194-5p and miR-1246) were upregulated in exosomes from AIDS combined with TM infection patients. ROC analyses showed that the AUC in combined diagnosis of the three miRNAs was 0.742, and the diagnostic sensitivity and specificity were 0.568 and 0.861, respectively. In the biological process analysis, all the 3 miRNAs were involved in transcription, DNA-templated and positive regulation of transcription from RNA polymerase II promoter. At the same time, the related pathways were involved in TGF-β signaling pathway, AMPK signaling pathway, Wnt signaling pathway, MAPK signaling pathway, cGMP-PKG and cAMP signaling pathway, etc.Conclusion: miR-192-5p, miR-194-5p and miR-1246 in serum exosomes might be a potential biomarker for AIDS combined with TM infection patients, which may be involved in TGF-β signaling pathway, AMPK signaling pathway, Wnt signaling pathway, MAPK signaling pathway, cGMP-PKG and cAMP signaling pathway, etc. Further research is needed on the biological functions and mechanisms of these miRNAs.Keywords: exosomes, AIDS, Talaromyces marneffei, microRNA, biomarkers

Introduction In order to find the early diagnostic markers of AIDS combined with TM infection, we detected and analyzed the serum exosomal miRNAs of AIDS patients with or without TM infection. Materials and Methods We profiled the expression levels of miRNAs via RNA sequencing in serum exosomes from the pooled samples of 17 AIDS patients combined without TM infection and 15 AIDS combined with TM infection patients. For external validation, we validated these results using real-time quantification polymerase chain reaction (qRT-PCR) in an independent cohort of 35 AIDS patients combined without TM infection and 33 AIDS combined with TM infection patients. Finally, bioinformatics was used to predict the target genes and pathways of meaningful miRNAs. Results A total of 131 serum exosomal miRNAs including 73 up-regulated and 59 down-regulated miRNAs were found to be differentially expressed (log2FC≥1 and FDR

Objectives For migrant female sex workers (FSWs) at the Sino-Vietnamese border, the impact of work time in their current location on the spread of HIV/AIDS is not clear. Methods Data were collected from the Sino-Vietnamese border cities of Guangxi, China. Migrant FSWs working in these cities were studied. FSWs who worked less than 6 months in their current location were assigned to the short-term work group (ST FSWs), and FSWs who worked equal to or longer than 6 months in their current location were assigned to the long-term work group (LT FSWs). Logistic regression was performed to examine the impact of work time in the current location and factors associated with HIV infection. Results Among the 1667 migrant FSWs, 586 (35.2%) and 1081 (64.9%) were assigned to the ST FSW and LT FSW groups, respectively. Compared to LT FSWs, ST FSWs were more likely to be of Vietnamese nationality, be less than 18 years old when they first engaged in commercial sex work, and have a low-level of HIV-related knowledge and had higher odds of using condoms inconsistently, having more male clients, having no regular male clients, and having a history of male clients who used aphrodisiacs but lower odds of receiving free condoms distribution and education/HIV counselling and testing programme. The analysis of factors associated with HIV infection revealed that Vietnamese FSWs, less than 18 years old when they first engaged in commercial sex work, having no regular male clients, and having lower average charge per sex transaction were correlated with HIV infection. Conclusion FSWs with short-term work at the Sino-Vietnamese border had a higher risk of risky sex and were correlated with HIV risk factors. Vietnamese FSWs were at higher risk of HIV infection, and they were more likely to have short-term work. More targeted HIV prevention should be designed for new FSWs who recently began working in a locality to further control the spread of HIV, particularly cross-border FSWs.

Using latent profile analyses and based on two-wave data from 5,388 Chinese adolescents (Mage = 15.79, SD = 0.66; 51.99% females), this study examined the variety of ways in which adolescents' perceived career-related parental processes (i.e., parental expectations, support, interference, barriers to engagement, and parent-child congruence) may be configured within families and how such configurations may be associated with adolescents' career adaptability and ambivalence one year later. Three meaningful profiles were identified: the "Supportive but not Intrusive" (SNI) profile, the "Unsupportive but not Permissive" (UNP) profile, and the "Ambivalent and Controlling" (AC) profile. Adolescents in the UNP profile reported higher levels of career ambivalence and lower levels of career adaptability than did those in either the SNI or the AC profiles. Implications for career development among Chinese adolescents were discussed.

Glycosyltransferases (GTs) are enzymes that catalyze reactions attaching an activated sugar to an acceptor substrate, which may be a polysaccharide, peptide, lipid, or small molecule. In the past decade, notable progress has been made in revealing and cloning genes encoding polysaccharide-synthesizing GTs. However, the vast majority of GTs remain structurally and functionally uncharacterized. The mechanism by which they are organized in the Golgi membrane, where they synthesize complex, highly branched polysaccharide structures with high efficiency and fidelity, is also mostly unknown. This review will focus on current knowledge about plant polysaccharide-synthesizing GTs, specifically focusing on protein-protein interactions and the formation of multiprotein complexes.

This study aimed to investigate the anti-quorum sensing (QS) activity of Artemisia argyi leaf extracts (AALE) towards Pseudomonas aeruginosa PAO1 as well as the underlying molecular mechanisms. Using a biosensor Chromobacterium violaceum CV026, AALE were found to have anti-QS activity as AALE treatment significantly inhibited the violacein production of C. violaceum CV026 while produced little effect on the cell growth. Beyond that a higher dosage of AALE inhibited cell growth, sub-MIC of AALE significantly reduced the production of QS-regulated virulence factors (pyocyanin, elastase, and rhamnolipid), biofilm formation, and the swarming and swimming motility in P. aeruginosa PAO1 with a dosage-dependent manner. Quantitative real-time PCR (qRT-PCR) analysis did not detect the direct inhibitory effect of AALE on the expression of QS genes (lasI, lasR, rhlI, and rhlR). By iTRAQ-based quantitative proteomic analysis, 129 proteins were found to be differentially expressed upon AALE treatment, with 85 upregulated and 44 downregulated proteins, respectively. Functional enrichment analysis of the differential proteins revealed that AALE exerted anti-QS activity towards P. aeruginosa PAO1 by upregulating the expression of the global regulator CsrA, inducing oxidative stress, and perturbing protein homeostasis. Moreover, the inhibitory effect of AALE on the virulence of P. aeruginosa PAO1 was likely to be achieved by attenuating the expression of QS-regulated genes instead of QS genes. Collectively, the results of this study provide a basis for the future use of AALE as a preservative in controlling food spoilage caused by P. aeruginosa.

This study aimed to investigate the anti-quorum sensing (QS) activity of Artemisia argyi leaf extracts (AALE) towards Pseudomonas aeruginosa PAO1 as well as the underlying molecular mechanisms. Using a biosensor Chromobacterium violaceum CV026, AALE were found to have anti-QS activity as AALE treatment significantly inhibited the violacein production of C. violaceum CV026 while produced little effect on the cell growth. Beyond that a higher dosage of AALE inhibited cell growth, sub-MIC of AALE significantly reduced the production of QS-regulated virulence factors (pyocyanin, elastase, and rhamnolipid), biofilm formation, and the swarming and swimming motility in P. aeruginosa PAO1 with a dosage-dependent manner. Quantitative real-time PCR (qRT-PCR) analysis did not detect the direct inhibitory effect of AALE on the expression of QS genes (lasI, lasR, rhlI, and rhlR). By iTRAQ-based quantitative proteomic analysis, 129 proteins were found to be differentially expressed upon AALE treatment, with 85 upregulated and 44 downregulated proteins, respectively. Functional enrichment analysis of the differential proteins revealed that AALE exerted anti-QS activity towards P. aeruginosa PAO1 by upregulating the expression of the global regulator CsrA, inducing oxidative stress, and perturbing protein homeostasis. Moreover, the inhibitory effect of AALE on the virulence of P. aeruginosa PAO1 was likely to be achieved by attenuating the expression of QS-regulated genes instead of QS genes. Collectively, the results of this study provide a basis for the future use of AALE as a preservative in controlling food spoilage caused by P. aeruginosa. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02663-5.

An emerging (yet still scant) body of research has linked interparental hostility to youth compromised social competence over time among adolescents. Moreover, little is known about the conditions under which and the processes through which this association might occur. Using prospective data from 878 youth (50.23% females) and their parents and teachers, this study examined how interparental hostility and cooperative conflict might work in conjunction with each other to predict youth social competence over time via parent-child relationship quality. Results demonstrated that interparental cooperative conflict at grade 5 buffered the negative association between interparental hostility at grade 5 and mother-child but not father-child relationship quality at grade 6. Mother-child relationship quality, in turn, was associated positively with youth social competence at age 15. As such, interparental hostility at grade 5 was negatively related to youth social competence at age 15 via mother-child relationship quality at grade 6 only when interparental cooperative conflict at grade 5 was low. This study represents a more nuanced and specific examination of the implications of interparental hostility for child later social development by highlighting underlying moderating and mediating mechanisms. Relevant implications for the development of more targeted and effective interventions are also discussed.Un número cada vez mayor (aunque aún escaso) de investigaciones han vinculado la hostilidad interparental con la competencia social comprometida de los jóvenes conforme avanza el tiempo entre adolescentes. Además, se sabe poco acerca de las condiciones en las cuales podría producirse esta asociación, así como acerca de los procesos por los cuales podría producirse. Utilizando datos prospectivos de 878 jóvenes (el 50.23 % de sexo femenino) y de sus padres y maestros, este estudio analizó cómo la hostilidad interparental y el conflicto cooperativo podrían funcionar en conjunto para predecir la competencia social de los jóvenes conforme avanza el tiempo mediante la calidad de la relación entre padres e hijos. Los resultados demostraron que el conflicto cooperativo interparental en el grado 5 amortiguó la asociación negativa entre la hostilidad interparental en el grado 5 y una menor calidad de la relación entre madre e hijo, pero no entre padre e hijo, en el grado 6. La calidad de la relación entre madre e hijo, a su vez, estuvo asociada positivamente con la competencia social de los jóvenes a los 15 años. Como tal, la hostilidad interparental en el grado 5 estuvo asociada negativamente con la competencia social de los jóvenes a los 15 años mediante la calidad de la relación entre madre e hijo en el grado 6 solo cuando el conflicto cooperativo interparental en el grado 5 fue bajo. Este estudio representa un análisis más matizado y específico de las implicancias de la hostilidad interparental para el desarrollo social posterior de los niños destacando un posible factor moderador y mecanismo de mediación. Se debaten algunas implicancias relevantes para el desarrollo de intervenciones más dirigidas y eficaces.研究父母间的敌意對青少年社会能力發展的影響是一個新興且重要的研究課題。但是对二者之間產生聯繫的具體条件和过程，我們目前仍知之甚少。基於878名青少年(50.23%为女性)及其父母和老师的前瞻性数据，本研究考察了父母间的敌意和合作冲突如何交互作用並通过影響亲子关系质量而最終预测青少年的社会能力的發展變化。结果显示，五年级時候父母间的合作冲突对五年级時候父母间敌对行为与六年级母子关系质量间的負向聯繫有缓冲作用，而对其與六年级父子关系质量的負向聯繫没有缓冲作用。進而，母子关系质量与青少年15岁时的社交能力呈正相关。因此，只有在5年级父母间合作冲突较低时，5年级時候的父母间敌意才通过降低6年级時的母子关系质量而与青少年15歲時的社会能力產生負向聯繫。本研究通过揭示潜在的调节因素和中介机制，对父母间敌对行为对儿童日后社会性发展的影响进行了更为细致和具体的研究。本研究对于開發更有针对性和更有效的干预措施具有啟示意义。.

Background Identification of new HIV infections (HIV incidence) is critical for monitoring AIDS epidemic and assessing the effectiveness of intervention measures. However, current methods for distinguishing new infections from newly diagnosed HIV-1 patients are still imperfect. We explored utilizing miRNAs as biomarker to identify HIV new infections. Methods According to the HIV-1 status and the estimated duration of infection (EDI), we enrolled participants and divided them into three groups: healthy control, new infection (within 1 year), and old infection (longer than 1 year). Participants were assigned into screening set or validation set. miRNA microarray was performed in screening set and the differentially expressed miRNAs were screened out. The differentially expressed miRNAs were further confirmed in validation set and HIV-1 IIIB-MT2 cells infection system. Results In screening set, 5 miRNAs including miR-1291, miR-3609, miR-3162-3p, miR-874-5p and miR-4258 were screened out for their differential expression in plasma among three groups. In validation set, down- trend of miR-3162-3p was validated from healthy control, new infection to old infection groups. In HIV-1 IIIB-MT2 system, the levels of miR-3162-3p also decreased along with infection duration in vitro. Sensitivity and specificity for miR-3162-3p to distinguish new infection from old infection were 100.0% and 71.43%, respectively, with the cut-off value of 0.916. Conclusion miR-3162-3p in plasma could be a potential microRNA biomarker to identify HIV new infections in HIV-1 infected patients.

It is a daunting task to eradicate tuberculosis completely in Heng County due to a large transient population, human immunodeficiency virus/tuberculosis coinfection, and latent infection. Thus, a high-precision forecasting model can be used for the prevention and control of tuberculosis. In this study, four models including a basic autoregressive integrated moving average (ARIMA) model, a traditional ARIMA–generalized regression neural network (GRNN) model, a basic GRNN model, and a new ARIMA–GRNN hybrid model were used to fit and predict the incidence of tuberculosis. Parameters including mean absolute error (MAE), mean absolute percentage error (MAPE), and mean square error (MSE) were used to evaluate and compare the performance of these models for fitting historical and prospective data. The new ARIMA–GRNN model had superior fit relative to both the traditional ARIMA–GRNN model and basic ARIMA model when applied to historical data and when used as a predictive model for forecasting incidence during the subsequent 6 months. Our results suggest that the new ARIMA–GRNN model may be more suitable for forecasting the tuberculosis incidence in Heng County than traditional models.

Rural-to-urban migrants are at high risk of HIV infection. The goal of this survey was to explore the commercial sexual behavior and condom use among male rural-to-urban migrants in western China. A cross-sectional survey on male rural-to-urban migrants in western China was conducted. Among all the subjects surveyed, 140 (7.4%) had commercial sexual behavior, which is associated with being aged older than 24 years, being of Han or other ethnic minorities, being divorced, separated, or widowed, having experienced drug abuse, having had heterosexual behavior, having had casual sexual partners, having had sex with a homosexual, and being from Xinjiang. A total of 31.4% of them never use condoms when buying sex. Not using condoms is associated with being from Chongqing, having a high school or above education, and having commercial sex monthly. Commercial sexual behavior and not using condoms are common among male rural-to-urban migrants in western China. Strategies and appropriate education should be developed to prevent HIV transmission due to high-risk sexual behaviors.

China's HIV/AIDS epidemic continues to grow in rural and less developed areas. This consecutive cross-sectional study examines demographic and behavioral factors associated with HIV/STI infection, Hepatitis C (HCV) and other sexually transmitted infections (STIs) among Vietnamese female sex workers (FSW), a vulnerable population who cross into Guangxi, China. This study is a secondary data analysis of 303 Vietnamese and 4,348 Chinese FSWs recruited over seven years from two Chinese counties that border Vietnam. Logistic regression models compared demographics, HIV/STI status, HIV/AIDS-related knowledge, attitudes, and risk behaviors between Vietnamese FSWs and Chinese FSWs. Compared with Chinese FSWs, Vietnamese FSWs were younger, had attained lower education levels, were highly mobile, more likely to report using drugs, and were more vulnerable to HIV/STIs. Younger age, less educational attainment, shorter time in their current working location, no voluntary HIV testing in the last year, greater drug use, and not using condoms for all commercial sex in the last month were associated with higher HIV/STIs. In conclusion, several factors were associated with HIV/STI risk in Vietnamese cross-border FSWs. There is a pressing need to improve support systems for Vietnamese cross-border FSW and health system cooperation across the Chinese/Vietnamese border.

Berbamine is a plant-derived alkaloid with amazing and wide diversity of pharmacological properties which range from antimicrobial and anticancer. Nonetheless, the anticancer properties of Berbamine have not been thoroughly evaluated against colon cancer cells. This study was undertaken to evaluate the anticancer effects of Berbamine against human colon cancer cells (HT-29 colon cancer cells). Μethods: CCK-8 assay was used to determine the cell viability. DAPI and propidium iodide (PI) staining assays were used for the detection of apoptosis. Electron microscopy was used for the determination of autophagy. Wound healing assay was used to monitor cell migration. Protein expression was determined by western blotting.The results showed that Berbamine caused a remarkable decrease in the HT-29 cell viability with an IC50 of 14 µM, while the high IC50 of Berbamine against the normal CDD-18Co cells indicated low toxicity of this molecule against the normal cells. DAPI and PI staining assays showed nuclear fragmentation, indicative of apoptosis in HT-29 cells. Berbamine also caused activation of caspase-3 and 9 and increased the Bax/Bcl-2 ratio. Electron microscopic analysis showed that Berbamine triggered the development of autophagic vesicles in the HT-29 cells which was concomitant with the increase in protein levels of LC3B-I, ATG-5, ATG-12 and Beclin-1. Wound healing assay showed that Berbamine decreased the migration potential of the HT-29 and also blocked the MEK/ERK signalling pathway in colon cancer cells.Berbamine may prove an efficient lead molecule for the development of more potent anticancer agents through semi-synthetic approaches.

Aims Deguelin, a natural compound derived from Mundulea sericea (Leguminosae) and some other plants exhibits an activity to inhibit autophagy, a cellular machinery required for hepatitis C virus (HCV) replication. This study aimed to illuminate the impact of deguelin on HCV replication and mechanism(s) involved. Methods HCV JFH-1-Huh7 infectious system was used for the investigation. Real time RT-PCR, Western blot, fluorescent microscopy assay were used to measure the expression levels of viral or cellular factors. Overexpression and silencing expression techniques were used to determine the role of key cellular factors. Results Deguelin treatment of Huh7 cells significantly inhibited HCV JFH-1 replication in a dose- and time-dependent manner. Deguelin treatment suppressed autophagy in Huh7 cells, evidenced by the decrease of LC3B-II levels, the conversion of LC3B–I to LC3B-II, and the formation of GFP-LC3 puncta as well as the increase of p62 level in deguelin-treated cells compared with control cells. HCV infection could induce autophagy which was also suppressed by deguelin treatment. Mechanism research reveals that deguelin inhibited expression of Beclin1, which is a key cellular factor for the initiation of the autophagosome formation in autophagy. Overexpression or silencing expression of Beclin1 in deguelin-treated Huh7 cells could weaken or enhance the inhibitory effect on autophagy by deguelin, respectively, and thus partially recover or further inhibit HCV replication correspondingly. Conclusions: Deguelin may serve as a novel anti-HCV compound via its inhibitory effect on autophagy, which warrants further investigation as a potential therapeutic agent for HCV infection.

The discovery of medicinal plants is crucial for drug development. Eucalyptus globulus leaves are used as a traditional medicine in many areas of world due to herbicidal and insecticidal activity. While natural products are difficult to be separated and activity assayed, a new approach is needed to predict the active ingredients therein. In this study, a new method for screening active compounds extracted from E. globulus leaves was developed by GC-MS/MS and UPLC-MS/MS combined with molecular docking technology. Predicted compounds with high activity were proposed. Firstly, 35 volatile compounds and 34 aqueous extracted compounds were extracted from E. globulus leaves, and identified by GC-MS/MS and UPLC-MS/MS. The herbicidal receptor (1BX9) was then docked with the identified compounds by docking software, evaluated by docking models and seven scoring functions. The results showed that gallic acid had a strong inhibitory activity of 1BX9, which was speculated to be the main reason for the inhibitory effect of E. globulus leaves. Finally, allelopathic tests of gallic acid, citric acid, and isopulegol were carried out on grass seeds to verify its inhibitory activity against herbicide receptor 1BX9. The results show that the method can screen compounds with specific activity from a complex system of medicinal plants, which is very important for the screening of new active ingredients, confirmation of new medicinal ingredients, and the in-depth development of animal and plant medicines.

ObjectiveTo characterise the association between duration of exposure to antiretroviral treatment (ART) and liver damage in HIV patients with an initially normal baseline liver function and without hepatitis B virus (HBV)/hepatitis C virus (HCV) infection.MethodsA retrospective cohort study was conducted in HIV-infected individuals with normal liver function parameters at ART initiation and without HBV/HCV infection, from 14 April 2004 to 13 April 2015 in Guigang city, Guangxi, China. The association between duration of ART and liver damage (grade II–IV liver enzyme elevation [LEE] and/or total bilirubin elevation [TBE]), was analysed. Cox regression was used to examine the factors related to liver damage.ResultsOf 2119 eligible patients, 12.41% (263/2119) developed liver damage (grade II–IV LEE/TBE) and contributed 4.11/100 person-years crude incidence rate. The highest liver damage incidence was observed in patients with 6–12 months’ ART (15.16/100 person-years). The incidence decreased to 5.56/100 person-years in patients with 12–18 months’ ART and 3.13/100 person years in patients with 18–24 months’ ART, and then maintained at a relatively low and stable level in patients with 2 years’ ART or longer (average of 3.65/100 person-years). Cox regression analysis revealed that current WHO disease stage II, III or IV (compared with stage I) were the risk factors for liver damage, while baseline disease stage II, III (compared with stage I) and current regimen 3TC+AZT+NVP were the protective factors for liver damage.ConclusionsLiver damage always exists among HIV-infected patients on ART with normal baseline liver function and without HBV/HCV infection. Nevertheless, cumulative ART duration does not increase the risk of liver damage. ART could tend to be long-term, however, monitoring and management of liver damage among patients on ART are also important in clinical therapy.

Objectives: The epidemiological evidence is inconsistent about whether HIV-positive injection drug users (IDUs) are at higher risk of developing antiretroviral resistance than any other HIV-positive populations. This study aims to investigate and compare transmitted drug resistance (TDR) between IDUs and non-IDUs in Lingshan County, an HIV-hit region in Guangxi, China, where IDU and heterosexual transmission were the two dominant transmission routes and roughly equally contributed to the local HIV transmission. Methods: A cross-sectional study was conducted among newly diagnosed and antiretroviral-treatment (ART)-naïve HIV-1 patients from Lingshan County. The pol gene of HIV-1 from the individuals was sequenced followed by genotyping and TDR analysis. Results: Two dominant transmission routes, heterosexual contact and IDU, accounted for 49.2 and 45.9% of 183 HIV-1 infection cases, respectively. Three genotypes, including CRF08_BC (70.6%), CRF01_AE (24.4%), and CRF07_BC (5.0%), and three unique recombinant forms (1.6%), were identified. There was a significant difference in genotype distribution among the different transmission routes (F = 21.814, p < 0.001). The overall TDR prevalence was 5.5%. There were no significant differences in TDR prevalence among the different transmission routes (F = 1.420, p = 0.439). Conclusions: Injection drug use has little impact on TDR prevalence compared with other routes of transmission.

Both alcohol and hepatitis C virus (HCV) infection could induce cellular autophagy in liver cells, which is considered to be essential for productive HCV replication. However, whether alcohol-induced autophagy is involved in the pathogenesis of HCV infection is still poorly understood. Alcohol treatment could induce autophagy in Huh7 cells (a hepatoma cell line that supports HCV JFH-1 replication), evidenced by the increase of LC3B-II levels, the conversion of LC3B-I to LC3B-II, and the formation of GFP-LC3 puncta as well as the decrease of p62 level in alcohol-treated cells compared with control cells. Alcohol treatment also significantly increased PIASy (a member of the PIAS family) expression, which can act as a SUMO (small ubiquitin-like modifier protein) E3 ligase to regulate a broader range of cellular processes including autophagy. Overexpression or the silencing expression of PIASy in alcohol-treated Huh7 cells could increase or decrease autophagic activation caused by alcohol treatment, respectively, and thus affect HCV replication correspondingly. In the absence of alcohol, overexpression or silencing expression of PIASy increase or decrease the level of cellular autophagy, judged by the changes of LC3B-II and p62 levels in the presence or absence of chloroquine (CQ), a lysosome inhibitor. More importantly, in the presence of 3-methyladenine (3-MA), an inhibitor in the early stage of autophagy, the effects of overexpression or silencing expression of PIASy on HCV replication were largely blocked. Furthermore, PIASy could selectively drive the accumulation of SUMO1-conjugated proteins, along with upregulation of the expression of several important autophagy factors, including ATG7 and ATG5–ATG12. In conclusion, alcohol promotes HCV replication through activation of autophagy in Huh7 cells, which partly attributes to its induction of PIASy expression. PIASy-enhanced accumulation of SUMO1-conjugated proteins may contribute to its inducing effect of autophagy. Our findings provide a novel mechanism for the action of alcohol-promoting HCV replication in the context of cellular autophagy.

Background To examine the accuracy of Rapid Diagnosis of Talaromyces marneffei (RDTM) in order to improve diagnosis and treatment for clinical measures and reduce the mortality due to associated infections. Methods In this systematic review and meta-analysis, we screened PubMed, Ovid (Cochrane library) and Web of Science, Chinese database CNKI and Wanfang for articles published between 1956 and December, 2017. Data were taken from cross-sectional studies as well as from baseline measurements in longitudinal studies with clinical follow-up. Articles were excluded if they did not contain a cohort with T. marneffei and a control cohort or a cohort with standard fungus culture. Data were extracted by two authors and checked by three for accuracy. For quality assessment, modified QUADAS-2 criteria were used. Results The 26 included diagnostic studies enrolled 5,594 objectives in 632 patients with T. marneffei infections and 2,612 negative controls between 1996 and 2017 in Thailand, Vietnam and China. The total combined sensitivity and specificity of rapid diagnosis of T. marneffei was 0.82 (95% CI: 0.68–0.90) and 0.99 (95% CI: 0.98–1.00). According to the experimental method, the included studies can be divided into three subgroups, including PCR-based, ELISA-based and others. The results showed these three subgroups had a highly pooled specificity of 1.00 (95% CI: 0.99–1.00), 0.99 (0.98–1.00) and 0.97 (95% CI: 0.91–1.00), respectively, while combined sensitivity was 0.84 (95% CI: 0.37–0.98), 0.82 (95% CI: 0.64–0.92) and 0.77 (95% CI: 0.54–0.91), respectively. Conclusions Although serological methods with a high specificity is essential for potential rapid diagnostic, false-negative results can be obtained in the serum samples, there is no suitable rapid serological test to refer to as is the case with TM infection.

BACKGROUND Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer-related death in adults. Despite recent advances in the clinical technologies, the screening and diagnostic efficacy for HCC remains poor. Discovering novel and reliable HCC biomarkers is urgently needed. MATERIAL AND METHODS We performed a transcriptome-proteome integrated assay to track the possible HCC biomarkers from the process of HCC-derived gene expression in malignant cells to its protein product released into serum. RESULTS Our screening results demonstrated that heat shock protein 90A (HSP90A), which participates in the PI3K-Akt signaling pathway and many other cancer-related pathways, warrants further investigation. The expression of HSP90A was increased in the HCC cells, serum, and tissues. Immunohistochemistry analysis on 76 clinical tissue samples also suggested the relevance between HSP90A expression and HCC metastatic behavior. CONCLUSIONS These findings suggest a role for HSP90A in HCC pathogenesis and the potential use of HSP90A for the screening and diagnosis of this malignancy.

Objectives. Identifying recent infections is necessary to monitor HIV/AIDS epidemic; however, it needs to be further developed. Methods and Results. Participants were defined as having recent infection or older infection according to the estimated duration of HIV-1 infection and further assigned into training set and validation set according to their entering time points. Western blot (WB) confirmatory test and BED-CEIA were performed. The performance of the two methods on recent HIV-1 diagnosis was evaluated and compared. 81 subjects were enrolled in the training set and 72 in the validation set. Relative grey ratios of p24, p39, p31, p66, gp41, and gp160 were significantly higher in older infected patients of the training set. The present status of p55 was more frequently missing in recently infected patients in both sets. The logistic stepwise regression analysis of WB method shows sensitivity, specificity, and accuracy of 93.02%, 92.11%, and 92.59%. For BED-CEIA, they were 76.74%, 86.84%, and 81.48%. In the validation set, overall agreement rate, sensitivity, and specificity were 88.46%, 84.78%, and 86.11% in the WB-based method and 50.00%, 84.78%, and 72.22% in the BED-CEIA method. Conclusions. WB-based method is a promising approach to predict recent HIV-1 infection, especially in resource-limited regions.