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To investigate the effect of the interaction between protocatechuic acid (PCA) and gelatin on the functional properties and stability of gelatin-PCA complexes. Gelatin-PCA complexes were prepared by non-covalent and covalent binding. Afterward, the interaction between PCA and gelatin was analyzed using UV-Vis spectroscopy, fluorescence spectroscopy, and Fourier transform infrared spectroscopy. Meanwhile, an analysis was also performed on the antioxidant activity, antibacterial activity, and stability of the complexes. The findings showed a higher PCA binding rate for the covalent complexes than the non-covalent complexes. Additionally, the interaction between PCA and gelatin resulted in the fluorescence quenching of gelatin, with a higher level of fluorescence quenching observed for the covalent binding. Moreover, in addition to excellent DPPH and ABTS+ radical scavenging abilities. Compared with GPCA-2，the non-covalent complex GPCA-1 showed more significant (P

BackgroundHIV notification and testing integrated into partner service (PS) practices among HIV-positive individuals have been proven to be an efficient approach for case finding, although it remains a weak link in China. Although nonmarital sexual activities accounted for a large proportion of newly diagnosed HIV-positive cases in China, little is known about PS uptake and associated factors within nonmarital partnerships. ObjectiveThis study aimed to describe HIV PS utilization and its associated factors among HIV-positive individuals with nonmarital sexual partners. MethodsWe recruited newly diagnosed HIV-positive individuals who had nonmarital sexual partners in 2022 in Zhejiang Province and offered them PS. We described the PS uptake cascade within sexual partner categories and analyzed the associated factors with 3 primary outcomes from the participants’ perspective: nonmarital partner enumeration, HIV testing, and HIV positivity. ResultsIn this study, 3509 HIV-positive individuals were recruited as participants, and they enumerated 2507 nonmarital sex partners (2507/14,556, 17.2% of all nonmarital sex partners) with contact information. Among these, 43.1% (1090/2507) underwent an HIV test, with an HIV-positive rate of 28.3% (309/1090). Heterosexual commercial partners were the least likely of being enumerated (441/4292, 10.3%) and had the highest HIV-positive rate (40/107, 37.4%). At the participant level, 48.1% (1688/3509) of the participants enumerated at least one nonmarital sex partner with contact information, 52.7% (890/1688) had a sex partner tested for HIV, and 31% (276/890) had at least one nonmarital sex partner who tested positive. Multivariate analysis indicated that gender and transmission route were associated with both nonmarital sex partner enumeration and HIV testing. Age and occupation were associated with nonmarital sex partner enumeration and HIV positivity. Compared with participants who had no regular nonmarital sex partner, those who had a regular nonmarital sex partner were more likely to enumerate nonmarital sex partners (adjusted odds ratio [aOR] 3.017, 95% CI 2.560-3.554), have them get tested for HIV (aOR 1.725, 95% CI 1.403-2.122), and have an HIV-positive nonmarital sex partner (aOR 1.962, 95% CI 1.454-2.647). ConclusionsThe percentage of partner enumeration was low, and HIV testing rate was moderate among nonmarital partnerships of HIV-positive individuals. More efforts should be made to improve PS practices among HIV-positive individuals and address the gap in partner enumeration, especially for heterosexual commercial nonmarital partnerships. Additionally, enhancing PS operational skills among health care personnel could increase the overall efficiency of PS uptake in China.

BackgroundAntiretroviral therapy (ART) has been shown to reduce human immunodeficiency virus (HIV) viral replication and ultimately achieve viral suppression and eliminate HIV transmission. However, little is known about the impact of viral suppression on high-risk behaviors and sexually transmitted infections (STIs).ObjectiveThis study aimed to assess the rates of current syphilis infection in virally suppressed people living with HIV (PLWH) and whether with the duration of ART can reduce the current syphilis infection in eastern China.MethodWe conducted a cross-sectional survey of PLWH in Zhejiang Province, China, in 2022. PLWH who were on ART >6 months and were virally suppressed (viral load

Engineering probiotics have emerged as a potential strategy for the treatment of metabolic diseases. However, due to the exceptional complexity of these metabolic disorders and the intricate relationship between gut microbes, it is difficult to achieve an ideal therapeutic effect in a specific metabolic disorder using only a single engineered strain. In this work, we proposed a probiotic cocktail strategy by engineering two cascade metabolic bacteria to treat hyperlysinemia, an inherited lysine metabolic disorder with loss of α-aminoadipate semialdehyde synthase (AASS) activity. A probiotic E. coli Nissle 1917 strain EcNT (pTLS) with a heterologous enzyme pathway in Saccharomyces cerevisiae was engineered to metabolize the excess lysine. Another one EcNT (pK25) was engineered to consume the products of lysine metabolism. The bacterial cocktail enables the maintenance of a metabolic cascade with AASS-like functional activity to maintain the blood lysine concentrations and downstream metabolites. In vitro experimental results showed that the cocktail bacteria had a better metabolic capacity and metabolites balance at a ratio of EcNT (pTLS) and EcNT (pK25) of 1:2. Feeding of the cocktail bacteria to the mouse model effectively reduced the concentration of lysine and balanced saccharopine in the plasma of hyperlysinemia-like mice. These findings not only provide a promising strategy of probiotic stains for the treatment of hyperlysinemia but also highlight the potential of engineered cascade cocktails to intervene and even cure other inherited metabolic diseases.

BackgroundIn recent years, the number and proportion of newly reported HIV/AIDS cases among older adults have increased dramatically. However, research on the pattern of temporal and spatial changes in newly reported HIV/AIDS among older adults remains limited. ObjectiveThis study analyzed the spatial and temporal distribution of HIV/AIDS cases and its influencing factors among older adults in Eastern China from 2004 to 2021, with the goal of improving HIV/AIDS prevention and intervention. MethodsWe extracted data on newly reported HIV/AIDS cases between 2004 and 2021 from a case-reporting system and used a Joinpoint regression model and an age-period-cohort model to analyze the temporal trends in HIV/AIDS prevalence. Spatial autocorrelation and geographically weighted regression models were used for spatial aggregation and influence factor analysis. ResultsA total of 12,376 participants with HIV/AIDS were included in the study. The newly reported HIV infections among older adults increased from 0.13 cases per 100,000 people in 2004 to 7.00 cases per 100,000 people in 2021. The average annual percent change in newly reported HIV infections was 28.0% (95% CI –21.6% to 34.8%). The results of the age-period-cohort model showed that age, period, and cohort factors affected the newly reported HIV infections among older adults. The newly reported HIV/AIDS cases among men who have sex with men (MSM) had spatial clustering, and the hotspots were mainly concentrated in Hangzhou. The disposable income of urban residents, illiteracy rate among people aged 15 years or older, and number of hospital beds per 1000 residents showed a positive association with the newly reported HIV infections among older MSM in the Zhejiang province. ConclusionsHIV/AIDS among older adults showed an increasing trend and was influenced by age, period, and cohort effects. Older MSM with HIV/AIDS showed regional clustering and was associated with factors such as the disposable income of urban residents, the illiteracy rate among people aged 15 years or older, and the number of hospital beds per 1000 people. Targeted prevention and control measures are needed to reduce HIV infection among those at higher risk.

Abstract Chlamydia pneumoniae (C. pneumoniae) infection in humans is universal and causes various respiratory infectious diseases, making a safe and effective preventive vaccine essential. In this study, a multi-epitope vaccine with CTLA-4 extracellular structure was constructed by an immunoinformatics approach. Since MOMP protein is the major extracellular protein in C. pneumoniae and has good immunogenicity and high conservation, we selected the MOMP protein of C. pneumoniae as the antigen target, predicted the T and B cell epitopes of the MOMP protein and then connected the CTLA-4 extracellular structure with the predicted dominant epitopes by various linkers to construct a multi-epitope vaccine. The biochemical characterization of the multi-epitope vaccine showed its immunogenicity and anti-allergic properties. The tertiary structure of this vaccine, along with molecular docking, molecular dynamics simulation, and principal component analysis, showed that the multi-epitope vaccine structure interacted with B7 (B7-1, B7-2) and toll-like receptors (TLR-2, TLR-4). Ultimately, the vaccine was cloned and effectively expressed in silico on an insect baculovirus expression vector (pFastBac1). These analyses showed that the designed vaccine could potentially target antigen-presenting cells and was immune to C. pneumoniae, which provided novel strategies for developing the vaccine.

Carbamate is a key structural motif in the development of fungicidal compounds, which is still promising and robust in the discovery of green pesticides. Herein, we report the synthesis and evaluation of the fungicidal activity of 35 carbamate derivatives, among which 19 compounds were synthesized in our previous report. These derivatives were synthesized from aromatic amides in a single step, which was a green oxidation process for Hofmann rearrangement using oxone, KCl and NaOH. Their chemical structures were characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry. Their antifungal activity was tested against seven plant fungal pathogens. Many of the compounds exhibited good antifungal activity in vitro (inhibitory rate > 60% at 50 μg/mL). Compound 1ag exhibited excellent broad-spectrum antifungal activities with inhibition rates close to or higher than 70% at 50 μg/mL. Notably, compound 1af demonstrated the most potent inhibition against F. graminearum, with an EC50 value of 12.50 μg/mL, while compound 1z was the most promising candidate fungicide against F. oxysporum (EC50 = 16.65 μg/mL). The structure–activity relationships are also discussed in this paper. These results suggest that the N-aryl carbamate derivatives secured by our green protocol warrant further investigation as potential lead compounds for novel antifungal agents.

ObjectivesThe characteristics of men who have sex with men (either exclusively or with both men and women; MSM) who engaged in casual sex among Chinese male university students have not been compared with the characteristics of men who have sex with only women (MSW). This information is important for tailoring targeted behavioral interventions to prevent human immunodeficiency virus (HIV)/sexually transmitted infection (STI) transmission in this subgroup of MSM.MethodsData were derived from a large cross-sectional electronic questionnaire survey conducted at 13 universities in Zhejiang Province, China, in 2018. Bivariate analyses were used to compare demographic, HIV-related psychosocial, and behavioral characteristics between MSM and MSW students who engaged in casual sex during the previous year. Proportion differences between the two groups and their 95% confidence intervals were analyzed.ResultsAmong the 583 sexually active male students who engaged in casual sex during the previous year, 128 and 455 were MSM and MSW, respectively. Compared with MSW students, larger proportions of MSM students reported knowing that male-to-male sexual behavior was the main mode of HIV transmission among Chinese students (62.5% vs. 45.5%), consenting to commercial sex (67.2% vs. 53.4%), wanting to know the HIV serostatus of partners before casual sex (65.8% vs. 51.3%), feeling at risk of HIV infection (40.5% vs. 11.8%), high condom-decision scale scores (55.3% vs. 42.6%), engaging in sex with ≥ 5 casual sex partners (44.6% vs. 25.9%), searching for casual partners online (89.2% vs. 51.3%), consuming alcohol before casual sex (64.8% vs. 45.0%), engaging in sex with regular partners (83.1% vs. 67.0%), engaging in commercial sex (54.2% vs. 26.4%), and visiting a clinic for voluntary counselling and testing (VCT) (16.4% vs. 8.4%). However, compared with MSW students, smaller proportions of MSM students reported knowing that consistent condom use could prevent HIV transmission (80.5% vs. 95.2%) and that VCT should be actively sought after risky sexual behavior (78.9% vs. 93.8%), using condoms sometimes/often (26.4% vs. 44.3%), and consistently using condoms (28.9% vs. 40.1%) while engaging in sex with casual partners.ConclusionsMSM students who engaged in casual sex were at a greater risk of HIV/STI transmission, compared with MSW students. Comprehensive interventions to address the risks of unprotected male-to-male sex, searching for casual sex partners online, and non-use of HIV testing services are needed to reduce the burden of HIV/STI transmission among this subgroup of MSM.

Abstract Background Immune checkpoint inhibitors (ICIs) have been widely used in the treatment of cancer. Moreover, immune-related adverse events (irAEs) have become a new clinical challenge. ICI-associated myocarditis is a rare but fatal condition among diverse organ injuries, and early recognition and effective interventions are critical for patients. Case presentation In this report, we present the case of a healthy 60-year-old male who was diagnosed with lung squamous cell carcinomas following chemotherapy and received ICIs. The patient presented with asymptomatic cardiac biomarker elevation followed by immune-related myocarditis. Fortunately, the patient achieved a good clinical result after receiving high-dose steroids. The treatment with ICIs was discontinued because of recurrent increases in troponin T. Conclusion ICI-mediated associated myocarditis is an uncommon but potentially life-threatening adverse event. The current data suggest that clinicians need to be cautious about reinitiation in low-grade patients; however, further study of the diagnosis and treatment is necessary.

The traditional synthesis of nano silver chloride involves chemical precipitation or physical methods. Due to the hazardous substances generated during the synthesis, it can cause environmental pollution. In this study, a green and facile method is described to biosynthesize nano-silver chloride with excellent antibacterial activity via in situ reduction of Ag + using the extract of Bacillus thuringiensis (Bt). Compared with previous reports, the minimal inhibition concentration (MIC) against Escherichia coli (E. coli) is 3.0 μg/mL, which is 2– to 800-fold higher than that of nano silver chloride. Subsequent in vitro studies involving agricultural bacteria such as Ralstonia solanacearum (R. solanacearum) revealed a 92.95% antibacterial rate when the concentration of nano-silver chloride was 2.0 μg/mL. Previous studies of antibacterial activity of nano-silver chloride focused more on the basic antibacterial properties without describing its antibacterial molecular mechanisms. The microscopic investigations and DNA damage experiments indicated that the nano-silver chloride adsorbed to the bacterial surface, leading to cell wall rupture, DNA damage, and cytoplasmic leakage. In addition, electron paramagnetic resonance (EPR) spectroscopy indicated the synthesis of reactive oxygen species (·OH, ·O2− and 1O2) in the bacteria. Our study provides evidence supporting the use of nano-silver chloride as an antibacterial agent in agriculture, and theoretical insight into the antibacterial mechanism thereof.

On the basis of the structure of natural product lansiumamide B (1), a total of 27 novel cis-enamide compounds were designed and synthesized via Intermediate Derivatization Method. Their chemical structures were characterized by 1H and 13C nuclear magnetic resonance and high-resolution mass spectrometry. The in vitro antifungal activities against Sclerotinia sclerotiorum, Thanatephorus cucumeris and Botrytis cinerea were evaluated by the mycelium linear growth rate method. Most of the compounds showed some activity against each of the fungi at 25 or 50 μg/mL. The relationship between structure and antifungal activity was also discussed, which showed the cinnamic double bond was critical to maintain the antifungal activity. Notably, among the title compounds, 3e and 3h could inhibit mycelia growth of Botrytis cinerea by approximately 50% (EC50) at 39.17 and 41.25 μg/mL respectively, which showed better antifungal activity than lansiumamide B (1) with more concise chemical structure. The present study pointed out the correct direction for the development and optimization of lansiumamide B derivatives as potential inhibitors of pathogenic fungi.

ABSTRACT: Objectives: This study aimed to establish a collaborative approach to quantify local HIV transmission, which is an issue of great concern to public health. Methods: We linked HIV-1 pol gene sequences to demographic information and epidemiological investigations in Hangzhou (a central city in East China). We estimated local acquisition rates from a collaboration of molecular network analysis (with a distance-based approach) and epidemiological investigations. Results: Among 1064 newly diagnosed patients with HIV, 857 pol sequences were acquired and subsequently analyzed. Multiple subtypes were identified, with circulating recombinant form (CRF)07_BC (42.5%) and CRF01_AE (39.2%) predominating, followed by 13 other subtypes and 26 unique recombinant forms. By integrating the molecular network analysis and epidemiological investigations, we estimated that the proportion of local infection was 63.2%. The multivariable analyses revealed that individuals in clusters were more likely to be local residents, be aged 50 years or older, work as farmers, and have a higher first cluster of differentiation 4 count level (P

Bacillus thuringiensis Vip3 toxins form a tetrameric structure crucial for their insecticidal activity. Each Vip3Aa monomer comprises five domains. Interaction of the first four α-helices in domain I with the target cellular membrane was proposed to be a key step before pore formation. In this study, four N-terminal α-helix-deleted truncations of Vip3Aa were produced and, it was found that they lost both liposome permeability and insecticidal activity against Spodoptera litura. To further probe the role of domain I in membrane permeation, the full-length domain I and the fragments of N-terminal α-helix-truncated domain I were fused to green fluorescent protein (GFP), respectively. Only the fusion carrying the full-length domain I exhibited permeability against artificial liposomes. In addition, seven Vip3Aa-Cry1Ac fusions were also constructed by combination of α-helices from Vip3Aa domains I and II with the domains II and III of Cry1Ac. Five of the seven combinations were determined to show membrane permeability in artificial liposomes. However, none of the Vip3Aa-Cry1Ac combinations exhibited insecticidal activity due to the significant reduction in proteolytic stability. These results indicated that the N-terminal helix α1 in the Vip3Aa domain I is essential for both insecticidal activity and liposome permeability and that domain I of Vip3Aa preserved a high liposome permeability independently from domains II–V.

Abstract Background Septic arthritis requires prompt diagnosis and treatments. Rare pathogens should be considered when patients respond poorly to the initial antibiotic treatments. Ureaplasma parvum is an opportunistic pathogen that commonly resides in the human urogenital tract. Its infection commonly causes hyperammonemia. Hyperammonemia from Ureaplasma parvum septic arthritis has never been reported previously. Case presentation A 65-year-old male presented with fever and left lower leg pain and swelling for more than ten days. Septic arthritis and sepsis were considered after laboratory tests and arthrocentesis. However, he responded poorly to the antibiotic treatments, including cefoperazone-sulbactam, imipenem-cilastatin, and linezolid. His mental status deteriorated rapidly with elevated blood ammonia levels with unremarkable liver function test and sonogram examination results. Despite the treatments with lactulose, L-ornithine L-aspartate, mannitol, and hemodialysis therapy to lower his ammonia level, his blood ammonia level remained persistently high. Finally, metagenomic sequencing of the left knee synovial fluid reported Ureaplasma parvum, which was considered to contribute to his hyperammonemia. Conclusion Ureaplasma parvum could cause septic arthritis with hyperammonemia. Genetic tests, such as polymerase chain reaction and next-generation sequencing techniques, could provide a sensitive and fast diagnosis of Ureaplasma parvum.

In this study, we conducted a detailed molecular epidemiological analysis of HIV-1 epidemic strains in various sexual risk behaviour groups in a developed area in eastern China based on phylogenetic inference, molecular transmission networks, and Bayesian analyses. A total of 1083 pol sequences (91.23%, 1083/1187) from newly diagnosed HIV-1-positive patients from 2017 to 2020 were successfully obtained and involved thirteen HIV-1 subtypes, in which the major HIV-1 subtypes were CRF07_BC (36.10%, 391/1083) and CRF01_AE (34.63%, 375/1083). 485 individuals (44.78%,485/1083) formed 146 clusters in the network. Of which CRF07_BC showed extensive clustering driven by men who have sex with men (MSM) within larger networks, CRF01_AE and other subtypes were generally driven by small clusters (SCs) and medium clusters (MCs) among various risk groups. Through Sankey diagrams, the MSM group infected with CRF07_BC had a greater impact on the non-commercial heterosexual group among all cross-risk groups. In addition, a higher number of key individuals infected with CRF07_BC (40.22%, 74/127), suggests the crucial role of CRF07_BC-infected individuals as a local epidemic driver in the context of a mixed HIV-1 epidemic. Further Bayesian analysis confirmed that CRF07_BC was introduced into Jiaxing city from other provinces multiple times and spread rapidly among MSM and heterosexual individuals. Overall, our study provided some insights and information to explore the local transmission dynamics of HIV-1 epidemic strains involving various sexual risk groups, and emphasize that it is necessary to conduct in-depth research and precise intervention targeting key clusters/ individuals to effectively block the continued transmission of AIDS.

In this study, a green and highly efficient method was proposed to synthesize nano-silver chloride (nano-AgCl) using spent mushroom substrate (SMS) extract as a cheap reactant. Nanoparticles were characterized by a series of techniques like x-ray diffraction (XRD), energy dispersive spectroscopy (EDS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM), which showed the formation of near-spherical silver chloride nanoparticles with an average size of about 8.30 nm. Notably, the synthesized nano-silver chloride has a more prominent antibacterial effect against Ralstonia solanacearum (EC _50 = 5.18 mg L ^−1 ) than non-nano-sized silver chloride particles, nano-silver chloride synthesized by chemical method, and commercial pesticides. In-depth, the study of the mechanism revealed that nano-silver chloride could cause cell membrane disruption, DNA damage and intracellular generation of reactive oxygen species (·OH, ·O ^2− and ^1 O _2 ), leading to peroxidation damage in Ralstonia solanacearum ( R. solanacearum ). Moreover, the reaction between nano-silver chloride and bacteria could be driven by intermolecular forces instead of electrostatic interactions. Our study provides a new approach to synthesizing nano-silver chloride as a highly efficient antibacterial agent and broadens the utilization of agricultural waste spent mushroom substrate.

BackgroundPrimary cardiac tumors are very rare, and about 20–30% of them are malignant tumors. Since early signs of cardiac tumors are non-specific, diagnosis can be challenging. There is a lack of the recommended guidelines or standardized strategies for diagnosis and optimal treatment for this disease. As the definite diagnoses of most tumors are made by pathologic confirmation, biopsied tissue is essential in determining the treatment for patients with cardiac tumors. Recently, intracardiac echocardiography (ICE) has been introduced to assist biopsy procedures of cardiac tumors and it provides high-quality imaging.Case DescriptionDue to its low prevalence and variable presentation, cardiac malignant tumors usually are easily missed. Hereby, we report three cases of patients who presented with non-specific signs of cardiac disorder and was initially suspended diagnosis as lung infection or cancer. Under the guidance of ICE, cardiac biopsies were successfully on cardiac masses, giving critical data for diagnosis and treatment planning. No procedural complications were obtained in our cases. These cases are intended to highlight the clinical value and importance of ICE-guided biopsy of intracardiac mass.ConclusionsThe diagnosis of primary cardiac tumors relies on the histopathological results. In our experience, using ICE for biopsy of an intracardiac mass is an attractive tool to increase diagnostic results and reduce the risk of cardiac complications associated with inadequate targeting of the biopsy catheters.

Abstract Protopanaxadiol (PPD) has potential immunomodulatory effects, but the underlying mechanism remains unclear. Here, we explored the potential roles of gut microbiota in the immunity regulation mechanisms of PPD using a cyclophosphamide (CTX)‐induced immunosuppression mouse model. Our results showed that a medium dose of PPD (PPD‐M, 50 mg/kg) effectively ameliorated the immunosuppression induced by CTX treatment by promoting bone marrow hematopoiesis, increasing the number of splenic T lymphocytes and regulating the secretion of serum immunoglobulins and cytokines. Meanwhile, PPD‐M protected against CTX‐induced gut microbiota dysbiosis by increasing the relative abundance of Lactobacillus, Oscillospirales, Turicibacter, Coldextribacter, Lachnospiraceae, Dubosiella, and Alloprevotella and reducing the relative abundance of Escherichia‐Shigella. Importantly, PPD‐M lost the ability to promote bone marrow hematopoiesis and enhance immunity when the gut microbiota was depleted by broad‐spectrum antibiotics. Moreover, PPD‐M promoted the production of microbiota‐derived immune‐enhancing metabolites including cucurbitacin C, l‐gulonolactone, ceramide, DG, prostaglandin E2 ethanolamide, palmitoyl glucuronide, 9R,10S‐epoxy‐stearic acid, and 9′‐carboxy‐gamma‐chromanol. KEGG topology analysis showed that the PPD‐M treatment significantly enriched the sphingolipid metabolic pathway with ceramide as a main metabolite. Our findings reveal that PPD enhances immunity by manipulating gut microbiota and has the potential to be used as an immunomodulator in cancer chemotherapy.

On the basis of the three-component synthetic methodology developed by us, a total of twenty-six pyrazole compounds bearing aryl OCF3 were designed and synthesized. Their chemical structures were characterized by 1H and 13C nuclear magnetic resonance and high-resolution mass spectrometry. These compounds were evaluated systematically for antifungal activities in vitro against six plant pathogenic fungi by the mycelium growth rate method. Most of the compounds showed some activity against each of the fungi at 100 μg/mL. Compounds 1t and 1v exhibited higher activity against all the tested fungi, and 1v displayed the highest activity against F. graminearum with an EC50 value of 0.0530 μM, which was comparable with commercial pyraclostrobin. Structure–activity relationship analysis showed that, with respect to the R1 substituent, the straight chain or cycloalkyl ring moiety was a key structural moiety for the activity, and the R2 substituent on the pyrazole ring could have significant effects on the activity. Simple and readily available pyrazoles with potent antifungal activity were obtained, which are ready for further elaboration to serve as a pharmacophore in new potential antifungal agents.

Background: 20(S)-protopanaxadiol (20(S)-PPD), one of the main active metabolites of ginseng, performs a broad spectrum of anti-tumor effects. Our aims are to search out new strategies to enhance anti-tumor effects of natural products, including 20(S)-PPD. In recent years, fasting has been shown to be multi-functional on tumor progression. Here, the effects of fasting combined with 20(S)-PPD on hepatocellular carcinoma growth, apoptosis, migration, invasion and cell cycle were explored. Methods: CCK-8 assay, trypan blue dye exclusion test, imagings photographed by HoloMonitorTM M4, transwell assay and flow cytometry assay were performed for functional analyses on cell proliferation, morphology, migration, invasion, apoptosis, necrosis and cell cycle. The expressions of genes on protein levels were tested by western blot. Tumor-bearing mice were used to evaluate the effects of intermittent fasting combined with 20(S)-PPD. Results: We firstly confirmed that fasting-mimicking increased the anti-proliferation effect of 20(S)-PPD in human HepG2 cells in vitro. In fasting-mimicking culturing medium, the apoptosis and necrosis induced by 20(S)-PPD increased and more cells were arrested at G0-G1 phase. Meanwhile, invasion and migration of cells were decreased by down-regulating the expressions of matrix metalloproteinase (MMP)-2 and MMP-9 in fasting-mimicking medium. Furthermore, the in vivo study confirmed that intermittent fasting enhanced the tumor growth inhibition of 20(S)-PPD in H22 tumor-bearing mice without obvious side effects. Conclusion: Fasting significantly sensitized HCC cells to 20(S)-PPD in vivo and in vitro. These data indicated that dietary restriction can be one of the potential strategies of chinese medicine or its active metabolites against hepatocellular carcinoma.

Hereditary transthyretin cardiac amyloidosis (hATTR-CA) is a rare autosomal dominantly inherited disease caused by mutations in the transthyretin (TTR) gene. TTR mutations often cause the instability of transthyretin, production of misfolded proteins, and ultimately excessive deposition of insoluble amyloid fibrils in the myocardium, thereby leading to cardiac dysfunction. Herein, we report a novel transthyretin D39Y mutation in a Chinese family. We characterized the kinetic and thermodynamic stabilities of D39Y mutant TTR, revealing that TTR D39Y mutant was less stable than WT TTR and more stable than amyloidogenic mutation TTR L55P. Meanwhile, the only FDA approved drug Tafamidis showed satisfactory inhibitory effect toward ATTR amyloid formation and strong binding affinity in test tube revealed by isothermal titration calorimetry. Finally, we measured the well-folded tetrameric TTR concentration in patient’s and his descents’ blood serum using a previously reported UPLC-based assay. Notably, the tetramer concentrations gradually increased from symptomatic D39Y gene carrier father, to asymptomatic D39Y gene carrier daughter, and further to wild type daughter, suggesting the decrease in functional tetrameric TTR concentration may serve as an indicator for disease age of onset in D39Y gene carriers. The study described a Chinese family with hATTR-CA due to the TTR variant D39Y with its destabilizing effect in both kinetic and thermodynamic stabilities.

Hereditary transthyretin (ATTRv) amyloidosis is a rare disease caused by transthyretin gene (TTR) mutation. We identified that the p.G103R mutation of the TTR gene in a Han Chinese family was associated with vitreous hemorrhage. The proband was a 48-year-old woman who had progressive visual impairment in both eyes for 12 years. A Glass wool–like posterior vitreous cortex attached to the posterior retinal surface of both eyes was found using ocular coherence tomography. Visual acuity improved after the first vitrectomy. Two years later, the patient underwent two more vitrectomies because of vitreous opacity recrudescence. Four years later, she presented with vitreous hemorrhage in the right eye. The vitreous fluids acquired during the vitrectomy showed increased vascular endothelial growth factor, basic fibroblast growth factor, interleukin-6, interleukin-10, vascular cell adhesion molecule, and interleukin-8. Mutation sequencing revealed a heterozygous mutation in nucleotide c.307G > C (p.G103R) in exon 3 of the TTR gene in the proband (IV-13), her daughter (IV-9), and her fourth sister (III-11). To our knowledge, this is the first case of ATTRv amyloidosis caused by a p.G103R mutation of the TTR gene associated with vitreous hemorrhage in China.

BackgroundLeft ventricular thrombus (LVT) is a serious complication in patients with left ventricular dysfunction. However, there is still a paucity of data on treatments and prognosis of patients with LVT. This study aims to evaluate the clinical characteristics of patients with LVT and to determine the impact of LVT on the incidence of major adverse cardiovascular events (MACEs) and all-cause mortality.MethodsFrom January 2010 to January 2020, 237 patients diagnosed with LVT at The Second Affiliated Hospital Zhejiang University School of Medicine in East China were retrospectively included. Clinical characteristics, treatments, MACEs, and bleeding events [thrombolysis in myocardial infarction (TIMI) I and II] were collected. MACE is determined as the composite of all-cause mortality, ischemic stroke, acute myocardial infarction (MI), and acute peripheral artery emboli.ResultsThe all-cause mortality rate was 28.3% (89.6% due to cardiovascular death), ischemic stroke 8.4%, MI 3%, peripheral artery emboli 1.7%, and bleeding events (TIMI I and II) 7.6% were found during a median follow-up of 736 days. Total LVT regression occurred in 152 patients (64.1%). Atrial fibrillation [hazard ratio (HR), 3.049; 95% confidence interval (95% CI) 1.264–7.355; p = 0.013], moderate and severe renal function injuries (HR, 2.097; 95% CI, 1.027–4.281; p = 0.042), and left ventricular ejection fraction (LVEF) ≤ 50% (HR, 2.243; 95% CI 1.090–4.615; p = 0.028) were independent risk factors for MACE, whereas the use of β-blocker (HR, 0.397; 95% CI 0.210–0.753; p = 0.005) was its protective factor. Age (HR, 1.021; 95% CI 1.002–1.040; p = 0.031), previous caronary artery bypass grafting (CABG; HR, 4.634; 95% CI 2.042–10.517; p < 0.001), LVEF ≤ 50% (HR, 3.714; 95% CI 1.664–8.290; p = 0.001), and large thrombus area (HR, 1.071; 95% CI 1.019–1.126; p = 0.007) were independent risk factors for increasing all-cause mortality, whereas the use of β-blocker (HR, 0.410; 95% CI 0.237–0.708; p = 0.001) was protective factor.ConclusionThis study showed that atrial fibrillation, moderate and severe renal dysfunction, and LVEF ≤ 50% were independent risk factors for MACE; age, previous CABG, LVEF ≤ 50%, and large thrombus area were independent risk factors for all-cause mortality. It was found that the use of β-blockers could improve the prognosis of patient with LVT for the first time. It is recommended that clinicians could be more active in applying patient with LVT with anticoagulants.

Abstract Background The upsurge in HIV infections among students is a matter of particular concern. However, few studies have explored the epidemiological characteristics including the risky sexual networking of HIV-infected students in Zhejiang province, China. Methods Using the provincial surveillance data of HIV-infected students, we conducted a retrospective epidemiology study to describe the epidemiological characteristics of 628 newly diagnosed cases from 2011 to 2016 and detailed information of 124 cases from 2015 to 2016. Spatial analyses were conducted using ArcGIS software, and statistical analyses were performed using SPSS software. Results A total of 628 cases of HIV/AIDS were diagnosed among students in Zhejiang Province, China between 2011 and 2016. The cases showed an overall increasing trend over time, while the proportions of students with HIV disease status, cases diagnosed by HIV voluntary counseling and testing (VCT), and cases of homosexual transmission remained stable over time. Significant spatial heterogeneity in the cases was seen at the county level. Detailed data on 124 HIV-positive individuals collected from the local Center for Disease Control and Prevention (CDC) from 2015 and 2016, showed that the majority of them (85.5%,) engaged in homosexual behavior, and 93.4% had sex with casual partners. These partners included not only social members, but also other students. Online dating applications represented the most common means of seeking and communicating with homosexual partners. The level of awareness regarding the risk of HIV infection, and the amount coverage of face-to-face education towards students were both low. Conclusions HIV infections among students were characterized by increasing trend and spatial clustering in Zhejiang Province between 2011 and 2016, with homosexual sexual activity being the main mode of infection. Interventions are urgently required to prevent HIV infection in this population by increasing awareness of the disease. HIV testing programs and information regarding disease prevention specifically through online dating applications are needed.

Abstract Background In China, an HIV-infected man (complainant; P2) alleged that another man (defendant; P1) had unlawfully infected him with HIV through unprotected homosexual contact in 2018. Methods We employed epidemiological, serological and phylogenetic analyses to investigate the transmission linkage between two men who have sex with men (MSM). Partial segments of three HIV-1 gene regions (gag, pol, and env) were amplified and sequenced by cloning. Maximum-likelihood (ML) and Bayesian methods were used to determine the direction and estimate the timing of transmission. Local control sequences and database control sequences were also used in the phylogenetic analysis. Results It indicated that P2 underwent HIV seroconversion after P1 was diagnosed as HIV positive. The time to the most recent common ancestor (tMRCA) estimates consistently showed that P1 most likely became HIV-1 infected at an earlier date than P2. P1 and P2 were infected with the same HIV-1 CRF01_AE subtype according to segments of all three gene regions (gag, pol, and env). All three genetic regions of P1 have been subject to more potential selective forces than those of P2, indicating a longer evolutionary history. Bayesian and ML trees showed similar paraphyletic-monophyletic topologies of gag and env, with the virus from P1 located at the root, which supported a P1-to-P2 transmission direction. Conclusions Phylogenetic investigations can elucidate HIV transmission linkage and might empower its use in the opposition of the intentional transmission of HIV-1 as a forensic tool.

We aimed to elucidate the characteristics of HIV molecular epidemiology and identify transmission hubs in eastern China using genetic transmission network and lineage analyses. HIV-TRACE was used to infer putative relationships. Across the range of epidemiologically-plausible genetic distance (GD) thresholds (0.1-2.0%), a sensitivity analysis was performed to determine the optimal threshold, generating the maximum number of transmission clusters and providing reliable resolution without merging different small clusters into a single large cluster. Characteristics of genetically linked individuals were analyzed using logistic regression. Assortativity (shared characteristics) analysis was performed to infer shared attributes between putative partners. 1,993 persons living with HIV-1 were enrolled. The determined GD thresholds within subtypes CRF07_BC, CRF01_AE, and B were 0.5%, 1.2%, and 1.7%, respectively, and 826 of 1,993 (41.4%) sequences were linked with at least one other sequence, forming 188 transmission clusters of 2-80 sequences. Clustering rates for the main subtypes CRF01_AE, CRF07_BC, and B were 50.9% (523/1027), 34.2% (256/749), and 32.1% (25/78), respectively. Median cluster sizes of these subtypes were 2 (2-52, n = 523), 2 (2-80, n = 256), and 3 (2-6, n = 25), respectively. Subtypes in individuals diagnosed and residing in Hangzhou city (OR = 1.423, 95% CI: 1.168-1.734) and men who have sex with men (MSM) were more likely to cluster. Assortativity analysis revealed individuals were more likely to be genetically linked to individuals from the same age group (AIage = 0.090, P

In this study, a spherical silica nanoparticle was explored as a gatifloxacin carrier synthesized by the chemical precipitation method. It was found that there was no new chemical bond formation during the loading process between gatifloxacin and silica, which implies that the binding was driven by physical interaction. In addition, the drug loading and encapsulation efficiency could be improved by appropriately increasing nano-silica content in the loading process. Meanwhile, the release rate of gatifloxacin after loading nano-silica was also improved, suggesting the successful design of a controlled-release delivery composite. The silica nanocarrier could significantly improve the antibacterial performance of Escherichia coli by 2.1 times, which was higher than the pure gatifloxacin. The 24 h bacteriostatic rate was higher than that of a simple mixture of silica nanoparticles and gatifloxacin. Strong reactive oxygen species (ROS) in GAT-SiO2 NPs suggests that ROS might be associated with bactericidal activity. The synergy between the physicochemical effect and ROS production of this material is proposed as the mechanism of its antibacterial activity, which can also be confirmed by the cell membrane damage observed under electron microscopy and DNA damage experiments. Collectively, our finding indicates that nano-silica microspheres could serve as a promising carrier for the sustained release of gatifloxacin, thereby providing a new carrier design scheme for the improvement of the antibacterial effect.

Objectives To characterise low-tier female sex workers (FSWs) who engage in commercial sex with old male clients (OMCs).Design Cross-sectional study.Setting Twenty-one counties in Zhejiang province, China.Participants A total of 2647 low-tier FSWs who participated in our survey from September to November 2013, and responded to the question regarding whether they engaged in commercial sex with OMCs during the previous month.Main outcome measures Data on sociodemographic characteristics, sexual behaviours, risk perception of HIV/sexually transmitted infection (STI), ever exposure to an HIV prevention service and degree of self-efficacy regarding condom use were collected via a face-to-face questionnaire administered by trained interviewers.Results Of the 2647 participants, 1165 (44.0%) had engaged in commercial sex with OMCs in the previous month. Low-tier FSWs working out of roadside shops, those who had engaged in sex work for longer, those with a larger number of clients, those who had engaged in anal or oral sex during the previous month, those currently using contraception measures, those who had STI symptoms and those who had been exposed to HIV prevention services during the previous 6 months were more likely to engage in commercial sex with OMCs. FSWs with a high level of education; those working out of small venues other than streets, hair salons and roadside shops; those who charged more for commercial sex; those who had sex with young clients during the previous month and those who had seen a doctor during the previous 6 months were less likely to engage in commercial sex with OMCs.Conclusions Low-tier FSWs who engaged in commercial sex with OMCs reported more risky behaviours than those who did not engage in this behaviour. Attention should be paid to these behaviours in future interventions targeting low-tier FSWs.

Angucyclines and angucyclinones represent the largest family of type II PKS-engineered natural products. Chemical analysis of a marine Streptomyces sp. KCB-132 yielded three new members, actetrophenone A (1) and actetrophenols A–B (2–3). Their structures were elucidated by NMR spectroscopy, X-ray crystallography and CD calculations. Actetrophenone A (1) is the first representative of a novel-type angucyclinone bearing a nonaromatic D-ring. Actetrophenol A (2) features a highly reduced and aromatized four-ring system, which is unprecedented for natural products. While (Ra)- and (Sa)-actetrophenol B (3) bear an unprecedented N-acetyltryptamine-substituted tetraphene core skeleton, this is the first report of a pair of atropisomeric isomers in the angucyclinone family. Actetrophenol A (2) exhibits remarkable antibiotic activity, notably including potent activity to multiple resistant Staphylococcus aureus and Enterococcus faecium with MIC values of 4 μg/ml, in contrast, the positive control antimicrobial agent penicillin was inactive up to 32 μg/ml.

BackgroundFinding casual sex partners on the internet has been considered a huge challenge for HIV transmission among men who have sex with men (MSM) in China. ObjectiveThis study aimed to identify the characteristics and risk factors of finding causal sex partners on the internet among MSM in Zhejiang Province, China. MethodsThis was a cross-sectional study. Participants were enrolled by 4 community-based organizations (CBOs) and 10 Voluntary Counselling and Testing (VCT) clinics through advertisements in bathrooms, bars, and gay hook-up apps from June to December 2018. A CBO- or physician-assisted survey was conducted to collected information on finding casual sex partners, perceived HIV infection, and HIV risk behaviors. ResultsAmong 767 participants, 310 (40.4%) reported finding causal sex partners on the internet. Factors associated with finding casual sex partners on the internet included watching pornographic videos on the internet more than once a week (adjusted odds ratio [aOR]=1.881, 95% CI 1.201-2.948), discussing “hooking-up online” with friends (aOR=4.018, 95% CI 2.910-5.548), and perceiving that the likelihood of HIV infection among casual sex partners sought on the internet was “medium” (aOR=2.034, 95% CI 1.441-2.873) or “low” (aOR=2.548, 95% CI 1.524-4.259). Among the participants who reported finding casual sex partners on the internet, 30.2% (91/310) reported having unprotected sex with casual sex partners encountered on the internet in the past 6 months. On multivariate logistic regression analyses, knowing the HIV infection status of casual sex partners sought on the internet was significantly associated with performing inserted intercourse (aOR=1.907, 95% CI 1.100-3.306) and a decreased risk of inconsistent condom use (aOR=0.327, 95% CI 0.167-0.642). ConclusionsWeb-based casual sexual behavior is becoming more prevalent, and the rate of unprotected sex among MSM in Zhejiang Province is high. Future HIV prevention approaches should emphasize the importance for MSM to proactively determine the HIV infection status of potential casual sex partners sought on the internet.

Abstract Background To investigate the status of anti-tuberculosis treatment in critically ill patients, and to explore the value of APACHE-II score in guiding anti-tuberculosis treatment. Methods This analysis included critically ill patients with tuberculosis. The utility of APACHE-II score for predicting drug withdrawal was evaluated using receiver operating characteristic (ROC) curve analysis. Results Among 320 patients enrolled (58 ± 22 years; 256 males), 147 (45.9%) had drugs withdrawn. The drug withdrawal group had higher APACHE-II score (median [interquartile range]: 21 [3–52] vs. 17 [4–42] points), higher CD4%, lower hemoglobin level, higher rates of chronic obstructive pulmonary disease (COPD) and chronic renal failure, and lower rate of extrapulmonary tuberculosis (P 18 (odds ratio [95% confidence interval]: 2.099 [1.321–3.334], P 18 points might predict patient tolerance of anti-tuberculosis treatment.

On January 25, 2017, a physician from ZC Hospital in Hangzhou, China, reported to the Zhejiang Provincial Center for Disease Control and Prevention that a potential HIV outbreak might have occurred during lymphocyte immunotherapy (LIT) performed at the hospital on December 30, 2016. We immediately began investigating and identified the index case-patient as an LIT patient’s husband who donated lymphocytes for his wife’s LIT and later screened HIV-reactive. Subsequent contamination by a technician resulted in the potential exposure of 34 LIT patients. Acute HIV infection was diagnosed in 5 persons. Phylogenetic analysis confirmed that the HIV-1 gag, pol, and env gene sequences from the index and outbreak-related cases had >99.5% similarity. Rapid investigation and implementation of effective control measures successfully controlled the outbreak. This incident provides evidence of a lapse in infection control causing HIV transmission, highlighting the need for stronger measures to protect patients from infectious disease exposure.

Abstract Background Treatment of hemophiliacs with inhibitors remains challenging, and new treatments are in urgent need. Coagulation factor X plays a critical role in the downstream of blood coagulation cascade, which could serve as a bypassing agent for hemophilia therapy. Base on platelet‐targeted gene therapy for hemophilia by our and other groups, we hypothesized that activated factor X (FXa) targeted stored in platelets might be effective in treating hemophilia A (HA) and B (HB) with or without inhibitors. Methods To achieve the storage of FXa in platelets, we constructed a FXa precursor and used the integrin αIIb promoter to control the targeted expression of FXa precursor in platelets. The expression cassette (2bFXa) was carried by lentivirus and introduced into mouse hematopoietic stem and progenitor cells (HSPCs), which were then transplanted into HA and HB mice. FXa expression and storage in platelets was examined in vitro and in vivo. We evaluated the therapeutic efficacy of platelet‐stored FXa by tail bleeding assays and the thrombelastography. In addition, thrombotic risk was assessed in the recipient mice and the lipopolysaccharide induced inflammation mice. Results By transplanting 2bFXa lentivirus‐transduced HSPCs into HA and HB mice, FXa was observed stably stored in platelet α‐granules, the stored FXa is releasable and functional upon platelet activation. The platelet‐stored FXa can significantly ameliorate bleeding phenotype in HA and HB mice as well as the mice with inhibitors. Meanwhile, no FXa leakage in plasma and no signs of increased risk of hypercoagulability were found in transplantation recipients and lipopolysaccharide induced septicemia recipients. Conclusions Our proof‐of‐principle data indicated that target expression of the FXa precursor to platelets can generate a storage pool of FXa in platelet α‐granules, the platelet‐stored FXa is effective in treating HA and HB with inhibitors, suggesting that this could be a novel choice for hemophilia patients with inhibitors.

Bacillus thuringiensis (Bt) has been regarded as a biopesticide with high efficiency and safety, while it still cannot be popularized and mass-produced because of its high production costs. In the present study, we aimed to develop a cost-effective biopesticide via the secondary use of discharged vegetable wastes as the raw fermentation medium, and the insecticidal activity of Bt strain prepared by this cheap cultivation approach was evaluated. The suitable carbon source, nitrogen source additives and optimal metal ions were screened by the single-factor test, and the optimal combination of additives was determined by orthogonal test and ANOVA analysis. We found that soluble starch (6 g l−1), soya bean meal (6 g l−1), Al3+ (0.4 g l−1) and Fe2+ (0.4 g l−1) were the optimal exogenous additives, and the optimal fermentation conditions were as follows: pH 7.0, temperature of 35°C and aeration of 80 ml/250 ml. Meanwhile, the bioactivity test results showed that the Bt strain prepared by cheap cultivation still exhibited a good insecticidal effect on Helicoverpa armigera compared with the standard LB medium. Collectively, our findings provided a new strategy for vegetable waste utilization with less environmental impact and reduced production cost.

To analyze the results of HIV screening and the HIV-positive rate based on different HIV detection strategies in Zhejiang Province, China. Data were downloaded from the AIDS Prevention and Control Information System on May 1, 2019. HIV screening, prevalence, and incidence data were analyzed from 2008 to 2018. The incidence of HIV was calculated from the results of BED testing. SPSS software (ver. 19.0) was used for the analysis. The number of people screened for HIV increased by 229.7% from 2008 to 2018, while the incidence of HIV increased from 1.14‱ (2010) to 1.67‱ (2018), peak by 2015 (2.28‱). The proportion of people screened for HIV in medical institutions increased from 62.0% in 2008 to 67.1% in 2018, while of all positive tests, 47.9% were conducted at medical institutions in 2008, which increased to 63.2% in 2018. VCT and STD clinic attendees, who had only 4.5% of all those undergoing HIV tests, accounted for 23.7% of all HIV positive in 2018. The rate of HIV-positive people and incidence of HIV both increased in Zhejiang Province between 2008 and 2015. The most effective strategy for detecting HIV new cases is screening visitors to VCT and STD clinics.

Few studies have considered psychosocial characteristics when investigating the associations between sleep duration and blood pressure (BP). In this study, we took propensity score matching (PSM) to adjust for psychosocial characteristics when comparing BP between individuals with short sleep duration and those with normal sleep duration. A total of 429 participants were included. 72 participants with sleep duration ≤6 h and 65 participants with sleep duration >6 h were matched after PSM. We compared office BP, 24-hour BP, and prevalence of hypertension in the populations before and after PSM, respectively. In the unmatched population, participants with sleep duration ≤6 h were observed with higher office diastolic BP (DBP) and 24-h systolic BP (SBP)/DBP (all P6 h) in office DBP (88.4 ± 10.9 vs. 82.5 ± 11.1 mm Hg; P=0.002), 24-h SBP (134.7 ± 12.0 vs. 129.3 ± 11.6 mm Hg; P=0.009), and 24-h DBP (83.4 ± 9.9 vs. 78.1 ± 10.1 mm Hg; P=0.002) become more significant. Participants with sleep duration ≤6 h only show higher prevalence of hypertension based on 24-h BP data, while analysis after PSM further revealed that these with sleep duration ≤6 h presented about 20% higher prevalence of elevated BP up to office diagnosed hypertension threshold. Therefore, psychosocial characteristics accompanied with short sleep duration should be fully valued in individuals at risks for elevated BP. This trial is registered with NCT03866226.

BACKGROUND:Measures to effectively expand tracing and testing to identify undiagnosed HIV infections are significant for the control of HIV/AIDS epidemic among men who have sex with men (MSM). We piloted a choice-based tracing and testing package aimed at improving partner tracing, uptake, and yield of HIV testing for sexual partners of newly diagnosed HIV-positive MSM. METHODS:This package was piloted in the cities of Hangzhou and Ningbo, Zhejiang province, China from June 2014 to June 2016. The package adopted four modes: couples' HIV counseling and testing (CHCT), information assisted partner notification (IAPN), assisted HIV self-testing (HIVST) and patient referral. Data regarding sociodemographic factors and sexual behaviors between HIV-positive MSM and their sexual partners, as well as tracing and testing outcomes of each mode, were collected. RESULTS:Among 2,495 newly diagnosed HIV-positive MSM, 446(18%) were enrolled as index cases (ICs) through two rounds of contact tracing. The ICs disclosed a total of 4,716 sexual partners, of whom 548 (12%) were reachable. The pilot study resulted in a testing uptake of 87% (478/548), and a yield of 16% (74/478) among sexual partners. The generalized linear mixed model showed that the odds of a reachable sexual partner enrolled via IAPN taking an HIV test were 290% greater than that of a partner traced via CHCT (95% CI: 1.6, 9.3). CONCLUSIONS:A choice-based tracing and testing package can feasibly expand HIV testing uptake and case finding among sexual partners of HIV-positive MSM. IAPN may be an acceptable option to reach sexual partners for whom limited contact information is available.

ObjectivesOral sex and its associated factors among low-tier female sex workers (FSWs) have not been documented in the Chinese literature. Here, we report this perspective in this group.MethodsThe data were derived from a large cross-sectional study conducted among low-tier FSWs using a structured questionnaire in 21 counties in Zhejiang province, China. The prevalence of oral sex and its associated factors among 2645 low-tier FSWs were analyzed using bivariate and multivariate analysis.ResultsOf all participants, 579 (21.9%) had performed oral sex with clients over the previous month. Multivariate analysis revealed that oral sex is related to being unmarried, low income, early initiation of commercial sex, having conducted commercial sex in more counties, longer duration of commercial sex, larger number of clients, ever having engaged in anal sex, less use of condoms and oral contraceptives during the previous month, low rate of adoption for contraception at the present time, and STI-related symptoms during the previous half year.ConclusionOral sex practitioners among low-tier FSWs in China are at a higher risk of STI, HIV, and unwanted pregnancy compared to those who did not engage in oral sex. Behavioral interventions carried out among low-tier FSWs should specifically target low-tier FSWs who practice oral sex, should carefully take into account the characteristics of these FSWs, provide risk awareness education and training for condom use negotiation, and promote the availability of condom and reproductive health care, timely diagnosis, and treatment of STIs.

BackgroundCurrently, human immunodeficiency virus (HIV) sentinel surveillance among men who have sex with men (MSM) in China conducted in large and medium-sized cities, and no HIV sentinel surveillance conducted in rural areas. HIV testing and intervention is predominantly conducted in urban areas, there have been a limited number of studies in rural areas MSM, it is necessary to conduct the investigation of HIV risk sexual behavior, HIV testing among rural and urban MSM.MethodBetween December 2013 and August 2015, a cross-sectional study was conducted in rural and urban areas in Zhejiang Province using respondent-driven sampling (RDS). Participants completed face-to-face interviewer-administered questionnaire surveys and were tested for HIV.ResultsA total of 710 MSM participants were recruited, of whom 36.1% were from rural areas. The overall HIV prevalence was 16.6%, and was considerably lower among MSM living in rural areas (3.9%) than those living in urban areas (24.2%). 61.1% participants had not condom use with male sexual behavior in the past 6 months (86.7% in rural areas and 46.7% in urban areas). The social demographic and behavioral characteristics had significance difference among rural and urban MSM. Multivariate logistic regression revealed that, compared to men living in urban areas, MSM living in rural areas MSM were more likely to use dating apps to find sexual partners, were more likely to engage in bisexual behavior, and had lower condom use. 43.0% participants had been tested for HIV in the past year (41.8% in rural areas and 43.6% in urban areas). Multivariate logistic regression also revealed that among participants living in rural areas, having rural health insurance and not accepting HIV intervention were associated with lower HIV testing rates, while a higher monthly income and through use of internet to find sexual partner were associated with higher rates of HIV testing.ConclusionHigh risk behavior was prevalent, and HIV testing rates were low among MSM living in rural areas compare to urban areas in Zhejiang Province, therefore, preventative intervention measures should be immediately among rural MSM urgently to reduce HIV transmission and to promote HIV testing.

Though succinate accumulation is associated with reactive oxygen species (ROS) production and neuronal injury, which play critical roles in epilepsy, it is unclear whether succinate accumulation contributes to the onset of epilepsy or seizures. We sought to investigate changes in succinate, oxidative stress, and mito-SOX levels, as well as mitophagy and neuronal change, in different status epilepticus (SE) rat models. Our results demonstrate that KA-induced SE was accompanied by increased levels of succinate, oxidative stress, and mito-SOX, as well as mitophagy and neuronal degeneration. The similarly increased levels of succinate, oxidative stress, and mito-SOX were also found in pilocarpine-induced SE. Moreover, the reduction of succinate accumulation by the inhibition of succinate dehydrogenase (SDH), malate/aspartate shuttle (MAS), or purine nucleotide cycle (PNC) served to reduce succinate, oxidative stress, and mito-SOX levels, thereby preventing oxidative stress-related neuronal damage and lessening seizure severity. Interestingly, simulating succinate accumulation with succinic acid dimethyl ester may induce succinate accumulation and increased oxidative stress and mito-SOX levels, as well as behavior and seizures in electroencephalograms similar to those observed in rats exposed to KA. Our results indicate that succinate accumulation may contribute to the increased oxidative stress/mitochondrial ROS levels, neuronal degeneration, and SE induced by KA administration. Furthermore, we found that succinate accumulation was mainly due to the inverse catalysis of SDH from fumarate, which was supplemented by the MAS and PNC pathways. These results reveal new insights into the mechanisms underlying SE and that reducing succinate accumulation may be a clinically useful therapeutic target in SE. Keywords: Status epilepticus, Succinate, Reactive oxygen species, Neurodegeneration, Mitophagy

Huganpian (HGP), a traditional chinese medicine composed of 6 herbs, possesses excellent therapeutic effects in clinical application. In this study, we aimed to elucidate the anti-tumor activity and the underlying mechanisms of HGP in liver cancer. The results of this study indicated that HGP effectively inhibited liver cancer growth in vitro and in vivo in a dose-dependent manner. Mechanistically, HGP exerted its anti-tumor effects by triggering autophagy with increased LC3Ⅱ and beclin1 levels and arrested the cell cycle on G0-G1 phase by downregulating the expressions of cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4) and cyclinE1 in vitro and in vivo. Meanwhile, HGP did not induce apoptosis significantly. Importantly, we also confirmed that there were fewer side effects of HGP on immune system. Taken together, our findings suggest for the first time that HGP may become a promising drug or adjuvant drug with a lower toxicity for liver cancer treatment in the future.

Abstract Background The use of new types of drugs has become more common among men who have sex with men (MSM). The aim of this study was to describe the patterns of the use of new types of drugs, such as methamphetamine, ketamine, ecstasy, and rush poppers, and to examine the factors associated with drug use and HIV infection among MSM in Hangzhou, China. Methods This cross-sectional study was conducted between August 2015 and April 2016. We used snowball sampling to recruit MSM; participants were recruited from voluntary counseling and testing centers, baths, bars, Blued (an app for the gay community), QQ groups, clubs, and other types of venues. MSM were included if their previous HIV test results were negative or unknown, or they had not been tested for HIV. MSM were excluded if they were known to be HIV positive before the survey. Face-to-face questionnaires were conducted and a venous blood specimen was drawn from each participant following the interview. Results In total, 555 MSM were included; 18.2% (101/555) of the participants had used new types of drugs in the past 3 months. Among the users, 65.3% used single-use rush poppers, while the remainder used ketamine, methamphetamine, ecstasy, or other mixed combinations of drugs. The HIV positivity rate was 14.8% (82/555). Factors associated with increased odds of using new types of drugs in the past 3 months were higher education levels (adjusted odds ratio [AOR] 4.45, 95% confidence interval [CI] 2.12–9.37), having multiple sexual partners (AOR 1.76, 95 CI 1.02–3.05), alcohol use before sexual intercourse (AOR 33.44, 95% CI 10.80–103.50), and seeing friends using new types of drugs. Conclusion We revealed the widespread use of new types of drugs, as well as a high diagnosis rate of new HIV infection, among MSM in Hangzhou. The use of new types of drugs was associated with an increased number of sexual partners among MSM; the high-risk sexual behaviors increased the risk of HIV infection. Attention should be given to the use of new types of drugs in MSM, and supervision programs should be strengthened to combat drug use.

Abstract Background Previous studies have shown that the increased coverage of antiretroviral therapy (ART) could reduce the community viral load (CVL) and reduce the occurrence of new HIV infections. However, the impact on the reduction of HIV transmission among men who have sex with men (MSM) is much less certain. The frequency of HIV infections in MSM have been rapidly increasing in recent years in Hangzhou, China. The “Treatment as Prevention” strategy was implemented at a population-level for HIV-infected MSM from January 2014 to June 2016 in Hangzhou; it aimed to increase the ART coverage, reduce the CVL, and reduce HIV transmission. Methods We investigated a subset of MSM diagnosed with HIV pre- and post-implementation of the strategy, using random sampling methods. Viral load (VL) testing was performed for all enrolled individuals; the lower limits of detection were 20 and 50 copies/mL. The data on infections were collected from the national epidemiology database of Hangzhou. Logistic regression analyses were conducted to identify factors associated with the differences in social demographic characteristics and available VL data. Results The ART coverage increased from 60.7% (839/1383) during the pre-implementation period to 92.3% (2183/2365) during the post-implementation period in Hangzhou. A total of 940 HIV-infected MSM were selected for inclusion in this study: 490 (52.1%) and 450 (47.9%) MSM in the pre- and post-implementation periods, respectively. In total, 89.5% (841/940) of patients had data available on VL rates. The mean CVL was 579 copies/mL pre-implementation and this decreased to 33 copies/mL post-implementation (Kruskal-Wallis

Abstract Background This study investigated condom use among female sex workers (FSWs) at hair salons during commercial sexual interactions over 1 month. We explored the associations of such use with various sexual behaviours, HIV/STI risk perception and related knowledge, self-efficacy regarding condom use, exposure to behavioural interventions, and other factors. This type of information has not been reported in China and is critical for designing and modifying programs aimed at preventing HIV/STI transmission in this group of FSWs and their clients. Methods Our data were derived from a large cross-sectional study conducted among low-tier FSWs in 21 counties within Zhejiang province, China. Data were collected from September to November 2013.Bivariable and multiple logistic regression analyses were used to identify factors associated with self-reported consistent condom use among FSWs working at hair salons. Results Of 1682 FSWs working at hair salons, 50.5% consistently used condom with clients during the previous month. Multivariable analysis revealed that condom use for commercial sex, consistent vaginal douching after commercial sex, adopting contraceptive measures, high scores on perceived self-efficacy regarding condom use, and exposure to interventions were associated with self-reported consistent condom use; early initiation of commercial sex, experiences with oral sex, rarely/sometimes/often using oral contraceptives, and having seen a doctor were associated with not using condoms. Conclusions Commercial sex is not effectively protected, and behavioural interventions targeting FSWs should take into account the various factors that are correlated to condom use.

Abstract Background Men who have sex with men (MSM) have become one of high-risk population for human immunodeficiency virus (HIV) infection, due to their multiple sex partners and unprotected anal intercourse. Promoting HIV testing is an effective strategy for the prevention and control of HIV infection. We assessed the factors associated with a prior HIV testing history, which could provide guidance for implementation of future HIV intervention programs. Methods A cross-sectional study was conducted in three cities of Zhejiang Province, namely, Hangzhou, Ningbo and Wenzhou, using respondent-driven sampling, between December 2013 and June 2014. A face-to-face questionnaire survey was employed to collect relevant information about HIV testing. Univariate and multivariate logistic regression analyses were used to identify the factors associated with a prior HIV testing history. Results The adjusted rate of prior HIV testing among MSM in Zhejiang Province was 55.9 %. The adjusted rates of HIV and syphilis infections among MSM in Zhejiang Province were 14.0 % and 11.4 %, respectively. A weighted multivariate analysis showed that MSM of older age were more likely to be tested, as were MSM with higher level of education, self-reported homosexuality and a higher frequency of receiving AIDS/sexually transmitted infections educational intervention in the past year. MSM with suicidal inclination and self-perceived lower possibility of HIV infection were less likely to report ever having undergone an HIV test. Conclusions The prevalence of prior HIV testing among MSM in Zhejiang Province, China is low. Effective and more frequent interventional measures should be adopted to improve risk awareness and psychosocial support for younger, less educated MSM, and to encourage more MSM to undergo HIV testing.

Previous studies have reported the possible neuroprotective effects of xenon treatment. The purpose of this study was to define the range of effective xenon ratio, most effective xenon ratio, and time-window for intervention in the kainic acid (KA) – induced status epilepticus (SE) rat model. Different ratios of xenon (35% xenon, 21% oxygen, 44% nitrogen, 50% xenon, 21% oxygen, 29% nitrogen, 70% xenon, 21% oxygen, and 9% nitrogen) were used to treat the KA-induced SE. Our results confirmed the anti-seizure role of 50 and 70% xenon mixture, with a stronger effect from the latter. Further, 70% xenon mixture was dispensed at three time points (0 min, 15 min delayed, and 30 min delayed) after KA administration, and the results indicated the anti-seizure effect at all treated time points. The results also established that the neuronal injury in the hippocampus and entorhinal cortex (EC), assessed using Fluoro-Jade B (FJB) staining, were reversed by the xenon inhalation, and within 30 min after KA administration. Our study, therefore, indicates the appropriate effective xenon ratio and time-window for intervention that can depress seizures. The prevention of neuronal injury and further reversal of the loss of effective control of depress network in the hippocampus and EC may be the mechanisms underlying the anti-seizure effect of xenon.

Previous studies suggested that the thrombospondin-1/transforming growth factor-β1 (TSP-1/TGF-β1) pathway might be critical in synaptogenesis during development and that the purinergic P2 receptor family could regulate synaptogenesis by modulating TSP-1 signaling. However, it is unclear whether this pathway plays a role in synaptogenesis during epileptic progression. This study was designed to investigate this question by analyzing the dynamic changes and effects of TSP-1 levels on the density of synaptic markers that are related to epileptic seizure activity. In addition, we evaluated whether P2-type receptors could regulate these effects. We generated a rat seizure model via amygdala kindling and inhibited TSP-1 activity using small interfering RNA (siRNA) interference and pharmacological inhibition. We treated the rats with antagonists of P2 or P2Y receptors, pyridoxalphosphate-6-azophenyl-2’,4’-disulfonic (PPADS) or Reactive Blue 2. Following this, we quantified TSP-1 and TGF-β1 immunoreactivity (IR), the density of synaptic markers, and seizure activity. There were significantly more synapses/excitatory synapses in several brain regions, such as the hippocampus, which were associated with progressing epileptic discharges after kindling. These were associated with increased TSP-1 and TGF-β1-IR. Genetic or pharmacologic inhibition of TSP-1 significantly reduced the density of synaptic/excitatory synaptic markers and inhibited the generalization of focal epilepsy. The administration of PPADS or Reactive Blue 2 attenuated the increase in TSP-1-IR and the increase in the density of synaptic markers that follows kindling and abolished most of the epileptic seizure activity. Altogether, our results indicate that the TSP-1/TGF-β1 pathway and its regulation by P2, particularly P2Y-type receptors, may be a critical promoter of synaptogenesis during the progression of epilepsy. Therefore, components of this pathway may be targets for novel antiepileptic drug development.