Nickel-Catalyzed Three-Component Alkylarylation of Alkenyl N-Heteroarenes.

A nickel-catalyzed three-component alkylarylation of alkenyl N-heteroarenes with α-bromocarboxylates and aryl boronic acids is reported. The protocol provides a new method to access a variety of N-heteroarene substituted diarylalkanes in moderate to good yields. It features mild reaction conditions, cheap nickel catalyst, readily available substrates, and broad substrate scope.

The related factors of new HIV infection among older men in Sichuan, China: a case-control study.

Human immunodeficiency virus (HIV) has been widely prevalent among older men (aged ≥50 years old) in Sichuan Province. The study aimed to discover associated factors with the new HIV infection in older men, and provide a scientific basis for the prevention and control of acquired immunodeficiency syndrome (AIDS) in this group. A cross-sectional survey study of newly reported HIV/AIDS and general male residents aged 50 years and older was conducted between April and June 2019, with a resample of respondents to identify cases and controls, followed by a case-control study. Logistic regression was applied to analyse the association between the selected factors and new HIV infection among older men. At last, 242 cases and 968 controls were included. The results of multiple logistic regression suggested that many factors including living alone/concentrated (OR 1.56, 95% CI 1.20-2.04, P = 0.001), have a history of migrant worker (OR 2.10, 95% CI 1.61-2.73, P < 0.001), have commercial sexual behaviour (OR 1.71, 95% CI 1.32-2.22, P < 0.001), married (OR 0.48, 95% CI 0.37-0.64, P < 0.001), have a history of HIV antibody testing (OR 0.73, 95% CI 0.56-0.96, P = 0.026), HIV-related knowledge (OR 0.55, 95% CI 0.42-0.72, P < 0.001) were associated with new HIV infection among older men. The present study revealed some potential risky/protective factors altogether. The results highlighted the direction of HIV/AIDS prevention and control among older men, and it is a social issue that requires the joint participation of the whole society.

Epidemiological and spatiotemporal analyses of HIV/AIDS prevalence among older adults in Sichuan, China between 2008 and 2019: A population-based study.

OBJECTIVES: To describe epidemiological trends and spatial distributions of HIV/AIDS among older adults (aged ≥50) in Sichuan Province, China during 2008-19, and provide scientific reference for HIV/AIDS prevention, intervention and treatment. METHODS: Data on HIV/AIDS cases reported in 2008-19 was extracted from the Case Report System. The Cochran-Armitage trend test was used to determine epidemic trends. Spatial autocorrelation and space-time analysis were conducted with ArcGIS10.6 and ArcGIS Pro2.4, respectively. RESULTS: A total of 77854 HIV/AIDS cases among older adults were included in the study. Newly reported cases increased from 320 in 2008 to 22189 in 2019, and the reported incidence rate (number of new reported cases/older adult population) rose from 0.001% to 0.077%. Infections through heterosexual transmission increased from 65.3% to 98.2% of total cases in older adults in this period. Spatial analysis at the county-level showed significant clustering throughout Sichuan, with the main hot spots concentrated in the southeast. Spatiotemporal analysis indicated that most of the southeastern counties/districts were Consecutive Hot Spots. CONCLUSIONS: Older adults have become a key population in the HIV/AIDS epidemic in Sichuan; comprehensive prevention and intervention measures targeted to older adults are urgently needed to control the spread of HIV/AIDS.

Copper-catalyzed asymmetric silyl addition to alkenyl-substituted N-heteroarenes.

Asymmetric conjugate addition of PhMe2SiBPin to a wide range of N-heteroaryl alkenes proceeded in the presence of a copper catalyst coordinated with an easily accessible chiral phosphoramidite ligand to afford useful ß-silyl N-heteroarenes in high yields (up to 96%) and excellent enantioselectivities (up to 97% ee).

CuH-Catalyzed Asymmetric 1,6-Conjugate Reduction of p-Quinone Methides: Enantioselective Synthesis of Triarylmethanes and 1,1,2-Triarylethanes.

The first copper hydride (CuH)-catalyzed asymmetric 1,6-conjugate reduction of p-quinone methides is reported. This protocol provides a new method to access a variety of triarylmethanes and 1,1,2-triarylethanes in good yields with excellent enantioselectivities and broad functional group tolerance.

Rapid Identification of the Receptor-Binding Specificity of Influenza†A Viruses by Fluorogenic Glycofoldamers.

The re-emergence of influenza raises a global concern that viral pandemics can unpredictably occur. However, effective approaches that can probe the infection risk of influenza viruses for humans are rare. In this work, we develop a glycofoldamer that can rapidly identify the glycan-receptor specificity of influenza viruses in a high-throughput manner. The coupling of glycan receptors that can be recognized by hemagglutinin (a surface protein on the virion capsid of influenza) to a fluorogenic-dye foldamer produces the glycofoldamers with minimal fluorescence in aqueous solution. After interaction with human-infecting virus strains for only five minutes, the fluorescence intensity of the glycofoldamer is remarkably enhanced with a blue-shifted emission peak. The probes have also proven effective for the rapid identification of 1) the human- or bird-infecting properties of influenza viruses in a high-throughput manner and 2) the receptor-specificity switch of a virus strain by mutations.

Supramolecular Ensembles Formed between Charged Conjugated Polymers and Glycoprobes for the Fluorogenic Recognition of Receptor Proteins.

This paper describes the simple construction of a unique class of supramolecular ensembles formed by electrostatic self-assembly between charged conjugated polymers and fluorophore-coupled glycoligands (glycoprobes) for the selective fluorogenic detection of receptor proteins at both the molecular and cellular levels. We show that positively and negatively charged diazobenzene-containing poly(p-phenylethynylenes) (PPEs) can be used to form stable fluorogenic probes with fluorescein-based (negatively charged) and rhodamine B based (positively charged) glycoprobes by electrostatic interaction. The structures of the ensembles have been characterized by spectroscopic and microscopic techniques. The supramolecular probes formed show quenched fluorescence in an aqueous buffer solution, which can be specifically recovered, in a concentration-dependent manner, through competitive complexation with a selective protein receptor, over a range of other unselective proteins. The ensembles also show selective fluorescence enhancement with a live cell that expresses the glycoligand receptor but not a control cell without receptor expression.

Carbohydrate CuAAC click chemistry for therapy and diagnosis.

Carbohydrates are important as signaling molecules and for cellular recognition events, therefore offering scope for the development of carbohydrate-mimetic diagnostics and drug candidates. As a consequence, the construction of carbohydrate-based bioactive compounds and sensors has become an active research area. While the advent of click chemistry has greatly accelerated the progress of medicinal chemistry and chemical biology, recent literature has seen an extensive use of such approaches to construct functionally diverse carbohydrate derivatives. Here we summarize some of the progress, covering the period 2010 to mid-2015, in Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition CuAAC "click chemistry" of carbohydrate derivatives, in the context of potential therapeutic and diagnostic tool development.

[Comparative study of the cytotoxicity induced by chrysotile asbestos, rock wool and substitute fibers in vitro].

OBJECTIVE: To study the cytotoxicity induced by chrysotile asbestos (CA), rock wool (RW) and wollastonite (WS). METHODS: V79 cells were divided into 4 groups. i.e. CA group, WS group, RW group and control group (200 microl PBS). The exposure concentration of dusts was 100 mg/L, The cell viability was detected by MTT and lactate dehydrogenase (LDH) activity assays. The technique of scanning electron microscopy was used to examine the change of V79 cells. RESULTS: SiO2 was main constituent for 3 kinds of dusts. In MTT assay, the cell viability of RW and WS groups was 64.8% and 65.7%, respectively, which were significantly higher than that (54.5%) of CA group (P < 0.01). In LDH assay, the LDH activity of RW and WS groups [(15.7 +/- 50.9), (12.3 +/- 3.7) U/L, respectively] was significantly lower than that [(20.2 +/- 0.9) U/L] of CA group (P < 0.05). In scanning electron microscopy examination, it was found that the two ends of V79 cells in CA group contained a great deal of fibers remaining bodies, but the V79 cell appearance in RW and WS groups was normal. CONCLUSION: The cytotoxicity induced by RW and WS is significantly lower than that induced by CA for V79 cell.

[Sharing of needles and paraphernalia injection in new and long-term injection drug users in Sichuan, China].

OBJECTIVE: To examine the prevalence and correlates for needle-sharing among new and long-term injection drug users (IDUs) in Sichuan province, China. METHODS: Three consecutive cross-sectional surveys were conducted in 6 prefectures of Sichuan province, from 2003 to 2005. Questionnaire-based interviews provided information including socio-demographics, drug-use, sexual behaviors, and HIV-related services. Multivariable logistic regression methodology was used for data analysis. RESULTS: Of 3852 eligible participants, the rates of needle-sharing in the last 6 months for IDUs with a less than one year, one to three year, and more than three year injection history were 19.9%, 29.1%, and 36.3%, respectively. Needle-sharing for IDUs with a less than one-year injection history was independently associated with factors as: being female, having minority background, higher frequency of injection, sharing injecting equipments, ever having had a non-regular sex partner, or a regular sex partner who injected drugs, never had a test on HIV, being recruited in 2005, and from Zigong prefectures of Sichuan. Needle-sharing for IDUs with a 1-3 year injection history were independently associated with receiving less education, having higher frequency of injecting behavior, sharing injecting equipments, ever having had a non-regular sex partner/a regular sex partner who injected drugs, ever having had unprotected sex with a non-regular sex partner, ever having had unprotected sex with a commercial sex partner or client, never attended skill training for HIV/STD prevention, being recruited in 2005 and 2004, and being recruited from Deyang, Zigong, and Liangshan prefectures. Needle-sharing for IDUs with a more than three-year injection history was independently associated with factors as: less education, higher frequency of injecting, sharing injecting equipment, ever had a non-regular sex partner, ever had unprotected sex with a non-regular sex partner, ever had unprotected sex with a commercial sex partner or client, having had regular sex partners who inject drugs, never attended needle exchange programs, being recruited in 2005 and 2004, and being recruited from Deyang, Zigong, and Liangshan prefectures. CONCLUSION: The rates for both needle/paraphernalia sharing and unprotected sex behaviors were high in the IDUs in Sichuan province. These rates were higher among longer-term IDUs than in new IDUs. Our data underlined that better targeted, in-depth and sustained comprehensive intervention packages which including needle exchange, condom promotion along with distribution, and education, were urgently needed to reduce both IDU-related and sex-related risk behaviors among both new and longer term IDUs.

Mechanism of simvastatin-induced K562 cell apoptosis.

Statins are being widely used for the therapy and prevention of several types of tumors, including human chronic myelogenous leukemia, but the underlying molecular mechanisms still remain unknown. Therefore, inhibition of cell proliferation, apoptosis and involved molecules were investigated in K562 cells after incubation with simvastatin.The results showed that simvastatin diminished K562 cell proliferation and induced apoptosis. At the same time, the level of reactive oxygen species (ROS) and intracellular calcium concentration increased. Furthermore, nitric oxide (NO) content and inducible NO synthase (iNOS) mRNA expression were significantly higher in the simvastatin-treated group than in the corresponding control group. The elevated ROS level and intracellular calcium concentration, enhanced mRNA expression of iNOS and total NO content might be responsible for the apoptotic and anti-proliferative effects of simvastatin in K562 cells.

In vitro and in vivo study of cell growth inhibition of simvastatin on chronic myelogenous leukemia cells.

BACKGROUND: Statins, a family of 3-hydroxy-3-methylglutaryl CoA (HMG CoA) reductase inhibitors, are being investigated for the therapy and prevention of cancers. Here we aimed to investigate the effects of simvastatin on chronic myelogenous leukemia (CML) cells in vitro and in vivo, and to elucidate the mechanisms. METHODS: Cell proliferation and cell cycle were measured after K562 cells were incubated with simvastatin, and differentially expressed genes were determined by oligonucleotide microarray. Changes of 2 genes obtained by oligonucleotide microarray were validated by real-time RT-PCR, and immunohistochemistry was performed to determine expression of proliferating cell nuclear antigen (PCNA). Finally, a xenograft tumor model was constructed to evaluate the effects of simvastatin in vivo. RESULTS: Simvastatin could inhibit K562 cell proliferation, and the inhibition rate was approximately 30% after treatment with 20 mumol/l simvastatin for 48 h. Cell cycle was arrested in G(1) phase, as shown by flow cytometry results. Fifteen downregulated, 9 upregulated cell cycle-related genes and decreased PCNA protein were observed in the presence of simvastatin. Furthermore, simvastatin exhibited impairment of xenograft tumor growth in nude mice and also blocked cell cycle in G(1) phase. CONCLUSION: Simvastatin can inhibit CML cell proliferation in vitro and in vivo, and its mechanisms might be involved in cell cycle regulation.

[A study on acquired immune deficiency syndrome related behaviors in male clients of female sex workers].

OBJECTIVE: To study the socio-demographic characteristics, acquired immune deficiency syndrome (AIDS) related behaviors of male clients of female sex workers and their determinants. METHODS: Contacting subjects through 5 ways including volunteers of female sex workers (FSWs), sexually transmitted disease (STD) clinics, long-distance bus stations, long-distance cargo station while adopting methods as snowballing, employing an anonymous questionnaire. Data was analyzed by logistic regression analysis. RESULTS: (1) The majority of clients were 25-45 years old, married and of junior high school or above educational levels; (2) Among male clients of FSWs, numbers of having had commercial sexual intercourse was between 1 to 240, averaged 24 in the previous year. It significantly related to their occupation and the experience of their friends or colleagues who ever visited female sex workers; (3) 27.98% of them used condom every time during commercial sexual intercourse, which significantly related to the score of knowledge on AIDS, concourse of sex intercourse and inhabitation; (4) 28.36% of them had ever contracted STD, which significantly related to the frequency of commercial sexual intercourse in the previous year, risk awareness of being infected with human immunodeficiency virus, and frequency of condom use during commercial sexual intercourse. CONCLUSION: The proportion of always using condom was low among male clients of FSWs, and had had STDs. And it's necessary for active and specific intervention programs to them.