Rapid Electrophilic Cysteine Arylation with Pyridinium Salts.

Here, we present a series of fluorinated cationic reagents that enable rapid arylation of cysteine under mild conditions compatible with proteins and peptides. The highly polarized C-F bond and attractive nucleophile-electrophile Coulombic interactions substantially accelerate cysteine arylation, leading to unusually high rate constants on the order of 100 M-1·s-1 and allowing for equimolar labeling of substrates at micromolar concentrations. The synthetic modularity of this approach promotes the direct coupling of structurally diverse phenol-containing functional motifs to cysteine residues of biomacromolecules with high efficiency. This user-friendly chemistry enables fast bond formation between commonly used bioconjugation partners, thus greatly streamlining the synthetic chemistry workflow, and can be easily developed as convenient kits for chemical biology and medicinal chemistry applications.

Effect of health education based on information-motivation-behavioral skills model on patients with unilateral vestibular dysfunction.

BACKGROUND: Vestibular dysfunction (VH) is a common concomitant symptom of late peripheral vestibular lesions, which can be trauma, poisoning, infection, heredity, and neurodegeneration, but about 50% of the causes are unknown. The study uses the information-motivation-behavioral skills (IMB) model for health education, effectively improve the quality of life, increase their self-confidence, reduce anxiety and depression, and effectively improve the psychological state of patients. AIM: To explore the effect of health education based on the IMB model on the degree of vertigo, disability, anxiety and depression in patients with unilateral vestibular hypofunction. METHODS: The clinical data of 80 patients with unilateral vestibular hypofunction from January 2019 to December 2021 were selected as the retrospective research objects, and they were divided into the control group and the observation group with 40 cases in each group according to different nursing methods. Among them, the control group was given routine nursing health education and guidance, and the observation group was given health education and guidance based on the IMB model. The changes in self-efficacy, anxiety and depression, and quality of life of patients with unilateral VH were compared between the two groups. RESULTS: There was no significant difference in General Self-Efficacy Scale (GSES) scale scores between the two groups of patients before nursing (P > 0.05), which was comparable; after nursing, the GSES scale scores of the two groups were higher than those before nursing. The nursing group was higher than the control group, and the difference was statistically significant (P < 0.05). There was no significant difference in the scores of Hospital Anxiety and Depression Scale (HADS) and anxiety and depression subscales between the two groups before nursing (P > 0.05). After nursing, the HADS score, anxiety, and depression subscale scores of the two groups of patients were lower than those before nursing, and the nursing group was lower than the control group, and the difference was statistically significant (P < 0.05). After nursing, the Dizziness Handicap Inventory (DHI) scale and DHI-P, DHI-E and DHI-F scores in the two groups were decreased, and the scores in the nursing group were lower than those in the control group, and the difference was statistically significant (P < 0.05). CONCLUSION: Health education based on the IMB model can effectively improve patients' quality of life, increase self-efficacy of patients with unilateral vestibular hypofunction, enhance patients' confidence, enable patients to resume normal work and life as soon as possible, reduce patients' anxiety and depression, and effectively improve patients' psychological status.

Changes in blood lipid levels and influencing factors among treatment-naïve adult male HIV/AIDS patients following BIC/FTC/TAF vs . 3TC+EFV+TDF.

BACKGROUND: Antiretroviral therapy (ART) was often associated with dyslipidemia among human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients. This study aimed to assess treatment-naïve adult male patients with HIV/AIDS who initiated ART with either co-formulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) or lamivudine, efavirenz, and tenofovir disoproxil fumarate (3TC+EFV+TDF), monitoring at weeks 4, 12, 24, and 48. METHODS: A case-control retrospective study was conducted. The newly diagnosed HIV-infected individuals attending the sexual transmission disease (STD)/AIDS clinic of Beijing Youan Hospital, Capital Medical University, from January to December 2021. The patients were divided into BIC/FTC/TAF group or 3TC+EFV+TDF group. High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) at different time points over 48 weeks between two groups were compared. A multivariate Cox regression model was used to identify relevant influencing factors for the population at high risk of increased LDL-C. RESULTS: A total of 870 participants, with 510 in BIC/FTC/TAF group and 360 in 3TC+EFV+TDF group. There were no statistically significant differences in median age, baseline CD4/CD8 ratio, median body mass index (BMI) between the two groups. In both two groups, levels of TG, TC, and LDL-C were higher at 4 weeks, 12 weeks, and 24 weeks of treatment (all P <0.05), and there were no statistically significant differences at 48 weeks compared to those at baseline (all P >0.05). In addition, the differences in average changes of the level of TG, TC, HDL-C, and LDL-C from weeks 4, 12, 24, and 48 to baseline between two groups were not statistically significant (all P >0.05). Multivariate Cox proportional risk model analysis showed that initiating ART with HIV RNA ≥10 5 copies/mL (compared with <10 5 copies/mL) was associated with an increased risk of elevated LDL-C (hazard ratio = 1.26, 95% confidence interval: 1.07-1.48, P  = 0.005). CONCLUSIONS: Transient elevations in blood lipid levels (TC, TG, HDL-C, and LDL-C) were observed in treatment-naïve adult male HIV/AIDS patients with BIC/FTC/TAF at 4 weeks, 12 weeks, and 24 weeks of treatment. However, these levels did not differ significantly from baseline after 48 weeks of treatment, regardless of whether patients were in the BIC/FTC/TAF or 3TC+EFV+TDF group.

Crosstalk between human immunodeficiency virus infection and salivary bacterial function in men who have sex with men.

Background: Engaging in anal sexual intercourse markedly increases the risk of developing HIV among men who have sex with men (MSM); oral sexual activities tend to uniquely introduce gut-derived microbes to salivary microbiota, which, combined with an individual's positive HIV status, may greatly perturb oral microecology. However, till date, only a few published studies have addressed this aspect. Methods: Based on 16S rRNA sequencing data of bacterial taxa, MicroPITA picks representative samples for metagenomic analysis, effectively revealing how the development and progression of the HIV disease influences oral microbiota in MSM. Therefore, we collected samples from 11 HIV-negative and 44 HIV-positive MSM subjects (stage 0 was defined by HIV RNA positivity, but negative or indeterminate antibody status; stages 1, 2, and 3 were defined by CD4+ T lymphocyte counts ≥ 500, 200-499, and ≤ 200 or opportunistic infection) and selected 25 representative saliva samples (5 cases/stage) using MicroPITA. Metagenomic sequencing analysis were performed to explore whether positive HIV status changes salivary bacterial KEGG function and metabolic pathway in MSM. Results: The core functions of oral microbiota were maintained across each of the five groups, including metabolism, genetic and environmental information processing. All HIV-positive groups displayed KEGG functions of abnormal proliferation, most prominently at stage 0, and others related to metabolism. Clustering relationship analysis tentatively identified functional relationships between groups, with bacterial function being more similar between stage 0-control groups and stage 1-2 groups, whereas the stage 3 group exhibited large functional changes. Although we identified most metabolic pathways as being common to all five groups, several unique pathways formed clusters for certain groups; the stage 0 group had several, while the stage 2 and 3 groups had few, such clusters. The abundance of K03046 was positively correlated with CD4 counts. Conclusion: As HIV progresses, salivary bacterial function and metabolic pathways in MSM progressively changes, which may be related to HIV promoting abnormal energy metabolism and exacerbate pathogen virulence. Further, infection and drug resistance of acute stage and immune cell destruction of AIDS stage were abnormally increased, predicting an increased risk for MSM individuals to develop systemic and oral diseases.

Identification and genetic characteristics of tusavirus in fecal samples of patients with chronic diseases in Guangzhou, China.

Purpose: The Tunisian stool-associated parvovirus [Tusavirus (TuV)] is a novel member of the genus Protoparvovirus, which may be linked to diarrhea. Herein, we investigated the prevalence of TuV in different populations and analyzed its genetic and bioinformatic characteristics. Methods: This study was conducted in a tertiary hospital in Guangzhou (China) from February 2018 to July 2022. Demographic and clinical information and stool samples were collected from individuals who visited the hospital. ProtScale, SwissModel, Datamonkey, and other tools were used to analyze and predict the physicochemical parameters, tertiary structure, selection pressure, and B-cell epitopes of capsid viral protein 2 of TuV (VP2-TuV). Results: A total of 3,837 participants were enrolled, among which two stool samples from patients with chronic illnesses were tested positive for TuV DNA. However, no positive sample was detected among patients with diarrhea. Two near-complete genome sequences were amplified. The genetic analysis revealed the presence of diversity among TuVs isolated from distinct host species. Bioinformatics analysis revealed that VP2-TuV exhibited hydrophilic properties and lacked transmembrane domains and signal peptides. The secondary structure of VP2-TuV was composed mainly of random coils and ß-strands. Selective-pressure analysis of the VP2 region suggested that TuV primarily underwent negative selection during evolution. Negatively selected codon sites coincided with residues comprising of B-cell epitopes, suggesting minimal changes in the immunogenicity of TuV over time. Conclusion: TuV was detected in patients with chronic diseases but not in patients with diarrhea. The putative roles of TuV in the pathogenicity of human diseases and zoonotic viruses must be determined by additional studies.

[Prevalence of laboratory aspirin resistance in 431 old patients].

OBJECTIVE: To evaluate correlation between and agreement in light transmittance aggregation (LTA) and thromboelastography (TEG) in laboratory diagnosing aspirin resistance (AR), and to determine the prevalence of AR in old patients. METHODS: Patients in the Wanshoulu District of Beijing with ischemic atherothrombotic diseases were recruited. Inclusion criteria were age ≥ 65 years, and having received regular aspirin therapy (75-100 mg daily) for at least 4 weeks. On the basis of LTA assay, the definition of AR was taken as aggregation of ≥ 20% with AA (arachidonic acid), and of ≥ 70% with ADP (adenosine diphosphate). Aspirin-sensitivity was indicated by the absence of either of these criteria; aspirinsensitivity was indicated as both criteria being met. The definition of AR by TEG is ≥ 50% via AA-induced whole blood aggregation. RESULTS: There were 13.69% prevalence of aspirin resistance for LTA using AA as the agonist, 30.16% prevalence of aspirin resistance for LTA using ADP as the agonist, and 23.67% prevalence of aspirin resistance for TEG using AA as the agonist. Results from these tests showed poor agreement (Kappa<0.4). However, by the method of LTA using AA and ADP as the agonists, prevalence of AR was 8.35%. By methods of AA-induced LTA and AA-induced TEG, prevalence of AR was 8.82%. Results from these two latter methods showed good agreement (Kappa = 0.793). CONCLUSION: Combined methods, as described here, have good correlation and agreement in the assays of AR, and the results with them represent a realistic measure of the prevalence of AR. Prevalence of AR of elderly patients from Wanshoulu district of Beijing is about 9%.

An open-label evaluation of safety and tolerability of coformulated bictegravir/emtricitabine/tenofovir alafenamide for post-exposure prophylaxis following potential exposure to human immunodeficiency virus-1.

BACKGROUND: Single-tablet regimen (STR) provides a convenient once-daily regimen for the prevention of human immunodeficiency virus (HIV) infection. Here, we investigated the safety and tolerability of coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a three-drug, STR for post-exposure prophylaxis (PEP) in Chinese individuals. METHODS: This was a prospective, open-label, single-arm trial conducted in a sexually transmitted diseases and acquired immunodeficiency syndrome clinic of a tertiary hospital in Beijing, China. Adults requiring PEP were prescribed BIC/FTC/TAF one pill once a day for 28 days. Clinical and laboratory data were collected and analyzed at baseline, weeks 2, 4, 8, 12, and 24. RESULTS: Of 112 participants enrolled in the study, 109 (97.3%) were male and the mean age was 30 ±â€Š8 years. PEP completion was 96.4% (95% confidence interval: 91.1-99.0%). Two participants stopped PEP after 2 days because the source partner was identified as HIV uninfected. One participant was excluded due to hepatitis B virus infection according to the exclusion criteria. One discontinued due to the participant's decision. No participant acquired HIV through week 24. Adherence was 98.9% (standard deviation [SD]: 3.3%) by self-reporting and 98.5% (SD: 3.5%) by pill count. Only five participants experienced mild clinical adverse events attributed to the study drug (including headache, diarrhea, and nausea) and four participants had elevated serum creatinine (grade 1). CONCLUSIONS: A once daily, STR of BIC/FTC/TAF used as PEP was safe and well-tolerated with a high rate of completion and adherence in Chinese. BIC/FTC/TAF may be a good option for PEP. TRIAL REGISTRATION: ChiCTR.org.cn, ChiCTR2100048080.

Genetic polymorphisms of HO-1 and COX-1 are associated with aspirin resistance defined by light transmittance aggregation in Chinese Han patients.

BACKGROUND: Cyclooxygenase 1 (COX-1), COX-2, and HO-1 are involved in the process of aspirin's effect. The genetic susceptibility of these enzymes to aspirin resistance (AR) is unclear. METHODS: A total of 431 patients took aspirin. Using arachidonic acid-induced light transmittance aggregation combined with adenosine diphosphate-induced light transmittance aggregation, 36 participants served for AR, 164 participants for semi-AR, and 231 participants for aspirin sensitivity (AS). The AR with 9 single-nucleotide polymorphism in COX-1, COX-2, and HO-1 genes was investigated. RESULTS: COX-1 rs1330344 (-1676A>G) is associated with AR. G-Allele carriers significantly increased the risk of AR. For patients with AS as control, P is .02 (odds ratio [OR] = 1.77, confidence interval [CI]: 1.07-2.92). For patients with semi-AR as control, P is .05. HO-1 rs2071746 (-413A>T) is associated with AR. T-Allele carriers significantly increased the risk of AR. For patients with AS as control, P is .04 (OR = 1.70, CI: 1.02-2.79). For patients with semi-AR as control, P is .05 (OR = 1.68, CI: 1.00-2.80). CONCLUSION: rs2071746 in HO-1 gene, rs1330344 in COX-1 gene contribute to AR.