Identification and genetic characterization of a recently identified enterovirus C116 in China.

Enterovirus C116 (EV-C116) is a new member of the enterovirus C group which is closely associated with several infectious diseases. Although sporadic studies have detected EV-C116 in clinical samples worldwide, there is currently limited information available. In this study, two EV-C-positive fecal specimens were detected in apparently healthy children, which harbored low abundance, through meta-transcriptome sequencing. Based on the prototypes of several EV-Cs, two lineages were observed. Lineage 1 included many types that could not cause EV-like cytopathic effect in cell culture. Three genogroups of EV-C116 were divided in the maximum likelihood tree, and the two strains in this study (XZ2 and XZ113) formed two different lineages, suggesting that EV-C116 still diffuses worldwide. Obvious inter-type recombination events were observed in the XZ2 strain, with CVA22 identified as a minor donor. However, another strain (XZ113) underwent different recombination situations, highlighting the importance of recombination in the formation of EV-Cs biodiversity. The EV-C116 strains could propagate in rhabdomyosarcoma cell cultures at low titer; however, EV-like cytopathic effects were not observed. HEp-2, L20B, VERO, and 293T cell lines did not provide an appropriate environment for EV-C116 growth. These results challenge the traditional recognition of the uncultured nature of EV-C116 strains and explain the difficulty of clinical detection.

Effect of exposures to multiple metals on blood pressure and hypertension in the elderly: a community-based study.

A chronic disease, hypertension (HTN) is prevalent among the elderly. Exploring the factors that influence HTN and blood pressure (BP) changes is of great public health significance. However, mixed exposure to multiple serum metals has had less research on the effects on BP and HTN for the elderly. From April to August 2019, 2372 people participated in the community physical examination program for the elderly in Tongling City, Anhui Province. We measured BP and serum levels of 10 metals and collected basic demographic information. We analyzed the relationship between metal levels and changes in BP and HTN by the least absolute shrinkage and selection operator regression, Bayesian kernel machine regression model, and generalized linear model. In multiple models, lead (Pb) and cadmium (Cd) were still significantly associated with HTN occurrence after adjusting for potential confounders (Pb: ORquartile 4 VS quartile 1 = 1.20, 95% CI 1.01-1.43; Cd: ORquartile 4 VS quartile 1 = 1.37, 95% CI 1.16-1.62). In the male subgroup, results were similar to those of the general population. In the female group, Cd was positively correlated with HTN and systolic blood pressure, while Pb was not. According to this study, Pb and Cd were correlated with BP and HTN positively, and there was a certain joint effect. To some extent, our findings provide clues for the prevention of hypertension in the elderly.

Interaction of biomass fuels use and metals exposure on hypertension: A prospective cohort study in rural areas along the Yangtze River, China.

Humans maybe simultaneously exposed to multiple-metals and indoor air pollution in daily life. However, limited prospective studies have assessed the interaction between multiple metals exposure and biomass fuels use on hypertension in China. The prospective cohort study in rural areas along the Yangtze River included 2625 adults in 2014-2015, and they were followed up till 2019. Among 1248 rural residents who were without hypertension at baseline, 377 hypertension events (30.21%) were observed after 4.5 years of average follow-up time. First-morning urine samples of residents were collected at baseline, the association between urinary metals level and hypertension were assessed using quantile g-computation. Additionally, we also examined the effect of biomass fuels use, fuels switching, and cookstove ventilation on the association of metals exposure with hypertension. Quantile g-computation analyses showed a positive joint effect of 17 metals on hypertension, with the odds ratio (OR) of 1.68 (95% CI: 0.89, 3.14) when increasing all seventeen metals by one quartile, and cadmium, lithium, copper contributed the largest positive weights. Biomass fuels use can interact with cadmium exposure on hypertension with OR for interaction of 1.28 (95%CI: 1.00, 1.73), and increase the association between copper, manganese and zinc exposure and systolic blood pressure, lithium exposure and diastolic blood pressure at the follow-up visit. Moreover, switching from biomass fuels to clean fuels during follow up, cookstove ventilation can alleviate the risk of higher blood pressure from metals exposure. In rural areas along the Yangtze River, China, biomass fuels use for cooking can interact with multiple-metals exposure on hypertension. Residents who switched from biomass fuels to clean fuels and who used ventilation had a lower risk of hypertension. Further cohort studies are needed to clarify the mechanism of combined effects of metals exposure and biomass fuels use on the human health.

Early chronic obstructive pulmonary disease: A new perspective.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease with a high incidence, mortality, and disability rate. Because there are few symptoms in the early stages of COPD, diagnosis and treatment are seriously insufficient. It is necessary to find effective clues for early COPD diagnosis and provide appropriate interventions. Several studies suggest that small airway disease is the earliest stage of COPD because it is correlated with subsequent development of airflow obstruction. However, there are currently no globally accepted criteria for defining early COPD. This study mainly introduced risk factors, definition, diagnosis, and treatment of early COPD from a new perspective.

Model for Identifying High Carotid Body Chemosensitivity in Patients with Obstructive Sleep Apnea.

OBJECTIVE: The carotid body (CB) is a major peripheral respiratory chemoreceptor. In patients with obstructive sleep apnea (OSA), high CB chemosensitivity (CBC) is associated with refractory hypertension and insulin resistance and known to further aggravate OSA. Thus, the identification of high CB (hCBC) among OSA patients is of clinical significance, but detection methods are still limited. Therefore, this study aimed to explore the association of CBC with OSA severity and to develop a simplified model that can identify patients with hCBC. METHODS: In this cross-sectional study of subjects who underwent polysomnography (PSG), CBC was measured using the Dejours test. We defined hCBC as a decrease of >12% in respiratory rate (RR) after breathing of pure O2. The association of CBC with OSA severity was explored by logistic regression, and a model for identifying hCBC was constructed and confirmed using receiver operating characteristic analysis. RESULTS: Patients with OSA (n=142) and individuals without OSA (n=38) were enrolled. CBC was higher in patients with OSA than in those without OSA (% decrease in RR, 15.2%±13.3% vs 9.1%±7.5%, P<0.05). Apnea-hypopnea index (AHI), fraction of apnea-hypopnea events in rapid-eye-movement sleep (Fevents-in-REM), and longest time of apnea (LTA) were associated with hCBC independently (odds ratio [OR]=1.048, OR=1.082, and OR=1.024 respectively; all P<0.05). The model for identifying hCBC allocated a score to each criterion according to its OR values, ie, 1 (LTA >48.4 s), 2 (AHI >15.7 events/hour), and 3 (Fevents-in-REM >12.7%). A score of 3 or greater indicated hCBC with a sensitivity of 79.4% and specificity of 88.2%. CONCLUSION: High CBC is associated with the severity of OSA. A simplified scoring system based on clinical variables from PSG can be used to identify hCBC.

Light-Promoted Nickel Catalysis: Etherification of Aryl Electrophiles with Alcohols Catalyzed by a NiII -Aryl Complex.

A highly effective C-O coupling reaction of (hetero)aryl electrophiles with primary and secondary alcohols is reported. Catalyzed by a NiII -aryl complex under long-wave UV (390-395 nm) irradiation in the presence of a soluble amine base without any additional photosensitizer, the reaction enables the etherification of aryl bromides and aryl chlorides as well as sulfonates with a wide range of primary and secondary aliphatic alcohols, affording synthetically important ethers. Intramolecular C-O coupling is also possible. The reaction appears to proceed via a NiI -NiIII catalytic cycle.

Advances in diarylpyrimidines and related analogues as HIV-1 nonnucleoside reverse transcriptase inhibitors.

HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs) have been playing an important role in the fight against acquired immunodeficiency syndrome (AIDS). Diarylpyrimidines (DAPYs) as the second generation NNRTIs, represented by etravirine (TMC125) and rilpivirine (TMC278), have attracted extensive attention due to their extraordinary potency, high specificity and low toxicity. However, the rapid emergence of drug-resistant virus strains and dissatisfactory pharmacokinetics of DAPYs present new challenges. In the past two decades, an increasing number of novel DAPY derivatives have emerged, which significantly enriched the structure-activity relationship of DAPYs. Studies of crystallography and molecular modeling have afforded a lot of useful information on structural requirements of NNRTIs, which contributes greatly to the improvement of their resistance profiles. In this review, we reviewed the discovery history and their evolution of DAPYs including their structural modification, derivatization and scaffold hopping in continuous pursuit of excellent anti-HIV drugs. And also, we discussed the prospect of DAPYs and the directions of future efforts.

Structural modifications of diarylpyrimidines (DAPYs) as HIV-1 NNRTIs: Synthesis, anti-HIV activities and SAR.

30 new analogues of diarylpyrimidines were synthesized for further structural modifications, involving not only the linker but also the wing α of DAPYs. The anti-HIV-1 activities of all target molecules were evaluated, and most of them exhibited potent anti-HIV-1 (WT) activities and low cytotoxicities. Among which, compound 4g showed excellent activities against WT HIV-1 with an EC50 value of 5.8nM and SI of up to 26,034. Another compound 4ab bearing a novel pyridinyl Wing α also displayed attractive activities. The structure-activity relationship (SAR) study was also summarized.

Design and synthesis of hybrids of diarylpyrimidines and diketo acids as HIV-1 inhibitors.

Based on the strategy of molecular hybridization, diketo acid fragment as a classical phamacophore of integrase inhibitors was introduced to reverse transcriptase inhibitors diarylpyrimidines to design a series of diarylpyrimidine-diketo acid hybrids (DAPY-DKAs). The target molecules 10b and 11b showed inhibitory activities against WT HIV-1 with EC50 values of 0.18µM and 0.14µM, respectively. And the results of molecular docking demonstrated the potential binding mode and revealed that the DKA moiety and its ester could both be tolerated in the nonnucleoside binding site (NNBS) of HIV-1 RT.