Copper-Mediated and Palladium-Catalyzed Cross-Coupling of Indoles and N-Methylpyridinium Salts: A Practical Way to Prepare 3-(Pyridin-2-yl)indoles.

Herein, a Pd/Cu bimetallic-catalyzed direct C-H heteroarylation of pyridines via the traceless protecting group strategy is described. A series of N-methyl-activated pyridines and 1-methylindoles are coupled with high regioselectivity to produce the corresponding 3-(pyridin-2-yl)indoles in moderate to good yields, wherein related electron-rich heterocycles (e.g., indole, 1-methylpyrrole, benzofuran, benzo[b]thiophene) are also applicable. Streamlined operation, good functional group tolerance, and late-stage modifications make this twofold C-H activation protocol an attractive route for the synthesis of 3-(pyridin-2-yl)indole derivatives.

Characterization of Altered Oropharyngeal Microbiota in Hospitalized Patients With Mild SARS-CoV-2 Infection.

Coronavirus disease 2019 (COVID-19) remains a serious emerging global health problem, and little is known about the role of oropharynx commensal microbes in infection susceptibility and severity. Here, we present the oropharyngeal microbiota characteristics identified by full-length 16S rRNA gene sequencing through the NANOPORE platform of oropharynx swab specimens from 10 mild COVID-19 patients and 10 healthy controls. Our results revealed a distinct oropharyngeal microbiota composition in mild COVID-19 patients, characterized by enrichment of opportunistic pathogens such as Peptostreptococcus anaerobius and Pseudomonas stutzeri and depletion of Sphingomonas yabuuchiae, Agrobacterium sullae, and Pseudomonas veronii. Based on the relative abundance of the oropharyngeal microbiota at the species level, we built a microbial classifier to distinguish COVID-19 patients from healthy controls, in which P. veronii, Pseudomonas fragi, and S. yabuuchiae were identified as the most prominent signatures for their depletion in the COVID-19 group. Several members of the genus Campylobacter, especially Campylobacter fetus and Campylobacter rectus, which were highly enriched in COVID-19 patients with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and showed a significant correlation with disease status and several routine clinical blood indicators, indicate that several bacteria may transform into opportunistic pathogen in COVID-19 patients when facing the challenges of viral infection. We also found the diver taxa Streptococcus anginosus and Streptococcus alactolyticus in the network of disease patients, suggesting that these oropharynx microbiota alterations may impact COVID-19 severity by influencing the microbial association patterns. In conclusion, the low sample size of SARS-CoV-2 infection patients (n = 10) here makes these results tentative; however, we have provided the overall characterization that oropharyngeal microbiota alterations and microbial correlation patterns were associated with COVID-19 severity in Anhui Province.

TLR3 polymorphisms are associated with the severity of hand, foot, and mouth disease caused by enterovirus A71 in a Chinese children population.

Hand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) is a contagious viral disease, and toll-like receptors (TLRs) play essential roles in resisting the pathogen. The aim of this study was to assess the potential relationship between several TLRs polymorphisms and the HFMD severity in a Chinese children population. A total of 328 Chinese children with HFMD were included in the present study. The polymorphisms of TLR3 (rs3775290, rs3775291, rs3775296, rs1879026, rs5743312, rs5743313, rs5743303, rs13126816, and rs3775292), TLR4 (rs4986790, rs4986791, rs2149356, rs11536889, and rs41426344), TLR7 (rs179009, rs179010, rs179016, rs3853839, rs2302267, rs1634323, and rs5741880), and TLR8 (rs3764880, rs2159377, rs2407992, rs5744080, rs3747414, rs3764879, and rs5744069) genes were selected. The study indicated that individuals with the GG genotype of TLR3 single-nucleotide polymorphism rs1879026 had a higher risk of developing severe cases (GG vs. GT: OR = 1.875; 95% CI, 1.183-2.971; p = .007). Meanwhile, TLR3 rs3775290 CC genotype and C allele were associated with lower disease severity in females (CC vs. CT: OR = 0.350; 95% CI, 0.163-0.751; p = .006; C vs. T: OR = 0.566; 95% CI, 0.332-0.965; p = .036). TLR3 rs3775291 CC genotype showed 2.537 folds higher risk of developing severe cases in females (CC vs. CT: OR = 2.537; 95% CI, 1.108-5.806; p = .026). Moreover, TLR3 rs1879026 GG genotype was found to be related to increased risk of severe cases in males (GG vs. GT: OR = 2.076; 95% CI, 1.144-3.768; p = .016). The current findings show that the genetic variants of TLR3 rs1879026, rs3775290, and rs3775291 are associated with the severity of EV-A71-associated HFMD in a Chinese children population.

Sporadic occurrence of H9N2 avian influenza infections in human in Anhui province, eastern China: A notable problem.

H9N2 viruses can cause great economic losses to the domestic poultry industry when co-infected with other influenza viruses or pathogens. . To better understand the molecular characteristics of H9N2 avian influenza viruses (AIVs) and analyze the genetic evolutionary relationship, we isolated three H9N2 subtypes AIVs from nasopharyngeal swab specimens from the three cases reported in Anhui province since 2015, and systematically reviewed the genome-wide data of 21 poultry--isolated H9N2 viruses during 1998-2017. The six internal genes of three human-isolated viruses and recent poultry-isolated viruses (since 2014) in Anhui province presented high gene homologies with HPAI H7N9, even including H10N8 and H5N6. The three human-isolated H9N2 AIVs and poultry-isolated viruses (since 2008) in Anhui province were highly similar, and classified into genotype S. Seven N-linked potential glycosylation sites in the HA protein were detected in the three human-isolated viruses, which also appeared in poultry-isolated H9N2 AIVs. None of the human-isolated H9N2 AIVs had the I368V mutation in PB1 protein, but all the poultry-isolated H9N2 viruses in 2017 carried this mutation. Multidisciplinary, cross-regional and cross-sectoral approaches are warranted to address complex public health challenges and achieve the goal of 'one health'.

Orientia tsutsugamushi infection in rodents in Anhui Province of China.

We conducted an investigation of Orientia tsutsugamushi infection among rodents in non-endemic areas in Anhui Province. Fifty-six (56) rodents including 44 Apodemus agrarius and 12 Niviventer niviventer were trapped and captured in autumn in the fields of three counties in Anhui Province. DNA samples were amplified and sequenced for the 56kDa protein gene of Orientia tsutsugamushi. The overall infection rate in the rodents was 23.2%(13/56). The rate of detection of O. tsutsugamushi in Apodemus agrarius and Niviventer niviventer were 27.3% and 8.3% respectively. Moreover, we identified two genotypes (Karp and Gilliam strains) of Orientia tsutsugamushi in rodents. Our study demonstrated that Apodemus agrarius is the main host for O. tsutsugamushi pathogen and this is the first report of Karp and Gilliam strains in these non-endemic areas in Anhui Province.