A sensitive UPLC-MS/MS method for simultaneous determination of polyphenols and theaflavins in rat plasma: Application to a pharmacokinetic study of Da Hong Pao tea.

A method based on ultra-performance liquid chromatography-tandem mass spectrometry has been developed for the rapid and simultaneous determination of five catechins and four theaflavins in rat plasma using ethyl gallate as internal standard. The pharmacokinetic profiles of these compounds were compared after oral administration of five kinds of Da Hong Pao tea to rats. Biosamples processed with a mixture of ß-glucuronidase and sulfatase were extracted with ethyl acetate-isopropanol. Chromatographic separation was achieved by gradient elution using 10 mm HCOONH4 solution and methanol as the mobile phase. Analytes were detected using negative ion electrospray ionization in multiple reaction monitoring mode. The lower limits of quantification were 1.0, 0.74 and 0.5 ng/mL for theaflavins, two catechins and three catechins, respectively. The validation parameters were well within acceptable limits. The average half-lives (t1/2 ) in blood of the reference solution group was much shorter than those of tea samples. The values of AUC0-t and Cmax of the polyphenols and theaflavins exhibited linear pharmacokinetic characteristics which were related to the dose concentration.

[Bactericidal effect of ozonated camellia oil on Staphylococcus aureus in vitro].

OBJECTIVE: To explore a new method for detecting the bactericidal effect of oiling agent in vitro, and to determine the disinfectant effecacy of ozonated camellia oil on Staphylococcus aureus.
 Methods: Suspension of Staphylococcus aureus was prepared and innoculated on the LB plate by plate scribing method. After culture overnight, 21 bacterial monoclones with the same diameter were selected and divided into 3 groups: A negative control group, a baseoil (camellia oil) group and an ozonated camellia oil group. We used a ring to isolate the single clone and added oil inside the ring, cultured the whole plate over night, picked out each single clone (with gel) to 5 mL LB medium and cultured it for 12 h. The final concentration of the LB medium was detected by plate count method and turbidimetry.
 Results: According to the plate count method and turbidimetry, the bacterial concentration in the ozonated camellia oil group was lower than that in the negative control group and base oil group (P<0.001).
 Conclusion: Bacterial monoclone culture method shows that ozonated camellia oil can significantly kill Staphylococcus aureus, and this method is an effective method for evaluating the bactericidal function of the oiling agent in vitro.

Combined effects of age and polymorphisms in Notch3 in the pathogenesis of cerebral infarction disease.

Cerebral infarction disease is a severe hypoxic ischemic tissue necrosis in the brain, often leading to long-term functional disability and residual impairments. The Notch signaling pathway plays key roles in proliferation and survival of the stem/progenitor cells of the central and peripheral nervous systems. Notch3 is an important member of the pathway, but the relationships between the genetic abnormalities and cerebral infarction disease still remain unclear. The aim of this work was to evaluate variations in Notch3 gene for their possible associations with the cerebral infarction disease. We sequenced the Notch3 gene for 260 patients with cerebral infarction disease, 300 normal controls with old ages and 300 normal controls with younger ages, and identified the variations. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 19.0). The Hardy-Weinberg equilibrium test of the population was carried out using the online software OEGE. Six variations, including rs1044116, rs1044009, rs1044006, rs10408676, rs1043996 and rs16980398 within or near the Notch3 gene, were found. The genetic heterozygosity of rs1044116, rs1044009, rs1044006, and rs1043996 was very high, whereas that of rs10408676 and rs16980398 was very low. Statistical analyses showed that rs1044009 and rs1044006 were associated with the risk of cerebral infarction disease in the Chinese Han agedness population. The SNPs rs1044009 and rs1044006 in the Notch3 gene were associated with the risk of cerebral infarction diseases in the Chinese Han agedness population.

Inherited neurovascular diseases affecting cerebral blood vessels and smooth muscle.

Neurovascular diseases are among the leading causes of mortality and permanent disability due to stroke, aneurysm, and other cardiovascular complications. Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and Marfan syndrome are two neurovascular disorders that affect smooth muscle cells through accumulation of granule and osmiophilic materials and defective elastic fiber formations respectively. Moyamoya disease, hereditary hemorrhagic telangiectasia (HHT), microcephalic osteodysplastic primordial dwarfism type II (MOPD II), and Fabry's disease are disorders that affect the endothelium cells of blood vessels through occlusion or abnormal development. While much research has been done on mapping out mutations in these diseases, the exact mechanisms are still largely unknown. This paper briefly introduces the pathogenesis, genetics, clinical symptoms, and current methods of treatment of the diseases in the hope that it can help us better understand the mechanism of these diseases and work on ways to develop better diagnosis and treatment.

Identification of two novel critical mutations in PCNT gene resulting in microcephalic osteodysplastic primordial dwarfism type II associated with multiple intracranial aneurysms.

Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a highly detrimental human autosomal inherited recessive disorder. The hallmark characteristics of this disease are intrauterine and postnatal growth restrictions, with some patients also having cerebrovascular problems such as cerebral aneurysms. The genomic basis behind most clinical features of MOPD II remains largely unclear. The aim of this work was to identify the genetic defects in a Chinese family with MOPD II associated with multiple intracranial aneurysms. The patient had typical MOPD II syndrome, with subarachnoid hemorrhage and multiple intracranial aneurysms. We identified three novel mutations in the PCNT gene, including one single base alteration (9842A>C in exon 45) and two deletions (Del-C in exon 30 and Del-16 in exon 41). The deletions were co-segregated with the affected individual in the family and were not present in the control population. Computer modeling demonstrated that the deletions may cause drastic changes on the secondary and tertiary structures, affecting the hydrophilicity and hydrophobicity of the mutant proteins. In conclusion, we identified two novel mutations in the PCNT gene associated with MOPD II and intracranial aneurysms, and the mutations were expected to alter the stability and functioning of the protein by computer modeling.

Mechanism and use strategy of uric acid-lowering drugs on coronary heart disease.

Coronary heart disease (CHD) is a serious cardiovascular illness, for which an elevated uric acid (UA) level presents as a considerable risk factor. This can be treated with UA-lowering drugs such as allopurinol and benzbromarone, which can reduce UA levels by the inhibition of UA production or by promoting its excretion. Such drugs can also be beneficial to CHD in other ways, such as reducing the degree of coronary arteriosclerosis, improving myocardial blood supply and alleviating ventricular remodeling. Different UA-lowering drugs are used in different ways: allopurinol is preferred as a single agent in clinical application, but in absence of the desired response, a combination of drugs such as benzbromarone with ACE inhibitors may be used. Patients must be monitored regularly to adjust the medication regimen. Appropriate use of UA-lowering drugs has great significance for the prevention and treatment of CHD. However, the specific mechanisms of the drugs and individualized drug use need further research. This review article expounds the mechanisms of UA-lowering drugs on CHD and their clinical application strategy, thereby providing a reference for further optimization of treatment.

Comparison of Hypervirulent and Non-Hypervirulent Carbapenem-Resistant Acinetobacter baumannii Isolated from Bloodstream Infections: Mortality, Potential Virulence Factors, and Combination Therapy In Vitro.

Hypervirulent carbapenem-resistant Acinetobacter baumannii (hv-CRAB) has emerged in bloodstream infections (BSI). Cases of BSI caused by hv-CRAB (hv-CRAB-BSI) had posed a significant threat to hospitalized patients. In this study, 31 CRAB strains isolated from Chinese BSI patients were analyzed, of which 24 were identified as hv-CRAB-BSI and 7 as non-hv-CRAB-BSI, using the Galleria mellonella infection model. Patients with hv-CRAB-BSI had higher rates of septic shock (79.2% vs. 14.3%, p = 0.004) and mortality (66.7% vs. 14.3%, p = 0.028). All strains were resistant to most antibiotics but sensitive to colistin. Hv-CRAB-BSI showed lower resistance to minocycline than non-hv-CRAB-BSI (54.2% vs. 100%, p = 0.03). Whole-genome sequencing revealed that the detection rates of immune modulation genes ptk and epsA in hv-CRAB-BSI were significantly higher than in non-hv-CRAB-BSI (91.7% vs. 28.6%, p = 0.002). Additionally, all ST457 hv-CRAB-BSI lacked abaR, and all ST1486 non-hv-CRAB-BSI lacked adeG. The checkerboard dilution method assessed the efficacies of various antibiotic combinations, revealing that although synergism was rarely observed, the combination of colistin and minocycline showed the best efficacy for treating CRAB-BSI, regardless of whether the infections were hv-CRAB-BSI or non-hv-CRAB-BSI. These findings highlight the importance of analyzing molecular characteristics and exploring effective treatment strategies for hv-CRAB-BSI.

Antibiotic prescription for children with acute respiratory tract infections in rural primary healthcare in Guangdong province, China: a cross-sectional study.

OBJECTIVES: The objective of this study is to understand the characteristics and patterns of the first antibiotic prescriptions for children with acute respiratory infections (ARIs) in rural primary healthcare (PHC) in Guangdong province, China. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: We used prescription data generated from the electronic medical record system of 37 township hospitals in two counties of Shaoguan City, Guangdong province. 46 699 first prescriptions for ARIs in children aged 0-18 years were screened from 444 979 outpatient prescriptions recorded between November 2017 and October 2018. OUTCOME MEASURES: Descriptive analyses were used to report sociodemographic characteristics and antibiotic prescribing profiles. χ2 analysis and binary logistic regression were used to analyse the factors associated with antibiotic prescriptions in children. RESULTS: Of the 46 699 sampled cases, 83.00% (n=38 759) received at least one antibiotic as part of their first prescription. Of the 38 759 sampled cases treated with antibiotics, 40.76% (n=15 799), 56.15% (n=21 762) and 31.59% (n=12 244) received parenteral antibiotics, broad-spectrum antibiotics and two or more kinds of antibiotics, respectively. Multivariable analysis showed that children aged ≤5 years were less likely to be prescribed with antibiotics than those aged 16-18 years (OR 0.545, p<0.001). Those with health insurance were more likely to be prescribed with antibiotics than those without health insurance (OR 1.677, p<0.001). CONCLUSIONS: Misuse and overuse of antibiotics were found in the prescriptions of children with ARIs in rural PHC. Antibiotic stewardship programme should be established to reduce the level of antibiotic prescriptions among children with ARIs in rural PHC, especially regarding the prescriptions of broad-spectrum antibiotics and parenteral antibiotics, tailored to different ages, sex and health insurance groups.

A portable sensor for glucose detection in Huangshui based on blossom-shaped bimetallic organic framework loaded with silver nanoparticles combined with machine learning.

In this work, we propose a blossom-like Ni, Co bimetallic metal-organic framework (NiCo-MOF) synthesized hydrothermally and decorated with silver nanoparticles (AgNPs) via chemical reduction for electrochemical enzyme-free glucose sensing. The NiCo-MOF nanostructures had large specific surface area and good sensing performance. The AgNPs enhanced the electrochemical performance of the MOF, resulting in excellent electrochemical activity. The sensor exhibited sensitivities of 1191.84 and 271.19 µA mM-1 cm-2 in the linear ranges of 0.005-1.125 and 1.525-5.325 mM, respectively, with a detection limit of 2.3 µM. The sensor was successfully applied for glucose determination in Huangshui (HS) using an artificial neural network as machine learning (ML) model. The R2 value near 1, low RMSE, and high RPD values of the proposed ML model demonstrate its excellent fitting and prediction performance. This will provide a fast and portable intelligent sensing analysis technology for the detection of glucose in HS.

Circadian rhythms and sleep quality among undergraduate students in China: The mediating role of health-promoting lifestyle behaviours.

BACKGROUND: Poor sleep quality have become one of the most pressing public health problems for undergraduate students. The aim of this cross-sectional study was to investigate the relationship between circadian rhythms and sleep quality and the meditating role of health-promoting lifestyles in the relationship of Chinese undergraduate students. METHODS: A total of 3423 students participated. The online survey consisted of the reduced Morningness-Evening Questionnaire (rMEQ), the Pittsburgh Sleep Quality Index (PSQI) and Health-Promoting Lifestyle Profile-II (HPLP-II). Logistic regression models were employed. RESULTS: The prevalence of poor sleep quality is 43.03 %. The total mean scores of HPLP - II, PSQI, and rMEQ are 96.94 ± 17.26, 5.20 ± 2.70 and 14.83 ± 2.10, respectively. A significant negative correlation exists between the rMEQ and PSQI scores (r = -0.262, p < 0.001), but a positive correlation exists between the rMEQ and HPLP scores (r = 0.232, p < 0.001). The total and sub-domain scores of HPLP are also negatively correlated with the PSQI scores (r = -[0.166, 0.291], p < 0.001). Mediation analysis demonstrates the mediation of HPLP (indirect effect = -0.036, p < 0.001) on the effect of the rMEQ on PSQI scores that accounts for 13.30 % of the total effect. LIMITATIONS: Cross-sectional design and recall bias in data collection. CONCLUSIONS: The effect of circadian rhythm on sleep quality is partially mediated by the health-promoting lifestyle. In addition to maintaining a normal circadian rhythm, helping undergraduate students develop a healthy lifestyle is also an effective measure to improve sleep quality.

A sensitive enzyme-free electrochemical sensor based on a rod-shaped bimetallic MOF anchored on graphene oxide nanosheets for determination of glucose in huangshui.

In this work, we propose a bimetallic Ni-Co based MOF attached to graphene oxide (GO) by a one-step hydrothermal approach which may be employed as an electrochemical enzyme-free glucose sensor. Due to the obvious synergistic catalysis of Ni and Co, as well as the combination of NiCo-MOF and GO, NiCo-MOF/GO not only enhances energy transfer and electrocatalytic performance but also provides a larger surface area and more active sites. Electrochemical studies show that NiCo-MOF/GO exhibits outstanding electrochemical activity, with a sensitivity of 11 177 µA mM-1 cm-2 and 4492 µA mM-1 cm-2 in the linear ranges of 1-497 µM and 597-3997 µM, a detection limit of 0.23 µM, and a response time of 2 seconds. More importantly, the newly fabricated sensor is successfully applied for glucose determination in huangshui. This method provides a novel strategy for the controlled fermentation process and product quality of Chinese baijiu.

Adaptive Evolution Compensated for the Plasmid Fitness Costs Brought by Specific Genetic Conflicts.

New Delhi metallo-ß-lactamase (NDM)-carrying IncX3 plasmids is important in the transmission of carbapenem resistance in Escherichia coli. Fitness costs related to plasmid carriage are expected to limit gene exchange; however, the causes of these fitness costs are poorly understood. Compensatory mutations are believed to ameliorate plasmid fitness costs and enable the plasmid's wide spread, suggesting that such costs are caused by specific plasmid-host genetic conflicts. By combining conjugation tests and experimental evolution with comparative genetic analysis, we showed here that the fitness costs related to ndm/IncX3 plasmids in E. coli C600 are caused by co-mutations of multiple host chromosomal genes related to sugar metabolism and cell membrane function. Adaptive evolution revealed that mutations in genes associated with oxidative stress, nucleotide and short-chain fatty acid metabolism, and cell membranes ameliorated the costs associated with plasmid carriage. Specific genetic conflicts associated with the ndm/IncX3 plasmid in E. coli C600 involve metabolism and cell-membrane-related genes, which could be ameliorated by compensatory mutations. Collectively, our findings could explain the wide spread of IncX3 plasmids in bacterial genomes, despite their potential cost.

The protective effects of uric acid against myocardial ischemia via the Nrf2 pathway.

Uric acid (UA) possesses both pro- and anti-oxidative properties in ischemic heart disease, but the underlying mechanism remains unclear. We aimed to investigate UA's protective effect on myocardial ischemia by examining its effects on ECG Ischemic Alterations (EIA) and H2O2-induced oxidative stress in H9C2 myocardial cells. The incidence of EIA decreased over time and was more prevalent among women than men. A U-shaped relationship was observed between UA levels and EIA incidence, with the third quartile exhibiting a protective association. Addition of 237.9 µmol/L UA improved cellular damage and oxidative stress in H2O2-treated H9C2 cells, as determined by cell viability, LDH release, ROS levels, and total antioxidant capacity assays. UA activated the Nrf2 pathway, evidenced by increased expression of Nrf2, GCLC, and HO-1 proteins. By reversing cell cycle blockage, promoting wound healing ability, improving colony-forming capacity, and increasing angiogenesis in H2O2-treated cells, UA exhibited positive effects on cardiomyocyte growth characteristics. Additionally, use of Nrf2 inhibitor ML385 confirmed the involvement of the Nrf2 pathway by negating UA's effects on oxidatively damaged cardiomyocytes. Our findings suggest that UA induces downstream antioxidant factors to ameliorate oxidative stress by activating the Nrf2 pathway, which could be one of the targets responsible for UA's beneficial effects in myocardial ischemia.

Antibiotic Prescription Patterns for Acute Respiratory Infections in Rural Primary Healthcare Settings in Guangdong, China: Analysis of 162,742 Outpatient Prescriptions.

Overuse and inappropriate use of antibiotics are important contributors to bacterial antimicrobial resistance (AMR), especially in ambulatory primary healthcare (PHC) settings in low- and middle-income countries. This study aimed to investigate antibiotic prescription patterns among patients with acute respiratory infections (ARIs) in rural PHC facilities in the Guangdong Province, China. A total of 444,979 outpatient prescriptions were extracted from the electronic medical record system of 35 township health centers (THCs) and 2 community health centers (CHCs) between November 2017 and October 2018. We used the chi-square test to analyze the antibiotic prescription patterns and binary logistic regression to explore patient-related factors associated with antibiotic prescriptions. Of the 162,742 ARI prescriptions, 85.57% (n = 139,259) included at least one antibiotic. Among the 139,259 prescriptions with antibiotics, 37.82% (n = 52,666) included two or more antibiotics, 55.29% (n = 76,993) included parenteral antibiotics, and 56.62% (n = 78,852) included Watch group antibiotics. The binary logistic regression indicated that (1) female patients were slightly less likely to be prescribed antibiotics than males (adjusted odds ratio (OR) = 0.954, 95% confidence interval [CI] [0.928-0.981]; p = 0.001); and (2) compared to patients aged ≤5 years, those who were 6-15 years old (adjusted OR = 1.907, 95% CI [1.840-1.978]; p < 0.001), 16-60 years old (adjusted OR = 1.849, 95% CI [1.785-1.916]; p < 0.001), and >60 years old (adjusted OR = 1.915, 95% CI [1.810-2.026]; p < 0.001) were more likely to be prescribed antibiotics. The overuse and irrational use of antibiotics in PHC settings remain major healthcare challenges in rural Guangdong. Thus, it is imperative to implement targeted antimicrobial stewardship (AMS) policies to address this problem.

Perceptions towards online learning among medical students during the COVID-19 pandemic.

Social distancing has been essential during the COVID-19 pandemic to slow the spread of the disease. Online learning ensures students can participate in learning activities while also maintaining a physical distance from other students. Although online learning was used to prevent the spread of COVID-19, the development of online learning has also been promoted. Here, we sought to explore the perceptions and responses of students to online learning during the pandemic using a cross-sectional study. Electronic questionnaire was used for data collection. Statistical analyses were performed for 1614 valid questionnaires and P < 0.05 was considered statistically significant. Overall, COVID-19 had more effect on female students, such as fear of COVID-19 (2.4 times higher than the number of male students) and length of time spent learning (H = 42.449, P < 0.05). However, the higher the students' grades were, the less the impact of COVID-19. For the style of lessons, all students would prefer shorter lessons (P < 0.05). Female and fifth-grade students were more prefer combined online and face-to-face learning, and male and freshmen students were more likely to prefer face-to-face learning after the pandemic. More than 50% of students thought the main advantage of online learning was convenience, with low efficiency being a disadvantage. The main factors negatively influencing online learning were eyestrain, poor network connections, and poor learning environments at home. In conclusion, synchronous online and face-to-face learning may become more common in future curricula, however the efficiency of online learning and the female students more attentions.

Structural Genomic Analysis of SARS-CoV-2 and Other Coronaviruses.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. In this study, we conducted a comparative analysis of the structural genes of SARS-CoV-2 and other CoVs. We found that the sequence of the E gene was the most evolutionarily conserved across 200 SARS-CoV-2 isolates. The E gene and M gene sequences of SARS-CoV-2 and NC014470 CoV were closely related and fell within the same branch of a phylogenetic tree. The absolute diversity of E gene and M gene sequences of SARS-CoV-2 isolates was similar to that of common CoVs (C-CoVs) infecting other organisms. The absolute diversity of the M gene sequence of the KJ481931 CoV that can infect humans was similar to that of SARS-CoV-2 and C-CoVs infecting other organisms. The M gene sequence of KJ481931 CoV (infecting humans), SARS-CoV-2 and NC014470 CoV (infecting other organisms) were closely related, falling within the same branch of a phylogenetic tree. Patterns of variation and evolutionary characteristics of the N gene and S gene were very similar. These data may be of value for understanding the origins and intermediate hosts of SARS-CoV-2.

In silico Evolution and Comparative Genomic Analysis of IncX3 Plasmids Isolated From China Over Ten Years.

IncX3 plasmids are correlated with the dissemination and acquisition of carbapenem resistance in Enterobacteriaceae and have been prevalent in China over the last 10 years. Since the distribution characteristics of IncX3 plasmids across China as well as their evolutionary traits for 10 years remain unclear, here we conducted a retrospective literature review and in silico comparative analysis of IncX3 plasmids in publicly available IncX3 plasmid genomes. IncX3 plasmids distributed in 17 provinces or cities were extracted for analysis, which tend to be specifically associated with hospital-isolated Escherichia coli ST410 from phylogroup A. Although the backbones of IncX3 plasmids have remained highly conservative over the last 10 years, the bla NDM resistance genetic contexts on these plasmids could fall into five subtypes, among which AR_N1_I has been identified in Enterobacter cloacae174 chromosome and AR_N5_I was simultaneously located on IncF and IncA/C plasmids. This suggests that the bla NDM resistance gene environment can spread between different plasmids, between different bacterial genera, or between strains and plasmids, highlighting that it is imperative to adopt more stringent infection control measures targeting IncX3 plasmid spread.

Mutations in porin LamB contribute to ceftazidime-avibactam resistance in KPC-producing Klebsiella pneumoniae.

Ceftazidime-avibactam (CAZ-AVI) shows promising activity against carbapenem-resistant Klebsiella pneumoniae (CRKP), however, CAZ-AVI resistance have emerged recently. Mutations in KPCs, porins OmpK35 and/or OmpK36, and PBPs are known to contribute to the resistance to CAZ-AVI in CRKP. To identify novel CAZ-AVI resistance mechanism, we generated 10 CAZ-AVI-resistant strains from 14 CAZ-AVI susceptible KPC-producing K. pneumoniae (KPC-Kp) strains through in vitro multipassage resistance selection using low concentrations of CAZ-AVI. Comparative genomic analysis for the original and derived mutants identified CAZ-AVI resistance-associated mutations in KPCs, PBP3 (encoded by ftsI), and LamB, an outer membrane maltoporin. CAZ-AVI susceptible KPC-Kp strains became resistant when complemented with mutated blaKPC genes. Complementation experiments also showed that a plasmid borne copy of wild-type lamB or ftsI gene reduced the MIC value of CAZ-AVI in the induced resistant strains. In addition, blaKPC expression level increased in four of the six CAZ-AVI-resistant strains without KPC mutations, indicating a probable association between increased blaKPC expression and increased resistance in these strains. In conclusion, we here identified a novel mechanism of CAZ-AVI resistance associated with mutations in porin LamB in KPC-Kp.

Comparative analysis of SARS-CoV-2 and its receptor ACE2 with evolutionarily related coronaviruses.

The pandemic COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is spreading very rapidly worldwide. To date, the origin and intermediate hosts of SARS-CoV-2 remain unclear. In this study, we conducted comparative analysis among SARS-CoV-2 and non-SARS-CoV-2 coronavirus strains to elucidate their phylogenetic relationships. We found: 1, the SARS-CoV-2 strains analyzed could be divided into 3 clades with regional aggregation; 2, the non-SARS-CoV-2 common coronaviruses that infect humans or other organisms to cause respiratory syndrome and epizootic catarrhal gastroenteritis could also be divided into 3 clades; 3, the hosts of the common coronaviruses closest to SARS-CoV-2 were Apodemus chevrieri (a rodent), Delphinapterus leucas (beluga whale), Hypsugo savii (bat) , Camelus bactrianus (camel) and Mustela vison (mink); and 4, the gene sequences of the receptor ACE2 from different hosts could also be divided into 3 clades. The ACE2 gene sequences closest to that of humans in evolution include those from Nannospalax galili (Upper Galilee mountains blind mole rat), Phyllostomus discolor (pale spear-nosed bat), Mus musculus (house mouse), Delphinapterus leucas (beluga whale), and Catharus ustulatus (Swainson's thrush). We conclude that SARS-CoV-2 may have evolved from a distant common ancestor with the common coronaviruses but not a branch of any of them, implying that the prevalent pandemic COVID-19 agent SARS-CoV-2 may have existed in a yet to be identified primary host for a long time.

Associations of CXCL1 gene 5'UTR variations with ovarian cancer.

BACKGROUND: There are about 2.4 hundred thousand new cases and 1.5 hundred thousand deaths of ovarian cancer (OC) annually in the world. Chronic inflammation is a risk factor for OC. C-X-C motif chemokine ligand 1 (CXCL1) defects may facilitate inflammation and transactivate EGFR in ovarian cancer, but the precise haplotypes associated with the potential diseases remained largely unknown. In this work, we characterized CXCL1 gene variations to elucidate their possible associations with OC. METHODS: We analyzed the CXCL1 gene for 300 OC patients with 400 healthy participants as controls. The statistical analyses and Hardy-Weinberg equilibrium tests of the patients and control populations were conducted using the SPSS software (version 19.0) and Plink (version 1.9). RESULTS: The variants rs11547681, rs201090116, rs199791199, rs181868085, rs4074 and rs1814092 within or near the CXCL1 gene were characterized. The genetic heterozygosity of rs11547681 and rs4074 was very high. Statistical analysis showed that the variant rs11547681 in the gene was closely associated with the risk of OC in the Chinese Han population, although this variant was not associated with FIGO stages or pathological grades of the patients. CONCLUSIONS: Rs11547681 in CXCL1 gene was associated with the risk of OC in the Chinese Han population.