A Recalibrated Molecular Clock and Independent Origins for the Cholera Pandemic Clones

Cholera, caused by Vibrio cholerae, erupted globally from South Asia in 7 pandemics, but there were also local outbreaks between the 6th (1899–1923) and 7th (1961–present) pandemics. All the above are serotype O1, whereas environmental or invertebrate isolates are antigenically diverse. The pre 7th pandemic isolates mentioned above, and other minor pathogenic clones, are related to the 7th pandemic clone, while the 6th pandemic clone is in the same lineage but more distantly related, and non-pathogenic isolates show no clonal structure. To understand the origins and relationships of the pandemic clones, we sequenced the genomes of a 1937 prepandemic strain and a 6th pandemic isolate, and compared them with the published 7th pandemic genome. We distinguished mutational and recombinational events, and allocated these and other events, to specific branches in the evolutionary tree. There were more mutational than recombinational events, but more genes, and 44 times more base pairs, changed by recombination. We used the mutational single-nucleotide polymorphisms and known isolation dates of the prepandemic and 7th pandemic isolates to estimate the mutation rate, and found it to be 100 fold higher than usually assumed. We then used this to estimate the divergence date of the 6th and 7th pandemic clones to be about 1880. While there is a large margin of error, this is far more realistic than the 10,000–50,000 years ago estimated using the usual assumptions. We conclude that the 2 pandemic clones gained pandemic potential independently, and overall there were 29 insertions or deletions of one or more genes. There were also substantial changes in the major integron, attributed to gain of individual cassettes including copying from within, or loss of blocks of cassettes. The approaches used open up new avenues for analysing the origin and history of other important pathogens

Impact of changing the prevalence of smoking, alcohol consumption and overweight/obesity on cancer incidence in China from 2021 to 2050: a simulation modelling studyResearch in context

Summary: Background: Smoking, alcohol consumption and overweight/obesity are key cancer risk factors contributing to the cancer burden in China. We aimed to quantify the cancer burden in China associated with smoking, alcohol consumption and overweight/obesity, and estimate the potential effect for cancer prevention interventions under different scenarios. Methods: We used a macro-simulation approach called Prevent Model to estimate for a 30-year study period (2021–2050) numbers and proportions of future avoidable cancer cases under different scenarios of reducing the prevalence of smoking, alcohol consumption and overweight/obesity in Chinese adults. Cancer incidence was predicted under three scenarios: elimination, ambitious target (between elimination and manageable target) and manageable target (from national policy or global action plan). Risk factor prevalence was obtained from China Chronic Disease and Risk Factor Surveillance, and cancer incidence data were derived from the China Cancer Registry Annual Report. Relative risks were obtained from several recent large-scale studies or high-quality meta-analysis. Population data were extracted from the China Population & Employment Statistical Yearbook, China Health Statistical Yearbook and World Population Prospects. Findings: Estimates of the avoidable cancer burden varied with different scenarios. In the theoretical maximum intervention scenario, where the prevalence of smoking, alcohol consumption and overweight/obesity would be eliminated, 9.17% (males: 13.50%; females: 1.47%) of smoking-related cancer cases, 7.06% (males: 11.49%; females: 1.00%) of cancer cases related to alcohol consumption and 8.22% (males: 7.91%; females: 8.52%) of overweight/obesity-related cancer cases were estimated to be avoidable during 2021–2050. Other scenarios, with more moderate goals in the exposure prevalence of smoking, alcohol use and overweight/obesity were also found to be associated with substantial reductions in the future cancer burden. Interpretation: Our results suggested that a substantial number of future cancer cases could be avoided in Chinese adults by reducing the prevalence of smoking, alcohol consumption and overweight/obesity. Funding: National Science & Technology Fundamental Resources Investigation Program of China; Sanming Project of Medicine in Shenzhen

Solid component proportion is an important predictor of tumor invasiveness in clinical stage T1N0M0 (cT1N0M0) lung adenocarcinoma

Abstract Background Preoperative tumor invasiveness in clinical stage T1N0M0 lung adenocarcinoma is critical for optimal surgical procedure. The aim of the present study was to evaluate the relationship between the ground-glass opacity component (GGOc) / solid component (Sc) proportion measured using three-dimensional (3D) computer-quantified computer tomography (CT) number analysis to explore radiographic features for invasiveness prediction in cT1N0M0 lung adenocarcinomas. Methods A total of 375 surgically resected cT1N0M0 lung adenocarcinoma patients were included. The relativity between the GGOc/Sc proportion and lepidic growth pattern percentage was assessed using Spearman’s rank analysis. Multiple logistic regression analysis was used to determine independent factors from radiographic features for tumor invasiveness. Prediction probability for tumor invasiveness was analysed using a receiver operating characteristic curve (ROC). Results We found that the GGOc proportion was positively correlated with lepidic growth pattern percentage (r = 0.67, P <  0.01), while the Sc proportion was negatively correlated with it (r = − 0.74, P <  0.01). Multivariate analysis showed that tumor size and Sc proportion were identified as independent predictors for tumor invasiveness. The area under the ROC curve (AUC) of Sc proportion was 0.875, which was higher than that of tumor size (0.750) (P <  0.001), and had no significant difference with that of combination of these two factors (0.884) (P = 0.28). Conclusions The GGOc/Sc proportion measured using 3D computer-quantified CT number analysis reflects the lepidic growth pattern percentage in tumors, and the Sc proportion may be an important factor for the prediction of tumor invasiveness in cT1N0M0 lung adenocarcinoma

Circadian Disruption and Breast Cancer Risk: Evidence from a Case-Control Study in China

Studies had suggested an association between circadian disruptors (including night shift work, domestic light exposure at night, sleep duration, and circadian gene polymorphism) and breast cancer, while rare studies had been conducted in the Chinese population. This study was a case-control study conducted to explore the impact of circadian disruptors on the risk of breast cancer in China. Four hundred and sixty-four cases and 464 controls, admitted from the Department of Breast Surgery, Cancer Hospital, Chinese Academy of Medical Sciences, were included in this study. Adjusting age, BMI group, smoking, alcohol consumption, menopausal status, family history of breast cancer, duration of breastfeeding, age at menarche, number of pregnancies, age at first full-term pregnancy, use of estrogen and use of oral contraceptive, multivariate logistic regression analysis showed that the risk of breast cancer was higher in short sleep duration group (OR = 4.86, 95%CI: 1.73–17.33). Meanwhile, rs2292912 in CRY2, rs2253820 in PER1, rs2289591 in PER1 and rs3027188 in PER1 were positively associated with the risk of breast cancer. This study supported that the short duration of sleep and four SNPs in crucial circadian genes played a role in the development of breast cancer

High thermoelectric performance at room temperature of n-type Mg3Bi2-based materials by Se doping

Bi2Te3 based alloys have been the most widely used thermoelectric material at low temperature for many decades. Here we report Se doped n-type Mg3Bi2 based materials with a thermoelectric figure-of-merit ZT of 0.82 at 300 K and a peak ZT of 1.24 at 498 K, which is comparable to the n-type Bi2Te3 and Te doped Mg3Bi1.4Sb0.6. The improved thermoelectric performance is benefited from the high carrier concentration and mobility as well as the thermal conductivity reduction. The reduced resistivity increased the power factor at all measured temperatures, leading to a higher engineering ZT (ZTeng) and engineering power factor (PFeng) for n-type Mg3Bi2. The n-type Mg3Bi1.4Sb0.6 materials are promising for thermoelectric power generation and cooling applications near room temperature

Construction, Characterization and Application of Recombinant Porcine Deltacoronavirus Expressing Nanoluciferase

Porcine deltacoronavirus (PDCoV), an emerging enteropathogenic coronavirus, causes diarrhoea in suckling piglets and has the potential for cross-species transmission. No effective PDCoV vaccines or antiviral drugs are currently available. Here, we successfully generated an infectious clone of PDCoV strain CHN-HN-2014 using a combination of bacterial artificial chromosome (BAC)-based reverse genetics system with a one-step homologous recombination. The recued virus (rCHN-HN-2014) possesses similar growth characteristics to the parental virus in vitro. Based on the established infectious clone and CRISPR/Cas9 technology, a PDCoV reporter virus expressing nanoluciferase (Nluc) was constructed by replacing the NS6 gene. Using two drugs, lycorine and resveratrol, we found that the Nluc reporter virus exhibited high sensibility and easy quantification to rapid antiviral screening. We further used the Nluc reporter virus to test the susceptibility of different cell lines to PDCoV and found that cell lines derived from various host species, including human, swine, cattle and monkey enables PDCoV replication, broadening our understanding of the PDCoV cell tropism range. Taken together, our reporter viruses are available to high throughput screening for antiviral drugs and uncover the infectivity of PDCoV in various cells, which will accelerate our understanding of PDCoV