The COVID-19 outbreak has already become a global pandemic and containing this rapid worldwide transmission is of great challenge. The impacts of temperature and humidity on the COVID-19 transmission rate are still under discussion. Here, we elucidated these relationships by utilizing two unique scenarios, repeated measurement and natural experiment, using the COVID-19 cases reported from January 23 - February 21, 2020, in China. The modeling results revealed that higher temperature was most strongly associated with decreased COVID-19 transmission at a lag time of 8 days. Relative humidity (RH) appeared to have only a slight effect. These findings were verified by assessing SARS-CoV-2 infectivity under the relevant conditions of temperature (4°C-37°C) and RH (> 40%). We concluded that temperature increase made an important, but not determined, contribution to restrain the COVID-19 outbreak in China. It suggests that the emphasis of other effective controlling polices should be strictly implemented to restrain COVID-19 transmission in cold seasons.
Background: The relationship between the levels of various environmental chemicals and the high prevalence of neural tube defects (NTDs) in north China remains unclear. This study aimed to classify the associations of maternal exposure to polycyclic aromatic hydrocarbons (PAHs), passive smoking, and widely concerned trace metal elements with NTD risk. Methods: Our case-control study recruited a total of 828 subjects: 285 women who delivered a fetus with NTDs (cases) and 543 women a healthy newborn without NTDs (controls). We measured the concentrations of PAHs, nicotine/cotinine, and various trace metal elements in two hair sections grown near the early pregnancy. Findings: Overall, no significant associations were found between the risk of any NTD subtypes and the hair levels of PAHs, nicotine/cotinine, and some metals (i.e., Cd, Sb, Pb, Cr, Mn, Fe, Ni, Co, and Cu). According to the cross-validation results for the two hair sections, hair concentrations of Mo and Sn were inversely associated with anencephaly risk, and the hair concentration of Zn was inversely associated with the risk of spina bifida. Interpretation: We concluded that maternal exposure to either PAHs or passive smoking was not a significant risk factor for NTDs, whereas the maternal less intake of certain trace metal elements may contribute to the high NTD prevalence in north China. It suggested that much effort should be spent to improve the dietary quality of various essential trace metal elements to reduce NTD risk for population living in North China. Funding: This research was supported by grants from the National Key Research and Development Program, P.R. China (Grant No. 2016YFC1000501) and the National Natural Science Foundation of China (No. 41771527 and 81373014). Conflict of Interest: The authors declare they have no actual or potential competing financial interests. Ethics Approval Statement: The study protocol was approved by the Institutional Review Board of Peking University (PU-IRB) and the signed consent was obtained from all subjects.
Abstract Objective: Association was found between tea and neural tube defects. However, few studies investigated the relationship between tea consumption and blood folate levels. We aimed to investigate the association between tea consumption and plasma folate concentrations among women aged 18–30 years in different ethnicities of China. Design: Data were obtained from a national cross-sectional study conducted from 2005 to 2006 of women aged 18–30 years in China. Socio-demographic characteristics and lifestyle were obtained from a questionnaire. Dietary folate intake was determined by 24-h dietary recall. Plasma folate concentrations were measured by a microbiological assay. Multiple linear regression model was used to calculate partial regression coefficients after adjusting for confounding factors. Setting: Nine provinces or autonomous regions in China. Participants: A total of 2932 women aged 18–30 years in China. Results: After stratifying by ethnicity and tea type, tea consumption was significantly positively associated with plasma folate levels in Han women who drank unfermented tea weekly ( β = 0·067, and P = 0·037) or daily ( β = 0·119, and P = 0·031) and in Uighur women who drank fermented tea weekly ( β = 0·325, and P = 0·028). For women who drank unfermented tea in Han ethnicity, weekly and daily tea drinkers had 6·77 % (95 % CI: 6·36 %, 7·21 %) and 7·13 % (95 % CI: 6·40 %, 7·96 %) increase in plasma folate concentration compared with no tea drinkers. Conclusions: There is a suggestion of possible positive association between unfermented tea drinking in Han ethnicity and plasma folate concentrations, for Chinese women aged 18–30 years. The relationship between tea drinking in other ethnic groups and plasma folate still needs to be further explored.
4556 Background: Sunitinib produces objective response rate of nearly 50% with improved progression-free survival compared to interferon in a randomized phase III trial (JCO 2009;27:22). Identification of molecular markers could improve outcome prediction and improve our understanding of mechanisms of resistance. Methods: Expression profiling was performed on 43 clear cell RCC fresh frozen tumors from pts treated with sunitinib. Median progression-free survival (PFS) was 10 mos (95% CI 6.6-11.9); median OS was 23 mos (95% CI 14-49). Eleven pts had complete and partial response (CR+PR) and 32 pts had progressive and stable disease (SD+PD). RNA isolated from tumor samples was amplified and profiled using Affymetrix microarray. The prognosis predictor models were built using a Support Vector Machine classifier with different sets of genes, by using ranker based feature selection methods on differentially expressed genes. Results: 414 differentially expressed genes were identified (P<0.05 by t-test) between the sunitinib response (CR+PR) and nonresponse (SD+PD) in the pts (2/3 of cohort) used as training set. The number of marker genes were reduced to 10, 15, 20, 30, 70, 100 and 150 sets based on the rank by using the Information gain and reliefF feature selection algorithms. Further evaluating these classifiers using the independent cohort (test set) yielded a 20 gene signature set (Table), as possible best clinical predictor of sunitinib response with 68.5% accuracy. The top ranking marker gene identified, AMFR, is highly downregulated in sunitinib sensitive patients. Conclusions: Gene expression profiling discriminates between sunitinib sensitive and resistant pts. AMFR gene is associated with angiogenesis, tumor cell motility, and regulates two known HIF1-α target genes (IGFB3, VCP). Studies on a larger cohort are ongoing by using PFS/OS as the clinical outcomes. Genes associated with sunitinib sensitivity Fold change AMFR -2.69 LOC283177 1.85 ERLIN2 -1.56 NUTF2 -1.92 C5orf46 -7.05 234254_at 1.63 MEX3D -2.17 THRAP3 -1.59 LPGAT1 -1.61 IQSEC3 1.62 CRIPT -1.57 SLC39A7 -1.64 KIAA1324L 1.59 LOC572558 1.51 TNRC6B 1.91 POU4F1 2.30 ATP1B1 -1.52 MCCC2 1.57 PPP3R1 -1.62 GNG4 1.58
Abdominal aortic aneurysm (AAA) is a multifactorial disease characterized by various pathophysiological processes, including chronic inflammation, oxidative stress, and proteolytic activity in the aortic wall. Stress-induced premature senescence (SIPS) has been implicated in regulating these pathophysiological processes, but whether SIPS contributes to AAA formation remains unknown. Here, we detected SIPS in AAA from patients and young mice. The senolytic agent ABT263 prevented AAA development by inhibiting SIPS. Additionally, SIPS promoted the transformation of vascular smooth muscle cells (VSMCs) from a contractile phenotype to a synthetic phenotype, whereas inhibition of SIPS by the senolytic drug ABT263 suppressed VSMC phenotypic switching. RNA sequencing and single-cell RNA sequencing analysis revealed that fibroblast growth factor 9 (FGF9), secreted by stress-induced premature senescent VSMCs, was a key regulator of VSMC phenotypic switching and that FGF9 knockdown abolished this effect. We further showed that the FGF9 level was critical for the activation of PDGFRβ/ERK1/2 signaling, facilitating VSMC phenotypic change. Taken together, our findings demonstrated that SIPS is critical for VSMC phenotypic switching through the activation of FGF9/PDGFRβ/ERK1/2 signaling, promoting AAA development and progression. Thus, targeting SIPS with the senolytic agent ABT263 may be a valuable therapeutic strategy for the prevention or treatment of AAA.
Hair metal(loid)s are often measured as biomarkers to evaluate population internal exposure, however, hair samples could be easily contaminated by ambient particulate matter (PM) pollution. Here, we evaluated the potential external interference from ambient PM pollution on using hair metal(loid)s for population biomarker-based exposure assessment. The raw hair samples were strictly washed and placed under various indoor and outdoor scenarios for ~6 months at sites with high PM pollution. The contaminated hair was then washed using the same method. A total of 33 hair elements were quantified by inductively coupled plasma-mass spectrometry. The surface residual PM on hair after washing was observed by scanning electron microscopy. In addition, we chose a practical exposure scenario including 77 housewives in Shanxi Province, China for validation. The results for the hair exposure experiment revealed that external contamination of some elements that had relatively high concentrations in hair was generally mild in both indoor and outdoor exposure scenarios (i.e., Zn, Mg, Se, Fe, Sr, Ti, Mn, Sn, Ge, U, Co, Mo, and As). A relatively higher external contamination of other elements (e.g., Al, Cr, Pb, Cd, Li, and most rare earth elements (REEs)) was observed, especially for those elements with relatively low hair concentrations (e.g., Cd, and REEs) in the outdoor environment. This finding was due mainly to some small ambient PM not being fully removed by the current washing strategy when the hair sample was heavily contaminated. However, results from practical exposure scenario of the housewives showed that there were overall no significant differences of hair metal(loid)s between the housewives using coal and clean energy for cooking. We concluded that the external interference on hair internal metal(loid) analysis could be negligible when hair was efficiently washed, especially for population with relatively longer indoor activities. It is therefore promising to use hair analysis for their population exposure assessment.
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