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The proportion of lung cancer in never smokers is rising, especially among Asian women, but there is no effective early detection tool. Here, we developed a polygenic risk score (PRS), which may help to identify the population with higher risk of lung cancer in never‐smoking women. We first performed a large GWAS meta‐analysis (8595 cases and 8275 controls) to systematically identify the susceptibility loci for lung cancer in never‐smoking Asian women and then generated a PRS using GWAS datasets. Furthermore, we evaluated the utility and effectiveness of PRS in an independent Chinese prospective cohort comprising 55 266 individuals. The GWAS meta‐analysis identified eight known loci and a novel locus (5q11.2) at the genome‐wide statistical significance level of P < 5 × 10−8. Based on the summary statistics of GWAS, we derived a polygenic risk score including 21 variants (PRS‐21) for lung cancer in never‐smoking women. Furthermore, PRS‐21 had a hazard ratio (HR) per SD of 1.29 (95% CI = 1.18‐1.41) in the prospective cohort. Compared with participants who had a low genetic risk, those with an intermediate (HR = 1.32, 95% CI: 1.00‐1.72) and high (HR = 2.09, 95% CI: 1.56‐2.80) genetic risk had a significantly higher risk of incident lung cancer. The addition of PRS‐21 to the conventional risk model yielded a modest significant improvement in AUC (0.697 to 0.711) and net reclassification improvement (24.2%). The GWAS‐derived PRS‐21 significantly improves the risk stratification and prediction accuracy for incident lung cancer in never‐smoking Asian women, demonstrating the potential for identification of high‐risk individuals and early screening. [ABSTRACT FROM AUTHOR]

Using a sample of listed firms in China, we aim to examine the motivation of blockchain adoption and propose two opposite hypotheses, namely value creation hypothesis and insider selling hypothesis. The empirical results demonstrate that initial blockchain adoption announcement leads to approximately 2% CAAR over the three-day interval around the release, whereas the abnormal return quickly reverses after the announcement, implying that the blockchain adoption can only provide short-term value and against the value creation hypothesis. The finding remains robust for largest industries (manufacturing and information technology) and release channels. On the contrary, we observe a significant positive effect of insider selling on the blockchain adoption announcement, which supports the insider selling hypothesis. Our findings can provide a better understanding on firms' motivation of blockchain adoption, warn the investors to keep a rational attitude to 'blockchain hysteria' when making investment decisions, and motivate the regulators to propose strict information disclosure mechanism and prevent insider selling behaviours. [ABSTRACT FROM AUTHOR]

We explore the dynamics and determinants of volatility spillover between financial technology (FinTech) and the traditional financial industry (TFI). The total, directional, and net spillover indices are measured, and we further decompose volatility spillovers in a time–frequency framework. Economic fundamentals, risk contagion, and market attention are examined as potential determinants of volatility spillovers. We reveal that the total spillover index is time-varying and exhibits an inverse U-shape between 2017 and 2021. FinTech is a net volatility receiver in most cases, and exported volatility to the TFI during the COVID-19 pandemic. The long-term components are the main driving force of volatility spillovers based on the frequency domain decomposition. Meanwhile, the economic fundamental determinants are the main contributing factors of volatility spillovers, explaining over 60% of total spillover between FinTech and the TFI. The findings remain robust under different settings of forecasting horizons, lag lengths, and proxy of the risk contagion determinant. [ABSTRACT FROM AUTHOR]

Antimicrobial acroautophagy/autophagy plays a vital role in degrading intracellular pathogens or microbial molecules in host-microbe interactions. However, microbes evolved various mechanisms to hijack or modulate autophagy to escape elimination. Vector-transmitted phloem-limited bacteria, Candidatus Liberibacter (Ca. Liberibacter) species, cause Huanglongbing (HLB), one of the most catastrophic citrus diseases worldwide, yet contributions of autophagy to HLB disease proliferation remain poorly defined. Here, we report the identification of a virulence effector in "Ca. Liberibacter asiaticus" (Las), SDE3, which is highly conserved among the "Ca. Liberibacter". SDE3 expression not only promotes the disease development of HLB and canker in sweet orange (Citrus sinensis) plants but also facilitates Phytophthora and viral infections in Arabidopsis, and Nicotiana benthamiana (N.benthamiana). SDE3 directly associates with citrus cytosolic glyceraldehyde-3-phosphate dehydrogenases (CsGAPCs), which negatively regulates plant immunity. Overexpression of CsGAPCs and SDE3 significantly inhibits autophagy in citrus, Arabidopsis, and N.benthamiana. Intriguingly, SDE3 undermines autophagy-mediated immunity by the specific degradation of CsATG8 family proteins in a CsGAPC1-dependent manner. CsATG8 degradation is largely rescued by treatment with an inhibitor of the late autophagic pathway, E64d. Furthermore, ectopic expression of CsATG8s enhances Phytophthora resistance. Collectively, these results suggest that SDE3-CsGAPC interactions modulate CsATG8-mediated autophagy to enhance Las progression in citrus. Abbreviations: ACP: asian citrus psyllid; ACD2: ACCELERATED CELL DEATH 2; ATG: autophagy related; Ca. Liberibacter: Candidatus Liberibacter; CaMV: cauliflower mosaic virus; CMV: cucumber mosaic virus; Cs: Citrus sinensis; EV: empty vector; GAPC: cytosolic glyceraldehyde-3-phosphate dehydrogenase; HLB: huanglongbing; H2O2: hydrogen peroxide; Las: liberibacter asiaticus; Laf: liberibacter africanus; Lam: liberibacter americanus; Pst: Pseudomonas syringae pv. tomato; PVX: potato virus X; ROS: reactive oxygen species; SDE3: sec-delivered effector 3; TEM: transmission electron microscopy; VIVE : virus-induced virulence effector; WT: wild-type; Xcc: Xanthomonas citri subsp. citri; [ABSTRACT FROM AUTHOR]

Background: Studies have shown a close association between home and community-based healthcare services (HCBHS) utilization and depressive symptoms in older adults. However, no studies have explored the underlying mechanism of this relationship in rural China. This study was designed to evaluate the roles of instrumental activities of daily living (IADL) and marital status in the association between HCBHS utilization and depressive symptoms in Chinese rural older adults. Methods: Data were obtained from the 2018 China Health and Retirement Longitudinal Study, and 5,981 rural respondents (≥ 60 years old) were included. Depression scores were calculated using the ten-item Center for Epidemiological Studies Depression Scale. Moderated mediation analysis was carried out applying Hayes' PROCESS macro (Model 7). Results: HCBHS utilization had a direct and negative effect on depressive symptoms. Furthermore, marital status moderated the association between HCBHS utilization and IADL, which belonged to the indirect influence of the first half on the association between HCBHS utilization and depressive symptoms. HCBHS utilization was associated with IADL in single but not in married respondents. Conclusion: The results demonstrated that marital status moderated the indirect relationship between HCBHS utilization and depressive symptoms, with HCBHS utilization being negatively associated with IADL among single but not married respondents. The government should focus on rural older adults, especially those who are single and have poor IADL function, and improve the provision of HCBHS to alleviate depressive symptoms. [ABSTRACT FROM AUTHOR]