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With Brønsted and Lewis acidic sites, a new Ag(i) phosphonate has been developed and verified to have excellent performance in the cycloaddition reaction of CO2 and epoxides.

Whether screening can attenuate the influence of genetic risk and environmental risk factors for colorectal cancer (CRC) mortality risk remains unknown. Our study is to investigate the association of the screening history, genetic risk and environmental risk factors with CRC incidence and mortality risks using UK Biobank data. Screening history was associated with lower CRC incidence (hazard ratio [HR]: 0.63, 95% confidence interval [CI]: 0.58-0.69) and mortality risk (HR: 0.56, 95% CI: 0.49-0.63). Compared to the HRs of participants with a low genetic risk, low environmental risk and no screening history, the HRs of participants with a high genetic risk, high environmental risk and no screening history were 3.42 (95% CI: 2.76-4.24) for CRC incidence and 3.36 (95% CI: 2.48-4.56) for CRC mortality. In contrast, the HRs of participants with a high genetic risk and no screening history, but a low environmental risk, were 1.92 (95% CI: 1.55-2.36) for CRC incidence and 1.88 (95% CI: 1.39-2.53) for CRC mortality. Furthermore, the HRs of participants with a high genetic risk and a low environmental risk, but a screening history were 1.62 (95% CI: 1.15-2.28) for CRC incidence and 1.77 (95% CI: 1.08-2.89) for CRC mortality. Participants benefited more substantially from screenings for CRC mortality than for CRC incidence risk. A higher environmental risk was associated with higher risk of CRC incidence and mortality within each category of genetic risk. These findings emphasize the importance of CRC screening and identifying environmental factors to reduce CRC incidence and mortality risks.

Fish oil is one of the most popular supplements in the UK and other developed countries. However, the relationship between fish oil use and chronic obstructive pulmonary disease (COPD) is unclear.To prospectively examine the association of habitual fish oil supplementation with incident COPD risk and to evaluate potential effect modification by genetic predisposition.This study included 484,414 participants (mean and standard deviation [SD] age: 56.5 [8.1] years) from the UK Biobank who completed a touchscreen questionnaire on habitual fish oil supplement use between 2006 and 2010 and were followed up through 2018. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for sociodemographic and lifestyle behaviours, health conditions, and other potential confounding factors. A weighted genetic risk score (GRS) for COPD was derived from 112 validated single nucleotide polymorphisms.During a median follow-up of 9.0 years, 8860 incident COPD events were recorded. A total of 31.4% (152,230) of the study participants reported habitual fish oil supplementation at baseline. Habitual fish oil supplementation was significantly associated with a lower risk of incident COPD (adjusted HR: 0.88; 95% CI: 0.84-0.93). The association with COPD did not differ by GRS strata (P for interaction = 0.880). The results from subgroup and sensitivity analyses supported the robustness of our findings.Our findings suggest that habitual fish oil supplementation is associated with a lower risk of incident COPD, irrespective of genetic predisposition.

Traffic is the main noise source in urban environment, which has a significant impact on people's physical and mental health and labor productivity. To solve the problem of highway noise pollution, we should not only strengthen the prevention and control measures in the later stage but also scientifically and accurately predict and evaluate its noise impact in the early stage. The selection of the noise prediction model and the determination of its parameters is the necessary premise for the accurate prediction of highway noise. This paper introduces several traditional noise prediction algorithms based on statistical methods. Then the application of the artificial neural network method in traffic noise prediction is analyzed. The results show that artificial neural network is an effective noise prediction tool with high prediction accuracy. Compared with other statistical methods, the artificial neural network method has obvious advantages in traffic noise prediction.

Kidney diseases can cause severe morbidity, mortality, and health burden. Determining the risk factors associated with kidney damage and deterioration has become a priority for the prevention and treatment of kidney disease. This study followed 497 patients with stage 3–5 chronic kidney disease (CKD) who were treated at the ward of Taipei Veterans General Hospital from January 2006 to 2019 in Taiwan. The patients underwent 3-year-long follow-up sessions for clinical measurements, which occurred every 3 months. Three time-dependent survival models, namely the Cox proportional hazard model (Cox PHM), random survival forest (RSF), and an artificial neural network (ANN), were used to process patient demographics and laboratory data for predicting progression to renal failure, and important features for optimal prediction were evaluated. The individual prediction of CKD progression was validated using the Kaplan–Meier estimation method, based on patients’ true outcomes during and beyond the study period. The results showed that the average concordance indexes for the cross-validation of the Cox PHM, ANN, and RSF models were 0.71, 0.72, and 0.89, respectively. RSF had the best predictive performances for CKD patients within the 3 years of follow-up sessions, with a sensitivity of 0.79 and specificity of 0.88. Creatinine, age, estimated glomerular filtration rate, and urine protein to creatinine ratio were useful factors for predicting the progression of CKD patients in the RSF model. These results may be helpful for instantaneous risk prediction at each follow-up session for CKD patients.

Background Previous studies have shown that secondary metabolites of Bacillus subtilis strain Z15 (BS-Z15) are effective in treating fungal infections in mice. To evaluate whether it also modulates immune function in mice to exert antifungal effects, we investigated the effect of BS-Z15 secondary metabolites on both the innate and adaptive immune functions of mice, and explored its molecular mechanism through blood transcriptome analysis. Results The study showed that BS-Z15 secondary metabolites increased the number of monocytes and platelets in the blood, improved natural killer (NK) cell activity and phagocytosis of monocytes-macrophages, increased the conversion rate of lymphocytes in the spleen, the number of T lymphocytes and the antibody production capacity of mice, and increased the levels of Interferon gamma (IFN-γ), Interleukin-6 (IL-6), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) in plasma. The blood transcriptome analysis revealed 608 differentially expressed genes following treatment with BS-Z15 secondary metabolites, all of which were significantly enriched in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms for immune-related entries and pathways such as Tumor Necrosis Factor (TNF) and Toll-like receptor (TLR) signaling pathways, and upregulated expression levels of immune-related genes such as Complement 1q B chain (C1qb), Complement 4B (C4b), Tetracyclin Resistant (TCR) and Regulatory Factor X, 5 (RFX5). Conclusions BS-Z15 secondary metabolites were shown to enhance innate and adaptive immune function in mice, laying a theoretical foundation for its development and application in the field of immunity.

Background Little is known about the combined relationship of night shifts and lifestyle risks with incident dementia or their potential interactions. To evaluate the association of night shifts and lifestyle risks with incident dementia and further analyze their interactions. Methods A total of 276,059 participants were included in this study from the UK Biobank cohort. Cox proportional hazards models were used to investigate the combined association of night shifts and lifestyle risks with incident dementia. Results Participants with always night shifts and three or four unhealthy lifestyle factors had the highest risk of incident all-cause dementia (hazard ratio: 3.15, 95% confidence interval [CI]: 1.74-5.69). An additive interaction was found between night shifts and lifestyle risks for incident all-cause dementia (P < 0.001), with a relative excess risk due to the interaction of 0.14 (95% CI: 0.11-0.45). The attributable proportions of the combined effect on the incidence of all-cause dementia were 22.6% (95% CI: 20.91%-26.75%) for night shift work, 65.0% (95% CI: 63.12%-69.80%) for unhealthy lifestyle factors, and 12.1% (95% CI: 8.67%-18.04%) for their interaction. Conclusions Both night shifts and lifestyle risks were associated with a higher risk of incident dementia. The combined impact was higher than the increase in the risks related to each single factor. Our results indicated that most incident dementia cases might be prevented by a healthy lifestyle, and the benefits would be greater among night shift workers. Further studies are needed to confirm our results and explore the underlying mechanisms.

IntroductionEarly and accurate identification of pathogens is essential for improved outcomes in patients with viral encephalitis (VE) and/or viral meningitis (VM).MethodsIn our research, Metagenomic next-generation sequencing (mNGS) which can identify viral pathogens unbiasedly was performed on RNA and DNA to identify potential pathogens in cerebrospinal fluid (CSF) samples from 50 pediatric patients with suspected VEs and/or VMs. Then we performed proteomics analysis on the 14 HEV-positive CSF samples and another 12 CSF samples from health controls (HCs). A supervised partial least squaresdiscriminant analysis (PLS-DA) and orthogonal PLS-DA (O-PLS-DA) model was performed using proteomics data.ResultsTen viruses in 48% patients were identified and the most common pathogen was human enterovirus (HEV) Echo18. 11 proteins overlapping between the top 20 DEPs in terms of P value and FC and the top 20 proteins in PLS-DA VIP lists were acquired.DiscussionOur result showed mNGS has certain advantages on pathogens identification in VE and VM and our research established a foundation to identify diagnosis biomarker candidates of HEV-positive meningitis based on MS-based proteomics analysis, which could also contribute toward investigating the HEV-specific host response patterns.

Introduction: About half of adults aged ≥ 80 years suffer from frailty. Exercise is considered effective in preventing frailty but may be inapplicable to adults aged ≥ 80 years due to physical limitations. As an alternative, we aimed to explore the association of leisure activities with frailty and identify potential interaction with established polygenic risk score (PRS) among adults aged ≥ 80 years. Methods: Analyses were performed in a prospective cohort study of 7471 community-living older adults aged ≥ 80 years who were recruited between 2002 and 2014 from 23 provinces in China. Leisure activity was assessed using a seven-question leisure activity index and frailty was defined as a frailty index ≥ 0.25 using a validated 39-item health-related scale. The PRS was constructed using 59 single-nucleotide polymorphisms associated with frailty in a subsample of 2541 older adults. Cox proportional hazards models were used to explore the associations of leisure activities, PRS with frailty. Results: The mean age of participants was 89.4 ± 6.6 years (range: 80–116). In total, 2930 cases of frailty were identified during 42,216 person-years of follow-up. Each 1 unit increase in the leisure activity index was associated with 12% lower risk of frailty (hazard ratio [HR]: 0.88 [95%CI, 0.85-0.91]). Participants with high genetic risk (PRS>2.47×10-4) suffered from 26% higher risk of frailty. Interaction between leisure activity and genetic risk was not observed. Conclusion: Evidence is presented for the independent association of leisure activities and genetic risk with frailty. Engagement in leisure activities suggested to be associated with lower risk of frailty across all levels of genetic risk among adults aged ≥ 80 years.

The purpose of the study is to present a mathematical model capable of describing drug particle dissolution in 3-dimensional (3D) space, and to provide experimental model verification. Through this study, we also aim to elaborate limitations of the classic, 1D-based Nernst-Brunner formalism in dissolution modeling.The 3D dissolution model was derived by treating the dissolution of a spherical particle as a diffusion-driven process, and by solving Fick's 2A set of working equations was developed to describe drug particle dissolution in 3D space. The predicted dissolution time and profile are in good agreement with the experimental results. The model clearly shows that the concentration gradient within the diffusion layer, in realistic 3D condition, must not be a constant value as implicated in the Nernst-Brunner formalism. The actual concentration profile is a hyperbola, and the concentration gradient at the surface of the particle can be significantly higher than the classic 1D-based dissolution model.The study demonstrates that the classic, 1D-based dissolution models may lead to significant under-estimation of drug dissolution rates. In contrast, modeling dissolution in 3D space yields more reliable results. This study merits further development of comprehensive 3D drug dissolution models, by considering polydispersed particle ensemble and imposing the changes of diffusion layer thickness during dissolution.

Background COVID-19, which is caused by SARS-CoV-2, is a major global health threat. The dominant variant of SARS-CoV-2 has changed over time due to continuous evolution. We aimed to evaluate the coverage of SARS-CoV-2 vaccination among employees in China, explore their willingness to receive the SARS-CoV-2 variant vaccine and examine the potential factors influencing vaccination coverage and willingness. Methods A cross-sectional epidemiological survey was conducted online from January 1, 2022, to January 30, 2022. The information collected in the survey included sociodemographic characteristics, lifestyle habits, vaccination coverage, willingness to be vaccinated against SARS-CoV-2 variants and the reasons for vaccination and willingness. Multivariable logistic regression models were used to assess the associations of potential factors with the rate of vaccination and the willingness to be vaccinated. Results Among 62,395 eligible participants, the coverage of SARS-CoV-2 vaccination was 98.9% for at least one dose and 70.1% for a booster. The great majority of vaccinated individuals (94.4%) voluntarily received the vaccine. A total of 60,694 respondents (97.7%) were willing to be vaccinated against SARS-CoV-2 variants, mainly due to confidence in the effectiveness of vaccines (92.8%). A total of 1431 respondents were unwilling to be vaccinated, mainly because of concerns about the adverse effects of vaccines (77.6%). Longer education duration was associated with a higher rate of SARS-CoV-2 vaccination and willingness to be vaccinated. General or poor health status and having no history of influenza vaccination were associated with a lower rate of SARS-CoV-2 vaccination and willingness to be vaccinated. Additionally, we observed a significant positive association of abuse experience with the willingness to be vaccinated. Conclusion Although the rate of SARS-CoV-2 vaccination and the willingness to be vaccinated were relatively high in the study population, there were still some respondents with vaccine hesitancy. Relevant strategies based on significant related factors should be developed and implemented to encourage vaccination.

Immunotherapy based on immune checkpoint inhibitors (ICIs) has provided revolutionary results in treating various cancers. However, its efficacy in colorectal cancer (CRC), especially in microsatellite stability-CRC, is limited. This study aimed to observe the efficacy of personalized neoantigen vaccine in treating MSS–CRC patients with recurrence or metastasis after surgery and chemotherapy. Candidate neoantigens were analyzed from whole-exome and RNA sequencing of tumor tissues. The safety and immune response were assessed through adverse events and ELISpot. The clinical response was evaluated by progression-free survival (PFS), imaging examination, clinical tumor marker detection, circulating tumor DNA (ctDNA) sequencing. Changes in health-related quality of life were measured by the FACT-C scale. A total of six MSS–CRC patients with recurrence or metastasis after surgery and chemotherapy were administered with personalized neoantigen vaccines. Neoantigen-specific immune response was observed in 66.67% of the vaccinated patients. Four patients remained progression-free up to the completion of clinical trial. They also had a significantly longer progression-free survival time than the other two patients without neoantigen-specific immune response (19 vs. 11 months). Changes in health-related quality of life improved for almost all patients after the vaccine treatment. Our results shown that personalized neoantigen vaccine therapy is likely to be a safe, feasible and effective strategy for MSS–CRC patients with postoperative recurrence or metastasis.

Fast radio bursts (FRBs) are highly dispersed millisecond-duration radio bursts,[1,2] of which the physical origin is still not fully understood. FRB 20201124A is one of the most actively repeating FRBs. In this paper, we present the collection of 1863 burst dynamic spectra of FRB 20201124A measured with the Five-hundred-meter Aperture Spherical radio Telescope (FAST). The current collection, taken from the observation during the FRB active phase from April to June 2021, is the largest burst sample detected for any FRB so far. The standard PSRFITs format is adopted, including dynamic spectra of the burst, and the time information of the dynamic spectra, in addition, mask files help readers to identify the pulse positions are also provided. The dataset is available in Science Data Bank, with the link https://www.doi.org/10.57760/sciencedb.j00113.00076.

Additional file 1. Figure S1 Schematic procedure used in the knock-out of ZM532, ZMO_RS02740 and ZMO_RS06525 in ZM4 and ZM532. Figure S2 Venn diagram depicting the unique and shared differentially expressed genes between the two Z. mobilis, ZM532 strains, (A) AF_ZM532vsRM_532 (yellow) and its wild type AF_ZM4 vsRM_ZM4 (purple); (B) AF_ZM532vsAF_ZM4 (purple) and RM_ZM532vsRM_ZM4 in response to acetic acid and furfural combine treatments. Figure S3 Overview of the quantitative mass spectrometry results (A) Number of proteins identified in each sample; (B) Distribution of peptide length range; (C) Protein molecular weight distribution; (D) Reproducibility between biological replicates. Figure S4 Represented DEPs subcellular localization analysis. Figure S5 Venn diagram showing the shared and specific (DEP) between ZM4 and ZM532 in response to acetic acid and furfural treatments. Figure 6 KEEG enrichment analysis of the DEPs p < 0.05 in (A) ZM532_AF_vsZM532_RM and (B) ZM4_AF_vs_ZM4_RM; (C) AF_ZM532_vs_AF_ZM4; (D) RM_ZM532_vs_RM_ZM; (E) COG functional classification of the DE proteins. The proteins with significant homologies in the COG database were classified into 21 COG categories. Capital letters on the x-axis indicate COG categories on the right side of the histogram. Figure S7 KEGG pathway annotation for Z. Mobilis. The abscissa represents the number of proteins; the pathway categories are shown on the y-axis. Figure S8 Transcript abundance of 10 selected differentially expressed genes (DEGs) in the two samples (brown bar represents either ZM4 or ZM532 which gave similar expression; gray bar represents expression in the wild type, ZM4; ash bar represents expression in the mutant strain, ZM532. The error bar represents standard error of the three technical repeats. Table S1. List of Primer pairs used in study. Table S2. List of primers used for qPCR experiment. Table S3. List of primers, strains and plasmids. Table S4. List of primers, strains and plasmids. Table S5. INDEL in re-sequence ZM532 by comparing with previous published ten genome-shuffled mutant strain and Z. mobilis ZM4 (GenBank: AE008692.2). Table S6. Overview of the transcriptome sequencing dataset and quality check. Table S7 Differentially Expressed Genes of ZM532 strain in rich media and media with acetic + furfural treatments. Table S8 Differentially Expressed Genes of wild type ZM4 in rich media and media with acetic + furfural treatment. Table S9 Differentially Expressed proteins of ZM4 strain in rich media and media with acetic + furfural treatments. Table S10 Differentially Expressed proteins of ZM532 strain in rich media and media with acetic + furfural treatments.

Both knowledge graphs and user-item interaction graphs are frequently used in recommender systems due to their ability to provide rich information for modeling users and items. However, existing studies often focused on one of these sources (either the knowledge graph or the user-item interaction graph), resulting in underutilization of the benefits that can be obtained by integrating both sources of information. In this paper, we propose DEKGCI, a novel double-sided recommendation model. In DEKGCI, we use the high-order collaborative signals from the user-item interaction graph to enrich the user representations on the user side. Additionally, we utilize the high-order structural and semantic information from the knowledge graph to enrich the item representations on the item side. DEKGCI simultaneously learns the user and item representations to effectively capture the joint interactions between users and items. Three real-world datasets are adopted in the experiments to evaluate DEKGCI's performance, and experimental results demonstrate its high effectiveness compared to seven state-of-the-art baselines in terms of AUC and ACC., Comment: 24 pages, 6 figures,6 tables

Xiao Zhen Zhang,1,&ast; Mao Jian Chen,2,3,&ast; Ping Ming Fan,4 Wei Jiang,3 Shi Xiong Liang1 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People’s Republic of China; 3Department of Respiratory Oncology, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China; 4Department of Breast-Thoracic Tumor Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, 570102, Hainan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shi Xiong Liang; Wei Jiang, Email shixliang@vip.sina.com; weicy2016@163.comBackground: B-cell translocation gene 2 (BTG2) has been revealed to be involved in the occurrence and development of multiple cancers. However, the role of BTG2 in lung adenocarcinoma (LUAD) is still ambiguous. Thus, this study aims to investigate the prognostic value of BTG2 and its correlation with immune infiltration in LUAD.Methods: The expression of BTG2 in LUAD was analyzed using the TIMER and UALCAN databases. The correlations between BTG2 expression and clinicopathological factors were investigated using the UALCAN databases. The Kaplan–Meier plotter, GEPIA, and TCGA databases were employed to assess the prognostic value of BTG2. The STRING database and Cytoscape software were used to construct an interaction network and mine co-expression genes. The TISIDB database was examined for a correlation between BTG2 and driver genes in LUAD. Enrichment analysis of co-expressed genes and BTG2 was performed using the LinkedOmics database. Finally, the correlations between BTG2 and immune infiltrates were investigated using the TIMER, GEO, and TISIDB database.Results: BTG2 was significantly downregulated in LUAD. The decreased expression of BTG2 in LUAD was significantly correlated with higher cancer stages and shorter duration of overall survival. The expressions of BTG2-related co-expression genes were associated with the prognosis in LUAD. The expression of BTG2 was closely associated with the mutations of TP53 and ROS1. Enrichment analysis revealed that BTG2 was significantly correlated with immune‐associated signaling pathways and function. In addition, the expression of BTG2 was found to be closely related to immune infiltration, multiple gene markers of immune cells, chemokines, and chemokine receptors.Conclusion: Our findings have effectively demonstrated that BTG2 expression was downregulated in LUAD, indicating poor prognosis. Closely relating to immune cell infiltration, BTG2 may be a promising immune-related biomarker and molecular target for patients with LUAD.Keywords: BTG2, lung adenocarcinoma, prognosis biomarker, gene mutation, immune infiltration

Rationale Both genetic variants and chronic obstructive pulmonary disease (COPD) contribute to the risk of incident severe coronavirus disease (COVID-19). Whether genetic risk of incident severe COVID-19 is the same regardless of preexisting COPD is unknown. Objectives In this study, we aimed to investigate the potential interaction between genetic risk and COPD in relation to severe COVID-19. Methods We constructed a polygenic risk score for severe COVID-19 by using 112 single-nucleotide polymorphisms in 430,582 participants from the UK Biobank study. We examined the associations of genetic risk and COPD with severe COVID-19 by using logistic regression models. Results Of 430,582 participants, 712 developed severe COVID-19 as of February 22, 2021, of whom 19.8% had preexisting COPD. Compared with participants at low genetic risk, those at intermediate genetic risk (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.09–1.66) and high genetic risk (OR, 1.50; 95% CI, 1.18–1.92) had higher risk of severe COVID-19 (P for trend = 0.001), and the association was independent of COPD (P for interaction = 0.76). COPD was associated with a higher risk of incident severe COVID-19 (OR, 1.37; 95% CI, 1.12–1.67; P = 0.002). Participants at high genetic risk and with COPD had a higher risk of severe COVID-19 (OR, 2.05; 95% CI, 1.35–3.04; P

The localization of shaking forces acting on an operating machine is an important step to identify vibration and noise sources. The forced vibration response of a linearly vibrating structure is assumed to be linear. However, the energy distribution of a linearly vibrating structure contains “coupled terms” in the modal decomposition of the vibration energy density function. These coupled energy terms represent the cross-modal energy density associated with the exciting force of a dynamic structure under forced vibration. In this research, it is proved analytically that the high-order cross-modal energy densities of a linear dynamic structure are highly correlated to the location of the external exciting force. Using this finding, a new force localization index based on the high-order cross-modal energy densities of a dynamic structure is proposed and tested. Numerical tests on uniform and step beam structures under force excitation with different frequencies and locations have been carried out to test the effectiveness of the proposed force localization method. It is found that the proposed force localization method works well on vibrating beam structures. Experiments are carried out to verify the proposed force localization method.

Background Several guidelines have suggested alternative glycemic markers for hemoglobin A1c among older adults with limited life expectancy or multiple coexisting chronic illnesses. We evaluated associations between fructosamine, albumin-corrected fructosamine (AlbF), fasting plasma glucose (FPG), and mortality in the diabetic and nondiabetic subpopulations, and compared which marker better predicts mortality among participants aged 80 and older. Methods Included were 2 238 subjects from the Healthy Ageing and Biomarkers Cohort Study (2012–2018) and 207 participants had diabetes at baseline. Multivariable Cox proportional hazards regression models investigated the associations of fructosamine, AlbF, FPG, and all-cause, cardiovascular disease (CVD), and non-CVD mortality in the diabetic and nondiabetic subpopulations. Restricted cubic splines explored potential nonlinear relations. C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) evaluated the additive value of different glycemic markers to predict mortality. Results Overall, 1 191 deaths were documented during 6 793 person-years of follow-up. In the linear model, per unit increases of fructosamine, AlbF, and FPG were associated with a higher risk of mortality in nondiabetic participants, with hazard ratios of 1.02 (1.00, 1.05), 1.27 (1.14, 1.42), and 1.04 (0.98, 1.11) for all-cause mortality, and 1.04 (1.00, 1.07), 1.38 (1.19, 1.59), and 1.10 (1.01, 1.19) for non-CVD mortality, respectively. Comparisons indicated that AlbF better predicts all-cause and non-CVD mortality in nondiabetic participants with significant improvement in IDI and NRI. Conclusions Higher concentrations of fructosamine, AlbF, and FPG were associated with a higher risk of all-cause or non-CVD mortality among the very elderly where AlbF may constitute an alternative prospective glycemic predictor of mortality.

The purpose of the study is to present the finite difference method (FDM) and demonstrate its utility in modeling mass transport processes that are pharmaceutically relevant. In particular, diffusion processes are ideally suited for FDM because the governing equation, Fick's second law of diffusion, can be readily solved using FDM over a finite space and time. The method entails the mesh creation, space and time discretization, and solving Fick's second law at each node using finite difference-based numerical schemes. We applied FDM to study tablet disintegration, in which the tablet water uptake was simulated with an effective water diffusion coefficient; the tablet disintegration was controlled by a designated critical water content parameter, beyond which the node is treated as being disintegrated from the tablet. The resulting simulation agreed with the experimental tablet disintegration behaviors, under both disintegration-controlled and water uptake-controlled conditions. This study highlighted the unique advantage of FDM, capable of providing spatial-temporal information on water uptake and evolution of tablet size and shape during tablet disintegration, which was otherwise not available using other methods. The FDM method enabled more in-depth tablet disintegration studies. The model also has the potential to be calibrated and incorporated in tablet formulation DoE studies.

Objective To examine the association of incident type 2 diabetes (T2D) risk with sleep factors, genetic risk, and their combination effects. Design Large prospective population-based cohort study. Methods This population-based prospective cohort study included 360 403 (mean (s.d.) age: 56.6 (8.0) years) participants without T2D at baseline from the UK Biobank. Genetic risk was categorised as high (highest quintile), intermediate (quintiles: 2–4), and low (lowest quintile) based on a polygenic risk score for T2D. Sleep scores, including long or short sleep duration, insomnia, snoring, late chronotype, and excessive daytime sleepiness, were categorized as an unfavourable, intermediate, or favourable sleep and circadian pattern. Results During a median follow-up of 9.0 years, 13 120 incident T2D cases were recorded. Among the participants with an unfavourable sleep and circadian pattern, 6.96% (95% CI: 6.68–7.24%) developed T2D vs 2.37% (95% CI: 2.28–2.46%) of participants with a favourable sleep and circadian pattern (adjusted hazard ratio (HR): 1.53, 95% CI: 1.45–1.62). Of participants with a high genetic risk, 5.53% (95% CI: 5.36–5.69%) developed T2D vs 2.01% (95% CI: 1.91–2.11%) of participants with a low genetic risk (adjusted HR: 2.89, 95% CI: 2.72–3.07). The association with sleep and circadian patterns was independent of genetic risk strata. Participants in the lowest quintile with an unfavourable sleep and circadian pattern were 3.97-fold more likely to develop T2D than those in the lowest quintile with a favourable sleep and circadian pattern. Conclusions Sleep and circadian patterns and genetic risk were independently associated with incident T2D. These results indicate the benefits of adhering to a healthy sleep and circadian pattern in entire populations, independent of genetic risk.

Previous studies have shown that secondary metabolites of Bacillus subtilis strain Z15 (BS-Z15) are effective in treating fungal infections in mice. To evaluate whether it also modulates immune function in mice to exert antifungal effects, we investigated the effect of BS-Z15 secondary metabolites on both the innate and adaptive immune functions of mice, and explored its molecular mechanism through blood transcriptome analysis. The study showed that BS-Z15 secondary metabolites increased the number of monocytes and platelets in the blood, improved NK cell activity and phagocytosis of monocytes-macrophages, increased the conversion rate of lymphocytes in the spleen, the number of T lymphocytes and the antibody production capacity of mice, and increased plasma levels of IFN-γ, IL-6, IgG and IgM. The blood transcriptome analysis revealed 608 differentially expressed genes following treatment with BS-Z15 secondary metabolites, all of which were significantly enriched in the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes terms for immune-related entries and pathways such as TNF and TLR signaling pathways, and upregulated expression levels of immune-related genes such as C1qb, C4b, TCR and RFX5. BS-Z15 secondary metabolites were shown to enhance innate and adaptive immune function in mice, laying a theoretical foundation for its development and application in the field of immunity.

With the advent of continuous direct compression (CDC) process, it becomes increasingly desirable to characterize inherent powder blend heterogeneity at a small batch scale for a robust and CDC-amenable formulation. To accomplish this goal, a near infrared spectroscopy (NIRS)-based characterization approach was developed and implemented on multiple direct compression (DC) blends in this study, with the intended purpose of complementing existing formulation development tools and enabling to build an early CMC data package for late-phased process analytical technology (PAT) method development. Three fumaric acid DC blends, designed to harbor varied degrees of inherent blend heterogeneity, were employed. Near infrared spectral data were collected on a kg-scale batch blender via both time- and angle-based triggering modes. The time-triggered data were used to investigate the blending heterogeneity with respect to rotation angles, while the angle-triggered data were used to provide blending variability characterization and compare against off-line HPLC-based results. The time-triggered data revealed that the greatest blend variability was observed between revolutions, while the blending variability within a single revolution stayed relatively low with respect to rotation angles. This confirmed earlier literature findings that the bottom layer of powder blends tends to move with the blender within each revolution, and the most intense powder mixing takes place across revolutions. This also indicates the use of blending speed and the number of co-adds are not able to increase sampling volume to improve signal-to-noise ratio under a tumble-bin blender as what were typically done in a feedframe application. The angle-triggered data showed that there is a consistent trend between NIRS and HPLC-based methods on characterizing blend heterogeneity across the blends at a given sample size. This study contributes to establishing NIRS as a potential characterization approach for inherent powder blend heterogeneity for early RD. It also highlights the promise of continuous characterization of inherent powder blend heterogeneity from gram scale to mini-batch CDC scale.

Background The interplay between physical activity (PA) and air pollution in relation to type 2 diabetes (T2D) remains largely unknown. Based on a large population-based cohort study, this study aimed to examine whether the benefits of PA with respect to the risk of T2D are moderated by exposure to air pollution. Methods UK Biobank participants (n = 359,153) without diabetes at baseline were included. Information on PA was obtained using the International Physical Activity Questionnaire short form. Exposure to air pollution, including PM2.5, PMcoarse (PM2.5−10), PM10, and NO2, was estimated from land use regression models. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results During a median of 8.9 years of follow-up, 13,706 T2D events were recorded. Compared with a low PA level, the HRs for the risk of T2D among individuals with moderate and high PA were 0.82 (95% CI, 0.79–0.86) and 0.73 (95% CI, 0.70–0.77), respectively. Compared with low levels of air pollution, the HRs for risk of T2D for high levels of air pollution (PM2.5, PMcoarse, PM10, and NO2) were 1.19 (1.14–1.24), 1.06 (1.02–1.11), 1.13 (1.08–1.18), and 1.19 (1.14–1.24), respectively. There was no effect modification of the associations between PA and T2D by air pollution (all P-interactions > 0.05). The inverse associations between PA and T2D in each air pollution stratum were generally consistent (all P for trend Conclusion A higher PA and lower air pollution level were independently associated with a lower risk of T2D. The beneficial effects of PA on T2D generally remained stable among participants exposed to different levels of air pollution. Further studies are needed to replicate our findings in moderately and severely polluted areas.

Regular use of non-steroidal anti-inflammatory drugs (NSAIDs) was associated with the lower risk of colorectal cancer (CRC). However, whether regular use of NSAIDs could attenuate the effect of genetic risk and environmental risk factors on CRC is unknown. We aimed to evaluate the association of NSAID use, genetic risk, and environmental risk factors with CRC. Using data from a UK Biobank, a Cox proportional hazards model was performed to estimate the risk of CRC according to NSAID use, polygenic risk score, and environmental risk factors. Regular use of NSAIDs was associated with a 36.0% lower risk of CRC. No statistically significant interaction was observed between NSAID use and the genetic risk score (p = 0.190), and between NSAID use and the environmental risk score (p = 0.740). However, regular NSAID use was still associated with lower CRC incidence among subjects with either high environmental risk or high genetic risk. Furthermore, the genetic and environmental risk of CRC were additives. These findings appear to support the chemopreventive effect of regular NSAID use. Furthermore, controlling of modifiable environmental risk factors can reduce the CRC risk, especially among individuals with a moderate or high genetic risk of CRC.

Tripeptide NCW identified in Mizuhopecten yessoensis has been shown to possess in vivo antihypertensive effect. However, the poor understanding of the absorption of NCW across the membrane limits its application. In this study, we have investigated the interaction of NCW with DPPC membrane via 400 ns all-atom molecular dynamic simulation using GROMACS software. The structural variations of NCW during absorption, the location and distribution of NCW in the membrane, and the effect of NCW on the properties of membranes during simulation were analyzed to understand the dynamic behavior of NCW in DPPC membrane system. The results suggested that the structures of NCW were stable during simulation. Further, NCW could bind on the surface of the DPPC membrane and enter the hydrophobic interior of the DPPC membrane. Residue Try played an important role in the absorption of NCW across the membrane. Hydrogen bonds and hydrophobic interactions stabilized the interaction of NCW with the membrane. All the above studies analyzed the interaction mechanism between NCW and DPPC membranes at the atomic level and laid the foundation for further transmembrane studies of NCW.

In tablet manufacturing, mixing operations in tumble blending (TB) and in the feed frame (FF) of the rotary press can both increase lubricity, negatively influencing the tablet mechanical strength. While the TB-driven lubrication was systematically studied, no reliable bench-scale methods exist for the effect of FF lubrication. Because TB and FF mixing are usually two successive operations in tablet manufacturing, we developed a phenomenological model to incorporate the impact of TB-driven lubrication and the FF lubrication on the tablet tensile strength (TS). We noted that exponential decay functions can describe the evolution of the tablet TS as the function of the extent of TB, as well as the residence time in FF. Hence, the overall lubrication sensitivity can be modeled by incorporating two distinct exponential decay functions. The model can be calibrated through bench-scale experiments. Using an investigational powder blend, we showed that this approach accurately predicted the tablet TS in a scale-up tablet compression study, thereby verifying its utility. This model can serve as a scale-up diagnostic and risk-assessment tool, with the ability to adjust the overall effect of lubrication by changing the TB scale and the FF residence time commensurate with the large-scale operations.

Two biotin-polyethylene glycol (PEG)4‑diarylidenyl piperidone (DAP) prodrugs, compounds 3a and 3b, were designed as antineoplastic agents and synthesized by coupling biotin to bifluoro- and binitro-substituted DAP derivatives (DAP-F and DAP-NO

Background To examine the association between regular use of proton pump inhibitors and the risk of incident dementia, including dementia subtypes, and whether the association differs between APOE genotypes. Methods Based on a prospective analysis of data from the UK Biobank, 501,002 individuals (female, 54.4%) aged between 40 and 70 years, who had no prevalent dementia at baseline, were enrolled between 2006 and 2010 and followed up to 2018. We compared all-cause dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) incidence rates between proton pump inhibitor users and non-users by the Cox proportional hazard model. Results During 4,438,839 person-years of follow-up (median length of follow-up, 9.0 years), there were 2505 incident cases of all-cause dementia, including 932 cases of AD and 524 cases of VaD. The incident rate of all-cause dementia among proton pump inhibitor users was 1.06 events per 1000 person-years, compared with 0.51 events per 1000 person-years among non-users. After adjustment for multiple confounders and indications, the hazard ratios (HRs) of the proton pump inhibitor users were 1.20 (95% CI, 1.07–1.35) for incident all-cause dementia, 1.23 (95% CI, 1.02–1.49) for incident AD, and 1.32 (95% CI, 1.05–1.67) for incident VaD. In addition, the association between proton pump inhibitor use and all-cause dementia differed by APOE genotype (P for interaction = 0.048). Among APOE ε4 heterozygotes, the fully adjusted HR of proton pump inhibitor use was 1.46 (95% CI, 1.22–1.75) and 1.68 (95% CI, 1.36–2.07), especially for individuals aged 65 years and older. Conclusions The finding of this large population-based cohort study indicates that the use of proton pump inhibitors is associated with an increased risk of incident dementia, particularly among APOE ε4 heterozygotes.

BackgroundGaps remained in the updated information of the firearm violence (FV) burden from a global landscape. Understanding the global burden of FV could contribute to decision-making.MethodsData on the FV burden, including physical violence by firearm (PVF), self-harm by firearm (SHF), and unintentional firearm injuries (UFI), were extracted from the Global Burden of Disease 2019. The temporal trends of age-standardized rate (ASR) were estimated using estimated annual percentage change (EAPC).ResultsIn 2019, PVF, SHF, and UFI reported 710.64 × 103, 335.25 × 103, and 2,133.88 × 103, respectively, incident cases worldwide. Their ASR (/100,000 people-years) were 9.31, 4.05, and 28.07. During 1990–2019, the overall incident ASRs of PVF presented an increasing trend (EAPC = 0.61, 95% confidence interval [CI]: 0.48 to 0.75). Notably, pronounced increasing trends were observed in Tropical Latin America, and North Africa and Middle East. However, incident trends of SHF and UFI declined globally, with the respective EAPCs being −0.68 (95% CI: −0.83 to −0.54) and −0.98 (95% CI: −1.19 to −0.77). In 2019, the ASR of death due to PVF, SHF, and UFI were 2.23, 0.65, and 0.26, and that of DALYs were 127.56, 28.10, and 17.64, respectively. Decreasing trends in the ASRs of FV were observed in most regions and countries worldwide over the past three decades, particularly that of PVF in Estonia.ConclusionThe FV burden was heterogeneous across regions and countries, which was deeply subjected to socioeconomic factors. The findings highlighted that specific prevention strategies and interventions were required, particularly in the high prevalent settings.

Background We investigated college students’ attitude and compliance towards a prevention strategy involving use of non-pharmaceutical interventions (NPIs) against coronavirus disease 2019 (COVID-19). Methods We conducted a cross-sectional online survey in four universities in Guangdong Province (China) based on purposive sampling. A self-administered questionnaire was given to College students (CSs) to measure the supportive attitude towards an outbreak control strategy and adoption of NPIs in respondents. Results A total of 44,446 CSs participated between 31 January and 10 February 2020; 92.7% of respondents supported the outbreak control strategy. The proportion of respondents who avoided public places, wore a facemask, avoid gatherings, and washed hands more frequently than usual was 94.8, 92.8, 91.2 and 86.9%. respectively. A total of 76.5% respondents adopted all four measures. A supportive attitude was associated with NPI adoption. Students who were female, postgraduate, anxious, and not depressed tended to have a higher supportive attitude and higher chance of NPI adoption. Conclusions Higher supportiveness towards the disease control strategy for the Chinese public may lead to higher adoption rate of NPIs. Psychosocial factors were related to a supportive attitude and adoption of the NPI. We believe that our findings could aid policymakers to create NPIs to prevent and control emerging infectious diseases such as COVID-19.

Previous observational studies have suggested an association between coffee intake and reduced risk for death, but these studies did not distinguish between coffee consumed with sugar or artificial sweeteners and coffee consumed without.To evaluate the associations of consumption of sugar-sweetened, artificially sweetened, and unsweetened coffee with all-cause and cause-specific mortality.Prospective cohort study.Data were extracted from the UK Biobank.A total of 171 616 participants (mean age, 55.6 years [SD, 7.9]) without cardiovascular disease (CVD) or cancer at baseline were eligible. Baseline demographic, lifestyle, and dietary data from the UK Biobank were used, with follow-up beginning in 2009 and ending in 2018.Dietary consumption of sugar-sweetened, artificially sweetened, and unsweetened coffee was self-reported. All-cause, cancer-related, and CVD-related mortality were estimated.During a median follow-up of 7.0 years, 3177 deaths were recorded (including 1725 cancer deaths and 628 CVD deaths). Cox models with penalized splines showed U-shaped associations of unsweetened coffee, sugar-sweetened coffee, and artificially sweetened coffee with mortality. Compared with nonconsumers, consumers of various amounts of unsweetened coffee (0 to 1.5,1.5 to 2.5,2.5 to 3.5,3.5 to 4.5, and4.5 drinks/d) had lower risks for all-cause mortality after adjustment for lifestyle, sociodemographic, and clinical factors, with respective hazard ratios of 0.79 (95% CI, 0.70 to 0.90), 0.84 (CI, 0.74 to 0.95), 0.71 (CI, 0.62 to 0.82), 0.71 (CI, 0.60 to 0.84), and 0.77 (CI, 0.65 to 0.91); the respective estimates for consumption of sugar-sweetened coffee were 0.91 (CI, 0.78 to 1.07), 0.69 (CI, 0.57 to 0.84), 0.72 (CI, 0.57 to 0.91), 0.79 (CI, 0.60 to 1.06), and 1.05 (CI, 0.82 to 1.36). The association between artificially sweetened coffee and mortality was less consistent. The association of coffee drinking with mortality from cancer and CVD was largely consistent with that with all-cause mortality. U-shaped associations were also observed for instant, ground, and decaffeinated coffee.Exposure assessed at baseline might not capture changes in intake over time.Moderate consumption of unsweetened and sugar-sweetened coffee was associated with lower risk for death.National Natural Science Foundation of China, Young Elite Scientist Sponsorship Program by CAST, and Project Supported by Guangdong Basic and Applied Basic Research Foundation.

As one of the fatal complications, venous thromboembolism (VTE) is associated with increased mortality. However, the combined effects of adopting multiple healthy lifestyles have not been firmly demonstrated. This study was to evaluate the association of combined healthy lifestyles and genetic risk factors with VTE and to investigate their interaction. A prospective cohort study from UK Biobank with a total of 442,963 men and women aged between 38 to 73 years were recruited from 2006 to 2010 and followed up through 2017 or 2018. A polygenic risk score was constructed and a weighted healthy lifestyle score, including no current smoking, regular physical exercises, healthy diet, and healthy body mass index, was categorized. During a median follow-up 9.0 years (3,912,396 person-years), there were 6,736 (172 per 100,000 person-years) incident VTE cases recorded. Among the participants with an unfavorable lifestyle, 1.80% developed VTE, versus 1.03% of the participants with a favorable lifestyle (hazard ratio [HR]: 1.58; 95% confidence interval [CI]: 1.48–1.68). Of the participants with high genetic risk, 2.42% developed VTE, versus 0.97% of the participants with low genetic risk (HR: 2.60; 95% CI: 2.39–2.81). Moreover, of the participants with high genetic risk and unfavorable lifestyle, 2.90% developed VTE, versus 0.66% of the participants with low genetic risk and favorable lifestyle (HR: 4.09; 95% CI: 3.48–4.79). No significant interaction between genetic risk and lifestyle factors was observed (p for interaction = 0.727). An unfavorable lifestyle was associated with a substantially higher risk of VTE, regardless of the genetic risk strata.

Polarization conversion metasurfaces are widely used in optical devices, microwave devices and communication systems, owing to their unique polarization modulation characteristics. However, in some applications (such as folded reflectarrays), the unit cell must be capable of polarization conversion and phase modulation. To the best of our knowledge, there are only a few related designs with both the functionalities. In this paper, we propose a well-performing 1-bit reconfigurable coding metasurface with polarization conversion. It realizes linear-to-linear polarization conversion in a 1.32 GHz bandwidth, and the conversion loss is within 1 dB. Simultaneously, the metasurface achieves a phase difference of approximately 180° by switching the working state of the PIN diodes. This metasurface has great potential for radar detection, folded reflectarrays, and other fields.

Exposure to trichloroacetic acid (TCAA) has been associated with impaired semen quality; however, its association with spermatozoa apoptosis and DNA damage remains unclear. We, therefore, collected single semen and repeated urine samples from male partners of couples attending a reproductive center, which were measured for spermatozoa apoptosis and DNA damage parameters and TCAA concentrations, respectively. Multivariable linear regression models were used to explore the associations between urinary TCAA concentrations and spermatozoa apoptosis (

Background Candidate genes of neuromuscular junction (NMJ) pathway increased risk of frailty, but the extent and whether can be offset by exercises was unclear. The aim of this study was to investigate the association between aerobic exercises and incident frailty regardless of NMJ pathway‐related genetic risk. Methods A cohort study on participants from Chinese Longitudinal Healthy Longevity Survey was conducted from 2008 to 2011. A total of 7006 participants (mean age of 80.6 ± 10.3 years) without frailty at baseline were interviewed to record aerobic exercise status, and 4053 individuals among them submitted saliva samples. NMJ pathway‐related genes were genotyped and weighted genetic risk scores were constructed. Results During a median follow‐up of 3.1 years (19 634 person‐years), there were 1345 cases (19.2%) of incident frailty. Persistent aerobic exercises were associated with a 26% lesser frailty risk [adjusted hazard ratio (HR) = 0.74, 95% confidence interval (CI) = 0.64–0.85]. This association was stronger in a subgroup of 1552 longevous participants (age between 90 and 111 years, adjusted HR = 0.72, 95% CI = 0.60–0.87). High genetic risk was associated with a 35% increased risk of frailty (adjusted HR = 1.35, 95% CI = 1.16–1.58). Of the participants with high genetic risk and no persistent aerobic exercises, there was a 59% increased risk of frailty (adjusted HR = 1.59, 95% CI = 1.20–2.09). HRs for the risk of frailty increased from the low genetic risk with persistent aerobic exercise to high genetic risk without persistent aerobic exercise (P trend

Objective we aimed to investigate the association of smoking cessation with risk of all-cause mortality amongst oldest old people (aged ≥ 80 years). Design this was a prospective cohort study. Setting the Chinese Longitudinal Healthy Longevity Survey, implemented in 23 provinces of China. Participants a total of 28,643 community-dwelling oldest old people (mean age, 92.9 ± 7.5 years) were included. Methods in this community-based cohort study, Cox proportional hazards models were used to examine the association of smoking cessation with risk of all-cause mortality. Results during 136,585 person-years of follow-up from baseline to 1 September 2014, compared with never smokers, hazard ratios and 95% confidence intervals for all-cause mortality were 1.06 (1.02–1.10) for current smokers, 1.23 (1.09–1.39) for transient quitters (≤1 consecutive years since smoking cessation), 1.22 (1.12–1.32) for recent quitters (2–6 consecutive years since smoking cessation) and 1.11 (1.02–1.22) for long-term quitters (>6 consecutive years since smoking cessation). Cox models with penalised splines revealed an increased risk of all-cause mortality after smoking cessation; the highest mortality risk was observed within 2–4 years after smoking cessation and the risk gradually decreased with duration of smoking cessation. We further conducted subgroup analyses and sensitivity analyses to reduce the impact of reverse causation. Conclusions smoking is harmful to health in all populations. Our study findings indicated smoking cessation in late life to be associated with increased risk of all-cause mortality amongst oldest old people who have smoked for a long time.

As the proportion of the elderly population increases, more and more people suffer from aging-related diseases. Even if aging is inevitable, prolonging the time of healthy aging, delaying the progression of aging-related diseases, and the incidence of morbidity can greatly alleviate the pressure on individuals and society. Current research and exploration in the field of materials related to aging are expanding tremendously. Here, we present a summary of recent research in the field of nanomaterials relevant to aging. Some nanomaterials, such as silica nanomaterials (NMs) and carbon nanotubes, cause damage to the cells similar to aging processes. Other nanomaterials such as fullerenes and metalbased nanomaterials can protect the body from endogenous and exogenous harmful substances such as ROS by virtue of their excellent reducing properties. Another new type of nucleic acid nanomaterial, tetrahedral framework nucleic acids, works effectively against cell damage. This material selectively clears existing senescent cells in the tissue and thus prevents the development of the chronic inflammatory environment caused by senescent cells secreting senescence-associated secretory phenotype to the surroundings. We believe that nanomaterials have tremendous potential to advance the understanding and treatment of aging-related disorders, and today's research only represents the beginning stages.

BACKGROUND The high-degree atrioventricular block (HAVB) in patients with bicuspid aortic valve (BAV) treated with transcatheter aortic valve implantation (TAVI) remains high. The study aims to explore this poorly understood subject of mechanisms and predictors for HAVB in BAV self-expandable TAVI patients. METHODS We retrospectively included 181 BAV patients for analysis. Using computed tomography data, the curvature of ascending aorta (AAo) was quantified by the angle (AAo angle) between annulus and the cross-section at 35 mm above annulus (where the stent interacts with AAo the most). The valvular anatomy and leaflet calcification were also characterized. RESULTS The 30-day HAVB rate was 16.0% (median time to HAVB was three days). Type-1 morphology was found in 79 patients (43.6%) (left- and right-coronary cusps fusion comprised 79.7%). Besides implantation below membrane septum, large AAo angle [odds ratio (OR) = 1.08, P = 0.016] and type-1 morphology (OR = 4.97, P = 0.001) were found as the independent predictors for HAVB. Together with baseline right bundle branch block, these predictors showed strong predictability for HAVB with area under the cure of 0.84 (sensitivity = 62.1%, specificity = 92.8%). Bent AAo and calcified raphe had a synergistic effect in facilitating high implantation, though the former is associated with at-risk deployment (device implanted above annulus + prothesis pop-out, versus straight AAo: 9.9% vs. 2.2%, P = 0.031). CONCLUSIONS AAo curvature and type-1 morphology are novel predictors for HAVB in BAV patients following self-expandable TAVI. For patients with bent AAo or calcified raphe, a progressive approach to implant the device above the lower edge of membrane septum is favored, though should be done cautiously to avoid pop-out.