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Background: Little is known about the long-term risks of stroke and ischemic heart disease (IHD) in women who had a hysterectomy alone (HA) or with bilateral oophorectomy (HBO) for benign diseases, particularly in China where the burden of cardiovascular diseases (CVD) is high. We assessed mean levels of cardiovascular risk factors and relative risks of stroke and IHD in Chinese women who had a HA or HBO. Methods: A total of 302 510 women, aged 30 to 79 years were enrolled in the China Kadoorie Biobank from 2004 to 2008 and followed up for a mean of 9.8 years. The analysis involved premenopausal women without prior cardiovascular disease or cancer at enrollment. We calculated adjusted hazard ratios for incident cases of CVD and their pathological types (ischemic stroke, hemorrhagic stroke, and IHD) after HA and HBO. Analyses were stratified by age and region and adjusted for levels of education, household income, smoking status, alcohol consumption, physical activity, body mass index, systolic blood pressure, diabetes, self-reported health, and number of pregnancies. Results: Among 282 722 eligible women, 8478 had HA, and 1360 had HBO. Women who had HA had 9% higher risk of CVD after HA (hazard ratio, 1.09 [95% CI, 1.06–1.12]) and 19% higher risk of CVD after HBO (1.19 [95% CI, 1.12–1.26]) compared with women who did not. Both HA and HBO were associated with higher risks of ischemic stroke and IHD but not with hemorrhagic stroke. The relative risks of CVD associated with HA and HBO were more extreme at younger age of surgery. Conclusions: Women who had either HA or HBO have higher risks of ischemic stroke and IHD, and these risks should be evaluated when discussing these interventions. Additional screening for risk factors for CVD should be considered in women following HA and HBO operations, especially if such operations are performed at younger age.

Symmetrical multi-inlet vortex separators/reactors have been demonstrated to be beneficial for gas-particle separation and mass transfer, but their internal energy dissipation has remained unknown. This work designed a series of microscale vortex separators/reactors with single-, dual-, and quadruple inlet(s), to conduct a comparative investigation on their energy-loss characteristics and nature. The response of energy loss to inlet configuration and flow rate was experimentally determined. It is found that in 30–100 L/min flow rate, the Euler number depends insignificantly upon the Reynolds number. The introduction of the multi-inlets improves the symmetry of the flow pattern but increases the gradients of vortex velocity and static pressure. RSM-based CFD simulation can effectively reveal the effect of multiple inlets on the inside flow, static pressure, and energy-loss composition. Finally, an improved semi-empirical correlation of energy loss was developed. The results may provide a positive reference for the design, optimization, and application of vortex-based separators/reactors.

Cyclone separators have been widely used for gas–particle separation in chemical engineering. However, their enhancement in separation performances usually increases the pressure drop, which inevitably leads to an increase in operating energy consumption. One of the challenging issues is how to reduce the cyclone pressure drop while improving separation performances. To gain insight into the pathways and impacts of cyclone pressure drop reduction, this work reviews the state-of-the-art technical principles, performances and effects, focusing on the processes, mechanisms, and characteristics of pressure drop reduction by inlet/outlet variations, additional auxiliary devices, local cyclone dimension improvement, and global optimization based on intelligent algorithms. The cyclone performances are assessed using a proposed index that combines the Euler number and the square-root particle cut-off Stokes number. It is suggested that the pressure drop and separation capability usually have a dynamic compromise. Considering the comprehensive performances, the technology using helical roof inlet, cross cone, increasing cylindrical height with h/D = 4.3 (H/D = 6.35), and globally optimized design by Sun et al. (2017) are respectively considered to the others. Particularly, the last one is recommended to be more representative in practice. Finally, the key issues to be considered in further research were also prospected.

The potential for mitigating climate change is growing worldwide, with an increasing emphasis on reducing CO2 emissions and minimising the impact on the environment. African continent is faced with the unique challenge of climate change whilst coping with extreme poverty, explosive population growth and economic difficulties. CO2 emission patterns in Africa are analysed in this study to understand primary CO2 sources and underlying driving forces further. Data are examined using gravity model, logarithmic mean divisia index and Tapio's decoupling indicator of CO2 emissions from economic development in 20 selected African countries during 1984-2014. Results reveal that CO2 emissions increased by 2.11% (453.73 million ton) over the research period. Gravity centre for African CO2 emissions had shifted towards the northeast direction. Population and economic growth were primary driving forces of CO2 emissions. Industrial structure and emission efficiency effects partially offset the growth of CO2 emissions. The economic growth effect was an offset factor in central African countries and Zimbabwe due to political instability and economic mismanagement. Industrial structure and emission efficiency were insufficient to decouple economic development from CO2 emissions and relieve the pressure of population explosion on CO2 emissions in Africa. Thus, future efforts in reducing CO2 emissions should focus on scale-up energy-efficient technologies, renewable energy update, emission pricing and long-term green development towards sustainable development goals by 2030.

Since the promulgation of the first school education regulations in the early 20th century, Chinese school aesthetic education has gone through its first century of history. Six stages of development have been formed in this century of vicissitudes, namely, the budding period, the starting period, the salvation movement period, the tortuous development period, the reconstruction period, and the modernization period of the new era. From a historical point of view, we can sort out and analyze the policies of school aesthetic education, and we can learn that Chinese school aesthetic education has always insisted on the direction of building socialism with Chinese characteristics, guided by the principles of Marxist aesthetics and the achievements of specific Chinese practice as the methodology, adhered to the direction of cultural development of socialism with Chinese characteristics, and aimed at cultivating qualified builders and successors for the comprehensive development of socialism with Chinese characteristics. Aesthetic education in Chinese schools places a prominent place on “establishing, cultivating and clarifying morality”, emphasizes the role of “beauty” in “goodness”, and follows the aesthetic guideline of “unity of beauty and goodness”. Art education and its practical activities are the main content of school aesthetic education. The formation mechanism, laws, and characteristics of the sustainable development of school aesthetic education in China are summarized from the perspective of the century-old school aesthetic education policy, which is of theoretical guidance for the study of the future development of school aesthetic education in China.

Background Tobacco smoking is estimated to account for more than 1 million annual deaths in China, and the epidemic continues to increase in men. Large nationwide prospective studies linked to different health records can help to periodically assess disease burden attributed to smoking. We aimed to examine associations of smoking with incidence of and mortality from an extensive range of diseases in China. Methods We analysed data from the prospective China Kadoorie Biobank, which recruited 512 726 adults aged 30–79 years, of whom 210 201 were men and 302 525 were women. Participants who had no major disabilities were identified through local residential records in 100–150 administrative units, which were randomly selected by use of multistage cluster sampling, from each of the ten diverse study areas of China. They were invited and recruited between June 25, 2004, and July 15, 2008. Upon study entry, trained health workers administered a questionnaire assessing detailed smoking behaviours and other key characteristics (eg, sociodemographics, lifestyle, and medical history). Participants were followed up via electronic record linkages to death and disease registries and health insurance databases, from baseline to Jan 1, 2018. During a median 11-year follow-up (IQR 10–12), 285 542 (55·7%) participants were ever hospitalised, 48 869 (9·5%) died, and 5252 (1·0%) were lost to follow-up during the age-at-risk of 35–84 years. Cox regression yielded hazard ratios (HRs) associating smoking with disease incidence and mortality, adjusting for multiple testing. Findings At baseline, 74·3% of men and 3·2% of women (overall 32·4%) ever smoked regularly. During follow-up, 1 137 603 International Classification of Diseases, 10th revision (ICD-10)-coded incident events occurred, involving 476 distinct conditions and 85 causes of death, each with at least 100 cases. Compared with never-regular smokers, ever-regular smokers had significantly higher risks for nine of 18 ICD-10 chapters examined at age-at-risk of 35–84 years. For individual conditions, smokers had significantly higher risks of 56 diseases (50 for men and 24 for women) and 22 causes of death (17 for men and nine for women). Among men, ever-regular smokers had an HR of 1·09 (95% CI 1·08–1·11) for any disease incidence when compared with never-regular smokers, and significantly more episodes and longer duration of hospitalisation, particularly those due to cancer and respiratory diseases. For overall mortality, the HRs were greater in men from urban areas than in men from rural areas (1·50 [1·42–1·58] vs 1·25 [1·20–1·30]). Among men from urban areas who began smoking at younger than 18 years, the HRs were 2·06 (1·89–2·24) for overall mortality and 1·32 (1·27–1·37) for any disease incidence. In this population, 19·6% of male (24·3% of men residing in urban settings and 16·2% of men residing in rural settings) and 2·8% of female deaths were attributed to ever-regular smoking. Interpretation Among Chinese adults, smoking was associated with higher risks of morbidity and mortality from a wide range of diseases. Among men, the future smoking-attributed disease burden will increase further, highlighting a pressing need for reducing consumption through widespread cessation and uptake prevention. Funding British Heart Foundation, Cancer Research UK, Chinese Ministry of Science and Technology, Kadoorie Charitable Foundation, UK Medical Research Council, National Natural Science Foundation of China, Wellcome Trust.

The purpose of this study was to analyze the influence of the injection pressure and orifice diameter on the spray characteristics of soybean biodiesel. The macroscopic spray characteristics of the spray tip penetration (STP) and spray cone angle (SCA) were tested with a high-speed camera system. The microscopic spray characteristics, such as the statistical size distribution, Sauter mean diameter (SMD), representative diameters and dispersion boundary, were obtained using a Malvern laser particle size analyzer (PSA). The test results showed that with an increasing injection pressure, the STP and the SCA of the biodiesel increased, but the curves of size-volume distribution and cumulative volume distribution of the atomized droplets shifted to smaller diameters. The SMD and representative diameters decreased, and the dispersion boundary was reduced. Moreover, with a decreasing orifice diameter, longer STP and smaller SCA values were observed. Similarly, the size distribution curves of the atomized biodiesel droplets shifted to smaller diameters. The SMD and representative diameters were reduced, and the relative size range of the atomized biodiesel droplets was enlarged. Higher injection pressures and smaller orifice diameters improved the biodiesel atomization; however, the smaller orifice diameters caused an inhomogeneous size distribution of the atomized biodiesel droplets.

To investigate the clinical efficacy and safety of polaprezinc compared with rebamipide in the treatment of gastric ulcers (GU).GU patients (n = 224) from 10 clinical centers were prospectively enrolled and randomly divided into a control (n = 113) or test (n = 111) group. The control group was treated with rebamipide tablets, while the test group was treated with polaprezinc. The primary endpoint was the effective treatment rate, which was confirmed by gastroscopy after 8 weeks of treatment. The secondary efficacy endpoint was the improvement rate of gastrointestinal symptoms after 4 and 8 weeks of treatment.The basic characteristics of the two groups were well balanced. For the primary efficacy endpoint, the effective rates confirmed by gastroscopy, after treatment for the test and control groups were 81.48% and 74.31% (P = 0.1557), respectively. After 4 and 8 weeks of treatments, both treatment groups had comparable improvements rates in gastrointestinal symptoms (test vs. control: 44.44% vs. 39.45% [P = 0.4559] and 81.48% vs. 77.06% [P = 0.4223]). Further, the two groups had similar adverse events and reactions to the study drugs.These findings suggest that the efficacy and safety of polaprezinc were similar to those of rebamipide in the treatment of GU.

Background Adherence to a healthy lifestyle is associated with substantially lower risks of mortality from all causes, cardiovascular diseases, and cancer in white populations. However, little is known about the health benefits among non-white populations. Also, no previous studies have focused on respiratory disease mortality in both white and non-white populations. We assessed the relationships between a combination of healthy lifestyle factors and multiple death outcomes in Chinese adults. Methods This study included 487,198 adults aged 30–79 years from the China Kadoorie Biobank without heart disease, stroke, and cancer at study enrolment. We defined five healthy lifestyle factors as never smoking or smoking cessation not due to illness; non-daily drinking or moderate alcohol drinking; median or higher level of physical activity; a diet rich in vegetables, fruits, legumes and fish, and limited in red meat; a body mass index of 18.5 to 27.9 kg/m2 and a waist circumference Results During a median follow-up of 10.2 years (IQR 9.2–11.1), we documented 37,845 deaths. After multivariable adjustment, the number of healthy lifestyle factors exhibited almost inverse linear relationships with the risks of all-cause and cause-specific mortality. Compared with participants without any healthy factors, the hazard ratio of participants with five healthy factors was 0.32 [95% confidence interval (CI): 0.28, 0.37] for all-cause mortality. The corresponding HRs in specific cause of death were 0.42 (95% CI: 0.26, 0.67) for ischaemic heart disease, 0.21 (95% CI: 0.09, 0.49) for ischaemic stroke, 0.37 (95% CI: 0.22, 0.60) for haemorrhage stroke, 0.36 (95% CI: 0.29, 0.45) for cancer, 0.26 (95% CI: 0.14, 0.48) for respiratory diseases, and 0.29 (95% CI: 0.22, 0.39) for other causes. Theoretically, 38.5% (95% CI: 33.0, 43.8%) of all-cause mortality was attributable to nonadherence to a healthy lifestyle, and the proportions of preventable deaths through lifestyle modification ranged from 26.9 to 47.9% for cause-specific mortality. Conclusions Adherence to a healthy lifestyle was associated with substantially lower risks of all-cause, cardiovascular, respiratory, and cancer mortality in Chinese adults. Promotion of a healthy lifestyle may considerably reduce the burden of non-communicable diseases in China.

A general framework for the analysis of the urban water-energy nexus (WEN) was proposed and a dynamic and quantitative WEN model was developed based on the Long-range Energy Alternatives Planning System (LEAP) and Water Evaluation and Planning (WEAP) tools. Using Xiamen, China, as a case study, eleven future scenarios were designed to explore the impacts of different factors, from both supply and demand sides, on urban WEN. Both water-related energy (WRE) and energy-related water (ERW) were studied to reveal the interconnected relationship between water and energy. We found that most WRE and ERW savings lie on the supply side, except for demand management scenarios, and most scenarios have larger trans-boundary effects than in-boundary effects due to the import of large quantities of energy and water. Industry structure adjustments (oriented toward energy or water savings) and energy-saving measures have better co-benefits in terms of energy and water savings than other measures. Promoting electric vehicles increases electricity imports and related trans-boundary ERW. Such effects should be considered before importing resources from outside city boundaries. Developing high-tech industries might also increase energy or water burdens. Finally, the boundaries of urban WEN research were discussed to promote additional comparable studies.

The water footprint (WF) vividly links water resources with virtual water of food, providing a novel perspective on food demand and water resources management. This study estimates the per capita WF of food consumption for six provinces in North China. Then, the study applies the logarithmic mean Divisia index method to decompose the driving forces of their WF changes. Results show that the per capita WF of food consumption in Beijing, Tianjin, and Inner Mongolia increases significantly in 2005–2017, whereas that in the other three provinces in North China varies slightly. All provinces have shown the same trend of food structure changes: the grain decreased, whereas the meat increased. In general, the urban effect was positive, and the rural effect was negative for all regions. The urban effects in Beijing and Tianjin played a leading role, whereas the rural effects in the other four provinces played a leading role from 2005–2009. However, the urban effects in all provinces played a leading role in 2010–2017. The WF efficiency increased in each province, and the effect in urban areas is stronger due to the higher water use efficiency. For most provinces, the consumption structure was positive because the diet shifted toward more meat consumption. The food consumption per capita effect was the major driving force in Beijing and Tianjin due to the increased consumption level, whereas the population proportion effect exerted a weak effect. To alleviate the pressure on water resources, further improving water use efficiency in food production and changing the planting structure should be emphasized for all regions in North China.

Background and aims Observational studies have associated resting heart rate with incident diabetes. Whether the associations are causal remains unclear. We aimed to examine the shape and strength of the associations and assessed the causal relevance of such associations in Chinese adults. Methods and results The China Kadoorie Biobank enrolled 512,891 adults in China. Cox proportional hazard regression models was conducted to estimate hazard ratios (HRs) for the associations of resting heart rate with type 2 diabetes and total diabetes. Among 92,724 participants, 36 single-nucleotide polymorphisms (SNPs) related to resting heart rate were used to construct genetic risk score. We used Mendelian randomization analyses to make the causal inferences. During a median follow-up of 9 years, 7872 incident type 2 diabetes and 13,349 incident total diabetes were documented. After regression dilution bias adjustment, each 10 bpm higher heart rate was associated with about a 26% higher risk of type 2 diabetes (HR, 1.26 [95% CI, 1.23, 1.29]) and 23% higher risk of total diabetes (HR, 1.23 [95% CI, 1.20, 1.26]). Instrumental variable analyses showed participants at top quintile compared with those at bottom quintile had 30% higher risk for type 2 diabetes (HR, 1.30 [95% CI, 1.17, 1.43]), and 10% higher risk for total diabetes (HR, 1.10 [95% CI, 1.02, 1.20]). Conclusions This study provides evidence that resting heart rate is an important risk factor for diabetes risk. The results suggest that novel treatment approaches targeting reduction of high heart rate for incidence of diabetes may be worth further investigation.

Elymus tangutorum (Nevski) Handel-Mazzetti (Poaceae: Triticeae), a hexaploid perennial herb, is a kind of forage plant with large biomass. In this study, the complete plastome sequence of E. tangutorum was reported. The size of the plastome is 134,949 bp in length, including a large single copy region (LSC) of 80,556 bp, a small single copy region (SSC) of 12,767 bp, and a pair of inverted repeat (IR) regions with 20,813 bp. Moreover, a total of 131 functional genes were annotated, including 85 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. The maximum likelihood (ML) phylogenetic tree suggested that E. tangutorum was closely related to Elymus libanoticus and Dasypyrum villosum.

A carbon footprint (CF) assessment of Chinese high‐speed railways (HSRs) can help guide further development of the world's longest HSR network. In this research, a hybrid economic input‐output and life cycle assessment (EIO‐LCA) method was applied to estimate the CF of the Beijing‐Shanghai HSR line. Specific CFs were analyzed of different subsystems of the line, different stages of production, and three calculation scopes. Results showed that the annual CF of the Beijing‐Shanghai HSR is increasing, whereas the per‐passenger CF constantly declined between 2011 and 2014. Scope 1 emissions account for an average of 4% of the total annual CF, Scope 2 contribute 71%, and Scope 3 comprise 25%. Among the different stages, operation contributes the largest (71%), followed by construction (20%) and maintenance (9%). In the construction stage, the bridges have the largest CF, followed by trains, and then rails. A trade‐off exists between the increase in carbon emissions due to construction of bridges and the reduction in operation emissions affected by leveling changes in terrain. The Beijing‐Shanghai HSR line has a relatively higher per‐passenger CF than eight other HSR lines, which is largely due to China's coal‐based carbon‐intensive energy mix of electricity generation, high proportion of bridges, higher operating speed, and heavier train body. In the future, cleaner electricity supply options, more efficient raw material production, and improvement of trains are keys to reducing the CF of Chinese HSRs.

The environmental footprints of China&rsquo, s high-speed railway (HSR) have attracted much attention nationally and internationally. Although there is some research focusing on CO2 emissions, a comprehensive environmental impacts assessment of HSR construction is still lacking. In this study, the emissions of the Beijing&ndash, Tianjin intercity HSR line was calculated using a hybrid input&ndash, output life cycle assessment method to quantify the environmental impacts of HSR throughout its construction. The environmental footprints during the construction stage were analyzed in terms of different subsystems and sectors. The results showed that bridges contribute the largest environmental footprints at approximately 60%, followed by rail and electric multiple unit (EMU) systems. The top three sectors that contribute to pollutant emissions are the metal smelting and rolling industry, transport equipment manufacturing, and non-metallic mineral production. CO2 and NOx are the major pollutants directly emitted by site equipment operation. More chemical oxygen demand (COD), total phosphorus (TP), total nitrogen (TN), and petroleum are emitted in EMU production than in rail construction, while NH3-N is emitted more in rails instead. Cd, Pb, As, and Hg are the significant pollutants in the metal smelting and rolling industry, whereas Cr, Cu, and Zn are the main heavy metal emissions in the transport equipment manufacturing sector. Heavy metals are the main types of environmental footprints in bridges, stations, and electric systems. Water pollutants are the main environmental impacts for rail and EMU systems, and the emissions of air pollutants are significant in subgrades. The production efficiency of upstream materials, desulfurization and denitration in fossil combustion, and the length of the bridge construction should be considered for an HSR under construction, in order to become environmentally friendly and sustainable.

This paper reports a non-phase separation method to prepare a novel type of Janus vesicle, which contains different quantum dots (QDs) in its two hemispheres. The Janus vesicles were generated through the fusion of cyclodextrin or adamantane-functionalized hyperbranched polymer vesicles incorporated with QDs, driven by the intervesicular host–guest molecular recognition. Both the vesicle structure and the real-time membrane fusion process were revealed under fluorescence microscopy, by taking advantage of the giant size, great stability, and controllable surface functionality of the hyperbranched polymer vesicles (BPs). More interestingly, a potential magnetically controlled printing application of the Janus vesicles with Fe3O4-containing hemispheres by their monolayer patterning in water was demonstrated, which realized the first “printing” of ordered vesicles.

Due to the impacts of globe climate change and human activities, dramatic variations in runoff and sediment load were observed for the Yellow River. Analyses of nearly 65 years’ data measured at main hydrologic-stations on the Yellow River from 1950 to 2014 indicated that, except for the Tangnaihai station in the head region, sharp downward trends existed in both the annual runoff and annual sediment load according to the Mann–Kendal trend test; and their abrupt changes occurred in 1986 and in 1980, respectively, according to the rank sum test. Factors affecting the changes in the runoff and sediment load were very complicated. Results indicated that the reducing precipitation and the increasing water consumption were the main causes for the runoff decline, while the impoundment of the Longyangxia Reservoir and its combined operation with the Liujiaxia Reservoir exerted a direct bearing on the abrupt change in the annual runoff. In addition to the sediment load decrease associated with the runoff reduction, the reduced storm intensity, the conducted soil erosion control, and the constructed dam buildings all played an important role in the trends and abrupt changes of sediment load decline.

In this paper, a kind of novel water-soluble chitosan-polydopamine (CHT-PDA) nanoparticles with a hydrodynamic diameter (Dh) around 10 nm were reported by the combination of self-polymerization of PDA and electrostatic complexation between PDA and CHT in water/DMSO (W/D) mixture at the molar fraction of DMSO (xDMSO = 0.37). The preparation method was efficient with a yield of 98% around. The as-prepared water-soluble CHT-PDA nanoparticles exhibited effective UV-screen ability, enhanced visible-light transmittance and good cytocompatibility via MTT assay, which might be used in transparent formulation for UV protection usage, especially in biological field including sun care application.

Cornus bretschneideri L.Henry (Cornaceae), a shrub or small tree, is a potential horticultural plant or a soil-fixing plant. In this study, the complete sequence and characterization of the chloroplast genome of C. bretschneideri was studied. The size of the chloroplast genome is 158,270 bp in length, including a large single copy region (LSC) of 87,466 bp, a small single copy region (SSC) of 18,730 bp, and a pair of inverted repeat (IR) regions with 26,037 bp. The GC content of the chloroplast genome was 37.86%. Moreover, a total of 132 functional genes were annotated, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The neighbor-joining phylogenetic tree suggested that C. bretschneideri was closely related to C. sanguinea and C. macrophylla.

Background Lean body mass has been identified as a key determinant of left ventricular mass and wall thickness. However, the importance of lean body mass or other body‐size measures as normative determinants of carotid intima‐media thickness ( cIMT ), a widely used early indicator of atherosclerosis, has not been well established. Methods and Results Carotid artery ultrasound measurements of cIMT and carotid artery plaque burden (derived from plaque number and maximum size) and measurements of body size, including height, body mass index, weight, body fat proportion, and lean body mass ([1−body fat proportion]×weight), were recorded in 25 020 participants from 10 regions of China. Analyses were restricted to a healthy younger subset (n=6617) defined as never or long‐term ex‐regular smokers aged cIMT , but was not associated with plaque burden: overall, each 10 kg higher lean body mass was associated with a 0.03 (95% CI , 0.03–0.04) mm higher cIMT ( P =5×10 −33 ). Fat mass, height, and other body‐size measures were more weakly associated with cIMT . Conclusions The strong association of lean body mass with cIMT, but not with plaque burden, in healthy adults suggests a normative relationship rather than reflecting atherosclerotic pathology. Common mechanisms may underlie the associations of lean body mass with cIMT and with nonatherosclerotic vascular traits.

A pre-mixing and post-polymerization strategy has been developed for one-pot preparation of pomegranate-like polydopamine (PDA) stabilized small gold nanoparticles (AuNPs) with sizes smaller than 5 nm in aqueous media. Firstly, the pre-mixing of dopamine (DA) and HAuCl4 was used to generate the Au clusters as nucleating seeds. Secondly, the rapid self-polymerization of DA into polydopamine (PDA) and simultaneous Au redox reaction were initiated when the pH of the reaction system was tuned to 8 by the injection of a NaOH solution into the mixture, leading to the formation of the pomegranate-like PDA–AuNPs nanocomposites with small AuNPs well dispersed inside. The as-prepared nanocomposites exhibited superior stability in high saline conditions (500 mM NaCl) and were able to be coated onto a filter paper to form paper catalysts, which were used as recyclable catalysts for the reduction of high concentrated (50 mM) 4-nitrophenol (4-NP) with a TOF of 1006 h−1.

This cohort study compares observational associations with genetic associations of body mass index with hepatobiliary diseases and liver biomarkers., Key Points Question Are there genetic associations of body mass index with hepatobiliary diseases in the Chinese population? Findings In this cohort study including 473 938 adults, genetically instrumented body mass index was associated with higher risks of hepatobiliary diseases with different underlying causes and was associated with liver biomarkers, steatosis score, and fibrosis score. The genetic associations of body mass index with liver diseases and biomarkers were consistently observed regardless of hepatitis B virus infection. Meaning These findings suggest that maintaining a healthy weight through diet and physical activity may help lower risk of hepatobiliary diseases in Chinese individuals regardless of the underlying causes of disease., Importance There is some support for the existence of genetic associations between adiposity and certain hepatobiliary diseases in Western populations. However, there is little evidence of such genetic associations in China, where the causes of these diseases may differ from those in Western populations and the mean body mass index (BMI) is much lower. Objectives To compare the observational associations of BMI with hepatobiliary diseases and liver biomarkers with the genetic associations between BMI and these factors and to assess whether the genetic associations of BMI with liver diseases differed by hepatitis B virus infection status. Design, Setting, and Participants This cohort study used data from the prospective China Kadoorie Biobank, including 473 938 adults aged 30 to 79 years without hepatobiliary diseases at baseline from 10 diverse areas in China from June 25, 2004, to July 15, 2008. A random sample of 75 736 participants with genotyping data was included in the Mendelian randomization analysis. Follow-up was completed January 1, 2017 (median [interquartile range] length of follow-up, 10.2 [9.2-11.1] years). Data were analyzed from January to October 2019. Exposures Measured BMI obtained during the baseline survey and genetically instrumented BMI derived using 92 single-nucleotide variations. Main Outcomes and Measures Incident cases of hepatobiliary diseases, liver enzymes, fatty liver index, and fibrosis score. Results Among 473 938 individuals (276 041 [58.2%] women), the mean (SD) age was 52 (10.9) years and mean (SD) BMI was 23.8 (3.4). Baseline BMI was associated with higher risks of chronic liver disease (adjusted risk ratio per 1-SD increase, 1.14; 95% CI, 1.11 to 1.17) and gallbladder disease (adjusted risk ratio per 1-SD increase, 1.29; 95% CI, 1.27 to 1.31), with heterogeneity by disease subtype (P

3039 Background: The limitations of chimeric antigen receptor T cells (CAR-T) in solid tumors are immunosuppressive tumor microenvironment and difficult infiltration to tumor. In order to reduce on-target off-tumor toxicities and circumvent the immune-suppressive tumor microenvironment(TME), we modified autologous CAR-T to be specific for mesothelin (MSLN) on cancer cells and secrete PD-1 antibodies (aPD1-MSLN-CAR T cells). Here, we report the safety and efficacy of aPD1-MSLN-CAR T cells in 10 patients with relapsed/refractory solid cancers in this single-arm, open-label, first-in-human phase I pilot study (ClinicalTrial.gov: NCT03615313). Methods: aPD1-MSLN-CAR T cells were prepared from peripheral blood mononuclear cells and engineered using PiggyBac Transposon System to target MSLN and secrete PD-1 antibodies. 10 patients with mesothelin positive relapsed/refractory solid cancers after failure to standard therapies were treated with aPD1-MSLN-CAR T cells for two or more cycles until disease progression or intolerable toxicity. The dose escalation of CAR T cells was designed to be 5×106/kg, 5×107/kg, and 1×108/kg, respectively. Adverse events were evaluated according to CTCAE-V4.03 and clinical response was assessed by RECIST 1.1. CAR expression was analyzed using quantitative real-time polymerase chain reaction. PD-1 antibodies were detected by ELISA. Serum IL-2, IL-4, IL-6, IL-10, IFN-γ and TNF-α were measured using flow cytometry. Results: The most common adverse events were mild fatigue and fever. Abdominal pain was also observed in 1 patient. Grade 1 and 2 cytokine release syndromes were observed without neurologic symptoms in 10 patients. After aPD1-MSLN-mRNA-CAR T cells treatment, 2 patients (20%) achieved partial response (PR), 4 (40%) remained stable (SD), and the rest 4 (40%) patients developed disease progression (PD). The median PFS was 97 days [95% CI (13, 180)] estimated by Kaplan-Meier method. Conclusions: These findings lend support that the combination of modified CAR T cells targeting MSLN with PD1 inhibition for solid tumors is safe. Modified CAR-T cells expressing PD-1 antibodies maybe an option to improve CAR-T efficacy as a result of refined TME. Clinical trial information: NCT03615313 . [Table: see text]