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BackgroundPer- and poly-fluoroalkyl substances (PFAS) are a class of emerging persistent organic pollutants, and their negative health impacts have been widely concerned. There is a lack of epidemiological studies on the associations of PFAS exposure with lipid homeostasis. ObjectiveTo investigate the associations of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) exposure with blood lipid levels and dyslipidemia in middle-aged and elderly women. MethodsThis study was based on 795 middle-aged and elderly women from a female sub-cohort of the Dongfeng-Tongji cohort study, excluding the participants without blood lipid measurements and/or reported use of lipid-lowering drugs at baseline. The concentrations of plasma PFOS and PFOA were measured by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The concentrations of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured using an automatic analyzer. The normally distributed continuous variables were presented as mean ± standard deviation (\begin{document}$ \bar{x}\pm s) $\end{document}, while the skewedly distributed continuous variables were presented as median (M) and the 25th and 75th percentiles (P25, P75). Generalized linear models (GLM), generalized additive models (GAM), and logistic regression models were applied to evaluate the associations of PFOS and PFOA exposure with blood lipid levels and the risk of dyslipidemia. Stratified analyses were also implemented to explore potential modification effects of sociodemographic characteristics, lifestyles, and menopause on associations of PFOS and PFOA exposure and blood lipids. ResultsThe \begin{document}$ \bar{x}\pm s $\end{document} of baseline age for the study participants was (59.4±8.6) years old, and their baseline body mass index (BMI) was (24.3±3.4) kg·m−2. The M (P25, P75) of baseline plasma concentrations for PFOS and PFOA were 9.96 (6.24, 15.09) μg·L−1 and 1.20 (0.84, 1.80) μg·L−1 respectively. The GLM analysis showed that plasma concentration of PFOS was positively associated with serum HDL-C [b (95%CI): 0.04 (0.01, 0.07)]. The plasma concentration of PFOA was also positively associated with serum TC [b (95%CI): 0.05 (0.02, 0.08)] and serum LDL-C [b (95%CI): 0.05 (0.01, 0.09)]. No significant association was observed between plasma PFOS and serum TC, TG, or LDL-C, nor between plasma PFOA and serum TG or HDL-C. The stratified analyses showed that the association between PFOA and LDL-C was significant among the participants aged

Abstract In eukaryotes, the nuclear membrane that encapsulates genomic DNA is composed of an inner nuclear membrane (INM), an outer nuclear membrane (ONM), and a perinuclear space. SUN proteins located in the INM and KASH proteins in the ONM form the SUN-KASH NM-bridge, which functions as the junction of the nucleocytoplasmic complex junction. Proteins containing the SUN domain showed the highest correlation with differentially accumulated proteins (DAPs) in the wheat response to fungal stress. To understand the characteristics of SUN and its associated proteins in wheat responding to pathogen stress, here we investigated and comprehensive analyzed SUN- and KASH-related proteins among the DAPs under fungi infection based on their conserved motifs. In total, four SUN proteins, one WPP domain-interacting protein (WIP), four WPP domain-interacting tail-anchored proteins (WIT), two WPP proteins and one Ran GTPase activating protein (RanGAP) were identified. Following transient expression of Nicotiana benthamiana, TaSUN2, TaRanGAP2, TaWIT1 and TaWIP1 were identified as nuclear membrane proteins, while TaWPP1 and TaWPP2 were expressed in both the nucleus and cell membrane. RT-qPCR analysis demonstrated that the transcription of TaSUN2, TaRanGAP2 and TaWPP1 were strongly upregulated in response to fungal infection. Furthermore, using the bimolecular fluorescence complementation, the luciferase complementation and a nuclear and split-ubiquitin-based membrane yeast two-hybrid systems, we substantiated the interaction between TaSUN2 and TaWIP1, as well as TaWIP1/WIT1 and TaWPP1/WPP2. Silencing of TaSUN2, TaRanGAP2 and TaWPP1 in wheat leaves promoted powdery mildew infection and hyphal growth, and reduced the expression of TaBRI1, TaBAK1 and Ta14-3–3, indicating that these NM proteins play a positive role in resistance to fungal stress. Our study reveals the characteristics of NM proteins and propose the preliminary construction of SUN-WIP-WPP-RanGAP complex in wheat, which represents a foundation for detail elucidating their functions in wheat in future.

Decarbonization of the electric power sector is essential for sustainable development. Low-carbon generation technologies, such as solar and wind energy, can replace the CO2-emitting energy sources (coal and natural gas plants). As a sustainable engineering practice, long-duration energy storage technologies must be employed to manage imbalances in the variable renewable energy supply and electricity demand. Compressed air energy storage (CAES) is an effective solution for balancing this mismatch and therefore is suitable for use in future electrical systems to achieve a high penetration of renewable energy generation. This study introduces recent progress in CAES, mainly advanced CAES, which is a clean energy technology that eliminates the use of fossil fuels, compared with two commercial CAES plants at Huntorf and McIntosh which are conventional ones utilizing fossil fuels. Advanced CAES include adiabatic CAES, isothermal CAES, liquid air energy storage, supercritical CAES, underwater CAES, and CAES coupled with other technologies. The principles and configurations of these advanced CAES technologies are briefly discussed and a comprehensive review of the state-of-the-art technologies is presented, including theoretical studies, experiments, demonstrations, and applications. The comparison and discussion of these CAES technologies are summarized with a focus on technical maturity, power sizing, storage capacity, operation pressure, round-trip efficiency, efficiency of the components, operation duration, and investment cost. Potential application trends were compiled. This paper presents a comprehensive reference for developing novel CAES systems and makes recommendations for future research and development to facilitate their application in several areas, ranging from fundamentals to applications.

This paper studied the numerical approximation of the stochastic differential equations driven by non-global Lipschitz drift coefficient and multiplicative noise. An efficient data-driven method, called extended continuous latent process flow, was proposed for the underlying problem. Compared with the piecewise construction of a variational posterior process used in the classical continuous latent process flow developed by Deng et al. [13], the principle idea of our method was to derive a variational lower bound by constructing a posterior latent process conditional on all information over the whole time interval to maximize the log-likelihood generated by the observations, which reduces the computational cost and, thus, provides a convenient way to approximate the considered equation. Particularly, our new method showed a better approximation to the underlying equation than the classical drift-$ \theta $ discretization scheme through numerical error comparison. Numerical experiments were finally reported to demonstrate the effectiveness and generalization performance of the proposed method.

The introduction of alleles into commercial crop breeding pipelines is both time consuming and costly. Two technologies that are disrupting traditional breeding processes are doubled haploid (DH) breeding and genome editing (GE). Recently, these techniques were combined into a GE trait delivery system called HI-Edit (Haploid Inducer-Edit) [1]. In HI-Edit, the pollen of a haploid inducer line is reprogrammed to deliver GE traits to any variety, obviating recurrent selection. For HI-Edit to operate at scale, an efficient transformable HI line is needed, but most maize varieties are recalcitrant to transformation, and haploid inducers are especially difficult to transform given their aberrant reproductive behaviors. Leveraging marker assisted selection and a three-tiered testing scheme, we report the development of new Iodent and Stiff Stalk maize germplasm that are transformable, have high haploid induction rates, and exhibit a robust, genetically-dominant anthocyanin native trait that may be used for rapid haploid identification. We show that transformation of these elite “HI-Edit” lines is enhanced using the BABYBOOM and WUSCHEL morphogenetic factors. Finally, we evaluate the HI-Edit performance of one of the lines against both Stiff Stalk and non-Stiff Stalk testers. The strategy and results of this study should facilitate the development of commercially scalable HI-Edit systems in diverse crops.

The concept of passenger-centric design has become increasingly significant in the intelligent automotive industry. Enhancing in-cabin thermal comfort while maintaining energy efficiency is crucial, and to this end, we leverage real-time passenger thermal sensation as a basis for HVAC control strategies. This study introduces a non-invasive, dual-phase prediction model that evaluates passenger thermal comfort by utilizing facial thermal imaging and environmental factors. The proposed model employs a deep learning neural network to extract pertinent features from the facial thermal images for an initial prediction. Then this prediction is refined by integrating it with environmental data through a machine learning algorithm, facilitating real-time personal thermal comfort assessment. Data collection for the model was performed across two distinct seasons, with 22 participants in summer and 18 in winter, gathering facial thermal images, environmental parameters, and thermal sensation votes to construct a comprehensive dataset. Analysis revealed a set of critical environmental factors that correlate strongly with thermal sensation votes, which were used as auxiliary features in the model. The performance of the proposed dual-phase approach, combining deep learning and machine learning techniques, demonstrated robust effectiveness on both summer and winter datasets. This substantiates the method's practicality for real-world application within vehicle environments.

Polymethoxyflavones (PMFs) are a type of uncommon dietary flavonoids, characterized by more than one methoxy group, which exist in limited plant species, like Citrus species and Kaempferia parviflora. In addition, different PMFs, such as nobiletin, sinensetin, tangeretin, and casticin, have been isolated from these natural sources. PMFs have received increasing attention due to their multiple bioactivities, such as antioxidant, anti-inflammatory, anti-cancer, metabolic regulatory, immunoregulatory, neuroprotective, and skin protective effects. These bioactivities of PMFs should be associated with the regulation of critical molecular targets and the interaction with gut microbiota. In order to provide a comprehensive and updated review of PMFs, their natural sources, refined extraction, biosynthesis, metabolism, and bioactivities are summarised and discussed, with the emphasis on the molecular mechanisms of PMFs on regulating different chronic diseases. Overall, PMFs may be promising flavonoids to the forefront of nutraceuticals for the prevention and/or treatment of certain human chronic diseases.

Summary: Symmetry analysis is a cutting-edge research approach in physics, yet its application in macroscopic energy systems remains limited. This study demonstrates its potential to provide valuable insights for a deeper understanding and development of thermodynamic cycles. This article first studies the symmetry of the proposed C-P diagrams and finds rich symmetries including reflection symmetry, translation symmetry, and rotational symmetry within Carnot cycles. Then, it emphasizes that one can use symmetry alone to prove that the highest efficiency for any cycle operating in a certain temperature range is the Carnot efficiency, without relying on the entropy concept in the second law of thermodynamics. Lastly, it is found that this symmetry analysis framework can also be used for thermal cycles with phase transitions, as exemplified by applying in Rankine cycles. This research not only contributes groundbreaking insights into unraveling the symmetry inherent in thermodynamic cycles, but also promotes symmetry analysis to be an alternative analysis mean.

Objective: Dementia is an important disease burden among the elderly, and its occurrence may be profoundly affected by environmental factors. Evidence of the relationship between air pollution and dementia is emerging, but the extent to which this can be offset by lifestyle factors remains ambiguous. Methods: This study comprised 155,828 elder adults aged 60 years and above in the UK Biobank who were dementia-free at baseline. Cox proportional hazard models were conducted to examine the associations of annual average levels of air pollutants in 2010, including nitrogen dioxide (NO2), nitrogen oxides (NOX), particulate matter (PM2.5, PM10, and PMcoarse) and lifestyle factors recorded at baseline [physical activity (PA), sleep patterns, or smoking status] with incident risk of dementia, and their interactions on both multiplicative and additive scales. Results: During a 12-year period of follow-up, 4,389 incidents of all-cause dementia were identified. For each standard deviation increase in ambient NO2, NOX or PM2.5, all-cause dementia risk increases by 1.07-fold [hazard ratio (HR) and 95 % confidence interval (CI) = 1.07 (1.04, 1.10)], 1.05-fold (95 % CI: 1.02, 1.08) and 1.07-fold (95 % CI: 1.04, 1.10), whereas low levels of PA, poor sleep patterns, and smoking are associated with an elevated risk of dementia [HR (95 % CI) = 1.17 (1.09, 1.26), 1.13 (1.00, 1.27), and 1.14 (1.07, 1.21), respectively]. Furthermore, these air pollutants show joint effects with low PA, poor sleep patterns, and smoking on the onset of dementia. The moderate to high levels of PA could significantly or marginally significantly modify the associations between NO2, NOX or PM2.5 (P-int = 0.067, 0.036, and 0.067, respectively) and Alzheimer’s disease (AD), but no significant modification effects are found for sleep patterns or smoking status. Conclusion: The increased exposures of NO2, NOX, or PM2.5 are associated with elevated risk of dementia among elderly UK Biobank population. These air pollutants take joint effects with low PA, poor sleep patterns, and smoking on the development of dementia. In addition, moderate to high levels of PA could attenuate the incident risk of AD caused by air pollution. Further prospective researches among other cohort populations are warranted to validate these findings.

Summary: Various energy storage systems (ESS) can be derived from the Brayton cycle, with the most representative being compressed air energy storage and pumped thermal electricity storage systems. Although some important studies on above ESS are reported, the topological structure behind those systems (i.e., derivations of the Brayton cycle) has not been studied, and the underlying thermodynamic ideas still need to be further explored. This paper first introduces the topological structure and the symmetry of ESS and their based Brayton cycles. The formation method of ESS based on paths and separation points is specified. It is found that round-trip path can form ESS directly. Then various ESS formed are compared. Finally, the synergistic effect and gain principle of thermal cycle and ESS are revealed. This work helps to reveal the intrinsic relationship between thermal cycles and ESS, understand the general laws behind ESS, and guide the combination of thermal cycles and ESS.

Epidemiologic studies have reported the positive relationship of benzo[a]pyrene (BaP) exposure with the risk of lung cancer. However, the mechanisms underlying the relationship is still unclear. Plasma microRNA (miRNA) is a typical epigenetic biomarker that was linked to environment exposure and lung cancer development. We aimed to reveal the mediation effect of plasma miRNAs on BaP-related lung cancer. We designed a lung cancer case-control study including 136 lung cancer patients and 136 controls, and measured the adducts of benzo[a]pyrene diol epoxide-albumin (BPDE-Alb) and sequenced miRNA profiles in plasma. The relationships between BPDE-Alb adducts, normalized miRNA levels and the risk of lung cancer were assessed by linear regression models. The mediation effects of miRNAs on BaP-related lung cancer were investigated. A total of 190 plasma miRNAs were significantly related to lung cancer status at Bonferroni adjusted P 2 between plasma samples before and after tumor resection surgery at Bonferroni adjusted P

Abstract Background Patients frequently die from cardiac causes after radiotherapy for esophageal cancer. Early detection of cardiac death risk in these patients is crucial to improve clinical decision‐making and prognosis. Thus, we modeled the risk of cardiac death after irradiation for esophageal cancer. Methods A retrospective analysis of 37,599 esophageal cancer cases treated with radiotherapy in the SEER database between 2000 and 2018 was performed. The selected cases were randomly assigned to the model development group (n = 26,320) and model validation group (n = 11,279) at a ratio of 7:3. We identified the risk factors most commonly associated with cardiac death by least absolute shrinkage and selection operator regression analysis (LASSO). The endpoints for model development and validation were 5‐ and 10‐year survival rates. The net clinical benefit of the models was evaluated by decision curve analysis (DCA) and concordance index (C‐index). The performance of the models was further assessed by creating a receiver operating characteristic curve (ROC) and calculating the area under the curve (AUC). Kaplan‐Meier (K‐M) survival analysis was performed on the probability of death. Patients were classified according to death probability thresholds. Five‐ and ten‐year survival rates for the two groups were shown using K‐M curves. Results The major risk factors for cardiac death were age, surgery, year of diagnosis, sequence of surgery and radiotherapy, chemotherapy and a number of tumors, which were used to create the nomogram. The C‐indexes of the nomograms were 0.708 and 0.679 for the development and validation groups, respectively. DCA showed the good net clinical benefit of nomograms in predicting 5‐ and 10‐year risk of cardiac death. The model exhibited moderate predictive power for 5‐ and 10‐year cardiac mortality (AUC: 0.833 and 0.854, respectively), and for the development and validation cohorts (AUC: 0.76 and 0.813, respectively). Conclusions Our nomogram may assist clinicians in making clinical decisions about patients undergoing radiotherapy for esophageal cancer based on early detection of cardiac death risk.

Abstract Early diagnosis of cancer treatment‐related cardiac dysfunction (CTRCD) is important as cancer therapy increases the risk of cardiac dysfunction. High‐sensitivity cardiac troponin T (hs‐cTnT) is a highly specific marker of myocardial injury. However, its diagnostic value for CTRCD has not been systematically evaluated. This meta‐analysis aimed to evaluate whether hs‐cTnT could be used as an early diagnostic biomarker for CTRCD. We systematically surveyed PubMed, Embase, Cochrane Library, and Web of Science databases for studies of hs‐cTnT for the diagnosis of CTRCD before 1 April 2022. Patients of all ages and all cancer types who underwent echocardiographic left ventricular ejection fraction assessment and blood hs‐cTnT and received anticancer therapy (including chemotherapy, radiotherapy, targeted therapy, immune checkpoint inhibitors, and other treatments) were included in this study, resulting in a total of eight studies with 1294 patients. The occurrence of CTRCD was associated with elevated hs‐cTnT [sensitivity: 0.78, 95% confidence interval (CI): 0.64–0.88; specificity: 0.75, 95% CI: 0.59–0.86; area under the curve (AUC): 0.83, 95% CI: 0.80–0.86]. We further performed subgroup analysis and found that the AUC of hs‐cTnT elevation for the diagnosis of CTRCD increased from 0.83 to 0.90 (95% CI: 0.87–0.92) at 3–6 months, suggesting a higher early diagnostic value of hs‐cTnT compared with echocardiography for CTRCD. In terms of clinical applicability, the Fagan plot showed pre‐test and post‐test probabilities of 51% and 9%, respectively, indicating that hs‐cTnT testing can improve the accuracy of clinical diagnosis of CTRCD. However, it was not possible to determine the optimal cut‐off value for early diagnosis of CTRCD with hs‐cTnT. The Deeks funnel plot was largely symmetrical (P = 0.74); hence, publication bias was not observed. Hs‐cTnT allowed early CTRCD diagnosis at 3–6 months. However, further high‐quality research is needed to determine the optimal cut‐off value for early CTRCD diagnosis with this biomarker.

Abstract Purpose Flap endonuclease 1 (FEN1) is highly upregulated in prostate cancer and promotes the growth of prostate cancer cells. Androgen receptor (AR) is the most critical determinant of the occurrence, progression, metastasis, and treatment of prostate cancer. However, the effect of FEN1 on docetaxel (DTX) sensitivity and the regulatory mechanisms of AR on FEN1 expression in prostate cancer need to be further studied. Methods Bioinformatics analyses were performed using data from the Cancer Genome Atlas and the Gene Expression Omnibus. Prostate cancer cell lines 22Rv1 and LNCaP were used. FEN1 siRNA, FEN1 overexpression plasmid, and AR siRNA were transfected into cells. Biomarker expression was evaluated by immunohistochemistry and Western blotting. Apoptosis and the cell cycle were explored using flow cytometry analysis. Luciferase reporter assay was performed to verify the target relationship. Xenograft assays were conducted using 22Rv1 cells to evaluate the in vivo conclusions. Results Overexpression of FEN1 inhibited cell apoptosis and cell cycle arrest in the S phase induced by DTX. AR knockdown enhanced DTX‐induced cell apoptosis and cell cycle arrest at the S phase in prostate cancer cells, which was attenuated by FEN1 overexpression. In vivo experiments showed that overexpression of FEN1 significantly increased tumour growth and weakened the inhibitory effect of DTX on prostate tumour growth, while AR knockdown enhance the sensitivity of DTX to prostate tumour. AR knockdown resulted in FEN1, pho‐ERK1/2, and pho‐ELK1 downregulation, and the luciferase reporter assay confirmed that ELK1 can regulate the transcription of FEN1. Conclusion Collectively, our studies demonstrate that AR knockdown improves the DTX sensitivity of prostate cancer cells by downregulating FEN1 through the ERK/ELK1 signalling pathway.

Abstract Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

Abstract Background Frailty describes an age-related state of deterioration in biological function. This study aimed to investigate the association between frailty and cognitive function and its combined effects with lifestyles. Methods A total of 3,279 participants from the Dongfeng-Tongji (DFTJ) cohort were tested the cognitive function by using the Chinese version of Mini-mental State Examination (MMSE). Frailty was evaluated based on a 35-item frailty index (FI). Frailty status was dichotomized into robust (FI

Objectives: This study aimed to describe the full scope of long-term outcomes and the ongoing pathophysiological alterations among COVID-19 survivors. Methods: We established a longitudinal cohort of 208 COVID-19 convalescents and followed them at 3.3 (interquartile range [IQR]: 1.3, 4.4, visit 1), 9.2 (IQR: 9.0, 9.6, visit 2), and 18.5 (IQR: 18.2, 19.1, visit 3) months after infection, respectively. Serial changes in multiple physical and psychological outcomes were comprehensively characterized. We, in addition, explored the potential risk factors of SARS-CoV-2 antibody response and sequelae symptoms. Results: We observed continuous improvement of sequelae symptoms, lung function, chest computed tomography (CT), 6-minute walk test, and the Borg dyspnea scale, whereas sequelae symptoms (at least one) and abnormal chest CT patterns still existed in 45.2% and about 30% of participants at 18.5 months, respectively. Anxiety and depression disorders were alleviated for the convalescents, although depression status was sustained for a longer duration. Conclusions: Most COVID-19 convalescents had an overall improved physical and psychological health status, whereas sequelae symptoms, residual lesions on lung function, exercise impairment, and mental health disorders were still observed in a small proportion of participants at 18.5 months after infection. Implementing appropriate preventive and management strategies for the ever-growing COVID-19 population is warranted.

Introduction: Load Redistribution (LR) attacks, as a common form of false data injection attack, have emerged as a significant cybersecurity threat to power system operations by manipulating load buses’ measurements at substations. Existing LR attack methods typically assume that any substation can be equally attacked, contributing to the analysis of LR attacks in power systems. However, the diversity of cyber vulnerabilities in substation communication links implies varying costs associated with falsifying load buses’ measurements. Thus, quantitatively evaluating these costs and analyzing the impact of LR attacks on power systems within cost constraints holds practical significance.Methods: In this paper, we employ a Bayesian attack graph model to characterize the intrusion process through cyber vulnerabilities. The costs of falsifying load buses’ measurements at substations are quantitatively evaluated using the mean time-to-compromise model. Subsequently, from the attacker’s perspective, we propose a bi-level optimization model for LR attacks, considering the mean time to compromise in conjunction with limited attack resources and power flow constraints.Results: Simulations conducted on the IEEE 14-bus system illustrate the influence of cyber vulnerabilities on LR attacks within power systems. Furthermore, we verify that the attack scenario of the existing LR attack model aligns with a case of the proposed bi-level LR attack model when there is sufficient attack time to compromise all communication links.Discussion: The findings of this research demonstrate that the impact of cyber vulnerabilities on LR attacks can be quantified by assessing the attack costs. Effective management of LR attacks can be achieved under cost constraints through optimization methods. These insights contribute to enhancing network security strategies for power systems, mitigating potential threats posed by LR attacks in power system operations.

This paper proposes a microgrid (MG) system integrating distributed renewable energy (RE) and hybrid energy storage system (HESS), which is an effective solution of power supply for remote areas and islands. The distributed generation (DG) unit of the system includes photovoltaic (PV) power and wind power, and the HESS includes lithium-ion (Li-ion) battery, super capacitor (SC) and compressed air energy storage (CAES). In this study, the Confidence Interval Method (CIM) is used to establish the wind power output and PV power output model, and the DG power curves under different confidence levels are calculated. Taking the minimum annual total cost of the system as the optimization objective, the capacity allocation of the wind-PV-Li-ion battery system is optimized by using the genetic algorithm (GA) tool. Based on the quadratic moving average filtering method, the energy storage power is divided into different frequencies, and the rated power, rated capacity and initial state of charge (SOC) of three kinds of ESSs are calculated. The results show that the wind-PV-HESS can better meet the power demand of users with a good economic performance.

Quinoa saponins are pentacyclic triterpene compounds composed of one triterpenoid glycoside and two different sugar chains. Previous studies have showed that natural quinoa saponins showed little or no antifungal activity, and there are few reports about their antifungal effects in recent decades. Fusarium wilt caused by Fusarium oxysporum f. sp. lycopersici (FOL) is the most serious for tomatoes in the field and under greenhouse conditions. The main objective of this study was to investigate the effectiveness of different concentrations and application modes of crude saponins from quinoa bran against the causal pathogen of tomato wilt under a greenhouse experiment. The results showed that the anti-FOL activity of quinoa saponins was weak in vitro, but significantly enhanced in vivo. Tomato seeds and seedlings treated with solution of quinoa saponins at 0.5 and 1.0 g/L significantly reduced the disease incidence (%) of tomato Fusarium wilt. The treatment types of saponin solution have influence on the preventive effects (%) of tomato seedlings against Fusarium wilt, among them, root soaking > foliar spray > seed soaking. The treatment of seed soaking with quinoa saponins inhibited germination of tomato seeds to some extent. However, the germination rate of tomato seeds after saponin soaking was comparable to the chemical pesticide (thiram carboxin); therefore, it could be used to control tomato wilt disease. This is due to the fact that the antifungal activity of quinoa saponins in vivo was much higher than that in vitro when the saponin concentration was between 0.5–1.0 g/L, indicating that the antifungal activity of quinoa saponins may be achieved mainly by inducing resistance. This investigation supports the potential use of quinoa saponins as a supplier of antifungal compounds, and could be the foundation for a future study examining the use of quinoa bran as a new resource against FOL.

IntroductionChina is one of the major producers and exporters of various kinds of citrus fruits. As one of China’s major citrus planting bases, Sichuan has a citrus planting area that exceeds 400,000 hectares. Meanwhile, citrus cultivation has become one of the important agricultural pillar industries in the region. Citrus fruits are reported to show various health-promoting effects, especially antioxidant activity. However, reports on the functional, nutritional and qualitative characteristics of different citrus varieties in Sichuan are still scarce.MethodsThe quality attributes (color parameters, shape, and size), juice properties (titratable acids and total soluble sugar), mineral elements, and health-promoting nutritional and functional components (protein, carbohydrates, fat, dietary fiber, ascorbic acid, phenolic acids, and flavonoids), as well as antioxidant properties of 10 typical citrus varieties cultivated in Sichuan, were systematically investigated and analyzed.Results and DiscussionSignificant differences among different citrus varieties were found. In particular, the total soluble sugar content of Mingrijian was higher than that of other citrus, suggesting its potential for fresh consumption and food processing. Moreover, a total of five flavonoids and nine phenolic acids were identified and quantified. Yuanhong, with higher contents of ascorbic acid and phenolic acids, was considered to be a valuable variety with excellent antioxidant capacity and can be used for value-added processing in the food industry. Principal component analysis and hierarchical cluster heatmap analysis suggested that there were significant differences among the 10 citrus varieties. Correlation analysis confirmed the significant contribution of ascorbic acid and phenolic acids to antioxidant capacity in citrus. The results can provide some references for the cultivation and selection of nutritious citrus fruits.

Nowadays, the mitigation of damage to a ship caused by the underwater explosion attracts more and more attention from the modern ship designers. In this study, two kinds of scale tests were conducted to investigate the effects of polyurea coatings on the blast resistance of hulls subjected to underwater explosion. Firstly, small-scale model tests with different polyurea coatings were carried out. Results indicate that polyurea has a better blast resistance performance when coated on the front face, which can effectively reduce the maximum deflection of the steel plate by more than 20% and reduce the deformation energy by 35.7%–45.4%. Next, a full-scale ship (approximately 50 m × 9 m) under loadings produced by the detonation of 33 kg of spherical TNT charges was tested, where a part of the ship was coated with polyurea on the front face (8 mm + 24 mm) and not on the contrast area. Damage characteristics on the bottom were statistically analyzed based on a 3D scanning technology, indicating that polyurea contributes to enhancing the blast protection of the ship. However, damage results of this test were different from those of the small-scale tests. Moreover, the deformation area of the bottom with polyurea was greatly increased by 40.1% to disperse explosion energy, a conclusion that cannot be drown from the small-scale tests.

Elymus nutans Griseb. is a dominant forage in the Qinghai–Tibetan Plateau. However, the combined cold and drought (CD) stress is a major problem inhibiting its growth, development, and yield. Here, the responses of morphological, photosynthetic, osmoregulation levels, and signal transduction under cold, drought, and CD stress were explored. Both cold- and drought-stressed plants showed varying degrees of damage. In addition, CD stress led to more severe damage than single stress, especially in total biomass, photosynthetic capacity, and electron transfer efficiency. The total biomass, net photosynthetic rate, and maximal quantum yield of photosystem II (PSII) photochemistry reduced by 61.47%, 95.80%, and 16.06% in comparison with the control, respectively. Meanwhile, CD stress was accompanied by lower chlorophyll contents, down-regulated expression level of key photosynthetic enzymes (EnRbcS, EnRbcL, and EnRCA), stomatal closure, disrupted chloroplast ultrastructure, and reduced starch content. Furthermore, CD stress induced some adaptability responses in cold- and drought-tolerant E. nutans seedlings. The combined stress provoked alterations in both cold- and drought-related transcription factors and responsive genes. EnCBF12, EnCBF9, EnCBF14, and EnCOR14α were significantly up-regulated under cold or drought stress, and the transcript level of EnCBF3 and EnCBF12 was even 2.94 and 12.59 times higher than control under CD treatment, which indicated the key role of transcription factors activation in coping with CD stress. In addition, the content of soluble sugar, reducing sugar, proline, glycine betaine, and other osmolytes was significantly improved under CD stress. Therefore, we demonstrated that exposure to CD stress led to severe morphological and photosynthetic damage and revealed the acclimation to the cold and drought stress combination via osmotic adjustment and transcription factors activation in the Tibetan wild E. nutans.

Abstract Marine cloud brightening is a proposal to counteract global warming by increasing sea salt aerosol emissions. In theory, this increases the cloud droplet number concentration of subtropical marine stratocumulus decks, increasing cloud brightness and longevity. However, this theoretical progression remains uncertain in coupled climate models, especially the response of liquid water path and cloud fraction to aerosol seeding. We use the GFDL CM4 climate model to simulate marine cloud brightening following the published G4sea‐salt protocol, in which sea salt aerosol emissions are uniformly increased over 30 S–30 N in addition to standard forcings from a SSP2‐4.5 future warming scenario. The perturbed radiative and cloud responses are temporally stable though spatially heterogeneous, and direct scattering by the added sea salt predominates over changes to cloud reflectance. In fact, feedbacks in the coupled simulation lead to a net warming, rather than cooling, response by clouds.

Data-independent acquisition (DIA) technology for protein identification from mass spectrometry and related algorithms is developing rapidly. The spectrum-centric analysis of DIA data without the use of spectra library from data-dependent acquisition data represents a promising direction. In this paper, we proposed an untargeted analysis method, Dear-DIAXMBD, for direct analysis of DIA data. Dear-DIAXMBD first integrates the deep variational autoencoder and triplet loss to learn the representations of the extracted fragment ion chromatograms, then uses the k-means clustering algorithm to aggregate fragments with similar representations into the same classes, and finally establishes the inverted index tables to determine the precursors of fragment clusters between precursors and peptides and between fragments and peptides. We show that Dear-DIAXMBD performs superiorly with the highly complicated DIA data of different species obtained by different instrument platforms. Dear-DIAXMBD is publicly available at https://github.com/jianweishuai/Dear-DIA-XMBD.

Background Invasive prenatal evaluation by chromosomal microarray analysis (CMA) and karyotyping might represent an important option in pregnant women, but limited reports have applied CMA and karyotyping of fetuses conceived by assisted reproductive technology (ART). This study aimed to examine the value of CMA and karyotyping in prenatal diagnosis after ART. Methods This retrospective study included all singleton fetuses conceived by ART from January 2015 to December 2021. Anomalies prenatally diagnosed based on karyotyping and CMA were analyzed. Prevalence rates for various CMA and karyotyping results were stratified based on specific testing indications including isolated—and non-isolated ART groups. The rates of CMA findings with clinical significance (pathogenic/likely pathogenic) and karyotype anomalies were assessed and compared to those of local control individuals with naturally conceived pregnancies and without medical indications. Results In total, 224 subjects were assessed by karyotyping and CMA. In the examined patients, chromosomal and karyotype abnormality rates were 3.57% (8/224) and 8.93% (20/224), respectively. This finding indicated a 5.35% (12/224)-incremental rate of abnormal CMA was obtained over karyotype analysis (p = 0.019). The risk of CMA with pathogenic findings for all pregnancies conceived by ART (5.80%, 13/224) was markedly elevated in comparison with the background value obtained in control individuals (1.47%, 9/612; p = 0.001). In addition, risk of CMA with clinically pathogenic results in isolated ART groups was significant higher compared to the background risk reported in the control cohort (p = 0.037). Conclusions Prenatal diagnosis including karyotyping and CMA is recommended for fetuses conceived by ART, with or without ultrasound findings.

Background: Metals in the human body represent both environmental exposure and nutritional status. Little is known about the miRNA signature in relation to circulating metals in humans. Objectives: To characterize metal-associated miRNAs in leukocytes, individually and collectively as networks. Methods: In a panel of 160 Chinese adults, we measured 23 metals/metalloids in plasma, and sequenced miRNAs and mRNAs in leukocytes. We used linear regression to model the associations between ln-transformed metal concentrations and normalized miRNA levels adjusting for potential confounders. We inferred the enriched leukocyte subtypes for the identified miRNAs using an association approach. We utilized mRNA sequencing data to explore miRNA functions. We also constructed modules to identify metal-associated miRNA networks. Results: We identified 55 metal-associated miRNAs at false discovery rate-adjusted P

Abstract Whether the definition of hypertension according to 2017 AHA/ACC guidelines and blood pressure (BP) changes was related to the increased risk of chronic kidney disease (CKD) remained debated. This prospective cohort study aimed to investigate the association of BP and long‐term BP change with CKD risk with different glucose metabolism according to the new hypertension guidelines. This study examined 12 951 participants and 11 183 participants derived from the older people cohort study, respectively. Participants were divided into three groups based on blood glucose and the risks were assessmented by the logistic regression model. During a 10 years of follow‐up period, 2727 individuals developed CKD (21.1%). Compared with those with BP

Abstract The optimum amounts and types of leisure-time physical activity (LTPA) for cardiovascular disease (CVD) prevention among Chinese retired adults are unclear. The prospective study enrolled 26,584 participants (mean age [SD]: 63.3 [8.4]) without baseline disease from the Dongfeng-Tongji cohort in 2013. Cox-proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a mean 5.0 (1.5) years of follow-up, 5704 incident CVD cases were documented. Compared with less than 7.5 metabolic equivalent of task-hours per week (MET-hours/week) of LTPA, participating LTPA for 22.5–37.5 MET-hours/week, which was equivalent to 3 to 5 times the world health organization (WHO) recommended minimum, was associated with a 18% (95% CI 9 to 25%) lower CVD risk; however, no significant additional benefit was gained when exceeding 37.5 MET-hours/week. Each log10 increment of MET-hours/week in square dancing and cycling was associated with 11% (95% CI 2 to 20%) and 32% (95% CI 21 to 41%), respectively, lower risk of incident CVD. In Chinese retired adults, higher LTPA levels were associated with lower CVD risk, with a benefit threshold at 3 to 5 times the recommended physical activity minimum. Encouraging participation in square dancing and cycling might gain favourable cardiovascular benefits.

To further examine the effectiveness of the ascending and descending sections of the new round-trip drifting sounding system in forecasting high-impact weather such as heavy rainfall, in this study, three assimilation experiments were designed for a rainstorm in eastern China using WRF (Weather Research and Forecast) and WRFDA-3DVAR. Then, the reasons for the improvement in the effects of forecasting rainfall after assimilation were analyzed from various perspectives. The results showed that the assimilation of round-trip drifting sounding data can increase the accuracy of regions of heavy precipitation and improve the effectiveness of rainstorm forecasting. The quality of the wind field improved after the assimilation of the round-trip drifting sounding data, which improved the conditions of moisture transport, resulting in increased humidity in the lower layer, which accumulated more unstable energy for the development of storms. In addition, the enhanced low-level convergence after the assimilation of the new sounding data created a strong upward motion, which was more conducive to triggering heavy rainfall, thus improving the ability to forecast such heavy rainfall.

Sweet sorghum is an important bioenergy grass and valuable forage with a strong adaptability to saline environments. However, little is known about the mechanisms of sweet sorghum coping with ion toxicity under salt stresses. Here, we first evaluated the salt tolerance of a sweet sorghum cultivar “Lvjuren” and determined its ion accumulation traits under NaCl treatments; then, we explored key genes involved in Na+, Cl−, K+ and NO3− transport using transcriptome profiling and the qRT-PCR method. The results showed that growth and photosynthesis of sweet sorghum were unaffected by 50 and 100 mM NaCl treatments, indicative of a strong salt tolerance of this species. Under NaCl treatments, sweet sorghum could efficiently exclude Na+ from shoots and accumulate Cl− in leaf sheaths to avoid their overaccumulation in leaf blades; meanwhile, it possessed a prominent ability to sustain NO3− homeostasis in leaf blades. Transcriptome profiling identified several differentially expressed genes associated with Na+, Cl−, K+ and NO3− transport in roots, leaf sheaths and leaf blades after 200 mM NaCl treatment for 6 and 48 h. Moreover, transcriptome data and qRT-PCR results indicated that HKT1;5, CLCc and NPF7.3-1 should be key genes involved in Na+ retention in roots, Cl− accumulation in leaf sheaths and maintenance of NO3− homeostasis in leaf blades, respectively. Many TFs were also identified after NaCl treatment, which should play important regulatory roles in salt tolerance of sweet sorghum. In addition, GO analysis identified candidate genes involved in maintaining membrane stability and photosynthetic capacity under salt stresses. This work lays a preliminary foundation for clarifying the molecular basis underlying the adaptation of sweet sorghum to adverse environments.

Soil salinization is one of the most serious abiotic stresses restricting plant growth. Buffalograss is a C4 perennial turfgrass and forage with an excellent resistance to harsh environments. To clarify the adaptative mechanisms of buffalograss in response to salinity, we investigated the effects of NaCl treatments on photosynthesis, water status and K+/Na+ homeostasis of this species, then analyzed the expression of key genes involved in these processes using the qRT-PCR method. The results showed that NaCl treatments up to 200 mM had no obvious effects on plant growth, photosynthesis and leaf hydrate status, and even substantially stimulated root activity. Furthermore, buffalograss could retain a large amount of Na+ in roots to restrict Na+ overaccumulation in shoots, and increase leaf K+ concentration to maintain a high K+/Na+ ratio under NaCl stresses. After 50 and 200 mM NaCl treatments, the expressions of several genes related to chlorophyll synthesis, photosynthetic electron transport and CO2 assimilation, as well as aquaporin genes (BdPIPs and BdTIPs) were upregulated. Notably, under NaCl treatments, the increased expression of BdSOS1, BdHKT1 and BdNHX1 in roots might have helped Na+ exclusion by root tips, retrieval from xylem sap and accumulation in root cells, respectively; the upregulation of BdHAK5 and BdSKOR in roots likely enhanced K+ uptake and long-distance transport from roots to shoots, respectively. This work finds that buffalograss possesses a strong ability to sustain high photosynthetic capacity, water balance and leaf K+/Na+ homeostasis under salt stress, and lays a foundation for elucidating the molecular mechanism underlying the salt tolerance of buffalograss.

With the strong advancement of the global carbon reduction strategy and the rapid development of renewable energy, compressed air energy storage (CAES) technology has received more and more attention for its key role in large-scale renewable energy access. This paper summarizes the coupling systems of CAES and wind, solar, and biomass energies from the perspective of system topology, and points out the advantages and limitations of each system. It is shown that the coupling of wind energy and CAES is mainly combined in series and in parallel, and sometimes part of the wind power can be converted into thermal energy when coupled to CAES. The coupling between solar heat and CAES is an important form of coupling between solar energy and CAES. Solar-heat-coupled CAES mainly uses solar energy to heat expander inlet air. The coupling forms of solar energy and CAES are based on various CAES forms, various heat heating sequences, reheating, bottom cycle, and other factors. The combination of biomass and CAES is generally based on biomass gasification power generation technology. In the future, a wind–solar–CAES multiple coupling system is expected to become a promising large-scale form for the utilization of renewable energy, and this integrated system has great potential as a system configuration, but has some technical challenges.

Chaolong Wang and colleagues report a large genome-wide association study for COVID-19 severity in Chinese individuals. By meta-analysis with European data, they identify 3 loci associated with severe disease that suggest key roles for the adaptive immune system and the ABO blood group system in development of severe COVID-19.

As the primary value system in Chinese culture for almost 2,000 years, Confucianism has profoundly influenced the mindset of Chinese people. Cultural psychology studies have highlighted that individuals with different cultural backgrounds vary in their preferences for certain personality traits, such as self-construal, and their metacognitive characteristics, such as thinking modes. Compared with Western cultures, Chinese culture shows a preference for the interdependent self and holistic thinking. To investigate the relationship between the relational-interdependent self, holistic thinking, and traditional Chinese values (which are represented by Confucian values), we surveyed 327 Chinese adults using the Confucian Traditional Values Survey, Holistic Thinking Scale, and Relational-Interdependent Self-Construal Scale. The results show that Confucian values positively influence both holistic thinking and the relational-interdependent self, the latter of which partially mediates the positive relationship between Confucian values and holistic thinking. This study deepens the understanding of the psychological features of Chinese culture.

Limited studies have evaluated the associations of multiple metal exposures with homocysteine (Hcy) levels, which were independent risk factor for cardiovascular disease (CVD). Furthermore, the interactions between genetic variants and plasma metals in relation to Hcy levels were largely unknown. We aimed to explore the associations of multiple plasma metals (including metalloids arsenic [As] and selenium [Se]) with Hcy levels and whether their associations were modified by genetic susceptibility. We included 2989 participants from the baseline of the Dongfeng-Tongji cohort (DFTJ cohort) and conducted a cross-sectional study to explore the associations of 17 plasma metals with serum Hcy levels. Both multi-variable linear regression model (single-metal model) and LASSO penalized regression model (multiple-metal model) were used to identify the Hcy-associated metals. The weighted genetic risk score (GRS) was calculated based on 18 established Hcy-associated genetic variants. For metals that were associated with Hcy, we further assessed the gene-metal interactions on Hcy levels. Among 17 metals, plasma molybdenum (Mo), strontium (Sr), and Zinc (Zn) were positively associated with Hcy levels, whereas Se was inversely associated with Hcy levels in both single- and multiple-metal models. We also observed that the genetic predisposition to Hcy significantly modified the association between plasma Se and serum Hcy levels (P for interaction = 0.003), while no significant gene-metal interactions were found for Mo, Sr, and Zn (all P for interactions > 0.05). These findings provide novel insight into the associations of the plasma concentrations of Mo, Se, Sr and Zn with Hcy levels and address the importance of Se as a potential upstream modifiable factor for the personalized prevention of elevated Hcy levels and CVD.

Previous evidences exploring the associations of BPA with lipid changes and dyslipidemia did not obtain consistent results. To evaluate whether serum BPA concentration was associated with changes in blood lipid levels and incident dyslipidemia risk in middle-elderly Chinese adults, we conducted a prospective study with 1093 participants (average 62.65 years old) derived from the Dongfeng-Tongji cohort which was founded in 2008 and followed up each 5 years. Serum BPA levels were measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS). Changes in lipid levels were named as Δ lipids which equal to Lipid2013 - Lipid2008. The diagnosis of dyslipidemia was according to Chinese Guidelines on Prevention and Treatment of Dyslipidemia in 2016. We used multivariable linear regression and Logistic regression to explore the relations between serum BPA levels and changes in lipid levels and incident dyslipidemia risk, respectively. Besides, restricted cubic splines were used to explore the dose-response relations. After 5 years’ follow-up, 51 individuals developed with hypercholesterolemia, 87 with hypertriglyceridemia, 34 with high-LDL-cholesterolemia, 74 with low-HDL-cholesterolemia, and 199 with dyslipidemia. At baseline serum BPA levels were positively related to TC, LDL-c, and Non-HDL-c levels. In the prospective study, each Ln-BPA increase was associated with 0.05 (95% CI: 0.02, 0.09) mmol/L increase in Δ TC, 0.07 (95% CI:0.03, 0.11) mmol/L increase in Δ Non-HDL-c, 0.05 (95% CI: 0.01, 0.08) increase in Δ TC/HDL-c, and 0.05 (95% CI: 0.01, 0.08) increase in Δ Non-HDL-c/HDL-c. We only observed significant associations in females but not in males. Besides, serum BPA levels were positively associated with hypercholesterolemia (OR=1.12, 95% CI: 1.01, 1.25). The restricted cubic splines obtained similar results. In conclusion, serum BPA was associated TC and Non-HDL-c changes, and BPA was also associated with increased risk of hypertriglyceridemia. Further prospective studies with large sample size are warranted to validate our findings.

Abstract Background Body mass index (BMI) has been reported to be inversely associated with incident risk of non‐small cell lung cancer (NSCLC). However, the underlying mechanism is still unclear. This study aimed to investigate the role of DNA methylation in the relationship between BMI and NSCLC. Methods We carried out a genome‐wide DNA methylation study of BMI in peripheral blood among 2266 Chinese participants by using Illumina Methylation arrays. For the BMI‐related DNA methylation changes, their associations with NSCLC risk were further analyzed and their mediation effects on BMI‐NSCLC association were also evaluated. Results The methylation levels of four CpGs (cg12593793, cg17061862, cg11024682, and cg06500161, annotated to LMNA, ZNF143, SREBF1, and ABCG1, respectively) were found to be significantly associated with BMI. Methylation levels of cg12593793, cg11024682, and cg06500161 were observed to be inversely associated with NSCLC risk [OR (95%CI) =0.22 (0.16, 0.31), 0.39 (0.30, 0.50), and 0.66 (0.53, 0.82), respectively]. Additionally, cg11024682 in SREBF1 and cg06500161 in ABCG1 mediated 45.3% and 19.5% of the association between BMI and decreased NSCLC risk, respectively. Conclusions In this study, we identified four DNA methylation sites associated with BMI in the Chinese populations at the genome‐wide significant level. We also found that the BMI‐related methylations of SREBF1 and ABCG1 could mediate about a quintile‐to‐half of the effect of BMI on reduced NSCLC risk, which adds a potential mechanism underlying this association.

Abstract Systemic immune-inflammation index (SII) emerged as a biomarker of chronic inflammation and an independent prognostic factor for many cancers. We aimed to investigate the associations of SII level with total and cause-specific mortality risks in the general populations, and the potential modification effects of lifestyle-related factors on the above associations. In this study, we included 30,521 subjects from the Dongfeng-Tongji (DFTJ) cohort and 25,761 subjects from the National Health and Nutrition Examination Survey (NHANES) 1999–2014. Cox proportional hazards regression models were used to estimate the associations of SII with mortality from all-cause, cardiovascular diseases (CVD), cancer and other causes. In the DFTJ cohort, compared to subjects in the low SII subgroup, those within the middle and high SII subgroups had increased risks of total mortality [hazard ratio, HR (95% confidence interval, CI) = 1.12 (1.03–1.22) and 1.26 (1.16–1.36), respectively) and CVD mortality [HR (95%CI) = 1.36 (1.19–1.55) and 1.50 (1.32–1.71), respectively]; those within the high SII subgroup had a higher risk of other causes mortality [HR (95%CI) = 1.28 (1.09–1.49)]. In the NHANES 1999–2014, subjects in the high SII subgroup had higher risks of total, CVD, cancer and other causes mortality [HR (95%CI) = 1.38 (1.27–1.49), 1.33 (1.11–1.59), 1.22 (1.04–1.45) and 1.47 (1.32–1.63), respectively]. For subjects with a high level of SII, physical activity could attenuate a separate 30% and 32% risk of total and CVD mortality in the DFTJ cohort, and a separate 41% and 59% risk of total and CVD mortality in the NHANES 1999–2014. Our study suggested high SII level may increase total and CVD mortality in the general populations and physical activity exerted a beneficial effect on the above associations.

Abstract We describe the third version of the Geophysical Fluid Dynamics Laboratory cloud microphysics scheme (GFDL MP v3) implemented in the System for High‐resolution prediction on Earth‐to‐Local Domains (SHiELD). Compared to the GFDL MP v2, the GFDL MP v3 is entirely reorganized, optimized, and modularized into functions. The particle size distribution (PSD) of all hydrometeor categories is redefined to better mimic observations, and the cloud droplet number concentration (CDNC) is calculated from the Modern‐Era Retrospective analysis for Research and Applications, version 2 (MERRA2) aerosol data. In addition, the GFDL MP has been redesigned so all processes use the redefined PSD to ensure overall consistency and easily permit the introduction of new PSDs and microphysical processes. A year's worth of global 13‐km, 10‐day weather forecasts were performed with the new GFDL MP. Compared to the GFDL MP v2, the GFDL MP v3 significantly improves SHiELD's predictions of geopotential height, air temperature, and specific humidity in the Troposphere, as well as the high, middle and total cloud fractions and the liquid water path. The predictions are improved even further by the use of reanalysis aerosol data to calculate CDNC, and also by using the more realistic PSD available in GFDL MP v3. However, the upgrade of the GFDL MP shows little impact on the precipitation prediction. Degradations caused by the new scheme are discussed and provide a guide for future GFDL MP development.

Effective drugs for the treatment of myocardial fibrosis (MF) are lacking. Traditional Chinese medicine (TCM) has garnered increasing attention in recent years for the prevention and treatment of myocardial fibrosis. This Article describes the pathogenesis of myocardial fibrosis from the modern medicine, along with the research progress. Reports suggest that Chinese medicine may play a role in ameliorating myocardial fibrosis through different regulatory mechanisms such as reduction of inflammatory reaction and oxidative stress, inhibition of cardiac fibroblast activation, reduction in extracellular matrix, renin-angiotensin-aldosterone system regulation, transforming growth Factor-β1 (TGF-β1) expression downregulation, TGF-β1/Smad signalling pathway regulation, and microRNA expression regulation. Therefore, traditional Chinese medicine serves as a valuable source of candidate drugs for exploration of the mechanism of occurrence and development, along with clinical prevention and treatment of MF.

ObjectivesThe first objective of this study was to probe the effects of genkwanin (GKA) on osteoclast. The second goal of this study was to study whether GKA can protect lipopolysaccharide (LPS) and ovariectomized (OVX) induced bone loss.Materials and MethodsVarious concentrations of GKA (1 and 10 mg/kg) were injected into mice. Different concentrations of GKA (1 and 5 μM) were used to detect the effects of GKA on osteoclast and osteoblast.Key FindingsGKA attenuated the osteoclast differentiation promoted by RANKL and expression of marker genes containing c-fos, ctsk as well as bone resorption related gene Trap and to the suppression of MAPK signaling pathway. In addition, GKA induced BMMs cell apoptosis in vitro. Moreover, GKA prevented LPS-induced and ovariectomized-induced bone loss in mice.ConclusionOur research revealed that GKA had a potential to be an effective therapeutic agent for osteoclast-mediated osteoporosis.

ObjectiveTo explore differentially expressed miRNAs in type 2 diabetes and their potential cellular functions.MethodsWe screened plasma miRNAs by miRNA array analysis and validated them by TaqMan real-time PCR in 113 newly diagnosed, untreated type 2 diabetes cases and 113 healthy controls. Low-abundance plasma proteins encoded by miR-193b-3p target genes were explored in this study population. We further investigated the potential cellular functions of the differentially expressed miRNAs in HepG2 cells.ResultsmiR-193b-3p was differentially expressed in type 2 diabetes cases compared to healthy controls (fold change = 2.01, P = 0.006). Plasma levels of triosephosphate isomerase (TPI1, a protein involved in the glycolytic pathway) decreased in type 2 diabetes cases (fold change = 1.37, P = 0.002). The effect of miR-193b-3p on TPI1 was verified by transfection of miR-193b-3p into HepG2 cells. miR-193b-3p inhibited the expression of YWHAZ/14-3-3ζ in the PI3K-AKT pathway, subsequently altering the expression of FOXO1 and PCK1. After transfection, cells were incubated in glucose-free medium for another 4 h. Glucose levels in medium from cells with elevated miR-193b-3p levels were significantly higher than those in medium from negative control cells (P = 0.016). In addition, elevated miR-193b-3p reduced glucose uptake by inhibiting insulin receptor (IR) and GLUT2 expression.ConclusionPlasma miR-193b-3p levels increased in type 2 diabetes cases, and TPI1 levels decreased in both plasma and HepG2 cells with increased miR-193b-3p levels, while extracellular lactate levels did not significantly changed. Moreover, miR-193b-3p may affect glucose metabolism by directly targeting YWHAZ/14-3-3ζ and upregulating the transcription factor FOXO1 downstream of the PI3K-AKT pathway.

Flowering time is an important trait that determines the breeding process of ornamental plants. The flowering period of lotus (Nelumbo nucifera Gaertn.) is mainly concentrated in June–August. During this period, the weather is hot and there are few tourists, which made many lotus scenic spots difficult to operate. People have a strong demand for early flowering lotus cultivars. In this paper, 30 lotus cultivars with high ornamental value were selected as materials and their phenological periods were observed for two consecutive years in 2019 and 2020. A number of cultivars with early flowering potential and stable flowering periods, such as ‘Fenyanzi’, ‘Chengshanqiuyue’, ‘Xianghumingyue’ and ‘Wuzhilian’, were screened by K-Means clustering method. The relationship between accumulated temperature and flowering time of 19 lotus cultivars at different growth stages was analyzed. It was found that lotus cultivars with early flowering traits could adapt well to the changes of early environmental temperature and were not affected by low temperature. On the other hand, by analyzing the relationship between different traits and flowering time of three typical cultivars, such as rhizome weight, phenological period, etc., it shows that the nutrient content of the rhizome and the early morphology of plants will affect the flowering time. These results provide a reference for the formation of a systematic lotus early flowering cultivar breeding mechanism and the establishment of a perfect flowering regulation technology system, which can further improve the ornamental value of lotus and promote industrial development.

SNARE protein is an essential factor driving vesicle fusion in eukaryotes. Several SNAREs have been shown to play a crucial role in protecting against powdery mildew and other pathogens. In our previous study, we identified SNARE family members and analyzed their expression pattern in response to powdery mildew infection. Based on quantitative expression and RNA-seq results, we focused on TaSYP137/TaVAMP723 and hypothesized that they play an important role in the interaction between wheat and Blumeria graminis f. sp. Tritici (Bgt). In this study, we measured the expression patterns of TaSYP132/TaVAMP723 genes in wheat post-infection with Bgt and found that the expression pattern of TaSYP137/TaVAMP723 was opposite in resistant and susceptible wheat samples infected by Bgt. The overexpression of TaSYP137/TaVAMP723 disrupted wheat’s defense against Bgt infection, while silencing these genes enhanced its resistance to Bgt. Subcellular localization studies revealed that TaSYP137/TaVAMP723 are present in both the plasma membrane and nucleus. The interaction between TaSYP137 and TaVAMP723 was confirmed using the yeast two-hybrid (Y2H) system. This study offers novel insights into the involvement of SNARE proteins in the resistance of wheat against Bgt, thereby enhancing our comprehension of the role of the SNARE family in the pathways related to plant disease resistance.

Epidemiological evidence regarding the possible link between multiple essential metals levels and all-cause mortality and cardiovascular disease (CVD) mortality among type 2 diabetes (T2D) patients is sparse. Here, we aimed to evaluate the longitudinal associations between 11 essential metals levels in plasma and all-cause mortality and CVD mortality among T2D patients. Our study included 5278 T2D patients from the Dongfeng–Tongji cohort. LASSO penalized regression analysis was used to select the all-cause and CVD mortality-associated metals from 11 essential metals (iron, copper, zinc, selenium, manganese, molybdenum, vanadium, cobalt, chromium, nickel, and tin) measured in plasma. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: With a median follow-up of 9.8 years, 890 deaths were documented, including 312 deaths of CVD. LASSO regression models and the multiple-metals model revealed that plasma iron and selenium were negatively associated with all-cause mortality (HR: 0.83; 95%CI: 0.70, 0.98; HR: 0.60; 95%CI: 0.46, 0.77), whereas copper was positively associated with all-cause mortality (HR: 1.60; 95%CI: 1.30, 1.97). Only plasma iron has been significantly associated with decreased risk of CVD mortality (HR: 0.61; 95%CI: 0.49, 0.78). The dose-response curves for the association between copper levels and all-cause mortality followed a J shape (Pfor nonlinear = 0.01). Our study highlights the close relationships between essential metals elements (iron, selenium, and copper) and all-cause and CVD mortality among diabetic patients.

Abstract Background Tumor angiogenesis, an essential process for cancer proliferation and metastasis, has a critical role in prognostic of kidney renal clear cell carcinoma (KIRC), as well as a target in guiding treatment with antiangiogenic agents. However, tumor angiogenesis subtypes and potential epigenetic regulation mechanisms in KIRC patient remains poorly characterized. System evaluation of angiogenesis subtypes in KIRC patient might help to reveal the mechanisms of KIRC and develop more target treatments for patients. Method Ten independent tumor angiogenesis signatures were obtained from molecular signatures database (MSigDB) and gene set variation analysis was performed to calculate the angiogenesis score in silico using the Cancer Genome Atlas (TCGA) KIRC dataset. Tumor angiogenesis subtypes in 539 TCGA-KIRC patients were identified using consensus clustering analysis. The potential regulation mechanisms was studied using gene mutation, copy number variation, and differential methylation analysis (DMA). The master transcription factors (MTF) that cause the difference in tumor angiogenesis signals were completed by transcription factor enrichment analysis. Results The angiogenesis score of a prognosis related angiogenesis signature including 189 genes was significantly correlated with immune score, stroma score, hypoxia score, and vascular endothelial growth factor (VEGF) signal score in 539 TCGA KIRC patients. MMRN2, CLEC14A, ACVRL1, EFNB2, and TEK in candidate gene set showed highest correlation coefficient with angiogenesis score in TCGA-KIRC patients. In addition, all of them were associated with overall survival in both TCGA-KIRC and E-MTAB-1980 KIRC data. Clustering analysis based on 183 genes in angiogenesis signature identified two prognosis related angiogenesis subtypes in TCGA KIRC patients. Two clusters also showed different angiogenesis score, immune score, stroma score, hypoxia score, VEGF signal score, and microenvironment score. DMA identified 59,654 differential methylation sites between two clusters and part of these sites were correlated with tumor angiogenesis genes including CDH13, COL4A3, and RHOB. In addition, RFX2, SOX13, and THRA were identified as top three MTF in regulating angiogenesis signature in KIRC patients. Conclusion Our study indicate that evaluation the angiogenesis subtypes of KIRC based on angiogenesis signature with 183 genes and potential epigenetic mechanisms may help to develop more target treatments for KIRC patients. Video Abstract

BackgroundObservational epidemiological studies have reported the associations of high body mass index (BMI) with elevated serum uric acid (UA) level and increased risk of postmenopausal breast cancer. However, whether UA is causally induced by BMI and functioned in the BMI–breast cancer relationship remains unclear.MethodsTo elucidate the causality direction between BMI and serum UA, the bidirectional Mendelian randomization (MR) analyses were performed by using summarized data from the largest Asian genome-wide association studies (GWAS) of BMI and UA carried out in over 150,000 Japanese populations. Then, a total of 19,518 postmenopausal women from the Dongfeng–Tongji (DFTJ) cohort (with a mean 8.2-year follow-up) were included and analyzed on the associations of BMI and serum UA with incidence risk of postmenopausal breast cancer by using multivariable Cox proportional hazard regression models. Mediation analysis was further conducted among DFTJ cohort to assess the intermediate role of serum UA in the BMI–breast cancer association.ResultsIn the bidirectional MR analyses, we observed that genetically determined BMI was causally associated with elevated serum UA [β(95% CI) = 0.225(0.111, 0.339), p < 0.001], but not vice versa. In the DFTJ cohort, each standard deviation (SD) increment in BMI (3.5 kg/m2) and UA (75.4 μmol/l) was associated with a separate 24% and 22% increased risk of postmenopausal breast cancer [HR(95% CI) = 1.24(1.07, 1.44) and 1.22(1.05, 1.42), respectively]. More importantly, serum UA could mediate 16.9% of the association between BMI and incident postmenopausal breast cancer.ConclusionsThe current findings revealed a causal effect of BMI on increasing serum UA and highlighted the mediating role of UA in the BMI–breast cancer relationship. Controlling the serum level of UA among overweight postmenopausal women may help to decrease their incident risk of breast cancer.

As extremely complex interactions exist in the process of economic research and development, a novel grey multivariable coupling model called CFGM(1,N) is proposed to evaluate the coordination degree between China’s technology and economy with limited information. This proposed model improves the aggregation in GM(1,N) model through the Choquet integral among λ-fuzzy measure, which can reflect interactions among factor indexes. Meanwhile, it can estimate the coordinate parameters via the whale optimization algorithm and obtains the coupling coordination degree combining with grey comentropy. To verify the proposed model, a case study using a dataset from China’s technology and the economic system is conducted. The CFGM(1,N) model has a better performance in the convergence and interpretability, as compared to the three heuristic algorithm and two classical approaches. Our finding suggests that China’s technology and the economic system is still relatively coordinated. Results also reveal that there exists strong negative cooperation between the comprehensive human input and the comprehensive capital investment in this system. First published online 19 November 2020

AbstractObjectives To appraise effective predictors for COVID-19 mortality in a retrospective cohort study.Methods A total of 1270 COVID-19 patients, including 984 admitted in Sino French New City Branch (training and internal validation sets randomly split at 7:3 ratio) and 286 admitted in Optical Valley Branch (external validation set) of Wuhan Tongji hospital, were included in this study. Forty-eight clinical and laboratory features were screened with LASSO method. Further multi-tree extreme gradient boosting (XGBoost) machine learning-based model was used to rank importance of features selected from LASSO and subsequently constructed death risk prediction model with simple-tree XGBoost model. Performances of models were evaluated by AUC, prediction accuracy, precision, and F1 scores.Results Six features, including disease severity, age, levels of high-sensitivity C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), ferritin, and interleukin-10 (IL-10), were selected as predictors for COVID-19 mortality. Simple-tree XGBoost model conducted by these features can predict death risk accurately with >90% precision and >85% sensitivity, as well as F1 scores >0.90 in training and validation sets.Conclusion We proposed the disease severity, age, serum levels of hs-CRP, LDH, ferritin, and IL-10 as significant predictors for death risk of COVID-19, which may help to identify the high-risk COVID-19 cases.KEY MESSAGESA machine learning method is used to build death risk model for COVID-19 patients.Disease severity, age, hs-CRP, LDH, ferritin, and IL-10 are death risk factors.These findings may help to identify the high-risk COVID-19 cases.