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Summary: Background: Mitochondrial dysfunction has been linked to the development of inflammatory bowel disease (IBD), but the genetic pathophysiology was not fully elucidated. We employed Mendelian randomization and colocalization analyses to investigate the associations between mitochondrial-related genes and IBD via integrating multi-omics. Methods: Summary-level data of mitochondrial gene methylation, expression and protein abundance levels were obtained from corresponding methylation, expression and protein quantitative trait loci studies, respectively. We obtained genetic associations with IBD and its two subtypes from the Inflammatory Bowel Disease Genetics Consortium (discovery), the UK Biobank (replication), and the FinnGen study (replication). We performed summary-data-based Mendelian randomization analysis to assess the associations of mitochondrial gene-related molecular features with IBD. Colocalization analysis was further conducted to assess whether the identified signal pairs shared a causal genetic variant. Findings: After integrating the multi-omics data between mQTL-eQTL and eQTL-pQTL, we identified two mitochondrial genes, i.e., PARK7 and ACADM, with tier 1 evidence for their associations with IBD and ulcerative colitis (UC). PDK1 and FISI genes were associated with UC risk with tier 2 and tier 3 evidence, respectively. The methylation of cg05467918 in ACADM was associated with lower expression of ACADM, which fits with the positive effect of cg05467918 methylation on UC risk. Consistently, the inverse associations between gene methylation and gene expression were also observed in PARK7 (cg10385390) and PDK1 (cg17679246), which were corroborated with the protective role in UC. At circulating protein level, genetically predicted higher levels of PARK7 (OR 0.36, 95% CI 0.25–0.52) and HINT1 (OR 0.47, 95% CI 0.30–0.74) were inversely associated with IBD risk; genetically predicted higher level of HINT1 was associated with a decreased risk of Crohn's disease (CD) (OR 0.26, 95% CI 0.14–0.49) and a higher level of ACADM (OR 0.67, 95% CI 0.55–0.83), PDK1 (OR 0.63, 95% CI 0.49–0.81), FIS1 (OR 0.63, 95% CI 0.47–0.83) was associated with a decreased risk of UC. Interpretation: We found that the mitochondrial PARK7 gene was putatively associated with IBD risk, and mitochondrial FIS1, PDK1, and ACADM genes were associated with UC risk with evidence from multi-omics levels. This study identified mitochondrial genes in relation to IBD, which may enhance the understanding of the pathogenic mechanisms of IBD development. Funding: XL is supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001) and Healthy Zhejiang One Million People Cohort (K-20230085).

Abstract Background The proteome is a major source of therapeutic targets. We conducted a proteome-wide Mendelian randomization (MR) study to identify candidate protein markers and therapeutic targets for colorectal cancer (CRC). Methods Protein quantitative trait loci (pQTLs) were derived from seven published genome-wide association studies (GWASs) on plasma proteome, and summary-level data were extracted for 4853 circulating protein markers. Genetic associations with CRC were obtained from a large-scale GWAS meta-analysis (16,871 cases and 26,328 controls), the FinnGen cohort (4957 cases and 304,197 controls), and the UK Biobank (9276 cases and 477,069 controls). Colocalization and summary-data-based MR (SMR) analyses were performed sequentially to verify the causal role of candidate proteins. Single cell-type expression analysis, protein-protein interaction (PPI), and druggability evaluation were further conducted to detect the specific cell type with enrichment expression and prioritize potential therapeutic targets. Results Collectively, genetically predicted levels of 13 proteins were associated with CRC risk. Elevated levels of two proteins (GREM1, CHRDL2) and decreased levels of 11 proteins were associated with an increased risk of CRC, among which four (GREM1, CLSTN3, CSF2RA, CD86) were prioritized with the most convincing evidence. These protein-coding genes are mainly expressed in tissue stem cells, epithelial cells, and monocytes in colon tumor tissue. Two interactive pairs of proteins (GREM1 and CHRDL2; MMP2 and TIMP2) were identified to be involved in osteoclast differentiation and tumorigenesis pathways; four proteins (POLR2F, CSF2RA, CD86, MMP2) have been targeted for drug development on autoimmune diseases and other cancers, with the potentials of being repurposed as therapeutic targets for CRC. Conclusions This study identified several protein biomarkers to be associated with CRC risk and provided new insights into the etiology and promising targets for the development of screening biomarkers and therapeutic drugs for CRC.

Abstract Tetraphenylethylene (TPE)-based ligands are appealing for constructing metal-organic frameworks (MOFs) with new functions and responsiveness. Here, we report a non-interpenetrated TPE-based scu Zr-MOF with anisotropic flexibility, that is, Zr-TCPE (H4TCPE = 1,1,2,2-tetra(4-carboxylphenyl)ethylene), remaining two anisotropic pockets. The framework flexibility is further anisotropically rigidified by installing linkers individually at specific pockets. By individually installing dicarboxylic acid L1 or L2 at pocket A or B, the framework flexibility along the b-axis or c-axis is rigidified, and the intermolecular or intramolecular motions of organic ligands are restricted, respectively. Synergistically, with dual linker installation, the flexibility is completely rigidified with the restriction of ligand motion, resulting in MOFs with enhanced stability and improved separation ability. Furthermore, in situ observation of the flipping of the phenyl ring and its rigidification process is made by 2H solid-state NMR. The anisotropic rigidification of flexibility in scu Zr-MOFs guides the directional control of ligand motion for designing stimuli-responsive emitting or efficient separation materials.

Brandt's Vole (Lasiopodomys brandtii) is one of the most abundant rodent species in the grasslands of Inner Mongolia, China, and one of the main carriers of Yersinia pestis, the plague bacterium. There have been several instances of plague transmission among L. brandtii, and all of their dominant flea species are known carriers of plague. Little work has been done to understand the regulation of flea abundance on L. brandtii by biotic and abiotic factors. Here, we examine the impacts of host and climate variation on flea abundance on L. brandtii in May, July, and September of 2021 in the East Ujumqin Banner, Xilinhot City, Inner Mongolia Autonomous Region. We arrived at the following conclusions: 1) There were 8 flea species representing 2 families and 5 genera collected from L. brandtii, and Frontopsylla luculenta, Neopsylla pleskei orientalis, and Amphipsylla primaris mitis were most common. 2) Host body weight, host age, season, temperature, and humidity are key factors influencing flea abundance on L. brandtii. 3) Flea species vary in their respective responses to factors.

The temperature damping capacities of Mg–3Al–1Zn-xSn (x=3, 6, 9) alloys were investigated using a Dynamic Mechanical Thermal Analyzer (DMA) under varied loading frequencies and Sn concentrations. The addition of Sn resulted in a leftward shift of the P1 dislocation damping peak around 80 °C and a rightward shift of the P3 peak around 220 °C, which were attributed to the second phases in the vicinity of grain boundaries. By combining the Granato-Lücke model and the Peguin model, the damping curves were analyzed, and the temperature damping mechanism of Mg–3Al–1Zn-xSn alloy was summarized. Before 220 °C, the addition of Sn significantly enhanced the damping capacity at different frequencies, which was attributed to the increased of point defects and precipitates. The damping mechanism was dominated by microplastic internal friction in the later part of the test. There is a negative correlation between frequency and damping. The observation of microstructures suggested that the dynamic recrystallization, the twining, and the non-basal slipping systems were the sources of the microplastic damping capacity. The dynamic recrystallization mechanism owing to cyclic loading was identified.

The ratoon rice planting area is gradually expanding, and decreasing Cadmium (Cd) accumulation in ratoon rice is important for food safety and human health. In this study, conventional indica rice (HHZ, Huanghuazhan), three-line indica–japonica hybrid rice (YY-4149, Yongyou 4149), and two-line indica hybrid rice (LY-121, Liangyou 121) were compared regarding ratoon rice yield and Cd uptake, transport, and accumulation. The distribution of Cd at different nodes in the ratoon crop was also examined. The rank-order of the Cd contents in each part (root, stem, leaf, stubble, and spike) of the main and ratoon crops of the tested cultivars was HHZ > LY-121 > YY-4149. The rank-order of the Cd content in each plant part at different nodes in the ratoon crop was HHZ > LY-121 > YY-4149. The Cd content in each plant part increased as the node position (i.e., according to the germination position of regenerated seedlings, the nodes are divided into the second, third, and fourth or fifth node from the top in stubble) was lowered. The redundancy analysis indicated that the low-node brown rice Cd content had the largest effect on the total brown rice Cd content in the ratoon crop. Accordingly, indica–japonica hybrid cultivars should be selected for the production of ratoon rice in mildly Cd-polluted areas, and the height of the main crop stubble should be maximized during harvest.

Abstract Thermal characteristic is one of the key performances of dry‐type on‐board traction transformer (D‐OBTT), which directly affects the operation safety of the new generation electric multiple units. However, due to the particularity of train‐induced wind cooling mode of D‐OBTT, the existing efficient thermal modelling methods cannot be used under fluctuating air velocity and load. A time‐saving transient thermal model for D‐OBTT is proposed. First, the framework of the transient thermal network model (TTNM) is proposed considering the coexistence of non‐fully and fully developed state of the train‐induced wind and the addition heat flow in the solid domain. Then, a novel formula for calculating the length of non‐fully developed section considering the geometric dimensions and heat flux density is proposed based on computational fluid dynamics (CFD) parametric sweeps for the first time. The accuracy of TTNM is validated by a D‐OBTT experimental setup, and the time consumption is significantly reduced compared with CFD.

Abstract The prognosis of lung cancer is poor with few effective therapies. Targeting ferroptosis is a new promising strategy for cancer therapy. LINC00641 has been involved in several cancers, however, its specific roles in lung cancer treatment remain largely unknown. Here, we reported that LINC00641 was down-regulated in tumor tissues and its downregulation was associated with poor outcomes in lung adenocarcinoma. LINC00641 was localized primarily in the nucleus and was modified by m6A. The nuclear m6A reader YTHDC1 regulated LINC00641 expression by affecting its stability. We demonstrated that LINC00641 suppressed lung cancer by inhibiting migration and invasion in vitro and metastasis in vivo. Knockdown of LINC00641 upregulated HuR protein level (especially in the cytoplasm), which subsequently increased N-cadherin levels by stabilizing its mRNA, then ultimately promoted EMT. Interestingly, LINC00641 knockdown in lung cancer cells increased the arachidonic acid metabolism and promoted ferroptosis sensitivity. Our findings identified LINC00641 as a tumor suppressor through inhibiting EMT. In another aspect, low expression of LINC00641 caused a ferroptotic vulnerability in lung cancer cells, which may serve as a potential ferroptosis-related therapeutic target for lung cancer.

Abstract Background Globally, despite prostate cancer (PCa) representing second most prevalent malignancy in male, the precise molecular mechanisms implicated in its pathogenesis remain unclear. Consequently, elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies, ultimately advancing the management of PCa. Methods A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan University. The advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in PCa. The expression of aspartoacylase (ASPA) in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting techniques. To elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis, a comprehensive set of in vitro and in vivo assays were conducted, including orthotopic and tumor-bearing mouse models (n = 8 for each group). A combination of experimental approaches, such as Western blotting, luciferase assays, immunoprecipitation assays, mass spectrometry, glutathione S-transferase pull-down experiments, and rescue studies, were employed to investigate the underlying molecular mechanisms of ASPA’s action in PCa. The Student’s t-test was employed to assess the statistical significance between two distinct groups, while one-way analysis of variance was utilized for comparisons involving more than two groups. A two-sided P value of less than 0.05 was deemed to indicate statistical significance. Results ASPA was identified as a novel inhibitor of PCa progression. The expression of ASPA was found to be significantly down-regulated in PCa tissue samples, and its decreased expression was independently associated with patients’ prognosis (HR = 0.60, 95% CI 0.40–0.92, P = 0.018). Our experiments demonstrated that modulation of ASPA activity, either through gain- or loss-of-function, led to the suppression or enhancement of PCa cell proliferation, migration, and invasion, respectively. The inhibitory role of ASPA in PCa was further confirmed using orthotopic and tumor-bearing mouse models. Mechanistically, ASPA was shown to directly interact with the LYN and inhibit the phosphorylation of LYN as well as its downstream targets, JNK1/2 and C-Jun, in both PCa cells and mouse models, in an enzyme-independent manner. Importantly, the inhibition of LYN activation by bafetinib abrogated the promoting effect of ASPA knockdown on PCa progression in both in vitro and in vivo models. Moreover, we observed an inverse relationship between ASPA expression and LYN activity in clinical PCa samples, suggesting a potential regulatory role of ASPA in modulating LYN signaling. Conclusion Our findings provide novel insights into the tumor-suppressive function of ASPA in PCa and highlight its potential as a prognostic biomarker and therapeutic target for the management of this malignancy.

Diabetes could directly induce cardiac injury, leading to cardiomyopathy. However, treatment strategies for diabetic cardiomyopathy remain limited. ZNF593-AS knockout and cardiomyocyte-specific transgenic mice were constructed. In addition, high-fat diet (HFD)-induced diabetic mouse model and db/db mice, another classic diabetic mouse model, were employed. ZNF593-AS was silenced using GapmeR, a modified antisense oligonucleotide, while overexpressed using a recombinant adeno-associated virus serotype 9-mediated gene delivery system. Transcriptome sequencing, RNA pull-down assays, and RNA immunoprecipitation assays were also performed to investigate the underlying mechanisms. ZNF593-AS expression was decreased in diabetic hearts. ZNF593-AS attenuated the palmitic acid-induced apoptosis of cardiomyocytes in vitro. In HFD-induced diabetic mice, ZNF593-AS deletion aggravated cardiac dysfunction and enhanced cardiac apoptosis and inflammation. In contrast, HFD-induced cardiac dysfunction was improved in ZNF593-AS transgenic mice. Consistently, ZNF593-AS exerted the same cardioprotective effects in db/db mice. Mechanistically, ZNF593-AS directly interacted with the functional domain of interferon regulatory factor 3 (IRF3), and suppressed fatty acid-induced phosphorylation and activation of IRF3, contributing to the amelioration of cardiac cell death and inflammation. In conclusion, our results identified the protective role of ZNF593-AS in diabetic cardiomyopathy, suggesting a novel potential therapeutic target.

Abstract The causality of the association between depression and gastrointestinal diseases is undetermined. We conducted Mendelian randomization (MR) analyses to systematically explore the associations of depression with 24 gastrointestinal diseases. Independent genetic variants associated with depression at the genome-wide significance level were selected as instrumental variables. Genetic associations with 24 gastrointestinal diseases were obtained from the UK Biobank study, the FinnGen study, and large consortia. Multivariable MR analysis was conducted to explore the mediation effects of body mass index, cigarette smoking, and type 2 diabetes. After multiple-testing corrections, genetic liability to depression was associated with an increased risk of irritable bowel syndrome, non-alcohol fatty liver disease, alcoholic liver disease, gastroesophageal reflux, chronic pancreatitis, duodenal ulcer, chronic gastritis, gastric ulcer, diverticular disease, cholelithiasis, acute pancreatitis, and ulcerative colitis. For the causal effect of genetic liability to depression on non-alcoholic fatty liver disease, a substantial proportion was mediated by body mass index. Genetic predisposition to smoking initiation mediated half of effect of depression on acute pancreatitis. This MR study suggests that depression may play a causal role in many gastrointestinal diseases.

The flow stress behavior of Mg–3Sn–1Mn alloy during thermal compression deformation was systematically studied. The thermal compression simulation experiment was carried out at different deformation temperatures and different strain rates in the range of 523–673 K and 0.001-1s−1, respectively. It is found that at low temperatures and high strain rates, a large number of twins were generated at the initial stage of thermal deformation, causing an increase in the corresponding flow stress, which makes the traditional constitutive relation model insensitive to predicting the thermal deformation behavior of Magnesium (Mg) alloys with twinning effect. To better evaluate the rheological behavior of Mg alloys, an artificial neural network (ANN) model based on a feedforward and back-propagation algorithm was developed to predict the thermal deformation behavior of Mg–3Sn–1Mn alloy affected by twinning phenomena. The inputs of the model were deformation temperature, strain rate and strain, the output was the flow stress. The comparative evaluation of the obtained results using statistical standard R2 and relative error R¯. The correlation coefficients predicted by the constitutive model were 0.964 and 0.869 at low and high stress levels, respectively. And the correlation coefficient of the neural network predictive model was 0.992. The result shows that the trained ANN is more accurate than the traditional constitutive relation model in predicting the thermal deformation behavior with the twinning effect.

Objective This study aimed to explore the global burden of early-onset cancer based on the Global Burden of Disease (GBD) 2019 study for 29 cancers worldwid.Methods and analysis Incidence, deaths, disability-adjusted life years (DALYs) and risk factors for 29 early-onset cancer groups were obtained from GBD.Results Global incidence of early-onset cancer increased by 79.1% and the number of early-onset cancer deaths increased by 27.7% between 1990 and 2019. Early-onset breast, tracheal, bronchus and lung, stomach and colorectal cancers showed the highest mortality and DALYs in 2019. Globally, the incidence rates of early-onset nasopharyngeal and prostate cancer showed the fastest increasing trend, whereas early-onset liver cancer showed the sharpest decrease. Early-onset colorectal cancers had high DALYs within the top five ranking for both men and women. High-middle and middle Sociodemographic Index (SDI) regions had the highest burden of early-onset cancer. The morbidity of early-onset cancer increased with the SDI, and the mortality rate decreased considerably when SDI increased from 0.7 to 1. The projections indicated that the global number of incidence and deaths of early-onset cancer would increase by 31% and 21% in 2030, respectively. Dietary risk factors (diet high in red meat, low in fruits, high in sodium and low in milk, etc), alcohol consumption and tobacco use are the main risk factors underlying early-onset cancers.Conclusion Early-onset cancer morbidity continues to increase worldwide with notable variances in mortality and DALYs between areas, countries, sex and cancer types. Encouraging a healthy lifestyle could reduce early-onset cancer disease burden.

The flow behavior of as-extruded Mg–3Sn-1.5Mn (wt.%) alloy was systematically researched via isothermal compression tests. The compressive temperatures (T) were from 250 °C to 400 °C, the strain rates were from 0.001 s−1 to 1s−1 and the true strain reached 0.69. Based on compression curves, flow stress apparently rose with increasing strain rate and/or decreasing temperature. Combined with the analysis of microstructure and processing map, the optimum working parameter was determined in the range of 350–400 °C, 0.01–1 s−1. According to electron backscatter diffraction (EBSD) analysis results, texture intensity significantly decreased and the basal (0001)//ED texture had transformed to basal //CD texture after compressive deformation obviously. Furthermore, the typical discontinue dynamic recrystallization (DDRX) and continue dynamic recrystallization (CDRX) were largely believed to be the major DRX mechanisms in Mg–3Sn-1.5Mn alloy. Both increasing temperature and decreasing strain rate had obvious influence on the degree of DRX. The activated slip systems in deformed grains were determined by the analysis of the in-grain misorientation axis (IGMA). As deformation temperature elevated, pyramidal slip greatly activated and dominated compressive deformation.

AimsEpidemiological evidence for the link of interleukin 1 (IL-1) and its inhibition with cardiovascular diseases (CVDs) remains controversial. We aim to investigate the cardiovascular effects of IL-1 receptor antagonist (IL-1Ra) and underlying mechanisms.MethodsGenetic variants identified from a genome-wide association study involving 30,931 individuals were used as instrumental variables for the serum IL-1Ra concentrations. Genetic associations with CVDs and cardiometabolic risk factors were obtained from international genetic consortia. Inverse‐variance weighted method was utilized to derive effect estimates, while supplementary analyses employing various statistical approaches.ResultsGenetically determined IL-1Ra level was associated with increased risk of coronary heart disease (CHD; OR, 1.07; 95% CI: 1.03-1.17) and myocardial infarction (OR, 1.13; 95% CI: 1.04-1.21). The main results remained consistent in supplementary analyses. Besides, IL-1Ra was associated with circulating levels of various lipoprotein lipids, apolipoproteins and fasting glucose. Interestingly, observed association pattern with CHD was reversed when adjusting for apolipoprotein B (OR, 0.84; 95%CI: 0.71-0.99) and slightly attenuated on accounting for other cardiometabolic risk factors. Appropriate lifestyle intervention was found to lower IL-1Ra concentration and mitigate the heightened CHD risk it posed.ConclusionApolipoprotein B represents the key driver, and a potential target for reversal of the causal link between serum IL-1Ra and increased risk of CHD/MI. The combined therapy involving IL-1 inhibition and lipid-modifying treatment aimed at apolipoprotein B merit further exploration.

A quantized plateau is typically considered to be the feature of a fractional quantum Hall state. Yan et al. report a series of plateaus quantized at unusual fractions in a confined two-dimensional electron gas, which is attributed to enhanced density in the confined region.

Sequencing-based genetic association analysis is typically performed by first generating genotype calls from sequence data and then performing association tests on the called genotypes. Standard approaches require accurate genotype calling (GC), which can be achieved either with high sequencing depth (typically available in a small number of individuals) or via computationally intensive multi-sample linkage disequilibrium (LD)-aware methods. We propose a computationally efficient two-stage combination approach for association analysis, in which single-nucleotide polymorphisms (SNPs) are screened in the first stage via a rapid maximum likelihood (ML)-based method on sequence data directly (without first calling genotypes), and then the selected SNPs are evaluated in the second stage by performing association tests on genotypes from multi-sample LD-aware calling. Extensive simulation- and real data-based studies show that the proposed two-stage approaches can save 80% of the computational costs and still obtain more than 90% of the power of the classical method to genotype all markers at various depths d≥2.

In this study, extruded deformed billet and extruded rod of Mg–6Al–1Zn–1.1Sc (wt. %) alloy were characterized by optical microscopy (OM) and electron backscatter diffraction (EBSD). The room temperature tensile properties and deformation behavior of extruded alloy were investigated using a universal testing machine and the visco-plastic self-consistent (VPSC) model. The results indicated that the coarse deformed grains (DGs) progressively disappeared and the degree of dynamic recrystallization (DRX) of the alloy increased as the sampling position approached the outlet of the extrusion die. In addition, the grain boundary strengthening induced by DRX increased the corresponding Vickers hardness. DRX mechanisms during extrusion included discontinuous DRX, continuous DRX, twin-induced DRX, and particle-stimulated nucleation (PSN). The EBSD-based in-grain misorientation axes (IGMA) analysis revealed that the slip modes within DGs were dominated by prismatic slip in the early stages of extrusion and by multiple slip modes in the later stages. The yield strength, ultimate tensile strength, and elongation of the extruded alloy were 172.4 MPa, 290.1 MPa, and 26.9%, respectively. The combination of grain boundary strengthening, texture strengthening, and secondary phase strengthening resulted in the high yield strength. The VPSC model well simulated the tensile deformation of the extruded alloy with (0001)//ED (extrusion direction) fiber texture. The superior plasticity of the extruded alloy was ascribed to the high Schmid factor (SF) of the non-basal slip and the activation of the non-basal slip facilitated by the reduction in the ratio of the critical resolved shear stress (CRSS) between the non-basal slip and the basal slip.

In this study, the hot compression test of the aged vacuum die-casting Mg-4Al-4(La, Ce) alloy was performed on Gleeble-3500 simulator. The mechanical properties of Mg-4Al-4(La, Ce) alloy were studied at different compression temperatures (100 °C, 150 °C, 200 °C, and 250 °C). During the compression, the microstructure evolution, texture, and dislocation slip of the Mg-4Al-4(La, Ce) alloy were systematically investigated by the electron backscatter diffraction (EBSD) technology. The results demonstrated that the flow stress decreased and the plasticity boosted with the increase in temperature. Mg-4Al-4(La, Ce) alloy exhibits excellent strength and toughness with elevated temperature. At 200 °C, it still has compressive strength of 204.5 MPa and compressive elongation of 59%. By observation of the microstructure, it has typical //CD texture after compression. It was found by in-grain misorientation axis (IGMA) analysis that the pyramidal slip is sufficiently activated, which effectively improves the toughness of the alloy. In addition, the dislocations and dislocations are observed at 200 °C. Therefore, the excellent mechanical properties of Mg-4Al-4(La, Ce) alloy at high temperature are the result of grain refinement strengthening, second-phase reinforcement and work hardening.

Intensive glycemic control is insufficient for reducing the risk of heart failure among patients with diabetes mellitus (DM). While the “hyperglycemic memory” phenomenon is well documented, little is known about its underlying mechanisms. In this study, a type 1 DM model was established in C57BL/6 mice using streptozotocin (STZ). Leptin receptor-deficient (db/db) mice were used as a model of type 2 DM. A type 9 adeno-associated virus was used to overexpress or knock down miR-320 in vivo. Diastolic dysfunction was observed in the type 1 DM mice with elevated miR-320 expression. However, glycemic control using insulin failed to reverse diastolic dysfunction. miR-320 knockdown protected against STZ-induced diastolic dysfunction. Similar results were observed in the type 2 DM mice. In vitro, we found that miR-320 promoted CD36 expression, which in turn induced further miR-320 expression. CD36 was rapidly induced by hyperglycemia at protein level compared with the much slower induction of miR-320, suggesting a positive feedback loop of CD36/miR-320 with CD36 protein induction as the initial triggering event. In conclusion, in DM-induced cardiac injury, miR-320 and CD36 mutually enhance each other’s expression, leading to a positive feedback loop and a sustained hyperlipidemic state in the heart.

The EAST ICRF system operating space has been extended in power and phase control with a low-level RF system for the new double-strap antenna. Then the multi-step power and periodic phase scanning experiment were conducted in L-mode plasma, respectively. In the power scanning experiment, the stored energy, radiation power, plasma impedance and the antenna's temperature all have positive responses during the short ramp-ups of PL,ICRF. The core ion temperature increased from 1 keV to 1.5 keV and the core heating area expanded from |Z|≤5cm to |Z|≤10cm during the injection of ICRF waves. In the phasing scanning experiment, in addition to the same conclusions as the previous relatively phasing scanning experiment, the superposition effect of the fluctuation of stored energy, radiation power and neutron yield caused by phasing change with dual antenna, resulting in the amplitude and phase shift, was also observed. The active control of RF output facilitates the precise control of plasma profiles and greatly benefits future experimental exploration.

During the construction of water conservancy and hydropower projects, the time series of safety monitoring data for slope engineering is often short. When establishing a slope safety monitoring model, it is necessary to study the modelling method under small sample conditions and closely examine the space–time information in the monitoring data for the limited length of each measuring point. To this end, this paper initially proposes using the Ward clustering method to spatially cluster anchor cable prestress measuring points in different parts of a slope; then, according to the clustering results, a safety monitoring model for slope anchor cable prestress is established for each type of measuring point based on a Bayesian panel vector autoregressive (BPVAR) model with highly accurate small sample modelling. Finally, slope anchor cable prestress monitoring data in China are taken as examples for verification analysis. The analysis results show that the prestressed measuring points of the slope anchor cable for this project are divided into four categories: excavation causes the prestress of some slope measuring points to continue to increase, and the tension or compression of the structural plane leads to an increase or decrease in prestress. The multiple correlation coefficients of the training set and test set data of the BPVAR model are all above 0.80, and the prediction error of the validation set is less than that of the vector autoregressive (VAR) model, the autoregressive moving average (ARMA) model and the long short-term memory (LSTM) model. The measured prestress values are all within the 95% confidence interval, which provides a reference for safety state identification in slope engineering.

The performance of green marketing refers to the realistic state of green marketing activities in terms of enterprise development, consumer demand and social ecological environment. These aspects are represented by the game equilibrium between green marketing subjects. The better the game equilibrium between green marketing subjects, the better the performance of green marketing. In the real market environment, this ideal balance is often broken, and green marketing activities are difficult to carry out normally, affecting the performance of green marketing. At the same time, the characteristics of green marketing performance have its particularity. On the one hand, green marketing performance cannot be formed in a short time. Once good performance is formed, this performance can play a role in a long time; On the other hand, there are many factors involved, and the quality of performance not only depends on the improvement of the social ecological environment, but also includes the achievement of enterprise goals and consumer satisfaction. The enterprise green marketing performance management evaluation is a classical multiple attribute decision making (MADM). Recently, the TODIM and TOPSIS method has been used to cope with MADM issues. The triangular fuzzy neutrosophic sets (TFNSs) are used as a tool for characterizing uncertain information during the enterprise green marketing performance management evaluation. In this manuscript, the triangular fuzzy neutrosophic TODIM-TOPSIS (TFN-TODIM-TOPSIS) method is built to solve the MADM under TFNSs. In the end, a numerical case study for enterprise green marketing performance management evaluation is given to validate the proposed method.

Traditional security surveillance detection relies on post-event forensics or is hosted on a backend server, making it impossible to identify behaviors filmed in the field online. This paper proposes the Smart City Security System (SCSS) for detecting anomalous activity in public locations online. SCSS combines the DeepSORT and YOLOv4 algorithms to generate the DS-YOLO aberrant behavior detection algorithm, which compares and matches the target detected in the previous picture frame with the target detected in the following frame to achieve detection and tracking. SCSS is equipped with GPS, WIFI, and Uninterruptible Power Supply (UPS). When a risky behavior is detected, the system will upload the abnormal event as well as the latitude and longitude that occurred to the cloud via the WIFI and notify the user. The recognition accuracy of three deviant behaviors, including Fight, Car Accident, and Fall, was examined using diverse situations, and the results were 89%, 90%, and 90.33% respectively. The findings demonstrate that SCSS has successfully made the transition from passive monitoring to active identification, offsetting the flaws of conventional security systems that can only post-mordem forensics, and bridging the gap of the construction of national smart cities.

Abstract Exposure to natural environments offers an array of mental health benefits. Virtual reality provides simulated experiences of being in nature when outdoor access is limited. Previous studies on virtual nature have focused mainly on single "doses" of virtual nature. The effects of repeated exposure remain poorly understood. Motivated by this gap, we studied the influence of a daily virtual nature intervention on symptoms of anxiety, depression, and an underlying cause of poor mental health: rumination. Forty college students (58% non-Hispanic White, median age = 19) were recruited from two U.S. universities and randomly assigned to the intervention or control group. Over several weeks, anxious arousal (panic) and anxious apprehension (worry) decreased with virtual nature exposure. Participants identifying as women, past VR users, experienced with the outdoors, and engaged with the beauty in nature benefited particularly strongly from virtual nature. Virtual nature did not help symptoms of anhedonic depression or rumination. Further research is necessary to distinguish when and for whom virtual nature interventions impact mental health outcomes.

Abstract The design of the dry‐type on‐board traction transformer (OBTT), a new lightweight method in the traction system of electric multiple units, needs to consider the transient hot spot temperature (HST) under different railroad line operating conditions. In order to quickly calculate the transient HST of dry‐type OBTT when operating under different railroad line conditions, a calculation method (hereinafter referred to as GP‐HST method) by combining an enhanced genetic programming algorithm (GP) with computational fluid dynamics (CFD) is presented. First, intercept a section from the railroad line to be calculated and use the CFD method to calculate the transient HST of the section railroad line. Then, the enhanced GP modelling is driven by this section of railroad line measured and simulated data. Next, a calculation model with an implicit mathematical correlation between railroad line operating conditions and the dry‐type OBTT transient HST is established. Finally, the calculation model quickly calculates the transient HST of the remaining railroad line in operation. To validate the presented method, the calculation model obtained using the presented method is used to calculate the transient HST for another railroad line with significantly different operating conditions, and it is compared with the direct use of the CFD method. The calculation results show that the GP‐HST method reduces the simulation time of the CFD method from 950 to 0.25 min with a maximum error, mean absolute error, and mean relative error of 1.856 K, 0.778 K, and 0.22%, respectively, for a railroad line with a running time of about half an hour. This shows that the GP‐HST method can effectively help to improve the design efficiency of dry‐type OBTT.

Abstract Background Pseudoaneurysm is a known complication of penetrating arterial injuries such as catheterization, gunshot wounds, and open fractures. Vaccination is an effective method for preventing multiple, serious, infectious diseases in children. Common adverse reactions related to vaccination include fever, swelling, redness, and pain. Brachial pseudoaneurysm after vaccination has not been previously reported. Case presentation Herein we describe a novel case of brachial pseudoaneurysm after vaccination in a child aged 1 year and 3 months. A pulsatile mass was formed in the medial left arm of the infant 10 days after vaccination at a community hospital and gradually grew larger. Preoperative images depicted an eccentric aneurysm in the brachial artery and a swirling flow pattern in the mass. The pseudoaneurysm was excised, and vein graft interpositioning was successfully performed. There were no short-term or long-term complications during the follow-up period. Conclusions Brachial pseudoaneurysm is a rare complication of vaccination via intramuscular injection. Medical staff should avoid puncture wounds to the brachial artery during vaccination, especially in infants.

Abstract SLC12A5, a neuron-specific potassium-chloride co-transporter, has been reported to promote tumor progression, however, the underlying mechanism remains unclear. Here we report that SLC12A5 functions as an oncogene to promote tumor progression and castration resistance of prostate cancer through the N6-methyladenosine (m6A) reader YTHDC1 and the transcription factor HOXB13. We have shown that the level of SLC12A5 was increased in prostate cancer, in comparison to its normal counterparts, and further elevated in castration-resistant prostate cancer (CRPC). The enhanced expression of SLC12A5 mRNA was associated with neuroendocrine prostate cancer (NEPC) progression and poor survival in prostate cancer. Furthermore, we demonstrated that SLC12A5 promoted the castration resistance development of prostate cancer in addition to the cell proliferation and migration. Interestingly, SLC12A5 was detected in the cell nucleus and formed a complex with nuclear m6A reader YTHDC1, which in turn upregulated HOXB13 to promote the prostate cancer progression. Therefore, our findings reveal a mechanism that how the potassium-chloride cotransporter SLC12A5 promotes the tumor progression and provide a therapeutic opportunity for prostate cancer to apply the neurological disorder drug SLC12A5 inhibitors.

On 6 June 2017, four severe clear-air turbulence (CAT) events were observed over northern China within 3 h. These events mainly occurred at altitudes between 8.1 and 9.5 km. The characteristics and possible mechanisms of the CAT events in the different regions are investigated here using the weather research and forecasting (WRF) model. The simulated wind and temperature fields in a 27 km coarse domain were found to be in good agreement with those of the ERA5 (European Centre for Medium-Range Weather Forecasts Reanalysis v5) and the observed soundings of operational radiosondes over northern China. In terms of synoptic features, the region where the turbulence occurred is characterized by a southwest–northeast upper-level jet stream. The upper-level jet stream observed at an altitude of 10.4 km consistently moved eastwards, with a maximum wind speed of 61.7 m/s. Simultaneously, the upper-level front–jet system on the cyclonic shear side of the upper-level jet stream also exhibited an eastward motion. The developed upper-level front–jet system induced significant vertical wind shear (VWS) and tropopause folding in the vicinity of these CAT events. Despite the high stability resulting from tropopause folding, the presence of strong VWS (1.90 × 10−2 s−1–2.55 × 10−2 s−1) led to a low Richardson number (Ri) (0.24–0.88) and caused Kelvin–Helmholtz instability (KHI), which ultimately induced CAT. Although a standard numerical weather forecast resolution of tens of kilometers is adequate to capture turbulence for most CAT events, it is still necessary to use high-resolution numerical simulations (such as 3 km) to calculate more accurate CAT indices (such as Ri) for CAT prediction in some specific cases.

This study investigates, for the first time, the urbanization effect (UE) on local extreme climate events in Urumqi, China, based on 22 indices of climate extremes, which are calculated with daily observation data from 1976 to 2018. These analyses reveal a pronounced nocturnal urban heat island (UHI) effect and a daytime urban cold island (UCI) effect. Due to Urumqi’s arid climate background, the UCI effect is considered a unique feature of the UE, which significantly differs from those in eastern and northern China. The UE on the TR20 index (number of days with minimum daily temperature exceeding 20 °C) reached 5.22 d/10a, indicating that urbanization has led to a fast increase in the number of hot nights in Urumqi. The absolute averaged UE on the indices measuring the frequency of warm events is about twice as large as that on the indices measuring the frequency of cold events, while that on the indices measuring the intensity of warm events is about one third of that on the indices measuring the intensity of cold events. The highest averaged urbanization contributions (UCs) to the extreme warm and cold events are represented by the frequency indices and the intensity indices, respectively, while those contributing to the extreme precipitation events are represented by the duration indices. Moreover, urbanization probably exacerbates the degree of wetting in the overall “warming and wetting” climate trend of the region. These findings can be seen as new evidence to provide scientific basis for further investigation of the UE on climate changes in arid regions.

Resource partitioning may allow species coexistence. Sand dunes in the typical steppe of Alxa Desert Inner Mongolia, China, consisting of desert, shrub, and grass habitats, provide an appropriate system for studies of spatial niche partitioning among small mammals. In this study, the spatial niche characteristics of four rodents, Orientallactaga sibirica, Meriones meridianus, Dipus sagitta, and Phodopus roborovskii, and their responses to environmental changes in the Alxa Desert were studied from 2017 to 2021. Using the capture-mark-recapture method, we tested if desert rodents with different biological characteristics and life history strategies under heterogeneous environmental conditions allocate resources in spatial niches to achieve sympatric coexistence. We investigated the influence of environmental factors on the spatial niche breadth of rodents using random forest and redundancy analyses. We observed that the spatial niche overlap between O. sibirica and other rodents is extremely low (overlap index ≤ 0.14). P. roborovskii had the smallest spatial niche breadth. Spatial niche overlap was observed in two distinct species pairs, M. meridianus and D. sagitta, and P. roborovskii and D. sagitta. The Pielou evenness index of rodent communities is closely related to the spatial distribution of rodents, and the concealment of habitats is a key factor affecting the spatial occupation of rodents.

Coral reefs are ecosystems that are highly vulnerable to external environmental impacts, including changes associated with ocean acidification and global warming. Assessing the vulnerability of coral reef growth environments over large areas of the sea is a difficult and complex process, as it is influenced by many variables. There are few studies on environmental vulnerability assessment of coral islands and reefs in the South China Sea. It is therefore particularly important to understand the environmental sensitivity of corals and how coral communities respond to changes in climate-related environmental variables. In this study, indicators were selected mainly from natural environmental factors that hinder the development of coral reefs. The sea surface temperature (SST), sea surface salinity (SSS), wind velocity (WV) and direction, sea level height (SL), ocean currents (OC), and chlorophyll concentration (Chl) of coral reefs in South China Sea Island were integrated to calculate the coral reef environmental vulnerability region. In a GIS environment, Spatial Principal Component Analysis (SPCA) was used to develop sensitivity models and evaluate the ecological vulnerability of coral reefs. Based on the Environmental vulnerability indicator (EVI) values, the study area was classified as 5 grades of ecological vulnerability: Potential (0.000–0.577), Light (0.577–0.780), Medium (0.780–0.886), Heavy (0.886–0.993) and Very Heavy (0.993–1.131). Sensitivity models identified regional gradients of environmental stress and found that some coral reefs in western Malaysia and southwestern Philippines have higher vulnerability. Meanwhile, the study found that the reefs of Paracel Islands and Macclesfield Bank areas of medium vulnerability. Future use of high-precision data from long time series will allow better estimates of site-specific vulnerability and allow for the precise establishment of marine protected areas so that the ecological diversity of coral reefs can be sustained.

BackgroundThe interleukin-1 pathway has been linked to pancreatic diseases. We applied the Mendelian randomization approach to explore whether higher interleukin-1 receptor antagonist (IL-1RA) levels reduce the risk of acute and chronic pancreatitis and pancreatic cancer.MethodsGenetic variants associated with blood IL-1RA levels at the genome-wide significance level and located 5MB downstream or upstream of the IL1RN gene were extracted from a genome-wide meta-analysis of 21,758 participants. After pruning, genetic variants without linkage disequilibrium were used as genetic instrument for IL-1RA. Summary-level data on acute and chronic pancreatitis and pancreatic cancer were obtained from the UK Biobank and FinnGen studies. The associations were meta-analyzed for one outcome from two sources.ResultsGenetically predicted higher levels of IL-1RA were associated with a lower risk of acute and chronic pancreatitis and pancreatic cancer. In the meta-analysis of UK Biobank and FinnGen, the combined odds ratio was 0.87 (95% confidence interval [CI] 0.77-0.97, P=0.003) for acute pancreatitis, 0.73 (95% CI 0.65-0.82, P=2.93×10-8) for chronic pancreatitis, and 0.86 (95% CI 0.77-0.96, P=0.009) for pancreatic cancer per one standard deviation increment in genetically predicted levels of IL-1RA.ConclusionThis study suggests a protective role of IL-1RA in three major pancreatic diseases, which hints the therapeutic potentials of IL-1RA in pancreatic diseases.

ObjectiveTo systematically estimate and compare the effectiveness and cost-effectiveness of the glucagon-like peptide-1 receptor agonists (GLP-1RAs) approved in China and to quantify the relationship between the burden of diabetic comorbidities and glycosylated hemoglobin (HbA1c) or body mass index (BMI).MethodsTo estimate the costs (US dollars, USD) and quality-adjusted life years (QALY) for six GLP-1RAs (exenatide, loxenatide, lixisenatide, dulaglutide, semaglutide, and liraglutide) combined with metformin in the treatment of patients with type 2 diabetes mellitus (T2DM) which is inadequately controlled on metformin from the Chinese healthcare system perspective, a discrete event microsimulation cost-effectiveness model based on the Chinese Hong Kong Integrated Modeling and Evaluation (CHIME) simulation model was developed. A cohort of 30,000 Chinese patients was established, and one-way sensitivity analysis and probabilistic sensitivity analysis (PSA) with 50,000 iterations were conducted considering parameter uncertainty. Scenario analysis was conducted considering the impacts of research time limits. A network meta-analysis was conducted to compare the effects of six GLP-1RAs on HbA1c, BMI, systolic blood pressure, and diastolic blood pressure. The incremental net monetary benefit (INMB) between therapies was used to evaluate the cost-effectiveness. China’s per capita GDP in 2021 was used as the willingness-to-pay threshold. A generalized linear model was used to quantify the relationship between the burden of diabetic comorbidities and HbA1c or BMI.ResultsDuring a lifetime, the cost for a patient ranged from USD 42,092 with loxenatide to USD 47,026 with liraglutide, while the QALY gained ranged from 12.50 with dulaglutide to 12.65 with loxenatide. Compared to exenatide, the INMB of each drug from highest to lowest were: loxenatide (USD 1,124), dulaglutide (USD −1,418), lixisenatide (USD −1,713), semaglutide (USD −4,298), and liraglutide (USD −4,672). Loxenatide was better than the other GLP-1RAs in the base-case analysis. Sensitivity and scenario analysis results were consistent with the base-case analysis. Overall, the price of GLP-1RAs most affected the results. Medications with effective control of HbA1c or BMI were associated with a significantly smaller disease burden (p

IntroductionCOVID-19 acutely shocked both socio-economic and food systems in 2020. We investigated the impact of COVID-19 on production and consumption of gardened produce, backyard poultry, wild game and fish, and foraged mushrooms, berries, and other plants in New York State, aiming to understand crisis influenced food choice and motivations, including food security.MethodsWe conducted an online, cross-sectional survey in October–December 2020 with a convenience sample of participants (n = 505) with an interest in gardening, poultry rearing, foraging, hunting, and/or fishing from six counties in upstate New York. We recruited through the New York Department of Environmental Conservation, Cornell Cooperative Extension, and other relevant email and social media pages.ResultsAcross the wild and backyard food production strategies, 4.0–14.3% of respondents reported engaging for the first time and 39.6–45.7% reported increased production (a little or a lot more), and 31.6–42.7% of respondents’ production was the same as the previous year. Consumption of foods produced was widespread, including fruit and vegetables (97.6% of producers also consumed), backyard eggs (92.7%), and foraged foods (93.8%). For meats, a majority consumed backyard poultry meat (51.2%), wild-caught fish (69.7%), and wild game they hunted (80.1%). The frequency of consumption of fruit and vegetables (average of 13.5 times/month) and eggs (16.4 times/month) was very high, while average consumption of poultry meat, foraged foods, fish, and wild game ranged from 3.1 to 5.8 times/month. The number of respondents who reported “have more control over food availability” as motivation to produce all wild and backyard foods increased from 2019 to 2020 (p

The K-Clip™ system is emerging as an alternative to correct tricuspid regurgitation (TR) for patients with high surgical risk. However, patients with recurrent severe tricuspid regurgitation after prior Kay’s annuloplasty are not generally deemed to be candidates for K-Clip™ implantation. Herein, we report a case of a 63-year-old woman with recurrent symptomatic torrential tricuspid regurgitation 5 years after double valve replacement with Kay’s annuloplasty of the tricuspid valve. The K-Clip™ was successfully implanted, and the severity of tricuspid regurgitation and dimensions of tricuspid annulus achieved significant reduction. In conclusion, K-Clip™ can still be feasible and effective for patients with prior Kay’s annuloplasty. However, indications become more rigorous, and evaluation should be more comprehensive.

Hordeum L. is widely distributed in mountain or plateau of subtropical and warm temperate regions around the world. Three wild perennial Hordeum species, including H. bogdanii, H. brevisubulatum, and H. violaceum, have been used as forage and for grassland ecological restoration in high-altitude areas in recent years. To date, the degree of interspecies sequence variation in the three Hordeum species within existing gene pools is still not well-defined. Herein, we sequenced and assembled chloroplast (cp) genomes of the three species. The results revealed that the cp genome of H. bogdanii showed certain sequence variations compared with the cp genomes of the other two species (H. brevisubulatum and H. violaceum), and the latter two were characterized by a higher relative affinity. Parity rule 2 plot (PR2) analysis illuminated that most genes of all ten Hordeum species were concentrated in nucleotide T and G. Numerous single nucleotide polymorphism (SNP) and insertion/deletion (In/Del) events were detected in the three Hordeum species. A series of hotspots regions (tRNA-GGU ~ tRNA-GCA, tRNA-UGU ~ ndhJ, psbE ~ rps18, ndhF ~ tRNA-UAG, etc.) were identified by mVISTA procedures, and the five highly polymorphic genes (tRNA-UGC, tRNA-UAA, tRNA-UUU, tRNA-UAC, and ndhA) were proved by the nucleotide diversity (Pi). Although the distribution and existence of cp simple sequence repeats (cpSSRs) were predicted in the three Hordeum cp genomes, no rearrangement was found between them. A similar phenomenon has been found in the cp genome of the other seven Hordeum species, which has been published so far. In addition, evolutionary relationships were reappraised based on the currently reported cp genome of Hordeum L. This study offers a framework for gaining a better understanding of the evolutionary history of Hordeum species through the re-examination of their cp genomes, and by identifying highly polymorphic genes and hotspot regions that could provide important insights into the genetic diversity and differentiation of these species.

Sentinel-2 imagery has garnered significant attention in many earth system studies due to free access and high revisit frequency. Since its spatial resolution is insufficient for many applications, e.g., fine-grained land cover mapping, some studies employ fusion technique that combines high-resolution RGB images with Sentinel-2 multispectral images to improve the resolution of the latter. However, there are two issues in the existing image fusion methods. First, these methods usually assume that the time intervals between images are short (within several days), which is a strong assumption for large-scale high-resolution images and many real-world applications. Second, the spectral discrepancy between multispectral and RGB images could induce spectral aberrations in Sentinel-2 imagery upon fusion. To alleviate these issues, we propose an adaptive image fusion approach named S2IFNet, adaptively fusing images with long-time intervals (from months to years) and spectral inconsistency, thereby increasing the multispectral band resolution of Sentinel-2 imagery. Building on top of the feature extraction and fusion modules, we propose a spectral feature compensation module and a change-aware feature reconstruction module. The former alleviates the possible degradation of spectral attributes in Sentinel-2 imagery resulting from feature fusion. The latter integrates semantic and texture information to avoid adding fake textures caused by land cover changes over time. The experiments demonstrate that S2IFNet surpasses existing image fusion and reference-based super-resolution methods on synthetic and real datasets, yielding fusion results that are clearer and more reliable.

Membrane-based separation processes has been recently of significant global interest compared to other conventional separation approaches due to possessing undeniable advantages like superior performance, environmentally-benign nature and simplicity of application. Computational simulation of fluids has shown its undeniable role in modeling and simulation of numerous physical/chemical phenomena including chemical engineering, chemical reaction, aerodynamics, drug delivery and plasma physics. Definition of fluids can be occurred using the Navier–Stokes equations, but solving the equations remains an important challenge. In membrane-based separation processes, true perception of fluid’s manner through disparate membrane modules is an important concern, which has been significantly limited applying numerical/computational procedures such s computational fluid dynamics (CFD). Despite this noteworthy advantage, the optimization of membrane processes using CFD is time-consuming and expensive. Therefore, combination of artificial intelligence (AI) and CFD can result in the creation of a promising hybrid model to accurately predict the model results and appropriately optimize membrane processes and phase separation. This paper aims to provide a comprehensive overview about the advantages of commonly-employed ML-based techniques in combination with the CFD to intelligently increase the optimization accuracy and predict mass transfer and the unfavorable events (i.e., fouling) in various membrane processes. To reach this objective, four principal strategies of AI including SL, USL, SSL and ANN were explained and their advantages/disadvantages were discussed. Then after, prevalent ML-based algorithm for membrane-based separation processes. Finally, the application potential of AI techniques in different membrane processes (i.e., fouling control, desalination and wastewater treatment) were presented.

Abstract Background Biliary tract cancers (BTCs) are a series of heterogeneous malignancies that are broadly grouped based on the anatomical site where they arise into subtypes including intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), gallbladder cancer (GBC), and ampulla of Vater cancer (AVC). Methods and Results The present study provides an overview of the epidemiology of the various BTCs based on data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2018. Distinct differences in both incidence and mortality rates were observed for these BTCs as a function of age, sex, ethnicity, and calendar year. In 2018, BTCs emerged as the fifth most prevalent form of alimentary tract cancer in the USA. While the incidence and mortality of ICC appear to be increasing, the incidence rates of GBC, ECC, and AVC have remained stable, as have the corresponding mortality rates. The most common and deadliest BTCs in 2018 were ICC and GBC among males and females, respectively. The ethnic groups exhibiting the highest incidence rates of these different BTCs were American Indians and Alaska Natives for GBC, and Asian and Pacific Islanders for ICC, ECC, and AVC. The incidence of all of these forms of BTC rose with age. There were some variations in BTCs in terms of staging, locoregional surgical treatments, adjuvant therapies, and prognostic outcomes from 2000 to 2018. Conclusions The epidemiological characteristics, staging, locoregional surgical treatments, adjuvant therapies, and prognostic outcomes were distinct for each of these BTCs.

Abstract The application of eco‐friendly C4F7N/CO2 gas mixture has become a hot topic in the power industry. To obtain the influence law of micro‐water on the AC insulation characteristics of C4F7N/CO2 gas mixture, breakdown tests were carried out under different non‐uniform electric fields and micro‐water volume fractions. With the gap distance of 1 mm and the electric field non‐uniform coefficient less than 4.42, the breakdown voltage is positively correlated with gas pressure. With the gap distance of 6 mm and the electric field non‐uniform coefficient of 9.28, the breakdown voltage shows a typical N‐type change trend with the increase of gas pressure. With the gap distance of 9 mm and the electric field non‐uniform coefficient up to 16.45, the breakdown voltage shows a typical N‐type change trend with the increase of gas pressure. Micro‐water has a negative effect on breakdown voltage under different electric fields, meanwhile the breakdown voltage of slightly non‐uniform electric field is greatly affected by micro‐water, and the influence of micro‐water on breakdown voltage is different under different gas pressures. Therefore, the influence of operating gas pressure and slightly non‐uniform electric field should be considered when the micro‐water control index of C4F7N/CO2 gas mixture insulated equipment is formulated.

Abstract Background The associations of rheumatoid arthritis (RA) with risk of site-specific cancers beyond lymphohematopoietic cancer have been scarcely explored. We conducted a Mendelian randomization investigation of the associations of RA with site-specific cancers in European and East Asian populations. Methods Independent genetic variants strongly associated with RA in European and East Asian populations were selected as instrumental variables from genome-wide association studies of 58,284 European individuals (14,361 cases and 43,923 controls) and 22,515 East Asian individuals (4873 cases and 17,642 controls), respectively. The associations of genetic variants with overall and 22 site-specific cancers were extracted from the UK Biobank study (n = 367,561), the FinnGen study (n = 260,405), Biobank Japan (n = 212,453), and international consortia. The associations for one outcome from different data sources were combined by meta-analysis. Results In the European population, the combined odds ratios per 1-unit increase in log odds of genetic liability to RA were 1.06 (95% confidence interval [CI] 1.03–1.10) for head and neck cancer, 1.06 (95% CI 1.02–1.10) for cervical cancer, 0.92 (95% CI 0.87–0.96) for testicular cancer, and 0.94 (95% CI 0.90–0.98) for multiple myeloma. In the East Asian population, the corresponding odds ratios were 1.17 (95% CI 1.06–1.29) for pancreatic cancer, 0.91 (95% CI 0.88–0.94) for breast cancer, and 0.90 (95% CI 0.84–0.96) for ovarian cancer. There were suggestive associations for breast and ovarian cancer and overall cancer in the European population. No other associations were observed. Conclusion This study suggests that RA may play a role in the development of several site-specific cancers.

Abstract Background We performed phenome-wide Mendelian randomization analysis (MR-PheWAS), two-sample MR analysis, and systemic review to comprehensively explore the health effects of milk consumption in the European population. Methods Rs4988235 located upstream of the LCT gene was used as the instrumental variable for milk consumption. MR-PheWAS analysis was conducted to map the association of genetically predicted milk consumption with 1081 phenotypes in the UK Biobank study (n=339,197). The associations identified in MR-PheWAS were examined by two-sample MR analysis using data from the FinnGen study (n=260,405) and international consortia. A systematic review of MR studies on milk consumption was further performed. Results PheWAS and two-sample MR analyses found robust evidence in support of inverse associations of genetically predicted milk consumption with risk of cataract (odds ratio (OR) per 50 g/day increase in milk consumption, 0.89, 95% confidence interval (CI), 0.84–0.94; p=3.81×10−5), hypercholesterolemia (OR, 0.91, 95% CI 0.86–0.96; p=2.97×10−4), and anal and rectal polyps (OR, 0.85, 95% CI, 0.77–0.94; p=0.001). An inverse association for type 2 diabetes risk (OR, 0.92, 95% CI, 0.86–0.97; p=0.003) was observed in MR analysis based on genetic data with body mass index adjustment but not in the corresponding data without body mass index adjustment. The systematic review additionally found evidence that genetically predicted milk consumption was inversely associated with asthma, hay fever, multiple sclerosis, colorectal cancer, and Alzheimer’s disease, and positively associated with Parkinson’s disease, renal cell carcinoma, metabolic syndrome, overweight, and obesity. Conclusions This study suggests several health effects of milk consumption in the European population.

The flexible DC grid has the capability to transport and distribute electric energy in multiterminal power system, and avoid the adverse impact on AC power grid in reactive power consumption and current harmonic. Unfortunately, because of the discharge of submodule capacitor facing the short-circuit fault of the overhead line, The overcurrent problem caused by the fault restricts the further development of the DC grid. At present, the research on short-circuit fault of flexible DC grid is mainly based on computer software simulation without mathematical expression to describe failure process quantitatively. This paper proposes a short-circuit fault current calculation method describing flexible DC grid fault process. Firstly, the linearized equivalent model of the MMC converter station is obtained by considering the discharge characteristics of the submodule capacitors. Secondly, considering the DC grid space topology, the parsed expression of overcurrent in short circuit fault is derived. Finally, the analysis results of the paper are compared with the software simulation results of the PSCAD/EMTDC platform to verify the validity and accuracy of the overcurrent algorithm.

The hot deformation behavior of as-cast Mg-2Zn-0.5Mn-0.2Ca alloys was investigated by hot compression tests conducted at 250–400 °C with strain rates of 0.001–1 s−1. The true stress–strain curves showed that flow stress increased with the increase of strain rates and decrease of temperatures. The constitutive equation was obtained, and the calculated average activation energy is 196.79 kJ mol−1. The processing map is developed. Combined with the analyses of microstructural and processing map, the optimal processing parameter is determined at 350 °C and 0.001–0.1 s−1. Based on EBSD analysis, the microstructures of the instability areas and the stable areas are quite different, yet both have a //CD texture. The slip system in deformed grains was determined by the in-grain misorientation axis (IGMA) analysis. Typical discontinuous dynamic recrystallization (DDRX) mechanism is the main dynamic recrystallization (DRX) mechanism. As the decrease of the strain rates and the increase of the deformation temperatures, the DRX fraction gradually increased, meanwhile, the behavior of DRX has an obvious weakening effect on texture strength.

Large number of photovoltaic (PV) power plants connected to a power grid can bring significant impacts to fault currents and the operation of protection systems. In this paper, short-circuit current characteristics of a PV system with low voltage ride through (LVRT) capability under a symmetrical fault is studied. PV system short-circuit experiments with different voltage dips at high and low output power levels are designed and conducted. The experiment results provide useful and valuable references for researches of PV system short-circuit current characteristics, modeling and PV system short-circuit current contribution to a power grid. Then, based on the experiment results, steady-state values, peak values and steady state short-circuit currents harmonic characteristics at different conditions are obtained and analyzed. It is found that, the DC component amplitude of a PV system short-circuit current is almost negligible compared with that of the power frequency component, which is different from conventional synchronous generator short-circuit current. Meanwhile, based on the LVRT control strategy and experimental results, the expression of steady-state short-circuit current RMS value is derived and verified, which provides an important basis for short-circuit current calculation of power system with large scale of PV plants.

Abstract Autoimmune diseases and coronavirus disease 2019 (COVID-19) share many similarities. Concerns have arisen that autoimmune diseases may increase the susceptibility and severity of COVID-19. We used Mendelian randomization to investigate whether liability to autoimmune diseases is related to COVID-19 susceptibility and severity. Genetic instruments for 8 autoimmune diseases, including type 1 diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, psoriasis, multiple sclerosis, primary sclerosing cholangitis, primary biliary cirrhosis and juvenile idiopathic arthritis, were obtained from published genome-wide association studies. Two-sample Mendelian randomization analyses of the associations of liability to each autoimmune disease with COVID-19 infection, hospitalized COVID-19, and very severe COVID-19 were performed using the latest publicly available genome-wide association study for COVID-19. Genetic liability to each of the autoimmune diseases was largely not associated with COVID-19 infection, hospitalized COVID-19, or very severe COVID-19 after accounting for multiple comparison. Sensitivity analysis excluding genetic variants in the human leukocyte antigen gene, which has an important role in the immune response, showed similar results. The autoimmune diseases examined were largely not genetically associated with the susceptibility or severity of COVID-19. Further investigations are warranted.

Abstract Background The Happiness Index Scale (HIS) is a newly developed scale by our group to screen for common psychological illnesses among general hospital inpatients. This study aimed to analyze the reliability, validity and screening effect of the HIS and to explore its clinical application. Methods From April 1, 2021, to December 31, 2021, a total of 8405 continuous inpatients were enrolled from different departments of a large tertiary general hospital with 1385 inpatient beds in Guangzhou, Guangdong Province, China. Using a cross-sectional survey design, each participant was assessed with the Patient Health Questionnaire 9(PHQ-9), Generalized Anxiety Disorder 7 items(GAD-7), Athens Insomnia Scale (AIS), Columbia Suicide Severity Rating Scale (C-SSRS) and HIS within 24 h of admission. McDonald's ω coefficient, the Guttman split-half coefficient and the test–retest reliability coefficient were used to evaluate the reliability of the HIS and the construct validity and criterion validity of the validity tests. Scores on the PHQ-9, GAD-7, AIS, and C-SSRS were used as the gold standard tools to analyze the screening effect of the HIS. Results The HIS exhibited very good reliability, with a McDonald's ω coefficient of 0.825, a Guttman split-half coefficient of 0.920 and a test–retest reliability coefficient of 0.745 (P

The useful mineral in a high-iron manganese ore in Zambia is hematite and various manganese minerals, and the iron grade is 44.71%, the manganese grade is 17.86%. In order to make an appropriate sorting process, the chemical composition, mineral composition and embedded characteristics of the ore were studied by optical microscope, chemical analysis and X-ray diffraction. The research results show that the main iron mineral is hematite, the content is 61.53%; the main manganese minerals are anthracite, limonite and soft manganese, the content are 18.62%, 4.82% and 4.66%. Finally, pre-concentration-magnetization roasting-magnetic separation test was carried out on the ore, and the average TFe grade was 67.97%, the average recovery rate was 94.67%; the average Mn grade was 49.85%; the average recovery rate was 88.24%. The research results have certain guiding significance for the formulation of the ore sorting process, and also can provide a reference for similar ore.

Abstract A considerable number of glioblastoma (GBM) patients developed drug resistance to Temozolomide (TMZ) during chemotherapy, resulting in therapeutic failure and tumor recurrence. However, the exact mechanism of TMZ chemoresistance in GBM is still poorly clarified. As a novel identified lncRNA, LINC00520 was located on chromosome 14 and overexpressed in multiple human cancers. This study was designed and conducted to investigate the role and underlying mechanism of LINC00520 in GBM chemoresistance to TMZ. The qRT-PCR assay demonstrated that LINC00520 was significantly overexpressed in TMZ-sensitive and/or TMZ-resistant GBM cells (P