Search

Abstract Background Postoperative thirst is one of the most intense, common and easily ignored subjective discomforts in patients after gynecological surgery. This study aimed to investigate whether early oral hydration on demand in the postanesthesia care unit (PACU) after gynecological laparoscopy under general anesthesia can appease postoperative thirst and increase patient comfort. Methods Participants were randomized into the intervention and control groups. Patients in the intervention group were allowed to achieve early oral hydration on demand in the PACU if they were evaluated as fully conscious, with stable vital signs, grade 5 muscle strength, and well-recovered cough and swallowing reflex. However, the total amount of water intake throughout the entire study should not exceed 0.5mL/kg. During the study, the frequency of water intake, the total amount of water intake and adverse events were accurately recorded. The control group was managed according to the routine procedures and began to drink water 2 h after anesthesia. The intensity of thirst and subjective comfort in patients were assessed using the visual analog scale (VAS) when they entered and left the PACU. Results No statistically significant differences were identified in age, height, weight, body mass index, pre-operative fasting time, duration of surgery, intraoperative fluid intake, intraoperative blood loss, intraoperative urine volume, and thirst intensity and subjective comfort scores between the groups before intervention (P > 0.05). After intervention, the VAS score for thirst intensity in the intervention group significantly decreased (P

Abstract A comprehensive understanding of the intricate cellular and molecular changes governing the complex interactions between cells within acne lesions is currently lacking. Herein, we analyzed early papules from six subjects with active acne vulgaris, utilizing single-cell and high-resolution spatial RNA sequencing. We observed significant changes in signaling pathways across seven different cell types when comparing lesional skin samples (LSS) to healthy skin samples (HSS). Using CellChat, we constructed an atlas of signaling pathways for the HSS, identifying key signal distributions and cell-specific genes within individual clusters. Further, our comparative analysis revealed changes in 49 signaling pathways across all cell clusters in the LSS— 4 exhibited decreased activity, whereas 45 were upregulated, suggesting that acne significantly alters cellular dynamics. We identified ten molecules, including GRN, IL-13RA1 and SDC1 that were consistently altered in all donors. Subsequently, we focused on the function of GRN and IL-13RA1 in TREM2 macrophages and keratinocytes as these cells participate in inflammation and hyperkeratinization in the early stages of acne development. We evaluated their function in TREM2 macrophages and the HaCaT cell line. We found that GRN increased the expression of proinflammatory cytokines and chemokines, including IL-18, CCL5, and CXCL2 in TREM2 macrophages. Additionally, the activation of IL-13RA1 by IL-13 in HaCaT cells promoted the dysregulation of genes associated with hyperkeratinization, including KRT17, KRT16, and FLG. These findings suggest that modulating the GRN-SORT1 and IL-13-IL-13RA1 signaling pathways could be a promising approach for developing new acne treatments.

The ovules or seeds (fertilized ovules) with wings are widespread and especially important for wind dispersal. However, the earliest ovules in the Famennian of the Late Devonian are rarely known about the dispersal syndrome and usually surrounded by a cupule. From Xinhang, Anhui, China, we now report a new taxon of Famennian ovules, Alasemenia tria gen. et sp. nov. Each ovule of this taxon possesses three integumentary wings evidently extending outwards, folding inwards along abaxial side and enclosing most part of nucellus. The ovule is borne terminally on smooth dichotomous branches and lacks a cupule. Alasemenia suggests that the integuments of the earliest ovules without a cupule evolved functions in probable photosynthetic nutrition and wind dispersal. It indicates that the seed wing originated earlier than other wind dispersal mechanisms such as seed plume and pappus, and that three- or four-winged seeds were followed by seeds with less wings. Mathematical analysis shows that three-winged seeds are more adapted to wind dispersal than seeds with one, two or four wings under the same condition.

BackgroundUpper tract urothelial carcinoma (UTUC) and bladder urothelial carcinoma (BLCA) both originate from uroepithelial tissue, sharing remarkably similar clinical manifestations and therapeutic modalities. However, emerging evidence suggests that identical treatment regimens may lead to less favorable outcomes in UTUC compared to BLCA. Therefore, it is imperative to explore molecular processes of UTUC and identify biological differences between UTUC and BLCA.MethodsIn this study, we performed a comprehensive analysis using single-cell RNA sequencing (scRNA-seq) on three UTUC cases and four normal ureteral tissues. These data were combined with publicly available datasets from previous BLCA studies and RNA sequencing (RNA-seq) data for both cancer types. This pooled analysis allowed us to delineate the transcriptional differences among distinct cell subsets within the microenvironment, thus identifying critical factors contributing to UTUC progression and phenotypic differences between UTUC and BLCA.ResultsscRNA-seq analysis revealed seemingly similar but transcriptionally distinct cellular identities within the UTUC and BLCA ecosystems. Notably, we observed striking differences in acquired immunological landscapes and varied cellular functional phenotypes between these two cancers. In addition, we uncovered the immunomodulatory functions of vein endothelial cells (ECs) in UTUC, and intercellular network analysis demonstrated that fibroblasts play important roles in the microenvironment. Further intersection analysis showed that MARCKS promote UTUC progression, and immunohistochemistry (IHC) staining revealed that the diverse expression patterns of MARCKS in UTUC, BLCA and normal ureter tissues.ConclusionThis study expands our multidimensional understanding of the similarities and distinctions between UTUC and BLCA. Our findings lay the foundation for further investigations to develop diagnostic and therapeutic targets for UTUC.

Abstract Objective To delineate the metabolomic differences in plasma samples between patients with coronary artery disease (CAD) and those with concomitant CAD and type 2 diabetes mellitus (T2DM), and to pinpoint distinctive metabolites indicative of T2DM risk. Method Plasma samples from CAD and CAD-T2DM patients across three centers underwent comprehensive metabolomic and lipidomic analyses. Multivariate logistic regression was employed to discern the relationship between the identified metabolites and T2DM risk. Characteristic metabolites' metabolic impacts were further probed through hepatocyte cellular experiments. Subsequent transcriptomic analyses elucidated the potential target sites explaining the metabolic actions of these metabolites. Results Metabolomic analysis revealed 192 and 95 significantly altered profiles in the discovery (FDR

BackgroundEchinococcosis is a natural focal, highly prevalent disease in China. Factors influencing the spread of echinococcosis are not only related to personal exposure but also closely related to the environment itself. The purpose of this study was to explore the influence of environmental factors on the prevalence of human echinococcosis and to provide a reference for prevention and control of echinococcosis in the future.MethodsData were collected from 370 endemic counties in China in 2018. By downloading Modis, DEM and other remote-sensing images in 2018. Data on environmental factors, i.e., elevation, land surface temperature (LST) and normalized difference vegetation index (NDVI) were collected. Rank correlation analysis was conducted between each environmental factor and the prevalence of echinococcosis at the county level. Negative binomial regression was used to analyze the impact of environmental factors on the prevalence of human echinococcosis at the county level.ResultsAccording to rank correlation analysis, the prevalence of human echinococcosis in each county was positively correlated with elevation, negatively correlated with LST, and negatively correlated with NDVI in May, June and July. Negative binomial regression showed that the prevalence of human echinococcosis was negatively correlated with annual LST and summer NDVI, and positively correlated with average elevation and dog infection rate. The prevalence of human cystic echinococcosis was inversely correlated with the annual average LST, and positively correlated with both the average elevation and the prevalence rate of domestic animals. The prevalence of human alveolar echinococcosis was positively correlated with both NDVI in autumn and average elevation, and negatively correlated with NDVI in winter.ConclusionThe prevalence of echinococcosis in the population is affected by environmental factors. Environmental risk assessment and prediction can be conducted in order to rationally allocate health resources and improve both prevention and control efficiency of echinococcosis.

Abdominal aortic aneurysm (AAA) is a chronic aortic disease that lacks effective pharmacological therapies. This study was performed to determine the influence of treatment with the gasdermin D inhibitor necrosulfonamide on experimental AAAs. AAAs were induced in male apolipoprotein E-deficient mice by subcutaneous angiotensin II infusion (1000 ng/kg body weight/min), with daily administration of necrosulfonamide (5 mg/kg body weight) or vehicle starting 3 days prior to angiotensin II infusion for 30 days. Necrosulfonamide treatment remarkably suppressed AAA enlargement, as indicated by reduced suprarenal maximal external diameter and surface area, and lowered the incidence and reduced the severity of experimental AAAs. Histologically, necrosulfonamide treatment attenuated medial elastin breaks, smooth muscle cell depletion, and aortic wall collagen deposition. Macrophages, CD4+ T cells, CD8+ T cells, and neovessels were reduced in the aneurysmal aortas of necrosulfonamide- as compared to vehicle-treated angiotensin II-infused mice. Atherosclerosis and intimal macrophages were also substantially reduced in suprarenal aortas from angiotensin II-infused mice following necrosulfonamide treatment. Additionally, the levels of serum interleukin-1β and interleukin-18 were significantly lower in necrosulfonamide- than in vehicle-treated mice without affecting body weight gain, lipid levels, or blood pressure. Our findings indicate that necrosulfonamide reduced experimental AAAs by preserving aortic structural integrity as well as reducing mural leukocyte accumulation, neovessel formation, and systemic levels of interleukin-1β and interleukin-18. Thus, pharmacologically inhibiting gasdermin D activity may lead to the establishment of nonsurgical therapies for clinical AAA disease.

IntroductionCoronary artery disease (CAD) is a highly heritable and multifactorial disease. Numerous genome-wide association studies (GWAS) facilitated the construction of polygenic risk scores (PRS) for predicting future incidence of CAD, however, exclusively in European populations. Furthermore, identifying CAD patients with elevated risks of all-cause death presents a critical challenge in secondary prevention, which will contribute largely to reducing the burden for public healthcare.MethodsWe recruited a cohort of 1,776 Chinese CAD patients and performed medical follow-up for up to 11 years. A pruning and thresholding method was used to calculate PRS of CAD and its 14 risk factors. Their correlations with all-cause death were computed via Cox regression.Results and discussionWe found that the PRS for CAD and its seven risk factors, namely myocardial infarction, ischemic stroke, angina, heart failure, low-density lipoprotein cholesterol, total cholesterol and C-reaction protein, were significantly associated with death (P ≤ 0.05), whereas the PRS of body mass index displayed moderate association (P

Carbon emissions and air pollutant emissions in China share common sources. A thorough examination of carbon and pollutant emissions is imperative for a comprehensive understanding. This study aims to assess carbon-pollutant emissions efficiency (CPEE) in 30 Chinese provinces from 2006 to 2020, focusing on the integration of carbon and air pollutant emissions. Previous research on CPEE is limited, and this article addresses this gap by investigating its spatiotemporal characteristics and identifying potential influencing factors. Our study employs a super-efficiency data envelopment analysis model, social network analysis, and spatial econometric models. The results indicate that: (1) During the research period, provincial CPEE in China follows a “W-shaped” trend and exhibits a “bimodal” asymmetric distribution, indicating notable regional heterogeneity. (2) Although spatial correlations are unstable and do not adhere to a strict hierarchical structure, positive spatial spillover effects are evident in the CPEE. (3) The spatial correlation network of CPEE displays various characteristics, including the Matthew effect, external preference, siphoning effect, and altruistic tendency. (4) Apart from technical input, explanatory variables affecting CPEE exert a significantly negative direct impact. Furthermore, the indirect effect of energy intensity on CPEE contradicts its direct effect when economic distance is considered in the spatial weight setting. These findings provide valuable theoretical insights and practical guidance for improving CPEE and its synergistic effects.

Passive differential optical absorption spectroscopy (DOAS) is widely used to monitor the three-dimensional distribution of atmospheric pollutants. However, the observational and retrieval accuracy of this technique is significantly influenced by the precise wavelength calibration of solar spectra. Current calibration methods face challenges in automation when dealing with complex remote-sensing conditions. We introduce a novel automatic wavelength calibration algorithm for passive DOAS based on sequence-matching technology to estimate the spectral parameters of the spectrometer channels, integrating advanced processing measures such as feature structure enhancement and sub-pixel interpolation. These measures significantly reduce the dependency on reference spectrum resolution and accurately correct even minor spectral shifts. We perform sensitivity experiments using synthetic spectra to determine optimal retrieval configurations, followed by field tests at four cities on the Yangtze River Delta, China, to calibrate and compare passive DOAS instruments of various resolutions. Comparative verification in these field studies demonstrated that our algorithm was suitable for rapid spectral calibration within a wider resolution range of 0.03 nm to 0.1 nm with a wavelength inversion error < 0.01 nm. This highlights the applicability and calibration precision of our algorithm.

Abstract Background Echinococcosis is a parasitic zoonotic disease that threatens human health and economic development. In China, 370 counties are endemic for echinococcosis. Qinghai-Tibet Plateau has the most patients and people at risk. Therefore, analyzing the societal factors related to susceptibility to the disease is critical for efficient prevention and control of echinococcosis. Methods The demographic characteristics and lifestyle of echinococcosis cases were clustered using K-means cluster analysis to determine the main factors of risk of echinococcosis. Results Middle-aged and young people as well as those with a low education level and herdsmen are at risk of contracting echinococcosis. Nomadism, domestic and feral dogs in the surrounding environment, and drinking heavily polluted natural surface water are the main behavioral risk factors. The cystic echinococcosis (CE) and alveolar echinococcosis (AE) cluster analysis focused on female, middle-aged, and young people, winter settlement and summer nomadism, and domestic and feral dogs in the surrounding environment. There were significant differences in lifestyle between Qinghai-Tibet Plateau cases and non-Qinghai-Tibet-Plateau cases. Conclusion According to the distribution of cases and CE and AE, this study identified the factors of risk of echinococcosis in the Qinghai-Tibet Plateau and non-Qinghai-Tibet Plateau. Adapted control techniques appropriate for the various epidemic areas should be established to serve as a reference for echinococcosis prevention. Graphical Abstract

Abstract Background Coronary artery disease (CAD) is a metabolically perturbed pathological condition. However, the knowledge of metabolic signatures on outcomes of CAD and their potential causal effects and impacts on left ventricular remodeling remains limited. We aim to assess the contribution of plasma metabolites to the risk of death and major adverse cardiovascular events (MACE) as well as left ventricular remodeling. Results In a prospective study with 1606 Chinese patients with CAD, we have identified and validated several independent metabolic signatures through widely-targeted metabolomics. The predictive model respectively integrating four metabolic signatures (dulcitol, β-pseudouridine, 3,3ʹ,5-Triiodo-l-thyronine, and kynurenine) for death (AUC of 83.7% vs. 76.6%, positive IDI of 0.096) and metabolic signatures (kynurenine, lysoPC 20:2, 5-methyluridine, and l-tryptophan) for MACE (AUC of 67.4% vs. 59.8%, IDI of 0.068) yielded better predictive value than trimethylamine N-oxide plus clinical model, which were successfully applied to predict patients with high risks of death (P = 0.0014) and MACE (P = 0.0008) in the multicenter validation cohort. Mendelian randomisation analysis showed that 11 genetically inferred metabolic signatures were significantly associated with risks of death or MACE, such as 4-acetamidobutyric acid, phenylacetyl-l-glutamine, tryptophan metabolites (kynurenine, kynurenic acid), and modified nucleosides (β-pseudouridine, 2-(dimethylamino) guanosine). Mediation analyses show that the association of these metabolites with the outcomes could be partly explained by their roles in promoting left ventricular dysfunction. Conclusions This study provided new insights into the relationship between plasma metabolites and clinical outcomes and its intermediate pathological process left ventricular dysfunction in CAD. The predictive model integrating metabolites can help to improve the risk stratification for death and MACE in CAD. The metabolic signatures appear to increase death or MACE risks partly by promoting adverse left ventricular dysfunction, supporting potential therapeutic targets of CAD for further investigation. Graphical Abstract

A new species of Late Devonian fossil lycopsid with large strobili and differentiated sporophylls provides insight into reproductive investment of early tree lycopsids.

Summary: By a survey of metagenome-wide association studies (MWAS), we found a robust depletion of Bacteroides cellulosilyticus, Faecalibacterium prausnitzii, and Roseburia intestinalis in individuals with atherosclerotic cardiovascular disease (ACVD). From an established collection of bacteria isolated from healthy Chinese individuals, we selected B. cellulosilyticus, R. intestinalis, and Faecalibacterium longum, a bacterium related to F. prausnitzii, and tested the effects of these bacteria in an Apoe/− atherosclerosis mouse model. We show that administration of these three bacterial species to Apoe−/− mice robustly improves cardiac function, reduces plasma lipid levels, and attenuates the formation of atherosclerotic plaques. Comprehensive analysis of gut microbiota, plasma metabolome, and liver transcriptome revealed that the beneficial effects are associated with a modulation of the gut microbiota linked to a 7α-dehydroxylation–lithocholic acid (LCA)–farnesoid X receptor (FXR) pathway. Our study provides insights into transcriptional and metabolic impact whereby specific bacteria may hold promises for prevention/treatment of ACVD.

Phyllostachys nigra has green young culms (S1) and purple black mature culms (S4). Anthocyanins are the principal pigment responsible for color presentation in ornamental plants. We employ a multi-omics approach to investigate the regulatory mechanisms of anthocyanins in Ph. nigra. Firstly, we found that the pigments of the culm of Ph. nigra accumulated only in one to four layers of cells below the epidermis. The levels of total anthocyanins and total flavonoids gradually increased during the process of bamboo culm color formation. Metabolomics analysis indicated that the predominant pigment metabolites observed were petunidin 3-O-glucoside and malvidin O-hexoside, exhibiting a significant increase of up to 9.36-fold and 13.23-fold, respectively, during pigmentation of Ph. nigra culm. Transcriptomics sequencing has revealed that genes involved in flavonoid biosynthesis, phenylpropanoid biosynthesis, and starch and sucrose metabolism pathways were significantly enriched, leading to color formation. A total of 62 differentially expressed structural genes associated with anthocyanin synthesis were identified. Notably, PnANS2, PnUFGT2, PnCHI2, and PnCHS1 showed significant correlations with anthocyanin metabolites. Additionally, certain transcription factors such as PnMYB6 and PnMYB1 showed significant positive or negative correlations with anthocyanins. With the accumulation of sucrose, the expression of PnMYB6 is enhanced, which in turn triggers the expression of anthocyanin biosynthesis genes. Based on these findings, we propose that these key genes primarily regulate the anthocyanin synthesis pathway in the culm and contribute to the accumulation of anthocyanin, ultimately resulting in the purple-black coloration of Ph. nigra.

Abstract Background In China the highest prevalence of echinococcosis is in Tibet Autonomous Region (TAR). The government has issued documents and implemented comprehensive prevention and control measures focusing on controlling the source of infection of echinococcosis. It was very important to understand the implementation and effect of infectious source control measures. The purpose of this study was to examine the implementation of measures to control infectious source (domestic and stray dogs) in TAR and to assess their effectiveness. Methods We collected data on domestic dog registration and deworming and stray dog sheltering in 74 counties/districts in the TAR from 2017 to 2019. Fecal samples from domestic dogs were collected from randomly selected towns to determine Echinococcus infection in dogs using coproantigen ELISA. We analyzed the data to compare the canine rate of infection between 2016 and 2019. The data analysis was performed by SPSS statistical to compare dog infection rate in 2016 and 2019 by chi-square test, and ArcGIS was used for mapping. Results From 2017 to 2019, 84 stray dog shelters were built in TAR, and accumulatively 446,660 stray or infected dogs were arrested, sheltered, or disposed of. The number of domestic dogs went downward, with an increased registration management rate of 78.4% (2017), 88.8% (2018), and 99.0% (2019). Dogs were dewormed 5 times in 2017, 12 times in 2018, and 12 times in 2019. The dog infection rate was 1.7% (252/14,584) in 2019, significantly lower than 7.3% (552/7564) from the survey of echinococcosis prevalence in Tibet in 2016 (P

Abstract Background Guangdedendron micrum is the Late Devonian tree lycopsid that made up Xinhang fossil forest in Anhui, China, showing the earliest stigmarian rooting system. Based on new specimens of this lycopsid, the roots bearing rootlets, terminal parts of stems, vegetative leaves and monosporangiate strobili containing megaspores are researched in detail. Results The roots with four robust rhizomorphs are largely expanded and approach the size of those of the Late Carboniferous giant tree lycopsids in swampy forests. The rootlets along rhizomorphic axis leave oval to circular scars after abscission. Narrow-fusiform leaf cushions display a leaf scar, vascular bundle and ligule pit. Cylindrical megasporangiate strobili are borne singly, in pairs, or occasionally once-dichotomized. Of each megasporophyll, the pedicel consists of a keel and possibly undeveloped alations, and the long-triangular lamina presents a heel. Megasporangium is sessile and contains multiple Lagenicula megaspores with distinct spines and a large gula. Conclusions G. micrum displays large terminal monosporangiate strobili probably adapted to turbulent condition, and its megasporophylls together with multiple Lagenicula-type megaspores hint a possible primitive evolutionary status. These characteristics provide new insights into the evolution of fertile traits of early lycopsids.

Abstract Background Echinococcosis, a zoonotic parasitic disease, is caused by larval stages of cestodes in the Echinococcus genus. Echinococcosis is highly prevalent in ten provinces/autonomous regions of western and northern China. In 2016, an epidemiological survey of Tibet Autonomous Region (TAR) revealed that the prevalence of human echinococcosis was 1.66%, which was much higher than the average prevalence in China (0.24%). Therefore, to improve on the current prevention and control measures, it is important to understand the prevalence and spatial distribution characteristics of human echinococcosis at the township level in TAR. Methods Data for echinococcosis cases in 2018 were obtained from the annual report system of echinococcosis of Tibet Center for Disease Control and Prevention. Diagnosis had been performed via B-ultrasonography. The epidemic status of echinococcosis in all townships in TAR was classified according to the relevant standards of population prevalence indices as defined in the national technical plan for echinococcosis control. Spatial scan statistics were performed to establish the geographical townships that were most at risk of echinococcosis. Results In 2018, a total of 16,009 echinococcosis cases, whose prevalence was 0.53%, were recorded in 74 endemic counties in TAR. Based on the order of the epidemic degree, all the 692 townships were classified from high to low degrees. Among them, 127 townships had prevalence rates ≥ 1%. The high prevalence of human echinococcosis in TAR, which is associated with a wide geographic distribution, is a medical concern. Approximately 94.65% of the villages and towns reported echinococcosis cases. According to spatial distribution analysis, the prevalence of human echinococcosis was found to be clustered, with the specific clustering areas being identified. The cystic echinococcosis primary cluster covered 88 townships, while that of alveolar echinococcosis’s covered 38 townships. Conclusions This study shows spatial distributions of echinococcosis with different epidemic degrees in 692 townships of TAR and high-risk cluster areas at the township level. Our findings indicate that strengthening the echinococcosis prevention and control strategies in TAR should directed at townships with a high prevalence and high-risk clustering areas. Graphical Abstract

Toxoplasma gondii is the most successful parasite worldwide. It is of great interest to understand how T. gondii induce different immune responses in different hosts. In this study, we found that a peptide of T. gondii microneme protein MIC3 induced TNF-α production, NF-κB phosphorylation, iNOS transcription and Ly6C expression in mouse macrophage RAW264.7 cells. MyD88 inhibition, small interfering RNA against Tlr11 and CRISPR/Cas9-mediated knock-out of Tlr11 all reduced MIC3-induced TNF-α production, NF-κB phosphorylation, iNOS transcription and Ly6C expression. Additionally, we determined the location of MIC3 peptide in mouse macrophages using immunofluorescence. MIC3 could both adhere to the cell membrane of mouse macrophages and enter the cells. These results suggest that MIC3 triggered the immune responses in mouse macrophages via TLR11/MyD88/NF-κB pathway. It is known that human macrophages lacking TLR11. We predicted that the immune responses induced by MIC3 in human macrophages were significantly different from those in mouse macrophages. As expected, MIC3 peptide failed to induce TNF-α expression, iNOS expression and NF-κB phosphorylation in human THP-1 derived macrophages. MIC3 induced macrophage immune responses via TLR11. Intriguingly, the amino acid sequence of MIC3 is completely different from the well-known TLR11 ligand profilin, which generates a potent IL-12p40, TNF-α and IL-6 response. In marked contrast to profilin, MIC3 could not induce IL-12p40 expression in both mouse RAW264.7 cells and human THP-1 derived macrophages. Furthermore, the simulated tertiary structure of MIC3 peptide shows poor similarity with the crystal structure of profilin, suggesting that MIC3 might be a different ligand from profilin. These findings about MIC3 and TLR11 will provide us with important insights into the pathogenesis of toxoplasmosis and coevolution during host-parasite interaction.

AbstractThe fault system is one of the structural carrier systems of gas hydrate accumulation, which plays a vital role in controlling the distribution of natural gas hydrate (NGH) accumulation. The previous studies mainly focus on summarizing the vertical migration mode of high flux fluid along the fault with obvious geophysical response characteristics on the seismic profile, such as “fault with gas chimney,” “fault with mud diapir,” and “fault with submarine collapse”, but lack of evaluation methods for the fault carrier system. We use the X sag in the deep-water continental margin slope area of the northern South China Sea as an example to study the fault systems closely related to NGH. This paper puts to use attribute technologies, such as coherence, curvature, and fusion, to analyze the characteristics and combination of the fault systems. We discussed migration patterns and evaluation methods of dominant fault carrier systems. This research proves that the strike-slip fault system in the platform area can directly connect the gas source bed with high-quality hydrocarbon generation to the gas hydrate stability zone (GHSZ). The activity of this fault system is more conducive to the accumulation of hydrocarbon in the GHSZ. This area has a good site for pore-filling gas hydrate prospecting and a preferential favorable fault carrier system. The composite fault system, consisting of a normal dip-slip fault system and a polygonal fault system, in the slope area can jointly communicate the biogenic gas-rich reservoir. Its activity and well-migration performance are the main reasons for the submarine gas leakage and collapse. It is a secondary favorable fault carrier system in the study area. There may be massive and vein natural gas hydrate formation in fractures in the leakage passage, and pore-filled gas hydrate may exist in the submarine nonleakage area. In this work, a three-factor evaluation method of the fault carrier system is proposed for the first time. This method is of great significance for the evaluation and exploration of NGH reservoirs in the continental margin slope area of the northern South China Sea.

BackgroundWith the rapid development of “Internet + medicine” and the impact of the COVID-19 epidemic, online health communities have become an important way for patients to seek medical treatment. However, the mistrust between physicians and patients in online health communities has long existed and continues to impact the decision-making behavior of patients. The purpose of this article is to explore the influencing factors of patient decision-making in online health communities by identifying the relationship between physicians' online information and patients' selection behavior.MethodsIn this study, we selected China's Good Doctor (www.haodf.com) as the source of data, scrapped 10,446 physician data from December 2020 to June 2021 to construct a logit model of online patients' selection behavior, and used regression analysis to test the hypotheses.ResultsThe number of types of services, number of scientific articles, and avatar in physicians' personal information all has a positive effect on patients' selection behavior, while the title and personal introduction hurt patients' selection behavior. Online word-of-mouth positively affected patients' selection behavior and disease risk had a moderating effect.ConclusionFocusing on physician-presented information, this article organically combines the Elaboration likelihood model with trust source theory and online word-of-mouth from the perspective of the trusted party–physician, providing new ideas for the study of factors influencing patients' selection behavior in online health communities. The findings provide useful insights for patients, physicians, and community managers about the relationship between physician information and patients' selection behavior.

Objective: The antibacterial activity of copper (Cu)-alloy biomaterials has shown a great potential in clinical application. Here, we evaluated the osteogenesis and antibacterial effects of Ti6Al4V-6.5wt%Cu alloy in an in vivo model of infected bone defects and determine their responsible proteins and pathways using proteomics. Methods: After bone defects were filled with Ti6Al4V and Ti6Al4V-6.5wt%Cu implants for 6 week, the tissue and bone samples around the implants were harvested for radiographic, micro-CT, histological, and bone-related gene expression analyses. An iTRAQ-based protein identification/quantification approach was used to analyze the osteogenic and antibacterial effects of Ti6Al4V-6.5wt%Cu alloy. Results: Imaging and histological results showed Ti6Al4V alloy induced a stronger inflammatory response than Ti6Al4V-6.5wt%Cu alloy; imaging results and osteogenic protein levels showed Ti6Al4V-6.5wt%Cu alloy exerted a stronger osteogenic effect. In vitro experiment, we found the Ti6Al4V-6.5wt%Cu had significant antibacterial effects and inhibited the activity of Staphylococcus aureus in the early stage. In addition, the bacterial biofilm formed in Ti6Al4V-6.5wt%Cu group was significantly lower than that in Ti6Al4V group. Proteomic screening of 4279 proteins resulted in 35 differentially expressed proteins for further examination which were mainly associated with the cellular process, metabolic process, stimulus response, and cellular component organization. In further exploration of the mechanism of osteogenic mineralization of Ti6Al4V-6.5wt%Cu alloy, we found out SDC4 and AGRN were the top two target proteins associated with osteogenic differentiation and bone mineralization. Conclusion: Ti6Al4V-6.5wt%Cu alloy shows a great potential as a bone implant material due to its positive effects against bacterial infection and on bone formation. The Translational potential of this article: At present, titanium alloys and other non-antibacterial metal materials are used in orthopedic internal fixation operations. Our study demonstrates that Ti6Al4V-6.5wt%Cu alloy has good antibacterial and osteogenic effects in vivo and in vitro. This means that Ti6Al4V-6.5wt%Cu alloy may become a new kind of antimicrobial metallic material as internal fixation material to continuously exert its antimicrobial effects and reduce the infection rate after clinical internal fixation.

Background: Gasdermin D, a molecule downstream of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing inflammasome, forms the membrane pore for the secretion of interleukin (IL)-1β and IL-18, and also mediates pyroptosis. This study was to explore the influence of treatment with disulfiram, a small molecule inhibitor to gasdermin D, on the formation and progression of experimental abdominal aortic aneurysms (AAA). Methods: AAAs were induced in 10-week-old male apolipoprotein E deficient mice by subcutaneous infusion of angiotensin II (1000 ng/min/kg body weight) for 28 days via osmotic minipumps. Three days prior to angiotensin II infusion, disulfiram (50 mg/kg) or an equal volume of saline as the vehicle control was administered daily via oral gavage. The influence on experimental AAAs was analyzed by serial measurements of aortic diameters via ultrasonography, grading AAA severity and histopathology at sacrifice. Serum IL-1β and IL-18 levels, systolic blood pressure, total cholesterol, and triglyceride were also measured. Additional experiments assayed the influences on the cell viability and IL-1β secretion of in vitro activated macrophages. Results: Disulfiram significantly reduced the enlargement, incidence, and severity of angiotensin II-induced experimental AAAs with attenuation of medial elastin breaks, mural macrophage accumulation, and systolic blood pressure. The AAA suppression was also associated with reduced systemic levels of IL-1β but not IL-18. However, disulfiram treatment had no impact on body weight gain and lipid levels in aneurysmal mice. Additionally, disulfiram treatment also markedly reduced the secretion of IL-1β from activated macrophages with a limited effect on cell viability in vitro. Conclusions: Gasdermin D inhibition by disulfiram attenuated angiotensin II-induced experimental AAAs with reduced systemic IL-1β levels and in vitro activated macrophage IL-1β secretion. Our study suggests that pharmacological gasdermin D inhibition may have translational potential for limiting clinical AAA progression.

This paper aims to establish a direct method for evaluating the internal corrosion in submarine pipelines, including four steps: pre-assessment, indirect inspection, detailed inspection, and post-assessment. The evaluation of corrosion severity and the determination of key monitoring points are particularly important in indirect detection. Taking CO2 gathering and transmission pipeline of an offshore oil field as an example, the overall internal corrosion rate of the pipeline is calculated to be 0.253 mm/a. The 12–45 m long pipeline is selected as the focus of corrosion monitoring. Through the comparative analysis of internal detection data and loss wall thickness, it is found that the results of indirect evaluation and direct evaluation are consistent, indicating the correctness of corrosion rate prediction model and loss wall thickness calculation method. The pipeline reevaluation time is five years. The evaluation method can accurately predict the corrosion status of multiphase flow pipeline and locate the corrosion.

AbstractAccurate determination of petrophysical and fluid transporting properties of rocks is essential for many engineering applications. In this paper, microcomputed tomography (CT) imaging technique is adopted to image the microstructure of tight sandstones drilled from Chang-7 member in Yanchang Formation. The pore geometry, pore-throat size distribution, pore connectivity, and tortuosity of the pore-throat structure are quantitatively characterized by extracting the pore network model (PNM). Direct numerical simulation (DNS) approach is applied on the segmented CT images to investigate the anisotropic permeability of tight sandstones. In addition, the unstructured mesh model of the pore space is reconstructed, and the pore scale immiscible two-phase flow is simulated by computational fluid dynamics (CFD) using the volume of fluid (VOF) model. The results indicate that the pore-throat system of tight sandstone reservoirs is mainly composed of discontinuous intergranular pores and grain margin microfractures with poor connectivity and diverse pore morphology. The two-phase flow simulations indicate that the strong heterogeneity of pore-throat structure can lead to obvious fingering phenomenon of the injected fluid, which reduces the sweep efficiency and the oil recovery as well. The residual fluids are mainly trapped in tiny throats and dead-end pores. It is found that the digital rock analysis based on CT imaging can be a cost-effective and time-saving alternative to routine core analysis of tight sandstone reservoirs.

The recycle split vapour (RSV) process is used for ethane recovery all over the world. However, improvements in RSV are required to treat unconventional feed gases under special conditions. In this paper, we propose three enhanced processes: RSV with propane refrigeration and pre-pressurization (RSVPP), RSV with propane and ethylene combined refrigeration (RSVPE) and RSV with propane and mixed refrigerant refrigeration (RSVPM). A comprehensive comparative analysis of the performances of these processes is carried out using conventional RSV as a reference. All the enhanced processes exhibit excellent performance in terms of the ethane recovery rate. However, the characteristics of each process cannot be differentiated using a single measure to compare the processes. The aim of this study is to evaluate the modified RSV processes in terms of economy, energy consumption and exergy. Thus, the advantages and disadvantages of each enhanced process are highlighted, enabling researchers to distinguish among the three proposed processes from different perspectives.

Abstract Background Cesarean section (CS) rate has risen dramatically and stayed at a very high level in China over the past two to three decades. Given the short- and long-term adverse effects of CS, effective strategies are needed to reduce unnecessary CS. We aimed to evaluate whether a multifaceted intervention would decrease the CS rate in China. Methods We carried out a cluster-randomized field trial with a multifaceted intervention in Shanghai, China, from 2015 to 2017. A total of 20 hospitals were randomly allocated into an intervention or a control group. The intervention consisted of more targeted health education to pregnant women, improved hospital CS policy, and training of midwives/doulas for 8 months. The study included a baseline survey, the intervention, and an evaluation survey. The primary outcome was the changes of overall CS rate from the pre-intervention to the post-intervention period. A subgroup analysis stratified by the Robson classification was also conducted to examine the CS change among women with various obstetric characteristics. Results A total of 10,752 deliveries were randomly selected from the pre-intervention period and 10,521 from the post-intervention period. The baseline CS rates were 42.5% and 41.5% in the intervention and control groups, respectively, while the post-intervention CS rates were 43.4% and 42.4%, respectively. Compared with the control group, the intervention did not significantly reduce the CS rate (adjusted OR = 0.92; 95% CI 0.73, 1.15). Similar results were obtained in subgroup analyses stratified by the risk level of pregnancy, maternal age, number of previous CS, or parity. Scarred uterus and maternal request remained the primary reasons for CS after the interventions in both groups. The intervention did not alter the perinatal outcomes (adjusted change of risk score = − 0.06; 95%CI − 0.43, 0.31). Conclusions A multifaceted intervention including more targeted prenatal health education, improved hospital CS policy, and training of midwives/doulas, did not significantly reduce the CS rate in Shanghai, China. However, our experience in implementing a multifaceted intervention may provide useful information to other similar areas with high CS use. Trial registration This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) (ChiCTR-IOR-16009041) on 17 August 2016.

The utilization of cement waste forms with high content of fly ash is a potential method in large-volume immobilization of low- and intermedium-level radioactive waste at near-surface. However, the migration behavior of radionuclides in fly ash/cement waste forms under geological environment is still unclear. This study researched the transformation of products, pore structure as well as the leachability of Ca2+, Na+, and simulated radioactive nuclides (Sr2+ and Cs+) in fly ash/cement waste forms under simultaneous effect through X-ray diffractometer (XRD), mercury intrusion porosimetry (MIP), and inductively coupled plasma optical emission spectroscopy (ICP-OES). Furthermore, the relationship between the decalcification and the leaching of Sr2+ and Cs+ was established by the fitting curves of apparent diffusion coefficient. The results indicated that the products of fly ash/cement waste forms were kept stable under simultaneous effect and the pore structure has excellent resistance to temperature. The increasing salt concentrations of leachant and temperature promoted the leaching of radionuclides while the protection layer formed at 60–80°C inhibited this phenomenon. The relationship of apparent diffusion coefficient between Sr2+ and Ca2+ was quadratic nonlinear, while the relationship between Cs+ and Ca2+ showed a linear relationship. Compared to cement waste forms, fly ash/cement waste forms were more stable. In addition, the long-term retention ability of fly ash/cement waste forms to Cs+ was more outstanding than Sr2+.

BackgroundEchinococcosis is a zoonotic parasitic disease caused by larval stages of cestodes belonging to the genus Echinococcus. The infection affects people's health and safety as well as agropastoral sector. In China, human echinococcosis is a major public health burden, especially in western China. Echinococcosis affects people health as well as agricultural and pastoral economy. Therefore, it is important to understand the prevalence status and spatial distribution of human echinococcosis in order to advance our knowledge of basic information for prevention and control measures reinforcement.MethodsReport data on echinococcosis were collected in 370 counties in China in 2018 and were used to assess prevalence and spatial distribution. SPSS 21.0 was used to obtain the prevalence rate for CE and AE. For statistical analyses and mapping, all data were processed using SPSS 21.0 and ArcGIS 10.4, respectively. Chi-square test and Exact probability method were used to assess spatial autocorrelation and spatial clustering.ResultsA total of 47,278 cases of echinococcosis were recorded in 2018 in 370 endemic counties in China. The prevalence rate of human echinococcosis was 10.57 per 10,000. Analysis of the disease prevalence showed obvious spatial positive autocorrelation in globle spatial autocorrelation with two aggregation modes in local spatial autocorrelation, namely high-high and low-high aggregation areas. The high-high gathering areas were mainly concentrated in northern Tibet, western Qinghai, and Ganzi in the Tibetan Autonomous Region and in Sichuan. The low-high clusters were concentrated in Gamba, Kangma and Yadong counties of Tibet. In addition, spatial scanning analysis revealed two spatial clusters. One type of spatial clusters included 71 counties in Tibet Autonomous Region, 22 counties in Qinghai, 11 counties in Sichuan, three counties in Xinjiang Uygur Autonomous Region, two counties in Yunnan, and one county in Gansu. In the second category, six types of spatial clusters were observed in the counties of Xinjiang Uygur Autonomous Region, and the Qinghai, Gansu, and Sichuan Provinces.ConclusionThis study showed a serious prevalence of human echinococcosis with obvious spatial aggregation of the disease prevalence in China. The Qinghai-Tibet Plateau is the "hot spot" area of human echinococcosis in China. Findings from this study indicate that there is an urgent need of joint strategies to strengthen efforts for the prevention and control of echinococcosis in China, especially in the Qinghai-Tibet Plateau.

Infertility affects lots of couples, half of which are caused by male factors. The LanCL1 gene is highly expressed in testis specifically, which might affect the development of sperms. In order to understand the potential functions of the LanCL1 gene in the testis, this study was conducted with constructed transgenic LanCL1 knockout mice. The mouse breeding experiment, semen analysis and single-cell RNAseq of testicular tissue were performed. Results suggested that the LanCL1 gene would significantly influence the reproduction ability and sperm motility of male mice. Single-cell RNAseq also confirmed the high expression of the LanCL1 gene in the spermatocytes and spermatids. Downregulating the LanCL1 gene expression could promote M2 macrophage polarity to maintain testicular homeostasis. Moreover, the LanCL1 gene could affect both the germ cells and stromal cells through various pathways such as the P53 signaling and the PPAR signaling pathway to disturb the normal process of spermatogenesis. However, no effects of the LanCL1 gene in testosterone synthesis and serum testosterone level were shown. Further studies are needed to discuss the mechanisms of the LanCL1 gene in the various cells of the testis independently.

This study aims to evaluate the association between free triiodothyronine (FT3) and outcomes of coronary artery disease (CAD) patients, as well as to assess the predictive power of FT3 and related functional markers from the perspective of potential mechanism. A total of 5104 CAD patients with an average follow-up of three years were enrolled into our study. Multivariate Cox regression was used to evaluate the associations between FT3, FT4 (free thyroxin), FT3/FT4 and death, MACE. We developed and validated an age, biomarker, and clinical history (ABC) model based on FT3 indicators to predict the prognosis of patients with CAD. In the multivariable Cox proportional hazards model, FT3 and FT3/FT4 were independent predictors of mortality (Adjusted HR = 0.624, 95% CI = 0.486–0.801; adjusted HR = 0.011, 95% CI = 0.002–0.07, respectively). Meanwhile, emerging markers pre-brain natriuretic peptide, fibrinogen, and albumin levels are significantly associated with low FT3 (p < 0.001). The new risk death score based on biomarkers can be used to well predict the outcomes of CAD patients (C index of 0.764, 95% CI = 0.731–0.797). Overall, our findings suggest that low levels of FT3 and FT3/FT4 are independent predictors of death and MACE risk in CAD patients. Besides, the prognostic model based on FT3 provides a useful tool for the death risk stratification of CAD patients.

IntroductionGastric cancer is one of the most common malignant tumors of the digestive tract. However, there are no adequate prognostic markers available for this disease. The present study used bioinformatics to identify prognostic markers for gastric cancer that would guide the clinical diagnosis and treatment of this disease.Materials and MethodsGene expression data and clinical information of gastric cancer patients along with the gene expression data of 30 healthy samples were downloaded from the TCGA database. The initial screening was performed using the WGCNA method combined with the analysis of differentially expressed genes, which was followed by univariate analysis, multivariate COX regression analysis, and Lasso regression analysis for screening the candidate genes and constructing a prognostic model for gastric cancer. Subsequently, immune cell typing was performed using CIBERSORT to analyze the expression of immune cells in each sample. Finally, we performed laboratory validation of the results of our analyses using immunohistochemical analysis.ResultsAfter five screenings, it was revealed that only three genes fulfilled all the screening requirements. The survival curves generated by the prognostic model revealed that the survival rate of the patients in the high-risk group was significantly lower compared to the patients in the low-risk group (P-value < 0.001). The immune cell component analysis revealed that the three genes were differentially associated with the corresponding immune cells (P-value < 0.05). The results of immunohistochemistry also support our analysis.ConclusionCGB5, MKNK2, and PAPPA2 may be used as novel prognostic biomarkers for gastric cancer.

Summary: Anti-PD-1/PD-L1 therapy shows long-term effects in many cancer types, but resistance and relapse remain the main limitations of this therapy. Here, we describe a protocol to evaluate the tumor response to immunotherapy in a mouse lung cancer model. The protocol includes the establishment of the lung cancer mouse model, anti-PD-1 treatment, tumor-infiltrating lymphocyte isolation, immunofluorescence, and flow cytometry analysis. This protocol can also be applied to other cancer types and immunotherapies.For complete details on the use and execution of this protocol, please refer to Yu et al. (2021)

Abstract PP2A is a major regulator of tau phosphorylation, which is principally regulated by an endogenous nuclear protein inhibitor 2 of PP2A (I2 PP2A), also named SET. However, how SET is post-translationally regulated and translocates from the nucleus to the cytoplasm remain incompletely understood. Here we show SET is SUMOylated at K68 residue that induces its cytoplasmic retention, resulting in Alzheimer disease (AD) like tau pathology and cognitive defects. SET is predominantly SUMOylated at K68 that leads to its translocation from the nucleus to the cytoplasm and subsequently induces inhibition of PP2A and hyperphosphorylation of tau in HEK-293 cells. Moreover, overexpression of wild type SET significantly inhibits PP2A activity, leading to tau hyperphosphorylation, less synapse loss and cognitive deficits. Conversely, blocking SET SUMOylation via mutating Lys 68 to Arg rescues tau pathology and cognitive impairments in C57/BL6 mice infected with adeno-associated virus encoding SET. Further, β-amyloid exposure of rat primary hippocampal neurons induces a dose-dependent SUMOylation of SET. Our findings suggest that SET SUMOylation stimulates its cytoplasmic retention and inhibits PP2A activity, consequently leading to tau hyperphosphorylation and cognitive impairments, which provides a new insight into the AD-like tau pathology.

Driven by the visions of the Internet of Things, more and more devices will join the network and generate large amounts of data. To analyze these data and provide useful information for intelligent applications, artificial neural networks are expected to be widely configured in data centers. However, it incurs excessive latency for the centers to aggregate data from massive distributed devices. To tackle this challenge, we propose wireless-network-based feedforward neural network (WN-FNN), a novel design that utilizes multiple-access communication to perform FNN computation in wireless networks. Based on a technology known as computation over multiple-access channel, the proposed design integrates communication and computation, which dramatically reduces the data aggregation latency. Furthermore, we analyze the impacts of the input noise and received noise on WN-FNN. A regularization strategy is proposed to improve the denoising ability of WN-FNN. An indoor localization application is simulated to verify the performances of WN-FNN and the regularization strategy.

To realize the Internet of Things, one of the essential elements is wireless sensor networks which can sense the physical conditions of the environment. The ubiquitous sensing is achieved by a large number of spatially dispersed sensors and distributed estimation technology. However, the low-cost sensors are insufficient to support conventional distributed estimation schemes. Since most conventional schemes include channel training process, the resource consumption of which is enormous. Thus, one key challenge in designing a feasible distributed estimation scheme is to reduce resource consumption from channel training. We tackle the challenge by proposing a distributed blind estimation scheme. The proposed scheme consists of two components: random transmission and statistical inference. Specifically, assuming sensors contain only two states that are active and inactive. The random transmission strategy turns the sensing value into a parameter to govern the sensor states. At the fusion center, statistical inference method is used to recover the sensing value. The specific design of the inference method involves the distribution approximation and clustering, which are accomplished by Gaussian mixture model and expectation-maximization principle. By the proposed scheme, the channel information is no longer needed in distributed estimation. Therefore, it is more energy-efficient and more applicable to the complicated wireless environment compared with conventional schemes. Besides, we investigate the impacts of the number of sensors and quantization on the estimation performance. Finally, simulation results demonstrate the effectiveness of the proposed blind estimation scheme.

Airport emissions have received increased attention because of their impact on atmospheric chemical processes, the microphysical properties of aerosols, and human health. At present, the assessment methods for airport pollution emission mainly involve the use of the aircraft emission database established by the International Civil Aviation Organization, but the emission behavior of an engine installed on an aircraft may differ from that of an engine operated in a testbed. In this study, we describe the development of a long-path differential optical absorption spectroscopy (LP-DOAS) instrument for measuring aircraft emissions at an airport. From 15 October to 23 October 2019, a measurement campaign using the LP-DOAS instrument was conducted at Hefei Xinqiao International Airport to investigate the regional concentrations of various trace gases in the airport’s northern area and the variation characteristics of the gas concentrations during an aircraft’s taxiing and take-off phases. The measured light path of the LP-DOAS passed through the aircraft taxiway and the take-off runway concurrently. The aircraft’s take-off produced the maximum peak in NO2 average concentrations of approximately 25 ppbV and SO2 average concentrations of approximately 8 ppbV in measured area. Owing to the airport’s open space, the pollution concentrations decreased rapidly, the overall levels of NO2 and SO2 concentrations in the airport area were very low, and the maximum hourly average NO2 and SO2 concentrations during the observation period were better than the Class 1 ambient air quality standards in China. Additionally, we discovered that the NO2 and SO2 emissions from the Boeing 737–800 aircraft monitored in this experiment were weakly and positively related to the age of the aircraft. This measurement established the security, feasibility, fast and non-contact of the developed LP-DOAS instrument for monitoring airport regional concentrations as well as NO2 and SO2 aircraft emissions during routine airport operations without interfering with the normal operation of the airport.

BackgroundAngiostrongylus cantonensis (A. cantonensis), is a food-borne zoonotic parasite that can cause central nervous system (CNS) injury characterized by eosinophilic meningitis. However, the pathogenesis of angiostrongylosis remains elusive. Natural killer cells (NK cells) are unique innate lymphocytes important in early defense against pathogens. The aim of this study was to investigate the role of NK cells in A. cantonensis infection and to elucidate the key factors that recruit NK cells into the CNS.MethodsMouse model of A. cantonensis infection was established by intragastric administration of third-stage larvae. The expression of cytokines and chemokines at gene and protein levels was analyzed by qRT-PCR and ELISA. Distribution of NK cells was observed by immunohistochemistry and flow cytometry. NK cell-mediated cytotoxicity against YAC-1 cells was detected by LDH release assay. The ability of NK cells to secrete cytokines was determined by intracellular flow cytometry and ELISA. Depletion and adoptive transfer of NK cells in vivo was induced by tail vein injection of anti-asialo GM1 rabbit serum and purified splenic NK cells, respectively. CX3CL1 neutralization experiment was performed by intraperitoneal injection of anti-CX3CL1 rat IgG.ResultsThe infiltration of NK cells in the CNS of A. cantonensis-infected mice was observed from 14 dpi and reached the peak on 18 and 22 dpi. Compared with uninfected splenic NK cells, the CNS-infiltrated NK cells of infected mice showed enhanced cytotoxicity and increased IFN-γ and TNF-α production ability. Depletion of NK cells alleviated brain injury, whereas adoptive transfer of NK cells exacerbated brain damage in A. cantonensis-infected mice. The expression of CX3CL1 in the brain tissue and its receptor CX3CR1 on the CNS-infiltrated NK cells were both elevated after A. cantonensis infection. CX3CL1 neutralization reduced the percentage and absolute number of the CNS-infiltrated NK cells and relieved brain damage caused by A. cantonensis infection.ConclusionsOur results demonstrate that the up-regulated CX3CL1 in the brain tissue recruits NK cells into the CNS and aggravates brain damage caused by A. cantonensis infection. The findings improve the understanding of the pathogenesis of angiostrongyliasis and expand the therapeutic intervention in CNS disease.

Background: Coronary stenosis severity determines ischemic symptoms and adverse outcomes. The metabolomic analysis of human fluids can provide an insight into the pathogenesis of complex disease. Thus, this study aims to investigate the metabolomic and lipidomic biomarkers of coronary artery disease (CAD) severity and to develop diagnostic models for distinguishing individuals at an increased risk of atherosclerotic burden and plaque instability.Methods: Widely targeted metabolomic and lipidomic analyses of plasma in 1,435 CAD patients from three independent centers were performed. These patients were classified as stable coronary artery disease (SCAD), unstable angina (UA), and myocardial infarction (MI). Associations between CAD stages and metabolic conditions were assessed by multivariable-adjusted logistic regression. Furthermore, the least absolute shrinkage and selection operator logistic-based classifiers were used to identify biomarkers and to develop prediagnostic models for discriminating the diverse CAD stages.Results: On the basis of weighted correlation network analysis, 10 co-clustering metabolite modules significantly (p < 0.05) changed at different CAD stages and showed apparent correlation with CAD severity indicators. Moreover, cross-comparisons within CAD patients characterized that a total of 72 and 88 metabolites/lipid species significantly associated with UA (vs. SCAD) and MI (vs. UA), respectively. The disturbed pathways included glycerophospholipid metabolism, and cysteine and methionine metabolism. Furthermore, models incorporating metabolic and lipidomic profiles with traditional risk factors were constructed. The combined model that incorporated 11 metabolites/lipid species and four traditional risk factors represented better discrimination of UA and MI (C-statistic = 0.823, 95% CI, 0.783–0.863) compared with the model involving risk factors alone (C-statistic = 0.758, 95% CI, 0.712–0.810). The combined model was successfully used in discriminating UA and MI patients (p < 0.001) in a three-center validation cohort.Conclusion: Differences in metabolic profiles of diverse CAD subtypes provided a new approach for the risk stratification of unstable plaque and the pathogenesis decipherment of CAD progression.

It is widely accepted that genetic polymorphisms impact atorvastatin (ATV) metabolism, clinical efficacy, and adverse events. The objectives of this study were to identify novel genetic variants influencing ATV metabolism and outcomes in Chinese patients with coronary artery disease (CAD). A total of 1079 CAD patients were enrolled and followed for 5 years. DNA from the blood and human liver tissue samples were genotyped using either Global Screening Array-24 v1.0 BeadChip or HumanOmniZhongHua-8 BeadChip. Concentrations of ATV and its metabolites in plasma and liver samples were determined using a verified ultra-performance liquid chromatography mass spectrometry (UPLC-MS/MS) method. The patients carrying A allele for the rs4148323 polymorphism (UGT1A1) showed an increase in 2-hydroxy ATV/ATV ratio (p = 1.69E−07, false discovery rate [FDR] = 8.66E−03) relative to the value in individuals without the variant allele. The result was further validated by an independent cohort comprising an additional 222 CAD patients (p = 1.08E−07). Moreover, the rs4148323 A allele was associated with an increased risk of death (hazard ratio [HR] 1.774; 95% confidence interval [CI], 1.031–3.052; p = 0.0198). In conclusion, our results suggested that the UGT1A1 rs4148323 A allele was associated with increased 2-hydroxy ATV formation and was a significant death risk factor in Chinese patients with CAD.

Plasma lipids have been at the center stage of the prediction and prevention strategies for cardiovascular diseases (CVDs), and novel lipidomic traits have been recognized as reliable biomarkers for CVD risk prediction. The mitochondria serve as energy supply sites for cells and can synthesize a variety of lipids autonomously. Therefore, investigating the relationships between mitochondrial single nucleotide polymorphism (SNPs) and plasma lipidomic traits is meaningful. Here, we enrolled a total of 1,409 Han Chinese patients with coronary artery disease from three centers and performed linear regression analyses on the SNPs of mitochondrial DNA (mtDNA) and lipidomic traits in two independent groups. Sex, age, aspartate aminotransferase, estimated glomerular filtration rate, antihypertensive drugs, hypertension, and diabetes were adjusted. We identified three associations, namely, D-loopm.16089T>C with TG(50:4) NL-16:0, D-loopm.16145G>A with TG(54:5) NL-18:0, and D-loopm.16089T>C with PC(16:0_16:1) at the statistically significant threshold of FDR < 0.05. Then, we explored the relationships between mitochondrial genetic variants and traditional lipids, including triglyceride, total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), and high-density lipoprotein cholesterol. Two significant associations were found, namely MT-ND6m.14178T>C with TC and D-loopm.215A>G with LDLC. Furthermore, we performed linear regression analysis to determine on the SNPs of mtDNA and left ventricular ejection fraction (LVEF) and found that the SNP D-loopm.16145G>A was nominally significantly associated with LVEF (P = 0.047). Our findings provide insights into the lipidomic context of mtDNA variations and highlight the importance of studying mitochondrial genetic variants related to lipid species.

Background: The outbreak of Covid-19 in the UK has seen many families unexpectedly brought back together. The circumstances and stories of individual families have been picked up in the press focussing on the difficulties of people adjusting to their changed living arrangements. Yet, there have been few empirical analyses on how such changes might influence people’s health and wellbeing. Therefore, this study explored the changing patterns of perceived stress by living arrangements change during the first wave of the Covid-19 pandemic in 2020. Methods: The data used relates to 12,532 cohort members in the special Covid-19 surveys conducted with the participants of the 1958, 1970, 2000-01 British birth cohorts and Next Steps (born in 1989–90) in May 2020. Probit regression models were used to assess the chance of reporting increased stress amongst those who had experienced changes in living arrangements during the pandemic compared to those who had not. Results: The results provide strong evidence that those individuals whose living arrangements changed during the Covid-19 pandemic have a higher likelihood of reported increased stress than those whose living arrangements remained unchanged. This was most clearly seen for older cohorts. Increased interpersonal conflict plays a role in mediating the association, especially for the younger cohort. Conclusions: The findings confirm that during the first lockdown, changing living arrangements were negatively associated with individuals’ mental wellbeing. As prolonged periods of stress can lead to serious health problems and policymakers need to be mindful that services may need to take these new, albeit for many temporary, forms of living arrangements into account.

Human echinococcosis is present worldwide but it is in China that disease prevalence is the highest. In western China, especially in the Tibetan Plateau, the burden of echinococcosis is the most important. Dogs are a major definitive host of Echinococcus and monitoring the presence of Echinococcus worms in dogs is therefore essential to efficiently control the disease. Detection kits based on three different technologies including sandwich ELISA, (indirect) ELISA, and gold immunodiffusion, are currently marketed and used in China. The objective of this work was to assess the efficacy of these kits, in particular with respect to sensitivity and specificity. Four fecal antigen detection kits for canine infection reflecting the three technologies were obtained from companies and tested in parallel on 220 fecal samples. The results indicate that the performance is lower than expected, in particular in terms of sensitivity. The best results were obtained with the sandwich ELISA technology. The gold immunofiltration yielded the poorest results. In all cases, further development is needed to improve the performance of these kits which are key components for the control of echinococcosis.

Sand production is a problem that is often encountered in unconventional oil and gas exploitation and that is difficult to effectively solve. Accurate online monitoring of sand production is one of the keys to ensuring the safety and long-term production of oil wells as well as efficient production throughout the life cycle of production wells. This paper proposes a method for monitoring sand production in offshore oil wells that is based on the vibration response characteristics of sand-carrying fluid flow impinging on the pipe wall. This method uses acceleration sensors to obtain the weak vibration response characteristics of sand particles impinging on the pipe wall on a two-dimensional time-frequency plane. The time-frequency parameters are further optimized, and the ability to identify weakly excited vibration signals of sand particles in the fluid stream is enhanced. The difference between the impact response of the sand particles and the impact response of the fluid flow to the pipe wall is identified, and corresponding indoor verification experiments are carried out. Under different sand contents, particle sizes, and flow rates (sand content 0-2‰, sand particle size 96-212 μm, and flow velocity 1-3 m/s), the impact response frequency of sand particles to the pipe wall exhibits good consistency. The characteristic frequency band of sand impacting the pipe wall is 30-50 kHz. A statistical method is used to establish the response law of the noise signal of the fluid. Based on this knowledge, a real-time calculation model of sand production in offshore oil wells is constructed, and the effectiveness of this model is verified. Finally, a field test is carried out with a self-developed sand production signal dynamic time-frequency response software system on 4 wells of an oil production platform in the Bohai Sea. This system can effectively distinguish sand-producing wells from non-sand-producing wells. The dynamic time-frequency response, field test results, and actual laboratory results are consistent, verifying the effectiveness of the method proposed in this paper and further providing a theory for improving the effectiveness of the sand production monitoring method under complex multiphase flow conditions. This study also provides technical guidance for the industrial application of sand production monitoring devices in offshore oil wells.

For improving the toughness and long-term strength of the fractured rock mass reinforced with epoxy resin and reducing the opening displacement of the crack tip, three types of converging cracks are established according to the deformation and failure characteristics of the rock mass, structural planes, and epoxy resin composite structure. The stress intensity factor of the type II compound crack and the analytical formula of the crack surface tip opening displacement are obtained. An improved Kelvin nonlinear creep model is proposed. Through the creep isochronous curve, the time and long-term strength of accelerated creep failure are obtained, as well as creep rupture coupling characteristics. The ductile plastic deformation is used to characterize the toughness, and the toughness of epoxy resin is enhanced by adding mud powder, and the relationship between toughness and long-term strength is established. Combined with experimental verification, when the drying mud powder content is 20%, the toughness of the epoxy resin has a good correlation with the long-term strength; when the mud powder content exceeds 30%, its ductility and long-term strength decrease, and at the same time the toughness effect is significantly weakened. The research results can provide a useful reference for toughened epoxy resin to strengthen fractured rock mass engineering.

Abstract Background Dyslipidaemia contributes to the progression of coronary artery disease (CAD) toward adverse outcomes. Plasma lipidomic measure may improve the prognostic performances of clinical endpoints of CAD. Our research is designed to identify the correlations between plasma lipid species and the risks of death, major adverse cardiovascular event (MACE) and left ventricular (LV) remodeling in patients with CAD. Methods A total of 1569 Chinese patients with CAD, 1011 single‐centre patients as internal training cohort, and 558 multicentre patients as external validation cohort, were enrolled. The concentration of plasma lipids in both cohorts was determined through widely targeted lipidomic profiling. Least absolute shrinkage and selection operator Cox and multivariate Cox regressions were used to develop prognostic models for death and MACE, respectively. Results Ten (Cer(d18:1/20:1), Cer(d18:1/24:1), PE(30:2), PE(32:0), PE(32:2), PC(O‐38:2), PC(O‐36:4), PC(16:1/22:2), LPC(18:2/0:0) and LPE(0:0/24:6)) and two (Cer(d18:1/20:1) and LPC(20:0/0:0)) lipid species were independently related to death and MACE, respectively. Cer(d18:1/20:1) and Cer(d18:1/24:1) were correlated with LV remodeling (P

The presence of voids in the ingot affects the mechanical properties of the final products of the forging process. It is essential to establish a void closure model to predict cavity closure in the forging process to optimize the forging process and improve forging quality. The main purpose of this study is to obtain an accurate prediction model of void closure for 316LN stainless steel. Using the FEM simulation method to study the closure of spherical voids during forging compression of 316LN materials, we can accurately characterize the state of void closure. The void closure ratio K under different deformations at 1,200°C was counted, and the relationship between K and the effective strain was established to obtain the void closure prediction model of 316LN stainless steel. The void closure prediction model is implanted into DEFORM software through the secondary development method to generate the void closure ratio K. In the postprocessing module of DEFORM software, the void closure status of each part during the forming process can be directly observed. Comparing the results of large-scale upsetting experiments and simulation results, the closure error of each part was only 3%, which indicates that the void closure model established in this paper has higher accuracy, which is helpful for the optimization of the forging process and the control of forging quality.

A series of tests were carried out to evaluate crack resistance and mechanical properties of polyvinyl alcohol fiber-reinforced cement-stabilized macadam, which is widely used as pavement base or subbase composite material. Three series of cement-stabilized macadam mixtures with cement content of 3.2%, 3.6%, and 4.0% were prepared by incorporating four various contents (0, 0.6, 0.9, and 1.2 kg/m3) and lengths (12, 18, 24, and 30 mm) of polyvinyl alcohol fiber. The optimum polyvinyl alcohol fiber content, fiber length, and cement content were determined based on the mechanical properties of cement-stabilized macadam mixtures. Then, unconfined compressive strength test, compressive resilience modulus test, splitting strength test, flexural tensile strength test, drying shrinkage test, and temperature shrinkage test were carried out in this study. The results show that polyvinyl alcohol fiber-reinforced cement-stabilized prepared by optimum proportions (cement 3.6%, fiber content 0.9 kg/m3, and fiber length 24 mm) has good crack resistance. The incorporation of polyvinyl alcohol fiber can effectively improve compressive strength and splitting strength, while its effect on CRM of cement-stabilized macadam is not remarkable. The anti-dry-shrinkage property and anti-temperature-shrinkage property of the specimens are also drastically improved due to the reinforcement effect of polyvinyl alcohol fiber. Moreover, the crack resistance index is proposed to evaluate the crack resistance of materials. The crack resistance of PVA fiber-reinforced cement-stabilized macadam prepared by optimum proportions is improved by 44.4%. Consequently, the mechanical properties and crack resistance of cement-stabilized macadam are obviously improved by adding polyvinyl alcohol fiber.

To adaptively identify the modal parameters for time-invariant structures excited by non-white noise, this paper proposes a new operational modal analysis (OMA) method using hybrid neural networks. In this work, taking the acceleration response directly as the input data of the networks not only simplifies the data processing, but also retains all the characteristics of the data. The data processed by the output function is the output data of the network, and its peak corresponds to the modal frequency. The proposed output function greatly reduces the computational cost. In addition, a small sample dataset ensures that the hybrid neural networks identify the modal parameters with the highest accuracy in the shortest possible time. Interestingly, the hybrid neural networks combine the advantages of the convolutional neural network (CNN) and gate recurrent unit (GRU). To illustrate the advantages of the proposed method, the cantilever beam and the rudder surface excited by white and non-white noise are taken as examples for experimental verification. The results reveal that the proposed method has a strong anti-noise ability and high recognition accuracy, and is not limited by ambient excitation type.