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Anxiety disorder is one of the most common mental diseases. It is mainly characterized by a sudden, recurring but indescribable panic, fear, tension and/or anxiety. Yangshendingzhi granules (YSDZ) are widely used in the treatment of anxiety disorders, but its active ingredients and underlying mechanisms are not yet clear. This study integrates network pharmacology and metabolomics to investigate the potential mechanism of action of YSDZ in a rat model of anxiety. First, potential active ingredients and targets were screened by network pharmacology. Then, predictions were verified by molecular docking, molecular dynamics and western blotting. Metabolomics was used to identify differential metabolites and metabolic pathways. All results were integrated for a comprehensive analysis. Network pharmacology analysis found that Carotene, β-sitosterol, quercetin, Stigmasterol, and kaempferol in YSDZ exert anxiolytic effects mainly by acting on IL1β, GABRA1, PTGS1, ESR1, and TNF targets. Molecular docking results showed that all the affinities were lower than −5 kcal/mol, and the average affinities were −7.7764 kcal/mol. Molecular dynamics simulation results showed that RMSD was lower than 2.5 A, and the overall conformational changes of proteins were small, indicating that the small molecules formed stable complexes with proteins. The results of animal experiments showed that YSDZ exerts anxiolytic effects by regulating GABRA1 and TNF-α, ameliorating pathological damage in hippocampal CA1, and regulating metabolic pathways such as thiamine, cysteine and methionine metabolism, lysine biosynthesis and degradation. Altogether, we reveal multiple mechanisms through which YSDZ exerts its anti-anxiety effects, which may provide a reference for its clinical application and drug development.

BackgroundEarly hematoma growth is associated with poor functional outcomes in patients with intracerebral hemorrhage (ICH). We aimed to explore whether quantitative hematoma heterogeneity in non-contrast computed tomography (NCCT) can predict early hematoma growth.MethodsWe used data from the Risk Stratification and Minimally Invasive Surgery in Acute Intracerebral Hemorrhage (Risa-MIS-ICH) trial. Our study included patients with ICH with a time to baseline NCCT 6 mL or a hematoma volume increase of 33% compared with the baseline NCCT.ResultsA total of 158 patients were enrolled in the study, of which 31 (19.6%) had hematoma growth. The multivariate logistic regression analysis revealed that time to initial baseline CT (P = 0.040, odds ratio [OR]: 0.824, 95 % confidence interval [CI]: 0.686–0.991), “heterogeneous” in the density category (P = 0.027, odds ratio [OR]: 5.950, 95 % confidence interval [CI]: 1.228–28.828), and CV of hematoma HUs (P = 0.018, OR: 1.301, 95 % CI: 1.047–1.617) were independent predictors of hematoma growth. By evaluating the receiver operating characteristic curve, the CV of hematoma HUs (AUC = 0.750) has a superior predictive value for hematoma growth than for heterogeneous density (AUC = 0.638). The CV of hematoma HUs had an 18% cutoff, with a specificity of 81.9 % and a sensitivity of 58.1 %.ConclusionThe CV of hematoma HUs can serve as a quantitative hematoma heterogeneity index that predicts hematoma growth in patients with early ICH independently.

Background and objectsA longer duration of hypertension (HTN) has been suggested to be associated with a greater risk of cardiovascular disease (CVD). Whether such an association is similar for mortality risk, and whether HTN duration is associated with CVD/mortality beyond blood pressure (BP) control levels are yet to be assessed. We aimed to examine the associations of HTN duration and the combination of HTN duration and systolic blood pressure (SBP)/diastolic blood pressure (DBP) with risks of CVD and all-cause mortality.MethodsWe used data on ∼450,000 UK residents. Participants were categorized by HTN status and HTN duration. The primary outcome was a composite of non-fatal myocardial infarction, non-fatal stroke and CVD death. We also explored the results for the above-mentioned CVD outcomes separately. All-cause mortality was also used as a secondary outcome. The age at HTN diagnosis was obtained by self-report. HTN duration was calculated as baseline age minus age at diagnosis.ResultsAmong all participants, compared with non-hypertensive participants, those with a longer HTN duration had increased risks of CVD and all-cause mortality. These associations persisted among hypertensive patients. Specifically, compared with patients with HTN durations of < 5 y, patients with a HTN duration of 5 to < 10 y, 10 to < 15 y, and ≥ 15 y had adjusted HRs (95% CI) of 1.09 (1.03, 1.17), 1.21 (1.13, 1.31), and 1.38 (1.29, 1.48) for composite CVD (P-trend < 0.001); and 1.03 (0.97, 1.08), 1.09 (1.02, 1.16), and 1.17 (1.11, 1.24) for all-cause mortality (P-trend < 0.001). When compared with hypertensive patients with BP < 140/90 mmHg and a HTN duration of < 5 y, adjusted HRs of CVD and all-cause mortality were 1.35 (1.15, 1.57) and 1.26 (1.11, 1.42) for those with BP < 140/90 mmHg and a duration of ≥ 15 y, and 1.43 (1.26, 1.60) and 1.13 (1.03, 1.25) for those with BP ≥ 140/90 mmHg and durations of ≥ 15 y, respectively.ConclusionA longer HTN duration was associated with increased risks of CVD and overall death in a linear fashion, and these associations were independent of BP control levels.

ObjectiveThe purpose of this study was to investigate the burden of musculoskeletal (MSK) health conditions in Gulf Cooperation Council (GCC) countries based on the Global Burden of Disease (GBD) data.MethodsThe data for GCC countries were obtained from the 2019 GBD study to evaluate the burden of MSK disorders which include the following countries: Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates (UAE). The main outcome measures were age-standardized prevalence and years of life lived with disability (YLDs) associated with MSK disorders. The burden of MSK disorders attributable to the category of behavioral, metabolic, or environmental/occupational was reported to estimate the risk-attributable fractions of disease.ResultsMSK disorders prevalence ranked fifth in Kuwait, sixth in Bahrain, Oman, Qatar, and UAE, and seventh in Saudi Arabia among all the diseases in 2019. For all GCC countries, MSK disorders were ranked the second leading cause of disability as measured by YLDs for the years 1990 and 2019. The age-standardized prevalence of MSK disorders in 2019 for Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and UAE was 18.56% (95% UI: 17.51–19.66), 19.35% (18.25–20.52), 18.23% (17.14–19.36), 18.93% (17.81–20.06), 19.05% (17.96–20.22), and 18.26% (17.18–19.38), respectively. The age-standardized YLDs per 100,000 individuals of MSK disorders in 2019 for Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and UAE were 1,734 (1,250–2,285), 1,764 (1,272–2,322), 1,710 (1,224–2,256), 1,721 (1,246–2,274), 1,715 (1,230–2,274), and 1,681 (1,207–2,235), respectively. For risk factors, high body mass index (BMI) had the highest contribution to MSK disorders YLDs in most GCC countries (Bahrain, Kuwait, Oman, and Saudi Arabia), followed by the exposure to occupational ergonomic factors which had the highest contribution to MSK disorders YLDs in Qatar and UAE.ConclusionThere was an increase in both age-standardized prevalence of MSK disorders and YLDs between 1990 and 2019 that was observed for all GCC countries. Some risk factors such as higher BMI and exposure to occupational ergonomic factors were highly associated with YLDs due to MSK disorders. The results of this study provide guidance for the potential nature of preventative and management programs to optimize the individual’s health.

ObjectiveThe present study aimed to investigate the clinical application value of the radiomics model based on gray-scale ultrasound (GSUS) and contrast-enhanced ultrasound (CEUS) images in the differentiation of inflammatory mass stage periductal mastitis/duct ectasia (IMSPDM/DE) and invasive ductal carcinoma (IDC).MethodsIn this retrospective study, 254 patients (IMSPDM/DE: 129; IDC:125) were enrolled between January 2018 and December 2020 as a training cohort to develop the classification models. The radiomics features were extracted from the GSUS and CEUS images. The least absolute shrinkage and selection operator (LASSO) regression model was employed to select the corresponding features. Based on these selected features, logistic regression analysis was used to aid the construction of these three radiomics signatures (GSUS, CEUS and GSCEUS radiomics signature). In addition, 80 patients (IMSPDM/DE:40; IDC:40) were recruited between January 2021 and November 2021 and were used as the validation cohort. The best radiomics signature was selected. Based on the clinical parameters and the radiomics signature, a classification model was built. Finally, the classification model was assessed using nomogram and decision curve analyses.ResultsThree radiomics signatures were able to differentiate IMSPDM/DE from IDC. The GSCEUS radiomics signature outperformed the other two radiomics signatures and the AUC, sensitivity, specificity, and accuracy were estimated to be 0.876, 0.756, 0.804, and 0.798 in the training cohort and 0.796, 0.675, 0.838 and 0.763 in the validation cohort, respectively. The lower patient age (p

Capsular contracture is one of the most common complications of breast implants, which often leads to secondary surgery. Patients with unconspicuous breast contracture do not need treatment, while for those with severe symptoms, a capsule revision surgery is of great necessity, including a total periprosthetic capsulectomy and replacement with a new implant. However, if the capsular contracture happens in the submuscular space, it will be very difficult to release it completely, and it may lead to more complications such as damage to surrounding tissue. The new method of pouch can create a new subpectoral plane for the insertion of a new implant instead of a total capsulectomy, but this method is unsuitable for patients who have little breast tissue or thin skin. To solve this thorny clinical problem, we invented a double-headed separating instrument and came up with a novel operation method to release the capsular contracture, which opened from the nipple by the punctiform-incision approach and caused only a mild and undetectable trauma. This operation went off without a hitch, and the postoperative breast shape was good, and the breast felt and moved naturally. In addition, there were no significant complications throughout the one-year follow-up period. This case was an excellent demonstration of the novel breast capsular contracture release surgery using our optimized double-headed capsule contracture separator.

Background: The prevalence of Type 1 Diabetes is increasing in pediatrics and diabetes education plays one of the most important role in the management of diabetes, especially in children. However, the related evidence concerned diabetes education is rare in children and adolescents. Therefore, we aimed to investigate the status of diabetes education in hospital, which could help us know the reality of diabetes education. Methods: We choose a nurse who is mainly responsible for diabetes education and management in each hospital to fill out the questionnaire. Overall, 98 nurses were enrolled from tertiary children's specialized hospitals and pediatric wards of general tertiary hospitals from Jan 2018 to Dec 2019. Results: Of 98 nurses enrolled, 61 (63.3%) nurses from 98 hospitals responded, 39 (63.9%) of them received specialized training in diabetes. There were no differences in education characteristics among regions of China. There were 26(42.6%) hospitals have a full-time nurse for diabetes education or nurses with endocrinology training increased with the number of cases/year (P=0.02 and P=0.009). The use of game-based education, knowledge assessment at discharge did not vary among hospital volumes, and the presence of a psychiatrist (P=0.41, P=0.65, and P=0.85, respectively). Diet management education is the most common (23.0%) difficulty in children diabetes education. Conclusion: The level of diabetes education in children and adolescents varied among hospitals, but not among regions in China. There was a lack of resources provided for children and adolescents diabetes education in terms of training and specialized services.

In this paper, we proposed a lattice composite tower damping system to reduce the seismic response of super-long-span suspension bridges. Taking the QiongZhou strait bridge as a case study, we evaluated seismic performances through a finite element analysis (FEA) and shaking-table tests. First, the seismic responses of a super-long-span suspension bridge with or without a lattice composite tower to far-fault and near-fault earthquakes were analyzed and compared. The influence of the lattice composite tower on the dynamic characteristics and seismic performance was then investigated using shaking-table tests. Finally, the influences of different damping systems on the seismic response were evaluated, considering factors such as the damper type, damper arrangement scheme and design parameters. The results indicated that lattice composite tower could significantly increase the seismic performance of super-long span suspension bridge, while the optimal damping system could markedly improve the energy dissipation ability of whole system. Subsequently, this could provide references to enhance the seismic safety of the super-long span suspension bridge under strong earthquakes.

Over the past few decades, drug-induced liver damage (DILI) has become a serious public health problem due to drug abuse. Among multifarious reactive oxygen species, mounting evidence attests that ClO− has been used as a potential biomarker in DILI. In this work, a new “turn-on” fluorescent probe 1 was designed and synthesized by modifying 4′-hydroxybiphenyl-4-carbonitrile (dye 2) with N, N-dimethylthiocarbamate as a response site for detecting ClO−. Probe 1 displayed a low detection limit (72 nM), fast response time (30 s), wide pH operating range (6–8), great tissue penetration, large Stokes shift (125 nm) and 291-fold fluorescence enhancement at 475 nm in the mapping of ClO−. Probe 1 could trace amounts of exogenous and endogenous ClO− with high sensitivity in MCF-7 cells and HeLa cells. Expectantly, the fluoxetine-induced liver injury model is successfully established, and probe 1 has been used for detecting the fluctuation of ClO− levels in the mouse model of fluoxetine-induced liver injury. All in all, probe 1 with its high specificity, good biological compatibility and liver tissue penetration ability is expected to assist with the early diagnosis of DILI and the clinical screening of various new drugs. We expect that probe 1 could be efficiently used as a powerful molecular tool to predict clinical DILI and explore molecular mechanisms between molecules and disease.

Gas fuel direct injection (DI) technology can improve the control precision of the in-cylinder mixing and combustion process and effectively avoid volumetric efficiency reduction in a compressed natural gas (CNG) engine, which has been a tendency. However, compared with the port fuel injection (PFI) method, the former’s mixing path and duration are shortened greatly, which often leads to poor mixing uniformity. What is worse, the in-cylinder mixing performance would be seriously affected by engine working conditions, such as engine speed and load. Based on this situation, the fluid mechanics software FLUENT is used in this article, and the computational fluid dynamics (CFD) model of the injection and mixing process in a gas-fueled direct injection engine is established. A quantitative evaluation mechanism of the in-cylinder mixing performance of the CNG engine is proposed to explore the influencing rule of different engine speeds and loads on the mixing process and performance. The results indicate that phase space analysis can accurately reflect the characteristics of the mixture mixing process. The gas fuel mixture rapidly occupies the cylinder volume in the injection stage. During the transition stage, the gas fuel mixture is in a highly transient state. The diffusion stage is characterized by the continuous homogenization of the mixture. The in-cylinder mixing performance is linearly dependent on the engine’s working condition in the phase space.

The process of coal adsorption and desorption of gas is accompanied by obvious thermal effects, and its variation pattern is of great value for the research of gas hazard prediction techniques such as coal and gas outburst prediction. Using self-designed multiparameter coal adsorption and desorption heat effect test system, we conducted pressure, temperature and heat flow test experiments for CO2, N2 and CH4 gas adsorption and desorption of bituminous coal at 0. 5 MPa, 0. 8 MPa and 1. 1 MPa, and analyzed the characteristics of heat flow changes of bituminous coal during the adsorption and desorption process. The study showed that: (1) during the whole process of adsorption and desorption of bituminous coal specimens, the change of heat flow density on the coal wall is divided into five processes: ①in the evacuation stage, the heat flow increases rapidly and then decreases slowly to 0; ②in the inflation stage, the heat flow is positively correlated with the inflation rate; ③in the adsorption stage, the heat flow is first fast up and then fast down and finally decreases slowly; ④in the deflation stage, the heat flow is positively correlated with the pressure relief rate; ⑤in the desorption stage, it is divided into two stages: the stage of fast down and slow rise. (2) The maximum heat flux values of N2, CH4, and CO2 three gases increase sequentially; for the same gas, the maximum heat flux values under the three gas pressures will increase with the increase of pressure. (3) The theoretical values of heat in the process of adsorption and desorption are always larger than the experimental values, but the overall trend is consistent. (4) The heat flux parameter has the characteristics of inflow and outflow direction vector, which is superior to the temperature index. The heat flux is consistent with the heat transfer change law, which can well characterize the change law of thermal effect of adsorption and desorption of bituminous coal, and provide reference for the research of new index of coal and gas outburst prediction.

Abstract Pancreatic cancer is an increasingly common cause of cancer mortality with a tight correspondence between disease mortality and incidence. Furthermore, it is usually diagnosed at an advanced stage with a very dismal prognosis. Due to the high heterogeneity, metabolic reprogramming, and dense stromal environment associated with pancreatic cancer, patients benefit little from current conventional therapy. Recent insight into the biology and genetics of pancreatic cancer has supported its molecular classification, thus expanding clinical therapeutic options. In this review, we summarize how the biological features of pancreatic cancer and its metabolic reprogramming as well as the tumor microenvironment regulate its development and progression. We further discuss potential biomarkers for pancreatic cancer diagnosis, prediction, and surveillance based on novel liquid biopsies. We also outline recent advances in defining pancreatic cancer subtypes and subtype-specific therapeutic responses and current preclinical therapeutic models. Finally, we discuss prospects and challenges in the clinical development of pancreatic cancer therapeutics.

Abstract Background Neuronal hyperactivity related to β-amyloid (Aβ) is considered an early warning sign of Alzheimer disease (AD). Although increasing evidence supports this opinion, the underlying mechanisms are still unknown. Methods Here, we recorded whole-cell synaptic currents and membrane potentials using patch clamping of acute hippocampal slices from human amyloid precursor protein (APP)/presenilin-1 transgenic (5XFAD) mice and their wild-type littermates. Biochemical methods, electron microscopic imaging, behavioral tests, and intraventricular drug delivery applied with osmotic pumps were used in this study. Results We confirmed hyperactivity of hippocampal CA1 pyramidal neurons in 5XFAD mice using whole-cell electrophysiological recording at 2.5 months old, when local Aβ-positive plaques had not developed and only mild cognitive dysfunction occurred. We further discovered attenuated inhibitory postsynaptic currents and unchanged excitatory postsynaptic currents in CA1 pyramidal neurons, in which the intrinsic excitability was unchanged. Moreover, the density of both γ-aminobutyric acid A (GABAA) receptor subunits, α1 and γ2, was reduced in synapses of the hippocampus in transgenic mice. Intriguingly, early intervention with the GABAA receptor agonist gaboxadol reversed the hippocampal hyperactivity and modestly ameliorated cognitive performance in 5XFAD mice under our experimental conditions. Conclusions Inhibitory postsynaptic disruption critically contributes to abnormalities in the hippocampal network and cognition in 5XFAD mice and possibly in AD. Therefore, strengthening the GABAergic system could be a promising therapy for AD in the early stages.

Background: Electrocardiogram (ECG) and carotid ultrasound (CUS) are important tools for the diagnosis and prediction of cardiovascular disease (CVD). This study aimed to investigate the associations between ECG and CUS parameters and explore the feasibility of assessing carotid health with ECG.Methods: This cross-sectional cohort study enrolled 319 healthy Chinese subjects. Standard 12-lead ECG parameters (including the ST-segment amplitude [STA]), CUS parameters (intima-media thickness [IMT] and blood flow resistance index [RI]), and CVD risk factors (including sex, age, and systolic blood pressure [SBP]) were collected for analysis. Participants were divided into the high-level RI group (average RI ≥ 0.76, n = 171) and the normal RI group (average RI < 0.76, n = 148). Linear and stepwise multivariable regression models were performed to explore the associations between ECG and CUS parameters.Results: Statistically significant differences in sex, age, SBP, STA and other ECG parameters were observed in the normal and the high-level RI group. The STA in lead V3 yielded stronger significant correlations (r = 0.27–0.42, p < 0.001) with RI than STA in other leads, while ECG parameters yielded weak correlations with IMT (|r| ≤ 0.20, p < 0.05). STA in lead V2 or V3, sex, age, and SBP had independent contributions (p < 0.01) to predicting RI in the stepwise multivariable models, although the models for IMT had only CVD risk factors (age, body mass index, and triglyceride) as independent variables. The prediction model for RI in the left proximal common carotid artery (CCA) had higher adjusted R2 (adjusted R2 = 0.31) than the model for RI in the left middle CCA (adjusted R2 = 0.29) and the model for RI in the right proximal CCA (adjusted R2 = 0.20).Conclusion: In a cohort of healthy Chinese individuals, the STA was associated with the RI of CCA, which indicated that ECG could be utilized to assess carotid health. The utilization of ECG might contribute to a rapid screening of carotid health with convenient operations.

ObjectiveTo develop and validate a radiomics nomogram that could incorporate clinicopathological characteristics and ultrasound (US)-based radiomics signature to non-invasively predict Ki-67 expression level in patients with breast cancer (BC) preoperatively.MethodsA total of 328 breast lesions from 324 patients with BC who were pathologically confirmed in our hospital from June 2019 to October 2020 were included, and they were divided into high Ki-67 expression level group and low Ki-67 expression level group. Routine US and shear wave elastography (SWE) were performed for each lesion, and the ipsilateral axillary lymph nodes (ALNs) were scanned for abnormal changes. The datasets were randomly divided into training and validation cohorts with a ratio of 7:3. Correlation analysis and the least absolute shrinkage and selection operator (LASSO) were used to select the radiomics features obtained from gray-scale US images of BC patients, and each radiomics score (Rad-score) was calculated. Afterwards, multivariate logistic regression analysis was used to establish a radiomics nomogram based on the radiomics signature and clinicopathological characteristics. The prediction performance of the nomogram was assessed by the area under the receiver operating characteristic curve (AUC), the calibration curve, and decision curve analysis (DCA) using the results of immunohistochemistry as the gold standard.ResultsThe radiomics signature, consisted of eight selected radiomics features, achieved a nearly moderate prediction efficacy with AUC of 0.821 (95% CI:0.764-0.880) and 0.713 (95% CI:0.612-0.814) in the training and validation cohorts, respectively. The radiomics nomogram, incorporating maximum diameter of lesions, stiff rim sign, US-reported ALN status, and radiomics signature showed a promising performance for prediction of Ki-67 expression level, with AUC of 0.904 (95% CI:0.860-0.948) and 0.890 (95% CI:0.817-0.964) in the training and validation cohorts, respectively. The calibration curve and DCA indicated promising consistency and clinical applicability.ConclusionThe proposed US-based radiomics nomogram could be used to non-invasively predict Ki-67 expression level in BC patients preoperatively, and to assist clinicians in making reliable clinical decisions.

BackgroundStroke-associated pneumonia (SAP) contributes to high mortality rates in spontaneous intracerebral hemorrhage (sICH) populations. Accurate prediction and early intervention of SAP are associated with prognosis. None of the previously developed predictive scoring systems are widely accepted. We aimed to derive and validate novel supervised machine learning (ML) models to predict SAP events in supratentorial sICH populations.MethodsThe data of eligible supratentorial sICH individuals were extracted from the Risa-MIS-ICH database and split into training, internal validation, and external validation datasets. The primary outcome was SAP during hospitalization. Univariate and multivariate analyses were used for variable filtering, and logistic regression (LR), Gaussian naïve Bayes (GNB), random forest (RF), K-nearest neighbor (KNN), support vector machine (SVM), extreme gradient boosting (XGB), and ensemble soft voting model (ESVM) were adopted for ML model derivations. The accuracy, sensitivity, specificity, and area under the curve (AUC) were adopted to evaluate the predictive value of each model with internal/cross-/external validations.ResultsA total of 468 individuals with sICH were included in this work. Six independent variables [nasogastric feeding, airway support, unconscious onset, surgery for external ventricular drainage (EVD), larger sICH volume, and intensive care unit (ICU) stay] for SAP were identified and selected for ML prediction model derivations and validations. The internal and cross-validations revealed the superior and robust performance of the GNB model with the highest AUC value (0.861, 95% CI: 0.793–0.930), while the LR model had the highest AUC value (0.867, 95% CI: 0.812–0.923) in external validation. The ESVM method combining the other six methods had moderate but robust abilities in both cross-validation and external validation and achieved an AUC of 0.843 (95% CI: 0.784–0.902) in external validation.ConclusionThe ML models could effectively predict SAP in sICH populations, and our novel ensemble model demonstrated reliable robust performance outcomes despite the populational and algorithmic differences. This attempt indicated that ML application may benefit in the early identification of SAP.

Our non-tube no fasting (early oral feeding and no nasogastric tube) fast-track surgery (FTS) was safe and effective to combine with neoadjuvant chemotherapy for McKeown minimally invasive esophagectomy. In addition, the two groups were similar in terms of the recovery time, hospital discharge day, and early resumption of oral feeding.ObjectivesTo evaluate the safety of early oral feeding (EOF) combined with neoadjuvant chemotherapy (NAC) of esophagectomy.Summary Background DataOur non-tube no fasting (early oral feeding and no nasogastric tube) fast-track surgery (FTS) was safe and effective for primary surgery esophageal cancer patients.MethodsWe retrospectively evaluated consecutive patients who underwent non-tube no fasting and McKeown minimally invasive (MIE). They were divided into two groups: one received NAC, and the other received primary surgery. Complications after the operation, postoperative CRG complications, operative time, operative bleeding, and length of stay were evaluated.ResultsBetween 01/2014 and 12/2017, there hundred and eighty two consecutive patients underwent MIE with total two-field lymphadenectomy under the non-tube no fasting fast-track surgery program. A total of 137 patients received NAC, and 245 accepted primary surgery. Propensity score matching was used to compare NAC patients with 62 matched patients from each group. The NAC group had a similar number of total complications as the primary surgery group (32.26% in the primary surgery group vs. 25.81% in the NAC group; p=0.429) and had the same median postoperative hospitalization duration (8 days, p=0.723).ConclusionsAfter McKeown MIE, the patients receiving NAC combined with “non-tube no fasting” FTS had a similar incidence of postoperative complications outcomes as those without NAC. In addition, the two groups were similar in terms of the recovery time, hospital discharge day, and early resumption of oral feeding.

Screening for superior cadmium (Cd) phytoremediation resources and uncovering the mechanisms of plant response to Cd are important for effective phytoremediation of Cd-polluted soils. In this study, the characteristics of Coreopsis grandiflora related to Cd tolerance and accumulation were analyzed to evaluate its Cd phytoremediation potential. The results revealed that C. grandiflora can tolerate up to 20 mg kg−1 of Cd in the soil. This species showed relatively high shoot bioconcentration factors (1.09–1.85) and translocation factors (0.46–0.97) when grown in soils spiked with 5–45 mg kg–1 Cd, suggesting that C. grandiflora is a Cd accumulator and can potentially be used for Cd phytoextraction. Physiological analysis indicated that antioxidant enzymes (i.e., superoxide dismutase, peroxidase, and catalase) and various free amino acids (e.g., proline, histidine, and methionine) participate in Cd detoxification in C. grandiflora grown in soil spiked with 20 mg kg–1 of Cd (Cd20). The overall microbial richness and diversity remained similar between the control (Cd0) and Cd20 soils. However, the abundance of multiple rhizospheric microbial taxa was altered in the Cd20 soil compared with that in the Cd0 soil. Interestingly, many plant growth-promoting microorganisms (e.g., Nocardioides, Flavisolibacter, Rhizobium, Achromobacter, and Penicillium) enriched in the Cd20 soil likely contributed to the growth and vitality of C. grandiflora under Cd stress. Among these, some microorganisms (e.g., Rhizobium, Achromobacter, and Penicillium) likely affected Cd uptake by C. grandiflora. These abundant plant growth-promoting microorganisms potentially interacted with soil pH and the concentrations of Cd and AK in soil. Notably, potassium-solubilizing microbes (e.g., Rhizobium and Penicillium) may effectively solubilize potassium to assist Cd uptake by C. grandiflora. This study provides a new plant resource for Cd phytoextraction and improves our understanding of rhizosphere-associated mechanisms of plant adaptation to Cd-contaminated soil.

On the one hand, fast social media and internet evolution has brought opportunities to the development of the organic food industry. On the other hand, the excessive utilization of social media and internet has also exerted some negative effects on consumers in terms of information disorder and hindered the industrial progression of organic foods. This study aimed to probe into the relationships between organic food information uncertainty, information search anxiety, information overload and purchase behavior under the mediating role of attitude and the moderating role of involvement, introducing the concept of information disorder in the context of this issue. The data (cross-sectional) of 620 organic food consumers in Jiangxi Province, China were subjected to SEM (structural equation modeling). The results showed that organic food information uncertainty and information search anxiety significantly affected attitude, and attitude had a positive impact on purchase behavior. In addition, attitude significantly mediated the effects of organic food information uncertainty and information search anxiety on purchase behavior. Moreover, the indirect relationship between organic food information uncertainty and purchase behavior was moderated by involvement.

Background: Acute respiratory distress syndrome (ARDS) is an unresolved challenge in the field of respiratory and critical care, and the changes in the lung microbiome during the development of ARDS and their clinical diagnostic value remain unclear. This study aimed to explore the role of the lung microbiome in disease progression in patients with sepsis-induced ARDS and potential therapeutic targets.Methods: Patients with ARDS were divided into two groups according to the initial site of infection, intrapulmonary infection (ARDSp, 111 cases) and extrapulmonary infection (ARDSexp, 45 cases), and a total of 28 patients with mild pulmonary infections were enrolled as the control group. In this study, we sequenced the DNA in the bronchoalveolar lavage fluid collected from patients using metagenomic next-generation sequencing (mNGS) to analyze the changes in the lung microbiome in patients with different infectious site and prognosis and before and after antibiotic treatment.Results: The Shannon–Wiener index indicated a statistically significant reduction in microbial diversity in the ARDSp group compared with the ARDSexp and control groups. The ARDSp group was characterized by a reduction in microbiome diversity, mainly in the normal microbes of the lung, whereas the ARDSexp group was characterized by an increase in microbiome diversity, mainly in conditionally pathogenic bacteria and intestinal microbes. Further analysis showed that an increase in Bilophila is a potential risk factor for death in ARDSexp. An increase in Escherichia coli, Staphylococcus aureus, Candida albicans, enteric microbes, or conditional pathogens may be risk factors for death in ARDSp. In contrast, Hydrobacter may be a protective factor in ARDSp.Conclusion: Different initial sites of infection and prognoses are likely to affect the composition and diversity of the pulmonary microbiome in patients with septic ARDS. This study provides insights into disease development and exploration of potential therapeutic targets.

Abstract The distinct climatic and geographical conditions make high‐altitude permafrost on the Tibetan Plateau suffer more severe degradation than polar permafrost. However, the microbial responses associated with greenhouse gas production in thawing permafrost remain obscured. Here we applied nanopore‐based long‐read metagenomics and high‐throughput RNA‐seq to explore microbial functional activities within the freeze‐thaw cycle in the active layers of permafrost at the Qilian Mountain. A bioinformatic framework was established to facilitate phylogenetic and functional annotation of the unassembled nanopore metagenome. By deploying this strategy, 42% more genera could be detected and 58% more genes were annotated to nitrogen and methane cycle. With the aid of such enlarged resolution, we observed vigorous aerobic methane oxidation by Methylomonas, which could serve as a bio‐filter to mitigate CH4 emissions from permafrost. Such filtering effect could be further consolidated by both on‐site gas phase measurement and incubation experiment that CO2 was the major form of carbon released from permafrost. Despite the increased transcriptional activities of aceticlastic methanogenesis pathways in the thawed permafrost active layer, CH4 generated during the thawing process could be effectively consumed by the microbiome. Additionally, the nitrogen metabolism in permafrost tends to be a closed cycle and active N2O consumption by the topsoil community was detected in the near‐surface gas phase. Our findings reveal that although the increased thawed state facilitated the heterotrophic nitrogen and methane metabolism, effective microbial methane oxidation in the active layer could serve as a bio‐filter to relieve the overall warming potentials of greenhouse gas emitted from thawed permafrost.

Colon adenocarcinoma (COAD) is one of the leading causes of cancer-associated deaths worldwide. Patients with microsatellite instability-high (MSI-H) tumors were shown to highly benefit from immune checkpoint inhibitors (ICIs) than patients with microsatellite stable (MSS) tumors. Furthermore, the infiltration of immune cells and the expression of cancer stem cells (CSCs) in COAD were associated with the anti-tumor immune response. However, the potential mechanisms showing the relationship between microsatellite instability and CSCs or tumor-infiltrating immune cells (TIICs) have not been elucidated. Accumulating evidence reveals that achaete-scute family bHLH transcription factor 2 (ASCL2) plays a crucial role in the initiation and progression of COAD and drug resistance. However, the specific biological functions of ASCL2 in COAD remain unknown. In this study, we performed weighted gene co-expression network analysis (WGCNA) between MSS and MSI-H subsets of COAD. The results revealed that ASCL2 was a potential key candidate in COAD. Subsequently, the single-cell RNA-seq revealed that ASCL2 was positively associated with CSCs. Further, ASCL2 was shown to indirectly affect tumor immune cell infiltration by negatively regulating the expression of DUSP4. Finally, we inferred that the immunotherapy-sensitive role of ASCL2/DUSP4 axis on COAD is partly attributed to the activation of WNT/β-catenin pathway. In conclusion, this study revealed that ASCL2 was positively correlated to CSCs and tumor immune infiltration in COAD. Therefore, ASCL2 is a promising predictor of clinical responsiveness to anti-PD-1/PD-L1 therapy in COAD.

Abstract Intercellular cross-talk plays important roles in cancer progression and metastasis. Yet how these cancer cells interact with each other is still largely unknown. Exosomes released by tumor cells have been proved to be effective cell-to-cell signal mediators. We explored the functional roles of exosomes in metastasis and the potential prognostic values for hepatocellular carcinoma (HCC). Exosomes were extracted from HCC cells of different metastatic potentials. The metastatic effects of exosomes derived from highly metastatic HCC cells (HMH) were evaluated both in vitro and in vivo. Exosomal proteins were identified with iTRAQ mass spectrum and verified in cell lines, xenograft tumor samples, and functional analyses. Exosomes released by HMH significantly enhanced the in vitro invasion and in vivo metastasis of low metastatic HCC cells (LMH). S100 calcium-binding protein A4 (S100A4) was identified as a functional factor in exosomes derived from HMH. S100A4rich exosomes significantly promoted tumor metastasis both in vitro and in vivo compared with S100A4low exosomes or controls. Moreover, exosomal S100A4 could induce expression of osteopontin (OPN), along with other tumor metastasis/stemness-related genes. Exosomal S100A4 activated OPN transcription via STAT3 phosphorylation. HCC patients with high exosomal S100A4 in plasma also had a poorer prognosis. In conclusion, exosomes from HMH could promote the metastatic potential of LMH, and exosomal S100A4 is a key enhancer for HCC metastasis, activating STAT3 phosphorylation and up-regulating OPN expression. This suggested exosomal S100A4 to be a novel prognostic marker and therapeutic target for HCC metastasis.

Abstract Objectives These 2 parallel studies (K031 and K032) aim to evaluate the safety of KB109 in addition to supportive self-care (SSC) compared with SSC alone in outpatients with mild to moderate coronavirus disease 2019 (COVID-19). KB109 is a novel synthetic glycan that was formulated to modulate the gut microbiome composition and metabolic output in order to increase beneficial short-chain fatty acid (SCFA) production in the gut. The K031 study is designed to evaluate the safety of KB109 and characterize its impact on the natural progression of COVID-19 in patients with mild to moderate disease. The K032 study is evaluating the effect of KB109 on the gut microbiota structure and function in this same patient population. Additionally, both studies are evaluating measures of health care utilization, quality of life (QOL), laboratory indices, biomarkers of inflammation, and serological measures of immunity in patients who received SSC alone or with KB109. Noteworthy aspects of these outpatient studies include study design measures aimed at limiting in-person interactions to minimize the risk of infection spread, such as use of online diaries, telemedicine, and at-home sample collection. Study design K031 and K032 are randomized, controlled, open-label, clinical food studies. Participants Inclusion Criteria: • Adults ≥18 years of age • Patients willing and able to give informed consent • Screening/randomization telemedicine visit within 2 days of testing positive test for COVID-19 ○ In K031 study, symptomatic patients at COVID-19 testing must report new or worsening symptoms at baseline that have not been present for more than 5 days ▪ Cardinal COVID-19 symptoms include fever, chills/repeated shaking with chills, cough, shortness of breath, headache, muscle pain, anosmia/ageusia, and sore throat. The 5 additional symptoms include gastrointestinal (GI) disturbance/symptoms (other than diarrhea), diarrhea, fatigue, nasal congestion, and chest tightness ○ In K031, at COVID-19 testing, pre-symptomatic patients must report new cardinal COVID-19 symptoms within 7 days of a positive test and they must be screened and randomized within 5 days of developing symptoms • Mild to moderate COVID-19 and self-reported outpatient management ○ In K032, mild to moderate COVID-19 was defined as having the following symptoms for no more than 72 hours before COVID-19 testing: a self- reported fever or cough (new or exacerbated) or presence of at least 2 of the following: anosmia, sore throat, or nasal congestion • Ability to adhere to the study visit schedule and other protocol requirements • Consistent internet or cell phone access with a data plan and access to a smartphone, tablet, or computer • The K031 and K032 studies are currently being conducted at 17 clinical institutions throughout the United States. Exclusion Criteria: • In the primary investigator’s (PI) judgement, patients likely to require hospitalization for COVID-19 • Patients who are hospitalized for in-patient treatment or currently being evaluated for potential hospitalization at the time of informed consent for conditions other than COVID-19 • History of chronic lung disease with chronic hypoxia • History of documented cirrhosis or end-stage liver disease • Ongoing requirement for oxygen therapy • Shortness of breath in resting position • Diagnosis of sleep apnea requiring bilevel positive airway pressure (BIPAP)/continuous positive airway pressure (CPAP) • Female patients who are pregnant, trying to become pregnant, or lactating • Concurrent use of immunomodulatory agent within 12 months; systemic antibiotics, antifungals, or antivirals for treatment of active infection within 28 days; systemic immunosuppressive therapy within 3 months; or drugs or other compounds that modulate GI motility (eg, stool softeners, laxatives, or fiber supplements) taken currently, or within 7 days. Antacid (histamine 2 blockers and proton pump inhibitors) and antidiarrheal agents are not prohibited • History of GI surgery (6 months prior to randomization), including but not limited to bariatric surgery and bowel resection, or history of, or active GI disease(s) that may affect assessment of tolerability, including but not limited to inflammatory bowel disease, irritable bowel syndrome, autoimmune disease, or GI malignancy • Participation in an interventional clinical trial or use of any investigational agent within 30 days before randomization • Clinically significant or uncontrolled concomitant medical condition that would put the patient at risk or jeopardize the objectives of the study in the opinion of the PI • In the opinion of the PI, patient unlikely for any reason to be able to comply with study procedures • Contraindications, sensitivities, or known allergy to the use of the study product or its components Intervention and comparator Patients will be randomized (1,1) to receive either SSC and KB109 or SSC alone. During SSC, patients should follow the steps as instructed by their healthcare provider to care for themselves and protect other people in the home and community from potentially contracting COVID-19. Management of COVID-19-related symptoms with over-the-counter cough, cold, and anti-pyretic medications by patients is permitted in accordance with the medications’ respective drug facts label or as instructed by the patient’s healthcare provider. Following randomization, patients assigned to receive KB109 and SSC will receive a Kaleido Biosciences, Inc at-home study kit including a thermometer, pulse oximeter, and KB109. During the Intake Period (days 1–14), KB109 will be reconstituted in water by the patient and consumed by the patient twice daily (at least 8 hours apart), following an up-titration dosing schedule: Days 1 to 2: 9 g twice daily for a total daily dose of 18 g Days 3 to 4: 18 g twice daily for a total daily dose of 36 g Days 5 to 14: 36 g twice daily for a total daily dose of 72 g During the intake period, patients will record their daily COVID-19–related symptoms, selected COVID-19 signs (as self-measured using the provided thermometer and pulse oximeter), responses to questions related to QOL measures, health care use measures, and concomitant medications taken in the previous 24 hours. Wellness visits by telephone will be conducted between days 1 and 14 to follow up on patient’s health status and to ascertain compliance with KB109 and completion of questions. On day 14, all patients will undergo a telemedicine visit where the following will be conducted: abbreviated physical examination, assessment of safety and other protocol-specified measures of health, and an evaluation of whether follow-up treatment is recommended owing to a progression of COVID-19 symptoms. If feasible, blood samples for clinical chemistries, biomarkers and serological measure of immunity, and nasal/oropharyngeal swabs for quantitative viral load assessments will be collected. Beginning on day 15, patients in both groups will enter the follow-up period (days 15–35) where COVID-19 signs, symptoms, and health care use indices will be collected. Wellness visits by telephone will be conducted on days 21, 28, and 35 to follow-up on the patient’s health status. On day 35, all patients will undergo a telemedicine visit where the same information as the day 14 telemedicine visit will be collected, including any blood samples. Main outcomes The primary outcome for the K031 and K032 studies is to evaluate the safety of KB109 in addition to SSC compared with SSC alone in outpatients with mild to moderate COVID-19 by assessing the number of patients experiencing KB109-related treatment-emergent adverse events (TEAEs) during the study. K031 will also evaluate duration of symptoms among outpatients with mild to moderate COVID-19. This will be as an assessment made during the intake and/or follow-up periods of the following: • Time to resolution of the 13 overall and the 8 cardinal COVID-19–related symptoms from day 1 until the day at which the composite score of the 13 overall and 8 cardinal COVID-19–related symptoms becomes 0 or 1 and remains at 0 or 1 for the rest of the intake period and for the follow-up period • Proportion of patients with a reduction from baseline in each of the 13 overall COVID-19–related symptoms • Proportion of patients in whom symptoms (present at baseline) become absent for each of the 13 overall COVID-19–related symptoms • Change from baseline in the overall composite score of the 13 overall COVID-19–related symptoms and the 8 cardinal COVID-19–related symptoms • Time to resolution of fever (defined as from day 1 until the day at which a patient’s daily maximum temperature achieves and remains below 100.4°F without antipyretic medication) • Proportion of patients with oxygen saturation

Abstract Objectives For patients with rheumatoid arthritis (RA) in China, little is known of how their illness perceptions affect their health-related quality of life (HRQoL). The present study investigated associations between specific illness perceptions due to RA and HRQoL features. Methods For 191 patients with RA, illness perceptions were measured using the Brief Illness Perceptions Questionnaire (BIPQ) comprising 8 domains. HRQoL was determined with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Multivariate linear regression analyses were performed. Results The overall BIPQ of patients with RA was 49.09 ± 11.06. The highest and lowest scores were for concern (9.15 ± 1.81) and personal control (4.30 ± 2.52), respectively. Multivariate stepwise regression analyses showed that the overall BIPQ was significantly negatively associated with each HRQoL feature, and HRQoL total score (β = − 0.343, P

Objectives: To evaluate the diagnostic accuracy of the Xpert MTB/RIF assay for bone and joint tuberculosis (BJTB) using tissue specimens, and to compare the diagnostic accuracy of different types of tissue specimens. Methods: This study involved 242 patients admitted with suspected BJTB between May 2018 and March 2020. The Xpert MTB/RIF assay was performed on surgically excised tissue. Diagnostic accuracy of the Xpert MTB/RIF assay was evaluated by culture, histopathology and a composite reference standard (CRS). Results: One hundred and seventy-five patients were excluded (91 based on the exclusion criteria, and 84 as pus specimens were used instead of tissue specimens). Of the 67 patients enrolled, 14 were confirmed as BJTB, 20 as probable BJTB, 11 as possible BJTB, and 22 as non-BJTB. Using culture as the reference standard, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and area under the curve (AUC) of the Xpert MTB/RIF assay were 92.9% (88.2–97.6%), 62.3% (56.1–68.5%), 39.4% (33.2–45.6%), 97.1% (92.3–100.0%), 2.464 (1.077–3.851), 0.114 (0.025–0.203) and 0.776 (0.654–0.897), respectively. When histopathology was used as the reference standard, the Xpert MTB/RIF assay had sensitivity, specificity, PPV, NPV, PLR, NLR and AUC of 79.3% (73.5–85.1%), 73.7% (67.8–79.6%), 69.7% (63.8–75.6%), 82.4% (76.5–88.3%), 3.015 (1.184–4.846), 0.281 (0.141–0.421) and 0.765 (0.646–0.884), respectively. Sensitivity, specificity, PPV, NPV, PLR, NLR and AUC obtained when using CRS as the reference were 73.3% (67.9–78.7%), 100.0% (100.0–100.0%), 100.0% (100.0–100.0%), 64.7% (58.5–70.9%), +∞, 0.267 (0.129–0.405) and 0.867 (0.781–0.952), respectively. Tissue samples were classified, and the positive rate of the Xpert MTB/RIF assay for BJTB using granulation tissue specimens was found to be significantly higher than that for caseous necrotic tissue, sequestrum and other necrotic connective tissues (P

Esophageal carcinoma (EC) is recognized as one of the most frequently occurring malignancies worldwide, and its high morbidity rate motivates efforts to identify potential therapeutic targets. Notably, forkhead box (FOX) family genes are highlighted as possible biomarkers for diagnostics, prognostics, and therapeutics of various malignancies, including EC. Our present study was performed to investigate the underlying mechanism of FOXO6 on the development of EC. We observed a significant upregulation of FOXO6 in EC tissues, contributing to the migration and proliferation in EC cells through gain- and loss-of-function assays. FOXO6 directly interacted with the ubiquitin-specific processing protease 7 (USP7) gene promoter and enhanced its transcriptional activity, which resulted in suppressed cancer cell apoptosis as revealed by chromatin immunoprecipitation (ChIP)-qPCR. USP7 enhanced the ubiquitination of Jumonji domain-containing protein D3 (JMJD3), elevated JMJD3-promoted growth of EC cells, and transcriptionally activated clusterin (CLU) expression at the promoter region via histone H3 lysine 27 tri-methyl (H3K27me3) demethylation, according to immunoprecipitation and ubiquitination assays. Finally, we verified that FOXO6 mediated effects on the USP7/JMJD3/CLU axis to exert an oncogenic role in vivo, which was blocked by USP7 and JMJD3 inhibitor. Our findings demonstrate an important role of the FOXO6/USP7/JMJD3/CLU pathway in EC progression and thus provide attractive potential therapeutic targets for EC patients.

Abstract Dysregulated lipid metabolism represents an important metabolic alteration in cancer. Fatty acids, cholesterol, and phospholipid are the three most prevalent lipids that act as energy producers, signaling molecules, and source material for the biogenesis of cell membranes. The enhanced synthesis, storage, and uptake of lipids contribute to cancer progression. The rewiring of lipid metabolism in cancer has been linked to the activation of oncogenic signaling pathways and cross talk with the tumor microenvironment. The resulting activity favors the survival and proliferation of tumor cells in the harsh conditions within the tumor. Lipid metabolism also plays a vital role in tumor immunogenicity via effects on the function of the noncancer cells within the tumor microenvironment, especially immune‐associated cells. Targeting altered lipid metabolism pathways has shown potential as a promising anticancer therapy. Here, we review recent evidence implicating the contribution of lipid metabolic reprogramming in cancer to cancer progression, and discuss the molecular mechanisms underlying lipid metabolism rewiring in cancer, and potential therapeutic strategies directed toward lipid metabolism in cancer. This review sheds new light to fully understanding of the role of lipid metabolic reprogramming in the context of cancer and provides valuable clues on therapeutic strategies targeting lipid metabolism in cancer.

In this paper, we aim to design a lightweight underwater image enhancement algorithm that can effectively solve the problem of color distortion and low contrast in underwater images. Recently, enhancement methods typically optimize a perceptual loss function, using high-level features extracted from pre-trained networks to train a feed-forward network for image enhancement tasks. This loss function measures the perceptual and semantic differences between images, but it is applied globally across the entire image and does not consider semantic information within the image, which limits the effectiveness of the perceptual loss. Therefore, we propose an area contrast distribution loss (ACDL), which trains a flow model to achieve real-time optimization of the difference between output and reference in training. Additionally, we propose a novel lightweight neural network. Because underwater image acquisition is difficult, our experiments have shown that our model training can use only half the amount of data and half the image size compared to Shallow-UWnet. The RepNet network reduces the parameter size by at least 48% compared to previous algorithms, and the inference time is 5 times faster than before. After incorporating ACDL, SSIM increased by 2.70% and PSNR increased by 9.72%.

Objective: Numerous single nucleotide polymorphisms (SNPs) have been identified as genetic contributors to atrial fibrillation (AF). The aim of this study was to investigate the effects of genome-wide N 6 -methyladenosine (m 6 A)-SNPs on AF. Method: m 6 A-SNPs were identified by analysis of raw data from published AF GWAS datasets and the list of m 6 A-SNPs from the m 6 AVar database. Expression quantitative trait loci (eQTL) analysis was conducted to evaluate the effects of m 6 A-SNPs on gene expression. The expression of linked genes was validated in three independent AF-associated gene expression datasets (GSE14975, GSE108660 and GSE2240). Results: A total of 1429 (6.2%) unique m 6 A-SNPs that were significantly associated with AF were identified. Seventeen m 6 A-SNPs in 14 genes reached genome-wide significance. Eight m 6 A-SNPs demonstrated eQTL signals. Four m 6 A-SNPs (rs383692, rs3211105, rs1061259 and rs1152582) exhibited strong cis-eQTL signals associated with the gene expression levels of SMIM8 , JMJD1C and SYNE2 . SYNE2 and SMIM8 had differential gene expression levels between the AF and sinus rhythm groups. In addition, SYNE2 expression was uniformly downregulated in AF samples compared with normal control samples in the three datasets. Conclusions: Our results provide the first demonstration that m 6 A-SNPs are strongly associated with AF, and extend understanding of m 6 A modification as a potential biological pathway underlying AF.

Background: Hematoma expansion (HE) is a significant predictor of poor outcomes in patients with intracerebral hemorrhage (ICH). Non-contrast computed tomography (NCCT) markers in ICH are promising predictors of HE. We aimed to determine the association of the NCCT markers with HE by using different temporal HE definitions. Methods: We utilized Risa-MIS-ICH trial data (risk stratification and minimally invasive surgery in acute intracerebral hemorrhage). We defined four HE types based on the time to baseline CT (BCT) and the time to follow-up CT (FCT). Hematoma volume was measured by software with a semi-automatic edge detection tool. HE was defined as a follow-up CT hematoma volume increase of >6 mL or a 33% hematoma volume increase relative to the baseline CT. Multivariable regression analyses were used to determine the HE parameters. The prediction potential of indicators for HE was evaluated using receiver-operating characteristic analysis. Results: The study enrolled 158 patients in total. The time to baseline CT was independently associated with HE in one type (odds ratio (OR) 0.234, 95% confidence interval (CI) 0.077–0.712, p = 0.011), and the blend sign was independently associated with HE in two types (OR, 6.203–6.985, both p < 0.05). Heterogeneous density was independently associated with HE in all types (OR, 6.465–88.445, all p < 0.05) and was the optimal type for prediction, with an area under the curve of 0.674 (p = 0.004), a sensitivity of 38.9%, and specificity of 96.0%. Conclusion: In specific subtypes, the time to baseline CT, blend sign, and heterogeneous density were independently associated with HE. The association between NCCT markers and HE is influenced by the temporal definition of HE. Heterogeneous density is a stable and robust predictor of HE in different subtypes of hematoma expansion.

Background Life expectancy and life disparity are 2 useful indicators to assess the health condition of a society. Both Hong Kong and Japan have one of the longest life expectancies in the world. Recently, Hong Kong has overtaken Japan and topped the life expectancy rankings. However, whether Hong Kong has also outperformed Japan in life disparity is still unknown. Methods Decomposition analyses have been conducted to evaluate age-specific contributions to the changes in life expectancy and life disparity for each of the populations. Furthermore, the differences between the 2 populations were examined over the period 1977-2016. Results Reduction in mortality of the adult and the old age groups contributes most to the increase in life expectancy for the study period. Hong Kong has a higher life disparity than Japan, and due to the great improvement in reducing premature deaths, the Hong Kong-Japan gap has been narrowing. However, in recent years, further reduction in mortality of the oldest elderly in Hong Kong has actually contributed to the increase in its disparity, thus widening its gap with Japan again. Conclusion Increasing dominant influence of “saving lives at late ages” is very likely to cause the reemergence of increasing life disparity in these 2 long-lived populations.

Abstract Background Single-cell RNA sequencing (scRNA-seq) enables the possibility of many in-depth transcriptomic analyses at a single-cell resolution. It’s already widely used for exploring the dynamic development process of life, studying the gene regulation mechanism, and discovering new cell types. However, the low RNA capture rate, which cause highly sparse expression with dropout, makes it difficult to do downstream analyses. Results We propose a new method SCC to impute the dropouts of scRNA-seq data. Experiment results show that SCC gives competitive results compared to two existing methods while showing superiority in reducing the intra-class distance of cells and improving the clustering accuracy in both simulation and real data. Conclusions SCC is an effective tool to resolve the dropout noise in scRNA-seq data. The code is freely accessible at https://github.com/nwpuzhengyan/SCC .

The uncontrollable printed structure and poor toughness of three dimensional (3D) printed cement composites hamper their application in buildings. In this study, the polypropylene (PP) and polyvinyl alcohol (PVA) fibers were introduced into the 3D printed calcium sulphoaluminate cement composites (CSACCs) to achieve the stable shape retention and high mechanical strength by controlling the rheological parameters. Experimental results show that the PP and PVA fibers enlarge the linear viscoelastic region (LVR) and increase the elastic modulus of CSACCs. Moreover, these two fibers clearly increase the yield stress and improve the thixotropy of CSACCs in the fiber content of 0.50–1.25%. The relationship between the rheological parameters and structure deformation is revealed by the radar map, and it indicates that the printed structure deformation is improved by controlling the coupling rheological parameters. Furthermore, both PP and PVA fibers are beneficial to the improvement of toughness in the 3D printed CSACCs, and the optimal contents are 0.75 and 1.00%, respectively. In conclusion, developing the 3D printed fiber-reinforced CSACCs with the controllable rheological parameters is significant for improving the printed structures and toughness, which shows a considerable potential in buildings.

Abstract Metastasis is a major contributor to cancer-associated deaths. It involves complex interactions between primary tumorigenic sites and future metastatic sites. Accumulation studies have revealed that tumour metastasis is not a disorderly spontaneous incident but the climax of a series of sequential and dynamic events including the development of a pre-metastatic niche (PMN) suitable for a subpopulation of tumour cells to colonize and develop into metastases. A deep understanding of the formation, characteristics and function of the PMN is required for developing new therapeutic strategies to treat tumour patients. It is rapidly becoming evident that therapies targeting PMN may be successful in averting tumour metastasis at an early stage. This review highlights the key components and main characteristics of the PMN and describes potential therapeutic strategies, providing a promising foundation for future studies.

Background: Emerging evidence indicates that the worldwide incidence of early-onset coronary artery disease (EOCAD) is increasing. The genetic background has been assumed to harbor pathogenic risk, although the existing findings are mainly restricted to Caucasians. Little is known regarding the clinical profiles of patients with EOCAD and the extent to which genetic factors are related to disease susceptibility and outcomes in Asian people, especially ethnic Chinese. Methods and Results: The Genetic characteristics of coRonary Artery disease (CAD) in ChiNese young aDults (GRAND) study is a multicenter, hospital-based observational clinical study, combined of case-control design and longitudinal prospective cohort. Six thousand nationally representative patients who underwent coronary angiography at 38 centers have been enrolled since May 2017. Clinical data of patients with EOCAD (aged ≤45 years) are collected at the baseline to delineate conventional risk factors, clinical profiles, and therapeutic options of EOCAD and compared with data for patients with late-onset CAD (aged ≥65 years) and age-matched controls without CAD. The patients are followed for 3 years to trace major adverse cardiovascular (CV) events: cardiac death, nonfatal myocardial infarction, and ischemia-driven revascularization. Functional variants contributing to EOCAD risk are identified by high-depth whole-exome sequencing. The genetic profiles are further linked to disease severity and prognosis. A multi-dimensional risk score is established to predict prevalent EOCAD and incident CV events among young Chinese adults. Conclusions: The GRAND study will generate a thorough understanding of the clinical characteristics and genetic basis of EOCAD and may pave the way for genetic screening, early prevention, and future drug discovery for CAD in young Chinese generations.

This paper presents an energy-saving and high-resolution successive approximation register (SAR) analog-to-digital converter (ADC) with 14-nm CMOS FinFET technology for wireless communication system. An Equivalent Split-Capacitor is proposed to enlarge redundancy range and alleviate the settling error of the bridge capacitor array. A hybrid capacitor switching procedure is adopted to reduce power consumption and the variation of input common-mode voltage of the comparator. Measurement results of the 14-nm CMOS SAR-ADC achieves a SNDR of 61.29 dB and 58.34dB at low and Nyquist input frequency, respectively, resulting in figure-of-merits(FoMs) of 8.2 and 11.15fJ/conversion-step, respectively. The ADC core occupies an active area 0.112mm2.

Gentiana triflora is an important medicinal plant in China with economic and medicinal value. Here, we report the complete chloroplastsequences of G. trifloral. The cp genome of G. triflora of 149, 125 bp contains 130 unique genes, including 85 protein-coding genes,8 rRNA genes, and 37 tRNA genes. The analysis of repeat showed that palindromic had the highest frequency. Besides, a total numberof 45 SSR were identified, most of which were mononucleotide adenine-thymine. Comparative genome analysis of Gentiana speciesrevealed that the pair of the inverted repeat was more conserved than the single-copy region. This analysis resulted in identification of 8 hypervariable regions (trnH-GUG, trnG-UCC-intron, atpI, trnD-GUC, trnL-UAA, rpl32-trnL-UAG, petA and ycf1). Phylogenetic analysis revealed that G. triflora was most closely related to Gentiana manshurica. In conclusion, this study enriched the genomic resources of the Gentiana genus and provided a basis for evolution and phylogeny analyses.

Aloe-emodin (1,8-dihydroxy-3-hydroxymethyl-anthraquinone), derived from some Chinese edible medicinal herbs, exerts a potential anticancer activity on various cancer cells, making it a drug candidate for cancer therapy. Yet, the role of aloe-emodin in pyroptosis, a new type of cell death, is uncharacterized. In this study, we explored the molecular mechanisms of aloe-emodin-triggered pyroptosis. Aloe-emodin inhibited proliferation and migration and triggered caspase-dependent cell death of HeLa cells in a dose-dependent manner. Aloe-emodin caused mitochondrial dysfunction and induced pyroptosis by activating the caspase-9/3/GSDME axis. Transcriptional analysis showed extensive changes in gene expressions in cellular pathways, including MAPK, p53, and PI3K-Akt pathways when treated with aloe-emodin. This study not only identified a novel role of aloe-emodin in pyroptotic cell death, but also performed a systematical genome-wide analysis of cellular pathways responding to aloe-emodin, providing a theoretical basis for applying anthraquinone derivatives in the treatment of GSDME-expressing cancers.

Background: To compare the corneal biomechanics of thin normal cornea (TNC) with thinnest corneal thickness (TCT) (≤500 µm), forme-fruste keratoconus (FFKC) and cornea after small incision lenticule extraction (Post-SMILE) had their central corneal thickness (CCT) matched by Corneal Visualization Scheimpflug Technology (Corvis ST).Methods: CCT were matched in 23 eyes with FFKC, 23 eyes by SMILE in 3 months post-operatively, and 23 TNC eyes. The differences in corneal biomechanics by Corvis ST among the three groups were compared.Results: There was no significant difference in CCT among the three groups, and the biomechanically corrected intraocular pressure (bIOP) did not differ significantly among the three groups (all p > 0.05). There were significant differences in most DCR parameters between pre- and post-operatively (all p < 0.05). Compared with TNC, the values of corneal deflection amplitude during the first applanation (A1DA), length at the first applanation (A1L), corneal deflection amplitude during the second applanation (A2DA), and maximum deformation amplitude (DA) decreased in 3 months after SMILE (all p < 0.05), these values increased in the FFKC (all p < 0.05).Conclusion: The majority of the DCR parameters were different among the three groups. The parameters A1DA, A1L, A2DA, and DA may be different between TNC and Post-SMILE, TNC and FFKC, and Post-SMILE and FFKC.

There is a potential safety risk with ethyl carbamate (EC) in Hongqu Huangjiu production; 90% of the EC in rice wine is produced by the reaction of the urea with the alcohol of Saccharomyces cerevisiae. In our previous experiments, we screened and obtained a S. cerevisiae strain JH301 that offered low urea production. However, the key genes responsible for low urea production of strain JH301 remain unclear. Here, the whole genome sequencing of S. cerevisiae strain JH301 was accomplished via a next-generation high-throughput sequencing and long-read sequencing technology. There are six main pathways related to the urea metabolism of strain JH301 based on KEGG pathway mapping. Three species-specific genes are related to the urea metabolism pathways and were found in comparative genome analysis between strains JH301 and S288c during Hongqu Huangjiu production for the first time. Finally, the ARG80 gene was found to be likely a key gene responsible for low urea production of S. cerevisiae strain JH301, as determined by PCR and qRT-PCR check analyses from DNA and RNA levers. In conclusion, the results are useful for a scientific understanding of the mechanism of low urea production by Saccharomyces cerevisiae during Hongqu Huangjiu fermentation. It also is important to control the urea and EC contents in Hongqu Huangjiu production.

ABSTRACT: Adiponectin can participate in the regulation of glucose and lipid metabolism, energy regulation, immune response, resistance to inflammation, oxidative stress, and apoptosis. Studies in rodents demonstrated that the small molecule compound adiponectin receptor agonist AdipoRon could activate the adiponectin receptor and played the same biological role as adiponectin. To explore the influence and regulation of AdipoRon on lipid metabolism disorder in Huoyan goose liver, in this study, goslings were fed a high-fat diet and then administered different dosages of AdipoRon. Subsequently, goose body weight, liver index, liver histopathological changes, blood glucose, blood and liver lipid, biochemical indexes related to liver function and oxidative stress, and the expression levels of genes related to lipid metabolism, inflammation, apoptosis, and autophagy, adiponectin and its receptors, key molecules of adiponectin involved signal pathway, and transcription factors in the liver, were detected using H&E and Oil red O staining, ELISA, and qRT-PCR methods. The results indicated that AdipoRon could alter the expression of lipid metabolism-related genes, inflammatory factors, apoptosis and autophagy genes, and adiponectin and its receptor genes in liver tissues through signaling pathways such as AMPK and p38 MAPK, as well as the involvement of transcription factors such as PPARα, PPARγ, SIRT1, and FOXO1, reduce the lipid content in blood and liver tissues of geese fed high-fat diets, improve liver antioxidant capacity, regulate apoptosis and autophagy of hepatocytes, and reduce liver inflammatory injury. Our study suggests that AdipoRon has a protective effect on fatty liver injury in goslings fed a high-fat diet.

Pulmonary arterial hypertension (PAH) is an incurable disease with high mortality. Chemerin has been found to be associated with pulmonary hypertension (PH). However, the specific role of chemerin in mediating PH development remains unclear. This study aimed to elucidate the regulatory effects and the underlying mechanism of chemerin on PH and to investigate the expression levels of chemerin protein in plasma in PAH patients. In vivo, two animal models of PH were established in rats by monocrotaline (MCT) injection and hypoxia. We found that the expression levels of chemerin and its receptor, chemokine-like receptor 1 (CMKLR1), were significantly upregulated in the lungs of PH rats. Primary cultured pulmonary arterial smooth muscle cells [(PASMCs) (isolated from pulmonary arteries of normal healthy rats)] were exposed to hypoxia or treated with recombinant human chemerin, we found that CMKLR1 expression was upregulated in PASMCs in response to hypoxia or chemerin stimulation, whereas the exogenous chemerin significantly promoted the migration and proliferation of PASMCs. Notably, the regulatory effects of chemerin on PASMCs were blunted by PD98059 (a selective ERK1/2 inhibitor). Using enzyme linked immunosorbent assay (ELISA), we found that the protein level of chemerin was also markedly increased in plasma from idiopathic pulmonary arterial hypertension (IPAH) patients compared to that from healthy controls. Moreover, the diagnostic value of chemerin expression in IPAH patients was determined through receiver operating characteristic (ROC) curve analysis and the result revealed that area under ROC curve (AUC) for plasma chemerin was 0.949. Taken together, these results suggest that chemerin exacerbates PH progression by promoting the proliferation and migration of PASMCs via the ERK1/2 signaling pathway, and chemerin is associated with pulmonary hypertension.

IntroductionTo evaluate and compare the specificity of Toxocara canis-specific antibody detection in the serum and aqueous samples for the diagnosis of ocular toxocariasis (OT) and explore the cytokine profiles associated with the condition in children.Materials and MethodsThis is a prospective cohort study. The inclusion criteria were the clinical presentations of OT, which included unilateral vision reduction, typical peripheral or posterior pole granuloma with variable degrees of vitritis, and exclusion of other diagnoses. The titer of antibody against the excretory-secretory antigen of Toxocara canis [T-immunoglobulin G (IgG)] was measured in serum and aqueous samples that were taken from the affected eyes. The diagnosis of OT was made upon positive detection of T-IgG either in the serum or aqueous. The rest with typical clinical presentations as described above but a positive serum or aqueous T-IgG could not be confirmed were diagnosed as suspected OT. Cytokines were measured using multiplexed cytometric bead array system.ResultsTwo hundred and eleven eyes of 211 patients had participated in the study. One hundred and twenty-eight eyes were diagnosed as OT. The median age of the cohort was 7.7 years with a male to female ratio of 2.5:1. Major initial symptoms were decreased vision (74%) and strabismus (22%). The percentages of eyes with peripheral granuloma, posterior granuloma, and endophthalmitis were 40, 18, and 41%, respectively. Vitritis (100%), vitreous strands (64%), retinal fibrotic bands (57%), and retinal detachment (42%) were the most common signs. T-IgG was positive in 66.7% of the aqueous and 57.2% of the serum samples. Forty-four patients were diagnosed T-IgG negative in both serum and aqueous of the affected eyes. Interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, IL-8, eosinophil chemotactic protein (Eotaxin), MCP-1β, and vascular endothelial growth factor (VEGF) were higher in T-IgG negative eyes when compared to controls and further increased in T-IgG positive eyes. However, only T-IgG positive eyes showed increased IL-5, IL-13, and IL-10. IL-1β, tumor necrosis factor-alpha (TNF-α), IL-12, IL-2, interferon-gamma (IFN-γ), and IL-4 were undetectable in all eyes.ConclusionsPediatric OT is often present with severe retinal complications. Polarized intraocular Th2 response was only found in aqueous T-IgG positive eyes. Our results supported an aqueous sample-based antibody test for the more specific diagnosis of OT.