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ABSTRACT Background Cancer cachexia can impact prognosis, cause resistance to anticancer treatments and affect the tolerability of treatments. This study aims to identify hepatocellular carcinoma (HCC) with cachexia by characterizing longitudinal body composition (BC) trajectories. Methods This longitudinal, multicentre cohort study included unresectable HCC patients treated with first‐line programmed death‐(ligand)1 inhibitors plus anti‐vascular endothelial growth factor antibody/tyrosine kinase inhibitors between 01/2018–12/2022. BC measurements including skeletal muscle mass (SMM) and total adipose tissue area (TATA) were evaluated by computed tomography at the third lumbar vertebra at baseline and follow‐up imaging. Unsupervised latent class growth mixed models were applied to distinguish potential longitudinal SMM and TATA trajectories for identifying cachexia. The primary study endpoint was overall survival (OS), with secondary endpoints including progression‐free survival (PFS), objective response rate (ORR) and safety. Multiple Cox proportional hazards models were used to calculate adjusted hazard ratios (HRs) for survival. Results A total of 411 patients with 2138 time‐point measurements were included. The median age was 56 years, and 50 (12.2%) patients were female. Two distinct trajectories were identified for SMM and TATA: sharp‐falling and stable. SMM sharply declined in 58 patients (14.1%) and TATA in 71 of 406 patients (17.5%) with significant worse OS (for SMM, 17.0 vs. 24.9 months; p

The purpose of this study was to investigate the effects of different structures of corn starch (high amylose corn starch, normal corn starch, and waxy corn starch) on the processing quality of dough. The rheological properties, thermal properties, microstructure and physicochemical properties of gluten proteins in the simulated dough of corn starch were determined. The results showed that the viscoelasticity of the high-amylose corn starch mock dough was significantly higher than that of the normal/waxy cornstarch mock dough, which was attributed to its non-gelatinization and highly filling characteristics. Waxy corn starch significantly inhibited the thermal aggregation of gluten proteins through competitive water absorption, resulting in a relatively loose structure of the dough after heat treatment. The results of molecular weight distribution and intermolecular interactions also confirmed that waxy corn starch mainly inhibited the formation of high molecular weight gluten proteins by hindering the crosslinking of disulfide bonds, leading to the transition of gluten proteins from a rigid α-helix to a disordered β-turn structure. This study helps to gain a deeper understanding of the interaction mechanism between starch and gluten proteins, and provides a reference for improving the processing quality of flour products by regulating the structural characteristics of starch.

Abstract Tuberculosis has been one of the most common communicable diseases raising global concerns. Accurately predicting the incidence of Tuberculosis remains challenging. Here we constructed a time-series analysis and fusion tool using multi-source data, and aimed to more accurately predict the incidence trend of tuberculosis of Anhui Province from 2013 to 2023. Random forest algorithm (RF), Feature Recursive Elimination (RFE) and Least absolute shrinkage and selection operator (LASSO) were implemented to improve the derivation of features related to infectious diseases and feature work. Based on the characteristics of infectious disease data, a model of RF-RFE-LASSO integrated particle swarm optimization multiple inputs long short term memory recurrent neural network (RRL-PSO-MiLSTM) was created to perform more accurate prediction. Results showed that the PSO-MiLSTM achieved excellent prediction results compared with common single-input and multi-input time-series models (test set MSE:42.3555, MAE: 59.3333, RMSE: 146.7237, MAPE: 2.1133, R 2 : 0.8634). PSO-MiLSTM enriches and complements the methodological research content of calibrating the time-series predictive analysis of infectious diseases using multi-source data, and can be used as a brand-new benchmark for the analysis of influencing factors and trend prediction of infectious diseases at the public health level in the future, as well as providing a reference for incidence rate prediction of infectious diseases.

Abstract This study reanalyzes the detection prospects of dark matter (DM) annihilation signals in the Galactic Center, focusing on velocity-dependent dynamics within a spike density near the supermassive black hole (Sgr A⋆). We investigate three annihilation processes — p-wave, resonance, and forbidden annihilation — under semi-relativistic velocities, leveraging gamma-ray data from Fermi and DAMPE telescopes. Our analysis integrates a fermionic DM model with an electroweak axion-like particle (ALP) portal, exploring annihilation into two or four photons. Employing a comprehensive six-dimensional integration, we precisely calculate DM-induced gamma-ray fluxes near Sgr A⋆, incorporating velocity and positional dependencies in the annihilation cross-section and photon yield spectra. Our findings highlight scenarios of resonance and forbidden annihilation, where the larger ALP-DM-DM coupling constant C aχχ can affect spike density, potentially yielding detectable gamma-ray line spectra within Fermi and DAMPE energy resolution. We set upper limits for C aχχ across these scenarios, offering insights into the detectability and spectral characteristics of DM annihilation signals from the Galactic Center.

Abstract Triple-negative breast cancer (TNBC) represents a significant health concern for women worldwide, and the overproduction of MMP9 and CD151 is associated with various cancers, influencing tumour growth and progression. This study aimed to investigate how CD151 and MMP9 affect TNBC cell migration, apoptosis, proliferation, and invasion. Immunohistochemical experiments revealed that CD151 and MMP9 were positively expressed in triple-negative breast cancer, and lymph node metastasis, the histological grade, and CD151 and MMP9 expression were found to be independent prognostic factors for the survival of patients with triple-negative breast cancer. Cytological experiments indicated that the knockdown of CD151 or MMP9 slowed triple-negative breast cancer cell growth, migration, and invasion and increased the apoptosis rate. Compared with CD151 knockdown, double MMP9 and CD151 knockdown further promoted cell death and inhibited TNBC cell proliferation, migration, and invasion. Moreover, β-catenin and p-GSK-3β were significantly downregulated. In summary, simultaneously silencing CD151 and MMP9 further suppressed the proliferation, migration and invasion of TNBC cells and promoted their apoptosis. One possible strategy for inducing this effect is to block the GSK-3β/β-catenin pathway.

Abstract Objective Obesity is a common feature in women with polycystic ovary syndrome (PCOS) and potentially significantly influences reproductive function. However, opinions are divided as to which factor is a more appropriate obesity predictor of reproductive outcomes. The aim of this study was to investigate the discriminatory capability of anthropometric measures in predicting reproductive outcomes in Chinese women with PCOS. Methods A total of 998 women with PCOS from PCOSAct were included. Logistic regression models were used to compute the odds ratios (ORs) and 95% confidence interval (95% CIs) to assess the effect of anthropometric measures, including body mass index (BMI), waist circumference (WC), hip circumference (HC), the waist‒hip ratio (WHR) and the waist‒height ratio (WHtR), on reproductive outcomes. The discrimination abilities of the models were assessed and compared based on the area under the receiver operating characteristic curve (AUC), Akaike’s information criterion (AIC) and integrated discrimination improvement (IDI). Results Among PCOS women, there was a graded association between anthropometric measures and predicted reproductive outcomes across quintiles of anthropometric measures, including a linear association among WHR, BMI and reproductive outcomes and among waist circumference, WHtR and live birth, pregnancy, and ovulation. However, only a linear association was noted between the hip and ovulation. C-statistic comparisons and IDI analyses revealed a trend towards a significant superiority of BMI for ovulation and WHR for live birth, pregnancy and conception in the models. Combining obesity variables improved discrimination in the multivariable models for reproductive outcomes. Conclusions Our findings support that BMI is a better predictor of ovulation and that the WHR is a better predictor of live birth, pregnancy and conception, whereas the combination of obesity variables contributes to the discrimination of reproduction.

In this paper, we investigated the potential use of a new organic-inorganic hybrid crystal structure based on KNO3 in ignition compositions. H2dabco[K(NO3)3] (DAN-2) with organic-inorganic hybrid crystal structure is synthesized through intermolecular assembly technology. Scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) were used to detect the crystal morphology, structure and molecular structure of DAN-2, which has a regular cubic structure. Experimental data were obtained using thermogravimetric/differential scanning calorimetry (TG-DSC), closed bomb test and high-speed photography, which were then used to study and analyze the thermal decomposition properties and combustion properties of DAN-2. The initial thermal decomposition temperature of DAN-2 was low (194 °C) and the activation energy of the thermal decomposition was 154 kJ/mol. Possible thermal decomposition mechanisms are further discussed and proposed. This research pushed forward the application of organic-inorganic hybrid crystal structure oxidant DAN-2 in ignition system.

Acute pancreatitis (AP) is a potentially fatal condition with no targeted treatment options. Although inhibiting xanthine oxidase (XO) in the treatment of AP has been studied in several experimental models and clinical trials, whether XO is a target of AP and what its the main mechanism of action is remains unclear. Here, we aimed to re-evaluate whether XO is a target aggravating AP other than merely generating reactive oxygen species that trigger AP. We first revealed that XO expression and enzyme activity were significantly elevated in the serum and pancreas of necrotizing AP models. We also found that allopurinol and febuxostat, as purine-like and non-purine XO inhibitors, respectively, exhibited protective effects against pancreatic acinar cell death in vitro and pancreatic damage in vivo at different doses and treatment time points. Moreover, we observed that conditional Xdh overexpression aggravated pancreatic necrosis and severity. Further mechanism analysis showed that XO inhibition restored the hypoxia-inducible factor 1-alpha (HIF-1α)-regulated lactate dehydrogenase A (LDHA) and NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling pathways and reduced the enrichment of 13C6-glucose to 13C3-lactate. Lastly, we observed that clinical circulatory XO activity was significantly elevated in severe cases and correlated with C-reactive protein levels, while pancreatic XO and urate were also increased in severe AP patients. These results together indicated that proper inhibition of XO might be a promising therapeutic strategy for alleviating pancreatic necrosis and preventing progression of severe AP by downregulating HIF-1α-mediated LDHA and NLRP3 signaling pathways.

Steel fiber-reinforced concrete material has garnered significant attention in structure design due to its excellent resistance to fatigue damage. The application of the plain concrete microplane model is extended to steel fiber-reinforced concrete by modifying the stress-strain boundary conditions on the microplane and then extended to fatigue damage analysis by considering fatigue-related material stiffness, mainly concerned with tensile damage, mainly concerned with tensile damage. The normal positive strain on the micro-plane is regarded as the fatigue variable, and the fatigue history variable is the accumulation of the fatigue variable during the loading. The relationship between the fatigue history variable and the material stiffness fatigue degradation function is established. In the numerical implementation, the crack band model is combined to reduce the mesh sensitivity caused by strain localization. During the numerical simulation, the parameters of plain concrete, steel fiber-reinforced concrete, and the material fatigue degradation function can be calibrated sequentially, requiring only a few benchmark tests for accurate parameter calibration. The numerical results show that this model can be used for the fatigue damage analysis of plain concrete and steel fiber-reinforced concrete material. It is expected to be used for the refined analysis of concrete structures under complex loading conditions and structural forms in the future, providing convenience to engineering design, evaluation, and optimization.

AbstractBackground To investigate the effectiveness of the intervention with critical value management and push short messaging service (SMS), and to determine improvement in the referral rate of patients with positive hepatitis C antibody (anti-HCV).Methods No intervention was done for patients with positive anti-HCV screening results from 1 January 2015 to 31 October 2021. Patients with positive anti-HCV results at our hospital from 1 November 2021 to 31 July 2022 were informed vide critical value management and push SMS. For inpatients, a competent physician was requested to liaise with the infectious disease physician for consultation, and patients seen in the OPD (outpatient department) were asked to visit the liver disease clinic. The Chi-square correlation test, one-sided two-ratio test and linear regression were used to test the relationship between intervention and referral rate.Results A total of 638,308 cases were tested for anti-hepatitis C virus (HCV) in our hospital and 5983 of them were positive. 51.8% of the referred patients were aged 18–59 years and 10.8% were aged ≥75 years. The result of Chi-square correlation test between intervention and referral was p = .0000, p

Abstract Pharmacological agents regarding the most optimal treatments of acute pancreatitis remain. One‐carbon metabolism nutrients as therapeutic agents in many diseases might be involved in acute pancreatitis. The roles are acquired exploration in acute pancreatitis. We utilized Mendelian randomization to assess the causal impact of folate, homocysteine, and vitamin B12 (VB12) on acute pancreatitis. Wild‐type and corresponding genetically modified mouse models were used to verify the genetic correlating findings. A negative association between genetically predicted serum VB12 levels and risks of acute pancreatitis was identified in human population. The transcobalamin receptor (TCblR)/CD320 gene ablation that decreased cellular VB12 uptake and ATP production in pancreatic tissues promoted necrosis, resulting in much severe pathological changes of induced acute pancreatitis in mice. VB12 pretreatment and posttreatment dramatically increased ATP levels in pancreatic tissues and reduced the necrosis, then the elevated levels of amylase in serum, the levels of CK‐19, the activity of trypsin, and T lymphocyte infiltration in pancreatic tissues, prevented the pancreatic gross loss and ameliorated histopathological changes of mouse pancreases with induced acute pancreatitis. The results reveal that VB12 is potential as a therapeutic agent to inhibit tissue injuries and adaptive inflammatory responses in the pancreas in patients with acute pancreatitis.

Coagulopathy is a critical pathophysiological mechanism of acute pancreatitis (AP), arising from the complex interplay between innate immune, endothelial cells and platelets. Although initially beneficial for the host, uncontrolled and systemic activation of coagulation cascade in AP can lead to thrombotic and hemorrhagic complications, ranging from subclinical abnormalities in coagulation tests to severe clinical manifestations, such as disseminated intravascular coagulation. Initiation of coagulation activation and consequent thrombin generation is caused by expression of tissue factor on activated monocytes and is ineffectually offset by tissue factor pathway inhibitor. At the same time, endothelial-associated anticoagulant pathways, in particular the protein C system, is impaired by pro-inflammatory cytokines. Also, fibrin removal is severely obstructed by inactivation of the endogenous fibrinolytic system, mainly as a result of upregulation of its principal inhibitor, plasminogen activator inhibitor type 1. Finally, increased fibrin generation and impaired break down lead to deposition of (micro) vascular clots, which may contribute to tissue ischemia and ensuing organ dysfunction. Despite the high burden of coagulopathy that have a negative impact on AP patients’ prognosis, there is no effective treatment yet. Although a variety of anticoagulants drugs have been evaluated in clinical trials, their beneficial effects are inconsistent, and they are also characterized by hemorrhagic complications. Future studies are called to unravel the pathophysiologic mechanisms involved in coagulopathy in AP, and to test novel therapeutics block coagulopathy in AP.

The accumulation of foam cells in the subendothelial space of the vascular wall to form plaques is the real cause of atherosclerotic lesions. Conventional interventions, such as statins and anti-cytokine or anti-inflammatory therapies, suffer problems in terms of their short therapeutic outcomes and potential disruption of the immune system. The development of more efficient therapeutics to restrict the initial progression of plaques appears to be crucial for treating and preventing atherosclerosis. Decreasing foam cell formation by reversing the excessive phagocytosis of modified low-density lipoprotein (LDL) in macrophages is highly desirable. Here, we developed a strategy based on engineered monocytes to dynamically regulate lipid uptake by macrophages inspired by a CD47–SIRPα signaling-induced defect in the phagocytosis of lesional macrophages at the advanced stage of AS. Briefly, a complex called CD47p-GQDs-miR223, which is designed to interact with SIRPα, was synthesized to remodel monocytes by decreasing the uptake of oxidized LDL through the activation of CD47-SIRPα signaling. After injection, these monocytes compete for recruitment to atherosclerotic plaques, release gene drugs and mediate anti-inflammatory phenotypic remodeling of the aboriginal macrophages, effectively inhibiting the development of foam cells. Our strategy provides a new therapeutic for preventing the progression of atherosclerosis.

Tremella fuciformis (TF) stem accounts for about 10% of the whole mushroom, and most of them are dumped without utilization. To effectively utilize the waste, the effects of fine grinding and superfine grinding technology on the processing characteristics and physicochemical properties of Tremella fuciformis stem powder (TFSP) were investigated, and the effects of TFSP on the quality of steamed bun were analyzed. The findings indicate that the specific surface area of superfine Tremella fuciformis stem powder (STFSP) is 1.6 times larger than that of fine Tremella fuciformis stem powder (FTFSP). Despite this, the infrared spectra of STFSP and FTFSP are similar. The water solubility index and oil holding capacities of STFSP saw an increase of 18.81%, whereas its water holding capacity decreased by 11.34%. Superfine grinding not only enhanced the processing characteristics but also stabilized the powder form. Moreover, steamed buns incorporating 4% STFSP were judged to have the optimal taste. Superfine grinding significantly influences the physicochemical properties of TFSP, resulting in enhanced quality of steamed buns.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonosis caused by the SFTS virus (SFTSV). Understanding the prevalence of SFTSV RNA in humans, vertebrate hosts and ticks is crucial for SFTS control. Methods A systematic review and meta-analysis were conducted to determine the prevalence of SFTSV RNA in humans, vertebrate hosts and questing ticks. Nine electronic databases were searched for relevant publications, and data on SFTSV RNA prevalence were extracted. Pooled prevalence was estimated using a random effects model. Subgroup analysis and multivariable meta-regression were performed to investigate sources of heterogeneity. Results The pooled prevalence of SFTSV RNA in humans was 5.59% (95% confidence interval [CI] 2.78–9.15%) in those in close contact (close contacts) with infected individuals (infected cases) and 0.05% (95% CI 0.00–0.65%) in healthy individuals in endemic areas. The SFTSV infection rates in artiodactyls (5.60%; 95% CI 2.95–8.96%) and carnivores (6.34%; 95% CI 3.27–10.23%) were higher than those in rodents (0.45%; 95% CI 0.00–1.50%). Other animals, such as rabbits, hedgehogs and birds, also played significant roles in SFTSV transmission. The genus Haemaphysalis was the primary transmission vector, with members of Ixodes, Dermacentor, and Amblyomma also identified as potential vectors. The highest pooled prevalence was observed in adult ticks (1.03%; 95% CI 0.35–1.96%), followed by nymphs (0.66%; 95% CI 0.11–1.50%) and larvae (0.01%; 95% CI 0.00–0.46%). The pooled prevalence in ticks collected from endemic areas (1.86%; 95% CI 0.86–3.14%) was higher than that in ticks collected in other regions (0.41%; 95% CI 0.12–0.81%). Conclusions Latent SFTSV infections are present in healthy individuals residing in endemic areas, and close contacts with SFTS cases are at a significantly higher risk of infection. The type of animal is linked to infection rates in vertebrate hosts, while infection rates in ticks are associated with the developmental stage. Further research is needed to investigate the impact of various environmental factors on SFTSV prevalence in vertebrate hosts and ticks. Graphical Abstract

AIM: To compare high or low concentration of hyaluronic acid eye drops (HY) for dry eye syndromes (DES). METHODS: Randomized controlled trials (RCTs) comparing various concentrations of HY were searched in PubMed, Embase, Web of Science, Cochrane, SinoMed, CNKI, Wanfang Database, CQVIP, and Chinese journals databases between inception and July 2023. Pooled standardized mean differences (SMD) or weighted mean difference (WMD) with 95% confidence intervals (CI) from RCTs evaluating Schirmer's I test (SIT), corneal fluorescein staining score (CFS), tear breakup time (TBUT), DES score (DESS), and Ocular Surface Disease Index (OSDI) were calculated. Sensitivity analysis, Egger's test and Meta-regression analysis were performed for all indicators. RESULTS: We conducted a Meta-analysis of 10 RCTs that met the inclusion criteria, involving 1796 cases. High-concentrations group significantly improved the outcome of CFS according to random effects modelling (SMD, -3.37; 95%CI, -5.25 to -1.48; P=0.0005). The rest of the results were not statistically significant, including indicators such as SIT, TBUT, DESS and OSDI. CONCLUSION: For dry eyes with positive corneal staining, a high concentration of HY is recommended, whereas in other cases, a high concentration of HY does not offer a more pronounced advantage over a low concentration of HY in the treatment of dry eyes.

Abstract Large High Altitude Air Shower Observatory has detected 0.2 − 13 TeV emission of GRB 221009A within 2000 s since the trigger. Here we report the detection of a 400 GeV photon, without accompanying prominent low-energy emission, by Fermi Large Area Telescope in this direction with a 0.4 days’ delay. Given an intergalactic magnetic field strength of about 4 × 10−17 G, which is comparable to limits from TeV blazars, the delayed 400 GeV photon can be explained as the cascade emission of about 10 TeV gamma rays. We estimate the probabilities of the cascade emission that can result in one detectable photon beyond 100 GeV by Fermi Large Area Telescope within 0.3 − 1 days is about 2% whereas it is about 20.5% within 0.3 − 250 days. Our results show that Synchrotron Self-Compton explanation is less favored with probabilities lower by a factor of about 3 − 30 than the cascade scenario.

Abstract Investigations of one-dimensional segmented heteronanostructures (1D-SHs) have recently attracted much attention due to their potentials for applications resulting from their structure and synergistic effects between compositions and interfaces. Unfortunately, developing a simple, versatile and controlled synthetic method to fabricate 1D-SHs is still a challenge. Here we demonstrate a stress-induced axial ordering mechanism to describe the synthesis of 1D-SHs by a general under-stoichiometric reaction strategy. Using the continuum phase-field simulations, we elaborate a three-stage evolution process of the regular segment alternations. This strategy, accompanied by easy chemical post-transformations, enables to synthesize 25 1D-SHs, including 17 nanowire-nanowire and 8 nanowire-nanotube nanostructures with 13 elements (Ag, Te, Cu, Pt, Pb, Cd, Sb, Se, Bi, Rh, Ir, Ru, Zn) involved. This ordering evolution-driven synthesis will help to investigate the ordering reconstruction and potential applications of 1D-SHs.

Copper is one of the predominant water pollutants. Excessive exposure to copper can cause harm to animal health, affecting the central nervous system and causing blood abnormalities. Cuproptosis is a novel form of cell death that differs from previous programmed cell death methods. However, the impact of copper on the intestines remains unclear. Therefore, we investigated the effects of different concentrations of copper exposure on the intestinal proteome of Takifugu rubripes (T. rubripes). Relevant biomarkers were used to detect cuproptosis. We revealed the crosstalk relationship between cuproptosis and self-rescue at different concentrations, and discussed the feasibility of using potential cuproptosis indicators as anti-infection factors. We observed intestinal damage in the three copper exposure groups, especially in T. rubripes treated with 100 and 500 μg/L copper, with shedding and breakage of intestinal villus and fuzzy and loose structure of intestinal mucosa. The presence of copper stress not only causes cuproptosis but also oxidative damage caused by reactive oxygen species (ROS). The results of quantitative proteomics by TMT showed that compared to the 50 and 100 μg/L copper exposure groups, the expression of glutaminase, pyruvate kinase, and skin mucus lectin in the 500 μg/L group was significantly increased. The positive mediators COX5A and CTNNB1, as well as the negative mediators CD4 and FDXR, were found to be differentially expressed. Using the protein expression trends of cuproptosis indicator factors FDX1 and DLAT to indicate the concentration of copper ions in the environment. In addition, we found a new effect of promoting ferroptosis: providing additional copper ions can activate the phenomenon of ferroptosis. Our results expand our understanding of the potential health risks of copper in T. rubripes. At the same time, it is of great significance for the process of copper poisoning and the development of new environmental toxicology detection reagents.

PurposeThe rising prevalence of postpartum depression (PPD) is harmful to women and families. While there is a growing body of evidence suggesting an association between PPD and autoimmune diseases (ADs), the direction of causality remains uncertain. Therefore, Mendelian randomization (MR) study was employed to investigate the potential causal relationship between the two.MethodsThis study utilized large-scale genome-wide association study genetic pooled data from two major databases: the IEU OpenGWAS project and the FinnGen databases. The causal analysis methods used inverse variance weighting (IVW). The weighted median, MR-Egger method, MR-PRESSO test, and the leave-one-out sensitivity test have been used to examine the results’ robustness, heterogeneity, and horizontal pleiotropy.ResultsA total of 23 ADs were investigated in this study. In the IVW model, the MR study showed that PPD increased the risk of type 1 diabetes (OR , = 1.15 (1.05–1.26),p

Abstract Aim To explore the correlations between examination tolerance and anxiety, knowledge needs and examination cooperation in sedation‐free gastroscopy examinees. Design Cross‐sectional survey using convenience sampling. Methods A total of 170 healthy adults who underwent sedation‐free gastroenteroscopy were asked to complete a visual analogue scale (VAS) to rate their examination tolerance, the state anxiety questionnaire (S‐AI), a newly designed knowledge needs questionnaire and a cooperation questionnaire. Results The VAS score was 4.47 ± 1.96, the state anxiety score was 39.46 ± 9.81, the total score for knowledge needs was 44.89 ± 11.02, and the average cooperation score was 2.47 ± 0.38. The VAS score during the examination positively correlated with the pretest state anxiety score and pretest knowledge needs score and negatively correlated with the examination cooperation score. The results of multiple linear regression analysis showed that after undergoing the examination for the first time, anxiety, body position and swallowing control were the main factors influencing the examination tolerance of sedation‐free gastroscopy examinees. Patient or Public Contribution We would like to thank the staff and patients of the participating hospital for their assistance and cooperation in performing the current study.

The type I interferon (IFN) pathway is important for eukaryotic cells to resist viral infection, as well as an impediment to efficient virus replication. Therefore, this study aims to create an IFNAR1 knockout (KO) Madin-Darby bovine kidney (MDBK) cell line using CRISPR/Cas9 and investigate its application and potential mechanism in increasing viral replication of bovines. The IFNAR1 KO cells showed increased titers of bovine viral diarrhea virus (BVDV) (1.5 log10), with bovine enterovirus and bovine parainfluenza virus type 3 (0.5–0.8 log10). RNA-seq revealed reduced expression of the genes related IFN-I pathways including IFNAR1, STAT3, IRF9, and SOCS3 in IFNAR1 KO cells compared with WT cells. In WT cells, 306 differentially expressed genes (DEGs) were identified between BVDV-infected and -uninfected cells. Of these, 128 up- and 178 down-regulated genes were mainly associated with growth cycle and biosynthesis, respectively. In IFNAR1 KO cells, 286 DEGs were identified, with 82 up-regulated genes were associated with signaling pathways, and 204 down-regulated genes. Further, 92 DEGs were overlapped between WT and IFNAR1 KO cells including ESM1, IL13RA2, and SLC25A34. Unique DEGs in WT cells were related to inflammation and immune regulation, whereas those unique in IFNAR1 KO cells involved in cell cycle regulation through pathways such as MAPK. Knocking down SLC25A34 and IL13RA2 in IFNAR1 KO cells increased BVDV replication by 0.3 log10 and 0.4 log10, respectively. Additionally, we constructed an IFNAR1/IFNAR2 double-knockout MDBK cell line, which further increased BVDV viral titers compared with IFNAR1 KO cells (0.6 log10). Overall, the IFNAR1 KO MDBK cell line can support better replication of bovine viruses and therefore provides a valuable tool for bovine virus research on viral pathogenesis and host innate immune response.

Abstract Background The increasing prevalence of gestational diabetes mellitus (GDM) is a major challenge, particularly in rural areas of China where control rates are suboptimal. This study aimed to evaluate the effectiveness of a GDM subsidy program in promoting GDM screening and management in these underserved regions. Methods This multicenter, randomized controlled trial (RCT) was conducted in obstetric clinics of six rural hospitals located in three provinces in China. Eligible participants were pregnant women in 24–28 weeks’ gestation, without overt diabetes, with a singleton pregnancy, access to a telephone, and provided informed consent. Participants were randomly assigned in a 1:1 ratio to either the intervention or control groups using an internet-based, computer-generated randomization system. The intervention group received subsidized care for GDM, which included screening, blood glucose retesting, and lifestyle management, with financial assistance provided to health care providers. In contrast, the control group received usual care. The primary outcomes of this study were the combined maternal and neonatal complications associated with GDM, as defined by the occurrence of at least one pre-defined complication in either the mother or newborn. The secondary outcomes included the GDM screening rate, rates of glucose retesting for pregnant women diagnosed with GDM, dietary patterns, physical activity levels, gestational weight gain, and antenatal visit frequency for exploratory purposes. Primary and secondary outcomes were obtained for all participants with and without GDM. Binary outcomes were analyzed by the generalized linear model with a link of logistic, and odds ratios (OR) with 95% confidence intervals (CIs) were reported. Count outcomes were analyzed by Poisson regression, and incidence rate ratios with 95% CIs were reported. Results A total of 3294 pregnant women were randomly assigned to either the intervention group (n = 1649) or the control group (n = 1645) between 15 September 2018 and 30 September 2019. The proportion of pregnant women in the intervention group who suffered from combined maternal and/or neonatal complications was lower than in the control group with adjusted OR = 0.86 (0.80 to 0.94, P = 0.001), and a more significant difference was observed in the GDM subgroup (adjusted OR = 0.66, 95% CI 0.47 to 0.95, P = 0.025). No predefined safety or adverse events of ketosis or ketoacidosis associated with GDM management were detected in this study. Both the intervention and control groups had high GDM screening rates (intervention: 97.2% [1602/1649]; control: 94.5% [1555/1645], P

A virtual battery (VB) provides a succinct interface for aggregating distributed storage-like resources (SLR) to interact with a utility-level system. To overcome the drawbacks of existing VB models, including conservatism and neglecting network constraints, this paper optimizes the power and energy parameters of VB to enlarge its flexibility region. An optimal VB is identified by a robust optimization problem with decision-dependent uncertainty. An algorithm based on the Benders decomposition is developed to solve this problem. The proposed method yields the largest VB satisfying constraints of both network and SLRs. Case studies verify the superiority of the optimal VB in terms of security guarantee and less conservatism.

Market participants can only bid with lagged information disclosure under the existing market mechanism, which can lead to information asymmetry and irrational market behavior, thus influencing market efficiency. To promote rational bidding behavior of market participants and improve market efficiency, a novel electricity market mechanism based on cloudedge collaboration is proposed in this paper. Critical market information, called residual demand curve, is published to market participants in real-time on the cloud side, while participants on the edge side are allowed to adjust their bids according to the information disclosure prior to closure gate. The proposed mechanism can encourage rational bids in an incentive-compatible way through the process of dynamic equilibrium while protecting participants' privacy. This paper further formulates the mathematical model of market equilibrium to simulate the process of each market participant's strategic bidding behavior towards equilibrium. A case study based on the IEEE 30-bus system shows the proposed market mechanism can effectively guide bidding behavior of market participants, while condensing exchanged information and protecting privacy of participants.