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Abstract Background Higher red blood cell distribution width (RDW) levels are associated with mortality in patients with chronic obstructive pulmonary disease (COPD). However, more convincing evidence is still lacking, and the relationship between hemoglobin-to-red blood cell distribution width ratio (HRR) and mortality in patients with COPD remains unclear. Methods This study is a prospective cohort study that includes 3,745 adult patients with COPD from the National Health and Nutrition Examination Survey (NHANES) database spanning from 1999 to 2018 in the United States. COX proportional hazards regression analysis, Kaplan–Meier survival curves and restricted cubic spline models were employed to investigate the association of RDW and HRR levels with mortality. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to evaluate the accuracy of RDW and HRR in predicting mortality in patients with COPD. Results Higher RDW level was positively associated with increased risk of all-cause mortality (HR = 1.16, 95% CI = 1.11–1.21, P

Abstract Previous studies have shown that the heterogeneity of tumor-associated fibroblasts (CAFs) in the tumor microenvironment may play a critical role in tumorigenesis; however, the biological function of CAFs in pancreatic cancer is still controversial. In this study, we found that CD105-positive (CD105+) CAF-derived exosomes significantly promoted the proliferative and invasive metastatic abilities of pancreatic cancer cells. Furthermore, RNA-seq and qRT‒PCR experiments revealed circAMPK1 as a key molecule in exosomes from CD105+ CAFs that mediates the malignant progression of pancreatic cancer. Furthermore, we demonstrated that circAMPK1 encodes a novel protein (AMPK1-360aa) in pancreatic cancer cells. This protein competes with AMPK1 to bind to the ubiquitination ligase NEDD4, which inhibits AMPK1 protein degradation and ubiquitination and thereby increases AMPK1 levels. Finally, we demonstrated that AMPK1-360aa induces cellular autophagy via NEDD4/AMPK1 to promote the proliferation and invasion of pancreatic cancer cells. In summary, circAMPK1 in CD105+ CAF-derived exosomes may mediate pancreatic cancer cell proliferation and invasive metastasis by inducing autophagy in target cells. Moreover, circAMPK1 may competitively bind to ubiquitinating enzymes through the encoded protein AMPK1-360aa, which in turn inhibits the ubiquitination-mediated degradation of AMPK1 and contributes to the upregulation of AMPK1 expression, thus inducing cellular autophagy to mediate the malignant progression of pancreatic cancer.

Abstract Objective Early diagnosis and prediction of organ dysfunction are critical for intervening and improving the outcomes of septic patients. The study aimed to find novel diagnostic and predictive biomarkers of organ dysfunction for perioperative septic patients. Method This is a prospective, controlled, preliminary, and single-center study of emergency surgery patients. Mass spectrometry, Gene Ontology (GO) functional analysis, and the protein-protein interaction (PPI) network were performed to identify the differentially expressed proteins (DEPs) from sepsis patients, which were selected for further verification via enzyme-linked immunosorbent assay (ELISA). Logistic regression analysis was used to estimate the relative correlation of selected serum protein levels and clinical outcomes of septic patients. Calibration curves were plotted to assess the calibration of the models. Results Five randomized serum samples per group were analyzed via mass spectrometry, and 146 DEPs were identified. GO functional analysis and the PPI network were performed to evaluate the molecular mechanisms of the DEPs. Six DEPs were selected for further verification via ELISA. Cathepsin B (CatB), vascular cell adhesion protein 1 (VCAM-1), neutrophil gelatinase-associated lipocalin (NGAL), protein S100-A9, prosaposin, and thrombospondin-1 levels were significantly increased in the patients with sepsis compared with those of the controls (p

Abstract Background Mediation analysis is a powerful tool to identify factors mediating the causal pathway of exposure to health outcomes. Mediation analysis has been extended to study a large number of potential mediators in high-dimensional data settings. The presence of confounding in observational studies is inevitable. Hence, it’s an essential part of high-dimensional mediation analysis (HDMA) to adjust for the potential confounders. Although the propensity score (PS) related method such as propensity score regression adjustment (PSR) and inverse probability weighting (IPW) has been proposed to tackle this problem, the characteristics with extreme propensity score distribution of the PS-based method would result in the biased estimation. Methods In this article, we integrated the overlapping weighting (OW) technique into HDMA workflow and proposed a concise and powerful high-dimensional mediation analysis procedure consisting of OW confounding adjustment, sure independence screening (SIS), de-biased Lasso penalization, and joint-significance testing underlying the mixture null distribution. We compared the proposed method with the existing method consisting of PS-based confounding adjustment, SIS, minimax concave penalty (MCP) variable selection, and classical joint-significance testing. Results Simulation studies demonstrate the proposed procedure has the best performance in mediator selection and estimation. The proposed procedure yielded the highest true positive rate, acceptable false discovery proportion level, and lower mean square error. In the empirical study based on the GSE117859 dataset in the Gene Expression Omnibus database using the proposed method, we found that smoking history may lead to the estimated natural killer (NK) cell level reduction through the mediation effect of some methylation markers, mainly including methylation sites cg13917614 in CNP gene and cg16893868 in LILRA2 gene. Conclusions The proposed method has higher power, sufficient false discovery rate control, and precise mediation effect estimation. Meanwhile, it is feasible to be implemented with the presence of confounders. Hence, our method is worth considering in HDMA studies.

Background Ischemic stroke (IS) accounts large amount of stroke incidence. The aim of this study was to discover the risk and prognostic factors that affecting the occurrence of IS in hypertensive patients. Method Study data were obtained from the Medical Information Mart for Intensive Care (MIMIC)-IV database. To avoid biased factors selection process, several approaches were studied including logistic regression, elastic net regression, random forest, correlation analysis, and multifactor logistic regression methods. And seven different machine-learning methods are used to construct predictive models. The performance of the developed models was evaluated using AUC (Area Under the Curve), prediction accuracy, precision, recall, F1 score, PPV (Positive Predictive Value) and NPV (Negative Predictive Value). Interaction analysis was conducted to explore potential relationships between influential factors. Results The study included 92,514 hypertensive patients, of which 1746 hypertensive patients experienced IS. The Gradient Boosted Decision Tree (GBDT) model outperformed the other prediction model terms of prediction accuracy and AUC values in both ischemic and prognosis cases. By using the SHapley Additive exPlanations (SHAP), we found that a range of factors and corresponding interactions between factors are important risk factors for IS and its prognosis in hypertensive patients. Conclusion The study identified factors that increase the risk of IS and poor prognosis in hypertensive patients, which may provide guidance for clinical diagnosis and treatment.

Abstract Breast cancer (BC) ranks first among female malignant tumors and involves hormonal changes and genetic as well as environmental risk factors. In recent years, with the improvement of medical treatment, a variety of therapeutic approaches for breast cancer have emerged and have strengthened to accommodate molecular diversity. However, the primary way to improve the effective treatment of breast cancer patients is to overcome treatment resistance. Recent studies have provided insights into the mechanisms of resistance to exosome effects in BC. Exosomes are membrane-bound vesicles secreted by both healthy and malignant cells that facilitate intercellular communication. Specifically, exosomes released by tumor cells transport their contents to recipient cells, altering their properties and promoting oncogenic components, ultimately resulting in drug resistance. As important coordinators, non-coding RNAs (ncRNAs) are involved in this process and are aberrantly expressed in various human cancers. Exosome-derived ncRNAs, including microRNAs (miRNAs), long-noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as crucial components in understanding drug resistance in breast cancer. This review provides insights into the mechanism of exosome-derived ncRNAs in breast cancer drug resistance, thereby suggesting new strategies for the treatment of BC.

In this study, six types of commercially available water were selected for preparing cold brew coffee to explore the influence of water quality factors on the main components and sensory flavor of the coffee. High-performance liquid chromatography (HPLC) and headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) were used for analysis of the coffee. Physical and chemical indices, volatile and non-volatile components, and sensory evaluation were analyzed and compared, and correlations and principal component analysis (PCA) were performed. It was found that the different types of water had significantly different compositions of major ions. The contents of total phenol, chlorogenic acid, and caffeic acid, as well as antioxidant activity in the cold brew coffee were not significantly affected by the water ions, but they were significantly affected by the extraction concentration, extraction rate, pH, and titratable acid, caffeine, trigonelline, and furan volatile chemical components. The Ca2+, Mg2+, and HCO3− ions in the water were positively correlated with the extraction concentration, extraction rate, and caffeine and trigonelline concentrations in the cold brew coffee (P

ABSTRACTDeep learning has been extensively utilized in the assessment of building damage after disasters. However, the field of building damage segmentation faces challenges, such as misjudged regions, high network complexity, and long running times. Hence, this paper proposes a two-stage building damage assessment network called the Efficient Channel Attention and Depthwise Separable Convolutional Neural Network (ECADS-CNN). It aims to quickly detect the types of disaster damage in buildings. Deep object segmentation and deep damage classification networks were integrated into a unified building damage detection network. In this study, the efficient channel attention (ECA) module was used to enhance the performance of building semantic segmentation, and a depthwise separable (DS) module was added to the dimension upscaling process. Finally, untrained disaster dataset images were used to test the robustness of the proposed model by comparing the evaluation results of each disaster. The experiments involve testing a total of five common deep learning models, and the results indicate that the ECADS-CNN model improves the speed by 7.4% and the overall F1 score by 5.2% compared with the baseline model. The comprehensive performance is better than that of mainstream deep learning models.

Summary: Scent marking sites served as a primary means of chemical communication for giant pandas, enabling intraspecific communication. We integrated metabolomics and high-throughput sequencing techniques to examine the non-targeted metabolome and microbial community structure of scent marking sites and feces in the field. Integrative analysis revealed a more comprehensive array of chemical compounds compared to previous investigations, including ketones, acids, heterocycles, alcohols, and aldehydes. Notably, specific compounds such as 2-decenal, (E)-, octanal, decanal, L-α-terpineol, vanillin, and nonanal emerged as potential key players in scent signaling. Intriguingly, our study of the microbial domain identified dominant bacterial species from the Actinobacteria, Bacteroidetes, and Proteobacteria phyla, likely orchestrating metabolic processes at scent marking sites. Comparative analyses showed, for the first time, that feces do not share the same functions as scent markers, indicating distinct functional roles. This research deepens scientific understanding of chemical communication in wild pandas.

Composite natural emulsifiers such as whey protein isolate (WPI) and chitosan (CS) are commonly used in Pickering emulsions to address the effect of thermal deformation of proteins before complexation with CS and heating after complexation. In this study, the properties of WPI and CS composites were investigated by complexing CS with either unmodified WPI or thermally denatured WPI (DWPI). Three types of composite particles were prepared, WPI-CS, DWPI-CS, and D(WPI-CS). Atomic force microscopy revealed that the composite particles formed larger aggregates with increased contour size and surface roughness compared to CS and WPI, whereas the interfacial tension decreased, indicating improved emulsifying abilities. Fourier-transform infrared analysis revealed differences in the hydrogen bonds between CS and WPI/DWPI. All three composite particles formed stable emulsions with droplet sizes of 20.00 ± 0.15, 27.80 ± 0.35, and 16.77 ± 0.51 μm, respectively. Thermal stability experiments revealed that the curcumin emulsion stabilized with WPI-CS and DWPI-CS exhibited relatively better thermal stability than that stabilized with D(WPI-CS). In vitro experiments results indicated that the bioaccessibility of the curcumin emulsion stabilized with WPI-CS was 61.18 ± 0.16%, significantly higher than that of the emulsions prepared with the other two composite particles (p < 0.05). This study will enable the customized design of WPI composite-based Pickering emulsions for application in the food and nutrition industries.

Purpose: The objective is to create a comprehensive model that integrates clinical, semantic, and radiomics features to forecast the 5-year progression-free survival (PFS) of individuals diagnosed with non-distant metastatic Nasopharyngeal Carcinoma (NPC). Methods: In a retrospective analysis, we included clinical and MRI data from 313 patients diagnosed with primary NPC. Patient classification into progressive and non-progressive categories relied on the occurrence of recurrence or distant metastasis within a 5-year timeframe. Initial screening comprised clinical features and statistically significant image semantic features. Subsequently, MRI radiomics features were extracted from all patients, and optimal features were selected to formulate the Rad-Score.Combining Rad-Score, image semantic features, and clinical features to establish a combined model Evaluation of predictive efficacy was conducted using ROC curves and nomogram specific to NPC progression. Lastly, employing the optimal ROC cutoff value from the combined model, patients were dichotomized into high-risk and low-risk groups, facilitating a comparison of 10-year overall survival (OS) between the groups. Results: The combined model showcased superior predictive performance for NPC progression, reflected by AUC values of 0.84, an accuracy rate of 81.60%, sensitivity at 0.77, and specificity at 0.81 within the training group. In the test set, the AUC value reached 0.81, with an accuracy of 74.6%, sensitivity at 0.82, and specificity at 0.66. Conclusion: The amalgamation of Rad-Score, clinical, and imaging semantic features from multi-parameter MRI exhibited significant promise in prognosticating 5-year PFS for non-distant metastatic NPC patients. The combined model provided quantifiable data for informed and personalized diagnosis and treatment planning.

This paper proposes an evaluating and mapping methodology of terrain traversability for off-road navigation of autonomous vehicles in unstructured environments. Terrain features are extracted from RGB images and 3D point clouds to create a traversal cost map. The cost map is then employed to plan safe trajectories. Bayesian generalized kernel inference is employed to assess unknown grid attributes due to the sparse raw point cloud data. A Kalman filter also creates density local elevation maps in real time by fusing multiframe information. Consequently, the terrain semantic mapping procedure considers the uncertainty of semantic segmentation and the impact of sensor noise. A Bayesian filter is used to update the surface semantic information in a probabilistic manner. Ultimately, the elevation map is utilized to extract geometric characteristics, which are then integrated with the probabilistic semantic map. This combined map is then used in conjunction with the extended motion primitive planner to plan the most effective trajectory. The experimental results demonstrate that the autonomous vehicles obtain a success rate enhancement ranging from 4.4% to 13.6% and a decrease in trajectory roughness ranging from 5.1% to 35.8% when compared with the most developed outdoor navigation algorithms. Additionally, the autonomous vehicles maintain a terrain surface selection accuracy of over 85% during the navigation process.

Development of environment-friendly and efficient aquaculture effluent treatment system is crucial for sustainable intensification of aquaculture, in the face of the rapidly increasing environmental pressure in the mariculture industry. In this study, mariculture wastewater was treated by the anoxic-anaerobic-oxic biochemical treatment system (A2O system) with traditional activated sludge replaced by nitrifying bacteria, denitrification bacteria and phosphorus accumulating bacteria absorbed on PBS carrier biofilms suitable for saline/brackish water. The results showed that biofilm-enhanced A2O system can effectively remove pollutants from aquaculture wastewater. The removal efficiencies of CODMn, NH4+-N, TN and TP in A2O system were approximately 86.3%-90.8%, 97.7%-99.5%, 94.6%-95.2% and 97.0%-98.1%. The results further showed that CODMn, NH4+-N, and TN were mainly removed in anaerobic tank and anoxic tank, while TP was mainly removed in the anoxic tank and oxic tank. The biofilm-enhanced A2O system by adding nitrifying bacteria and phosphorus accumulating bacteria biofilms using PBS as carriers instead of conventional activated sludge could be applied to the treatment of circulating aquaculture wastewater. This study provides a feasible scheme for enhancing the efficiency of A2O system in the treatment of aquaculture tail water, and provides a reference for the immobilization of microorganisms.

Abstract Introduction Demyelination is a key factor in axonal degeneration and neural loss, leading to disability in multiple sclerosis (MS) patients. Transforming growth factor beta activated kinase 1 (TAK1) is a critical molecule involved in immune and inflammatory signaling pathways. Knockout of microglia TAK1 can inhibit autoimmune inflammation of the brain and spinal cord and improve the outcome of MS. However, it is unclear whether inhibiting TAK1 can alleviate demyelination. Methods Eight‐week‐old male c57bl/6j mice were randomly divided into five groups: (a) the control group, (b) the group treated with cuprizone (CPZ) only, (c) the group treated with 5Z‐7‐Oxozaenol (OZ) only, and (d) the group treated with both cuprizone and 15 μg/30 μg OZ. Demyelination in the mice of this study was induced by administration of CPZ (ig) at a daily dose of 400 mg/kg for consecutive 5 weeks. OZ was intraperitoneally administered at mentioned doses twice a week, starting from week 3 after beginning cuprizone treatment. Histology, rotarod test, grasping test, pole test, Western blot, RT‐PCR, and ELISA were used to evaluate corpus callosum demyelination, behavioral impairment, oligodendrocyte differentiation, TAK1 signaling pathway expression, microglia, and related cytokines. Results Our results demonstrated that OZ protected against myelin loss and behavior impairment caused by CPZ. Additionally, OZ rescued the loss of oligodendrocytes in CPZ‐induced mice. OZ inhibited the activation of JNK, p65, and p38 pathways, transformed M1 polarized microglia into M2 phenotype, and increased brain‐derived neurotrophic factor (BDNF) expression to attenuate demyelination in CPZ‐treated mice. Furthermore, OZ reduced the expression of proinflammatory cytokines and increases anti‐inflammatory cytokines in CPZ‐treated mice. Conclusion These findings suggest that inhibiting TAK1 may be an effective approach for treating demyelinating diseases.

Cell metabolite adenosine can induce extensive and persistent immunosuppression by binding to adenosine receptors on immune cells. Seriously, the hypoxia‐driven adenosinergic axis aggravates adenosine accumulation via dephosphorizing immune‐activating adenosine triphosphate (ATP) released during immunogenic cell death (ICD). Different from direct adenosine clearance or adenosine receptor blockade or directly using ecto‐enzyme (CD39/CD73) antagonist, it is hoped to use an innovative small science engineering to regulate the upstream hypoxia/HIF‐1α signal of the hypoxia‐adenosinergic axis, thereby reducing the immunosuppressive extracellular adenosine and enhancing ICD‐triggered antitumor immunity. PM@Mn is constructed by gradually integrating metformin and MnO2 on polydopamine (PDA) nanoparticles. PM@Mn can effectively suppress hypoxia‐adenosinergic axis via combining catalytic oxygen production with reduced endogenous oxygen consumption. Such motif of hypoxia relief suppresses the metabolism of ATP to adenosine via down‐regulating the expression of HIF‐1α, CD39, and CD73. Meanwhile, PDA in PM@Mn can induce local tumor ablation and trigger the “vaccine effect” of ICD under near‐infrared radiation. In a mouse breast cancer model with low immunogenicity, our strategy can effectively reduce adenosine accumulation, PM@Mn group exhibits 4.51‐fold cytotoxic T lymphocyte infiltration and tumor inhibition rate of 75.4%. This study provides a new strategy to advance ICD‐triggered antitumor immunity through supressing hypoxia‐adenosinergic axis.

ABSTRACT: The present study investigated the effects of replacing part of the basal diet with 2-stage fermented feed (FF) (soybean hulls:rapeseed cake (2:1, m/m)) on the growth performance, immunity, antioxidant capacity, and intestinal health of Chahua chicken. A total of 160 Chahua chickens were randomly divided into 4 groups to receive a control diet or diet with 5%, 10%, or 15% of the basal diet replaced by FF, respectively for 56 d. The results showed that FF significantly improved the average daily gain (ADG) and average daily feed intake (ADFI) of Chahua chickens (P < 0.05). Furthermore, the serum immunoglobulin (Ig) A, glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) in Chahua chicken receiving the diet added with 15% FF significantly increased (P < 0.05). Chahua chicken in both the 10% and 15% groups showed increased serum IgG and IgM and decreased malondialdehyde. Serum interleukin-2 and interferon-gamma significantly increased in all FF groups. Compared with the CON group, higher ileal villus height (VH) was found in the 10% FF group. Treatment with FF significantly increased the ileal villus height/crypt depth (VH/CD) ratio, jejunal VH, and jejunal VH/CD ratio while reducing ileal and jejunal CD. The modified gut microbiota composition was observed in the Chahua chicken fed a diet containing FF, in particular, with the increased abundance of Faecalibacterium and Lactobacillus. The abundance of Lactobacillus significantly increased in the 10% and 15% FF groups (all P < 0.05). Correlation analysis revealed a positive correlation between Lactobacillus and VH (R = 0.38, P = 0.10, Figure 3B), AH/CD ratio (R = 0.63, P = 0.003), and a negative correlation with CD (R = −0.72, P = 0.001). These results indicate that FF improves immunity, antioxidant capacity, and intestinal health and consequently enhances growth performance in Chahua chicken.

Abstract Background l-ascorbic acid (Asc) plays a pivotal role in regulating various biological processes, including somatic cell reprogramming, through multiple pathways. However, it remains unclear whether Asc regulates reprogramming directly or functions through its metabolites. Results Asc exhibited dual capabilities in promoting reprogramming through both 2,3-diketo-l-gulonic acid (DKG), a key metabolite during Asc degradation, dependent and independent routes. On the one hand, Asc facilitated reprogramming by promoting cell proliferation and inducing the conversion from pre-induced pluripotent stem cells (pre-iPSCs) to iPSCs through DKG-independent pathways. Additionally, Asc triggered mesenchymal-epithelial transition (MET) and activated glycolysis via DKG-dependent mechanisms. Notably, DKG alone activated a non-canonical tricarboxylic acid cycle characterized by increased succinate, fumarate, and malate. Consequently, this shift redirected oxidative phosphorylation toward glycolysis and induced MET. Moreover, owing to its antioxidant capabilities, Asc directly inhibited glycolysis, thereby preventing positive feedback between glycolysis and epithelial-mesenchymal transition, ultimately resulting in a higher level of MET. Conclusion These findings unveil the intricate functions of Asc in the context of reprogramming. This study sheds light on the DKG-dependent and -independent activities of Asc during reprogramming, offering novel insights that may extend the application of Asc to other biological processes.

Abstract Pancreatic cancer (PC), a gastrointestinal tract malignant tumor, has a poor prognosis due to early metastasis and limited response to chemotherapy. Therefore, identifying novel therapeutic approaches for PC is critical. Epithelial–mesenchymal transition (EMT) is known as the vital progress in PC development, we constructed the EMT-related prognosis model to screen out that FOXQ1 probably involving in the EMT regulation. FOXQ1 has been linked to the malignant process in a number of cancers. However, its function in PC is unknown. In our work, the expression of FOXQ1 was elevated in PC tissues, and a high level of FOXQ1 in PC was linked to patients’ poor prognosis. FOXQ1 overexpression promoted aerobic glycolysis and enhanced PC cell proliferation, tumor stemness, invasion, and metastasis. Whereas, FOXQ1 silencing showed the reverse effect. Furthermore, mechanistic studies indicated that FOXQ1 promotes LDHA transcription, and thus modulates aerobic glycolysis to enhance PC cell proliferation, tumor stemness, invasion, and metastasis by increasing LDHA expression. Therefore, these novel data suggest that FOXQ1 may be a possible therapeutic target in PC.

Hydrogen, as a renewable and clean energy carrier, has the potential to play an important role in carbon reduction. Crucial to achieving this is the ability to produce clean sources of hydrogen and to store hydrogen safely. With the rapid development of the hydrogen industry, the number of hydrogen refueling stations (HRS) is increasing. However, hydrogen safety at HRS is of great concern due to the high risk of hydrogen leakage during storage. This study focused on an integrated hydrogen production and refueling station (IHPRS) in Weifang, China, and numerically simulated a hydrogen leakage accident in its storage area. The effects of the leakage aperture, the leakage direction and the ambient wind direction and speed on the leakage and dissipation characteristics of hydrogen were investigated. The results showed that the volume, mass and dissipation time of the flammable hydrogen cloud (FHC) increased with an increase in the leakage aperture. The installation of a canopy or densely packed equipment near the hydrogen storage area will seriously hinder the dissipation of the FHC. Ambient winds in the opposite direction of the leakage may cause high-concentration hydrogen to accumulate near the hydrogen storage tanks and be difficult to dissipate, seriously threatening the safety of the integrated station.

With the rapid development of hydrogen energy worldwide, the number of hydrogen energy facilities, such as hydrogen refueling stations, has grown rapidly in recent years. However, hydrogen is prone to leakage accidents during use, which could lead to hazards such as fires and explosions. Therefore, research on the safety of hydrogen energy facilities is crucial. In this paper, a study of high-pressure hydrogen jet flame accidents is conducted for a proposed integrated hydrogen production and refueling station in China. The effects of leakage direction and leakage port diameter on the jet flame characteristics are analyzed, and a risk assessment of the flame accident is conducted. The results showed that the death range perpendicular to the flame direction increased from 2.23 m to 5.5 m when the diameter of the leakage port increased from 4 mm to 10 mm. When the diameter of the leakage port is larger than 8 mm, the equipment on the scene will be within the boundaries of the damage. The consequences of fire can be effectively mitigated by a reasonable firewall setup to ensure the overall safety of the integrated station.

Liquid hydrogen storage is an important way of hydrogen storage and transportation, which greatly improves the storage and transportation efficiency due to the high energy density but at the same time brings new safety hazards. In this study, the liquid hydrogen leakage in the storage area of a hydrogen production station is numerically simulated. The effects of ambient wind direction, wind speed, leakage mass flow rate, and the mass fraction of gas phase at the leakage port on the diffusion behavior of the liquid hydrogen leakage were investigated. The results show that the ambient wind direction directly determines the direction of liquid hydrogen leakage diffusion. The wind speed significantly affects the diffusion distance. When the wind speed is 6 m/s, the diffusion distance of the flammable hydrogen cloud reaches 40.08 m, which is 2.63 times that under windless conditions. The liquid hydrogen leakage mass flow rate and the mass fraction of the gas phase have a greater effect on the volume of the flammable hydrogen cloud. As the leakage mass flow rate increased from 5.15 kg/s to 10 kg/s, the flammable hydrogen cloud volume increased from 5734.31 m3 to 10,305.5 m3. The installation of a barrier wall in front of the leakage port can limit the horizontal diffusion of the flammable hydrogen cloud, elevate the diffusion height, and effectively reduce the volume of the flammable hydrogen cloud. This study can provide theoretical support for the construction and operation of hydrogen production stations.

Abstract Background Protein arginine methyltransferase 5 (Prmt5) is the main type II methyltransferase, catalyzes protein arginine residue symmetric dimethylation, and modulates normal cellular physiology and disease progression. Prmt5 inhibition or deletion in CD4+ T cells has been reported to ameliorate experimental autoimmune encephalomyelitis (EAE), but the detailed molecular mechanisms have not yet been elucidated. Methods EAE was induced by administration of myelin oligodendrocyte glycoprotein (MOG35–55) in T cells Prmt5 conditional knockout (CD4-cre-Prmt5fl/fl, Prmt5cko) and Prmt5fl/fl (WT) mice. Flow cytometry, single-cell RNA sequencing, ATAC sequencing and chromatin immunoprecipitation assay (ChIP) approaches were used to explore the detail mechanisms. Results We find that Prmt5cko mice are resistant to EAE; infiltrating inflammatory CD4+ T cells in the central nervous system (CNS) are greatly reduced. However, in Prmt5cko mice, T cells in the spleen show much more proliferation and activation properties, the total number of CD4+ T cells in the spleen is not reduced, and the percentage of Rora+ CD4+ T cells is elevated. Also, CD4+ T cells express lower levels of S1pr1 and Klf2 than WT mice, which may influence pathogenic CD4+ T-cell egress from the spleen and migration to the CNS. Moreover, the single-cell ATAC sequence and ChIP assay reveal that the transcription factor Klf2 is enriched at the S1pr1 promoter and that Klf2 motif activity is reduced in Prmt5cko mice. Conclusions Our study delineates the undiscovered role of Prmt5 in T-cell biology in which Prmt5 may inhibit Klf2-S1pr1 pathway to ameliorate EAE disease. Controlling T-cell Prmt5 expression may be helpful for the treatment of autoimmune diseases.

Abstract The ketogenic diet (KD) is a low carbohydrate and high-fat protein diet. It plays a protective role in neurodegenerative diseases by elevating the levels of ketone bodies in blood, regulating central and peripheral metabolism and mitochondrial functions, inhibiting neuroinflammation and oxidative stress, and altering the gut microbiota. However, studies on ketogenic therapy for Parkinson’s disease (PD) are still in their infancy. Therefore, we examined the possible protective effect of KD in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model, examined the mouse gut microbiota and its metabolites, and performed transcriptomics and metabolomics on the substantia nigra of mice. Our results showed that a long-term medium-chain triglyceride KD (MCT-KD) significantly reduced MPTP-induced damage to dopaminergic (DA) neurons, exerted antioxidant stress through the PI3K/Akt/Nrf2 pathway, and reversed oxidative stress in DA neurons. The MCT-KD also reduced mitochondrial loss, promoted ATP production, and inhibited the activation of microglia to protect DA neurons in MPTP-induced PD mice. MCT-KD altered the gut microbiota and consequently changed the metabolism of substantia nigra neurons through gut microbiota metabolites. Compared to the MPTP group, MCT-KD increased the abundance of gut microbiota, including Blautia and Romboutsia. MCT-KD also affects purine metabolism in the substantia nigra pars compacta (SNpc) by altering fecal metabolites. This study shows that MCT-KD has multiple protective effects against PD.

Abstract Increasing evidence indicates that long non-coding RNA (lncRNA) is one of the most important RNA regulators in the pathogenesis of neuroblastoma (NB). Here, we found that FAM201A was low expressed in NB and a variety of gain and loss of function studies elucidated the anti-tumor effects of FAM201A on the regulation of proliferation, migration and invasion of NB cells. Intriguingly, we identified the ability of FAM201A to encode the tumor-suppressing protein, NBASP, which interacted with FABP5 and negatively regulated its expression. In vivo assays also revealed NBASP repressed NB growth via inactivating MAPK pathway mediated by FABP5. In conclusion, our findings demonstrated that NBASP encoded by FAM201A played a tumor-suppressor role in NB carcinogenesis via down-regulating FABP5 to inactivate the MAPK pathway. These results extended our understanding of the relationship of lncRNA-encoded functional peptides and plasticity of tumor progression.

The ability of a robot to navigate through a dynamic environment, avoid obstacles, and reach its destination is crucial for safety and a major technological challenge in autonomous navigation, especially in crowded environments involving hospitals, hotels, and restaurants. Most prominent methods use distance metrics as a safety constraints in their planning algorithms, which leads to overly cautious navigation. Thus, a velocity obstacle guided motion planning method for mobile robots in moving obstacle environments is proposed. The approach automatically negotiates dynamic obstacles combining velocity obstacle (VO) and trajectory generating. First, a dynamic perception algorithm is developed to track and predict obstacles using only point cloud input. Subsequently, to obtain an initial trajectory that satisfies kinodynamic and the VO-based safety metric (VOSM), VO is applied to search the kinodynamic path to verify the safety of the extended motion primitives. Finally, the smoothness and safety of the robot trajectory are enhanced by nonlinear optimization, which incorporates the proposed safety constraints based on VO. Extensive simulations in challenging environments demonstrate a 40.0% success rate increase and a 44.8% trajectory smoothness improvement over obstacle distance-based methods. Practical testing prove our technology is reliable and can safely avoid dynamic obstacles.

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3′-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

Abstract Background The mutual compensatory relationship between the upper cervical sagittal alignment and the lower cervical sagittal alignment has been repeatedly reported. However, the evaluation of the upper cervical sagittal parameters are varied in previous studies. This retrospective study was performed to compare three methods for measuring the upper cervical sagittal parameters. Methods A total of 263 individuals with standing neutral lateral cervical radiographs were included in this study. The Frankfort horizontal line (FHL), foramen magnum line (FML), and McGregor line (ML) were separately used as the reference lines for measuring the C0-1 angle and C0-2 angle. Intraclass correlation (ICC) values were used to compare the consistency and repeatability of the three methods. Pearson’s correlation analysis was used to analyze the correlation between the sagittal parameters of the upper and lower cervical spine. Results The interobserver and intraobserver ICC values obtained from using the ML to measure the C0-1 angle and C0-2 angle were both higher than those obtained from using the FML or FHL. The C0-1 angle and C0-2 angle measured by the three methods were negatively correlated with the C2-7 angle. The upper sagittal parameters measured by the FHL were the most correlated with the C2-7 angle. The correlation between the C0-1 angle measured by the three methods and the C0-2 angle measured with the FHL or ML and the C2-7 angle increased with aging. Conclusion Use of the ML to measure the C0-1 angle and C0-2 angle has higher reliability. Use of the FHL to measure the sagittal alignment of the upper cervical spine is more suitable for evaluating the compensation mechanism between the upper and the lower cervical spine.

Atrazine residues can pose serious threats to soil ecology and human health. Currently, the underlying relationship between soil microbial communities and the degradation genes associated with atrazine degradation remains unclear. In this study, the degradation characteristics of atrazine was investigated in ten different soil types. Further, diversity and abundance of degradation genes and succession of the bacterial community were also studied. The degradation of 10 mg/kg atrazine in different soil types exhibited an initial rapid trend followed by a gradual slowdown, adhering to the first-order kinetic equation. Atrazine significantly increased the absolute abundance of atz degradation genes. The increase in the absolute abundance of atzC gene was the largest, whereas that of atzA gene was the smallest, and the trzD gene was only detected in the Binzhou loam soil. Co-occurrence network analysis showed that the number of potential bacterial hosts of atzC was the highest compared with the other atz genes. Atrazine also altered the structural composition of the soil microbial community. The relative abundances of Ochrobactrum, Nocardiopsis, Lactobacillus, and Brevibacterium was increased in the atrazine-treated soils, while those of Conexibate, Solirubacter, and Micromonospora was decreased significantly compared with the control. Additionally, four atrazine-degrading bacterial strains Rhizobium AT1, Stenotrophomonas AT2, Brevibacterium AT3, and Bacillus AT4 were isolated from the atrazine-treated soils. After 14 d for inoculation, their degradation rate for 10 mg/L atrazine ranged from 17.56 % to 30.55 %. Moreover, the relative abundances of the bacterial genera, including these four isolates, in the atrazine-treated soil were significantly higher than those in the control, indicating that they were involved in the synergistic degradation of atrazine in the soil. This study revealed the degradation characteristics of atrazine, distribution of degradation genes, and succession of microbial communities, and explored the internal relationship between microbial community structure and atrazine degradation mechanisms in different soil types.

On the basis of the conjugate gradient method, an inversion model of the transient convective heat transfer coefficient between the bore surface and the gunpowder gas is presented. In this study, the measured temperature at a certain depth from the bore surface is employed as input. The variation of the thermophysical properties of gun steel with respect to temperature is taken into consideration. After verifying the feasibility of the model with constant convective heat transfer coefficients, it is applied to the reconstruction of transient convective heat transfer coefficients that consistent with the classical interior ballistic laws. Results indicate that decreasing the measurement error and increasing the number of measurement points can effectively improve the performance of the model. As well, measurement points that placed further away from the inlet boundary offer superior accuracy. When studying the inverse heat transfer problem of the gun barrel, it is found that setting the monitoring time to be twice the duration of the interior ballistic period may guarantee sufficient input data. The inversion model may offer a promising theoretical framework for indirect measurement manner of the bore surface temperature of gun barrel.

Dissolved organic matter (DOM) in seawater, consisted of a complex mixture of compounds and accounted for about 90% of marine organic carbon, is an important part of the global carbon cycle and also a part of absolute salinity of seawater. As the components of DOM are non-ionized in seawater, electric conductivity measurement cannot observe its contribution to salinity, which could lead to measurement error in salinity. Salinity measurement based on optic refractive index could reveal contribution of all dissolved matters in seawater including both non-ionized and ionized components. In this paper, a comparative study of DOM contribution to the salinity measurement by optic refractive index method and electric conductivity method was carried out for the first time. Adding DOM, extracted from Aoshan Bay, Qingdao, China, into Chinese Standard Seawater, our experimental results showed an increase of optic refractive index at 1.19×10-4 ± 4×10-6 per 1g/kg of DOM, which corresponds to a practical salinity increase of 0.697 ± 0.036 PSU per 1 g/kg of DOM. While, the conductivity of seawater measured by a conductivity-temperature sensor showed a decrease of 0.00065 ± 0.00008 mS/cm per 1 g/kg of DOM, which corresponded to a decrease of salinity at 0.00052 ± 0.00007 PSU per 1 g/kg of DOM. By comparing the optic and electric measurement results, the contribution of non-conductive components in the dissolved organic matters to salinity could be distinguished, which has great significance for the measurement of absolute salinity, global carbon cycle etc.

A 2-D inversion model to reconstruct the transient inner wall heat flux of the coated barrel is proposed in this paper. Indirect measurement of the inner wall temperature of the barrel under harsh conditions is realized. Measurement points locate at specified distances from the inner surface. Temperature calculated from a direct problem plus the measurement errors is taken as measured temperature. Variations of the temperature dependent thermo-physical properties of materials are taken into consideration. The total heat input of the firing and thermal resistance between chromium coating and gun steel are determined by depths of gun steel phase transition and chromium recrystallization after firing. The direct problem, sensitivity problem and adjoint problem are solved with the finite difference method (FDM). After verifying the reliability of the inversion model with a special numerical example, it is promoted to reconstruction of general heat flux varying with time and space. Results indicate that decreasing the measurement error and increasing the number of measurement points can effectively improve the performance of the model. As well, measurement points closer to the inner wall offer superior accuracy. The inversion model herein can serve as a promising indirect measurement method of the inner wall temperature.

Due to the inherent limitations of matching algorithms and the complexities associated with image contents, mismatches are inevitable and can have detrimental effects on downstream tasks in computer vision and remote sensing. Researchers have published numerous reviews on mismatch removal, which may suffer from two primary deficiencies. Firstly, these reviews are often embedded within studies that primarily focus on image matching, thereby limiting the detailed and comprehensive analysis of mismatch removal methods. Secondly, reviews of deep learning (DL)-based methods, despite their numerous existence and interconnection, tend to be fragmentary and lack a systematic approach. To address these two shortcomings, this paper presents a comprehensive survey of DL-based mismatch removal principles and methods. We provide a summary of network architectures, techniques for extracting geometrical information, and various training modes. Specifically, we highlight the importance of permutation invariance in mining operations, enumerate a majority of existing mining methods, and provide an explanation of their permutation invariant properties. Furthermore, we present both the intuitive motivation and mathematical analysis of commonly used methods, elucidating their underlying principles and efficacy. In the conclusion, we predict upcoming trends based on the findings of our review, aiming to provide valuable insights into mismatch removal techniques and guide their practical applications.

Most learning-based methods require labelling the training data, which is time-consuming and gives rise to wrong labels. To address the labelling issues thoroughly, we propose an unsupervised learning framework to remove mismatches by maximizing the expected score of sample consensuses (MESAC). The proposed MESAC can train various permutation invariant networks (PINs) based on training data with no labels, and has three distinct merits: 1) the framework can train various PINs in an unsupervised mode such that these are immune to wrong labels; 2) the gradients of the expected score are explicitly calculated by a revised score-function estimator, which can avoid gradient explosion; 3) the distribution of matching probabilities is learned from the PIN and precisely modelled by a categorical distribution, which can decrease the sampling times and improve the computational efficiency accordingly. Experiments of testing datasets disclose that mean recall is increased by at most 77% when pure PINs are embedded in MESAC, and mean precision is also improved by 16%. Applications in pose recovery indicate that the success rates of MESAC-integrated PINs outperform the compared methods when training with neither matching labels nor ground truth epipolar geometry (EG) constraints, showing the great potential of MESAC in mismatch removal.

Aconitine, a common and main toxic component of Aconitum, is toxic to the central nervous system. However, the mechanism of aconitine neurotoxicity is not yet clear. In this work, we had the hypothesis that excitatory amino acids can trigger excitotoxicity as a pointcut to explore the mechanism of neurotoxicity induced by aconitine. HT22 cells were simulated by aconitine and the changes of target cell metabolites were real-time online investigated based on a microfluidic chip-mass spectrometry system. Meanwhile, to confirm the metabolic mechanism of aconitine toxicity on HT22 cells, the levels of lactate dehydrogenase, intracellular Ca2+, reactive oxygen species, glutathione and superoxide dismutase, and ratio of Bax/Bcl-2 protein were detected by molecular biotechnology. Integration of the detected results revealed that neurotoxicity induced by aconitine was associated with the process of excitotoxicity caused by glutamic acid and aspartic acid, which was followed by the accumulation of lactic acid and reduction of glucose. The surge of extracellular glutamic acid could further lead to a series of cascade reactions including intracellular Ca2+ overload and oxidative stress, and eventually result in cell apoptosis. In general, we illustrated a new mechanism of aconitine neurotoxicity and presented a novel analysis strategy that real-time online monitoring of cell metabolites can provide a new approach to mechanism analysis.

Abstract Background Amorpha-4,11-diene synthase (ADS) is a key enzyme in the artemisinin biosynthetic pathway. ADS promotes the first step of artemisinin synthesis by cyclizing faresyl pyrophosphate to synthesize the sesquiterpene product amorpha-4,11-diene. Thanks to the continuous improvement of genomic information, its evolutionary trace can be analyzed in a genome view. Methods Phylogenetic analysis was used to identify ADS-like genes in other Asteraceae. Gene structure and motif analysis was used to analyze the structural similarity of these identified genes. Heterologous expression and GC–MS analysis were performed to determine whether the functions of ADS and Cna4666 are consistent. Validation of ADS genes evolutionary trajectories was achieved by selective pressure and synteny analysis. Result In this study, we extracted 8 ADS genes from the Artemisia annua L. genome annotation and 121 ADS similar genes from the genomes of Artemisia annua L. and other plants in the Asteraceae, and further exploring their evolutionary relationship. Phylogenetic analysis showed that the genes most closely related to ADS genes were found in the genome of Chrysanthemum nankingense. Among them, the gene structure and motif composition of Cna4666 is very similar to ADS, we wondered whether it has the potential to synthesize amorpha-4,11-diene. Therefore, we extracted the products of recombinant p0_ADS.1 and Cna4666 proteins by HS-SPME combined with GC–MS analysis, the results indicate that Cna4666 is an α-bisabolol synthase, which cannot synthesize amorpha-4,11-diene. Through synteny analysis, we did not find collinear blocks of ADS genes in the Helianthus annuus and C. nankingense genomes. Furthermore, Ka/Ks ratios indicated that the evolution of ADS genes from their similar genes principally underwent purifying selection, and there was a strong positive selection between ADS genes. Conclusions This study proved that ADS is a multi-copy gene in Artemisia annua L., and they are not widely distributed in Asteraceae. The data will increase our understanding of the evolutionary selection pressure on ADS genes. The results suggest that ADS genes are subject to strong positive selection internally, and it is possible that they are a recently evolved gene in the Artemisia.

Abstract Pancreatic cancer (PC) is one of the most malignant types of cancer, and is characterized by early metastasis, limited response to chemotherapeutics, and poor prognosis. Therefore, there is an urgent need to explore new therapeutic strategies for PC treatment. Human rhomboid-like 2 (RHBDL2) is differentially expressed in cervical and breast cancer. However, the correlation between RHBDL2 and PC remains unclear. We found that RHBDL2 is highly expressed in human PC cells and tissues and is significantly associated with distant metastasis and poor survival of patients with PC. Gain- and loss-of-function assays indicated that RHBDL2 could accelerate PC cell proliferation and mobility in vitro and in vivo. The RNA-Seq results suggest that RHBDL2 may be involved in the activation of Notch signaling pathway. IMR-1 could restore the proliferation and metastatic capacity of PC cells mediated by RHBDL2. RHBDL2 interacted with and cleaved Notch1, resulting in the release of N1ICD. RHBDL2 decreased the ubiquitination level of N1ICD and collaborated with Ovarian tumor domain-containing 7B (OTUD7B) to stabilize N1ICD via the ubiquitin-proteasome pathway. RHBDL2 facilitated PC cell proliferation and mobility by stabilizing the N1ICD via the OTUD7B and activating the Notch signaling pathway. Thus, targeting this novel pathway may be a potential therapeutic strategy for PC.

Abstract Although FOXD1 has been found to be involved in the malignant processes of several types of cancers, its role in pancreatic cancer (PC) is not well understood. This study aimed to investigate the expression and function of FOXD1 in PC. We found that FOXD1 mRNA and protein expression were upregulated in PC tissues compared with non-tumor tissues, and high expression level of FOXD1 was associated with an adverse prognostic index of PC. The results of in vitro and in vivo assays indicate that overexpression of FOXD1 promotes aerobic glycolysis and the capacity of PC cells to proliferate, invade, and metastasize, whereas FOXD1 knockdown inhibits these functions. The results of mechanistic experiments suggest that FOXD1 can not only directly promote SLC2A1 transcription but also inhibit the degradation of SLC2A1 through the RNA-induced silencing complex. As a result, FOXD1 enhances GLUT1 expression and ultimately facilitates PC cell proliferation, invasion, and metastasis by regulating aerobic glycolysis. Taken together, FOXD1 is suggested to be a potential therapeutic target for PC.

BackgroundDespite the high prevalence of major depressive disorder and the related societal burden, access to effective traditional face-to-face or video-based psychotherapy is a challenge. An alternative that offers mental health care in a flexible setting is asynchronous messaging therapy. To date, no study has evaluated its efficacy and acceptability in a randomized controlled trial for depression. ObjectiveThe aim of this study was to compare the efficacy and acceptability of message-based psychotherapy for depression to once-weekly video-based psychotherapy. MethodsIn this 2-armed randomized controlled trial, individuals (N=83) with depressive symptomatology (Patient Health Questionnaire-9 ≥10) were recruited on the internet and randomly assigned to either a message-based intervention group (n=46) or a once-weekly video-based intervention group (n=37). Patients in the message-based treatment condition exchanged asynchronous messages with their therapist following an agreed-upon schedule. Patients in the video-based treatment condition met with their therapist once each week for a 45-minute video teletherapy session. Self-report data for depression, anxiety, and functional impairment were collected at pretreatment, weekly during treatment, at posttreatment, and at a 6-month follow-up. Self-reported treatment expectancy and credibility for the assigned intervention were assessed at pretreatment and therapeutic alliance at posttreatment. ResultsFindings from multilevel modeling indicated significant, medium-to-large improvements in depression (d=1.04; 95% CI 0.60-1.46), anxiety (d=0.61; 95% CI 0.22-0.99), and functional impairment (d=0.66; 95% CI 0.27-1.05) for patients in the message-based treatment condition. Changes in depression (d=0.11; 95% CI –0.43 to 0.66), anxiety (d=–0.01; 95% CI –0.56 to 0.53), and functional impairment (d=0.25; 95% CI –0.30 to 0.80) in the message-based treatment condition were noninferior to those in the video-based treatment condition. There were no significant differences in treatment credibility (d=–0.09; 95% CI –0.64 to 0.45), therapeutic alliance (d=–0.15; 95% CI –0.75 to 0.44), or engagement (d=0.24; 95% CI –0.20 to 0.67) between the 2 treatment conditions. ConclusionsMessage-based psychotherapy could present an effective and accessible alternative treatment modality for patients who might not be able to engage in traditional scheduled services such as face-to-face or video-based psychotherapy. Trial RegistrationClinicalTrials.gov NCT05467787; https://www.clinicaltrials.gov/ct2/show/NCT05467787

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

Background: The ‘obesity paradox’ in elderly patients suffering from percutaneous coronary intervention (PCI) remains a source of controversy. The present meta-analysis focused on exploring the real existence of ‘obesity paradox’ in these patients. Methods: As of November 2022, PubMed, Cochrane and Embase databases were comprehensively searched to identify articles reporting all-cause mortality according to diverse body mass index (BMI) categories after PCI among the old cases developing coronary artery disease (CAD). Summary estimates of risk ratios (RRs) were assigned four BMI groups, including underweight, normal weight, overweight, and obesity groups. Results: There were altogether nine articles involving 25,798 cases selected for further analysis. Relative to normal weight group, overweight and obesity groups had decreased all-cause mortality (RR 0.86, 95%CI 0.77-0.95 for overweight group; RR 0.57,95%CI 0.40-0.80 for obesity group), while underweight group had elevated all-cause mortality (RR 1.52, 95%CI 1.01-2.29). Conclusions: Our study revealed an ‘obesity paradox’ relation of BMI with all-cause mortality in elderly cases receiving PCI. In comparison with normal weight group, overweight and obesity groups had decreased all-cause mortality, while underweight group had increased all-cause mortality.

Nonlinear electric conductance of reinforced insulation can homogenize electric field distribution and suppress local electric field distortion inside high-voltage direct current cable accessories. To achieve a significant nonlinear electric conductance in ethylene–propylene–diene misch–polymere (EPDM) used for reinforced insulation of cable accessories, the inorganic micron crystal powder of calcium copper titanate (CCTO) is synthesized by the sol–gel method, which is filled into EPDM to prepare 5∼15 wt% CCTO/EPDM composites by melting blend and hot-press molding methods. Microscopic structure, electric conductivity, direct current (DC) dielectric breakdown strength, and charge trap characteristics of CCTO/EPDM composites are tested to reveal the underlying derivation of electric conduction nonlinearity. Scanning electron microscopy and X-ray diffraction (XRD) demonstrate that CCTO micron fillers are uniformly dispersed in the EPDM matrix. Dielectric breakdown strength of CCTO/EPDM composites gradually decreases with the increase in CCTO content while persisting qualified for electrical insulation of DC cable accessories. CCTO crystal macron fillers introduce shallower charge traps than the intrinsic charge traps derived from the structural defect EPDM matrix, which initiates the percolating conductive channels between charge traps under high electric fields, accounting for the significant nonlinearity in the profile of electric current density versus electric field strength. Finite-element simulations and analyses on the electrostatic field in DC cable terminals prove that employing 15 wt% CCTO/EPDM composite as reinforced insulation can efficiently homogenize the electric field at the interface between the main insulation and accessory insulation of power cables, which is of great interest to develop insulation materials used for DC cable accessories in severe environments.

IntroductionIn children, erythromelalgia is a rare chronic pain syndrome characterized by erythema, severe burning pain, and itching of affected feet. Unfortunately, there is no definitive therapy available currently.Case reportHere, we report a case of primary erythromelalgia and the treatment response in a 10-year-old boy, whose genetic findings for mutations in the SCN9A gene were positive and skin biopsy results were diagnosed as small fiber neuropathy, while he has suffered from excruciating burning pain, itching, erythema, and recurrent infections over the past 3 years. He did not respond well to conventional treatment, and the only way to receive minimal relief was to immerse his feet in ice water. After a successful trial of spinal cord stimulation (SCS), the implantable pulse generator (IPG) was successfully implanted without complications, and it proved partial response to therapy.ConclusionThere is no specific, efficient treatment for pediatric erythromelalgia currently, but this case demonstrates neuromodulation serves as part of the multimodal regimen to treat pediatric erythromelalgia.

Introduction: The majority of peppers in the US for fresh market and processing are handpicked, and harvesting can account for 20–50% of production costs. Innovation in mechanical harvesting would increase availability; lower the costs of local, healthy vegetable products; and perhaps improve food safety and expand markets. Most processed peppers require removal of pedicels (stem and calyx) from the fruit, but lack of an efficient mechanical process for this operation has hindered adoption of mechanical harvest. In this paper, we present characterization and advancements in breeding green chile peppers for mechanical harvesting. Specifically, we describe inheritance and expression of an easy-destemming trait derived from the landrace UCD-14 that facilitates machine harvest of green chiles.Methods: A torque gauge was used for measuring bending forces similar to those of a harvester and applied to two biparental populations segregating for destemming force and rate. Genotyping by sequencing was used to generate genetic maps for quantitative trait locus (QTL) analyses.Results: A major destemming QTL was found on chromosome 10 across populations and environments. Eight additional population and/or environment-specific QTL were also identified. Chromosome 10 QTL markers were used to help introgress the destemming trait into jalapeño-type peppers. Low destemming force lines combined with improvements in transplant production enabled mechanical harvest of destemmed fruit at a rate of 41% versus 2% with a commercial jalapeńo hybrid. Staining for the presence of lignin at the pedicel/fruit boundary indicated the presence of an abscission zone and homologs of genes known to affect organ abscission were found under several QTL, suggesting that the easy-destemming trait may be due to the presence and activation of a pedicel/fruit abscission zone.Conclusion: Presented here are tools to measure the easy-destemming trait, its physiological basis, possible molecular pathways, and expression of the trait in various genetic backgrounds. Mechanical harvest of destemmed mature green chile fruits was achieved by combining easy-destemming with transplant management.

Abstract Accumulating evidence has demonstrated the essential role of long noncoding RNAs (lncRNAs) in various types of human cancer, including pancreatic cancer (PC). However, the functions and regulatory mechanisms of nuclear receptor subfamily 2 group F member 1 antisense RNA 1 (NR2F1-AS1) that are responsible for its role in the malignant progression of PC cells remains to be investigated. In this study, the biological effects of NR2F1-AS1 and NR2F1 in PC were investigated by in vitro and in vivo experiments. The mechanisms of NR2F1-AS1 were monitored by bioinformatic predictive analysis and confirmatory experiments. Our results indicated that NR2F1-AS1 was overexpressed and positively correlated with poor survival in PC. Depletion of NR2F1-AS1 restrained PC cell proliferation, migration, invasion, and suppressed xenograft tumor growth and metastasis in vitro and in vivo. Mechanistic experiments suggested that NR2F1-AS1 positively regulated the neighboring NR2F1 gene, which subsequently activated AKT/mTOR signaling, resulting in the upregulation of hypoxia-inducible factor-1α (HIF-1α). Further investigations elucidated that NR2F1-AS1 expression was transcriptionally regulated by HIF-1α under hypoxia. These findings demonstrated that hypoxia-induced NR2F1-AS1 expression directly increased NR2F1 levels to promote PC cell proliferation, migration, and invasion by activating AKT/mTOR signaling. Together, these findings suggest that NR2F1-AS1 could be a prospective therapeutic target for PC.

Background: Predicting cognition decline in patients with mild cognitive impairment (MCI) is crucial for identifying high-risk individuals and implementing effective management. To improve predicting MCI-to-AD conversion, it is necessary to consider various factors using explainable machine learning (XAI) models which provide interpretability while maintaining predictive accuracy. This study used the Explainable Boosting Machine (EBM) model with multimodal features to predict the conversion of MCI to AD during different follow-up periods while providing interpretability. Methods: This retrospective case-control study is conducted with data obtained from the ADNI database, with records of 1042 MCI patients from 2006 to 2022 included. The exposures included in this study were MRI biomarkers, cognitive scores, demographics, and clinical features. The main outcome was AD conversion from aMCI during follow-up. The EBM model was utilized to predict aMCI converting to AD based on three feature combinations, obtaining interpretability while ensuring accuracy. Meanwhile, the interaction effect was considered in the model. The three feature combinations were compared in different follow-up periods with accuracy, sensitivity, specificity, and AUC-ROC. The global and local explanations are displayed by importance ranking and feature interpretability plots. Results: The five-years prediction accuracy reached 85% (AUC = 0.92) using both cognitive scores and MRI markers. Apart from accuracies, we obtained features’ importance in different follow-up periods. In early stage of AD, the MRI markers play a major role, while for middle-term, the cognitive scores are more important. Feature risk scoring plots demonstrated insightful nonlinear interactive associations between selected factors and outcome. In one-year prediction, lower right inferior temporal volume (4) is the most important. During four-year prediction, APOE4 is the most critical. For five-year prediction, lower right entorhinal volume (

Although cold brew coffee is becoming increasingly popular among consumers, the long coffee extraction time is not conducive to the further development of the market. This study explored the feasibility of ultrahigh pressure (UHP) to shorten the time required for preparing cold brew coffee. The effects of pressure and holding time on the physicochemical characteristics and sensory evaluation of UHP-assisted cold brew coffee were also determined. The extraction yield; total dissolved solid, total phenol, and melanoid content; antioxidant capacity; and trigonelline and chlorogenic acid contents of UHP-assisted cold brew coffee increased as the pressure increased. The extraction yield and the total dissolved solid, total phenol, total sugar, and chlorogenic acid and trigonelline contents were higher when the holding time was longer. The HS-SPME-GC/MS analysis demonstrated that the furan, aldehyde, and pyrazine contents in coffee increased as the pressure and holding time increased. The pressure did not significantly impact the concentrations of volatile components of esters and ketones in coffee samples. However, the increase in holding time significantly increased the ester and ketone contents. The sensory evaluation results revealed that as pressure rose, the intensities of nutty, fruity, floral, caramel, and sourness flavors increased, whereas bitterness and sweetness decreased. Longer holding time increased nutty, caramel, sour, bitter, sweet, and aftertaste flavors. Principal component analysis (PCA) results indicated that holding time is a more crucial factor affecting the physiochemical indices and flavor characteristics of coffee. UHP can shorten the preparation time of cold brew coffee. Pressure and holding time significantly affected the physiochemical indices and volatile components of UHP-assisted cold brew coffee. UHP-assisted cold brew coffee had lower bitterness, higher sweetness, and a softer taste than conventional cold brew coffee.

Recently, learning-based image inpainting has gained much attention. It widely utilizes an auto-encoder structure and can obtain compact feature representation in the encoder to achieve high-quality image inpainting. Although this approach has achieved encouraging inpainting results, it inevitably reduces the high-resolution representation due to interval downsampling. In order to solve this problem and achieve an excellent image inpainting effect, this paper proposes a brand-new generative network, Interactive Separation Network, which retains the high-resolution information and extracts the semantic features from corrupted images. Furthermore, this paper also discusses network designs with different complexity in different application scenarios. Finally, to improve the effectiveness and robustness of our proposal to large corrupted regions in the inpainting image, we further propose a flexible and highly reusable reconstruction scheme to complete the inpainting in the prediction process gradually. Experiments show that our proposed generation network and reconstruction scheme can significantly improve the quality of repaired images. The proposed method significantly outperforms the state-of-the-art image inpainting approaches in image quality.

Abstract Background Anxiety disorders are often the first presentation of psychopathology in youth and are considered the most common psychiatric disorders in children and adolescents. This study aimed to identify distinct student anxiety profiles to develop targeted interventions. Methods A cross-sectional study was conducted with 9738 students in Yingshan County. Background characteristics were collected and Mental Health Test (MHT) were completed. Latent profile analysis (LPA) was applied to define student anxiety profiles, and then the analysis was repeated using k-means clustering. Results LPA yielded 3 profiles: the low-risk, mild-risk and high-risk groups, which comprised 29.5, 38.1 and 32.4% of the sample, respectively. Repeating the analysis using k-means clustering resulted in similar groupings. Most students in a particular k-means cluster were primarily in a single LPA-derived student profile. The multinomial ordinal logistic regression results showed that the high-risk group was more likely to be female, junior, and introverted, to live in a town, to have lower or average academic performance, to have heavy or average academic pressure, and to be in schools that have never or occasionally have organized mental health education activities. Conclusions The findings suggest that students with anxiety symptoms may be categorized into distinct profiles that are amenable to varying strategies for coordinated interventions.

Background: High dimensional mediation analysis is frequently conducted to explore the role of epigenetic modifiers between exposure and health outcome. However, the issue of high dimensional mediation analysis with unmeasured confounders for survival analysis in observational study has not been well solved.Methods: In this study, we proposed an instrumental variable based approach for high dimensional mediation analysis with unmeasured confounders in survival analysis for epigenetic study. We used the Sobel‘s test, the Joint test, and the Bootstrap method to test the mediation effect. A comprehensive simulation study was conducted to decide the best test strategy. An empirical study based on DNA methylation data of lung cancer patients was conducted to illustrate the performance of the proposed method.Results: Simulation study suggested that the proposed method performed well in the identifying mediating factors. The estimation of the mediation effect by the proposed approach is also reliable with less bias compared with the classical approach. In the empirical study, we identified two DNA methylation signatures including cg21926276 and cg26387355 with a mediation effect of 0.226 (95%CI: 0.108-0.344) and 0.158 (95%CI: 0.065-0.251) between smoking and lung cancer using the proposed approach.Conclusion: The proposed method obtained good performance in simulation and empirical studies, it could be an effective statistical tool for high dimensional mediation analysis.