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BACKGROUND: Previous epidemiological studies have repeatedly found per- and polyfluoroalkyl substances (PFAS) exposure associated with higher circulating cholesterol, one of the greatest risk factors for development of coronary artery disease. The main route of cholesterol catabolism is through its conversion to bile acids, which circulate between the liver and ileum via enterohepatic circulation. Patients with coronary artery disease have decreased bile acid excretion, indicating that PFAS-induced impacts on enterohepatic circulation may play a critical role in cardiovascular risk. OBJECTIVES: Using a mouse model with high levels of low-density and very low-density lipoprotein (LDL and VLDL, respectively) cholesterol and aortic lesion development similar to humans, the present study investigated mechanisms linking exposure to a PFAS mixture with increased cholesterol. METHODS: Male and female Ldlr-/- mice were fed an atherogenic diet (Clinton/Cybulsky low fat, 0.15% cholesterol) and exposed to a mixture of 5 PFAS representing legacy, replacement, and emerging subtypes (i.e., PFOA, PFOS, PFHxS, PFNA, GenX), each at a concentration of 2 mg=L, for 7 wk. Blood was collected longitudinally for cholesterol measurements, and mass spectrometry was used to measure circulating and fecal bile acids. Transcriptomic analysis of ileal samples was performed via RNA sequencing. RESULTS: After 7 wk of PFAS exposure, average circulating PFAS levels were measured at 21.6, 20.1, 31.2, 23.5, and 1:5 [micro]g/mL in PFAS-exposed females and 12.9, 9.7, 23, 14.3, and 1:7 [micro]g/mL in PFAS-exposed males for PFOA, PFOS, PFHxS, PFNA, and GenX, respectively. Total circulating cholesterol levels were higher in PFAS-exposed mice after 7 wk (352 mg/dL vs. 415 mg/dL in female mice and 392 mg/dL vs. 488 mg/dL in male mice exposed to vehicle or PFAS, respectively). Total circulating bile acid levels were higher in PFAS-exposed mice (2,978 pg/[micro]L vs. 8,496 pg/[micro]L in female mice and 1,960 pg/[micro]L vs. 4,452 pg/[micro]L in male mice exposed to vehicle or PFAS, respectively). In addition, total fecal bile acid levels were lower in PFAS-exposed mice (1,797 ng/mg vs. 682 ng/mg in females and 1,622 ng/mg vs. 670 ng/mg in males exposed to vehicle or PFAS, respectively). In the ileum, expression levels of the apical sodium-dependent bile acid transporter (ASBT) were higher in PFAS-exposed mice. DISCUSSION: Mice exposed to a PFAS mixture displayed higher circulating cholesterol and bile acids perhaps due to impacts on enterohepatic circulation. This study implicates PFAS-mediated effects at the site of the ileum as a possible critical mediator of increased cardiovascular risk following PFAS exposure. https://doi.org/10.1289/EHP14339, Introduction Per- and polyfluoroalkyl substances (PFAS) are a large family of synthetically manufactured chemicals used for their surfactant properties in industrial and consumer products, including nonstick cookware and food storage, [...]

Abstract Background Fusobacterium nucleatum (F. nucleatum) is one of the key tumorigenic bacteria in colorectal cancer (CRC), yet how F. nucleatum is involved in colorectal cancer carcinogenesis remains unknown. Results In the present study, we carried out PathSeq analysis on RNA sequencing data from the 430 primary colon adenocarcinomas in TCGA database to assess the relationship between patients’ survival and F. nucleatum abundance. Among patients with cecum and ascending colon tumors, we found that F. nucleatum transcriptome abundance is positively correlated with mutation load. We further demonstrated that patients with both high tumoral abundance of F. nucleatum and high mutation load exhibited poorer survival and DNA damage. We furthermore determined that F. nucleatum-conditioned medium (Fn. CM) induces DNA damage in both in vitro and in vivo studies. In addition, two F. nucleatum-secreted mutagens, namely DL-homocystine and allantoic acid, were identified to lead to DNA damage. Conclusions Our finding delineates the genotoxicity of F.nucleatum-secreted mutagens, which provides a basis for further work to investigate the role of F. nucleatum in the pathogenicity of CRC.

Abstract Owing to patient-derived tumor tissues and cells, significant advances have been made in personalized cancer treatment and precision medicine, with cancer stem cell-derived three-dimensional tumor organoids serving as crucial in vitro models that accurately replicate the structural, phenotypic, and genetic characteristics of tumors. However, despite their extensive use in drug testing, genome editing, and transplantation for facilitating personalized treatment approaches in clinical practice, the inadequate capacity of these organoids to effectively model immune cells and stromal components within the tumor microenvironment limits their potential. Additionally, effective clinical immunotherapy has led the tumor immune microenvironment to garner considerable attention, increasing the demand for simulating patient-specific tumor–immune interactions. Consequently, co-culture techniques integrating tumor organoids with immune cells and tumor microenvironment constituents have been developed to expand the possibilities for personalized drug response investigations, with recent advancements enhancing the understanding of the strengths, limitations, and applicability of the co-culture approach. Herein, the recent advancements in the field of tumor organoids have been comprehensively reviewed, specifically highlighting the tumor organoid co-culture-related developments with various immune cell models and their implications for clinical research. Furthermore, this review delineates the current state of research and application of organoid models regarding the therapeutic approaches and related challenges for gynecological tumors. This study may provide a theoretical basis for further research on the use of patient-derived organoids in tumor immunity, drug development, and precision medicine.

Abstract This study aims to explore the expression profile of PANoptosis‐related genes (PRGs) and immune infiltration in Alzheimer's disease (AD). Based on the Gene Expression Omnibus database, this study investigated the differentially expressed PRGs and immune cell infiltration in AD and explored related molecular clusters. Gene set variation analysis (GSVA) was used to analyze the expression of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes in different clusters. Weighted gene co‐expression network analysis was utilized to find co‐expressed gene modules and core genes in the network. By analyzing the intersection genes in random forest, support vector machine, generalized linear model, and extreme gradient boosting (XGB), the XGB model was determined. Eventually, the first five genes (Signal Transducer and Activator of Transcription 3, Tumor Necrosis Factor (TNF) Receptor Superfamily Member 1B, Interleukin 4 Receptor, Chloride Intracellular Channel 1, TNF Receptor Superfamily Member 10B) in XGB model were selected as predictive genes. This research explored the relationship between PANoptosis and AD and established an XGB learning model to evaluate and screen key genes. At the same time, immune infiltration analysis showed that there were different immune infiltration expression profiles in AD.

Abstract The bearing capacity and settlements of surface foundations located on a soil slope are the important issues that have to be considered by geotechnical engineers for the design. The presence of an underground void beneath the footing can affect the foundation stability and can lead to serious structure damages. In this study, the results of two-dimensional (2D) discrete element (DE) and finite element (FE) analyses of a surface footing on a soil slope above a void are presented. To validate the numerical model results, the DE results obtained have been compared with experimental test presented in the previous study. After validation of the DE numerical model, parametric studies were carried out to evaluate the effect of important factors on the surface footing performance. The studied parameters include the horizontal spacing of the void axis relative to the slope edge (SH), the vertical spacing of the void crown relative to the footing base (SV), the horizontal spacing of the footing edge relative to the slope edge (De) and the void diameter (Dv). The effects of these parameters on the pressure-settlement curves and the contact force distributions in the soil slope are presented and discussed. The results showed that the footing bearing pressure increases with an increase of SH, SV and De but decreases when Dv increases. The behavior of a surface footing on a soil slope above a void significantly depends on the SV value.

Abstract Background Everolimus is an effective treatment for renal angiomyolipoma associated with TSC (TSC-RAML). However, its impact on hematologic parameters in TSC-RAML patients remains unclear. Methods Hematologic data were collected from TSC-RAML patients undergoing everolimus treatment in two registered clinical trials. Dynamic changes in hematologic parameters during treatment were analyzed. Additionally, we also explored variations in hematologic impact based on gender and age within the patient population. Result A total of 55 patients from the two clinical trials are included in this analysis. Hemoglobin, white blood cells (WBC), lymphocytes, neutrophils, and platelet showed significant decreases during everolimus treatment (P

Abstract Background It is uncertain whether the weekend warrior pattern is associated with all-cause mortality among adults living with type 2 diabetes. This study explored how the ‘weekend warrior’ physical activity (PA) pattern was associated with all-cause mortality among adults living with type 2 diabetes. Methods This prospective cohort study investigated US adults living with type 2 diabetes in the National Health and Nutrition Examination Survey (NHANES). Mortality data was linked to the National Death Index. Based on self-reported leisure-time and occupational moderate-to-vigorous PA (MVPA), participants were categorized into 3 groups: physically inactive (

Abstract Background There is increasing evidence that inflammation plays a key role in the pathophysiology of periodontitis (PT) and Alzheimer’s disease (AD), but the roles of inflammation in linking PT and AD are not clear. Our aim is to analyze the potential molecular mechanisms between these two diseases using bioinformatics and systems biology approaches. Methods To elucidate the link between PT and AD, we selected shared genes (SGs) with gene-disease-association scores of ≥ 0.1 from the Disease Gene Network (DisGeNET) database, followed by extracting the hub genes. Based on these genes, we constructed gene ontology (GO) enrichment analysis, pathway enrichment analysis, protein-protein interaction (PPI) networks, transcription factors (TFs)-gene networks, microRNAs (miRNAs)-gene regulatory networks, and gene-disease association analyses. Finally, the Drug Signatures database (DSigDB) was utilized to predict candidate molecular drugs related to hub genes. Results A total of 21 common SGs between PT and AD were obtained. Cell cytokine activity, inflammatory response, and extracellular membrane were the most important enriched items in GO analysis. Interleukin-10 Signaling, LTF Danger Signal Response Pathway, and RAGE Pathway were identified as important shared pathways. IL6, IL10, IL1B, TNF, IFNG, CXCL8, CCL2, MMP9, TLR4 were identified as hub genes. Both shared pathways and hub genes are closely related to endoplasmic reticulum (ER) stress and mitochondrial dysfunction. Importantly, glutathione, simvastatin, and dexamethasone were identified as important candidate drugs for the treatment of PT and AD. Conclusions There is a close link between PT and AD pathogenesis, which may involve in the inflammation, ER and mitochondrial function.

The high efficacy of metro network services not only enhances residents’ travel quality but also brings significant socio-economic benefits, thus is of great importance to urban land use and city development. Existing methods for measuring metro service efficacy often overlook metro network connectivity and rely heavily on subjective questionnaire data analysis from the user experience perspective. This paper proposes a method to measure metro network service efficacy from the user’s perspective. The approach first calculates the connectivity index of metro network and estimates the housing premium brought by metro network connectivity, which reveals users’ willingness to pay for metro network connectivity. This method objectively measures metro network service efficacy from the user’s perspective. Based on this, efficacy optimization methods are proposed, providing quantitative simulation methods for metro expansion, site selection, operation quality adjustments, etc., which are of great reference value to metro management departments and even urban sustainable development.

Abstract Background Both body mass index (BMI) and genetic factors independently contribute to cardiovascular disease (CVD). However, it is unclear whether genetic risk modifies the association between BMI and the risk of incident CVD. This study aimed to investigate whether BMI categories and genetic risk jointly and interactively contribute to incident CVD events, including hypertension (HTN), atrial fibrillation (AF), coronary heart disease (CHD), stroke, and heart failure (HF). Methods A total of 496,851 participants from the UK Biobank with one or more new-onset CVD events were included in the analyses. BMI was categorized as normal weight (

Fresh wet noodles (FWN) are popular staple foods due to its unique chewy texture and favorable taste. However, the development of FWN is limited by its short shelf life and high browning rate. It has been found that the quantity of original microorganisms in wheat flour produced by traditional method is relatively high, which is detrimental to the processing quality and storage stability of FWN. Consequently, it becomes imperative to decrease microorganisms in wheat flour. Microwave treatment has been regarded as a promising method in the food industry due to its potential in inhibiting microbial growth and inactivating enzymes without causing adverse effect on the food quality. This study aims to investigate the effects of microwave treatment of wheat kernels under different powers (1, 2, 3, 4, 5 kW) on the physicochemical properties of wheat flour and the quality of FWN. The results revealed that microwave treatment had a significant effect on microbial inhibition and enzyme inactivation, wherein the total plate count (TPC) and yeast and mold counts (YMC) decreased by 0.87 lg(CFU/g) and 1.13 lg(CFU/g) respectively, and PPO activity decreased from 11.40 U to 6.31 U. The dough quality properties, such as stability, extensibility, and starch viscosity, improved significantly under different microwave conditions. Confocal laser scanning microscopy (CLSM) images indicated that starch and proteins aggregated gradually in treated flour, altering rheological properties of dough. From the results of scanning electron microscopy (SEM), microwave treatment led to the appearance of disrupted structure in the gluten proteins, but the secondary structure of proteins altered slightly. Rheological properties of dough confirmed that the microwave treatment greatly affected processing characteristics of wheat flour products, with significant advantageous consequences on product quality, especially for textural properties of FWN. Furthermore, FWN darkening could be inhibited noticeably after microwave treatment, thereby prolonging its shelf life. Therefore, microwave treatment could thus be an effective, practical technology to produce low-bacterial flour and thereby enhance its product quality.

Abstract Mycoplasma bovis (M. bovis) is capable of causing a range of diseases in cattle, encompassing calf pneumonia, arthritis, conjunctivitis, meningitis, and mastitis. It is widely recognized as one of the predominant pathogens posing a significant threat to the global cattle industry. Therefore, accurate and sensitive methods are urgently needed to detect M. bovis. This study aims to detect M. bovis by combining colloidal gold with biotin-labeled oligonucleotides to improve detection sensitivity and form a chromogenic detection probe based on signal amplification technology. Here, we developed a sensitive and specific polymerase chain reaction-lateral flow dipstick assay (PCR-LFD) strip for efficient nucleic acid detection of M. bovis. A pair of specific primers with 5’ ends labeled with biotin and digoxigenin probes was designed for PCR experiments. Colloidal gold particles-labeled anti-digoxigenin IgG coated gold-labeled test strip was prepared, streptavidin was used as the detection probe, and nitrocellulose membrane coated goat anti-mouse IgG was used as the control line. Our results showed that the detection limit of the PCR-LFD was 89 fg/µL for the M. bovis DNA. The results from the test strip were highly consistent with those from real-time qPCR. This assay were highly specific for M. bovis, as there were no cross-reactions with other microorganisms tested and the detection sensitivity of the test was also relatively high (97.67%). The novel strips present a promising tool for the cost-effective and sensitive diagnosis of M. bovis.

Abstract Background Both ambient air pollution and lifestyle factors contribute to the incidence of non-alcoholic fatty liver disease (NAFLD), but previous studies usually focused on single-factor associations. We aimed to assess the joint associations of ambient air pollution and lifestyle with the NAFLD risk and investigate whether lifestyle modifies the association of air pollution with NAFLD risk. Methods A total of 417,025 participants from the UK Biobank were included in this study. Annual average concentrations of NO2, NOx, PM2.5, PM10, and PM2.5−10 were estimated. A composite lifestyle score was determined based on physical activity, alcohol intake, smoking status, dietary patterns, sedentary time, and sleep duration. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs), as well as the population attributable fraction (PAF). Potential additive interactions of air pollution with lifestyle were also examined by the relative excess risk due to the interaction (RERI) and the attributable proportion due to the interaction (AP). Results 4752 (1.14%) incident NAFLD events were recorded. Long-term exposure to air pollutants and an unhealthy lifestyle were significantly associated with the increased risk of incident NAFLD. Lifestyle was the primary factor of incident NAFLD, with a PAF of 37.18% (95% CI: 29.67%, 44.69%). In addition, a significant additive interaction between air pollution and lifestyle for NAFLD risk was observed (RERI: 0.36, 95% CI: 0.09–0.63). Conclusions Long-term exposure to ambient air pollutants and poor lifestyle were jointly associated with a higher risk of NAFLD.

In order to explore new methods for improving the strength-toughness matching of Fe-Cr-B-C alloy， the effect of B content on its microstructure， hardness， and impact toughness after heat treatment were investigated. The results showed that after air-cooling quenching at 1 050 ℃， a large amount of extremely fine secondary carbon-borides precipitated in the interdendritic region of low-B （0.000 6%） alloy， and fine dispersed secondary carbon-borides precipitated in the matrix of intermediate-B （0.51%） and high-B （2.89%） alloys. As the B content increased， the size of secondary carbon-borides increased but the particle density decreased. After air-cooling quenching at 1 050 ℃ plus tempering at 500 ℃， the number of secondary carbon-borides increased and the precipitation region expanded. For the low-B alloy， the dendrite arm was composed of coarse lath-like martensite， and the interdendritic region was composed of acicular martensite， high-density secondary carbon-borides and a small amount of solidification precipitates. For the intermediate-B alloy， the microstructure was composed of acicular martensite matrix with dispersed secondary carbon-borides， and network boron-carbides. For the high-B alloy， the microstructure was composed of γ matrix with a small amount of dispersed secondary carbon-borides， and denser network boron-carbides. The low-B alloy possesses the highest impact toughness and moderate Rockwell hardness. The intermediate-B alloy possesses the highest Rockwell hardness and moderate impact toughness. The high-B alloy possesses the lowest Rockwell hardness and impact toughness. Compared with the as-cast state， the solidification precipitates dissolved slightly after the quenching and tempering treatment， which resulted in the local rupture of netlike boron-carbides in intermediate-B and high-B alloys. Thus， after air-cooling quenching at 1 050 ℃ plus tempering at 500 ℃， the impact toughness of intermediate-B and high-B alloys improved obviously.

Coal mining engineering involves complex stress structure time effect issues, which are closely related to the occurrence and prevention of rock burst disasters. Therefore, this study conducts experimental research on the stress structure time effect of impact coal. Coal rock specimens were obtained from three coal mines in Shaanxi, Gansu, and Inner Mongolia. The stress-time effect of loading rate was studied through coal uniaxial compression static-dynamic load and creep tests. The stress-time effect under the condition of coal in situ release was investigated using a long-term segmented test method. Water immersion tests on coal and structural time-effect studies on coal-rock combinations were conducted. The experimental results indicate that there is a positive correlation between the uniaxial compressive strength of coal and the loading rate, and a negative correlation with the duration of in-situ relief and immersion time. The combined mode of coal-rock structure time effect significantly affects its energy and strength properties, while impact coal exhibits both stress and structural time effects. According to the experimental results, a plastic limit structure is proposed to explain the irreversible deformation of coal-rock mass under stress. Furthermore, by constructing a time-dependent model for plastic strain in coal under impact conditions and comparing the numerical approximations of non-elastic strain and irreversible strain, the plastic limit strain characteristics of shock-induced coal were verified.

This study aimed to analyze the effect of Issatchenkia orientalis on the microbial community structure and volatile flavor substance synthesis in Nongxiangxing Baijiu Jiupei in order to explore its effect on the microbial interaction and metabolism in the Jiupei. Under laboratory conditions, the microbial system for Nongxiangxing Baijiu brewing consisting of the Jiupei and Huangshui, a by-product of Baijiu brewing, was fermented directly (control group) or after inoculation with a strain of I. orientalis isolated from the Jiupei (experimental group). The composition of microbial communities, microbial interactions, and volatile flavor substances in the 2 groups were analyzed. The results showed that the microbial abundance of Jiupei changed after inoculation with I. orientalis; the relative abundance of Lactobacillus and Issatchenkia increased, and the relative abundance of Paenibacillus and Aspergillus decreased. Moreover, the microbial interaction was strengthened, making the microbial network structure more complex and compact. Compared with the control group, the volatile flavor substances in the experimental group increased significantly, 20 significantly differential volatile flavor substances were identified, and the contents of isopropanol, isoamylol and isobutanol increased significantly. The results of this study disclose the influences of inoculating I. orientalis on the microbial community structure and volatile flavor substances in Nongxiangxing Baijiu Jiupei and help to understand the impact of functional microorganisms on the microbial perturbation and metabolite synthesis in Jiupei.

Abstract Revealing key factors that modulate the regioselectivity in heterogeneous hydroformylation requires identifying and monitoring the dynamic evolution of the truly active center under real reaction conditions. However, unambiguous in situ characterizations are still lacking. Herein, we elaborately construct a series of Rh-POPs catalysts for propylene hydroformylation which exhibited tunable regioselectivity. Multi-technique approaches reveal the unique microenvironment of the diverse HRh(CO)(PPh3-frame)2 sites with distinct P-Rh-P bite angles ranging from 90° to 120° and 158° to 168°, respectively. In situ time-resolved XAFS, FT-IR, and quasi-in situ Solid-state NMR experiments combined with DFT calculations explain the dynamic evolution of the electronic and coordinate state of the distinct active sites induced by hemilabile PPh3-frame ligands and further disclose the regulatory mechanism of regioselectivity. These state-of-the-art techniques and multiscale analysis advance the understanding of how hemilabile coordination influences regioselectivity and will provide a new thought to modulate the regioselectivity in future industrial processes.

Abstract Background Inflammatory bowel disease (IBD) is a progressive and debilitating inflammatory disease of the gastrointestinal tract (GIT). Despite recent advances, precise treatment and noninvasive monitoring remain challenging. Methods Herein, we developed orally-administered, colitis-targeting and hyaluronic acid (HA)-modified, core-shell curcumin (Cur)- and cerium oxide (CeO2)-loaded nanoprobes (Cur@PC-HA/CeO2 NPs) for computed tomography (CT) imaging-guided treatment and monitoring of IBD in living mice. Results Following oral administration, high-molecular-weight HA maintains integrity with little absorption in the upper GIT, and then actively accumulates at local colitis sites owing to its colitis-targeting ability, leading to specific CT enhancement lasting for 24 h. The retained NPs are further degraded by hyaluronidase in the colon to release Cur and CeO2, thereby exerting anti-inflammatory and antioxidant effects. Combined with the ability of NPs to regulate intestinal flora, the oral NPs result in substantial relief in symptoms. Following multiple treatments, the gradually decreasing range of the colon with high CT attenuation correlates with the change in the clinical biomarkers, indicating the feasibility of treatment response and remission. Conclusion This study provides a proof-of-concept for the design of a novel theranostic integration strategy for concomitant IBD treatment and the real-time monitoring of treatment responses.

Abstract The groove density mismatching of compression gratings, an often-neglected key issue, can induce significant spatiotemporal aberrations especially for super-intense femtosecond lasers. We mainly investigate the angular chirp and the consequent degradation of the effective focused intensity introduced by the groove density mismatching of compression gratings in ultra-intense femtosecond lasers. The results indicate that the tolerances of grating groove density mismatching will rapidly decrease with the beam aperture or spectral bandwidth increases. For our 100PW laser under construction, the grating groove density mismatching should be as small as 0.001 gr/mm if the drop of effective focused intensity has to be controlled below 15%. More importantly, new angular chirp compensation schemes are proposed for both double-grating and four-grating compressors. This work reveals the importance of groove density matching of compression gratings, and can provide helpful guidelines for the design of ultra-intense femtosecond lasers.

Abstract In recent years, significant advancements have been made in molecular generation algorithms aimed at facilitating drug development, and molecular diversity holds paramount importance within the realm of molecular generation. Nonetheless, the effective quantification of molecular diversity remains an elusive challenge, as extant metrics exemplified by Richness and Internal Diversity fall short in concurrently encapsulating the two main aspects of such diversity: quantity and dissimilarity. To address this quandary, we propose Hamiltonian diversity, a novel molecular diversity metric predicated upon the shortest Hamiltonian circuit. This metric embodies both aspects of molecular diversity in principle, and we implement its calculation with high efficiency and accuracy. Furthermore, through empirical experiments we demonstrate the high consistency of Hamiltonian diversity with real-world chemical diversity, and substantiate its effects in promoting diversity of molecular generation algorithms. Our implementation of Hamiltonian diversity in Python is available at: https://github.com/HXYfighter/HamDiv . Scientific contribution We propose a more rational molecular diversity metric for the community of cheminformatics and drug development. This metric can be applied to evaluation of existing molecular generation methods and enhancing drug design algorithms.

Abstract Background Validated and comprehensive tools to measure treatment burden are needed for healthcare professionals to understand the treatment burden of patients in China. The study aimed to translate and validate the Chinese version of Patient Experience with Treatment and Self-management (PETS vs. 2.0) in patients with multimorbidity in primary care. Methodology The translation process of the 60-item PETS vs. 2.0 followed the Functional Assessment of Chronic Illness Therapy (FACIT) Translation, Formatting, and Testing Guidelines. Computer-assisted assessments were conducted in adult primary care patients with multimorbidity from three general out-patient clinics in Hong Kong. A sample of 502 patients completed the assessments from July to December 2023. Internal reliability was examined using Cronbach’s alphas for each domain of the PETS vs. 2.0. Concurrent validity was assessed through the correlations between different domains of PETS vs. 2.0 with established measures including quality of life, frailty, and depression. Confirmatory Factor Analysis (CFA) with maximum likelihood method was carried out to assess the construct validity. Results The mean age of participants was 64.9 years old and 56.2% were female. Internal consistency reliability was acceptable (alpha ≥ 0.70) for most domains. Higher scores of PETS domains were significantly correlated with worse quality of life, higher level of frailty, and more depressive symptoms (p

This research proposes a low-cost system consisting of a hardware setup and a deep learning-based model to estimate broiler chickens’ feed intake, utilizing audio signals captured by piezoelectric sensors. The signals were recorded 24/7 for 19 consecutive days. A subset of the raw data was chosen, and events were labeled in two classes, feed-pecking and non-pecking (including singing, anomaly, and silence samples). Next, the labeled data were preprocessed through a noise removal algorithm and a band-pass filter. Then, the spectrogram and the signal envelope were extracted from each signal and fed as inputs to a VGG-16-based convolutional neural network (CNN) with two branches for 1D and 2D feature extraction followed by a binary classification head to classify feed-pecking and non-pecking events. The model achieved 92% accuracy in feed-pecking vs. non-pecking events classification with an f1-score of 91%. Finally, the entire raw dataset was processed utilizing the developed model, and the resulting feed intake estimation was compared with the ground truth data from scale measures. The estimated feed consumption showed an 8 ± 7% mean percent error on daily feed intake estimation with a 71% R2 score and 85% Pearson product moment correlation coefficient (PPMCC) on hourly intake estimation. The results demonstrate that the proposed system estimates broiler feed intake at each feeder and has the potential to be implemented in commercial farms.

Long pressure short extraction ventilation and dust removal method is one of the effective methods for removing high mass concentration dust in the excavation area of coal mine comprehensive heading face. Especially, the local flow field generated by the combination of pressure and suction is conducive to the removal and reduction of respiratory dust. However, the dynamic changes in the location of dust production sources have an unclear impact on the dust removal performance of this method. By considering the movement paths and reciprocating times of the dust source location in both horizontal and vertical directions, four dust source movement paths were designed based on the long pressure short extraction test platform. Combined with the regulation of the parameters of the long pressure short extraction ventilation system, the impact of the dust source on the spatial dust mass concentration, particle size mass concentration, and particle size distribution under different movement conditions was tested and analyzed. The results show that under the same ventilation parameters, the dust mass concentration caused by the horizontal path on the respiratory belt positions of drivers and pedestrians is lower than that caused by the vertical path. In the horizontal path, when the pressure air duct is located on the side near the exhaust duct and the pressure air outlet is located in an area about 1 m in front of the driver, the particle size mass concentrations of PM1, PM2.5 and PM10 at the breathing zone between the driver and pedestrian are the lowest, and the ventilation and dust removal effect is the best. The diffusion of spatial dust is manifested as: particles with a particle size less than 2.5 µm are easily collected and removed by the exhaust flow field at the exhaust port, while the particles with a particle size greater than 10 µm will escape from the dust generation source and exhaust area to the driver and the area behind them, and mainly settle naturally. Based on the optimal dust source movement path and ventilation parameters obtained from preliminary experiments, on-site experiments were conducted on the 2304 fully mechanized heading face of a coal mine in northern Shaanxi. The results show that the total dust mass concentration at the driver's position and pedestrian breathing zone position under the lateral path decreased to 85.6 mg/m3 and 21.9 mg/m3, respectively, with the highest dust reduction rate reaching 76.9%. The mass concentration of respirable dust decreased to 15.3 mg/m3 and 10.5 mg/m3 respectively, with a maximum dust reduction rate of 85.2% and the dust removal performance was significantly improved.

There are various forms of multilateral horizontal wells for developing coalbed methane, and the role of cleats in the development process is unclear. It is necessary to investigate the impact of the discrete cleat distribution in coal seams and the multilateral horizontal well configuration on gas well productivity. Based on the density and orthogonal characteristics of face and butt cleats in coal seams, the low density, medium density, and high density discrete cleat systems in coal seams are constructed using random methods. Combined with four different forms of multilateral horizontal wells, namely equal-length type, spindle type, staggered type, and dumbbell type, a physical model for developing coalbed methane using multilateral horizontal wells is constructed. The stress sensitive model of coal matrix and cleat system is established considering the effective stress change of coal seams and the matrix shrinkage effect in the development process. The desorption of coal-bed methane is calculated using Langmuir theorem, and a development model of compressible coal-bed methane flowing in the coupling of coal matrix, cleat system and multi branch horizontal wells is established. Furthermore, the influence of the cleat density and the configuration of multilateral horizontal wells on the development of coal-bed methane is studied. The results show that the discrete cleats in coal seams can greatly increase the drainage area of multilateral horizontal wells in a short period of development time, but are only limited to the cleats directly connected to multilateral horizontal wells and surrounding matrix areas. The parts that are not connected to multilateral horizontal wells require longer development time, which is also an important reason for gas wells to achieve peak production in a short period of time and quickly reduce production. The drainage area controlled by equal-length multilateral horizontal wells is the largest, while the drainage area of staggered type, dumbbell type, and spindle type decreases sequentially. When the cleat density is the same in the coal seams, the daily peak production and cumulative production within 20 years of the equal-length multilateral horizontal wells are higher than those of the other three types of multilateral horizontal wells, which can achieve better development results. By increasing the angle between the main and secondary wellbore of multilateral horizontal wells, the development effect of equal-length multilateral horizontal wells becomes much better, and the peak daily production of spindle multilateral horizontal wells is significantly improved. The peak daily production of staggered and dumbbell multilateral horizontal wells is more sensitive to the number of branches. The number of branches in spindle multilateral horizontal wells should not be less than eight, while the number of branches in the dumbbell multilateral wells should not be more than six.

Abstract Background Endometriosis (EMs) is an enigmatic disease of yet-unknown pathogenesis. Disulfidptosis, a novel identified form of programmed cell death resulting from disulfide stress, stands a chance of treating diverse ailments. However, the potential roles of disulfidptosis-related genes (DRGs) in EMs remain elusive. This study aims to thoroughly explore the key disulfidptosis genes involved in EMs, and probe novel diagnostic markers and candidate therapeutic compounds from the aspect of disulfidptosis based on bioinformatics analysis, machine learning, and animal experiments. Results Enrichment analysis on key module genes and differentially expressed genes (DEGs) of eutopic and ectopic endometrial tissues in EMs suggested that EMs was closely related to disulfidptosis. And then, we obtained 20 and 16 disulfidptosis-related DEGs in eutopic and ectopic endometrial tissue, respectively. The protein-protein interaction (PPI) network revealed complex interactions between genes, and screened nine and ten hub genes in eutopic and ectopic endometrial tissue, respectively. Furthermore, immune infiltration analysis uncovered distinct differences in the immunocyte, human leukocyte antigen (HLA) gene set, and immune checkpoints in the eutopic and ectopic endometrial tissues when compared with health control. Besides, the hub genes mentioned above showed a close correlation with the immune microenvironment of EMs. Furthermore, four machine learning algorithms were applied to screen signature genes in eutopic and ectopic endometrial tissue, including the binary logistic regression (BLR), the least absolute shrinkage and selection operator (LASSO), the support vector machine-recursive feature elimination (SVM-RFE), and the extreme gradient boosting (XGBoost). Model training and hyperparameter tuning were implemented on 80% of the data using a ten-fold cross-validation method, and tested in the testing sets which determined the excellent diagnostic performance of these models by six indicators (Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value, Accuracy, and Area Under Curve). And seven eutopic signature genes (ACTB, GYS1, IQGAP1, MYH10, NUBPL, SLC7A11, TLN1) and five ectopic signature genes (CAPZB, CD2AP, MYH10, OXSM, PDLIM1) were finally identified based on machine learning. The independent validation dataset also showed high accuracy of the signature genes (IQGAP1, SLC7A11, CD2AP, MYH10, PDLIM1) in predicting EMs. Moreover, we screened 12 specific compounds for EMs based on ectopic signature genes and the pharmacological impact of tretinoin on signature genes was further verified in the ectopic lesion in the EMs murine model. Conclusion This study verified a close association between disulfidptosis and EMs based on bioinformatics analysis, machine learning, and animal experiments. Further investigation on the biological mechanism of disulfidptosis in EMs is anticipated to yield novel advancements for searching for potential diagnostic biomarkers and revolutionary therapeutic approaches in EMs.

Abstract This study investigated how structural parameters (including injection ducts and exhaust nozzle inner diameters) affect the internal flow field and dilution ratio of diesel particulate sampling diluters. Increasing air injection duct diameter increased the injection chamber pressure and decreased the air velocity peak, mixed gas flow velocity, sample temperature, and mixing rate. Excessively small tube diameters caused uneven and discontinuous flow field distributions, while substantial air blockage rendered the flow state poor. Increasing nozzle inner diameters increased the exhaust flow area and the sample temperature, but decreased the velocity of the exhaust and gas mixtures and the pressure drop. Compared with a 2.0 mm inner diameter, 2.5 and 3.0 mm diameters decreased the peak velocity by 11.18% and 14.41%, respectively, and mixing slowed significantly. Inner nozzle diameters of

Abstract The coalbed methane (CBM) productivity is directly determined by the fracture permeability during hydraulic fracturing, which is regulated by the distribution of proppants. The proppant may be unevenly distributed in the fracture because of variables like the architecture of the fracture and the characteristics of the sand‐carrying fluid. This study used two types of random functions to produce different ununiform distributions of proppant clusters in large‐scale fractures, with the aim of investigating the effect of these distributions on the overall permeability of the fracture. A model of fluid‐structure coupling is proposed. The closure of large‐scale fractures under in‐situ stress is analyzed using solid mechanics and the penalty function; the CBM flowing in proppant clusters and the high‐speed channel between them is simulated using Darcy's law and the Navier–Stokes equation, respectively; and the overall permeability of fractures is computed using the fluid pressure drop throughout the fracture and the fluid flowing velocity in the fracture's outlet. Since most CBM flows along high‐speed channels between the proppant clusters, the simulated findings show that the overall permeability of fractures with an uneven distribution of proppant clusters is significantly higher than that of the proppant cluster itself. As CBM becomes more discretely distributed, the proportion of CBM flowing within the proppant cluster continuously drops. As the permeability of the proppant cluster increases, the volume ratio of proppant clusters decreases, and the distribution of proppant clusters becomes more discrete, the overall permeability of the fracture continuously increases.

This study evaluated the protein identification capabilities of the Top14 high-abundance protein removal kit (Top14) and the DMB MagicOmics low-abundance enrichment kit (DMB) on serum samples from healthy individuals (HC) and hepatocellular carcinoma (HCC) patients. For HC samples, DMB treatment led to identifying 2.6 times proteins more than Top14 and 3.9 times more than untreated samples. For HCC samples, DMB achieved 3.7 times increase in protein identification over Top14 and 6.2 times increase over untreated samples. Although the Top14 kit was effective in removing high-abundance proteins, it was less proficient in detecting low-abundance proteins when compared to the DMB method. In terms of protein identification frequency, the DMB-treated samples had a significantly higher number of quantifiable proteins than both the Top14 and Blank groups. Over 50% of the proteins identified in the Top14 and Blank groups were also identified in the DMB group, ensuring a comprehensive proteome coverage as evidenced by KEGG analysis. The DMB method significantly outperformed the others in HCC serum samples, identifying 47 differentially expressed (DE) proteins, in contrast to 15 and 17 identified of the Top14 group and untreated samples, respectively, highlighting its superior ability to uncover critical biomarkers for disease analysis. KEGG pathway analysis showed that DE proteins identified by DMB were involved in 21 distinct pathways, significantly more than 5 and 1 pathways identified by Top14 group and untreated samples, demonstrating DMB’s advanced proteomic profiling capability. This study also underscored HSP90AB1, SPP1, ACTR3, SNCA, PECAM1, and SRC proteins increased in HCC serum samples based on DMB method, marking them as promising HCC biomarkers for disease screening.

Abstract The relationship between VISmax and mortality in patients undergoing major abdominal surgery remains unclear. This study aims to evaluate the association between VISmax and both short-term and long-term all-cause mortality in patients undergoing major abdominal surgery, VISmax was calculated (VISmax = dopamine dose [µg/kg/min] + dobutamine dose [µg/kg/min] + 100 × epinephrine dose [µg/kg/min] + 10 × milrinone dose [µg/kg/min] + 10,000 × vasopressin dose [units/kg/min] + 100 × norepinephrine dose [µg/kg/min]) using the maximum dosing rates of vasoactives and inotropics within the first 24 h postoperative ICU admission. The study included 512 patients first admitted to the intensive care unit (ICU) who were administered vasoactive drugs after major abdominal surgery. The data was extracted from the medical information mart in intensive care-IV database. VISmax was stratified into five categories: 0–5, > 5–15, > 15–30, > 30–45, and > 45. Compared to patients with the lowest VISmax (≤ 5), those with the high VISmax (> 45) had an increased risk of 30-day mortality (hazard ratio [HR] 3.73, 95% CI 1.16–12.02; P = 0.03) and 1-year mortality (HR 2.76, 95% CI 1.09–6.95; P = 0.03) in fully adjusted Cox models. The ROC analysis for VISmax predicting 30-day and 1-year mortality yielded AUC values of 0.69 (95% CI 0.64–0.75) and 0.67 (95% CI 0.62–0.72), respectively. In conclusion, elevated VISmax within the first postoperative 24 h after ICU admission was associated with increased risks of both short-term and long-term mortality in patients undergoing major abdominal surgery.

Abstract In contemporary manufacturing, the processing of structural materials plays a pivotal role in enabling the creation of robust, tailor-made, and precise components suitable for diverse industrial applications. Nonetheless, current material forming technologies face challenges due to internal stress and defects, resulting in a substantial decline in both mechanical properties and processing precision. We herein develop a processing strategy toward graphene superstructure with a curvature gradient, which allows us to fabricate robust structural materials with meticulously designed functional shapes. The structure consists of an arc-shaped assembly of graphene nanosheets positioned at co-axial curvature centers. During the dehydration-based evaporate-casting process, the assembly is tightened via capillary effect, inducing local bending. By precisely tuning the axis-center distance and tilt angle, we achieve accurate control over the shape of obtained structure. Notably, internal stress is harnessed to reinforce a designed mortise and tenon structure, resulting in a high joining strength of up to ~200 MPa. This innovative approach addresses the challenges faced by current material forming technologies and opens up more possibilities for the manufacturing of robust and precisely shaped components.