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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, [...]

Since Uzbekistan gained independence from the Soviet Union in 1991, nationalist discourses have been overtly masculinized, continuing to inform Uzbek males' daily lives. Drawing on ethnographic fieldwork in Uzbekistan, this article illustrates how Uzbek boys' domestic relations contribute to the way they learn to (re)produce masculinities, foregrounding a high degree of agency and utility. The analysis uncovered three themes central to the (re)production of Uzbek boyhood in Uzbek families as a site of informal learning: (1) being helpful through domestic labour; (2) being social through showing hospitality; and (3) being tarbiyali through practising national culture. Through scrutinizing the intersections of gender, education and nationalism, this article concludes by connecting Uzbek boyhood in the domestic sphere and nationalist campaigns fostering masculine hegemony in Uzbekistan's nation building process. Through domesticity -- a contentious concept in feminist criticism -- this article expands our understanding of the (re)production of boyhood in a conventionally feminized space.

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.