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Abstract Occult hepatitis B virus infection (OBI) is characterized by the presence of HBV DNA in the absence of detectable HBsAg. OBI is an important risk factor for cirrhosis and hepatocellular carcinoma, but its pathogenesis has not been fully elucidated. Mutations in the HBV preS/S genes can lead to impaired secretion of either HBsAg or S-protein resulting in the accumulation of defective viruses or S protein in cells. In our previous work, the M133S mutation was present in the HBV S gene of maintenance hemodialysis (MHD) patients with OBI. In this study, we investigated the potential role of amino acid substitutions in S proteins in S protein production and secretion through the construction of mutant S gene plasmids, structural prediction, transcriptome sequencing analysis, and in vitro functional studies. Protein structure prediction showed that the S protein M133S mutant exhibited hydrophilic modifications, with greater aggregation and accumulation of the entire structure within the membrane phospholipid bilayer. Differential gene enrichment analysis of transcriptome sequencing data showed that differentially expressed genes were mainly concentrated in protein processing in the endoplasmic reticulum (ER). The expression of heat shock family proteins and ER chaperone molecules was significantly increased in the wild-type and mutant groups, whereas the expression of mitochondria-associated proteins was decreased. Immunofluorescence staining and protein blotting showed that the endoplasmic reticulum-associated protein PDI, the autophagy marker LC3, and the lysosome-associated protein LAMP2 co-localized with the S proteins in the wild-type and mutant strains, and their expression was increased. The mitochondria-associated TOMM20 protein was also co-expressed with the S protein, but expression was significantly reduced in the mutant. The M133S mutation in the S gene is expressed as a defective and misfolded protein that accumulates in the endoplasmic reticulum causing secretion-impaired endoplasmic reticulum stress, which in turn triggers mitochondrial autophagy and recruits lysosomes to fuse with the autophagosome, leading to mitochondrial clearance. This study preliminarily demonstrated that the mutation of M133S in the S gene can cause OBI and is associated with disease progression, providing a theoretical basis for the diagnosis and treatment of OBI.

The lifespan of core graphite under neutron irradiation in a commercial molten salt reactor (MSR) has an important influence on its economy. Flattening the fast neutron flux (≥0.05 MeV) distribution in the core is the main method to extend the graphite irradiation lifespan. In this paper, the effects of the key parameters of MSRs on fast neutron flux distribution, including volume fraction (VF) of fuel salt, pitch of hexagonal fuel assembly, core zoning, and layout of control rod assemblies, were studied. The fast neutron flux distribution in a regular hexagon fuel assembly was first analyzed by varying VF and pitch. It was demonstrated that changing VF is more effective in reducing the fast neutron flux in both global and local graphite blocks. Flattening the fast neutron flux distribution of a commercial MSR core was then carried out by zoning the core into two regions under different VFs. Considering both the fast neutron flux distribution and burnup depth, an optimized core was obtained. The fast neutron flux distribution of the optimized core was further flattened by the rational arrangement of control rod channels. The calculation results show that the final optimized core could reduce the maximum fast neutron flux of the graphite blocks by about 30% and result in a more negative temperature reactivity coefficient, while slightly decreasing the burnup and maintaining a fully acceptable core temperature distribution.

Abstract Background Malnutrition increases the risk of poor prognosis in patients with cardiovascular disease, and our current research was designed to assess the predictive performance of the Geriatric Nutrition Risk Index (GNRI) for the occurrence of poor prognosis after percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (SCAD) and to explore possible thresholds for nutritional intervention. Methods This study retrospectively enrolled newly diagnosed SCAD patients treated with elective PCI from 2014 to 2017 at Shinonoi General Hospital, with all-cause death as the main follow-up endpoint. Cox regression analysis and restricted cubic spline (RCS) regression analysis were used to explore the association of GNRI with all-cause death risk and its shape. Receiver operating characteristic curve (ROC) analysis and piecewise linear regression analysis were used to evaluate the predictive performance of GNRI level at admission on all-cause death in SCAD patients after PCI and to explore possible nutritional intervention threshold points. Results The incidence of all-cause death was 40.47/1000 person-years after a mean follow-up of 2.18 years for 204 subjects. Kaplan-Meier curves revealed that subjects at risk of malnutrition had a higher all-cause death risk. In multivariate Cox regression analysis, each unit increase in GNRI reduced the all-cause death risk by 14% (HR 0.86, 95% CI 0.77, 0.95), and subjects in the GNRI > 98 group had a significantly lower risk of death compared to those in the GNRI

Abstract Background Toxocara canis is considered one of the most neglected parasitic zoonoses and threatens the health of millions of people worldwide with a predilection for pediatric and adolescent populations in impoverished communities. Exploring the invasion and developmental mechanisms associated with T. canis infection in its definitive canine hosts will help to better control zoonotic toxocariasis. Methods Proteomic changes in samples from the upper lobe of the left lung of Beagle puppies were systematically analyzed by quantitative proteomic technology of data-independent acquisition (DIA) at 96 h post-infection (hpi) with T. canis. Proteins with P-values 1.5 or

Abstract Background Body mass index (BMI) and lipid disorders are both known to be strongly associated with the development of diabetes, however, the indirect effect of lipid parameters in the BMI-related diabetes risk is currently unknown. This study aimed to investigate the mediating role of lipid parameters in the association of BMI with diabetes risk. Methods We assessed the association of diabetes risk with BMI, as well as lipid parameters including high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-CF and LDL-CS), triglycerides(TG), total cholesterol(TC), remnant cholesterol(RC), non-HDL-C, and combined indices of lipid parameters with HDL-C (RC/HDL-C ratio, TG/HDL-C ratio, TC/HDL-C ratio, non-HDL/HDL-C ratio, LDL/HDL-C ratio) using data from 15,453 subjects in the NAGALA project. Mediation models were used to explore the mediating role of lipid parameters in the association of BMI with diabetes risk, and mediation percentages were calculated for quantifying the strength of the indirect effects. Finally, receiver operating characteristic curve (ROC) analysis was used to compare the accuracy of BMI and BMI combined with lipid parameters in predicting incident diabetes. Results Multivariate regression models, adjusted for confounding factors, demonstrated robust associations of lipid parameters, BMI, with diabetes risk, with the exception of TC, LDL-CF, LDL-CS, and non-HDL-C. Mediation analysis showed that lipid parameters except TC, LDL-CF, LDL-CS, and Non-HDL-C were involved in and mediated the association of BMI with diabetes risk, with the largest mediation percentage being the RC/HDL-C ratio, which was as high as 40%; it is worth mentioning that HDL-C and HDL-C-related lipid ratio parameters also play an important mediating role in the association between BMI and diabetes, with the mediator proportion being greater than 30%. Finally, based on the ROC results, we found that the prediction performance of all lipid parameters in the current study except TC was significantly improved when combined with BMI. Conclusion Our fresh findings suggested that lipid parameters partially mediated the association of BMI with diabetes risk; this result indicated that in the context of diabetes risk screening and disease management, it is important to not only monitor BMI but also pay attention to lipid parameters, particularly HDL-C and HDL-C-related lipid ratio parameters.

Abstract Background Preeclampsia is a pregnancy-specific disease leading to maternal and perinatal morbidity. Hypertension and inflammation are the main characteristics of preeclampsia. Many factors can lead to hypertension and inflammation, including gut microbiota which plays an important role in hypertension and inflammation in humans. However, alterations to the gut microbiome and fecal metabolome, and their relationships in severe preeclampsia are not well known. This study aims to identify biomarkers significantly associated with severe preeclampsia and provide a knowledge base for treatments regulating the gut microbiome. Methods In this study, fecal samples were collected from individuals with severe preeclampsia and healthy controls for shotgun metagenomic sequencing to evaluate changes in gut microbiota composition. Quantitative polymerase chain reaction analysis was used to validate the reliability of our shotgun metagenomic sequencing results. Additionally, untargeted metabolomics analysis was performed to measure fecal metabolome concentrations. Results We identified several Lactobacillaceae that were significantly enriched in the gut of healthy controls, including Limosilactobacillus fermentum, the key biomarker distinguishing severe preeclampsia from healthy controls. Limosilactobacillus fermentum was significantly associated with shifts in KEGG Orthology (KO) genes and KEGG pathways of the gut microbiome in severe preeclampsia, such as flagellar assembly. Untargeted fecal metabolome analysis found that severe preeclampsia had higher concentrations of Phenylpropanoate and Agmatine. Increased concentrations of Phenylpropanoate and Agmatine were associated with the abundance of Limosilactobacillus fermentum. Furthermore, all metabolites with higher abundances in healthy controls were enriched in the arginine and proline metabolism pathway. Conclusion Our research indicates that changes in metabolites, possibly due to the gut microbe Limosilactobacillus fermentum, can contribute to the development of severe preeclampsia. This study provides insights into the interaction between gut microbiome and fecal metabolites and offers a basis for improving severe preeclampsia by modulating the gut microbiome.

ABSTRACT: Xanthine oxidase (XO), a rate-limiting enzyme in uric acid production, is the pivotal therapeutic target for gout and hyperuricemia. In this study, 57 peptides from α-lactalbumin and β-lactoglobulin were obtained via virtual enzymatic hydrolysis, and 10 XO inhibitory peptides were virtually screened using molecular docking. Then toxicity, allergenicity, solubility, and isoelectric point of the obtained 10 novel peptides were evaluated by in silico tools. The XO activity of these synthetic peptides was tested using an in vitro assay by high-performance liquid chromatography. Their inhibitory mechanism was further explored by molecular docking. The results showed that 4 peptides GL, PM, AL, and AM exhibited higher inhibitory activity, and their half maximal inhibitory concentration in vitro was 10.20 ± 0.89, 23.82 ± 0.94, 34.49 ± 0.89, and 40.45 ± 0.92 mM, respectively. The peptides fitted well with XO through hydrogen bond, hydrophobic interaction, and van der Waals forces, and amino acid residues Glu802, Leu873, Arg880, and Pro1076 played an important role in this process. Overall, this study indicated 4 novel peptides GL, PM, AL, and AM from whey protein exhibited XO inhibitory activity, and they might be useful and safe XO inhibitors for hyperuricemia prevention and treatment.

Objective This study aimed to evaluate the effects of 2 endoscopic spine surgeries on the biomechanical properties of normal and osteoporotic spines. Methods Based on computed tomography images of a healthy adult volunteer, 6 finite element models were created. After validating the normal intact model, a concentrated force of 400 N and a moment of 7.5 Nm were exerted on the upper surface of L3 to simulate 6 physiological activities of the spine. Five types of indices were used to assess the biomechanical properties of the 6 models, range of motion (ROM), maximum displacement value, intervertebral disc stress, maximum stress value, and articular protrusion stress, and by combining them with finite element stress cloud. Results In normal and osteoporotic spines, there was no meaningful change in ROM or disc stress in the 2 surgical models for the 6 motion states. Model N1 (osteoporotic percutaneous transforaminal endoscopic discectomy model) showed a decrease in maximum displacement value of 20.28% in right lateral bending. Model M2 (unilateral biportal endoscopic model) increased maximum displacement values of 16.88% and 17.82% during left and right lateral bending, respectively. The maximum stress value of L4–5 increased by 11.72% for model M2 during left rotation. In addition, using the same surgical approach, ROM, maximum displacement values, disc stress, and maximum stress values were more significant in the osteoporotic model than in the normal model. Conclusion In both normal and osteoporotic spines, both surgical approaches were less disruptive to the physiologic structure of the spine. Furthermore, using the same endoscopic spine surgery, normal spine biomechanical properties are superior to osteoporotic spines.

Abstract In this study we aimed to investigate the prevalence of SARS-CoV-2 infection in psoriasis patients, and outcomes of SARS-CoV-2 infection and associated risk factors. A cross-sectional survey was conducted from February 2023 to March 2023. Information was obtained with online questionnaire about psoriasis patients on demographic characteristics, clinical characteristics, SARS-CoV-2 infection and outcomes, vaccination, and routine protection against COVID-19. Logistic regression analysis was used to explore risk factors with SARS-CoV-2 infection and exacerbation of psoriasis. A total of 613 participants were recruited. 516 (84.2%) were infected, and associated factors were sex, working status, routine protection against COVID-19, COVID-19 vaccination, impaired nail, infection exacerbate psoriasis, and severity of psoriasis. Among the patients infected with SARS-CoV-2, 30 (5.8%) required hospitalization, 122 (23.6%) had psoriasis exacerbation due to SARS-CoV-2 infection, and associated factors were subtype of psoriasis, discontinuation of psoriasis treatment during SARS-CoV-2 infection, response following COVID-19 vaccination, and severity of psoriasis. Booster dose vaccination contributed a low probability of COVID-19 sequelae. COVID-19 vaccine’s effectiveness was unsatisfactory, while booster dose vaccination reduced the occurrence of COVID-19 sequelae in psoriasis patients of Southwest China. Patients treated with psoriasis shown to be safe, without a higher incidence of SARS-CoV-2 infection or COVID-19hospitalization compared to untreated patients. Stopping treatment during SARS-CoV-2 infection led to psoriasis exacerbation, so psoriasis treatment could be continued except severe adverse reaction.

Abstract Background Insulin resistance (IR) plays a crucial role in the occurrence and progression of diabetes. This study aimed to evaluate and compare the predictive value of four IR surrogates, including the triglycerides glucose (TyG) index, TyG and body mass index (TyG-BMI), triglycerides/high-density lipoprotein cholesterol (TG/HDL-C) ratio, and the metabolic score for IR (MetS-IR) for diabetes in two large cohorts. Methods A total of 116,661 adult participants from the China Rich Healthcare Group and 15,464 adult participants from the Japanese NAGALA cohort were included in the study. Multivariable Cox proportional hazards models were used to assess the standardized hazard ratio (HR) of the TyG index, TyG-BMI, TG/HDL-C ratio, and MetS-IR directly associated with diabetes. Receiver operating characteristic (ROC) curve and time-dependent ROC curve analysis were performed to evaluate and compare the predictive value of the four IR surrogates for diabetes. Results In the two independent cohorts, the average follow-up time was 3.1 years in the China cohort, with 2681(2.30%) incident cases of diabetes recorded, and 6.13 years in the Japan cohort, with 373 incident cases (2.41%) of diabetes recorded. After adjusting for potential confounding factors, we found that among the four IR surrogates, TyG-BMI and MetS-IR showed stronger associations with diabetes. The stronger associations persisted even after further stratification by age, sex, hypertension, and obese subgroups. In terms of diabetes prediction, based on ROC analysis, TyG-BMI demonstrated the highest predictive accuracy for diabetes in the Chinese population, while both TyG-BMI and MetS-IR showed the highest predictive accuracy in the Japanese population. The results of further subgroup ROC analysis confirmed the robustness of these findings. Furthermore, the time-dependent ROC results indicated that among the four IR surrogates, MetS-IR exhibited the highest accuracy in predicting future diabetes at various time intervals in the Japanese population. Conclusion Our findings suggest that evaluating TyG-BMI and MetS-IR as IR surrogates may be the most useful for predicting diabetes events and assessing the risk of developing diabetes in East Asian populations.

Abstract Background Prediabetes is a high-risk state for diabetes, and numerous studies have shown that the body mass index (BMI) and triglyceride-glucose (TyG) index play significant roles in risk prediction for blood glucose metabolism. This study aims to evaluate the relative importance of BMI combination with TyG index (TyG-BMI) in predicting the recovery from prediabetic status to normal blood glucose levels. Methods A total of 25,397 prediabetic subjects recruited from 32 regions across China. Normal fasting glucose (NFG), prediabetes, and diabetes were defined referring to the American Diabetes Association (ADA) criteria. After normalizing the independent variables, the impact of TyG-BMI on the recovery or progression of prediabetes was analyzed through the Cox regression models. Receiver Operating Characteristic (ROC) curve analysis was utilized to visualize and compare the predictive value of TyG-BMI and its constituent components in prediabetes recovery/progression. Results During the average observation period of 2.96 years, 10,305 individuals (40.58%) remained in the prediabetic state, 11,278 individuals (44.41%) recovered to NFG, and 3,814 individuals (15.02%) progressed to diabetes. The results of multivariate Cox regression analysis demonstrated that TyG-BMI was negatively associated with recovery from prediabetes to NFG and positively associated with progression from prediabetes to diabetes. Further ROC analysis revealed that TyG-BMI had higher impact and predictive value in predicting prediabetes recovering to NFG or progressing to diabetes in comparison to the TyG index and BMI. Specifically, the TyG-BMI threshold for predicting prediabetes recovery was 214.68, while the threshold for predicting prediabetes progression was 220.27. Additionally, there were significant differences in the relationship of TyG-BMI with prediabetes recovering to NFG or progressing to diabetes within age subgroups. In summary, TyG-BMI is more suitable for assessing prediabetes recovery or progression in younger populations (

Abstract Background Obesity is the most important driver of non-alcoholic fatty liver disease (NAFLD); nevertheless, the relationship of weight-adjusted waist index (WWI), a new obesity index, with NAFLD is unclear. Methods This retrospective study used data from the NAGALA project from 1994 to 2016. WWI values were calculated using waist circumference (WC) and weight measurements of the participants. Three stepwise adjusted logistic regression models were developed to assess the relationship of WWI with NAFLD in the whole population and in both sexes. Additionally, we also conducted a series of exploratory analysis to test the potential impact of body mass index (BMI), age, smoking status and exercise habits on the association of WWI with NAFLD. Receiver operating characteristic (ROC) curves were used to estimate cut-off points for identifying NAFLD in the entire population and in both sexes. Results The current study included a population of 11,805 individuals who participated in health screenings, including 6,451 men and 5,354 women. After adjusting for all non-collinear variables in the multivariable logistic regression model, we found a significant positive correlation of WWI with NAFLD. For each unit increase in WWI, the risk of NAFLD increased by 72% in the entire population, by 84% in men, and by 63% in women. Furthermore, subgroup analyses revealed no significant discrepancies in the correlation of WWI with NAFLD across individuals with varying ages, exercise habits, and smoking status (all P-interaction > 0.05), except for different BMI groups (P-interaction

The TMSR-SF0 simulator is an integral effect thermal-hydraulic experimental system for the development of thorium molten salt reactor (TMSR) program in China. The simulator has two heat transport loops with liquid FLiNaK. In literature, the 95% level confidence uncertainties of the thermophysical properties of FLiNaK are recommended, and the uncertainties of density, heat capacity, thermal conductivity and viscosity are ±2%, ±10, ±10% and ±10% respectively. In order to investigate the effects of thermophysical properties uncertainties on the molten salt heat transport system, the uncertainty and sensitivity analysis of the heat transfer characteristics of the simulator system are carried out on a RELAP5 model. The uncertainties of thermophysical properties are incorporated in simulation model and the Monte Carlo sampling method is used to propagate the input uncertainties through the model. The simulation results indicate that the uncertainty propagated to core outlet temperature is about ±10°C with a confidence level of 95% in a steady-state operation condition. The result should be noted in the design, operation and code validation of molten salt reactor. In addition, more experimental data is necessary for quantifying the uncertainty of thermophysical properties of molten salts.

An ultrasensitive electrochemical immunosensor was developed for detection of the cervical squamous cell carcinoma antigen (SCCA) biomarker using graphene-chitosan nanocomposites. Graphene oxide (GO) synthesized by a modified Hummer’s method was functionalized with chitosan biopolymer (CS) to produce CS-GO nanocomposites. Characterization by SEM, FTIR, Raman, XPS confirmed successful grafting of CS onto GO by electrostatic interactions. The CS-GO composite exhibited improved conductivity and biocompatibility. After optimizing the GO:CS ratio to 1:1, the nanocomposite was deposited on glassy carbon electrodes (GCE). Anti-SCCA antibodies were then immobilized covalently using pyrenebutyric acid crosslinker. The immunosensor fabrication was analyzed by EIS, CV, and DPV electrochemical techniques. The conditions including CS-GO ratio, antibody concentration, incubation time, pH, and voltage parameters were systematically optimized using orthogonal experimental design. Under optimal conditions, the immunosensor showed a linear detection range from 1 pg/mL to 100 ng/mL with a sensitivity of 196 μA/(ng/mL/cm2). The low limit of detection of 1 pg/mL was attributed to the high surface area and conductivity of the CS-GO transducer. Analysis of human serum samples spiked with SCCA demonstrated the reliability of the immunosensor for clinical applications. The graphene-nanocomposite electrochemical biosensing platform provides a rapid, low-cost, and ultrasensitive alternative to ELISA for SCCA detection in cervical cancer diagnostics.

A novel embedded GFRP grid framework-UHPC composite plate without steel rebar was proposed to solve the problems of conventional reinforced concrete plate, such as heavy weight, easily cracking and poor durability. The composite plate is expected to be superior in mechanical mechanism and durability benefiting from the combination of UHPC and GFRP, and only minimal construction process was needed. The flexural properties of the novel composite plate, varying in centroid height of GFRP grid and loading shear span ratio, were investigated via four-point loading tests. The failure mode, load-deflection curve, sectional strain and ductility of the composite plate were analyzed. Experimental results showed that the flexural failure process of the composite plate could be divided into three stages: elastic stage, working stage with cracks and descent stage. The flexural failure of the composite plate was characterized by the tensile fracture of GFRP grid. The flexural bearing capacity and stiffness of the composite plate can be significantly improved, since the GRFP grid was more completely tensioned as the centroid of the embedded GFRP grid framework fell. The maximum bearing capacity of composite plates could reach 317.9 kN when the distance between GFRP grid and the plate bottom was 25 mm and the shear span ratio was 1.5. Shear failure was only observed in the composite plate with the distance between GFRP grid and the plate bottom of 0 mm and the shear span ratio of 1.5. Finite element (FE) models were established considering both geometric and material nonlinearities to further analyze the flexural failure mechanism of the composite plate. The reliable connection between GFRP grid and UHPC without additional shear connector was proved, and the numerical results coincided well with the experimental ones. Finally, the calculation method introducing the stress distribution non-uniformity coefficient of the GFRP grid plate was proposed to predict the flexural capacity of the composite plate.

The Tibetan region is characterized by long winters and large diurnal temperature variations. Using prefabricated bridges combined with a small amount of cast-in-place concrete joints can address the challenging construction environment. To extend the bridge construction window for concrete in the joint, the performance of Ultra-High Performance Concrete (UHPC) under alternating positive and negative temperature environments was investigated. The effects of curing conditions (−10 to 10 °C and natural curing), different proportions of sulfoaluminate cement (0% / 6%), different concrete materials (UHPC/NC), and the presence of antifreeze admixtures on the macro-strength and late-stage microstructure of UHPC were explored. The results indicated that the slump expansion of the prepared UHPC in this study exceeds 600 mm. Alternating temperature environments significantly degrade the mechanical properties of UHPC without antifreeze admixtures. However, for self-made UHPC with antifreeze admixtures, the formed early structure can prevent freeze-thaw damage as long as the critical antifreeze strength is reached. After the temperature rebounded, the later-stage strength of UHPC can continue to develop and reach the compressive strength of samples that had not been exposed to low-temperature curing. The appropriate addition of sulfate aluminate cement positively affected the early compressive strength (1 day) and elastic modulus of UHPC. It also reduces the drying shrinkage of UHPC.

ObjectiveArteriosclerosis is a primary causative factor in cardiovascular diseases. This study aims to explore the correlation between the atherogenic index of plasma (AIP) and the 30-day mortality rate in patients with acute decompensated heart failure (ADHF).MethodsA total of 1,248 ADHF patients recruited from the Jiangxi-Acute Decompensated Heart Failure1 (JX-ADHF1) cohort between 2019 and 2022 were selected for this study. The primary outcome was the 30-day mortality rate. Multivariable Cox regression, restricted cubic splines (RCS), and stratified analyses were utilized to assess the relationship between AIP and the 30-day mortality rate in ADHF patients. Mediation models were employed for exploratory analysis of the roles of inflammation, oxidative stress, and nutrition in the association between AIP and the 30-day mortality rate in ADHF patients.ResultsDuring the 30-day follow-up, 42 (3.37%) of the ADHF patients died. The mortality rates corresponding to the quartiles of AIP were as follows: Q1: 1.28%, Q2: 2.88%, Q3: 2.88%, Q4: 6.41%. The multivariable Cox regression revealed a positive correlation between high AIP and the 30-day mortality rate in ADHF patients [Hazard ratio (HR) 3.94, 95% confidence interval (CI): 1.08–14.28], independent of age, gender, heart failure type, cardiac function classification, and comorbidities. It is important to note that there was a U-shaped curve association between AIP (

Abstract Background Atherosclerosis is closely linked with glucose metabolism. We aimed to investigate the role of the atherogenic index of plasma (AIP) in the reversal of prediabetes to normal blood glucose levels or its progression to diabetes. Methods This multi-center retrospective cohort study included 15,421 prediabetic participants from 32 regions across 11 cities in China, under the aegis of the Rich Healthcare Group’s affiliated medical examination institutions. Throughout the follow-up period, we monitored changes in the glycemic status of these participants, including reversal to normal fasting glucose (NFG), persistence in the prediabetic state, or progression to diabetes. Segmented regression, stratified analysis, and restricted cubic spline (RCS) were performed based on the multivariable Cox regression model to evaluate the association between AIP and the reversal of prediabetes to NFG or progression to diabetes. Results During a median follow-up period of 2.9 years, we recorded 6,481 individuals (42.03%) reverting from prediabetes to NFG, and 2,424 individuals (15.72%) progressing to diabetes. After adjusting for confounders, AIP showed a positive correlation with the progression from prediabetes to diabetes [(Hazard ratio (HR) 1.42, 95% confidence interval (CI):1.24–1.64)] and a negative correlation with the reversion from prediabetes to NFG (HR 0.89, 95%CI:0.81–0.98); further RCS demonstrated a nonlinear relationship between AIP and the reversion from prediabetes to NFG/progression to diabetes, identifying a turning point of 0.04 for reversion to NFG and 0.17 for progression to diabetes. In addition, we observed significant differences in the association between AIP and reversion from prediabetes to NFG/progression to diabetes across age subgroups, specifically indicating that the risk associated with AIP for progression from prediabetes to diabetes was relatively higher in younger populations; likewise, a younger age within the adult group favored the reversion from prediabetes to NFG in relation to AIP. Conclusion Our study, for the first time, reveals a negative correlation between AIP and the reversion from prediabetes to normoglycemia and validates the crucial role of AIP in the risk assessment of prediabetes progression. Based on threshold analysis, therapeutically, keeping the AIP below 0.04 was of paramount importance for individuals with prediabetes aiming for reversion to NFG; preventatively, maintaining AIP below 0.17 was vital to reduce the risk of diabetes onset for those with prediabetes.

Abstract This study delves into the polarization properties of various hair colors using several techniques, including polarization ray tracing, full Stokes, and Mueller matrix imaging. Our analysis involved studying hair in both indoor and outdoor settings under varying lighting conditions. Our results demonstrate a strong correlation between hair color and the degree of linear polarization. Specifically, light-colored hair, such as white and blond, exhibits high albedo and low DoLP. In contrast, dark hair, like black and brown hair, has low albedo and high DoLP. Our research also revealed that a single hair strand displays high diattenuation near specular reflections but high depolarization in areas with diffuse reflections. Additionally, we investigated the wavelength dependency of the polarization properties by comparing the Mueller matrix under illumination at 450 nm and 589 nm. Our investigation demonstrates the impact of hair shade and color on polarization properties and the Umov effect.

Abstract Background Toxoplasma gondii is an intracellular protozoan parasite that can infect a wide range of warm-blooded animals, including humans. It poses significant health risks, particularly in immunocompromised individuals and during pregnancy, leading to severe disease manifestations. The liver, being a crucial organ involved in immune response and metabolic regulation, plays a critical role in the host's defense against T. gondii infection. Methods In this study, we utilized RNA sequencing to investigate the expression profiles of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in the liver of mice infected with T. gondii. By employing this method, we obtained a comprehensive overview of the alterations in gene expression occurring in the liver during infection. Results By comparing the infected groups to the control groups, we identified numerous differentially expressed lncRNAs DElncRNAs and DEmRNAs at two stages of infection. Specifically, at the acute infection stage, we found 628 DElncRNAs, and 6346 DEmRNAs. At the chronic infection stage, we identified 385 DElncRNAs and 2513 DEmRNAs. Furthermore, we identified 1959 commonly expressed DEmRNAs, including IL27, Nos2, and Cxcr2, across two infection stages. Enrichment and co-location analyses revealed pathways linked to immune and inflammatory responses during T. gondii infection. Notably, through co-location analysis, our analysis revealed several DElncRNAs, including Gm29156, Gm29157, and Gm28644, which are potentially implicated in the progression of liver inflammation induced by T. gondii. Additionally, functional enrichment analysis disclosed stage-specific characteristics of liver inflammation and immune response, alongside changes in metabolic regulation and immunosuppression pathways. Conclusions Our findings provide valuable insights into the expression patterns of lncRNAs and mRNAs in the liver at different stages of T. gondii infection. We identified potential regulatory factors and pathways implicated in liver inflammation, thereby enhancing our understanding of the molecular mechanisms underlying liver inflammation and immune responses during T. gondii infection. These findings could contribute to the development of targeted therapeutic strategies for liver inflammation in the context of T. gondii infection. Graphical Abstract

ObjectiveWhile hypertension is a well-recognized risk factor for non-alcoholic fatty liver disease (NAFLD), the specific roles of various common blood pressure measurements [diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure (PP), mean arterial pressure (MAP)] in detecting NAFLD and evaluating the associated risk in adults remain unclear.MethodsA retrospective analysis was conducted on 14,251 adult participants undergoing health screenings in the NAfld in the Gifu Area, Longitudinal Analysis project (NAGALA). Following the Z-transformation of the independent variables, we evaluated the relationships between the four blood pressure indices and NAFLD through multivariable logistic regression models. This analysis documented the odds ratio (OR) and 95% confidence interval (CI) for each standard deviation (SD) increase. Additionally, the effectiveness of these indices in identifying NAFLD was comparatively analyzed using receiver operating characteristic (ROC) curves.ResultsAfter adequately adjusting for confounders, all blood pressure indices except PP showed a positive correlation with NAFLD. For each SD increment, MAP had the strongest association with NAFLD compared to SBP and DBP. This finding was confirmed in populations without exercise habits, under 60 years of age, with normal blood pressure, and in non-obese groups. Furthermore, based on ROC analysis, MAP was found to have the highest accuracy in identifying NAFLD compared to the other three blood pressure indices.ConclusionAmong the four blood pressure indices evaluated, MAP demonstrates the greatest efficacy in identifying NAFLD and assessing its associated risk. These findings underscore the potential of MAP as the most promising blood pressure index for screening NAFLD.

The Last Planner System (LPS) is a production planning and control system based on Lean Construction (LC) principles. Effectively implementing the LPS in the construction industry remains challenging, impeding the realization of LC principles. Automation of planning and control in the LPS has gained attention to address this challenge. However, research exploring the state-of-the-art of such automation and its impacts on realizing LC principles is still lacking. Therefore, this study performed a systematic literature review of 112 relevant studies, identifying 50 functionalities and associated benefits of automation across six LPS stages, with the lookahead planning stage having the maximum functionalities. Analyzing their interactions with LC principles revealed that automated planning and control in the LPS can support achieving ten LC principles. Future research directions are suggested in areas such as constraint management, knowledge reuse, dynamic replanning, and construction workforce training.

Abstract This study aimed to assess the safety, pharmacokinetics, and food impact on sudapyridine (WX‐081), a novel drug designed to inhibit mycobacterium ATP synthase, with clinical applications for drug‐resistant tuberculosis (TB) treatment. The research comprised two arms: a single ascending dose (SAD) arm (30 to 600 mg, N = 52) and a multiple ascending dose (MAD) arm (200 to 400 mg, N = 30). The influence of food was evaluated using a 400 mg dose within an SAD cohort. Plasma concentrations of WX‐081 and M3 (main metabolite of WX‐081) were analyzed using a validated liquid‐chromatography tandem mass spectrometry method. In the SAD arm, mean residence time (MRT0‐t), terminal half‐life, and clearance of WX‐081 ranged from 18.87 to 52.8 h, 31.39 to 236.57 h, and 6.4 to 80.34 L/h, respectively. The area under the curve from time zero to the last measurable timepoint (AUC0‐t) of WX‐081 showed dose‐proportional increases in the SAD arm. The disparity between fasted and fed states of WX‐081 was significant (p

Abstract Background With growing cases of breast cancer, WeChat public account, an important information publishing platform of WeChat, has become a breast cancer treatment health information provider to a huge audience. It is essential for health information to possess high-level accuracy and reliability. This work evaluates the quality of health information on breast cancer treatment in WeChat public accounts (WPAs), to benefit the patients while making treatment decisions and provide WPA authors with suggestions on publishing high-quality treatment health information. Methods With “breast cancer” as keywords, searches were implemented on weixin.sogou.com and the WeChat app. The WPAs oriented to patients with breast cancer were selected, and the four latest articles of each WPA were included in a set to be evaluated with DISCERN. Results A total of 37 WPAs and 136 articles published by them were included. The accounts operated by individual users were 54%. The median of overall quality of 136 articles was 44 (interquartile range = 10.75) and ranked as “fair”, of which only 28 (21%) were of “good” or higher quality. Among these articles, 74 (54%) were related to medical treatments, and 13 of them mentioned clinical trials; 36 (27%) dealt with surgery. 101 (74.26%) omitted additional sources of information; 102 (75%) did not explicitly suggest shared decision-making. A significant difference was not found in the dimensions “reliability of the articles” and “specific details of information on treatment choices” between the distinct categories of account subjects and various treatment options (P > 0.05). Conclusions The quality of the articles on breast cancer treatment health information in WPAs was moderate. WPA producers should focus on improving the reliability of information and providing more details on treatment options, to assist patients in making optimal decisions during treatment.

Abstract The kidney reabsorbs large amounts of glucose through Na+-glucose cotransporter 2 (SGLT2). P4-ATPase acts together with the β-subunit TMEM30A to mediate the asymmetric distribution of phosphatidylserine (PS), phosphatidylethanolamine (PE), and other amino phospholipids, promoting plasma membrane and internal vesicle fusion, and facilitating vesicle protein transport. We observed reduced TMEM30A expression in renal tubules of DKD and IgA patients, suggesting a potential role of TMEM30A in renal tubular cells. To investigate the role of TMEM30A in renal tubules, we constructed a TMEM30A knockdown cell model by transfecting mouse kidney tubular epithelium cells (TCMK-1) with TMEM30A shRNA. Knockdown of TMEM30A in TCMK-1 cells attenuated vesicle transporter protein synthesis, resulting in reduced transport and expression of SGLT2, which in turn reduced glucose absorption. These data suggested that TMEM30A plays a crucial role in renal tubules.

Abstract Background The 1RS arm of wheat-rye 1BL.1RS translocations contains several subtelomeric tandem repeat families. To study the effect of the difference in the composition of these tandem repeats on the meiotic recombination of 1RS arms can help to enrich the genetic diversity of 1BL.1RS translocation chromosomes. Results Five wheat-rye 1BL.1RS translocation cultivars/lines were used to build two cross combinations including group 1 (20T401 × Zhou 8425B, 20T401 × Lovrin 10 and 20T401 × Chuannong 17) and group 2 (20T360-2 × Zhou 8425B, 20T360-2 × Lovrin 10 and 20T360-2 × Chuannong 17). Oligonucleotide (oligo) probes Oligo-s120.3, Oligo-TR72, and Oligo-119.2-2 produced the same signal pattern on the 1RS arms in lines 20T401 and 20T360-2, and another signal pattern in the three cultivars Zhou 8425B, Lovrin 10 and Chuannong 17. The Oligo-pSc200 signal disappeared from the 1RS arms of the line 20T401, and the signal intensity of this probe on the 1RS arms of the line 20T360-2 was weaker than that of the three cultivars. The five cultivars/lines had the same signal pattern of the probe Oligo-pSc250. The recombination rate of 1RS arms in group 1 was significantly lower than that in group 2. In the progenies from group 1, unequal meiotic recombination in the subtelomeric pSc119.2 and pSc250 tandem repeat regions, and a 1BL.1RS with inversion of 1RS segment between the pSc200 and the nucleolar organizer region were found. Conclusions This study provides a visual tool to detect the meiotic recombination of 1RS arms. The meiotic recombination rate of 1RS arms was affected by the variation of pSc200 tandem repeat, indicating the similar composition of subtelomeric tandem repeats on these arms could increase their recombination rate. These results indicate that the 1RS subtelomeric structure will affect its recombination, and thus the localization of genes on 1RS by means of meiotic recombination might also be affected.

ObjectiveEvery distinct liver enzyme biomarker exhibits a strong correlation with non-alcoholic fatty liver disease (NAFLD). This study aims to comprehensively analyze and compare the associations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) with NAFLD from a gender perspective.MethodsThis study was conducted on 6,840 females and 7,411 males from the NAGALA cohort. Multivariable logistic regression analysis was used to compare the associations between liver enzyme markers and NAFLD in both genders, recording the corresponding adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Receiver operating characteristic (ROC) curves were used to evaluate the accuracy of individual liver enzyme markers and different combinations of them in identifying NAFLD.ResultsLiver enzyme markers ALT, AST, and GGT were all independently associated with NAFLD and exhibited significant gender differences (All P-interaction

A large number of early hollow slab beams suffer from inadequate load carrying capacity, stiffness and durability, resulting from the overloading, environmental deterioration mechanism and poor maintenance. Most of the existing studies on the reinforcement of pre-damaged reinforced concrete beam carried out in scale-down models. However, the artificial pre-damage (mechanical damage and accelerated corrosion) alters the deterioration mechanism of reinforced concrete beam. The scale effect leads to disparities in force ratios acting on scale-down models and full-scale structures. To solve these problems, three 15-year-old full-scale hollow slab beams (taken from a serving bridge in Guangxi, China, with 15.96 m long) were respectively strengthened with steel-reinforced UHPC layer, GFRP-reinforced UHPC layer and CFRP layer. The flexural behaviors of the strengthened beams and the control beam were investigated by field four-point bending test and numerical simulation. The experimental results indicate that the ultimate flexural load capacity and stiffness of hollow slab beams after strengthened are respectively increased by 17.6%− 47.1% and 4.7%− 17.9%, and the deflection under service load is decreased by 7.6%− 19.1%. Meanwhile, UHPC is beneficial to improve the energy absorption capacity of hollow slab beams. Moreover, the main bearer of load is the tensile steel bars in the hollow slab beams and the reinforcement layers played an auxiliary role in load bearing. Finally, the accurate prediction formulas for the ultimate flexural load of strengthened hollow slab beams with a maximum error of only 3.5% were proposed.

Ultra-high performance concrete (UHPC) as a joint material for precast bridge decks might reduce the width of the joint and improve its connection performance and durability. This study proposes a type of compact UHPC wet joint based on the mechanical properties of UHPC and the force characteristics of transverse joints in prefabricated bridge decks. The shear behavior of the novel joint was investigated through experimental study and numerical simulation. In addition, the shear properties of compact UHPC wet joints were compared with epoxy joints. The results indicated that the shear resistances of compact UHPC joints are comparable to those of epoxy joints. The failure process of the precast bridge deck with new joint might be divided into three stages: elastic stage, working stage with cracks, and yield stage. No interface cracks or reinforcement slippage was observed throughout the loading process, indicating that the UHPC joint and the epoxy joint exhibited adequate shear resistance. The ultimate load capacity and corresponding mid-span deflection of UHPC joint specimens were respectively increased by 8.6 % and 75.0 %, when compared with the epoxy joint specimens. Finite element analysis reveals that the transverse shear transfer range of the compact UHPC joints is within 57.1 %. Bending failure due to the yielding of the transverse reinforcement at the bottom of the precast bridge deck is the primary failure mode for both specimens. Moreover, the stresses applied to the deck system have good continuity at the joint.

ObjectiveBoth alanine aminotransferase (ALT) and high-density lipoprotein cholesterol (HDL-C) are closely related to glucose homeostasis in the body, and the main objective of this study was to investigate the association between ALT to HDL-C ratio (ALT/HDL-C ratio) and the risk of diabetes in a Chinese population.MethodsThe current study included 116,251 participants who underwent a healthy physical examination, and the study endpoint was defined as a diagnosis of new-onset diabetes. Multivariate Cox regression models and receiver operator characteristic curves were used to assess the association of the ALT/HDL-C ratio with diabetes onset.ResultsDuring the average observation period of 3.10 years, a total of 2,674 (2.3%) participants were diagnosed with new-onset diabetes, including 1,883 (1.62%) males and 791 (0.68%) females. After fully adjusting for confounding factors, we found a significant positive association between the ALT/HDL-C ratio and the risk of diabetes [Hazard ratios 1.06, 95% confidence intervals: 1.05, 1.06], and this association was significantly higher in males, obese individuals [body mass index ≥ 28 kg/m2] and individuals aged < 60 years (All P interaction < 0.05). In addition, the ALT/HDL-C ratio was significantly better than its components ALT and HDL-C in predicting diabetes in the Chinese population.ConclusionThere was a positive relationship between ALT/HDL-C ratio and diabetes risk in the Chinese population, and this relationship was significantly stronger in males, obese individuals, and individuals younger than 60 years old.

ObjectiveThe newly proposed Metabolic Visceral Fat Score (METS-VF) is considered a more effective measure for visceral adipose tissue (VAT) than other obesity indicators. This study aimed to reveal the association between METS-VF and non-alcoholic fatty liver disease (NAFLD), and its variations across age groups within both sexes.MethodsData from 14,251 medical examiners in the NAGALA project were employed in this study. 3D fitted surface plots were constructed based on multivariate logistic regression models to visualize the isolated and combined effects of aging and METS-VF on NAFLD. Receiver operating characteristic curve (ROC) analysis was conducted to compare the diagnostic performance of METS-VF with other VAT surrogate markers in predicting NAFLD.ResultsThe results of multivariate logistic regression analysis showed that each unit increase in METS-VF was independently associated with a 333% and 312% increase in the odds of NAFLD in males and females, respectively. Additionally, the 3D fitted surface plot showed that age significantly influenced the association between METS-VF and the odds of NAFLD in both sexes, as follows: (i) In males, when METS-VF was less than 6.2, the METS-VF-related odds of NAFLD increased gradually with age in the 20-45 age group, reached a plateau in the 45-65 age group, and then decreased in the group above 65 years old; however, when male METS-VF exceeded 6.2, aging and METS-VF combined to further increase the odds of NAFLD in all age groups, particularly in the 45-65 age group. (ii) In females, aging seemed to reduce METS-VF-related odds of NAFLD in the 18-40 age group, but significantly increased it in the 40-60 age group, particularly for those with higher METS-VF levels. Further ROC analysis revealed that compared to other VAT surrogate markers, METS-VF showed the highest diagnostic accuracy for NAFLD in females, especially in those under 45 years of age [area under the curve (AUC) = 0.9256].ConclusionsThis study firstly revealed a significant positive correlation between METS-VF and the odds of NAFLD, with METS-VF surpassing other VAT surrogate markers in NAFLD diagnosis. Moreover, age significantly influenced the METS-VF-related odds of NAFLD and METS-VF’s diagnostic efficacy for NAFLD in both sexes.

This study investigates the critical issue of mental health disparities within diverse populations in modern workplaces, a concern that significantly affects both individuals and organizational structures. By focusing on how prevailing workplace behaviors, including implicit biases, microaggressions, and the scarcity of diversity in leadership, exacerbate these disparities, the research highlights the urgent need for attention and action in this area. The mental health gap—disparities in conditions and access to care among different workplace groups—emerges from systemic inequalities and stigmatization, deeply influencing employee productivity, creativity, collaboration, and retention. Our research underscores the disproportionate impact of this gap on diverse populations, characterized by varying ethnicity, gender, age, socio-economic status, and other unique identity attributes. The paper articulates the substantial economic repercussions for organizations, manifesting as reduced productivity, increased absenteeism, and higher turnover rates. Recommendations include the implementation of cultural competency training, promotion of inclusive leadership, investment in tailored mental health resources and fostering open dialog about mental health. These strategies are pivotal in creating an inclusive, resilient, and harmonious work environment. Our findings aim to catalyze a shift in organizational practices toward mental well-being, advocating for comprehensive strategies to bridge the mental health divide in workplaces, thereby enhancing overall organizational health and cohesion.

ObjectiveThe increasing prevalence of diabetes is strongly associated with visceral adipose tissue (VAT), and gender differences in VAT remarkably affect the risk of developing diabetes. This study aimed to assess the predictive significance of lipid accumulation products (LAP) for the future onset of diabetes from a gender perspective.MethodsA total of 8,430 male and 7,034 female non-diabetic participants in the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) program were included. The ability of LAP to assess the risk of future new-onset diabetes in both genders was analyzed using multivariate Cox regression. Subgroup analysis was conducted to explore the impact of potential modifiers on the association between LAP and diabetes. Additionally, time-dependent receiver operator characteristics (ROC) curves were used to assess the predictive power of LAP in both genders for new-onset diabetes over the next 2-12 years.ResultsOver an average follow-up of 6.13 years (maximum 13.14 years), 373 participants developed diabetes. Multivariate Cox regression analysis showed a significant gender difference in the association between LAP and future diabetes risk (P-interaction

Salvianolic acid A (Sal A), extracted from Danshen, has proven efficacy in preventing cardiovascular diseases. However, its effect on mitigating vascular damage caused by chronic kidney disease remains unclear. This study investigated the therapeutic effects and underlying mechanisms of Sal A in a rat model of 5/6 Nephrectomized (5/6Nx). The results of our study showed that Sal A effectively reduced the levels of kidney injury markers. Histopathological analysis revealed that Sal A dose-dependently attenuated arterial injury. The attenuation was characterized by the thinning of vascular endothelium and reduced endothelial cell hyperplasia, accompanied by decreased expression of OPN and C-Reaction Protein (CRP). Further investigations revealed that Sal A alleviated oxidative stress-induced vascular injury by activating the Phosphoinositide 3-kinase (PI3K)/Protein Kinase B(Akt)/Nuclear factor erythroid2-related factor 2(Nrf2)/Heme Oxygenase 1(HO-1) signaling pathway. Furthermore, Sal A inhibited inflammation by suppressing the Sirtuin-1(SIRT1)/Toll-like receptor 4(TLR4)/Nuclear factor kappa-B(NF-κB)/P38 signaling pathway and reducing the expression of pro-inflammatory cytokines. Our oxidative stress and inflammation cell models also supported these findings. In conclusion, Sal A treatment effectively attenuated vascular injury in 5/6Nx rats and exerted dual antioxidant and anti-inflammatory effects.

Abstract Tissue-dwelling helminths affect billions of people around the world. They are potent manipulators of the host immune system, prominently by promoting regulatory T cells (Tregs) and are generally associated with a modified host gut microbiome. However, the role of the gut microbiota in the immunomodulatory processes for these non-intestinal parasites is still unclear. In the present study, we used an extra-intestinal cestode helminth model-larval Echinococcus multilocularis to explore the tripartite partnership (host-helminth-bacteria) in the context of regulating colonic Tregs in Balb/c mice. We showed that larval E. multilocularis infection in the peritoneal cavity attenuated colitis in Balb/c mice and induced a significant expansion of colonic Foxp3+ Treg populations. Fecal microbiota depletion and transplantation experiments showed that the gut microbiota contributed to increasing Tregs after the helminth infection. Shotgun metagenomic and metabolic analyses revealed that the gut microbiome structure after infection was significantly shifted with a remarkable increase of Lactobacillus reuteri and that the microbial metabolic capability was reprogrammed to produce more Treg cell regulator-short-chain fatty acids in feces. Furthermore, we also prove that the L. reuteri strain elevated in infected mice was sufficient to promote the colonic Treg frequency and its growth was potentially associated with T cell-dependent immunity in larval E. multilocularis infection. Collectively, these findings indicate that the extraintestinal helminth drives expansions of host colonic Tregs through the gut microbes. This study suggests that the gut microbiome serves as a critical component of anti-inflammation effects even for a therapy based on an extraintestinal helminth.

Abstract Background It is known that measuring the triglyceride glucose (TyG) index and TyG-related parameters [triglyceride glucose-body mass index (TyG-BMI), triglyceride glucose-waist circumference (TyG-WC), and triglyceride glucose-waist to height ratio (TyG-WHtR)] can predict diabetes; this study aimed to compare the predictive value of the baseline TyG index and TyG-related parameters for the onset of diabetes at different future periods. Methods We conducted a longitudinal cohort study involving 15,464 Japanese people who had undergone health physical examinations. The subject’s TyG index and TyG-related parameters were measured at the first physical examination, and diabetes was defined according to the American Diabetes Association criteria. Multivariate Cox regression models and time-dependent receiver operating characteristic (ROC) curves were constructed to examine and compare the risk assessment/predictive value of the TyG index and TyG-related parameters for the onset of diabetes in different future periods. Results The mean follow-up period of the current study cohort was 6.13 years, with a maximum of 13 years, and the incidence density of diabetes was 39.88/10,000 person-years. In multivariate Cox regression models with standardized hazard ratios (HRs), we found that both the TyG index and TyG-related parameters were significantly and positively associated with diabetes risk and that the TyG-related parameters were stronger in assessing diabetes risk than the TyG index, with TyG-WC being the best parameter (HR per SD increase: 1.70, 95% CI 1.46, 1.97). In addition, TyG-WC also showed the highest predictive accuracy in time-dependent ROC analysis for diabetes occurring in the short-term (2–6 years), while TyG-WHtR had the highest predictive accuracy and the most stable predictive threshold for predicting the onset of diabetes in the medium- to long-term (6–12 years). Conclusions These results suggest that the TyG index combined with BMI, WC, and WHtR can further improve its ability to assess/predict the risk of diabetes in different future periods, where TyG-WC was not only the best parameter for assessing diabetes risk but also the best risk marker for predicting future diabetes in the short-term, while TyG-WHtR may be more suitable for predicting future diabetes in the medium- to long-term.

This work involves the introduction of niobium oxide into lanthanum aluminate (LaAlO3) via a conventional solid-state reaction technique to yield LaAlO3:Nb (LaNbxAl1−xO3+δ) samples with Nb5+ doping levels ranging from 0.00 to 0.25 mol%. This study presents a comprehensive investigation of the effects of niobium doping on the phase evolution, defect control, and reflectance of LaNbxAl1−xO3+δ powder. Powder X-ray diffraction (XRD) analysis confirms the perovskite structure in all powders, and XRD and transmission electron microscopy (TEM) reveal successful doping of Nb5+ into LaNbxAl1−xO3+δ. The surface morphology was analyzed by scanning electron microscopy (SEM), and the results show that increasing the doping concentration of niobium leads to fewer microstructural defects. Oxygen vacancy defects in different compositions are analyzed at 300 K, and as the doping level increases, a clear trend of defect reduction is observed. Notably, LaNbxAl1−xO3+δ with 0.15 mol% Nb5+ exhibits excellent reflectance properties, with a maximum infrared reflectance of 99.7%. This study shows that LaNbxAl1−xO3+δ powder materials have wide application potential in the field of high reflectivity coating materials due to their extremely low microstructural defects and oxygen vacancy defects.

Abstract Remnant cholesterol (RC) is a highly atherogenic lipid. Previous studies have shown that RC was closely associated with many metabolism-related diseases. However, the relationship of RC with metabolic syndrome (MetS) remains unclear. This study’s objective is to investigate the relationship of RC with MetS. A total of 60,799 adults who received health assessments were included in this study. RC was calculated by subtracting the directly measured values for low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) from total cholesterol (TC) and divided into 5 groups according to its quintile. MetS diagnosis according to National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) definitions. Application of receiver operating characteristic (ROC) curve analysis and multivariate logistic regression to assess the association of RC with MetS. In RC quintile groups, the prevalence of MetS was 0.84, 1.10, 1.92, 3.87 and 37.71%, respectively. Multivariate logical regression analysis showed that RC and MetS maintained a stable independent positive correlation between both sexes. An interaction test further showed that the MetS risk associated with RC was significantly higher in women than in men. Moreover, ROC analysis results showed that RC had high accuracy in identifying MetS, especially among young and middle-aged men [(area under the curve: AUC)

Abstract Background Long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) play crucial roles in regulating various physiological and pathological processes. However, the role of lncRNAs and mRNAs in mediating the liver response during Toxocara canis infection remains incompletely understood. Methods In the present study, the expression profile of lncRNAs and mRNAs was investigated in the liver of Beagle dogs infected by T . canis using high-throughput RNA sequencing. Results Compared with the control groups, 876 differentially expressed (DE) lncRNAs and 288 DEmRNAs were identified at 12 h post-infection (hpi), 906 DElncRNAs and 261 DEmRNAs were identified at 24 hpi, and 876 DElncRNAs and 302 DEmRNAs were identified at 36 days post-infection (dpi). A total of 16 DEmRNAs (e.g. dpp4, crp and gnas) were commonly identified at the three infection stages. Enrichment and co-localization analyses identified several pathways involved in immune and inflammatory responses during T. canis infection. Some novel DElncRNAs, such as LNC_015756, LNC_011050 and LNC_011052, were also associated with immune and inflammatory responses. Also, LNC_005105 and LNC_005401 were associated with the secretion of anti-inflammatory cytokines, which may play a role in the healing of liver pathology at the late stage of infection. Conclusions Our data provided new insight into the regulatory roles of lncRNAs and mRNAs in the pathogenesis of T. canis and improved our understanding of the contribution of lncRNAs and mRNAs to the immune and inflammatory response of the liver during T. canis infection. Graphical Abstract

Abstract Background Tuberculosis (TB) is a serious infectious disease that is one of the leading causes of death worldwide. This study aimed to investigate the spatial and temporal distribution patterns and potential influencing factors of TB incidence risk, and to provide a scientific basis for the prevention and control of TB. Methods We collected reported cases of TB in 38 districts and counties in Chongqing from 2014 to 2020 and data on environment, population characteristics and economic factors during the same period. By constructing a Bayesian spatio-temporal model, we explored the spatio-temporal distribution pattern of TB incidence risk and potential influencing factors, identified key areas and key populations affected by TB, compared the spatio-temporal distribution characteristics of TB in populations with different characteristics, and explored the differences in the influence of various social and environmental factors. Results The high-risk areas for TB incidence in Chongqing from 2014 to 2020 were mainly concentrated in southeastern and northeastern regions of Chongqing, and the overall relative risk (RR) of TB showed a decreasing trend during the study period, while RR of TB in main urban area and southeast of Chongqing showed an increasing trend. The RR of TB was relatively high in the main urban area for the female population and the population aged 0–29 years, and the RR of TB for the population aged 30–44 years in the main urban area and the population aged 60 years or older in southeast of Chongqing had an increasing trend, respectively. For each 1 μg/m3 increase in SO2 and 1% increase in the number of low-income per 1000 non-agricultural households (LINA per 1000 persons), the RR of TB increased by 0.35% (95% CI: 0.08–0.61%) and 0.07% (95% CI: 0.05–0.10%), respectively. And LINA per 1000 persons had the greatest impact on the female population and the over 60 years old age group. Although each 1% increase in urbanization rate (UR) was associated with 0.15% (95% CI: 0.11–0.17%) reduction in the RR of TB in the whole population, the RR increased by 0.18% (95% CI: 0.16–0.21%) in the female population and 0.37% (95% CI: 0.34–0.45%) in the 0–29 age group. Conclusion This study showed that high-risk areas for TB were concentrated in the southeastern and northeastern regions of Chongqing, and that the elderly population was a key population for TB incidence. There were spatial and temporal differences in the incidence of TB in populations with different characteristics, and various socio-environmental factors had different effects on different populations. Local governments should focus on areas and populations at high risk of TB and develop targeted prevention interventions based on the characteristics of different populations.

Abstract Background Body mass index (BMI) and lipid parameters are the most commonly used anthropometric parameters and biomarkers for assessing nonalcoholic fatty liver disease (NAFLD) risk. This study aimed to assess and quantify the mediating role of traditional and non-traditional lipid parameters on the association between BMI and NAFLD. Method Using data from 14,251 subjects from the NAGALA (NAfld in the Gifu Area, Longitudinal Analysis) study, mediation analyses were performed to explore the roles of traditional [total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)] and non-traditional [non-HDL-C, remnant cholesterol (RC), TC/HDL-C ratio, LDL-C/HDL-C ratio, TG/HDL-C ratio, non-HDL-C/HDL-C ratio, and RC/HDL-C ratio] lipid parameters in the association of BMI with NAFLD and quantify the mediation effect of these lipid parameters on the association of BMI with NAFLD using the percentage of mediation. Result After fully adjusting for confounders, multivariate regression analysis showed that both BMI and lipid parameters were associated with NAFLD (All P-value

The SM-MSR (small modular molten salt reactor) has a good prospect for development with regards to combining the superiority of the molten salt reactor and modularization technologies, showing the advantages of safety, reliability, low economic cost and flexibility of site selection. However, because its internal structural parts are not easily replaced, and the outer shielding structure is limited, the lifespan of the reactor vessel and its in-reactor shielding design needs to be addressed. In order to find an optimal shielding model with both high fuel efficiency and strong radiation shielding capability, five different design schemes were proposed in this work, which varied in thickness and boron concentration in inner-shielding materials. The neutron/gamma flux and DPA (displacements per atom)/helium production rates were evaluated to obtain an appropriate scheme. Several beneficial results were obtained. Considering the above factors and the actual manufacturing process, 20 cm-thick boron graphite with a 5 wt% Boron-10 concentration combined with a 1 cm-thick Hastelloy barrel was chosen as the in-reactor shielding structure. Outside the reactor, the neutron flux was reduced to 8.33 × 1010 cm−2 s−1, and the gamma flux was decreased to 1.13 × 1011 cm−2 s−1. The vessel/barrel material could maintain a lifespan of more than 10 years, while the burnup depth was 6.25% lower than that of a model without inner-shielding. The conclusions of this research can provide important references for the shielding design and parameter selections of small molten salt reactors in the future.

ObjectiveSeveral recent reports have suggested the use of mean arterial blood pressure (MAP) to assess/predict the risk of developing atherosclerosis, chronic kidney disease, diabetes, metabolic syndrome, and poor prognosis in a variety of cardiovascular and cerebrovascular diseases. The current study aimed to investigate the association of MAP with non-alcoholic fatty liver disease (NAFLD) and to explore the differences in this association across populations.MethodsThis study used data from the NAGALA study from 1994 to 2016. MAP was calculated as 1/3 systolic blood pressure (SBP) + 2/3 diastolic blood pressure (DBP). Restricted cubic spline (RCS) and logistic regression models were used to examine the correlation of MAP with NAFLD.ResultsThe study population was 14,251 general people undergoing health screening, with a median (interquartile range) age of 42 (36–50) years; among them, 48% were women, and 2,507 (17.59%) were diagnosed with NAFLD. After fully controlling for confounders in the current dataset, MAP was positively and non-linearly associated with NAFLD [(odds ratios (ORs): 1.39, 95% confidence intervals (CIs): 1.15, 1.68); P for non-linearity = 0.024]; the dose-response curve showed that there was a transient saturation effect interval when MAP was between 85 and 95 mmHg, where the risk of NAFLD was neither increased nor decreased. The results of the stratified analysis showed that the risk of NAFLD associated with MAP appeared to be influenced only by age (P-interaction = 0.002), but not by sex, body mass index (BMI), habits of exercise, drinking status, or smoking status (P-interaction > 0.05); further age-stratified RCS analysis showed that the non-linear association between MAP and NAFLD in the young and middle-aged and the middle-aged and elderly populations was consistent with the results of the whole population, whereas, in the elderly population, a U-shaped curve association between MAP and NAFLD was observed, with both low and high MAP increasing the risk of NAFLD.ConclusionIn the general population, MAP was positively and non-linearly associated with NAFLD, and this association only differed significantly by age, but not by sex, BMI, habits of exercise, drinking status, and smoking status.

ObjectiveAlanine aminotransferase (ALT) and high-density lipoprotein cholesterol (HDL-C) are important predictive factors for non-alcoholic fatty liver disease (NAFLD). The aim of this study was to analyze the association between the ALT/HDL-C ratio and NAFLD.MethodsWe conducted a retrospective analysis of data from 14,251 individuals participating in the NAGALA project’s health screening program. The presence of NAFLD was diagnosed based on the participants’ alcohol consumption status and liver ultrasonography images. Multivariable logistic regression models were used to assess the association between the ALT/HDL-C ratio and NAFLD. Receiver operating characteristic (ROC) analysis was performed to determine and compare the effectiveness of ALT, HDL-C, the aspartate aminotransferase to HDL-C (AST/HDL-C) ratio, the gamma-glutamyl transferase to HDL-C (GGT/HDL-C) ratio and the ALT/HDL-C ratio in identifying NAFLD.ResultsWe observed a significant positive association between the ALT/HDL-C ratio and the prevalence of NAFLD. For each standard deviation (SD) increase in the ALT/HDL-C ratio, the adjusted odds ratio (OR) for NAFLD among the participants was 3.05 [95% confidence interval (CI): 2.63, 3.53], with the highest quartile of ALT/HDL-C ratio having a 9.96-fold increased risk compared to the lowest quartile. In further subgroup analyses stratified by gender, age, and waist circumference (WC), we observed a significantly higher risk of NAFLD associated with the ALT/HDL-C ratio among individuals aged ≥45 years, males, and those who were abdominal obesity. Furthermore, based on the results of ROC analysis, we found that the ALT/HDL-C ratio [area under the curves (AUC): 0.8553] was significantly superior to ALT, HDL-C, AST/HDL-C ratio and GGT/HDL-C ratio in identifying NAFLD (All Delong P

In free space optical (FSO) communication, acquisition, tracking and pointing (ATP) is the key technology to maintain a high-quality FSO link. Specifically, the detection of pointing angle deviation greatly affects the performance of ATP, especially under weak receiving power. However, the separated beacon laser beam commonly used in ATP will increase the structural complexity of the terminal such as the size, weight, and power. It is unwanted in some limited applications such as satellite. To improve the pointing accuracy with weak signal in beaconless FSO communication, we propose a delta-sigma enabled beaconless cross-correlation (CCR) method with four-quadrant detectors. In the proposed method, a low-frequency sine analog signal for CCR calculation is modulated into a 1-bit digital signal by delta-sigma modulation and then inserted into the communication data as a training sequence. The root means square error (RMSE) of the pointing angle deviation measurement is 14.17 μrad with the incident optical power of −40 dBm. Compared with the direct intensity method, of which RMSE is 67.61 μrad, the proposed method can effectively improve the pointing accuracy with weak power without a beacon laser in FSO communication.

Neddylation, as a reversible post-translational modification (PTM), plays a role in various cellular processes. Defects in neddylation are related to human diseases. Detecting neddylation sites is necessary for revealing the mechanisms of protein neddylation. As identifying such sites through experimental methods is expensive and time-consuming, it is essential to develop in silico methods to predict neddylation sites. In this study, we constructed a few classifiers integrating various algorithms and encoding features. However, they performed poorly (AUC $\approx 0.767$ ), mainly due to the limited number ( $\sim $ 1000) of identified neddylation sites. The large number ( $>$ 100,000) of other lysine PTM sites inspired us to employ a deep transfer learning (DTL) strategy for performance improvement. We constructed a predictor, dubbed DTL-NeddSite, which adopted the DTL-based convolution neural network using the one-hot encoding approach. Specifically, the massive number of lysine PTM sites were used to build the source model, followed by the fine-tuning of the target model using neddylation sites. DTL-NeddSite compared favourably with the corresponding model without the DTL strategy in cross-validation and independent tests. For instance, the AUC value increased to 0.818. Contrary to a general DTL model that combines frozen and unfrozen layers, all the layers in DTL-NeddSite were unfrozen to re-train. We expect the DTL strategy to be widely used in newly discovered modification types with limited known sites. Furthermore, DTL-NeddSite is freely accessible at https://github.com/XuDeli123/DTL-NeddSite.

Abstract Background Migration can be linked to the transmission of COVID-19. COVID-19 vaccine uptake and hesitancy among rural-to-urban migrant workers in China, the largest group of internal migrants in the world, has not been characterized. Objective To investigate COVID-19 vaccine uptake and identify vaccine hesitancy-associated factors among rural-to-urban migrant workers in the first round of COVID-19 vaccination in China. Methods A cross-sectional questionnaire-based survey was conducted, including 14,917 participants. Socio-demographics, COVID-19 vaccine uptake, vaccine hesitancy and its associated factors based on Vaccine Hesitancy Determinants Matrix (VHDM) were applied for the survey. Data were principally analyzed by logistic regression analysis. Results The COVID-19 vaccine uptake and vaccine hesitancy rates were 7.1% and 57.7%, respectively. Vaccine hesitancy was strongly associated with VHDM, including individual factors (female, higher annual income and fewer medical knowledge), group factors (less family support, friend support and public opinion support), COVID-19 epidemic factors (lower fatality, infection and emotional distress) and vaccine factors (less vaccine necessity, vaccine safety, vaccine efficacy, vaccine importance and vaccine reliability). Conclusion The VHDM model has the potential utility in efforts to reduce COVID-19 vaccine hesitancy. Greater efforts should be put into addressing positive predictors associated with vaccine hesitancy.

Abstract Background Toxocara canis is distributed worldwide, posing a serious threat to both human and dog health; however, the pathogenesis of T. canis infection in dogs remains unclear. In this study, the changes in microRNA (miRNA) expression profiles in the bone marrow of Beagle dogs were investigated by RNA-seq and bioinformatics analysis. Results Thirty-nine differentially expressed (DE) miRNAs (DEmiRNAs) were identified in this study. Among these, four DEmiRNAs were identified at 24 h post-infection (hpi) and all were up-regulated; eight DEmiRNAs were identified with two up-regulated miRNAs and six down-regulated miRNAs at 96 hpi; 27 DEmiRNAs were identified with 13 up-regulated miRNAs and 14 down-regulated miRNAs at 36 days post-infection (dpi). Among these DEmiRNAs, cfa-miR-193b participates in the immune response by regulating the target gene cd22 at 24 hpi. The novel_328 could participate in the inflammatory and immune responses through regulating the target genes tgfb1 and tespa1, enhancing the immune response of the host and inhibiting the infection of T. canis at 96 hpi. In addition, cfa-miR-331 and novel_129 were associated with immune response and self-protection mechanisms at 36 dpi. 20 pathways were significantly enriched by KEGG pathway analysis, most of which were related to inflammatory response, immune response and cell differentiation, such as Cell adhesion molecules (CAMs), ECM-receptor interaction and Focal adhesion. Conclusions These findings suggested that miRNAs of Beagle dog bone marrow play important roles in the pathogenesis of T. canis infection in dogs and provided useful resources to better understand the interaction between T. canis and the hosts.

Abstract Background A cross-sectional association between the combination indicator of high-density lipoprotein cholesterol (HDL-C) and gamma-glutamyl transferase (GGT) and fatty liver has been described in several recent studies, and this study aims to further evaluate the longitudinal relationship between the ratio of GGT to HDL-C (GGT/HDL-C ratio) and nonalcoholic fatty liver disease (NAFLD). Methods This cohort study included 12,126 individuals without NAFLD at baseline, followed prospectively for 5 years, and the endpoint of interest was new-onset NAFLD. The relationship of the GGT/HDL-C ratio with new-onset NAFLD and the shape of the association was assessed by Cox regression models and restricted cubic spline (RCS) regression, respectively. Time-dependent receiver operator characteristics (ROC) curves were constructed to evaluate the predictive value of GGT, HDL-C, GGT/HDL-C ratio and BMI for the occurrence of NAFLD at different time points in the future. Results The prevalence of NAFLD was 72.46/1000 person-years during the 5-year follow-up period. Results of multivariate Cox regression analysis showed a positive association of the GGT/HDL-C ratio with new-onset NAFLD after adequate adjustment of the related confounding factors, and the degree of correlation was slightly higher than that of GGT, and further subgroup analysis found that this association was more significant in the population with elevated systolic blood pressure (SBP). In addition, we also found a nonlinear relationship of the GGT/HDL-C ratio with the risk of new-onset NAFLD using the RCS regression, where the saturation threshold was about 31.79 U/mmol. Time-dependent ROC analysis results showed that the GGT/HDL-C ratio was increasingly valuable in predicting NAFLD over time, and was better than HDL-C in predicting NAFLD in the early stage (1–3 years), but was not superior to BMI and GGT. Conclusions In this large longitudinal cohort study based on a Chinese population, our results supported that the GGT/HDL-C ratio was positively and nonlinearly associated with the risk of new-onset NAFLD in a non-obese population. In the assessment of future NAFLD risk, the GGT/HDL-C ratio was slightly better than GGT alone; However, the GGT/HDL-C ratio did not appear to have a significant advantage over GGT and BMI alone in predicting NAFLD.

Abstract Bulk acoustic wave (BAW) filters have been extensively used in consumer products for mobile communication systems due to their high performance and standard complementary metal-oxide-semiconductor (CMOS) compatible integration process. However, it is challenging for a traditional aluminum nitride (AlN)-based BAW filter to meet several allocated 5G bands with more than a 5% fractional bandwidth via an acoustic-only approach. In this work, we propose an Al0.8Sc0.2N-based film bulk acoustic wave resonator (FBAR) for the design of radio frequency (RF) filters. By taking advantage of a high-quality Al0.8Sc0.2N thin film, the fabricated resonators demonstrate a large K eff 2 of 14.5% and an excellent figure of merit (FOM) up to 62. The temperature coefficient of frequency (TCF) of the proposed resonator is measured to be −19.2 ppm/°C, indicating excellent temperature stability. The fabricated filter has a center frequency of 4.24 GHz, a −3 dB bandwidth of 215 MHz, a small insertion loss (IL) of 1.881 dB, and a rejection >32 dB. This work paves the way for the realization of wideband acoustic filters operating in the 5G band.