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Selecting and breeding rice cultivars that enable strong cadmium (Cd) accumulation in rice straw but low accumulation in brown rice is a promising way to achieve Cd phytoremediation as well as to ensure the food safety of rice. Herein, we isolated a gene OsWNK9 from the quantitative trait locus associated with reducing Cd translocation from rice straw to brown rice and decreasing the Cd concentration in brown rice (BRCdC). Continuous strong expression of OsWNK9 was observed in nodes and internode and was induced after Cd supply. OsWNK9 was localized in the rice cell nucleus and participated in the regulation of Cd transport in yeast. Two independent oswnk9 rice mutants were generated via CRISPR/Cas9 gene-editing and showed significantly higher BRCdC than that of the wild type (WT). The BRCdC of knockout oswnk9 mutants was 0.227 mg kg−1and 0.238 mg kg−1, increased by 14 % and 19 % compared with that of the WT due to the lower Cd allocation in the basal stem, internode, and node III, which was unrelated to Cd uptake. Interestingly, OsWNK9 could promote iron (Fe) accumulation in rice under Cd-contaminated conditions, suggesting that OsWNK9 is an ideal gene for Cd phytoremediation and Fe biofortification in rice to support safe food production.

Abstract In the context of the epidemic, the daily routines of China’s elderly populace underwent substantial transformations. The implementation of home-based pandemic containment strategies led to heightened levels of social isolation and loneliness, exerting a discernible influence on the subjective well-being of this demographic. Consequently, residing in retirement apartments has emerged as a more advantageous alternative for elderly individuals capable of self-care. To meet their life and emotional needs and improve their sense of well-being, we used the KANO model to design a health management app for the self-care of older persons. We summarised the functional requirements for the self-care of elderly people, distributed questionnaires to generate a list of requirements, and conducted data analysis. We optimised the low-fidelity prototype based on the usability test results combined with relevant interface design elements to implement emotional interaction design practices for older persons’ self-care. Furthermore, we completed a design evaluation and program optimisation of the design practice to guide the final visual design. The research findings identify the core principles of interactive design for elderly users to enable visual design specifications for improving the lives of the elderly population. This research highlights the need to design more appropriate products that meet demographic characteristics. This work contributes to strengthening the connection between elderly people and society while bridging the ‘digital divide’ based on this population’s cautious approach to technologies and declining abilities to learn.

Abstract Background Type 1 diabetes mellitus (T1DM) has been associated with higher pulmonary tuberculosis (PTB) risk in observational studies. However, the causal relationship between them remains unclear. This study aimed to assess the causal effect between T1DM and PTB using bidirectional Mendelian randomization (MR) analysis. Methods Single nucleotide polymorphisms (SNPs) of T1DM and PTB were extracted from the public genetic variation summary database. In addition, GWAS data were collected to explore the causal relationship between PTB and relevant clinical traits of T1DM, including glycemic traits, lipids, and obesity. The inverse variance weighting method (IVW), weighted median method, and MR‒Egger regression were used to evaluate the causal relationship. To ensure the stability of the results, sensitivity analyses assess the robustness of the results by estimating heterogeneity and pleiotropy. Results IVW showed that T1DM increased the risk of PTB (OR = 1.07, 95% CI: 1.03–1.12, P

Summary: Background: The use of real-time continuous glucose monitoring (rtCGM) technology remains largely investigational in the hospital setting. The current study aimed to evaluate the effectiveness of rtCGM in inpatients with diabetes who were treated with short-term continuous subcutaneous insulin infusion (CSII). Methods: In this randomized, parallel controlled trial conducted on the endocrinology wards in a tertiary hospital located in Shanghai, adults with type 1 and type 2 diabetes who required short-term CSII during hospitalization were randomly assigned (1:1) to receive either rtCGM-based glucose monitoring and management program or point-of-care (POC) standard of care (8 times/day) with blinded CGM. Primary outcome measure was the difference in the percentage of time within the target glucose range of 3.9–10 mmol/L (TIR, %). This study was registered at www.chictr.org.cn (ChiCTR2300068933). Findings: Among the 475 randomized participants (237 in the rtCGM group and 238 in the POC group), the mean age of was 60 ± 13 years, and the mean baseline glycated hemoglobin level was 9.4 ± 1.8%. The CGM-recorded mean TIR was 71.1 ± 15.8% in the rtCGM group and 62.9 ± 18.9% in the POC group, with a mean difference of 8.2% (95% confidence interval [CI]: 5.1–11.4%, P 10 mmol/L was significantly lower in the rtCGM group than in the POC group (28.3 ± 15.8% vs. 36.6 ± 19.0%, P

Hepatitis B virus (HBV) infection is a crucial public health issue and a major cause of liver disease, such as cirrhosis and hepatocellular carcinoma. At present, orally administered small molecule drugs, such as nucleoside / nucleotide analogues, are recommended as the first‐line treatment for HBV. However, the therapeutic efficacy of these drugs is hindered by off‐target toxicity caused by the whole‐body permeation distribution of these oral drugs. As an emerging drug delivery technology, systemically administered nanocarriers can enhance the aqueous solubility and stability of encapsulated drugs, prolong circulation times, and deliver them efficiently to the liver, showing great promise for increasing the safety and efficacy of small molecule drugs. Furthermore, nanocarriers also accelerate the clinical translation of new therapies, such as nucleic acids and vaccines. This review article highlights the progress of nanoparticle delivery systems in anti‐HBV therapeutics and discusses the opportunities and challenges for the future development of anti‐HBV nanotherapeutics.

Summary: Sorafenib, a first-line drug for advanced hepatocellular carcinoma (HCC), unfortunately encounters resistance in most patients, leading to disease progression. Traditional approaches to counteract this resistance, particularly those targeting the RAF-MEK-ERK pathway, often face clinical feasibility limitations. Magnetic hyperthermia (MH), unlike conventional thermal therapies, emerges as a promising alternative. It uniquely combines magnetothermal effects with an increase in reactive oxygen species (ROS). This study found the potential of intracellular MH enhanced the efficacy of sorafenib, increased cellular sensitivity to sorafenib, and reversed sorafenib resistance by inhibiting the RAF-MEK-ERK pathway in an ROS-dependent manner in a sorafenib-resistant HCC cell. Further, in a sorafenib-resistant HCC mouse model, MH significantly sensitized tumors to sorafenib therapy, resulting in inhibited tumor growth and improved survival rates. This presents a promising strategy to overcome sorafenib resistance in HCC, potentially enhancing therapeutic outcomes for patients with this challenging condition.

Abstract A lasting imbalance between fatty acid synthesis and consumption leads to non-alcoholic fatty liver disease (NAFLD), coupled with hepatitis and insulin resistance. Yet the details of the underlying mechanisms are not fully understood. Here, we unraveled that the expression of the transcription factor Zbtb18 is markedly decreased in the livers of both patients and murine models of NAFLD. Hepatic Zbtb18 knockout promoted NAFLD features like impaired energy expenditure and fatty acid oxidation (FAO), and induced insulin resistance. Conversely, hepatic Zbtb18 overexpression alleviated hepato-steatosis, insulin resistance, and hyperglycemia in mice fed on a high-fat diet (HFD) or in diabetic mice. Notably, in vitro and in vivo mechanistic studies revealed that Zbtb18 transcriptional activation of Farnesoid X receptor (FXR) mediated FAO and Clathrin Heavy Chain (CLTC) protein hinders NLRP3 inflammasome activity. This key mechanism by which hepatocyte’s Zbtb18 expression alleviates NAFLD and consequent liver fibrosis was further verified by FXR’s deletion and forced expression in mice and cultured mouse primary hepatocytes (MPHs). Moreover, CLTC deletion significantly abrogated the hepatic Zbtb18 overexpression-driven inhibition of NLRP3 inflammasome activity in macrophages. Altogether, Zbtb18 transcriptionally activates the FXR-mediated FAO and CLTC expression, which inhibits NLRP3 inflammasome’s activity alleviating inflammatory stress and insulin resistance, representing an attractive remedy for hepatic steatosis and fibrosis.

Abstract Background Atrial fibrillation (AF) is highly prevalent in the population, yet the factors contributing to AF events in susceptible individuals remain partially understood. The potential relationship between meteorological factors and AF, particularly with abnormal electrocardiograph (ECG) repolarization, has not been adequately studied. This case-crossover study aims to investigate the association between meteorological factors and daily hospital visits for AF with abnormal ECG repolarization in Shanghai, China. Methods The study cohort comprised 10,325 patients with ECG-confirmed AF who sought treatment at Shanghai Sixth People's Hospital between 2015 and 2018. Meteorological and air pollutant concentration data were matched with the patient records. Using a case-crossover design, we analyzed the association between meteorological factors and the daily count of hospital visitors for AF with abnormal ECG repolarization at our AF center. Lag analysis models were applied to examine the temporal relationship between meteorological factors and AF events. Results The analysis revealed statistically significant associations between AF occurrence and specific meteorological factors. AF events were significantly associated with average atmospheric pressure (lag 0 day, OR 0.9901, 95% CI 0.9825–0.9977, P

Laser-induced graphene (LIG) possesses characteristics of easy handling, miniaturization, and unique electrical properties. We modified the surface of LIG by electropolymerizing β-cyclodextrin (β-CD), which was used to immobilize antibodies on the electrode surface for highly sensitive detection of targets. N6-methyladenosine (m6A) is the most prevalent reversible modification in mammalian messenger RNA and noncoding RNA, influencing the development of various cancers. Here, β-CD was electropolymerized to immobilize the anti-m6A antibody, which subsequently recognized the target m6A. This was integrated into the catalytic hydrogen peroxide–hydroquinone (H2O2-HQ) redox system using phos-tag-biotin to generate electrochemical signals from streptavidin-modified horseradish peroxidase (SA-HRP). Under optimal conditions, the biosensor exhibited a linear range from 0.1 to 100 nM with a minimum detection limit of 96 pM. The method was successfully applied to the recovery analysis of m6A from HeLa cells through spiking experiments and aims to inspire strategies for point-of-care testing (POCT).

Urban land resources are scarce in China. To utilize land effectively and economically, many cities are developing over-track buildings above metro depots. The vibration from the entrance and exit lines of metro depots under an over-track platform would significantly impact over-track buildings. To study the influence of train vibration in the throat area of a metro depot on over-track buildings, a simulation model was established using a finite element method. The reasonability of the simulation method and parameter settings was verified through comparing the vibration simulation results with vibration test results in the throat area of a metro depot. Furthermore, the impact of parameters of over-track platform and building on indoor vibration induced by a train was quantitatively studied. According to simulation results, a prediction model was developed to predict the impact of train vibration on over-track buildings in metro depots. From the perspective of architectural planning and design, this study provides a theoretical and technical basis for the prevention and control of indoor vibrations in over-track buildings of urban metro depots.

Abstract Aims Management of blood glucose fluctuation is essential for diabetes. Exercise is a key therapeutic strategy for diabetes patients, although little is known about determinants of glycemic response to exercise training. We aimed to investigate the effect of combined aerobic and resistance exercise training on blood glucose fluctuation in type 2 diabetes patients and explore the predictors of exercise‐induced glycemic response. Materials and Methods Fifty sedentary diabetes patients were randomly assigned to control or exercise group. Participants in the control group maintained sedentary lifestyle for 2 weeks, and those in the exercise group specifically performed combined exercise training for 1 week. All participants received dietary guidance based on a recommended diet chart. Glycemic fluctuation was measured by flash continuous glucose monitoring. Baseline fat and muscle distribution were accurately quantified through magnetic resonance imaging (MRI). Results Combined exercise training decreased SD of sensor glucose (SDSG, exercise‐pre vs exercise‐post, mean 1.35 vs 1.10 mmol/L, p = .006) and coefficient of variation (CV, mean 20.25 vs 17.20%, p = .027). No significant change was observed in the control group. Stepwise multiple linear regression showed that baseline MRI‐quantified fat and muscle distribution, including visceral fat area (β = −0.761, p = .001) and mid‐thigh muscle area (β = 0.450, p = .027), were significantly independent predictors of SDSG change in the exercise group, as well as CV change. Conclusions Combined exercise training improved blood glucose fluctuation in diabetes patients. Baseline fat and muscle distribution were significant factors that influence glycemic response to exercise, providing new insights into personalized exercise intervention for diabetes.

Abstract Testicular microcirculation is closely related to spermatogenic function and seminiferous tubular function. The diagnosis and monitoring of testicular diseases can be associated with testicular microcirculation; however, there are currently no effective non‐invasive methods for super‐resolution imaging of testicular microcirculation. In this study, we introduced state‐of‐the‐art graph‐based tracking with the Kalman motion model algorithm to non‐invasively image human testicular microcirculation for the first time with a regular frame‐rate clinical ultrasound imaging system (37 Hz). Two distinct testicular vessels with an 81 µm separation were resolved in the testicular vasculature, surpassing all other imaging modalities. In a retrospective study, we performed contrast‐enhanced ultrasound examinations(CEUS) and ultrasound localization microscopy (ULM) processing on the included 76 infertile patients and 15 healthy controls from August 2021 to May 2023 and obtained super‐resolution images of testicular microcirculation with sub‐diffraction resolution. Through the results of one‐way analysis of variance tests and receiver operating characteristic analyses, we found that the ULM‐based parameters hold promise as clinical guidance for differentiating between non‐obstructive and obstructive male infertility. The mean vessel diameter achieved an area under the curve (AUC) of 0.920 (95% confidence interval [CI]: 0.847–0.994, p

BackgroundIn addition to abnormal liver inflammation, the main symptoms of non-alcoholic steatohepatitis (NASH) are often accompanied by gastrointestinal digestive dysfunction, consistent with the concept of spleen deficiency (SD) in traditional Chinese medicine. As an important metabolic sensor, whether peroxisome proliferator-activated receptor alpha (PPARα) participates in regulating the occurrence and development of NASH with SD (NASH-SD) remains to be explored.MethodsClinical liver samples were collected for RNA-seq analysis. C57BL/6J mice induced by folium sennae (SE) were used as an SD model. qPCR analysis was conducted to evaluate the inflammation and metabolic levels of mice. PPARα knockout mice (PPARαko) were subjected to SE and methionine–choline-deficient (MCD) diet to establish the NASH-SD model. The phenotype of NASH and the inflammatory indicators were measured using histopathologic analysis and qPCR as well.ResultsThe abnormal expression of PPARα signaling, coupled with metabolism and inflammation, was found in the results of RNA-seq analysis from clinical samples. SD mice showed a more severe inflammatory response in the liver evidenced by the increases in macrophage biomarkers, inflammatory factors, and fibrotic indicators in the liver. qPCR results also showed differences in PPARα between SD mice and control mice. In PPARαko mice, further evidence was found that the lack of PPARα exacerbated the inflammatory response phenotype as well as the lipid metabolism disorder in NASH-SD mice.ConclusionThe abnormal NR signaling accelerated the vicious cycle between lipotoxicity and inflammatory response in NAFLD with SD. Our results provide new evidence for nuclear receptors as potential therapeutic targets for NAFLD with spleen deficiency.

Abstract Background Immune checkpoint inhibitor (ICI) combination therapies have shown promise in the first‐line treatment of advanced biliary tract cancer (BTC). However, the best partner remains to be validated. Moreover, progress on biomarkers predicting the efficacy of ICI in BTC is slow. This study aimed to assess the efficacy and investigate reliable predictive biomarkers of programmed cell death protein‐1 (PD‐1) antibody combination therapy in the first‐line treatment of advanced BTC. Methods Clinical data from patients with advanced BTC who received chemotherapy or anti‐PD‐1 combination therapy as first‐line were collected. The primary outcome was overall survival (OS). Biomarkers, including peripheral blood inflammation scores, genetic alterations, and tumor microenvironment were investigated. Findings Sixty‐four patients were recruited and divided into four treatment groups: chemotherapy, anti‐PD‐1 plus chemotherapy, anti‐PD‐1 plus targeted therapy, and triple group (anti‐PD‐1 plus chemotherapy and targeted therapy). The median OS was 7.9, 11.3, 12.8, and 28.7 months, respectively. Compared to chemotherapy, mOS significantly prolonged in the triple group (p = 0.031). It showed that patients with five different peripheral blood inflammation scores had significantly prolonged mOS (p 2) group showed significantly superior OS (p = 0.003). Interpretation First‐line anti‐PD‐1 combination therapy was superior to chemotherapy, and triple therapy significantly improved survival. Peripheral blood immune‐inflammation score, FOXP3/CD8 ratio, and PLUS have potential as biomarkers for predicting the efficacy of first‐line anti‐PD‐1 therapy in advanced BTC.

Abstract The cortical population code is pervaded by activity patterns evoked by movement, but it remains largely unknown how such signals relate to natural behavior or how they might support processing in sensory cortices where they have been observed. To address this we compared high-density neural recordings across four cortical regions (visual, auditory, somatosensory, motor) in relation to sensory modulation, posture, movement, and ethograms of freely foraging male rats. Momentary actions, such as rearing or turning, were represented ubiquitously and could be decoded from all sampled structures. However, more elementary and continuous features, such as pose and movement, followed region-specific organization, with neurons in visual and auditory cortices preferentially encoding mutually distinct head-orienting features in world-referenced coordinates, and somatosensory and motor cortices principally encoding the trunk and head in egocentric coordinates. The tuning properties of synaptically coupled cells also exhibited connection patterns suggestive of area-specific uses of pose and movement signals, particularly in visual and auditory regions. Together, our results indicate that ongoing behavior is encoded at multiple levels throughout the dorsal cortex, and that low-level features are differentially utilized by different regions to serve locally relevant computations.

Abstract Aim To explore the genetic effects of CYP2C8, CYP2C9, CYP2J2, and EPHX2, the key genes involved in epoxyeicosatrienoic acid processing and degradation pathways in gestational diabetes mellitus (GDM) and metabolic traits in Chinese pregnant women. Methods A total of 2548 unrelated pregnant women were included, of which 938 had GDM and 1610 were considered as controls. Common variants were genotyped using the Infinium Asian Screening Array. Association studies of single nucleotide polymorphisms (SNPs) with GDM and related traits were performed using logistic regression and multivariable linear regression analyses. A genetic risk score (GRS) model based on 12 independent target SNPs associated with GDM was constructed. Logistic regression was used to estimate odds ratios and 95% confidence intervals, adjusting for potential confounders including age, pre-pregnancy body mass index, history of polycystic ovarian syndrome, history of GDM, and family history of diabetes, with GRS entered both as a continuous variable and categorized groups. The relationship between GRS and quantitative traits was also evaluated. Results The 12 SNPs in CYP2C8, CYP2C9, CYP2J2, and EPHX2 were significantly associated with GDM after adjusting for covariates (all P

Abstract Background The relationship between air pollution and atrial fibrillation (AF) recorded by electrocardiograph (ECG) has not yet been illustrated which worsens AF precaution and treatment. This research evaluated the association between air pollution and daily hospital visits for AF with ECG records. Methods The study enrolled 4933 male and 5392 female patients whose ECG reports indicated AF from 2015 to 2018 in our hospital. Such data were then matched with meteorological data, including air pollutant concentrations, collected by local weather stations. A case-crossover study was performed to assess the relationship between air pollutants and daily hospital visits for AF recorded by ECG and to investigate its lag effect. Results Our analysis revealed statistically significant associations between AF occurrence and demographic data, including age and gender. This effect was stronger in female (k = 0.02635, p

We aimed to determine the molecular characteristics of carbapenem-resistant Pseudomonas aeruginosa strains 18081308 and 18083286, which were isolated from the urine and the sputum of two Chinese patients, respectively. Additionally, we conducted a comparative analysis between Tn6411 carrying blaIMP-1 in strain 18083286 and transposons from the same family available in GenBank. Bacterial genome sequencing was carried out on strains 18081308 and 18083286 to obtain their whole genome sequence. Average nucleotide identity (ANI) was used for their precise species identification. Serotyping and multilocus sequence typing were performed. Furthermore, the acquired drug resistance genes of these strains were identified. The carbapenem-resistant P. aeruginosa strains isolated in the present study were of sequence type ST865 and serotype O6. They all carried the same resistance genes (aacC2, tmrB, and blaIMP-1). Tn6411, a Tn7-like transposon carrying blaIMP-1, was found in strain 18083286 by single molecule real time (SMRT) sequencing. We also identified the presence of this transposon sequence in other chromosomes of P. aeruginosa and plasmids carried by Acinetobacter spp. in GenBank, indicating the necessity for heightening attention to the potential transferability of this transposon.

Acoustic wave velocity has been commonly utilized to predict subsurface geopressure using empirical relations. Acoustic wave velocity is, however, affected by many factors. To estimate pore pressure accurately, we here propose to use elastic rock physics models to understand and analyze quantitatively the various contributions from these different factors affecting wave velocity. We report a closed-form relationship between the frame flexibility factor (γ) in a rock physics model and differential pressure, which presents the major control of pressure on elastic properties such as bulk modulus and compressional wave velocity. For a gas-bearing shale with abundant micro-cracks and fractures, its bulk modulus is much lower at abnormally high pore pressure (high γ values) where thin cracks and flat pores are open than that at normal hydrostatic pressure (low γ values) where pores are more rounded on average. The developed relations between bulk modulus and differential pressure have been successfully applied to the Upper Ordovician Wufeng and Lower Silurian Longmaxi formations in the Dingshan area of the Sichuan Basin to map the three-dimensional spatial distribution of pore pressure in the shale, integrating core, log and seismic data. The estimated results agree well with field measurements. Pressure coefficient is positively correlated to gas content. The relations and methods reported here could be useful for hydrocarbon exploration, production, and drilling safety in both unconventional and conventional fields.

BackgroundWohlfahrtiimonas chitiniclastica is an emerging fly-borne zoonotic pathogen, which causes infections in immunocompromised patients and some animals. Herein, we reported a W. chitiniclastica BM-Y from a dead zebra in China.MethodsThe complete genome sequencing of BM-Y showed that this isolate carried one chromosome and one novel type of blaVEB–1-carrying plasmid. Detailed genetic dissection was applied to this plasmid to display the genetic environment of blaVEB–1.ResultsThree novel insertion sequence (IS) elements, namely ISWoch1, ISWoch2, and ISWoch3, were found in this plasmid. aadB, aacA1, and gcuG were located downstream of blaVEB–1, composing a gene cassette array blaVEB–1–aadB–aacA1–gcuG bracketed by an intact ISWoch1 and a truncated one, which was named the blaVEB–1 region. The 5′-RACE experiments revealed that the transcription start site of the blaVEB–1 region was located in the intact ISWoch1 and this IS provided a strong promoter for the blaVEB–1 region.ConclusionThe spread of the blaVEB–1-carrying plasmid might enhance the ability of W. chitiniclastica to survive under drug selection pressure and aggravate the difficulty in treating infections caused by blaVEB–1-carrying W. chitiniclastica. To the best of our knowledge, this is the first report of the genetic characterization of a novel blaVEB–1-carrying plasmid with new ISs from W. chitiniclastica.

Introduction Obesity is a complex and multifactorial disease that has affected many adolescents in recent decades. Clinical practice guidelines recommend exercise as the key treatment option for adolescents with overweight and obesity. However, the effects of virtual reality (VR) exercise on the physical and brain health of adolescents with overweight and obese remain unclear. This study aims to evaluate the effects of physical and VR exercises on physical and brain outcomes and explore the differences in benefits between them. Moreover, we will apply a multiomics analysis to investigate the mechanism underlying the effects of physical and VR exercises on adolescents with overweight and obesity.Methods and analysis This randomised controlled clinical trial will include 220 adolescents with overweight and obesity aged between 11 and 17 years. The participants will be randomised into five groups after screening. Participants in the exercise groups will perform an exercise programme by adding physical or VR table tennis or soccer classes to routine physical education classes in schools three times a week for 8 weeks. Participants in the control group will maintain their usual physical activity. The primary outcome will be the change in body fat mass measured using bioelectrical impedance analysis. The secondary outcomes will include changes in other physical health-related parameters, brain health-related parameters and multiomics variables.Ethics and dissemination This study was approved by the Ethics Committee of Shanghai Sixth People’s Hospital and registered in the Chinese Clinical Trial Registry. Dissemination of the findings will include peer-reviewed publications, conference presentations and media releases.Trial registration number ChiCTR2300068786.

BackgroundDepression and anxiety are common comorbidities in cardiovascular clinic outpatients. Timely identification and intervention of these mental and psychological disorders can contribute to correct diagnosis, better prognosis, less medical expenses, and improved quality of life. The convenience of online doctor-patient communication platforms has increasingly attracted patients to online consultations. However, online health care and offline health care are very different. Research on how to identify psychological disorders in patients who engage in an online cardiology consultation is lacking. ObjectiveThis study aimed to explore the feasibility of using a self-rating scale to assess mental illness among patients who consult with a cardiologist online and to compare the differences in anxiety and depression between online and offline patients. MethodsFrom June 2022 to July 2022, we conducted follow-up visits with 10,173 patients on the Haodf platform. We conducted detailed consultations with 286 patients who visited the same cardiologist in the outpatient department. We used the self-rated Generalized Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9) scales to assess anxiety and depression, respectively. We analyzed the influencing factors related to the degree of coordination of online patients. We also compared the prevalence of anxiety or depression between online and offline patients and analyzed the factors related to anxiety or depression. ResultsOf the 10,173 online consultation patients, only 186 (1.8%) responded effectively. The response rate of the offline consultation patients was 96.5% (276/286). Frequent online communication and watching live video broadcasts were significantly related to effective responses from online patients (P

Abstract Background Hepatic fibrosis is a common pathologic stage in chronic liver disease development, which might ultimately lead to liver cirrhosis. Accumulating evidence suggests that adipose-derived stromal cells (ADSCs)-based therapies show excellent therapeutic potential in liver injury disease owing to its superior properties, including tissue repair ability and immunomodulation effect. However, cell-based therapy still limits to several problems, such as engraftment efficiency and immunoreaction, which impede the ADSCs-based therapeutics development. So, ADSCs-derived extracellular vesicles (EVs), especially for exosomes (ADSC-EXO), emerge as a promise cell-free therapeutics to ameliorate liver fibrosis. The effect and underlying mechanisms of ADSC-EXO in liver fibrosis remains blurred. Methods Hepatic fibrosis murine model was established by intraperitoneal sequential injecting the diethylnitrosamine (DEN) for two weeks and then carbon tetrachloride (CCl4) for six weeks. Subsequently, hepatic fibrosis mice were administrated with ADSC-EXO (10 μg/g) or PBS through tail vein infusion for three times in two weeks. To evaluate the anti-fibrotic capacity of ADSC-EXO, we detected liver morphology by histopathological examination, ECM deposition by serology test and Sirius Red staining, profibrogenic markers by qRT-PCR assay. LX-2 cells treated with TGF-β (10 ng/ml) for 12 h were conducted for evaluating ADSC-EXO effect on activated hepatic stellate cells (HSCs). RNA-seq was performed for further analysis of the underlying regulatory mechanisms of ADSC-EXO in liver fibrosis. Results In this study, we obtained isolated ADSCs, collected and separated ADSCs-derived exosomes. We found that ADSC-EXO treatment could efficiently ameliorate DEN/CCl4-induced hepatic fibrosis by improving mice liver function and lessening hepatic ECM deposition. Moreover, ADSC-EXO intervention could reverse profibrogenic phenotypes both in vivo and in vitro, including HSCs activation depressed and profibrogenic markers inhibition. Additionally, RNA-seq analysis further determined that decreased glutamine synthetase (Glul) of perivenous hepatocytes in hepatic fibrosis mice could be dramatically up-regulated by ADSC-EXO treatment; meanwhile, glutamine and ammonia metabolism-associated key enzyme OAT was up-regulated and GLS2 was down-regulated by ADSC-EXO treatment in mice liver. In addition, glutamine synthetase inhibitor would erase ADSC-EXO therapeutic effect on hepatic fibrosis. Conclusions These findings demonstrated that ADSC-derived exosomes could efficiently alleviate hepatic fibrosis by suppressing HSCs activation and remodeling glutamine and ammonia metabolism mediated by hepatocellular glutamine synthetase, which might be a novel and promising anti-fibrotic therapeutics for hepatic fibrosis disease.

Abstract Background: To investigate the Coronavirus Disease 2019 (COVID-19) vaccination coverage and the influential factors of vaccination among patients with mental disorders, we conducted a cross-sectional study in China. Method: The anonymous questionnaires including demographic data, vaccination status, intention to be vaccinated and its reasons were collected in the Second Xiangya Hospital, one of the biggest four psychiatric centers in China. Mental health of these participants were measured by the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder-7 items (GAD-7). The influential factors associated with vaccination status were analyzed by Fisher exact tests and binary logistical analysis. Result: 1328 patients and 922 family members completed the survey. The vaccination rate of patients included was 69.4%, whereas 85.5% patients were willing to be vaccinated. Being hospitalized (aOR 0.41, 95% CI:0.27–0.60), suffering from schizophrenia (aOR 0.38, 95% CI: 0.19–0.75) and secondary school educational background (aOR 0.58, 95% CI: 0.37–0.93) were significantly associated with less likelihood to get vaccinated. Uptaking vaccines could reduce depressive (aOR 0.63, 95% CI: 0.41–0.98) or anxious symptoms (aOR 0.40, 95% CI: 0.25–0.63) in these patients for a short period. Conclusion: Further COVID-19 immunization programme should prioritize hospitalized psychiatric patients and schizophrenic patients since their demands for vaccination had been partly ignored during the current inoculation.

The impulsive vibration induced by human running and jumping, object falling, striking during decoration, etc., significantly disturbs the learning, work, and life of people through building structure transmission. To study the influence of impulsive vibration in buildings, a vacant frame building was selected as a tested building. The vibration at each floor besides hitting spot would be measured when a solid metal ball falling freely hit the first floor of this building. The vibration response at each floor caused by the excitation above was simulated through a finite element method. The parameters of the simulation model were optimized according to measured results. Furthermore, the influence of building structure, the total amount of stories, and slab dimension on the transmission of vibration from 1 Hz to 80 Hz which can be perceived by human bodies was quantitatively studied. Results showed that the vertical weighted vibration acceleration level at each floor linearly decreased with the increase of the logarithm of the distance between each floor and the hitting spot. A prediction model of vertical weighted vibration acceleration level from 1 Hz to 80 Hz induced by the impulsive vibration in buildings was developed according to simulation results. The corrections relating to the number of story, building structure, slab span, slab length-to-width ratio, and slab thickness were respectively introduced in the model which can predict the vertical weighted vibration acceleration level at each floor above the hitting spot. The results of this study can provide a basis for the prediction and control of impulsive vibration caused by an impact source with great stiffness in buildings.

Summary: Overdose acetaminophen (APAP) can cause acute liver injury (ALI), but the underlying mechanism remains undetermined. This study explored the role of hepatic Zinc Finger And BTB Domain Containing 22 (ZBTB22) in defense against APAP-mediated hepatotoxicity. The results showed that hepatic ZBTB22 expression was significantly reduced in patients with ALI and mice. In mouse primary hepatocytes (MPHs), ZBTB22 deletion aggravated APAP overdose-induced ALI, whereas ZBTB22 overexpression attenuated that pathological progression. The results were further verified in ZBTB22 over-express or knockout mice models. In parallel, hepatocyte-specific ZBTB22 knockout also enhanced ALI. Furthermore, ZBTB22 decreased pregnane X receptor (PXR) expression, and the PXR activator pregnane-16α-carbonitrile suppressed the protective effect of ZBTB22 in APAP-induced ZBTB22-overexpressing mice. Collectively, our findings highlight the protective effect of ZBTB22 against APAP-induced ALI and unravel PXR signaling as the potential mechanism. Strategies to increase hepatic ZBTB22 expression represent a promising therapeutic approach for APAP overdose-induced ALI.

IntroductionCombination therapeutic mode is likely to be the key to enhance the efficacy of immunotherapy in a wider range of cancer patients. Herein, we conducted an open-label, single-arm, multicenter, phase II clinical trial that enrolled patients with advanced solid tumors who had progressed after standard treatments.MethodsRadiotherapy of 24 Gy/3 fractions/3-10 days was given to the targeted lesions. Liposomal irinotecan (80mg/m2, dose could be adjusted to 60 mg/m2 for intolerable cases) was intravenously (IV) administered once within 48 hours after radiotherapy. Then, camrelizumab (200mg IV, q3w) and anti-angiogenic drugs were given regularly until disease progression. The primary endpoint was objective response rate (ORR) in the target lesions evaluated by investigators per RECIST 1.1. The secondary endpoints were disease control rate (DCR) and treatment-related adverse events (TRAEs).ResultsBetween November 2020 and June 2022, 60 patients were enrolled. The median follow-up was 9.0 months (95% confidence interval (CI) 5.5-12.5). Of 52 evaluable patients, the overall ORR and DCR were 34.6% and 82.7%, respectively. Fifty patients with target lesions were evaluable, the ORR and DCR of the target lesions were 35.3% and 82.4%, respectively. The median progression-free survival was 5.3 months (95% CI 3.6, 6.2), and the median overall survival was not reached. TRAEs (all grades) occurred in 55 (91.7%) patients. The most common grade 3-4 TRAEs were lymphopenia (31.7%), anemia (10.0%), and leukopenia (10.0%).ConclusionThe combination of radiotherapy, liposomal irinotecan, camrelizumab, and anti-angiogenesis therapy demonstrated promising anti-tumor activity and well tolerance in various advanced solid tumors.Clinical trial registrationhttps://clinicaltrials.gov/ct2/home, identifier NCT04569916.

Abstract There are few reports on the material transformation and dominant microorganisms in the process of greening waste (GW) composting. In this study, the target microbial community succession and material transformation were studied in GW composting by using MiSeq sequencing and PICRUSt tools. The results showed that the composting process could be divided into four phases. Each phase of the composting appeared in turn and was unable to jump. In the calefactive phase, microorganisms decompose small molecular organics such as FA to accelerate the arrival of the thermophilic phase. In the thermophilic phase, thermophilic microorganisms decompose HA and lignocellulose to produce FA. While in the cooling phase, microorganisms degrade HA and FA for growth and reproduction. In the maturation phase, microorganisms synthesize humus using FA, amino acid and lignin nuclei as precursors. In the four phases of the composting, different representative genera of bacteria and fungi were detected. Streptomyces, Myceliophthora and Aspergillus, maintained high abundance in all phases of the compost. Correlation analysis indicated that bacteria, actinomycetes and fungi had synergistic effect on the degradation of lignocellulose. Therefore, it can accelerate the compost process by maintaining the thermophilic phase and adding a certain amount of FA in the maturation phase.

【Objective】The research was performed in order to have a full utilization of the long-podded cowpea germplasm resources.【Method】11 agronomic traits of 37 germplasm resources of long-podded cowpea were tested with the methods of principle component analysis, cluster analysis and grey relational analysis.【Result】Among the 37 germplasm resources of long-podded cowpea, the coefficient of variation of agronomic traits ranged from 7.99% to 42.02%. The coefficient of variation of pod length and pod width was the smallest (< 10%), and these traits showed the highest stability. Thus, the breeding of long-podded cowpea could be focused on screening and improving other 9 agronomic traits that had relatively high coefficient of variation (> 10%). These agronomic traits could be transferred into 6 principle components and the accumulative contribution rate of the first 6 components was 87.17%, thus they could be used to replace the 11 agronomic traits for evaluation and breeding of 37 germplasm resources of long-podded cowpea. When genetic distance degree was 10, 37 germplasm resources of long-podded cowpea cultivars could be divided into 3 cluster types: 28 cultivars were divided into type Ⅰ; 5 cultivars were divided into type Ⅱ; 4 cultivars-Heshun, Nanbin708-K, Hongfeng 708 and Hanmei No.8 belonging to type Ⅲ had relatively high yield and better quality, which were suitable for the planting and promotion of long-podded cowpea in Hainan. According to the weighted grey relational analysis, the cultivar Heshun, which had the highest weighted correlation of 0.7285, was the best for planting in Hainan. The principle component analysis and weighted grey relational analysis showed consistent result when comparing agronomic traits of 37 long-podded cowpea cultivars.【Conclusion】Through principle component analysis and weighted grey relational analysis, 10 germplasm resources of long-podded cowpea with better quality were obtained, respectively. Comparing these germplasm resources, 6 of them (Heshun, Ruixianggui, Nanbin 708-K, Jiangjun 708, Hanmei No. 7 and Hanmei No. 8) are in common. This indicate that both methods can be used for screening and evaluation of germplasm resources.

Gastrointestinal diseases are complex diseases that occur in the gastrointestinal tract. Common gastrointestinal diseases include chronic gastritis, peptic ulcers, inflammatory bowel disease, and gastrointestinal tumors. These diseases may manifest a long course, difficult treatment, and repeated attacks.Gastroscopy and mucosal biopsy are the gold standard methods for diagnosing gastric and duodenal diseases, but they are invasive procedures and carry risks due to the necessity of sedation and anesthesia. Recently, several new approaches have been developed, including serological examination and magnetically controlled capsule endoscopy (MGCE). However, serological markers lack lesion information, while MGCE images lack molecular information.This study proposes combining these two technologies in a collaborative noninvasive diagnostic scheme as an alternative to the standard procedures. We introduce an interpretable framework for the clinical diagnosis of gastrointestinal diseases. Based on collected blood samples and MGCE records of patients with gastrointestinal diseases and comparisons with normal individuals, we selected serum metabolite signatures by bioinformatic analysis, captured image embedding signatures by convolutional neural networks, and inferred the location-specific associations between these signatures.Our study successfully identified five key metabolite signatures with functional relevance to gastrointestinal disease. The combined signatures achieved discrimination AUC of 0.88. Meanwhile, the image embedding signatures showed different levels of validation and testing accuracy ranging from 0.7 to 0.9 according to different locations in the gastrointestinal tract as explained by their specific associations with metabolite signatures. Overall, our work provides a new collaborative noninvasive identification pipeline and candidate metabolite biomarkers for image auxiliary diagnosis. This method should be valuable for the noninvasive detection and interpretation of gastrointestinal and other complex diseases.

Recording technologies for rodents have seen huge advances in the last decade, allowing users to sample thousands of neurons simultaneously from multiple brain regions. This has prompted the need for digital tool kits to aid in curating anatomical data, however, existing tools either provide limited functionalities or require users to be proficient in coding to use them. To address this we created HERBS (Histological E-data Registration in rodent Brain Spaces), a comprehensive new tool for rodent users that offers a broad range of functionalities through a user-friendly graphical user interface. Prior to experiments, HERBS can be used to plan coordinates for implanting electrodes, targeting viral injections or tracers. After experiments, users can register recording electrode locations (e.g. Neuropixels and tetrodes), viral expression, or other anatomical features, and visualize the results in 2D or 3D. Additionally, HERBS can delineate labeling from multiple injections across tissue sections and obtain individual cell counts.Regional delineations in HERBS are based either on annotated 3D volumes from the Waxholm Space Atlas of the Sprague Dawley Rat Brain or the Allen Mouse Brain Atlas, though HERBS can work with compatible volume atlases from any species users wish to install. HERBS allows users to scroll through the digital brain atlases and provides custom-angle slice cuts through the volumes, and supports free-transformation of tissue sections to atlas slices. Furthermore, HERBS allows users to reconstruct a 3D brain mesh with tissue from individual animals. HERBS is a multi-platform open-source Python package that is available on PyPI and GitHub, and is compatible with Windows, macOS, and Linux operating systems.

Background: The injury of femoral head varies among femoral head fractures (FHFs). In addition, the injury degree of the femoral head is a significant predictor of femoral neck fracture (FNF) incidence in patients with FHFs. However, the exact measurement methods have yet been clearly defined based on injury models of FHFs. This study aimed to design a new measurement for the injury degree of the femoral head on 2D and 3D models with computed tomography (CT) images and investigate its association with FHFs with FNF.Methods: A consecutive series of 209 patients with FHFs was assessed regarding patient characteristics, CT images, and rate of FNF. New parameters for injury degree of femoral head, including percentage of maximum defect length (PMDL) in the 2D CT model and percentage of fracture area (PFA) in the 3D CT-reconstruction model, were respectively measured. Four 2D parameters included PMDLs in the coronal, cross-sectional and sagittal plane and average PMDL across all three planes. Reliability tests for all parameters were evaluated in 100 randomly selected patients. The PMDL with better reliability and areas under curves (AUCs) was finally defined as the 2D parameter. Factors associated with FNF were determined by binary logistic regression analysis. The sensitivity, specificity, likelihood ratios, and positive and negative predictive values for different cut-off values of the 2D and 3D parameters were employed to test the diagnostic accuracy for FNF prediction.Results: Intra- and inter-class coefficients for all parameters were ≥0.887. AUCs of all parameters ranged from 0.719 to 0.929 (p < 0.05). The average PMDL across all three planes was defined as the 2D parameter. The results of logistic regression analysis showed that average PMDL across all three planes and PFA were the significant predictors of FNF (p < 0.05). The cutoff values of the average PMDL across all three planes and PFA were 91.65% and 29.68%. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, predictive positive value and negative predictive value of 2D (3D) parameters were 91.7% (83.3%), 93.4% (58.4%), 13.8 (2.0), 0.09 (0.29), 45.83% (10.87%), and 99.46% (98.29%).Conclusion: The new measurement on 2D and 3D injury models with CT has been established to assess the fracture risk of femoral neck in patients with FHFs in the clinic practice. 2D and 3D parameters in FHFs were a feasible adjunctive diagnostic tool in identifying FNFs. In addition, this finding might also provide a theoretic basis for the investigation of the convenient digital-model in complex injury analysis.

N 6-methyladenosine (m6A) is the most prevalent mRNA internal modification and has been shown to regulate the development, physiology, and pathology of various tissues. However, the functions of the m6A epitranscriptome in the visual system remain unclear. In this study, using a retina-specific conditional knockout mouse model, we show that retinas deficient in Mettl3, the core component of the m6A methyltransferase complex, exhibit structural and functional abnormalities beginning at the end of retinogenesis. Immunohistological and single-cell RNA sequencing (scRNA-seq) analyses of retinogenesis processes reveal that retinal progenitor cells (RPCs) and Müller glial cells are the two cell types primarily affected by Mettl3 deficiency. Integrative analyses of scRNA-seq and MeRIP-seq data suggest that m6A fine-tunes the transcriptomic transition from RPCs to Müller cells by promoting the degradation of RPC transcripts, the disruption of which leads to abnormalities in late retinogenesis and likely compromises the glial functions of Müller cells. Overexpression of m6A-regulated RPC transcripts in late RPCs partially recapitulates the Mettl3-deficient retinal phenotype. Collectively, our study reveals an epitranscriptomic mechanism governing progenitor-to-glial cell transition during late retinogenesis, which is essential for the homeostasis of the mature retina. The mechanism revealed in this study might also apply to other nervous systems.

Repairing critical bone defects is a complex problem in the clinic. The periosteum rich in nerve plays a vital role in initiating and regulating bone regeneration. However, current studies have paid little attention to repairing nerves in the periosteum to promote bone regeneration. Thus, it is essential to construct bionic periosteum with the targeted injured nerves in the periosteum. We coupled phosphatidylserine (PS) targeted aptamers with repair Schwann cell exosomes to construct exosome@aptamer (EA). Then through PEI, EA was successfully built on the surface of the electrospun fiber, which was PCL@PEI@exosome@aptamer (PPEA). Through SEM, TEM, and other technologies, PPEA was characterized. Experiments prove in vivo and in vitro that it has an excellent repair effect on damaged nerves and regeneration of vascular and bones. In vivo, we confirmed that biomimetic periosteum has an apparent ability to promote nerve and bone regeneration by using Microcomputer tomography, hematoxylin-eosin, Masson, and Immunofluorescence. In vitro, we used Immunofluorescence, Real-Time Quantitative PCR, Alkaline phosphatase staining, and other tests to confirm that it has central nerve, blood vessel, and bone regeneration ability. The PPEA biomimetic periosteum has apparent neurogenic, angiogenic, and osteogenic effects. The PPEA biomimetic periosteum will provide a promising method for treating bone defects.

Acetaminophen (APAP) intake leads to excessive NAPQI deposition, stimulating inflammatory and oxidative stress and causing fatal liver injury. However, the detailed molecular mechanism involved is unknown, and effective therapeutic approaches remain insufficient. In this study, we discovered that treatment with ginsenoside Rc can prevent the inflammatory response caused by APAP and oxidative stress in mouse primary hepatocytes (MPHs), along with the corresponding changes in related genes. Additionally, Ginsenoside Rc effectively alleviates APAP-induced cellular apoptosis and NAPQI accumulation in MPHs. In vivo, Ginsenoside Rc administration remarkably attenuates APAP-induced hepatotoxicity, repairing liver damage and improving survival. Moreover, Ginsenoside Rc treatment modulates genes involved in APAP metabolism, leading to a decrease in NAPQI and resulting in the alleviation of fatal oxidative stress and inflammatory response after APAP exposure, along with the expression of their related indicators. Furthermore, our RNA-seq and molecular docking analysis implies that FXR expression and FXR transcriptional activity are stimulated by Ginsenoside Rc treatment. Notably, due to the lack of FXR in mice and MPHs, ginsenoside Rc can no longer play its original protective role against hepatotoxicity and cell damage caused by APAP, and it is difficult to improve the corresponding survival rate and prevent hepatic apoptosis, NAPQI generation, fatal oxidative stress, and the inflammatory response induced by APAP and the expression of related genes. In summary, our results indicate that Ginsenoside Rc could act as an effective FXR activator and effectively regulate FXR-induced antioxidant stress and eliminate inflammation while also having an anti-apoptotic function.

Objectives: Farnesoid X receptor (FXR) activation is involved in ameliorating inflammatory bowel disease (IBD), such as ulcerative colitis (UC), and inflammatory regulation may be involved in its mechanism. Ginsenoside Rc (Rc) is a major component of Panax ginseng, and it plays an excellent role in the anti-inflammatory processes. Our aim is to explore the alleviative effect of Rc on dextran sulfate sodium (DSS)-induced inflammation and deficiencies in barrier function based on FXR signaling.Materials and Methods:In vitro, we treated human intestinal epithelial cell lines (LS174T) with LPS to explore the anti-inflammatory effect of Rc supplementation. In vivo, a DSS-induced IBD mice model was established, and the changes in inflammatory and barrier function in colons after Rc treatment were measured using the disease activity index (DAI), hematoxylin and eosin (H&E) staining, immunofluorescence, ELISA, and qPCR. Molecular docking analysis, luciferase reporter gene assay, and qPCR were then used to analyze the binding targets of Rc. DSS-induced FXR-knockout (FXR−/-) mice were used for further validation.Results: Rc significantly recovered the abnormal levels of inflammation indexes (TNF-α, IL-6, IL-1β, and NF-KB) induced by LPS in LS174T. DSS-induced C57BL/6 mice exhibited a significantly decreased body weight and elevated DAI, as well as a decrease in colon weight and length. Increased inflammatory markers (TNF-α, IL-6, IL-1β, ICAM1, NF-KB, F4/80, and CD11b displayed an increased expression) and damaged barrier function (Claudin-1, occludin, and ZO-1 displayed a decreased expression) were observed in DSS-induced C57BL/6 mice. Nevertheless, supplementation with Rc mitigated the increased inflammatory and damaged barrier function associated with DSS. Further evaluation revealed an activation of FXR signaling in Rc-treated LS174T, with FXR, BSEP, and SHP found to be upregulated. Furthermore, molecular docking indicated that there is a clear interaction between Rc and FXR, while Rc activated transcriptional expression of FXR in luciferase reporter gene assay. However, these reversal abilities of Rc were not observed in DSS-induced FXR−/- mice.Conclusion: Our findings suggest that Rc may ameliorate inflammation and barrier function in the intestine, which in turn leads to the attenuation of DSS-induced UC, in which Rc may potentially activate FXR signaling to protect the intestines from DSS-induced injury.

Green entrepreneurial self-efficacy (ESE) refers to individuals’ conviction that they can contribute to solving environmental issues and shows self-assurance in their efforts to protect the environment. The present investigation attempts to determine the role of employees’ green ESE in the green innovation (GI) of SMEs. It is also proposed that GI positively impacts organizational environmental, economic, and social performance. This study also evaluates the mediating role of GI and moderating role of the green knowledge-sharing culture. This study tested the hypothesis using a partial least squares structural equation modeling (PLS-SEM) by applying smart PLS software. A total of 289 employees from SMEs in China were targeted for data collection. The results confirmed that green ESE positively impacts GI. Additionally, the findings verified that GI positively enhances firms’ environmental, economic, and social performance. The results validate the mediating role of GI. The moderating results revealed that green knowledge-sharing culture does not play a moderating role in proposed relationships. This study serves the existing body of literature by providing empirical evidence on the significance of green ESE. The study outcomes highlighted the bridging role of employees’ green ESE for firms’ GI. The results also offer companies a road map for how staff members’ green ESE might help the businesses to improve their performance in terms of the environment, economy, and society.

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, and the demographics of pregnant women have changed in recent decades. GDM is a metabolic disease with short- and long-term adverse effects on both pregnant women and newborns. The metabolic changes and corresponding risk factors should be of great significance in understanding the pathological mechanism of GDM and reducing the incidence of adverse pregnancy outcomes in patients with GDM. The well-known GDM-associated lipids used in clinical tests, such as triglyceride (TG), are thought to play a major role in metabolic changes during GDM, which have a potential causal relationship with abnormal pregnancy outcomes of GDM. Therefore, this study analyzed the relationship between clinical lipid indicators, metabolic profiles, and abnormal pregnancy outcomes in GDM through mediation analysis. By constructing a metabolic atlas of 399 samples from GDM patients in different trimesters, we efficiently detected the key metabolites of adverse pregnancy outcomes and their mediating roles in bridging abnormal lipids and adverse pregnancy outcomes in patients with GDM. Our study confirmed that TG and total cholesterol were independent risk factors for adverse pregnancy outcomes in patients with GDM. Several key metabolites as mediators (e.g., gamma-linolenic acid, heptadecanoic acid, oleic acid, palmitic acid, and palmitoleic acid) have been identified as potential biomarkers for adverse pregnancy outcomes in patients with GDM. These metabolites mainly participate in the biosynthesis of unsaturated fatty acids, which may shed new light on the pathology of GDM and provide insights for further exploration of the molecular mechanisms underlying adverse pregnancy outcomes.

IntroductionType 2 diabetes patients have abdominal obesity and low thigh circumference. Previous studies have mainly focused on the role of exercise in reducing body weight and fat mass, improving glucose and lipid metabolism, with a lack of evaluation on the loss of muscle mass, diabetes complications, energy metabolism, and brain health. Moreover, whether the potential physiological benefit of exercise for diabetes mellitus is related to the modulation of the microbiota-gut-brain axis remains unclear. Multi-omics approaches and multidimensional evaluations may help systematically and comprehensively correlate physical exercise and the metabolic benefits.Methods and AnalysisThis study is a randomized controlled clinical trial. A total of 100 sedentary patients with type 2 diabetes will be allocated to either an exercise or a control group in a 1:1 ratio. Participants in the exercise group will receive a 16-week combined aerobic and resistance exercise training, while those in the control group will maintain their sedentary lifestyle unchanged. Additionally, all participants will receive a diet administration to control the confounding effects of diet. The primary outcome will be the change in body fat mass measured using bioelectrical impedance analysis. The secondary outcomes will include body fat mass change rate (%), and changes in anthropometric indicators (body weight, waist, hip, and thigh circumference), clinical biochemical indicators (glycated hemoglobin, blood glucose, insulin sensitivity, blood lipid, liver enzyme, and renal function), brain health (appetite, mood, and cognitive function), immunologic function, metagenomics, metabolomics, energy expenditure, cardiopulmonary fitness, exercise-related indicators, fatty liver, cytokines (fibroblast growth factor 21, fibroblast growth factor 19, adiponectin, fatty acid-binding protein 4, and lipocalin 2), vascular endothelial function, autonomic nervous function, and glucose fluctuation.DiscussionThis study will evaluate the effect of a 16-week combined aerobic and resistance exercise regimen on patients with diabetes. The results will provide a comprehensive evaluation of the physiological effects of exercise, and reveal the role of the microbiota-gut-brain axis in exercise-induced metabolic benefits to diabetes.Clinical Trial Registrationhttp://www.chictr.org.cn/searchproj.aspx, identifier ChiCTR2100046148.

Glycosylated hemoglobin A1c (HbA1c) level has strong relevance to microvascular disorders, which are also thought to be the current main aspect of sudden sensorineural hearing loss (SSNHL), so we aim to elucidate the association of the HbA1c level with the severity, types, and prognosis of SSNHL. In this study, comparative analyses based on propensity score matching of the severity, types, and prognosis of SSNHL with the HbA1c level in 116 patients diagnosed as SSNHL were conducted, where they were divided into diabetes mellitus (DM) group and non-DM group. We finally found that, among patients with SSNHL, diabetic patients had a higher HbA1c level, more severe hearing loss, and poorer prognosis than non-diabetic patients. The HbA1c level was found to be significantly correlated with the severity and types of SSNHL, while no strong relevance was found between the higher HbA1c level and the poorer prognosis of SSNHL.

Subway station projects are characterized by complex construction technology, complex site conditions, and being easily influenced by the surrounding environment; thus, construction safety accidents occur frequently. In order to improve the computing performance of the early risk warning system in subway station construction, a novel model based on least-squares support vector machines (LSSVM) optimized by quantum-behaved particle swarm optimization (QPSO) was proposed. First, early warning factors from five aspects (man, machine, management, material, and the environment) were selected based on accident causation theory and literature research. The data acquisition method of each risk factor was provided in detail. Then, the LSSVM with strong small sample analysis and nonlinear analysis abilities was chosen to give the early warning. To further ameliorate the early warning accuracy of the LSSVM, QPSO with a strong global retrieval ability was used to find the optimal calculation parameters of the LSSVM. Seventeen subway stations of Chengdu Metro Line 11 in China were picked as the empirical objects. The results demonstrated that the best regularization parameter was 1.742, and the best width parameter was 14.167. The number of misjudged samples of the proposed model was 1, and the early warning error rate was only 4.41%, which met the needs of engineering practice. Compared with the classic and latest methods, the proposed model was found to have a faster prediction speed and higher prediction accuracy.

Abstract Mitochondrial DNA depletion syndrome (MDS) is a group of severe inherited disorders caused by mutations in genes, such as deoxyribonucleoside kinase (DGUOK). A great majority of DGUOK mutant MDS patients develop iron overload progressing to severe liver failure. However, the pathological mechanisms connecting iron overload and hepatic damage remains uncovered. Here, two patients’ skin fibroblasts are reprogrammed to induced pluripotent stem cells (iPSCs) and then corrected by CRISPR/Cas9. Patient‐specific iPSCs and corrected iPSCs‐derived high purity hepatocyte organoids (iHep‐Orgs) and hepatocyte‐like cells (iHep) are generated as cellular models for studying hepatic pathology. DGUOK mutant iHep and iHep‐Orgs, but not control and corrected one, are more sensitive to iron overload‐induced ferroptosis, which can be rescued by N‐Acetylcysteine (NAC). Mechanically, this ferroptosis is a process mediated by nuclear receptor co‐activator 4 (NCOA4)‐dependent degradation of ferritin in lysosome and cellular labile iron release. This study reveals the underlying pathological mechanisms and the viable therapeutic strategies of this syndrome, and is the first pure iHep‐Orgs model in hereditary liver diseases.

The E3 deubiquitinating enzyme ubiquitin-specific proteolytic enzyme 21 (USP21) plays vital roles in physiological activities and is required for Treg-cell-mediated immune tolerance. Using a murine model infected with Schistosoma japonicum, we observed that there were more cercariae developed into adults and more eggs deposited in the livers of the USP21fl/flFOXP3Cre (KO) mice. However, immunohistochemistry showed that the degree of egg granuloma formation and liver fibrosis was reduced. In USP21fl/flFOXP3Cre mice, levels of IFN-gamma, IL-4, anti-soluble egg antigen (SEA) IgG and anti-soluble worm antigen preparation (SWAP) IgG increased in blood, as determined using ELISAs and multiplex fluorescent microsphere immunoassays, while the levels of IL-10, lL-17A, IL-23, IL-9, and anti-SEA IgM decreased. In addition, the levels of the USP21 protein and mRNA in the liver and spleen of KO mice decreased. We further observed increased Th1 responses amplified by Tregs (regulatory T cells) and compromised Th17 responses, which alleviated the liver immunopathology. We speculated that these changes were related to polarization of Th1-like Tregs. Our results revealed the roles of USP21 in Treg-cell-mediated regulation of immune interactions between Schistosoma and its host. USP21 may have potential for regulating hepatic fibrosis in patients with schistosomiasis.

Commodity housing is the most important product in the development of modern civil engineering, and it is also the frontier problem of modern engineering project management research. The progress of civil engineering in China can be seen to a great extent through the development of commercial housing. In order to solve the severe problem of rapid growth of commodity housing price in China, considering the advantages of system dynamics theory, a system dynamics model of commodity housing price is constructed. Eight subsystems, namely, housing demand, housing supply, housing price, urban population, urban economy, housing land, housing tenancy, and macro-control, are studied. Taking the relevant data of Wuhan as an example, the Vensim DSS is used for simulations. In addition, a validity test and sensitivity test are used to verify the validity and feasibility of the model, respectively. Based on the model, it is successfully predicted that the price of commercial housing in Wuhan will reach 18,207.9 yuan/m2 in 2030, which provides a more systematic method of prediction for synthesis simulation of commercial housing markets. From the perspective of the developer loan interest rate, real estate tax rate, purchase restriction, and other policies, we show that the developer loan interest rate regulation policy has the strongest effect on guiding the change in commercial housing prices in Wuhan. Generally, this study provides insight into the responses that the national government could use to control housing prices.

To solve the problem of blockage of crystallization in tunnel drainage pipes in hard water area, electric field devices are designed and applied in the transversal tunnel drainage pipe according to the fundamental law of crystallization. Laboratory tests were carried out to test the crystallizing tunnel drainage pipe under the effect of electric field in order to study the law of electric field impact on crystallization in tunnel drainage pipes in hard water area. The test results indicate that the arranged circumferential and parallel plate electric field devices can form an electrical field within a narrow and small space inside the pipe and influence the ion movement in water and adsorption performance between crystals and the pipe. Under the condition of full flow, the amount of crystals in the ordinary pipe without electric field treatment increases progressively along water flow direction and remains relatively uniform later. The amount of crystals along the water flow direction of the pipe treated with circumferential and parallel plate electric fields presents signs of fluctuation in the early stage and then stableness later. The amount of crystals in the fluctuating section is higher and lower in the uniform section, and its uniform section length is longer than that in ordinary pipes. Under the condition of full current, crystallizing speed declines with elapse of running time. After the electric field is imposed, crystallizing acceleration progressively decreased to a relatively lower level. Comparing three voltages of 5 V, 12 V, and 24 V, the effect of scale inhibition under 5 V is superior. When water amount in the pipe varies, the effects of scale inhibition under different electric field modes are different. The electric field effect causes the changes of the external form of calcium carbonate crystal and its surface abrasion, porous crystal, and structural looseness.

Objective: A potential solution for islet transplantation and drug discovery vis-à-vis treating diabetes is the production of functional islets in a three-dimensional extracellular matrix. Although several scaffold materials have been reported as viable candidates, a clinically applicable one that is injectable and can maintain long-term functionality and survival of islet pancreatic beta-cells (β-cells) is far from being established. Results: In the current study, we evaluated a ready-to-use and injectable hydrogel’s impact on β-cells’ function and viability, both in vitro and in vivo. We found that β-cells in high concentration with hydrogels functionalized via Arg-Gly-Asp (RGD) demonstrated better viability and insulin secretory capacity in vitro. Moreover, it is a biocompatible hydrogel that can maintain β-cell proliferation and vascularization without stimulating inflammation after subcutaneous injection. Meanwhile, modifying the hydrogel with RGD can maintain β-cells’ secretion of insulin, regulating the blood glucose levels of mice with streptozotocin-induced diabetes. Conclusions: Thus, these preliminary results indicate that this RGD-modified hydrogel is a potential extracellular matrix for islet transplantation at extrahepatic sites, and they also provide a reference for future tissue engineering study.

Metabolic reprogramming is an emerging hallmark of cancer cells, in which cancer cells exhibit distinct metabolic phenotypes to fuel their proliferation and progression. The significant advancements made in the area of metabolic reprogramming make possible new strategies for overcoming malignant cancer, including triple-negative breast cancer. Triple-negative breast cancer (TNBC) is associated with high histologic grade, aggressive phenotype, and poor prognosis. Even though triple-negative breast cancer patients benefit from standard chemotherapy, they still face high recurrence rates and are more likely to develop resistance to chemotherapeutic drugs. Therefore, there is an urgent need to explore vulnerabilities of triple-negative breast cancer and develop novel therapeutic drugs to improve clinical outcomes for triple-negative breast cancer patients. Metabolic reprogramming may provide promising therapeutic targets for the treatment of triple-negative breast cancer. In this paper, we primarily discuss how triple-negative breast cancer cells reprogram their metabolic phenotype and that of stromal cells in the microenvironment to survive under nutrient-poor conditions. Considering that metastasis and chemoresistance are the main contributors to mortality in triple-negative breast cancer patients, we also focus on the role of metabolic adaption in mediating metastasis and chemoresistance of triple-negative breast cancer tumors.

This paper introduces the R package meta4diag for implementing Bayesian bivariate meta-analyses of diagnostic test studies. Our package meta4diag is a purpose-built front end of the R package INLA. While INLA offers full Bayesian inference for the large set of latent Gaussian models using integrated nested Laplace approximations, meta4diag extracts the features needed for bivariate meta-analysis and presents them in an intuitive way. It allows the user a straightforward model specification and offers user-specific prior distributions. Further, the newly proposed penalized complexity prior framework is supported, which builds on prior intuitions about the behaviors of the variance and correlation parameters. Accurate posterior marginal distributions for sensitivity and specificity as well as all hyperparameters, and covariates are directly obtained without Markov chain Monte Carlo sampling. Further, univariate estimates of interest, such as odds ratios, as well as the summary receiver operating characteristic (SROC) curve and other common graphics are directly available for interpretation. An interactive graphical user interface provides the user with the full functionality of the package without requiring any R programming. The package is available from the Comprehensive R Archive Network (CRAN) at https://CRAN.R-project.org/package=meta4diag/ and its usage will be illustrated using three real data examples.