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Abstract Objective To delineate the clinical characteristics of preterm birth (PTB) in the context of gestational diabetes mellitus (GDM). Methods A retrospective cohort study was conducted, including 14,314 pregnant women with GDM who delivered at Fujian Provincial Maternity and Children’s Hospital from January 1, 2018, to December 31, 2021. PTB was stratified into late PTB (34–36 weeks of gestation) and early PTB (

Abstract Background Currently, obesity has been recognized to be an independent risk factor for osteoarthritis (OA), and the Metabolic Score for Visceral Fat (METS-VF) has been suggested to be potentially more accurate than body mass index (BMI) in the assessment of obesity. Nevertheless, the correlation of METS-VF with OA has not been obviously revealed yet. Therefore, this study aimed to delve into the potential relationship between METS-VF and OA. Methods By examining data from the NHANES (2009–2018), weighted multivariate logistic regression analyses were used for assessing the correlation between METS-VF and OA. Subgroup analyses were then performed to validate the findings. Moreover, the nonlinear relationship between the two was assessed by restricted cubic spline (RCS). Receiver operating characteristic (ROC) curves were plotted to examine the diagnostic accuracy of METS-VF versus previous obesity index for OA. Results This study involved 7639 participants. According to our results, METS-VF was notably related to an elevated risk of OA, regardless of the METS-VF and the trend of positive association was more pronounced with the elevating METS-VF level (p for trend

Abstract Objective Chronic kidney disease (CKD) and osteoarthritis (OA) represent two frequently seen disorders among the general population, and they share several similar risk factors. The present work focused on assessing the relation of CKD with OA. Methods This cohort study included 26,280 eligible participants aged ≥ 20 years who had valid data on CKD and OA from the National Health and Nutrition Examination Survey (NHANES) 2011–2020. The association between CKD and OA was studied by logistic regression, adjusting for demographics, body mass index (BMI), socioeconomic factors, physical activity, ever smoking, alcohol using, diabetes status and hypertension status. Results Among the participants of this study, 26.69% of OA patients had concurrent CKD, whereas this proportion was only 13.83% among non-OA patients.CKD was related to OA[OR:2.269 (95%CI:2.266–2.271), p

Abstract Bovine viral diarrhea virus (BVDV) is considered to be the most common agent of severe diarrhea in cattle worldwide, causing fever, diarrhea, ulcers, and abortion. Bovine herpesvirus 1 (BoHV-1) is also a major bovine respiratory disease agent that spreads worldwide and causes extensive damage to the livestock industry. Recombinase polymerase amplification (RPA) is a novel nucleic acid amplification method with the advantages of high efficiency, rapidity and sensitivity, which has been widely used in the diagnosis of infectious diseases. A dual RPA assay was developed for the simultaneous detection of BVDV and BoHV-1. The assay was completed at a constant temperature of 37 °C for 30 min. It was highly sensitive and had no cross-reactivity with other common bovine viruses. The detection rate of BVDV RPA in clinical samples (36.67%) was higher than that of PCR (33.33%), the detection rate of BoHV-1 RPA and PCR were equal. Therefore, the established dual RPA assay for BVDV and BoHV-1 could be a potential candidate for use as an immediate diagnostic.

The CIE hue angle has significant potential in marine ecology and environment monitoring using remote sensing methods. It is calculated from the remote sensing reflectance (Rrs) of all visible bands, which serves as a comprehensive indicator of seawater radiance information and represents one of the key quantitative parameters for assessing seawater color. In this study, a remote sensing retrieval model of total suspended matter concentration (TSM) was developed using the in situ measured data acquired in the coastal waters of Qinhuangdao from 2013 to 2021. This model, based on the CIE hue angle, achieved performance metrics of R2 = 0.68, MAPE=24.47%, and RMSE=2.72 mg/L, demonstrating better accuracy than traditional empirical models that utilize fewer bands. Based on this model, the monthly and interannual TSM in the coastal waters of Qinhuangdao from 2003 to 2023 were retrieved. Influenced by natural factors, such as the monsoons, the TSM in the coastal waters of Qinhuangdao generally exhibited a trend of first decreasing and then increasing from January to December. Except for certain anomalous years (2007, 2008, 2017, etc.), the overall variation process of TSM from 2003 to 2023 showed an initial increase followed by a decrease, closely related to the pollution reduction management requirements implemented by the Chinese government in different periods. The findings of this paper demonstrate that the coastal waters of Qinhuangdao have become clearer, and the ecological environment has been effectively improved as a result of the Chinese government’s vigorous promotion of ecological civilization construction, adhering to the development concept that ‘lucid waters and lush mountains are invaluable assets’, and by introducing the action plan for the comprehensive treatment of pollution in the Bohai Sea.

Recognition of ship traffic patterns can provide insights into the rules of navigation, maneuvering, and collision avoidance for ships at sea. This is essential for ensuring safe navigation at sea and improving navigational efficiency. With the popularization of the Automatic Identification System (AIS), numerous studies utilized ship trajectories to identify maritime traffic patterns. However, the current research focuses on the spatiotemporal behavioral feature clustering of ship trajectory points or segments while lacking consideration for multiple factors that influence ship behavior, such as ship static and maritime geospatial features, resulting in insufficient precision in ship traffic pattern recognition. This study proposes a ship traffic pattern recognition method that considers multi-attribute trajectory similarity (STPMTS), which considers ship static feature, dynamic feature, port geospatial feature, as well as semantic relationships between these features. First, A ship trajectory reconstruction method based on grid compression was introduced to eliminate redundant data and enhance the efficiency of trajectory similarity measurements. Subsequently, to quantify the degree of similarity of ship trajectories, a trajectory similarity measurement method is proposed that combines ship static and dynamic information with port geospatial features. Furthermore, trajectory clustering with hierarchical methods was applied based on the trajectory similarity matrix for dividing trajectories into different clusters. The quality of the similarity measurement results was evaluated by quality criterion to recognize the optimal number of ship traffic patterns. Finally, the effectiveness of the proposed method was verified using actual port ship trajectory data from the Tianjin Port of China, ranging from September to November 2016. Compared with other methods, the proposed method exhibits significant advantages in identifying traffic patterns of ships entering and leaving the port in terms of geometric features, dynamic features, and adherence to navigation rules. This study could serve as an inspiration for a comprehensive exploration of maritime transportation knowledge from multiple perspectives.

Abstract Background Motor neuron disease (MND) is a fatal neurodegenerative disorder that leads to progressive loss of motor neurons. Chlamydia psittaci (C. psittaci) is a rare etiology of community-acquired pneumonia characterized primarily by respiratory distress. We reported a case of C. psittaci pneumonia complicated with motor neuron disease (MND). Case presentation A 74-year-old male was referred to the Shaoxing Second Hospital at January, 2022 complaining of fever and fatigue for 2 days. The patient was diagnosed of MND with flail arm syndrome 1 year ago. The metagenomic next-generation sequencing (mNGS) of sputum obtained through bedside fiberoptic bronchoscopy showed C. psittaci infection. Then doxycycline was administrated and bedside fiberoptic bronchoscopy was performed to assist with sputum excretion. Computed Tomography (CT) and fiberoptic bronchoscopy revealed a significant decrease in sputum production. On day 24 after admission, the patient was discharged with slight dyspnea, limited exercise tolerance. One month later after discharge, the patient reported normal respiratory function, and chest CT showed significant absorption of sputum. Conclusions The mNGS combined with bedside fiberoptic bronchoscopy could timely detect C. psittaci infection. Bedside fiberoptic bronchoscopy along with antibiotic therapy may be effective for C. psittaci treatment.

Resistance to targeted therapy and immunotherapy in non-small cell lung cancer (NSCLC) is a significant challenge in the treatment of this disease. The mechanisms of resistance are multifactorial and include molecular target alterations and activation of alternative pathways, tumor heterogeneity and tumor microenvironment change, immune evasion, and immunosuppression. Promising strategies for overcoming resistance include the development of combination therapies, understanding the resistance mechanisms to better use novel drug targets, the identification of biomarkers, the modulation of the tumor microenvironment and so on. Ongoing research into the mechanisms of resistance and the development of new therapeutic approaches hold great promise for improving outcomes for patients with NSCLC. Here, we summarize diverse mechanisms driving resistance to targeted therapy and immunotherapy in NSCLC and the latest potential and promising strategies to overcome the resistance to help patients who suffer from NSCLC.

Aims: Heart failure with preserved ejection fraction (HFpEF) is a devastating health issue although limited knowledge is available for its pathogenesis and therapeutics. Given the perceived involvement of mitochondrial dysfunction in HFpEF, this study was designed to examine the role of mitochondrial dynamics in the etiology of HFpEF. Method and results: Adult mice were placed on a high fat diet plus l-NAME in drinking water (‘two-hit’ challenge to mimic obesity and hypertension) for 15 consecutive weeks. Mass spectrometry revealed pronounced changes in mitochondrial fission protein Drp1 and E3 ligase FBXL4 in ‘two-hit’ mouse hearts. Transfection of FBXL4 rescued against HFpEF-compromised diastolic function, cardiac geometry, and mitochondrial integrity without affecting systolic performance, in conjunction with altered mitochondrial dynamics and integrity (hyperactivation of Drp1 and unchecked fission). Mass spectrometry and co-IP analyses unveiled an interaction between FBXL4 and Drp1 to foster ubiquitination and degradation of Drp1. Truncated mutants of FBXL4 (Delta-Fbox) disengaged interaction between FBXL4 and Drp1. Metabolomic and proteomics findings identified deranged fatty acid and glucose metabolism in HFpEF patients and mice. A cellular model was established with concurrent exposure of high glucose and palmitic acid as a ‘double-damage’ insult to mimic diastolic anomalies in HFpEF. Transfection of FBXL4 mitigated ‘double-damage’-induced cardiomyocyte diastolic dysfunction and mitochondrial injury, the effects were abolished and mimicked by Drp1 knock-in and knock-out, respectively. HFpEF downregulated sarco(endo)plasmic reticulum (SR) Ca2+ uptake protein SERCA2a while upregulating phospholamban, RYR1, IP3R1, IP3R3 and Na+-Ca2+ exchanger with unaltered SR Ca2+ load. FBXL4 ablated ‘two-hit’ or ‘double-damage’-induced changes in SERCA2a, phospholamban and mitochondrial injury. Conclusion: FBXL4 rescued against HFpEF-induced cardiac remodeling, diastolic dysfunction, and mitochondrial injury through reverting hyperactivation of Drp1-mediated mitochondrial fission, underscoring the therapeutic promises of FBXL4 in HFpEF.

BackgroundLeukemia patients undergoing cryopreserved ovarian tissue transplantation (OTT) may carry a high risk of disease induction. Measurable residual disease (MRD) in bone marrow is linked to an elevated risk of relapse. It is controversial whether leukemia patients must be allowed to achieve measurable residual disease negative (MRD-negative) status instead of measurable residual disease positive (MRD-positive) status before ovarian tissue cryopreservation (OTC).ObjectiveTo explore the safety and efficacy of OTT in acute leukemia patients with different MRD status by using xenotransplantation.MethodCryopreserved ovarian tissue from 19 leukemia patients was thawed and xenotransplanted to ovariectomized BALB/C nude mice (n=36). The mice were divided into 2 groups based on the patient’s MRD status before OTC: MRD-negative group (n=18) and MRD-positive group (n=18), additionally, a control group consisted of ovariectomized mice (n=9). Body weight was measured weekly and mortality, emaciation, and other abnormalities were recorded. Twenty-six weeks post-surgery, livers, spleens, uteruses, and ovarian grafts were removed for macroscopic and histological examinations to evaluate the efficacy of xenotransplantation and assess malignant cell contamination in mice.ResultsFollicle growth was visible in the ovarian grafts of the MRD-negative and MRD-positive groups. Compared with the ovariectomized group, a significant decrease in body weight (p

Due to the physiological alteration during pregnancy, maternal gut microbiota changes following the metabolic processes. Recent studies have revealed that maternal gut microbiota is closely associated with the immune microenvironment in utero during pregnancy and plays a vital role in specific pregnancy complications, including preeclampsia, gestational diabetes, preterm birth and recurrent miscarriages. Some other evidence has also shown that aberrant maternal gut microbiota increases the risk of various diseases in the offspring, such as allergic and neurodevelopmental disorders, through the immune alignment between mother and fetus and the possible intrauterine microbiota. Probiotics and the high-fiber diet are effective inventions to prevent mothers and fetuses from diseases. In this review, we summarize the role of maternal gut microbiota in the development of pregnancy complications and the health condition of future generations from the perspective of immunology, which may provide new therapeutic strategies for the health management of mothers and offspring.

Soil-based irrigation and the partial substitution of chemical fertilizers with manure are promising practices to improve water and nitrogen (N) use efficiency. We hypothesize that their combination would simultaneously benefit potato production, tuber quality and profitability. A two-year experiment was conducted in semiarid northern China to investigate the combined effects of three water treatments [rainfed (W0), soil-based irrigation (W1), conventional irrigation (W2)] and three N treatments [no N (N0), chemical N (N1), 25% manure substitution (N2)] on these indicators, and to perform a comprehensive evaluation and correlation analysis. The results showed that water and N treatments separately affected all indicators except vitamin C content. Compared to W2, W1 significantly increased water productivity by 12% and irrigation water use efficiency (IWUE) by 30% due to 10% lower evapotranspiration and 21% lower water use. However, W1 and W2 negatively affected crude protein content. Conversely, this was compensated by the combination with N1 and N2. There were slight differences between N1 and N2 for all indicators on average across water treatments, while under W1, N2 significantly increased leaf area index (LAI) and N recovery efficiency (REN) by 18% and 29.4%, respectively, over N1. Also, comprehensive evaluations showed that W1N2 performed best, with the highest tuber yield, profit and acceptable quality. This can be explained by the increase in LAI, IWUE and REN due to the positive correlations with tuber yield and net return. Consequently, soil-based irrigation combined with 25% manure substitution had complementary effects on tuber quality and synergistic effects on potato productivity and profitability.

PurposeSarcopenia is considered to be an important predictor of adverse outcomes following spinal surgery, but the specific relationship between the two is not clear. The purpose of this meta-analysis is to systematically review all relevant studies to evaluate the impact of sarcopenia on spinal surgery outcomes.MethodsWe systematically searched PubMed, Embase and the Cochrane Library for relevant articles published on or before January 9, 2023. The pooled odds ratio (OR) with 95% confidence intervals (CIs) was calculated in a random effects meta-analysis. The main outcome was the risk of adverse outcomes after spinal surgery, including adverse events and mortality. This systematic review and meta-analysis was conducted following the PRISMA guidelines to evaluate the impact of sarcopenia on spinal surgery outcomes. In addition, we also conducted a subgroup analysis and leave-one-out sensitivity analyses to explore the main sources of heterogeneity and the stability of the results.ResultsTwenty-four cohort studies, with a total of 243,453 participants, met the inclusion criteria. The meta-analysis showed that sarcopenia was significantly associated with adverse events (OR 1.63, 95% CI 1.17-2.27, P < 0.001) but was no significantly associated with mortality (OR 1.17, 95% CI 0.93-1.46, P = 0.180), infection (OR 2.24, 95% CI 0.95-5.26, P < 0.001), 30-day reoperation (OR 1.47, 95% CI 0.92-2.36, P = 0.413), deep vein thrombosis (OR 1.78, 95% CI 0.69-4.61, P = 0.234), postoperative home discharge (OR 0.60, 95% CI 0.26-1.37, P = 0.002) and blood transfusion (OR 3.28, 95% CI 0.74-14.64, P = 0.015).ConclusionThe current meta-analysis showed that patients with sarcopenia have an increased risk of adverse events and mortality after spinal surgery. However, these results must be carefully interpreted because the number of studies included is small and the studies are significantly different. These findings may help to increase the clinicians' awareness of the risks concerning patients with sarcopenia to improve their prognosis.

BackgroundPeople living with HIV (PLWH) are susceptible to social isolation as a result of stigma and discrimination, which not only diminishes adherence to antiretroviral therapy but also heightens the risks of hospital readmission, depression, and mortality. However, there is currently no systematic review addressing the occurrence and impact of social isolation in individuals with HIV. Therefore, this study undertook a comprehensive systematic review and meta-analysis of existing literature to examine the prevalence and influencing factors associated with social isolation among PLWH.Methods and analysisPubMed, EMBASE, CINAHL, Cochrane Library, Web of Science, Google Scholar, China Science and Technology Journal Database, The China National Knowledge Infrastructure, WanFang Data and Chinese Biomedicine Literature Database will be searched from the establishment of the database to the latest search date. Literature screening, data extraction and literature quality assessment will be done independently by two researchers and results will be cross-referenced. Data analysis will be performed using stata15.1 software. Risk of publication bias will be assessed using Begg's and Egger's methods. Heterogeneity between studies will then be assessed using the I2 index and its 95% CI and Q statistics. Sources of heterogeneity will be accounted for by subgroup and sensitivity analyses.ResultsThe results may reveal the prevalence of social isolation among PLWH and provide data support for understanding its etiology and prevention.ConclusionBy systematically reviewing the existing literature on social isolation among PLWH, this study aims to provide a comprehensive understanding of the prevalence of social isolation within this population, elucidate the detrimental effects it poses for people affected by HIV, and effectively inform targeted interventions for high-risk groups. Furthermore, these findings offer valuable insights to support evidence-based decision-making in public health policy.Systematic review registrationPROSPERO registration number: CRD42024499044.

BackgroundAngiogenesis response plays a crucial role in the occurrence and development of Crohn’s disease (CD) and may involve the mechanism of infliximab non-response. However, the role of angiogenesis-related genes in Crohn’s disease has not been comprehensively studied. This study aimed to explore the expression profiles of angiogenesis-related genes in CD patients and construct models for disease diagnosis and prediction of infliximab non-response.MethodsCD-related microarray datasets were collected from the GEO database. Unsupervised consensus clustering analysis was performed based on differentially expressed angiogenesis-related genes to divide CD samples into two distinct clusters. Weighted gene co-expression network analysis (WGCNA) was conducted on the clusters to identify angiogenesis-related module. Based on the differentially expressed genes in the module, machine learning algorithms were employed to further identify hub genes and construct a disease diagnostic model. Subsequently, treatment outcome-related genes were extracted from these hub genes, and a predictive model for infliximab non-response in CD patients was ultimately built.ResultsBased on angiogenesis-related genes, we identified two distinct CD clusters (C1 and C2). Compared to C1, the metabolic pathways in C2 were significantly upregulated, and there was a higher abundance of cell clusters such as M1 macrophages and plasma cells. Additionally, C2 showed a poorer response to infliximab. Furthermore, a predictive model for infliximab non-response in CD patients was constructed based on the hub genes, and it was successfully validated using an external dataset.ConclusionComprehensive analysis of angiogenesis-related genes revealed different clusters of CD, which exhibited differential response rates to infliximab. The construction of models provides a reference for disease diagnosis and drug selection, aiding in clinical decision-making.

Objective To establish a cutoff level of AMH which could help for the diagnosis of PCOS, to investigate the predictive value of AMH combined with androgens in Chinese women to diagnose PCOS.Materials and Methods This is a prospective case control study, 550 women recruited (aged 20–40 years), in which 450 PCOS women recruited according to the Rotterdam criteria and 100 non-PCOS women in the control group were from the women for the pregnancy preparation examination. AMH were measured by the Elecsys AMH Plus immunoassay. Androgens and other sex hormone were measured. The validity of AMH toward the diagnosis of PCOS, or AMH combined with total testosterone, free testosterone, bioavailable testosterone and androstenedione was estimated by receiver operating characteristic (ROC)curves, and correlations between paired variables was estimated by Spearman’s rank correlation coefficient.Results The cutoff value of AMH in Chinese reproductive-age women with PCOS is 4.64 ng/mL, AUC under the curve is 0.938, with 81.6% sensitivity, and 92.0% specificity. Total testosterone, free testosterone, bioactive testosterone, and androstenedione are significantly higher in women with PCOS of reproductive age than in controls. The combination of AMH and free testosterone resulted in a higher AUC of 94.8%, with higher sensitivity (86.1%) and excellent specificity (90.3%) for the prediction of PCOS.Conclusion The Elecsys AMH Plus immunoassay, with a cutoff of 4.64 ng/mL, is a robust method for identifying PCOM to aid in PCOS diagnosis. The combination of AMH and free testosterone resulted in a higher AUC of 94.8% for the diagnose of PCOS.

Introduction Acute kidney injury (AKI) is a common complication in patients with community-acquired pneumonia (CAP) and negatively affects both short-term and long-term prognosis in patients with CAP. However, no study has been conducted on developing a clinical tool for predicting AKI in CAP patients. Therefore, this study aimed to develop a predictive tool based on a dynamic nomogram for AKI in CAP patients.Methods This retrospective study was conducted from January 2014 to May 2017, and data from adult inpatients with CAP at Nanjing First Hospital were analysed. Demographic data and clinical data were obtained. The least absolute shrinkage and selection operator (LASSO) regression model was used to select important variables, which were entered into logistic regression to construct the predictive model for AKI. A dynamic nomogram was based on the results of the logistic regression model. Calibration and discrimination were used to assess the performance of the dynamic nomogram. A decision curve analysis was used to assess clinical efficacy.Results A total of 2883 CAP patients were enrolled in this study. The median age was 76 years (IQR 63–84), and 61.3% were male. AKI developed in 827 (28.7%) patients. The LASSO regression analysis selected five important factors for AKI (albumin, acute respiratory failure, CURB-65 score, Cystatin C and white cell count), which were then entered into the logistic regression to construct the predictive model for AKI in CAP patients. The dynamic nomogram model showed good discrimination with an area under the receiver operating characteristics curve of 0.870 and good calibration with a Brier score of 0.129 and a calibration plot. The decision curve analysis showed that the dynamic nomogram prediction model had good clinical decision-making.Conclusion This easy-to-use dynamic nomogram may help physicians predict AKI in patients with CAP.

Tuberculosis (TB), attributed to the Mycobacterium tuberculosis complex, is one of the most serious zoonotic diseases worldwide. Nevertheless, the host mechanisms preferentially leveraged by Mycobacterium remain unclear. After infection, both Mycobacterium tuberculosis (MTB) and Mycobacterium bovis (MB) bacteria exhibit intimate interactions with host alveolar macrophages; however, the specific mechanisms underlying these macrophage responses remain ambiguous. In our study, we performed a comparative proteomic analysis of bovine alveolar macrophages (BAMs) infected with MTB or MB to elucidate the differential responses of BAMs to each pathogen at the protein level. Our findings revealed heightened TB infection susceptibility of BAMs that had been previously infected with MTB or MB. Moreover, we observed that both types of mycobacteria triggered significant changes in BAM energy metabolism. A variety of proteins and signalling pathways associated with autophagy and inflammation-related progression were highly activated in BAMs following MB infection. Additionally, proteins linked to energy metabolism were highly expressed in BAMs following MTB infection. In summary, we propose that BAMs may resist MTB and MB infections via different mechanisms. Our findings provide critical insights into TB pathogenesis, unveiling potential biomarkers to facilitate more effective TB treatment strategies. Additionally, our data lend support to the hypothesis that MTB may be transmitted via cross-species infection.

A new type of lithium niobate (LiNbO3) acousto-optic Q-switched Er,Cr:YSGG laser with high peak power was designed and the thermal lensing effect compensation was studied. The values of thermal focal length in the gain medium were calculated theoretically and measured experimentally. The experimental results validate the designed plane-convex resonator validity, and the output performance of the 2.79 μm Er,Cr:YSGG laser was obviously improved. When the laser operated at free running region, the maximum values of pulse energy was 160 mJ at 60 Hz, compared with the plane-parallel resonator, the pulse energy was increased by 2 times in the plane-convex resonator. When the LiNbO3 Q-switched laser operated at 60 Hz, the maximum values of pulse energy was 8.5 mJ, and the minimum values of pulse duration was 60.8 ns, and the corresponding peak power approximately was 140 kW, respectively. Compared with the plane-parallel resonator, the pulse energy was increased by 1.6 times in the plane-convex resonator, the corresponding peak power was increased by 2.3 times.

Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease caused by Crimean-Congo hemorrhagic fever virus (CCHFV), which can cause severe clinical disease and even death in humans. In recent years, the disease has spread to a wider area, posing a major public health threat to China as well as the Middle East, Europe and Africa, and there is no safe and effective vaccine to prevent the disease. Recently, it has been shown that using the Zera fusion to target proteins can enhance immunogenicity and improve the potential for developing viral vaccines. Based on this finding, in this study, two vaccine candidates, Zera-Gn and Zera-Np, were prepared using an insect baculovirus system expressing CCHFV glycoprotein (Gn) and nucleocapsid protein (Np) fused with Zera tags, and evaluated for immunogenicity in BALB/c mice. The obtainedresults showed that both Zera-Gn and Zera-Np recombinant nanoparticles were successfully expressed, and Zera-Gn had good induction of humoral and cellular immunity in mice, and its immunogenicity was significantly higher than that of Zera-Np. The results indicated that Zera-Gn self-assembled nanoparticles prepared by fusing Zera tags with CCHFV spike-in protein Gn have the potential to be a candidate vaccine for CCHF, and this study provides a reference for the development of Zera self-assembled nanoparticle vaccine for CCHF.

The objective of this study was to develop an indirect ELISA utilizing a polyclonal antibody against bovine rotavirus (BRV) VP6 protein. To achieve this, pcDNA3.1-VP6, a recombinant eukaryotic expression plasmid, was constructed based on the sequence of the conserved BRV gene VP6 and was transfected into CHO-K1 cells using the transient transfection method. The VP6 protein was purified as the coating antigen using nickel ion affinity chromatography, and an indirect ELISA was subsequently established. The study found that the optimal concentration of coating for the VP6 protein was 1 μg/mL. The optimal blocking solution was 3% skim milk, and the blocking time was 120 min. The secondary antibody was diluted to 1:4000, and the incubation time for the secondary antibody was 30 min. A positive result was indicated when the serum OD450 was greater than or equal to 0.357. The coefficients of variation were less than 10% both within and between batches, indicating the good reproducibility of the method. The study found that the test result was positive when the serum dilution was 217, indicating the high sensitivity of the method. A total of 24 positive sera and 40 negative sera were tested using the well-established ELISA. The study also established an indirect ELISA assay with good specificity and sensitivity for the detection of antibodies to bovine rotavirus. Overall, the results suggest that the indirect ELISA method developed in this study is an effective test for detecting such antibodies.

BackgroundThere is limited information about the efficacy of ovarian tissue cryopreservation (OTC) in children. In the present study, we report eight patients with rare diseases who underwent OTC in China’s first and largest ovarian tissue cryobank.ProcedureData from girls with rare diseases who underwent OTC between September 2020 and November 2022 were retrospectively analyzed. We also compared the number of cryopreserved cortex pieces, follicle number, and AMH in those with rare diseases and age-matched children with non-rare diseases who also underwent OTC in our cryobank.ResultsThe median age of the children was 5.88 ± 3.52 (range 2-13) years old. Unilateral oophorectomy was undertaken via laparoscopy in all of the children. The diseases in the 8 patients were: 4 mucopolysaccharidoses (MPS I two cases, IVA two cases), 1 Diamond-Blackfan anemia (DBA), 1 Fanconi anemia (FA), 1 hyperimmunoglobulin E syndrome (HIES), 1 Niemann-Pick disease. The number of cryopreserved cortex pieces was 17.13 ± 6.36, and the follicle count per 2 mm biopsy was 447.38 ± 524.35. No significant difference in age, the count of cryopreserved cortex pieces, follicle number per 2 mm biopsy, and AMH level was seen between the 20 children with non-rare diseases and those with rare diseases.ConclusionsThe reports help practitioners counsel girls with rare diseases about fertility preservation. The demand for OTC in pediatrics will likely grow as a standard of care.

Crimean-Congo hemorrhagic fever (CCHF), which has a fatality rate of 20–30%, is widely prevalent in several regions in Asia, Europe, and Africa and has spread to a wider range of areas in recent years. At present, there is a lack of safe and effective vaccines for the prevention of CCHF. In this study, we prepared three vaccine candidates, rvAc-Gn, rvAc-Np, and rvAc-Gn-Np, that encoded the CCHF virus (CCHFV) glycoprotein Gn and the nucleocapsid protein (Np) on the surface of baculovirus using an insect baculovirus vector expression system (BVES) and evaluated their immunogenicity in BALB/c mice. The experimental results showed that both CCHFV Gn and Np were expressed by the respective recombinant baculoviruses and anchored to the viral envelope. BALB/c mice were immunized, and all three recombinant baculoviruses showed significant humoral immunity. At the cellular level, the level of immunity in the rvAc-Gn group was significantly higher than that in the rvAc-Np and rvAc-Gn-Np groups, and the rvAc-Gn-Np coexpression group exhibited the lowest level of cellular immunity. In conclusion, the strategy of coexpressing Gn and Np in the baculovirus surface display system did not result in improvements in immunogenicity, whereas the recombinant baculovirus displaying Gn alone could induce significant humoral and cellular immunity in mice, indicating that rvAc-Gn has potential as a CCHF vaccine candidate. This study thus provides new ideas for the development of a CCHF baculovirus vaccine.

Abstract Background This study investigated the relationships of neutrophil count (NC), neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) with cerebral small vessel disease (CSVD). Methods A total of 3052 community-dwelling residents from the Poly-vasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study were involved in this cross-sectional study. CSVD burden and imaging markers, including white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces in basal ganglia (BG-EPVS), were assessed according to total CSVD burden score. The associations of NC, NLR and SII with CSVD and imaging markers were evaluated using logistic regression models. Furthermore, two-sample Mendelian randomization (MR) analysis was performed to investigate the genetically predicted effect of NC on CSVD. The prognostic performances of NC, NLR and SII for the presence of CSVD were assessed. Results At baseline, the mean age was 61.2 ± 6.7 years, and 53.5% of the participants were female. Higher NC was suggestively associated with increased total CSVD burden and modified total CSVD burden (Q4 vs. Q1: common odds ratio (cOR) 1.33, 95% CI 1.05–1.70; cOR 1.28, 95% CI 1.02–1.60) and marginally correlated with the presence of CSVD (OR 1.29, 95% CI 1.00–1.66). Furthermore, elevated NC was linked to a higher risk of lacune (OR 2.13, 95% CI 1.25–3.62) and moderate-to-severe BG-EPVS (OR 1.67, 95% CI 1.14–2.44). A greater NLR was related to moderate-to-severe BG-EPVS (OR 1.68, 95% CI 1.16–2.45). Individuals with a higher SII had an increased risk of modified WMH burden (OR 1.35, 95% CI 1.08–1.69) and moderate-to-severe BG-EPVS (OR 1.70, 95% CI 1.20–2.41). MR analysis showed that genetically predicted higher NC was associated with an increased risk of lacunar stroke (OR 1.20, 95% CI 1.04–1.39) and small vessel stroke (OR 1.21, 95% CI 1.06–1.38). The addition of NC to the basic model with traditional risk factors improved the predictive ability for the presence of CSVD, as validated by the net reclassification index and integrated discrimination index (all p

Abstract Aim To investigate the effects of free fatty acids on mitochondrial oxidative stress and the pathogenesis of preeclampsia. Methods Human primary trophoblast cells at 6–8 weeks of gestation were retrieved and cultured to 70–80% confluence, then incubated in serum from women with a normal pregnancy (normal pregnancy group), women with preeclampsia (PE group), and a combination of serum from women with 24 h preeclampsia-like symptoms and free fatty acids (FFA group). Mitochondrial membrane potential was assessed by fluorescent dye concurrent with detection of membrane channel conversion pore activity by fluorescence microscope. Enzyme labeling instruments and RT-PCR were used to detect mitochondrial DNA (mtDNA) levels. Results The preeclampsia and free fatty acids groups both exhibited significantly higher levels of mitochondria oxidative stress damage when compared to the normal pregnancy group. However, no significant differences in mitochondrial oxidative stress damage were observed between the FFA and PE groups. Conclusions Serum free fatty acids might play an important role in the pathogenesis of preeclampsia by enhancing mitochondrial oxidative stress damage.

In this study, we explored the relationship between the platelet endothelial aggregation receptor 1 (PEAR1) polymorphisms, platelet reactivity, and clinical outcomes in patients with minor stroke or transient ischemic attack (TIA). Randomized controlled trial subgroups were assessed, wherein patients received dual antiplatelet therapy for at least 21 days. Platelet reactivity was measured at different time intervals. Genotypes were categorized as wild-type, mutant heterozygous, and mutant homozygous. Clinical outcomes were evaluated after 90 days. The rs12041331 polymorphism predominantly influenced adenosine diphosphate channel platelet activity, with the AA genotype displaying significantly lower residual platelet activity to the P2Y12 response unit (p < 0.01). This effect was more evident after 7 days of dual antiplatelet treatment (p = 0.016). Mutant A allele carriers had decreased rates of recurrent stroke and complex endpoint events but were more prone to bleeding (p = 0.015). The rs2768759 polymorphism majorly impacted arachidonic acid (AA) channel platelet activity, which was particularly noticeable in the C allele carriers. Our regression analysis demonstrated that rs12041331 AA + GA and rs2768759 CA predicted 90-day post-stroke bleeding. In conclusion, the PEAR1 polymorphisms rs12041331 and rs2768759 interfere with platelet aggregation and the performance of antiplatelet drugs. These genetic variations may contribute to bleeding events associated with minor stroke and TIA.

Background: Major depression is one of the most common psychiatric disorders worldwide, inflicting suffering, significant reduction in life span, and financial burdens on families and society. Mounting evidence implicates that exposure to chronic stress can induce the dysregulation of the immune system, and the activation of brain-resident innate immune cells, microglia, leading to depression-like symptoms. However, the specific mechanisms need to be further elucidated.Method: Animal models of depression were established by chronic restraint stress (CRS), and depression-like behavior was assessed by sucrose preference test (SPT), open field test (OFT), tail suspension test (TST) and forced swimming test (FST). Microglial activation was visualized by immunofluorescent and immunohistochemical staining, and microglial morphological changes were further analyzed by skeleton analysis. The levels of inflammatory cytokines were detected by western blotting and qPCR.Result: Microglial Dlg1 knockout ameliorates CRS-induced mice depression-like behavior. In contrast to the effect of Dlg1 in the LPS-induced mouse model, Dlg1 knockout had little effect on microglial density, but significantly decreased the number of activated microglia and reversed microglia morphological changes in mice challenged with CRS. Moreover, the upregulation of inflammatory cytokines following CRS exposure was partially reversed by Dlg1 deletion.Conclusion: Our study provides the evidence that Dlg1 ablation in microglia remarkedly reverses microglial activation and depression-like behavior in mice exposed to CRS, implicating a potential target for the treatment of clinical depression.

Particulate organic carbon (POC) in the surface ocean contributes to understanding the global ocean carbon cycle system. The surface POC concentration can be effectively detected using satellites. In open oceans, the blue-to-green band ratio (BG) algorithm is often used to obtain global surface ocean POC concentrations. However, POC concentrations are underestimated in waters with complex optical environments. To generate a more accurate global POC mapping in the surface ocean, we developed a new ocean color algorithm using a mixed global-scale in situ POC dataset with the concentration ranging from 11.10 to 4389.28 mg/m3. The new algorithm (a-POC) was established to retrieve the POC concentration using the strong relationship between the absorption coefficient at 490 nm (a(490)) and POC, in which a(490) was from the Ocean Color Climate Change Initiative (OC-CCI) v5.0 suite. Afterward, the a-POC algorithm was applied to OC-CCI v5.0 data for special regions and the global ocean. The performances of the a-POC algorithm and the BG algorithm were compared by combining the match-ups of satellite data and in situ dataset. The results showed that the statistical parameters of the a-POC algorithm were similar to those of the BG algorithm in the Atlantic oligotrophic gyre regions, with a median absolute percentage deviation (MAPD) value of 22.04%. In the eastern coastal waters of the United States and the Chesapeake Bay, the POC concentration retrieved by the a-POC algorithm was highly consistent with the match-ups, and MAPD values were 33.06% and 26.11%. The a-POC algorithm was also applied to the Ocean and Land Color Instrument (OLCI) data pre-processed with different atmospheric correction algorithms to evaluate the universality. The result showed that the a-POC algorithm was robust and less sensitive to atmospheric correction than the BG algorithm.

Detailed research on China's CO2 emission pathway of the 2030 peak and 2060 carbon neutrality goals is fundamental to promote China's climate change action. Previous studies on emission pathways have been based on long-term emission data or model analyses. However, few studies have achieved synergy and pathway optimization at both the micro and macro levels or focused on China's 2060 carbon neutrality goal, making it difficult to support the systematic management of national and regional emission pathways. In this study, we developed an integrated CO2 emission pathway model, the Chinese Academy of Environmental Planning Carbon Pathways 1.2 model, under China's climate change goals. Our pathway coupled the top–down and bottom–up approaches and conducted optimization analysis under social fairness and optimal cost conditions. The results provide a clear CO2 emission pathway and offer insights for implementing fine management of CO2 emissions at the national, regional, sectoral, and spatial gridded levels.

Abstract This study aimed to investigate the characteristics, moisture contents, chemical fingerprints changes and aflatoxins accumulation of Atractylodis rhizoma during storage, further to determine the optimum temperature and relative humidity conditions. Based on the suitable temperature (20–40 °C) and relative humidity (80–95%), 13 different temperature and humidity conditions were set up by the central composite design-response surface methodology (CCD-RSM) for Aspergillus flavus. After inoculation with Aspergillus flavus by artificial infection, A. rhizoma samples were stored under normal conditions and 13 different temperature and relative humidity levels. By taking the changes of characteristics, the contents of moisture, chemical fingerprints and aflatoxins as the evaluation indexes for A. rhizoma with or without Aspergillus flavus fungi to optimize the optimal storage conditions. After storage for 10 days, the color of A. rhizoma was deepened, the water content and chemical composition increased, and some unknown components were detected. The susceptible condition for aflatoxins production in A. rhizoma was identified at temperature 22–37 °C and relative humidity over 87.5%. Thus, the suitable storage conditions for A. rhizoma should be controlled at temperature below 20 °C and relative humidity less than 85%. This paper screened out the optimum temperature and humidity for the storage of A. rhizoma. Then, the storage specification for A. rhizoma was proposed, lying technical and data support for the scientific preservation of other food or herbs.

Background and Objective: Pre-eclampsia (PE) is a hypertensive gestational disease appearing during second trimester of pregnancy. Free radicals are released by the placenta in this condition that may cause oxidative damage. This study was designed to determine the serum ferritin (SF) levels in maternal blood, fetal umbilical cord blood and placenta and the changes associated with oxidative stress as well as cell apoptosis to understand the pathogenesis of PE. Methods: This cross-sectional analytical study recruited 60 pregnant females with severe PE and assigned into early and late onset PE groups. Another n = 60 cases of normal pregnant females with similar gestational weeks were selected in the control group. Maternal serum and fetal umbilical cord blood ferritin levels were determined by automatic biochemical immunoassay system. Reverse transcription real-time fluorescence, Western blot and colorimetry were used to determine mRNA expression levels of ferritin and ferritin heavy chain, relative expression of ferritin and superoxide dismutase, malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels, respectively. Results: Mean age was 30.89 ± 5.65 and 31.79 ± 5.06 years in early and late onset PE groups respectively. Serum uric acid and creatinine levels of both PE groups were significantly higher than the normal pregnant females. SF levels were also higher in the participants of PE groups. However, the mRNA and ferritin protein levels in placental tissue were significantly lower in PE groups while comparing to controls. The cleaved caspase-3 protein, GSH-Px and MDA levels were significantly higher in both PE groups (p < 0.05). Conclusion: The alterations in factors related to oxidative stress and cell apoptosis in placental tissue may be helpful to understand the pathogenesis of PE and may provide potential biomarkers for the diagnosis of PE.

ABSTRACT Blood-sucking ticks are obligate parasites and vectors of a variety of human and animal viruses. Some tick-borne viruses have been identified as pathogens of infectious diseases in humans or animals, potentially imposing significant public health burdens and threats to the husbandry industry. Therefore, identifying the profiles of tick-borne viruses will provide valuable information about the evolution and pathogen ecology of tick-borne viruses. In this study, we investigated the viromes of parasitic ticks collected from the body surfaces of herbivores in Xinjiang Uyghur Autonomous Region and Inner Mongolia Autonomous Region of China, two regions in northwest China. By using a metatranscriptomic approach, 17 RNA viruses with high diversity in genomic organization and evolution were identified. Among them, nine are proposed to be novel species. The classified viruses belonged to six viral families, including Phenuiviridae, Rhabdoviridae, Peribunyaviridae, Lispiviridae, Chuviridae, and Reoviridae, and unclassified viruses were also identified. In addition, although some viruses from different sampling locations shared significant similarities, the abundance and diversity of viruses notably varied among the different collection locations. This study demonstrates the diversity of tick-borne viruses in Xinjiang and Inner Mongolia and provides informative data for further study of the evolution and pathogenicity of these RNA viruses. IMPORTANCE Ticks are widely distributed in pastoral areas in northwestern China and act as vectors that carry and transmit a variety of pathogens, especially viruses. Our study revealed the diversity of tick viruses in Xinjiang and Inner Mongolia and uncovered the phylogenetic relationships of some RNA viruses, especially the important zoonotic tick-borne severe fever with thrombocytopenia syndrome virus in Inner Mongolia. These data suggest a complex and diverse evolutionary history and potential ecological factors associated with pathogenic viruses. The pathogenicity of these tick-borne viruses currently remains unclear. Therefore, future research should focus on evaluating the transmissability and pathogenicity of these tick-borne viruses.

Background and purposeThis study aimed to investigate the relationship between neutrophil-to-lymphocyte ratio (NLR) and early neurological deterioration (END) among cases suffering from single subcortical infarction (SSI) and diabetes.MethodsWe collected the data of patients with SSI admitted to our hospital between January 2019 and December 2020 retrospectively. A score of ≥2 elevations in overall National Institutes of Health Stroke Scale (NIHSS) score or ≥1 increase in motor NIHSS score in 5-day post-admission was considered END. Furthermore, logistic regression was used to analyze the relationship between NLR and END among SSI cases.ResultsAltogether, we enrolled 235 consecutive SSI cases, of which 53 (22.5%) were diagnosed with END, while 93 (39.5%) were diabetic. In patients with diabetes, the value of NLR increased markedly among the patients with END (median, 3.59; IQR, 2.18–4.84) compared to patients without END (median, 2.64; IQR, 1.89–3.18; P = 0.032). Meanwhile, in patients without diabetes, NLR was not significantly associated with END. In the multivariate analysis, NLR values were positively related to END (adjusted odds ratio (OR), 1.768; 95% CI, 1.166–2.682, P = 0.007) upon adjusting age, SSI type, lesion diameter, initial NIHSS, fasting blood glucose (FBG), 2-h postprandial blood glucose (2hPBG), and estimated glomerular filtration rate (eGFR). The subgroup analysis showed that the relationship between NLR and END was more pronounced in the branch atheromatous disease (BAD) (adjusted OR, 1.819; 95% CI, 1.049–3.153, P = 0.033) and anterior SSI subgroups (adjusted OR, 2.102; 95% CI, 1.095–4.037, P = 0.026).ConclusionNLR value was significantly related to END among SSI patients with diabetes and was recognized as an independent factor in predicting the risk of END.

Background: For localized disease, partial nephrectomy of small tumors continues to be the gold-standard treatment. However, temporary clamping is routinely performed during this process to control renal blood flow, which can cause renal ischemic/reperfusion injury. We evaluated whether dexmedetomidine postconditioning (DPOC) can reduce renal ischemic/reperfusion injury for patients receiving laparoscopic partial nephrectomy (LPN).Methods: This randomized double-blind controlled trial included 77 patients who were scheduled for LPN at our hospital. Patients were randomly allocated to the DPOC or control group. DPOC was performed via intravenous administration of dexmedetomidine at 0.6 μg kg−1 for 10 min immediately after unclamping the renal artery. In the control group, saline was administered in place of dexmedetomidine under the same protocol. All participants underwent a 6-month follow-up. The primary outcome were the values of 99mTc-DTPA-GFR in the affected kidney at one and 6 months post-LPN.Result: The GFR values in the DPOC group (35.65 ± 4.89 ml min−1.1.73 m−2) were significantly higher than those the control group (33.10 ± 5.41 ml min−1.1.73 m−2; p = 0.022) at 1 month after LPN. There was no statistically significant difference in GFR value between the two groups at 6 months after LPN.Conclusion: DPOC provides therapeutic benefits to LPN patients, at least on a short-term basis, by alleviating renal ischemic/reperfusion injury.Clinical Trial Registration: Chinese Clinical Trial Registry, identifier [ChiCTR-TRC-14004766].

N6-methyladenosine (m6A) modification regulates RNA translation, splicing, transport, localization, and stability at the post-transcriptional level. The m6A modification has been reported to have a wide range of effects on the nervous system, including neurogenesis, cerebellar development, learning, cognition, and memory, as well as the occurrence and development of neurological disorders. In this review, we aim to summarize the findings on the role and regulatory mechanism of m6A modification in the nervous system, to reveal the molecular mechanisms of neurodevelopmental processes, and to promote targeted therapy for nervous system-related diseases.

Background Annexin A5 (ANXA5) haplotypes can increase the risk of recurrent pregnancy loss (RPL). This study aimed to investigate the effect of ANXA5 haplotypes on ANXA5 expression in patients with RPL. Methods Female subjects with RPL, parous controls (those who intentionally aborted without medical conditions or complications), and population controls (normal delivery) were studied. Real-time polymerase chain reaction was carried out to evaluate ANXA5 expression in the placenta and peripheral blood. Western blotting and immunohistochemistry were used to assess ANXA5 protein expression. The luciferase assay was performed to detect the effect of M1 and M2 haplotypes on transcription efficiency of the ANXA5 promoter. Results We found that the percentage of the M2 carrier was highest in the RPL group. ANXA5 expression in the placenta and peripheral blood in subjects with RPL was significantly inhibited. Furthermore, ANXA5 expression in subjects carrying the M2 haplotype was remarkably suppressed compared with that in carriers of other haplotypes. Finally, the M2 haplotype decreased the transcription efficiency of the ANXA5 promoter. Conclusion Our findings show that ANXA5 expression is decreased in carriers of the M2 haplotype and that M1/M2 haplotypes in the ANXA5 gene are associated with an increased risk of RPL.

BackgroundOvarian tissue cryopreservation (OTC) is the only method of fertility preservation (FP) in prepubertal girls, but the experience remains limited. This study investigates the effectiveness and feasibility of FP of OTC in children facing gonadotoxicity treatment in Chinese first ovarian tissue cryobank.ProcedureOTC and evaluation of 49 children ≤14 years old in the cryobank of Beijing Obstetrics and Gynecology Hospital, Capital Medical University, from July 2017 to May 19, 2022, were analyzed retrospectively. We compared children’s general characteristics, follicle numbers, and hormone levels with and without chemotherapy before OTC.ResultsThe age of 49 children at the time of OTC was 7.55 (1–14) years old. There were 23 cases of hematological non-malignant diseases, eight cases of hematological malignant diseases, four cases of gynecological malignant tumors, one case of neurological malignant tumors, one case of bladder cancer, five cases of sarcoma, three cases of mucopolysaccharidosis, one case of metachromatic leukodystrophy, two cases of dermatomyositis, one case of Turner’s syndrome. The median follicular count per 2-mm biopsy was 705. Age and AMH were not correlated (r = 0.084, P = 0.585). Age and follicle count per 2-mm biopsy was not correlated (r = −0.128, P = 0.403). Log10 (follicle count per 2-mm biopsy) and Log10 (AMH) were not correlated (r = −0.118, P = 0.456). Chemotherapy before OTC decreased AMH levels but had no significant effect on the number of follicles per 2-mm biopsy.ConclusionsOTC is the only method to preserve the fertility of prepubertal girls, and it is safe and effective. Chemotherapy before OTC is not a contraindication to OTC.

Abstract Background The number of research articles on health-related quality of life (HRQoL) has been strikingly increasing. This study aimed to explore the general trends and hotspots of HRQoL. Methods Based on the Web of Science database, research on HRQoL published between 2000 and 2019 were identified. A bibliometric analysis was performed based on the number of articles, citations, published journals, authors' addresses, and keywords. Descriptive analysis, visualization of geographic distribution and keyword clustering analysis were applied to the collected data. Results The annual number of articles showed growth over the past twenty years, but the annual total citations and annual citations per article were both in decreasing trends. Articles about HRQoL were more likely to be published in journals of multi-subject categories. The HRQoL research was mainly distributed across North America and Europe throughout the twenty years and ushered in a vigorous development worldwide after 2015. Cooperation strength between domestic institutions was much greater than that of international institutions. HRQoL research had six concentrated clusters: HRQoL, Depression, Obesity, Disability, Oncology, Fatigue. Conclusion This study provided an overall perspective of global research trends and hotspots in HRQoL, and a potential insight for future research. HRQoL research had experienced significant increasing development during 2000–2019, especially the HRQoL measurement instruments, however, there were significant regional disparities in scientific output in HRQoL.

The role of inulin in alleviating obesity-related disorders has been documented; yet, its underlying mechanisms still need to be further investigated. This study attempted to elucidate the causative link between the gut microbiota and the beneficial effect of inulin on obesity-related disorders via transferring the fecal microbiota from inulin-dosed mice to high-fat diet (HFD)-induced obese recipient mice. The results show that inulin supplementation can decrease body weight, fat accumulation, and systemic inflammation and can also enhance glucose metabolism in HFD-induced obese mice. Treatment with inulin reshaped the structure and composition of the gut microbiota in HFD-induced obese mice, as characterized by increases in the relative abundances of Bifidobacterium and Muribaculum and decreases in unidentified_Lachnospiraceae and Lachnoclostridium. In addition, we found that these favorable effects of inulin could be partially transferable by fecal microbiota transplantation, and Bifidobacterium and Muribaculum might be the key bacterial genera. Therefore, our results suggest that inulin ameliorates obesity-related disorders by targeting the gut microbiota.

A full-band digital television (DTV) transmitting antenna array with dual-layer bowtie dipole unit is proposed in this paper. The dual-layer bowtie dipole is utilized as the antenna unit to broaden the frequency bandwidth, and its key parameters are discussed. Besides, a wideband impedance matching network with stepped complex impedance transformers is designed to achieve the full-band low voltage standing wave ratio (VSWR). For verification, a prototype is designed, fabricated, and measured. The experimental results agree well with the simulations. The measurement shows a relative bandwidth of 62.4% (455 MHz - 868 MHz) under the criterion of VSWR

In this study, a latest reanalysis dataset of atmospheric composition, the Global Exposure Mortality Model and a log-linear exposure-response function were employed to estimate the national deaths attributable to fine particulate matter (PM _2.5 ) and ozone (O _3 ) pollution in China for the period 2016–2020, including the lockdown due to COVID-19 pandemic in 2020. The national mortality attributable to long-term PM _2.5 exposure decreased year by year from 2.18 million (95% confidence interval (1.83, 2.51), the same hereinafter) in 2016 to 1.99 million (1.66, 2.30) in 2020. In particular, the number in 2020 was 133.16 thousand less than 2019 owing to the reduced emissions during the pandemic, and the mortality attributable to short-term PM _2.5 exposure dropped from 46.86 thousand in 2019 to 36.56 thousand in 2020. However, because O _3 concentrations have kept increasing during the period, the national mortality attributable to long-term O _3 exposure increased from 132.79 thousand (128.58, 137.00) in 2016 to 197.00 thousand (190.98, 203.03) in 2020. In addition, compared to before the pandemic, the national mortality attributable to short-term O _3 exposure showed an increase in February, April and May of 2020, and the sharpest year-on-year increase of 162% occurred in April. The different trends of mortality after anthropogenic emissions were reduced pose a challenge for policy-makers and researchers.

ObjectiveWe explored the gut microbiome and serum metabolome alterations in patients with premature ovarian insufficiency (POI) and the effects of hormone replacement therapy (HRT) with the aim to unravel the pathological mechanism underlying POI.MethodsFecal and serum samples obtained from healthy females (HC, n = 10) and patients with POI treated with (n = 10) or without (n = 10) HRT were analyzed using 16S rRNA gene sequencing and untargeted metabolomics analysis, respectively. Peripheral blood samples were collected to detect serum hormone and cytokine levels. Spearman’s rank correlation was used to evaluate correlations between sex hormones and cytokines and between the gut microbiota and serum metabolites. To further confirm the correlation between Eggerthella and ovarian fibrosis, the mice were inoculated with Eggerthella lenta (E. lenta) through oral gavage.ResultsThe abundance of genus Eggerthella significantly increased in the fecal samples of patients with POI compared to that observed in the samples of HCs. This increase was reversed in patients with POI treated with HRT. Patients with POI showed significantly altered serum metabolic signatures and increased serum TGF-β1 levels; this increase was reversed by HRT. The abundance of Eggerthella was positively correlated with altered metabolic signatures, which were, in turn, positively correlated with serum TGF-β1 levels in all subjects. Estrogen ameliorated ovarian fibrosis induced by E. lenta in mice.ConclusionsThe interactions between the gut microbiota, serum metabolites, and serum TGF-β1 in patients with POI may play a critical role in the development of POI. HRT not only closely mimicked normal ovarian hormone production in patients with POI but also attenuated gut microbiota dysbiosis and imbalance in the levels of serum metabolites and TGF-β1, which are reportedly associated with fibrosis. The findings of this study may pave the way for the development of preventive and curative therapies for patients with POI.

Our previous studies have proved that 17β-hydroxysteroid dehydrogenase 4 (HSD17B4) is a novel proliferation-promoting protein. The overexpression of HSD17B4 promotes hepatocellular carcinoma (HCC) cell proliferation. Vitamin K2 (VK2), a fat-soluble vitamin, has the function of promoting coagulation and can inhibit the progression of liver cancer. A previous study demonstrated that VK2 could bind to HSD17B4 in HepG2 cells. However, the mechanism of VK2 in inhibiting HCC cell proliferation is not clear. In this study, we investigate whether VK2 can inhibit the proliferation of HCC cell induced by HSD17B4 and the possible mechanism. We detected the effect of VK2 on HSD17B4-induced HCC cell proliferation, and the activation of STAT3, AKT, and MEK/ERK signaling pathways. We measured the effect of HSD17B4 on the growth of transplanted tumor and the inhibitory effect of VK2. Our results indicated that VK2 directly binds to HSD17B4, but does not affect the expression of HSD17B4, to inhibit the proliferation of HCC cells by inhibiting the activation of Akt and MEK/ERK signaling pathways, leading to decreased STAT3 activation. VK2 also inhibited the growth of HSD17B4-induced transplanted tumors. These findings provide a theoretical and experimental basis for possible future prevention and treatment of HCC using VK2.

Breast cancer is the most commonly diagnosed cancer in women. Resveratrol, a naturally occurring phytochemical, shows great promise in developing novel anti-cancer therapies. This study hypothesized that the mitochondria-targeted delivery of resveratrol would increase its potency and induce mitochondria-mediated apoptosis. The targeted delivery of resveratrol was achieved by conjugating resveratrol to triphenylphosphonium (TPP). The anti-cancer effects of TPP-resveratrol were studied in the murine breast cancer 4T1 and the human breast cancer MDA-MB-231 cell lines. Flow cytometry was used to study apoptosis induction, cell cycle arrest, and mitochondrial membrane potential loss. The morphological changes in the mitochondria in MDA-MB-231 cells after TPP-resveratrol treatments were examined using transmission electron microscopy. Moreover, the changes in MDA-MB-231 cell metabolism after resveratrol and TPP-resveratrol treatments were studied using metabolomic analysis. We demonstrate that TPP-resveratrol significantly improved cytotoxicity in 4T1 cells and MDA-MB-231 cells by inducing apoptosis and mitochondrial membrane potential loss. Swollen and vacuolated mitochondria were observed after the TPP-resveratrol treatment. Meanwhile, TPP-resveratrol treatment down-regulated amino acid and energy metabolism and caused the dysfunction of purine and pyrimidine metabolism. Our results provide evidence supporting the targeted delivery of resveratrol to mitochondria and suggest that TPP-resveratrol may be an effective agent for breast cancer treatment.

Abstract Background Auxin conjugates are hydrolyzed to release free auxin to ensure defined cellular auxin levels or gradients within tissues for proper development or response to environmental signals. The auxin concentration in the abscission zone (AZ) is thought to play an important role in mediating the abscission lag phase. Results In this study, the full cDNA sequences of seven tomato ILR1-like SlILL genes were identified and characterized, All SlILLs were found to have auxin conjugate hydrolysis activity. The effects of different auxin conjugates on abscission identified IAA-Ile as a candidate to determine the auxin conjugate and auxin conjugate hydrolysis functions in abscission. Treatment of pedicel explants with IAA-Ile for different times showed that application before 6 h could effectively delay abscission. IAA-Ile pre-incubation for 2 h was sufficient to inhibit abscission. These results showed that there is not sufficient auxin conjugates in the AZ to inhibit abscission, and the optimal time to inhibit abscission by the application of exogenous auxin conjugates is before 6 h. Treatment with cycloheximide (CHX, a protein biosynthesis inhibitor) indicated that de novo synthesis of auxin conjugate hydrolases is also required to delay abscission. During abscission, SlILL1, 5, and 6 showed abscission-related gene expression patterns, and SlILL1, 3, 5, 6, and 7 showed increasing expression trends, which collectively might contribute to delay abscission. Silencing the expression of SlILL1, 3, 5, 6, and 7 using virus-induced gene silencing showed that SlILL1, 5, and 6 are major mediators of abscission in tomato. Conclusions In the process of abscission, auxin inhibition is concentration dependent, and the concentration of auxin in the AZ was regulated by hydrolyzed auxin conjugates. SlILR1, 5, and 6 play a key role in flower pedicel abscission.

Activin A, a member of the transforming growth factor-beta (TGF-β) superfamily, contributes to tissue healing and fibrosis. As the innate tissue cells, fibroblasts also play an important role in wound healing and fibrosis. Herein, this study was aimed to investigate how activin A exhibited regulatory effects on adhesion and migration of fibroblasts. We found that activin A induced the migration of fibroblast cell line L929 cells in transwell chamber and microfluidic device. Activin A also promoted L929 cells adhesion, but did not affect L929 cells viability or proliferation. In addition, activin A induced α-SMA expression and TGF-β1 release, which were factors closely related to tissue fibrosis, but had no effect on IL-6 production, a pro-inflammatory cytokine. Furthermore, activin A elevated calcium levels in L929 cells and increased p-ERK protein levels. Activin A-induced migration of L929 cells was attenuated by ERK inhibitor FR180204. To conclude, these data indicated that activin A as a novel chemokine induced the chemotactic migration of L929 cells via ERK signaling and possessed the pro-fibrosis role. These findings provide a new insight into understanding of activin A in tissue fibrosis.

Summary: Activin A levels are elevated during multiple severe infections and associated with an increased risk of death. However, the role of activin A in bacterial infection is still unclear. Here, we found that activin A levels were increased during S. aureus skin infection in mice. Administration of activin A increased the bacterial burden and promoted the spread of bacteria in vivo. Moreover, activin A inhibited neutrophil chemotaxis to N-formylmethionine-leucyl-phenylalanine via the type IIA activin receptor (ActRIIA) in vitro and impaired ActRIIA+ neutrophil recruitment to infection foci in vivo. Additionally, we identified a novel subpopulation of neutrophils, ActRIIA+ neutrophils, which exhibit superior phagocytic capacity compared to ActRIIA− neutrophils and possess an N2-like immunoregulatory activity via secreting IL-10 and TGF-β. Taken together, these findings indicate that activin A inhibits the recruitment of ActRIIA+ neutrophils to infected foci, leading to the impairment of bacterial clearance, and thus may hamper early infection control.