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Abstract This study examined to evaluate the predictive value of a nomogram with Ki-67 in overall and disease-free survival in glioma patients, a total of 76 patients diagnosed with glioma by pathology in Tengzhou Central People’s Hospital were enrolled. The baseline data and follow ups were retrospectively collected from medical records. The associations between Ki-67 and survival status were examined using log-rank test, univariate and multivariate Cox proportional hazard regression models. Calibrations were performed to validate the established nomograms. Ki-67 negative group showed of a longer OS survival time and a longer PFS survival time with log-rank test (x2 = 16.101, P

Abstract Cell fate decisions remain poorly understood at the molecular level. Embryogenesis provides a unique opportunity to analyze molecular details associated with cell fate decisions. Works based on model organisms have provided a conceptual framework of genes that specify cell fate control, for example, transcription factors (TFs) controlling processes from pluripotency to immunity1. How TFs specify cell fate remains poorly understood. Here we report that SALL4 relies on NuRD (nucleosome-remodeling and deacetylase complex) to interpret BMP4 signal and decide cell fate in a well-controlled in vitro system. While NuRD complex cooperates with SALL4 to convert mouse embryonic fibroblasts or MEFs to pluripotency, BMP4 diverts the same process to an alternative fate, PrE (primitive endoderm). Mechanistically, BMP4 signals the dissociation of SALL4 from NuRD physically to establish a gene regulatory network for PrE. Our results provide a conceptual framework to explore the rich landscapes of cell fate choices intrinsic to development in higher organisms involving morphogen-TF-chromatin modifier pathways.

Vaccine co-administration can efficiently increase vaccination uptake and timely immunization. This study aimed to evaluate the safety of the enterovirus 71 (EV71) vaccine administered alone or concurrently with other vaccines in infants 6–11 months. A total of 3,769 EV71 vaccine doses were administered to children in the active surveillance area, of which 1,909 were administered concurrently with other vaccines and 1,860 doses were administered alone. Active surveillance was conducted to observe adverse events (AEs) within 0–7 and ≥8 days after vaccination and to determine the incidence of reported AEs. The overall AE incidence was 2.12% (95% CI: 1.66%–2.58%), with 1.56% (95% CI:1.00%–2.12%) for the EV71 vaccine alone and 2.67% (95% CI: 1.95%–3.40%) for simultaneous administration of the EV71 vaccine and other vaccines ([Formula: see text] = 5.612, p = .018). The solicited local AE incidence was 1.00% (95% CI: 0.55%–1.44%) in the EV71 vaccine co-administration group and 0.59% (95% CI: 0.24%–0.94%) in the EV71 vaccine alone group ([Formula: see text] = 1.946, p = .018). The solicited systemic AE incidence was 1.68% (95% CI: 1.10%–2.25%) and 0.86% (95% CI: 0.44%–1.28%) in the EV71 vaccine co-administered and EV71 vaccine alone groups, respectively ([Formula: see text] = 4.990, p = .025). No serious vaccine-related AEs were reported. Fever was the most common AE; no difference was observed in the incidence rate of fever between the two groups ([Formula: see text] = 3.467, p = .063). Overall, AE incidence following EV71 vaccination alone or concurrently with other vaccines was acceptable; concurrent vaccination did not increase AE risk or severity.

Clinical symptoms of Parkinson’s disease (PD) are classified into motor and non-motor symptoms. Mental disorders, especially depression, are one of the major non-motor manifestations of PD. However, the underlying mechanisms remain poorly understood. In the present study, 21 neurotransmitters associated with mental disorders were measured in serum samples from patients and controls using the ultra-high performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) assay. Additionally, five clinical scales—the MDS Unified Parkinson’s Disease Rating Scale (UPDRS), the Non-Motor Symptoms Scale (NMSS), the Mini-Mental State Examination (MMSE), the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD)—were used to evaluate the severity of both motor and non-motor symptoms in PD patients. Analysis of neurotransmitter metabolism revealed significant changes in the tryptophan (Trp) metabolic pathway in PD patients. Specifically, levels of Trp, kynurenine (KYN), kynurenic acid (KA), nicotinamide (NAM), and 5-methoxyltryptamine (MeOTA) were substantially decreased. Additionally, three other excitation/inhibiting amino acids—glutamic acid (Glu), 4-aminobutyric acid (GABA), and aspartic acid (Asp)—also declined. Moreover, neurotransmitter conversion ratios, such as KA/KYN, nicotinamide/niacin (NAM/NA), 5-hydroxytryptophan/tryptophan (5-HTP/Trp), and quinolinic acid/kynurenic acid (QA/KA), provided more dynamic insights into disrupted neurotransmitter metabolism. Correlation analyses between scale scores and neurotransmitter levels showed that concentrations of xanthurenic acid (XA) and the turnover rate of 3-hydroxykynurenine (3-HK) were negatively correlated with UPDRS scores, while 5-hydroxytryptamine (5-HT) and GABA levels were negatively correlated with non-motor symptoms in PD patients. In summary, this study elucidates, for the first time, the potential association and dynamics between altered neurotransmitter metabolism and the etiology of PD in terms of motor and non-motor functions. These findings offer novel biomarkers and therapeutic targets for the treatment of PD.

Purpose: To explore the characteristics of the clinical phenotype of ARDS based on Machine Learning. Methods: This is a study on Machine Learning. Screened cases of acute respiratory distress syndrome (ARDS) in the eICU database collected basic information in the cases and clinical data on the Day 1, Day 3, and Day 7 after the diagnosis of ARDS, respectively. Using the Calinski-Harabasz criterion, Gap Statistic, and Silhouette Coefficient, we determine the optimal clustering number k value. By the K-means cluster analysis to derive clinical phenotype, we analyzed the data collected within the first 24 h. We compared it with the survival of cases under the Berlin standard classification, and also examined the phenotypic conversion within the first 24 h, on day 3, and on day 7 after the diagnosis of ARDS. Results: We collected 5054 cases and derived three clinical phenotypes using K-means cluster analysis. Phenotype-I is characterized by fewer abnormal laboratory indicators, higher oxygen partial pressure, oxygenation index, APACHE IV score, systolic and diastolic blood pressure, and lower respiratory rate and heart rate. Phenotype-II is characterized by elevated white blood cell count, blood glucose, creatinine, temperature, heart rate, and respiratory rate. Phenotype-III is characterized by elevated age, partial pressure of carbon dioxide, bicarbonate, GCS score, albumin. The differences in ICU length of stay and in-hospital mortality were significantly different between the three phenotypes (P

Bifunctional photocatalysis for biomass conversion and fuel production not only utilizes abundant and renewable biomass resources, but also obtains high‐energy fuels while obtaining fine chemicals. It is a green, clean, efficient, low‐cost, and high‐value strategy, which is conducive to achieving carbon neutralization, carbon cycle, and solving energy and environmental problems. However, very few literatures have classified and analyzed the bifunctional photocatalysis of biomass. On the basis of latest research progress, the bifunctional photocatalysts based on the classification of biomass transformation coupled with fuel production (hydrogen production or CO2 reduction) by mainly using biomass conversion rate, biomass value‐added product yield, fuel (H2, CO) production rate, and so on as evaluation indicators are reviewed. The reaction mechanisms, development status, and prospects of bifunctional photocatalysts are analyzed, summarized and prospected. This review helps to better understand photocatalysts in a biomass transformation and fuel production bifunctional route.

Hexafluoropropylene oxide oligomer acids (HFPOs), an emerging environmental pollutant, are increasingly utilized in the manufacture of fluorinated synthetic materials as a substitute for traditional perfluorooctanoic acid (PFOA), resulting in a corresponding rise in detection rates in aquatic environments, which may present inherent safety hazards to ecosystems and public health. However, few data are available on the issue of their toxicity and mechanism. This study aimed to investigate the potential toxic effects of hexafluoroepoxypropane tetrameric acid (HFPO-TeA), a typical HFPO, on the early developmental stages of zebrafish larvae. It revealed that HFPO-TeA exposure resulted in significant detrimental effects, including adverse impacts on general morphological characteristics, such as eye area, heart rate, and swimming bladder, in zebrafish embryos and larvae. Targeted metabolomics and transcriptomics inquiries clarified that HFPO-TeA exposure reduced the levels of the neurotransmitter gamma-aminobutyric acid (GABA) and downregulated the expression of genes related to the GABA pathway. Simultaneously, transgenic zebrafish exhibited that exposure to HFPO-TeA impedes the growth of GABAergic neurons. Moreover, the molecular docking analysis indicated that GABAA receptors might be the potential targets of HFPO-TeA. Taken together, the current data highlights that the HFPO-TeA might not be safe alternatives to PFOA. This study presented a model for HFPO-TeA-induced neurotoxicity in developing zebrafish that can aid in ecological risk assessments.

Amidst escalating environmental pollution due to accelerated industrialization and urbanization, there is an acute demand for effective and sustainable environmental remediation strategies. Ultrasonic technology, recognized for its green and efficient characteristics, has gained significant prominence in mitigating environmental pollution in aquatic, soil, and atmospheric ecosystems. The review provides a comprehensive analysis of the role of ultrasonic treatment in wastewater treatment, air quality improvement, and soil remediation. We systematically evaluate existing research to assess the effectiveness of ultrasonic technology in degrading pollutants and its potential for large-scale deployment. The review also examines the challenges associated with ultrasonic remediation, including optimizing operational parameters, enhancing energy transfer efficiency, and understanding the unique degradation mechanisms for various pollutants. Furthermore, we discuss environmental and safety considerations, along with the economic implications related to equipment costs and energy consumption. This review aims to contribute to the advancement of ultrasonic technology in environmental remediation by presenting a forward-looking perspective, aligning with the goals of environmental protection and sustainable development.

Blue carbon refers to the carbon fixed in marine ecosystems such as mangroves, salt marshes, and seagrass beds. Considered a treasure house for capturing and storing carbon dioxide, it can alleviate environmental issues linked to climate change and positively influence the environments where people live. Thus, to clarify the hotspots and development trends of blue carbon research, bibliometric analysis incorporating ScientoPy and VOSviewer software were used to quantitatively analyze 4,604 blue carbon publications from Web of Science and Scopus databases between 1993 and 2023. The results indicate a rapidly growing number of published studies on blue carbon, with blue carbon research being multifaceted and gradually becoming an interdisciplinary and international topic. This study on blue carbon, which is based on keyword clustering analysis, comprises three stages. The analysis of the strength of the cooperative connections between scholars in various countries who have published work on blue carbon. found that the cooperation networks of developed countries are strong and those of developing countries are relatively weak. Quantitative trend analysis reveals a growing focus on the restoration and conservation of blue carbon ecosystems, with remote sensing being the predominant technology used in the blue carbon research field in recent years. In blue carbon research, increasing carbon sequestration capacity, climate change mitigation, and carbon sequestration in macroalgae remain potential hotspots for research and development.

Abstract Preeclampsia is a multifactorial and heterogeneous complication of pregnancy. Here, we utilize single-cell RNA sequencing to dissect the involvement of circulating immune cells in preeclampsia. Our findings reveal downregulation of immune response in lymphocyte subsets in preeclampsia, such as reduction in natural killer cells and cytotoxic genes expression, and expansion of regulatory T cells. But the activation of naïve T cell and monocyte subsets, as well as increased MHC-II-mediated pathway in antigen-presenting cells were still observed in preeclampsia. Notably, we identified key monocyte subsets in preeclampsia, with significantly increased expression of angiogenesis pathways and pro-inflammatory S100 family genes in VCAN+ monocytes and IFN+ non-classical monocytes. Furthermore, four cell-type-specific machine-learning models have been developed to identify potential diagnostic indicators of preeclampsia. Collectively, our study demonstrates transcriptomic alternations of circulating immune cells and identifies immune components that could be involved in pathophysiology of preeclampsia.

The InVEST model, with its ability to perform spatial visualization and quantification, is an important tool for mapping ecosystem services. However, the spatial accuracy and simulating performance of the model are deeply influenced by the land use parameter, which often relies on the accuracy of land use/cover data. To address this issue, we propose a novel method for optimizing the land use parameter of the InVEST model based on the vegetation–impervious surface–soil (V–I–S) model and a machine learning algorithm. The optimized model is called Sub-InVEST, and it improves the performance of assessing ecosystem services on a sub-pixel scale. The conceptual steps are (i) extracting the V–I–S fraction of remote sensing images based on the spectral unmixing method; (ii) determining the mapping relationship of the V–I–S fraction between land use/cover type using a machine learning algorithm and field observation data; (iii) inputting the V–I–S fraction into the original model instead of the land use/cover parameter of the InVEST model. To evaluate the performance and spatial accuracy of the Sub-InVEST model, we employed the habitat quality module of InVEST and multi-source remote sensing data, which were applied to acquire Sub-InVEST and estimate the habitat quality of central Guangzhou city from 2000 to 2020 with the help of the LSMA and ISODATA methods. The experimental results showed that the Sub-InVEST model is robust in assessing ecosystem services in sets of complex ground scenes. The spatial distribution of the habitat quality of both models revealed a consistent increasing trend from the southwest to the northeast. Meanwhile, linear regression analyses observed a robust correlation and consistent linear trends, with R2 values of 0.41, 0.35, 0.42, 0.39, and 0.47 for the years 2000, 2005, 2010, 2015, and 2020, respectively. Compared with the original model, Sub-InVEST had a more favorable performance in estimating habitat quality in central Guangzhou. The spatial depictions and numerical distribution of the results of the Sub-InVSET model manifest greater detail and better concordance with remote sensing imagery and show a more seamless density curve and a substantially enhanced probability distribution across interval ranges.

Our previous study highlighted the therapeutic potential of glutathione (GSH), an intracellular thiol tripeptide ubiquitous in mammalian tissues, in mitigating hepatic and cerebral damage. Building on this premise, we posited the hypothesis that GSH could be a promising candidate for treating acute hepatic encephalopathy (AHE). To verify this conjecture, we systematically investigated the feasibility of GSH as a therapeutic agent for AHE through comprehensive pharmacokinetic, pharmacodynamic, and mechanistic studies using a thioacetamide-induced AHE rat model. Our pharmacodynamic data demonstrated that oral GSH could significantly improve behavioral scores and reduce hepatic damage of AHE rats by regulating intrahepatic ALT, AST, inflammatory factors, and homeostasis of amino acids. Additionally, oral GSH demonstrated neuroprotective effects by alleviating the accumulation of intracerebral glutamine, down-regulating glutamine synthetase, and reducing taurine exposure. Pharmacokinetic studies suggested that AHE modeling led to significant decrease in hepatic and cerebral exposure of GSH and cysteine. However, oral GSH greatly enhanced the intrahepatic and intracortical GSH and CYS in AHE rats. Given the pivotal roles of CYS and GSH in maintaining redox homeostasis, we investigated the interplay between oxidative stress and pathogenesis/treatment of AHE. Our data revealed that GSH administration significantly relieved oxidative stress levels caused by AHE modeling via down-regulating the expression of NADPH oxidase 4 (NOX4) and NF-κB P65. Importantly, our findings further suggested that GSH administration significantly regulated the excessive endoplasmic reticulum (ER) stress caused by AHE modeling through the iNOS/ATF4/Ddit3 pathway. In summary, our study uncovered that exogenous GSH could stabilize intracerebral GSH and CYS levels to act on brain oxidative and ER stress, which have great significance for revealing the therapeutic effect of GSH on AHE and promoting its further development and clinical application.

BackgroundSepsis is commonly associated with a sudden impairment of brain function, thus leading to significant rates of illness and mortality. The objective of this research was to integrate microbiome and metabolome to reveal the mechanism of microbiota-hippocampus-metabolites axis dysfunction in a mouse model of sepsis.MethodsA mouse model of sepsis was established via cecal ligation and puncture. The potential associations between the composition of the gut microbiota and metabolites in the hippocampus of mice with sepsis were investigated by combining 16S ribosomal RNA gene sequencing and ultra-high-performance liquid chromatography tandem mass spectrometry.ResultsA total of 140 differential metabolites were identified in the hippocampal tissues of mice with sepsis when compared to those of control mice. These differential metabolites in mice with sepsis were not only associated with autophagy and serotonergic synapse, but also involved in the metabolism and synthesis of numerous amino acids. At the phylum level, the abundance of Bacteroidota was increased, while that of Firmicutes (Bacillota) was decreased in mice with sepsis. At the genus level, the abundance of Alistipes was increased, while that of Lachnospiraceae_NK4A136_group was decreased in mice with sepsis. The Firmicutes (Bacillota)/Bacteroidota (F/B) ratio was decreased in mice with sepsis when compared to that of control mice. Furthermore, the F/B ratio was positively correlated with 5′-methylthioadenosine, PC (18:3(9Z,12Z,15Z)/18:0) and curdione, and negatively correlated with indoxylsulfuric acid, corticosterone, kynurenine and ornithine.ConclusionAnalysis revealed a reduction in the F/B ratio in mice with sepsis, thus contributing to the disturbance of 5′-methylthioadenosine, curdione, PC (18:3(9Z,12Z,15Z)/18:0), corticosterone, ornithine, indoxylsulfuric acid and kynurenine; eventually, these changes led to hippocampus dysfunction. Our findings provide a new direction for the management of sepsis-induced hippocampus dysfunction.

Stenosis severity may escalate over the course of coronary artery disease (CAD), increasing the risk of death for the patient. Conventionally, the assessment of stenosis degree relies on invasive coronary angiography (ICA), an invasive examination unsuitable for patients in poor physical condition or those with contrast allergies and one that imposes a psychological burden on patients. Although abnormal serum N-glycan profiles have exhibited robust associations with various cardiovascular diseases, including CAD, their potential in diagnosing CAD stenosis remains to be determined. In this study, we performed a comprehensive analysis of serum N-glycome from 132 patients who underwent ICA and 27 healthy controls using MALDI-TOF-mass spectrometry. The patients who underwent ICA examination were categorized into four groups based on stenosis severity: no/mild/moderate/severe stenosis. Twenty-seven N-glycans were directly quantified, and 47 derived glycan traits were obtained. Notably, among these 74 glycan features, 18 exhibited variations across the study groups. Using a combination of least absolute shrinkage and selection operator and logistic regression analyses, we developed five diagnostic models for recognizing stenosis degree. Our results suggested that alterations in serum N-glycosylation modifications might be valuable for identifying stenosis degree and monitoring disease progression in individuals with CAD. It is expected to offer a noninvasive alternative for those who could not undergo ICA because of various reasons. However, the diagnostic potential of serum N-glycan panels as biomarkers requires multicenter, large cohort validation in the future.

Background: Mitophagy is a crucial process involved in maintaining cellular homeostasis by selectively eliminating damaged or surplus mitochondria. As the kidney is an organ with a high dynamic metabolic rate and abundant mitochondria, it is particularly crucial to control mitochondrial quality through mitophagy. Dysregulation of mitophagy has been associated with various renal diseases, including acute and chronic kidney diseases, and therefore a better understanding of the links between mitophagy and these diseases may present new opportunities for therapeutic interventions. Summary: Mitophagy plays a pivotal role in the development of kidney diseases. Upregulation and downregulation of mitophagy have been observed in various kidney diseases, such as renal ischemia-reperfusion injury, contrast-induced acute kidney injury, diabetic nephropathy, kidney fibrosis, and several inherited renal diseases. A growing body of research has suggested that PINK1 and Parkin， the main mitophagy regulatory proteins， represent promising potential therapeutic targets for kidney diseases. In this review, we summarize the latest insights into how the progression of renal diseases can be mitigated through the regulation of mitophagy, while highlighting their performance in clinical trials. Key Message: This review comprehensively outlines the mechanisms of mitophagy and its role in numerous kidney diseases. While early research holds promise, most mitophagy-centered therapeutic approaches have yet to reach the clinical application stage.

In this paper, we define the generalized Bertrand curves of non-light-like framed curves in Lorentz–Minkowski 3-space; their study is essential for understanding many classical and modern physics problems. Here, we consider two non-light-like framed curves as generalized Bertrand pairs. Our generalized Bertrand pairs can include Bertrand pairs with either singularities or not, and also include Mannheim pairs with singularities. In addition, we discuss their properties and prove the necessary and sufficient conditions for two non-light-like framed curves to be generalized Bertrand pairs.

Abstract The interaction between cerebral endothelial cells (CEC) and brain parenchymal cells is critical to maintain neurovascular homeostasis, whereas extracellular vesicles (EVs) are essential to mediate the cell–cell communication. Previous researches demonstrated that CEC-derived EVs (CEC-EVs) confer neuroprotective actions. However, the molecular mechanisms remain unknown. In this study, we isolated EVs from CEC and assessed their immune-regulatory actions in microglial cells and mice following lipopolysaccharide (LPS) exposure. We found that CEC-EVs treatment significantly ameliorated LPS-induced inflammatory activation, shifting microglial polarization from pro-inflammatory phenotype to anti-inflammatory phenotype. Meanwhile, microglial cells can effectively internalize CEC-EVs and this process was further enhanced by immune activation. Next, the miRNA microarray analysis revealed that CEC-EVs increased expression of miR-672-5p, which was demonstrated to be the cargo of CEC-EVs. TGFβ-activated kinase 1 (TAK1)-binding proteins 2 (TAB2) was identified to be the target of miR-672-5p. Through inhibiting TAB2, miR-672-5p derived from CEC-EVs suppressed TAK1-TAB signaling and thereby mitigating the downstream NF-κB activation. Furthermore, we found that by delivering miR-672-5p, CEC-EVs promoted autophagy and hence stimulating autophagic degradation of NLRP3 inflammasome. Our work firstly revealed the neuroimmune-modulating actions of CEC-EVs and further demonstrated that miR-672-5p secreted from CEC-EVs inhibits microglial pro-inflammatory polarization and facilitates autophagic process via targeting TAB2.

ObjectiveTo construct a prediction model for the intention of accepting recombinant zoster vaccine(RZV) vaccination among community residents based on reasoned action approach for promoting RZV vaccination in the population. MethodsTotally 1 480 attendees of four community health service centers were recruited with accidental sampling in three districts of Shanghai city for an online survey conducted during October – November 2022. The vaccination intention scale developed by Vissor et al was translated into Chinese and modified to collect participants′ information relevant to accept RZV vaccination. Of the 1 471 individual data from eligible respondents, 981 and 490 were randomly assigned into a training set and a test set. Lasso regression analysis on the data of training set was performed to explore the determinants of RZV vaccination intention. A nomogram prediction model for RZV vaccination intention was constructed using multivariate logistic regression analysis on the data of training set and the performance of the established model was evaluated with the receiver operating characteristic curve (ROC). ResultsThe intention to have RZV vaccination within 6 months was reported by 8.36% (123) of the eligible respondents. The results of Lasso regression analysis screened out nine predictive factors of RZV vaccination intention, including perception ability (β = 0.149), perceived infection risk (β = 0.074), moral norm (β = 0.061), decisional uncertainty (β = – 0.060), general vaccination beliefs (β = – 0.007), never having herpes zoster infection (β = 0.812), perceived cost-benefit (β = – 0.014), social norm (β = 0.019), and attitude (β = 0.003) and the nine factors were used to construct the prediction model. Based on the nomogram of the established prediction model, the possibility to have RZV vaccination within next 6 months is 9.00% for the respondents never having herpes zoster infection and with following scale items′ scores: 7 for perception ability, 7 for perceived infection risk, 7 for moral norm, 7 for decisional uncertainty, 42 for general vaccination beliefs, 28 for perceived cost-benefit, 49 for social norm, and 42 for the attitude towards RZV vaccination. The results of internal and external validation analysis showed that the established model is of good differentiation and calibration（the area under the curve [AUC]training set = 0.717, AUCtest set = 0.689; χ2training set = 9.061, degree of freedom [df]training set = 8, p training set = 0.337, χ2test set = 12.024, dftest set = 8, ptest set = 0.150）. ConclusionPerception ability, perceived infection risk, moral norm, decisional uncertainty, general vaccination beliefs, whether or not having herpes zoster infection, perceived cost-benefit, social norm, and attitude towards RZV vaccination are main predictive factors for RZV vaccination intention among community residents of Shanghai city.

Nonalcoholic steatohepatitis (NASH) is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder. Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH, while the other lipids associated with the NASH pathogenesis remained unexplored. The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH via profiling the metabolic characteristics of lipids. Herein, multi-omics techniques based on LC–Q-TOF/MS, LC–MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment. A methionine and choline deficient (MCD) diet-induced mouse model of NASH was then constructed, and Schisandra lignans extract (SLE) was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14. Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines (PEs), and SLE could significantly reduce the accumulation of intrahepatic PEs. Notably, exogenous PE (18:0/18:1) was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis. Supplementing PE (18:0/18:1) also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors, while PE synthase inhibitor exerted a prominent hepatoprotective role. The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.

Background: The potential effect of removing danger-associated molecular patterns (DAMPs) from gut lymph on reducing acute lung injury (ALI) induced by gut ischemia-reperfusion injury (GIRI) is uncertain. This study aimed to investigate whether gut lymph purification (GLP) could improve GIRI-induced acute lung injury in rats by clearing danger-associated molecular patterns. Materials and methods: Rats were divided into four groups: Sham, GIRI, GIRI + gut lymph drainage (GLD), and GIRI + GLP. After successful modeling, lung tissue samples were collected from rats for hematoxylin-eosin (HE) staining and detection of apoptotic indexes. We detected the DAMPs levels in blood and lymph samples. We observed the microstructure of AEC Ⅱ and measured the expression levels of apoptosis indexes. Results: The GIRI group showed destruction of alveolar structure, thickened alveolar walls, and inflammatory cell infiltration. This was accompanied by significantly increased levels of high mobility group protein-1 (HMGB-1) and Interleukin-6 (IL-6), while reduced levels of heat shock protein 70 (HSP 70) and Interleukin-10 (IL-10) in both lymph and serum. In contrast, the lung tissue damage in the GIRI + GLP group was significantly improved compared to the GIRI group. This was evidenced by a reduction in the expression levels of HMGB-1 and IL-6 in both lymph and serum and an increase in HSP 70 and IL-10 levels. Additionally, organelle structure of AEC II was significantly improved in the GIRI + GLP group compared to the GIRI group. Conclusions: GLP inhibits inflammation and cell apoptosis in GIRI-induced ALI by blocking the link between DAMPs and mononuclear phagocytes, reducing the severity of ALI.

The power-electronics converters are increasingly applied in modern power system, which contains various sub-systems, such as renewable energy power plants and high voltage direct current transmission systems, etc. The electromagnetic transient simulation has been one of the important tools for the study of complex system containing large numbers of power converters. The coordination control of the power converters and corresponding power generation and load units is one of the challenges ensuring stability and obtaining optimal efficiency. However, the detailed modeling of the power converters considering the conduction and switching losses can cost a great number of computation resources, which makes it difficult to simulate a large system. This work proposed a current injection method for converter power loss representation, which can accurately consider the conduction and switching losses of the power-electronics switches with low computation complexity. A look-up table (LUT) of the power loss ratio is calculated before the simulation, and a current source representing the power loss is connected in parallel with the converter to track the reference loss generated by the look-up table. The proposed method can be combined with multiple converter modeling schemes, such as the two-resistance model, the switching-function model, and the average value model, etc. The topologies of the two-level converter and the modular multi-level converter (MMC) were used in the case studies to demonstrate the effectiveness of the proposed method. Compared to the device-level model, the simulation power loss deviation is 0.64% and 4.13% applying the current injection method model in the case studies of the two-level converter and the MMC.

Abstract Background Adolescent depression is becoming one of the major public health concerns, because of its increased prevalence and risk of significant functional impairment and suicidality. Clinical depression commonly emerges in adolescence; therefore, the prevention and intervention of depression at this stage is crucial. Recent evidence supports the importance of the gut microbiota (GM) in the modulation of multiple functions associated with depression through the gut-brain axis (GBA). However, the underlying mechanisms remain poorly understood. Therefore, in the current study, we aimed to screen the microbiota out from healthy and depressive adolescents, delineate the association of the targeted microbiota and the adolescent depression, address the salutary effects of the targeted microbiota on anti-depressive behaviors in mice involving the metabolism of the tryptophan (Trp)-derived neurotransmitters along the GBA. Results Here, we found the gut microbiota from healthy adolescent volunteers, first diagnosis patients of adolescent depression, and sertraline interveners after first diagnosis displayed significant difference, the relative abundance of Faecalibacterium, Roseburia, Collinsella, Blautia, Phascolarctobacterium, Lachnospiraceae-unclassified decreased in adolescent depressive patients, while restored after sertraline treatment. Of note, the Roseburia abundance exhibited a high efficiency in predicting adolescent depression. Intriguingly, transplantation of the fecal microbiota from healthy adolescent volunteers to the chronic restraint stress (CRS)-induced adolescent depressed mice significantly ameliorated mouse depressive behaviors, in which the Roseburia exerted critical roles, since its effective colonization in the mouse colon resulted in remarkably increased 5-HT level and reciprocally decreased kynurenine (Kyn) toxic metabolites quinolinic acid (Quin) and 3-hydroxykynurenine (3-HK) levels in both the mouse brain and colon. The specific roles of the Roseburia were further validated by the target bacteria transplantation mouse model, Roseburia intestinalis (Ri.) was gavaged to mice and importantly, it dramatically ameliorated CRS-induced mouse depressive behaviors, increased 5-HT levels in the brain and colon via promoting tryptophan hydroxylase-2 (TPH2) or -1 (TPH1) expression. Reciprocally, Ri. markedly restrained the limit-step enzyme responsible for kynurenine (indoleamine2,3-dioxygenase 1, IDO1) and quinolinic acid (3-hydroxyanthranilic acid 3,4-dioxygenase, 3HAO) generation, thereby decreased Kyn and Quin levels. Additionally, Ri. administration exerted a pivotal role in the protection of CRS-induced synaptic loss, microglial activation, and astrocyte maintenance. Conclusions This study is the first to delineate the beneficial effects of Ri. on adolescent depression by balancing Trp-derived neurotransmitter metabolism and improving synaptogenesis and glial maintenance, which may yield novel insights into the microbial markers and therapeutic strategies of GBA in adolescent depression. Video Abstract

Abstract Background Previous studies have suggested that maternal overweight/obesity is asscociated with macrosomia. The present study aimed to investigate the mediation effects of fasting plasma glucose (FPG) and maternal triglyceride (mTG) in the relationship between maternal overweight/obesity and large for gestational age (LGA) among non-diabetes pregnant women. Methods This prospective cohort study was conducted in Shenzhen from 2017 to 2021. A total of 19,104 singleton term non-diabetic pregnancies were enrolled form a birth cohort study. FPG and mTG were measured at 24–28 weeks. We analyzed the association of maternal prepregancy overweight/obesity with LGA and mediation effects of FPG and mTG. Multivariable logistic regression analysis and serial multiple mediation analysis were performed. The odds ratio (OR) and 95% confidence intervals (CIs) were calculated. Results Mothers who were overweight or obese had higher odds of giving birth to LGA after adjusting potential confounders (OR:1.88, 95%CI: 1.60–2.21; OR:2.72, 95%CI: 1.93–3.84, respectively). The serial multiple mediation analysis found prepregnancy overweight can not only have a direct positive effect on LGA (effect = 0.043, 95% CI: 0.028–0.058), but also have an indirect effect on the LGA through two paths: the independent mediating role of FPG (effect = 0.004, 95% CI: 0.002–0.005); the independent mediating role of mTG (effect = 0.003,95% CI: 0.002–0.005). The chain mediating role of FPG and mTG has no indirect effect. The estimated proportions mediated by FPG and mTG were 7.8% and 5.9%. Besides, the prepregnancy obesity also has a direct effect on LGA (effect = 0.076; 95%CI: 0.037–0.118) and an indirect effect on LGA through three paths: the independent mediating role of FPG (effect = 0.006; 95%CI: 0.004–0.009); the independent mediating role of mTG (effect = 0.006; 95%CI: 0.003–0.008), and the chain mediating role of FPG and mTG (effect = 0.001; 95%CI: 0.000-0.001). The estimated proportions were 6.7%, 6.7%, and 1.1%, respectively. Conclusion This study found that in nondiabetic women, maternal overweight/obesity was associated with the occurence of LGA, and this positive association was partly mediated by FPG and mTG, suggesting that FPG and mTG in overweight/obese nondiabetic mothers deserve the attention of clinicians.

Abstract Objective To evaluate the safety and efficacy of computed tomography (CT)-guided microwave ablation combined with vertebral augmentation under real-time temperature monitoring in the treatment of painful osteogenic spinal metastases. Methods This retrospective study included 38 patients with 63 osteogenic metastatic spinal lesions treated using CT-guided microwave ablation and vertebral augmentation under real-time temperature monitoring. Visual analog scale scores, daily morphine consumption, and Oswestry Disability Index scores were used to evaluate efficacy of the treatment. Results Microwave ablation combined with vertebral augmentation reduced the mean visual analog scale scores from 6.40 ± 1.90 preoperatively to 3.32 ± 0.96 at 24 h, 2.24 ± 0.91 at 1 week, 1.92 ± 1.32 at 4 weeks, 1.79 ± 1.45 at 12 weeks, and 1.39 ± 1.12 at 24 weeks postoperatively (all p

Abstract Cell fate decision involves rewiring of the genome, but remains poorly understood at the chromatin level. Here, we report that chromatin remodeling complex NuRD participates in closing open chromatin in the early phase of somatic reprogramming. Sall4, Jdp2, Glis1 and Esrrb can reprogram MEFs to iPSCs efficiently, but only Sall4 is indispensable capable of recruiting endogenous components of NuRD. Yet knocking down NuRD components only reduces reprogramming modestly, in contrast to disrupting the known Sall4-NuRD interaction by mutating or deleting the NuRD interacting motif at its N-terminus that renders Sall4 inept to reprogram. Remarkably, these defects can be partially rescured by grafting NuRD interacting motif onto Jdp2. Further analysis of chromatin accessibility dynamics demonstrates that the Sall4-NuRD axis plays a critical role in closing the open chromatin in the early phase of reprogramming. Among the chromatin loci closed by Sall4-NuRD encode genes resistant to reprogramming. These results identify a previously unrecognized role of NuRD in reprogramming, and may further illuminate chromatin closing as a critical step in cell fate control.

Abstract We conducted a matched retrospective cohort study of two cohorts to estimate inactivated vaccine effectiveness (VE) and its comparative effectiveness of booster dose among older people in Shanghai. Cohort 1 consisted of a vaccinated group (≥1 dose) and an unvaccinated group (3,317,475 pairs), and cohort 2 consisted of a booster vaccinated group and a fully vaccinated group (2,084,721 pairs). The Kaplan–Meier method and Cox regression models were used to estimate risk and hazard ratios (HRs) study outcomes. For cohort 1, the overall estimated VEs of ≥1 dose of inactivated vaccine against SARS-CoV-2 infection, severe/critical Covid-19, and Covid-19 related death were 24.7% (95%CI 23.7%−25.7%), 86.6% (83.1%−89.4%), and 93.2% (88.0%−96.1%), respectively. Subset analysis showed that the booster vaccination provided greatest protection. For cohort 2, compared with full vaccination, relative VEs of booster dose against corresponding outcome were 16.3% (14.4%−17.9%), 60.5% (37.8%−74.9%), and 81.7% (17.5%−95.9%). Here we show, although under the scenario of persistent dynamic zero-Covid policy and non-pharmaceutical interventions, promoting high uptake of the full vaccination series and booster dose among older adults is critically important. Timely vaccination with the booster dose provided effective protection against Covid-19 outcomes.

The occurrence and profiles of organophosphate esters (OPEs) were studied in indoor and outdoor dusts from various microenvironments, including forty-seven outdoor dusts from green belts, roads, parks and residence areas, seventy-seven indoor dusts from private cars, print shops, taxis, furniture shops, offices, dormitories, shopping malls and residences house in different districts in Beijing. The total concentrations (Σ12OPEs) were eighteen times higher in indoor dusts (7.14 ×102 to 2.24 ×104 ng/g) than in outdoor dusts (36.0–1.56 ×103 ng/g). OPEs concentrations in samples from taxi and private cars were obviously higher than other indoor microenvironments. Both indoor and outdoor microenvironments also showed different compositional profiles of OPEs, indicating that polyurethane foam/building materials and hydraulic fluids/plastics were the greatest contributions in different microenvironments, with chlorinated alkyl phosphates (Cl-OPEs) being the predominant compound in both indoor dust (52.1–86.5%) and outdoor dust samples (42.6–81.3%). The uncertainty was reduced by Monte Carlo simulation, and the pollution levels of 50th and 95th percentiles were employed to calculate the average daily dosage, which was then used to calculate hazard quotient (HQ) for assessing the health risks to adults and children. Results showed that OPEs were safe even at extremely consumed concentration percentile (95th) in all groups.

To improve the finesse of the temperature-humidity index (THI), this study applies four machine learning methods in THI downscaling, including multiple linear regression, random forest (RF), support vector machine, and gradient boosting machine. The temperature data and specific humidity data of the China Meteorological Administration Land Data Assimilation System (CLDAS) are used to establish a downscaling model, and site observational data are used to test the model precision. By taking land surface temperature (LST), vegetation coverage, altitude, and slope as downscaling factors, the monthly average THI calculated by CLDAS-V2.0 data is downscaled from 6 to 1 km in Anhui Province in July and August from 2002 to 2021. The results show that the spatial resolution of THI is improved effectively by the four downscaling models, and there is a significant correlation between the downscaled values and the site values, with a correlation coefficient greater than 0.97. The downscaling effect of RF is slightly better than that of the other three algorithms and better describes the distribution of summer resort resources. Simulated results from RF are piecewise corrected by using the mean variation, and the correlation between corrected values and observations in July and August are both improved (>0.98). According to the estimation of the corrected THI (1 km × 1 km), the proportion of summer resort area in Anhui Province is 9.58% in July and 19.29% in August.

Abstract Tacrolimus (Tac) is a common immunosuppressant that used in organ transplantation. However, its therapeutic index is narrow, and it is prone to adverse side effects, along with an increased risk of toxicity, namely, cardio-, nephro-, hepato-, and neurotoxicity. Prior metabolomic investigations involving Tac-driven toxicity primarily focused on changes in individual organs. However, extensive research on multiple matrices is uncommon. Hence, in this research, the authors systemically evaluated Tac-mediated toxicity in major organs, namely, serum, brain, heart, liver, lung, kidney, and intestines, using gas chromatography−mass spectrometry (GC-MS). The authors also employed multivariate analyses, including orthogonal projections to the latent structure (OPLS) and t-test, to screen 8 serum metabolites, namely, D-proline, glycerol, D-fructose, D-glucitol, sulfurous acid, 1-monopalmitin (MG (16:0/0:0/0:0)), glycerol monostearate (MG (0:0/18:0/0:0)), and cholesterol. Metabolic changes within the brain involved alterations in the levels of butanamide, tartronic acid, aminomalonic acid, scyllo-inositol, dihydromorphine, myo-inositol, and 11-octadecenoic acid. Within the heart, the acetone and D-fructose metabolites were altered. In the liver, D-glucitol, L-sorbose, palmitic acid, myo-inositol, and uridine were altered. In the lung, L-lactic acid, L-5-oxoproline, L-threonine, phosphoric acid, phosphorylethanolamine, D-allose, and cholesterol were altered. Lastly, in the kidney, L-valine and D-glucose were altered. Our findings will provide a systematic evaluation of the metabolic alterations in target organs within a Tac-driven toxicity mouse model.

Abstract Background Limited data are available on the effectiveness of inactivated and Ad5-nCoV COVID-19 vaccines in real-world use—especially against Omicron variants in SARS-CoV-2 infection-naïve population. Methods A matched case-control study was conducted among people aged ≥ 3 years between 2 December 2021 and 13 May 2022. Cases were SARS-CoV-2-infected individuals, individuals with severe/critical COVID-19, or COVID-19-related deaths. Controls were selected from consecutively test-negative individuals at the same time as cases were diagnosed and were exact-matched on year-of-age, gender, birthplace, illness onset date, and residential district in ratios of 1:1 with infected individuals and 4:1 with severe/critical COVID-19 and COVID-19-related death. Additionally, two subsets were constructed to analyze separate vaccine effectiveness (VE) of inactivated vaccines (subset 1) and Ad5-vectored vaccine (subset 2) against each of the three outcomes. Results Our study included 612,597 documented SARS-CoV-2 infections, among which 1485 progressed to severe or critical illness and 568 died. Administering COVID-19 vaccines provided limited protection against SARS-CoV-2 infection across all age groups (overall VE: 16.0%, 95% CI: 15.1–17.0%) but high protection against severe/critical illness (88.6%, 85.8–90.8%) and COVID-19-related death (91.6%, 86.8–94.6%). In subset 1, inactivated vaccine showed 16.3% (15.4–17.2%) effective against infection, 88.6% (85.8–90.9%) effective against severe/critical COVIID-19, and 91.7% (86.9–94.7%) against COVID-19 death. Booster vaccination with inactivated vaccines enhanced protection against severe COVID-19 (92.7%, 90.1–94.6%) and COVID-19 death (95.9%, 91.4–98.1%). Inactivated VE against infection began to wane 12 weeks after the last dose, but two and three doses sustained high protection levels (> 80%) against severe/critical illness and death, while subset 2 showed Ad5-vectored vaccine was 13.2% (10.9–15.5%) effective against infection and 77.9% (15.6–94.2%) effective against severe/critical COVIID-19. Conclusions Our real-world study found high and durable two- and three-dose inactivated VE against Omicron-associated severe/critical illness and death across all age groups, but lower effectiveness against Omicron infection, which reinforces the critical importance of full-series vaccination and timely booster dose administration for all eligible individuals.

BackgroundStudies have revealed that the transplantation of mesenchymal stem cells (MSCs) might be a potential star candidate for premature ovarian failure (POF) in animal experiments. However, individual studies with a small sample size cannot be used to draw a clear conclusion. Therefore, we conducted a systematic review and meta-analysis to explore the potential of using MSCs in the treatment of POF in animals.MethodsSeven databases were searched for studies exploring the effect of the transplantation of MSCs on POF in animal models. The PRISMA guideline was followed, and the methodological quality was ensured using SYRCLE’s risk of bias tool. RevMan 5.4 and STATA 12.0 software was performed to meta-analysis.ResultsIn total, 37 studies involving 1,079 animals were included. Significant associations were found for MSCs with the levels of E2 (SMD 2.69 [95% CI 1.97, 3.41]), FSH (-2.02, [-2.74, -1.30]), primary follicles (2.04, [1.17, 2.92]), secondary follicles (1.93, [1.05, 2.81]), and primordial follicles (2.38, [1.19, 3.57]. Other outcomes, such as AMH, LH, INHB, antral follicles, growing follicles, mature follicles, and early antral were also found to be significant. There was no difference in FSH/LH, corpus leteum, follicles, and estruc cycle.ConclusionsOur meta-analysis result indicated that the transplantation of MSCs might exert therapeutic effects on animal models of POF, and these effects might be associated with improving the disorder of the sexual cycle, modulating serum hormone expressions to a better state, and restoring ovarian function.

Paroxetine (PRX) is a common antidepressant drug which widely existence in natural environment. Numerous studies in the past few decades have focused on the beneficial effects of PRX on depression, however, the toxic properties and the potential mechanisms remain unclear. In this study, zebrafish embryos were exposed to 1.0, 5.0, 10 and 20 mg/L of PRX from 4 to 120-hour-post-fertilization (hpf), and it showed that PRX exposure caused adverse effects in zebrafish embryos, including decreased body length, blood flow velocity, cardiac frequency, cardiac output and increased burst activity and atria area. Meanwhile, the Tg (myl7: EGFP) and Tg (lyz: DsRed) transgenic zebrafish were used to detect the cardiotoxicity and inflammation response of PRX. Moreover, the heart development associated genes (vmhc, amhc, hand2, nkx2.5, ta, tbx6, tbx16 and tbx20) and inflammatory genes (IL-10, IL-1β, IL-8 and TNF-α) were up-regulated after PRX challenge. In addition, Aspirin was used to alleviate the PRX-induced heart development disorder. In conclusion, our study verified the PRX induced inflammatory related cardiotoxicity in larva zebrafish. Meanwhile, the current study shown the toxic effects of PRX in aquatic organism, and provide for the environmental safety of PRX.

Abstract. Background:. The fetal growth charts in widest use in China were published by Hadlock >35 years ago and were established on data from several hundred of American pregnant women. After that, >100 fetal growth charts were published around the world. We attempted to assess the impact of applying the long-standing Hadlock charts and other charts in a Chinese population and to compare their ability to predict newborn small for gestational age (SGA). Methods:. For this retrospective observational study, we reviewed all pregnant women (n = 106,455) who booked prenatal care with ultrasound measurements for fetal biometry at the Shenzhen Maternity and Child Healthcare Hospital between 2012 and 2019. A fractional polynomial regression model was applied to generate Shenzhen fetal growth chart ranges for head circumference (HC), biparietal diameter (BPD), abdominal circumference (AC), and femur length (FL). The differences between Shenzhen charts and published charts were quantified by calculating the Z-score. The impact of applying these published charts was quantified by calculating the proportions of fetuses with biometric measurements below the 3rd centile of these charts. The sensitivity and area under the receiver operating characteristic curves of published charts to predict neonatal SGA (birthweight

Abstract In this study, we aimed to determine the specific roles of death‐associated protein kinase 1 (DAPK1) and Beclin1 in non‐small cell lung cancer (NSCLC) under oxygen and glucose deprivation (OGD). We found that OGD caused most cells to shrink, aggregate, and produce many vacuoles in the cytoplasm. Transmission electron microscopy revealed the presence of autophagic vesicles in the OGD group but not in the Control group. Moreover, the cell counting kit‐8 assay showed that cell proliferation was reduced in the OGD group. Quantitative reverse transcription‐polymerase chain reaction, western blot, and cell function assays showed that DAPK1 overexpression under OGD promoted apoptosis and autophagy in A549 cells. The coimmunoprecipitation assay confirmed the interaction between DAPK1 and Beclin1 protein. Moreover, knockdown of Beclin1 inhibited autophagy, but its overexpression promoted apoptosis in A549 cells. In vivo tumorigenesis experiment revealed that overexpression of DAPK1 promoted A549 cell apoptosis. Collectively, overexpression of DAPK1 and Beclin1 under OGD promoted excessive autophagy and apoptosis in A549 cells. Our study may provide a novel therapeutic target and theoretical basis for NSCLC treatment.

Abstract Exosomes are extracellular vesicles with diameters of about 100 nm that are naturally secreted by cells into body fluids. They are derived from endosomes and are wrapped in lipid membranes. Exosomes are involved in intracellular metabolism and intercellular communication. They contain nucleic acids, proteins, lipids, and metabolites from the cell microenvironment and cytoplasm. The contents of exosomes can reflect their cells’ origin and allow the observation of tissue changes and cell states under disease conditions. Naturally derived exosomes have specific biomolecules that act as the “fingerprint” of the parent cells, and the contents changed under pathological conditions can be used as biomarkers for disease diagnosis. Exosomes have low immunogenicity, are small in size, and can cross the blood–brain barrier. These characteristics make exosomes unique as engineering carriers. They can incorporate therapeutic drugs and achieve targeted drug delivery. Exosomes as carriers for targeted disease therapy are still in their infancy, but exosome engineering provides a new perspective for cell‐free disease therapy. This review discussed exosomes and their relationship with the occurrence and treatment of some neuropsychiatric diseases. In addition, future applications of exosomes in the diagnosis and treatment of neuropsychiatric disorders were evaluated in this review.

In this study, the flax (Linum usitatissimum L.) genes associated with resistance to the disease pasmo (Septoria linicola (Speg.) Garassini) were mapped using genome resequencing and bulked segregant analysis (BSA) of genomic DNA of the pasmo-resistant parent y62–9, pasmo-susceptible parent y64–5, and F2 generation segregants. Pasmo resistance genes were identified using Gene Ontology (GO) functional prediction and gene annotation methods. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed the biological information and molecular mechanisms associated with the flax-pathogen interaction. The results of a quantitative real-time PCR analysis revealed that the levels of expression of the three genes Lus10003106, Lus10022077, and Lus10021999 differed between the y62–9 (pasmo-resistant) and y64–5 (pasmo-susceptible) parental flax lines after the inoculation of plants with the pasmo pathogen. Thus, these genes may play key roles in the resistance of flax to pasmo. The results of this study provide a foundation to support future studies of the pathogenesis of flax disease and the discovery and cloning of resistance genes and development of new molecular markers toward the development of pasmo-resistant flax varieties.

Objective: To elucidate the potential causality of leukocyte telomere length (LTL) with immune-mediated inflammatory diseases (IMIDs), we conducted a Mendelian randomization (MR) study.Methods: The genetically predicted causation between LTL and IMIDs was evaluated using a two-sample MR method. We analyzed 16 major IMIDs, which included systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn’s disease (CD), ankylosing spondylitis (AS), sicca syndrome (SS), rheumatoid arthritis (RA), type 1 diabetes (T1D), primary sclerosing cholangitis (PSC), idiopathic pulmonary fibrosis (IPF), atopic dermatitis (AD), sarcoidosis, hypothyroidism, hyperthyroidism, psoriasis, and childhood asthma. The random-effects inverse-variance weighted (IVW) method was performed as the main analytical approach in MR. Various sensitivity analyses, including MR-Egger, MR robust adjusted profile score (MR-RAPS), weighted median, MR pleiotropy residual sum and outlier (MR-PRESSO) methods, weighted mode, radial plot, and radial regression, were used to guarantee the robustness of the results and detect horizontal pleiotropy. Cochran’s Q value was calculated to check for heterogeneity, and the MR Steiger approach was used to test the causal direction.Results: The MR results indicated significant inverse associations of LTL with risks of psoriasis (OR: 0.77, 95% CI: 0.66–0.89, and p = 3.66 × 10−4), SS (OR: 0.75, CI: 0.58–0.98, and p = 0.03), RA (OR: 0.77, 95% CI: 0.68–0.88, and p = 9.85 × 10−5), hypothyroidism (OR: 0.84, 95% CI: 0.78–0.91, and p = 7,08 × 10−6), hyperthyroidism (OR: 0.60, 95% CI: 0.44–0.83, and p = 1.90 × 10−3), sarcoidosis (OR: 0.67, 95% CI: 0.54–0.83, and p = 2.60 × 10−4), and IPF (OR: 0.41, 95% CI: 0.29–0.58, and p = 4.11 × 10−7) in the FinnGen study. We observed that longer LTL was associated with an increased risk of AS susceptibility (OR: 1.51, 95% CI: 1.18–1.94, and p = 9.66 × 10−4). The results of the IVW method showed no causal relationship between TL and SLE (OR: 0.92, 95% CI: 0.62–1.38, and p = 0.69) in the FinnGen study; however, a significantly positive correlation was shown between LTL and SLE in another larger GWAS (OR: 1.87, 95% CI: 1.37–2.54, and p = 8.01 × 10−5).Conclusion: Our findings reveal that abnormal LTL has the potential to increase the risk of IMIDs. Therefore, it could be treated as a predictor and may provide new potential treatment targets for IMIDs. However, the change of LTL may not be the direct cause of IMIDs. Further studies should aim at the pathogenic mechanism or potential protective effects of LTL in IMIDs.

Background: To compare the safety and efficacy of 2 different computed tomography-guided puncture techniques for simultaneous needle biopsy and microwave ablation of suspected malignant pulmonary nodules. Methods: This retrospective comparative before-and-after study analyzed the data of 81 patients (each with a suspected malignant pulmonary nodule) who underwent computed tomography-guided needle biopsy with simultaneous microwave ablation between September 2016 and September 2021. In group A, 41 patients (41 pulmonary nodules) underwent microwave ablation immediately through the biopsy channel, whereas in group B, 40 patients (40 pulmonary nodules) underwent computed tomography-guided percutaneous needle biopsy and microwave ablation through separate needle channels. Clinical data, technical success rates, complications, and short-term efficacy were compared between the groups to evaluate the advantages and disadvantages of both techniques. Results: Of the 81 patients, 78 successfully underwent needle biopsy and microwave ablation, with a technical success rate of 96.3%. The incidence of pneumothorax was 56.1% (23 out of 41) and 30% (12 out of 40) in groups A and B, respectively, while that of chest pain was 34.1% (14 out of 41) and 40% (16 out of 40) in groups A and B, respectively. The differences were statistically insignificant ( p = .127 and p = .759). However, the incidence of hemoptysis was 39.0% (16 out of 41) and 17.5% (7 out of 40), respectively, which was statistically significant ( P = .015). Air embolism, bronchopleural fistula, and needle implantation metastasis were not observed in both groups. At a 6-month follow-up, there were no other complications in both groups, and complete ablation was observed in all cases. Conclusion: Computed tomography-guided biopsy combined with microwave ablation is safe and effective for the treatment of suspected malignant pulmonary nodules, and clinicians can use both techniques.

Abstract Background The association between maternal obesity and preterm birth remains controversial and inconclusive, and the effects of gestational diabetes mellitus (GDM) and preeclampsia (PE) on the relationship between obesity and preterm birth have not been studied. We aimed to clarify the relationship between prepregnancy body mass index (BMI) and the phenotypes of preterm birth and evaluate the mediation effects of GDM and PE on the relationship between prepregnancy BMI and preterm birth. Methods We conducted a prospective cohort study of 43,056 women with live singleton births from 2017 through 2019. According to the WHO International Classification, BMI was classified as underweight (BMI

Abstract. Background:. Gestational weight gain (GWG) is associated with the risk of gestational diabetes mellitus (GDM). However, the effect of weight gain in different trimesters on the risk of GDM is unclear. This study aimed to evaluate the effect of GWG on GDM during different trimesters. Methods:. A birth cohort study was conducted from 2017 to 2020 in Shenzhen, China. In total, 51,205 participants were included comprising two models (early pregnancy model and middle pregnancy model). Gestational weight (kg) was measured at each prenatal clinical visit using a standardized weight scale. Logistic regression analysis was used to assess the risk of GDM. Interaction analysis and mediation effect analysis were performed in the middle pregnancy model. Results:. In the early pregnancy model, the risk of GDM was 0.858 times lower (95% confidence interval [CI]: 0.786, 0.937) with insufficient GWG (iGWG) and 1.201 times higher (95% CI: 1.097, 1.316) with excessive GWG after adjustment. In the middle pregnancy model, the risk of GDM associated with iGWG increased 1.595 times (95% CI: 1.418, 1.794) after adjustment; for excessive GWG, no significant difference was found (P = 0.223). Interaction analysis showed no interaction between GWG in early pregnancy (GWG-E) and GWG in middle pregnancy (GWG-M) (F = 1.268; P = 0.280). The mediation effect analysis indicated that GWG-M plays a partial mediating role, with an effect proportion of 14.9%. Conclusions:. eGWG-E and iGWG-M are associated with an increased risk of GDM. Strict control of weight gain in early pregnancy is needed, and sufficient nutrition should be provided in middle pregnancy.

Modular multilevel converters (MMCs) are widely utilized in dc applications. With the development of MMCs, many applications require the MMCs to have additional functions and characteristics, such as dc fault clearing capability and low submodule capacitance. A unidirectional current H-bridge submodule (UCH-SM) has been proposed, which uses low submodule capacitance and possesses dc fault clearing capability. However, the reactive power capability is limited during low active power because of the inadequate dc bias in arm currents caused by the low dc current. Although retaining a rated dc current even at zero active power has been proposed, it results in increasing the power losses and large capacitance. This study proposes a new operating mode based on variable dc voltage and variable dc current (VVVCM) for point-to-point dc systems. The basic idea is that both the dc voltage and current vary on the basis of active power and a lower limit is set for the dc current to provide adequate dc bias in the arm currents during reactive power exchange. Analysis shows that the UCH-MMC in VVVCM has an enlarged P–Q capability range and still retains low capacitor usage. Simulation results verify the effectiveness of the proposed mode.

Background Limited data are available for postpartum hypertension prediction after preeclampsia. Methods and Results We examined the association between maternal serum chemerin levels in patients with preeclampsia and blood pressure (BP) levels after delivery in a prospective birth cohort of 15 041 singleton pregnant women. A total of 310 cases among 322 patients with preeclampsia (follow‐up rate, 96.3%) were followed up during a mean 2.8 years after delivery. Compared with matched uncomplicated controls (n=310), serum chemerin measured at ≈35 gestational weeks was significantly increased in preeclampsia (171.8±49.2 versus 140.2±53.5 ng/mL; P

Objective. It is well known that paclitaxel (PTX)-induced neurotoxicity seriously affects the quality of life of patients and is the main reason for reducing the dose of chemotherapy or even stopping chemotherapy. The current data are limited, and further information is required for practice and verification. The aims of this study were to clarify the molecular mechanism underlying PTX-induced neurotoxicity by combining in vivo and in vitro metabolomics studies and provide new targets for the prevention and treatment of PTX-induced neurotoxicity. Methods. In the in vivo study, a PTX-induced neurotoxicity mouse model was established by intraperitoneal injection of PTX (6 mg/kg every three days) for two consecutive weeks. After verification by water maze tests and HE staining of pathological sections, hippocampal metabolites were measured and the differential metabolites and related metabolic pathways were identified by multivariate statistical analysis. In the in vitro study, we investigated the effects of PTX on mouse hippocampal neuron cells, assessing the concentration and time of administration by MTT assays. After modeling, the relevant metabolites in the TCA cycle were quantified by targeted metabolomics using stable isotope labeling. Finally, the key enzymes of the TCA cycle in tissues and cells were verified by RT-PCR. Results. Administration of PTX to model mice resulted in neurological damage, shown by both water-maze tests and hippocampal tissue sections. Twenty-four metabolites and five associated metabolic pathways were found to differ significantly between the hippocampal tissues of the model and control groups. These included metabolites and pathways related to the TCA cycle and pyruvate metabolism. Metabolomics analysis using stable isotope labeling showed significant changes in metabolites associated with the TCA cycle compared with the control group (P

PurposeType 1 diabetes is characterized by elevated blood glucose levels, which negatively impacts multiple organs and tissues throughout the body, and its prevalence is on the rise. Prior reports primarily investigated the serum and urine specimen from diabetic patients. However, only a few studies examined the overall metabolic profile of diabetic animals or patients. The current systemic investigation will benefit the knowledge of STZ-based type 1 diabetes pathogenesis.MethodsMale SD rats were arbitrarily separated into control and streptozotocin (STZ)-treated diabetic rats (n = 7). The experimental rats received 50mg/kg STZ intraperitoneal injection daily for 2 consecutive days. Following 6 weeks, metabolites were assessed via gas chromatography-mass spectrometry (GC-MS), and multivariate analysis was employed to screen for differentially expressed (DE) metabolites between the induced diabetic and normal rats.ResultsWe identified 18, 30, 6, 24, 34, 27, 27 and 12 DE metabolites in the serum, heart, liver, kidney, cortex, renal lipid, hippocampus, and brown fat tissues of STZ-treated diabetic rats, compared to control rats. Based on our analysis, the largest differences were observed in the amino acids (AAs), B-group vitamin, and purine profiles. Using the metabolic pathway analysis, we screened 13 metabolic pathways related to the STZ-exposed diabetes pathogenesis. These pathways were primarily AA metabolism, followed by organic acids, sugars, and lipid metabolism.ConclusionBased on our GC-MS analysis, we identified potential metabolic alterations within the STZ-exposed diabetic rats, which may aid in the understanding of diabetes pathogenesis.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is still an enormous threat to global health and the economy. Although China has adopted effective measures to control the outbreak, there is still a risk of local transmission from imported cases. Meanwhile, considering the high mortality rate and rapid spread of the disease, a safe and effective vaccine is urgently needed to control the pandemic. With COVID-19 vaccines becoming available to the population, it has become important to know about their acceptance in the population. This is important to enable high vaccination coverage rates and reflects the demand within the general population. An cross–sectional survey was conducted during October 2020 in Shanghai using a well-designed questionnaire, which aimed to evaluate the acceptability of COVID-19 vaccines and to identify the factors affecting its acceptability among working-age adults in Shanghai, China. We found that the acceptability of COVID-19 vaccines was high in work-age adults in Shanghai, China. The factors affecting the acceptability of vaccination identified in this study can provide guides to increase COVID-19 vaccine acceptability in future.

This study aimed to understand the willingness of and affecting factors of non-national immunization program (non-NIP) vaccines among children’s parents during the COVID-19 era in Shanghai, China. A cross-sectional survey was conducted with parents who attended vaccination clinics in four out of 16 districts in Shanghai, China. Data was obtained using a self-administered structured questionnaire. A multivariate logistic regression model was used to analyze factors associated with vaccination acceptability. In total, 1691 valid questionnaires were obtained. Of the participants, 69.5% (1,176/1,691) reported being interested in non-NIP vaccines for their children. Further, respondents were more likely to be willing to get non-NIP vaccines for their children if they had an income of 10,000–20,000CNY or more, an educational level of college or above, and if getting the vaccination was moderately convenient or convenient. Respondents were less likely to be willing to get the vaccines if they were in the 30–39 age group and had moderate or low satisfaction with the vaccine. Many parents are willing to get non-NIP vaccines for their children. However, some demographic factors, perceived convenience and satisfaction of vaccination, perceived necessity, safety and price barrier of non- NIP influenced the acceptability of non-NIP vaccines in Shanghai. Our findings can help guide future efforts to increase non-NIP vaccines acceptability.

Influenza is a common infectious disease resulting in substantial morbidity and mortality globally. The most effective strategy for preventing influenza is annual vaccination; however, the coverage rate of the influenza vaccine in Shanghai has not been well explored or reported. Therefore, this study aimed to determine coverage with the influenza vaccine and access trends in Shanghai city; data from Shanghai immunization information system was analyzed to estimate vaccination coverage during 2016–2017 through 2020–2021 influenza seasons. Vaccination coverage by age groups, immigration status, and districts was accessed. The influenza vaccination coverage (at least one dose) for 2016/2017 to 2020/2021 influenza seasons was 10.8‰ (95‰ CI: 10.7–10.8), 12.3‰ (95‰ CI: 12.3–12.4), 10.1‰ (95‰ CI: 10.0–10.1), 20.1‰ (95‰ CI: 20.0–20.2) and 50.8‰ (95‰ CI: 50.7–50.8) respectively. Although we found significantly higher vaccination coverage in females, children from 6 months to 17 years, and residents, it is still low in all subgroups of the population in Shanghai. Therefore, taking effective steps to promote influenza vaccination in Shanghai is recommended.

The interaction relationship of ecosystem services (ESs) is among the most critical objective in natural resource management. However, a complexity of the spatial heterogeneity of delivering multiple ESs from social-ecological system was seldomly considered. To enhance the linkage between the spatial concordance and interaction relationship of ESs, we presented a multi-criteria framework for identifying the trade-offs and synergies relationship of ESs. The conceptual steps were to i) divide the ES groups based on different ES bundles, ii) select appropriate methods for each ES bundle based on the number of dominant ESs and iii) determine the trade-offs and synergies relationship of pair-wise ESs among ES bundles. The framework was tested in the Guangdong- Hong Kong- Macao Greater Bay Area (GBA) in the period of 2000 to 2015, which can be implemented by using InVEST model, K-means clustering algorithm and correlation analysis method. The results show that 4 different ES bundles had been identified, which exhibits the spatial distribution of Bundle 1 to Bundle 4 had an extensive trend from central regions to fringe regions in the GBA. Partial correlation analysis and spearman correlation analysis were selected to quantify the trade-off and synergies relationship of ESs for each ES bundle. Meanwhile, the trade-offs and synergies relationship of ESs among each bundle was compared with the total areas of GBA, which exhibits a proportion of conspicuous differences. It indicated the framework could distinguish the spatiotemporal heterogeneity on the trade-offs and synergies relationship of ESs. A favorable application on the GBA underscored the interrelationship of multiple ESs should consider a spatiotemporal variation of the stability and ability to deliver multiple ESs from a social-ecological system. The framework for understanding the interaction relationship presented here offers a feasible workflow to evaluate trade-off strategies and policies of ecosystem management.