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Abstract Background Polyhydroxyalkanoates (PHAs) are optimal potential materials for industrial and medical uses, characterized by exceptional sustainability, biodegradability, and biocompatibility. These are primarily from various bacteria and archaea. Bacterial strains with effective PHA formation capabilities and minimal production cost form the foundation for PHA production. Detailed genomic analysis of these PHA-generating bacteria is vital to understand their PHA production pathways and enhance their synthesis capability. Results ZZQ-149, a halophilic, PHA-producing bacterium, was isolated from the sediment of China’s Qinghai Lake. Here, we decoded the full genome of ZZQ-149 using Single Molecule Real Time (SMRT) technology based on PacBio RS II platform, coupled with Illumina sequencing platforms. Physiological, chemotaxonomic traits, and phylogenetic analysis based on 16 S rRNA gene and single copy core genes of ninety-nine Halomonas type strains identified ZZQ-149 as the type strain of Halomonas qinghailakensis. Furthermore, a low average nucleotide identity (ANI,

Abstract Low-frequency repetitive transcranial magnetic stimulation (rTMS) has emerged as an effective intervention for alleviating symptoms of psychiatric disorders, particularly schizophrenia characterized by persistent auditory verbal hallucinations (AVH). However, the underlying mechanism of its action remain elusive. This study employed a randomized controlled design to investigate the impact of low-frequency rTMS on the neural connectivity at the stimulate site, specifically left temporoparietal junction (TPJ), in schizophrenia patients with suffering from AVH. Using Dynamic Causal Modeling (DCM), this study assessed changes in directed connectivity patterns and their correlations with clinical symptomatology. The results demonstrated significant improvements in AVH. Notably, significant changes in connectivity were observed, including both abnormal functional connectivity and effective connectivity among multiple brain regions. Particularly, the inhibition effects from the left precentral gyrus and left medial superior frontal gyrus to the left TPJ were closely associated with improvements in AVH. These findings underscore the potential of rTMS to effectively modulate neural pathways implicated in hallucinations in schizophrenia, thereby providing a neurobiological foundation for its therapeutic effects.

Abstract Biomolecular condensates formed by liquid-liquid phase separation (LLPS) have become an extensive mechanism of macromolecular metabolism and biochemical reactions in cells. Large molecules like proteins and nucleic acids will spontaneously aggregate and assemble into droplet-like structures driven by LLPS when the physical and chemical properties of cells are altered. LLPS provides a mature molecular platform for innate immune response, which tightly regulates key signaling in liver immune response spatially and physically, including DNA and RNA sensing pathways, inflammasome activation, and autophagy. Take this, LLPS plays a promoting or protecting role in a range of liver diseases, such as viral hepatitis, non-alcoholic fatty liver disease, liver fibrosis, hepatic ischemia-reperfusion injury, autoimmune liver disease, and liver cancer. This review systematically describes the whole landscape of LLPS in liver innate immunity. It will help us to guide a better-personalized approach to LLPS-targeted immunotherapy for liver diseases.

Abstract Background Chronic kidney disease (CKD) is a significant risk factor for pulmonary hypertension (PH), a complication that adversely affects patient prognosis. However, the mechanisms underlying this association remain poorly understood. A major obstacle to progress in this field is the lack of a reliable animal model replicating CKD-PH. Methods This study aimed to establish a stable rat model of CKD-PH. We employed a combined approach, inducing CKD through a 5/6 nephrectomy and concurrently exposing the rats to a high-salt diet. The model's hemodynamics were evaluated dynamically, alongside a comprehensive assessment of pathological changes in multiple organs. Lung tissues and serum samples were collected from the CKD-PH rats to analyze the expression of angiotensin-converting enzyme 2 (ACE2), evaluate the activity of key vascular components within the renin–angiotensin–aldosterone system (RAAS), and characterize alterations in the serum metabolic profile. Results At 14 weeks post-surgery, the CKD-PH rats displayed significant changes in hemodynamic parameters indicative of pulmonary arterial hypertension. Additionally, right ventricular hypertrophy was observed. Notably, no evidence of pulmonary vascular remodeling was found. Further analysis revealed RAAS dysregulation and downregulated ACE2 expression within the pulmonary vascular endothelium of CKD-PH rats. Moreover, the serum metabolic profile of these animals differed markedly from the sham surgery group. Conclusions Our findings suggest that the development of pulmonary arterial hypertension in CKD-PH rats is likely a consequence of a combined effect: RAAS dysregulation, decreased ACE2 expression in pulmonary vascular endothelial cells, and metabolic disturbances. Graphical Abstract

Abstract Background Microbes in the cold polar and alpine environments play a critical role in feedbacks that amplify the effects of climate change. Defining the cold adapted ecotype is one of the prerequisites for understanding the response of polar and alpine microbes to climate change. Results Here, we analysed 85 high-quality, de-duplicated genomes of Deinococcus, which can survive in a variety of harsh environments. By leveraging genomic and phenotypic traits with reverse ecology, we defined a cold adapted clade from eight Deinococcus strains isolated from Arctic, Antarctic and high alpine environments. Genome-wide optimization in amino acid composition and regulation and signalling enable the cold adapted clade to produce CO2 from organic matter and boost the bioavailability of mineral nitrogen. Conclusions Based primarily on in silico genomic analysis, we defined a potential cold adapted clade in Deinococcus and provided an updated view of the genomic traits and metabolic potential of Deinococcus. Our study would facilitate the understanding of microbial processes in the cold polar and alpine environments.

Abstract Background Tobacco use is recognized as a major cause of cardiovascular disease, which is associated with endothelial dysfunction. Endothelial function is evaluated using flow-mediated dilation (FMD), which is a noninvasive method. This meta-analysis aimed to investigate the association between smoking exposure and endothelial function evaluated using FMD values. Methods We searched the PubMed, Embase, Web of Science, and Cochrane Library databases for cohort studies of smokers or passive smokers that used FMD to assess endothelial function. The primary outcome of the study was the change in the rate of FMD. The risk of bias was evaluated using the Cochrane Collaboration tool and Newcastle–Ottawa Scale. Further, the weighted mean difference was used to analyze the continuous data. Results Overall, 14 of 1426 articles were included in this study. The results of these articles indicated that smoking is a major cause of endothelial dysfunction and altered FMD; a pooled effect size of − 3.15 was obtained with a 95% confidence interval of (− 3.84, − 2.46). Notably, pregnancy status, Asian ethnicity, or health status did not affect heterogeneity. Conclusions We found that smoking has a significant negative impact on FMD, and measures such as medication or education for smoking cessation may improve endothelial function and reduce the risk of cardiovascular disease. Trial Registration The meta-analysis was registered with PROSPERO on April 5th, 2023 (CRD42023414654).

Abstract Background Intensive care unit-acquired weakness (ICU-AW) is very common in ICU patients. It is important to understand the status quo of knowledge, attitude and behavior of ICU nurses about ICU-AW. This survey aimed to investigate the knowledge, attitude and behavior of ICU nurses about ICU-AW, to provide useful implications for clinical care. Methods ICU nurses from two tertiary hospitals in China from October 10 to November 15, 2023 were included. The ICU-AW knowledge, attitude and behavior questionnaire of ICU nurses with 31 items were used for survey. SPSS24.0 statistical software was used for data analysis. Results A total of 364 ICU nurses were included for survey. The ICU-AW knowledge of ICU nurses was 21.96 ± 5.72 (

Structural disorder is common in metal‐halide perovskites and important for understanding the functional properties of these materials. First‐principles methods can address structure variation on the atomistic scale, but they are often limited by the lack of structure‐sampling schemes required to characterize the disorder. Herein, structural disorder in the benchmark inorganic halide perovskites CsPbI3 and CsPbBr3 is computationally studied in terms of the three octahedral‐tilting angles. The subsequent variations in energetics and properties are described by 3D potential‐energy surfaces (PESs) and property landscapes, delivered by Bayesian optimization as implemented in the Bayesian optimization structure search code sampling density functional theory (DFT) calculations. The rapid convergence of the PES with about 200 DFT data points in 3D searches demonstrates the power of active learning and strategic sampling with Bayesian optimization. Further analysis indicates that disorder grows with increasing temperature and reveals that the material bandgap at finite temperatures is a statistical mean over disordered structures.

BackgroundCantharidin (CTD) extracted from the traditional Chinese medicine Mylabris has significant therapeutic effects on various tumors. However, the high toxicity of CTD can cause serious liver damage, although the related molecular mechanisms remain unclear.MethodsIn this study, we established models of CTD-induced liver and L-O2 cell damage in mice in vivo and in vitro. Subsequently, liver function indicators were detected in mouse serum, while liver tissues were subjected to pathological and transmission electron microscopy observations. L-O2 cell activity was investigated using the CCK-8 assay, and the mRNA and protein expression of DNA damage-induced transcription factor 4 (DDIT4) in liver tissue and L-O2 cells was detected using qPCR, immunohistochemistry, and western blotting. Western blotting was also used to detect the expression levels of autophagy- and apoptosis-related proteins in liver tissue and L-O2 cells. After RNAi interference with DDIT4, Rap, and 3-MA treatment, autophagy and apoptosis of L-O2 cells were detected using western blotting, flow cytometry, transmission electron microscopy, and confocal microscopy.ResultsFollowing CTD exposure, the mouse liver showed significant pathological damage and an increase in autophagic lysosomes, while the vitality of L-O2 cells showed a significant decrease. CTD led to a significant increase in the mRNA and protein levels of DDIT4 in both liver tissue and L-O2 cells, as well as a significant increase in LC3-II, Beclin1, and Bax, whereas p-mTOR and Bcl-2 were significantly decreased. Following DDIT4 interference and 3-MA treatment, the levels of autophagy and apoptosis induced by CTD in L-O2 cells were reduced. After Rap treatment, both autophagy and apoptosis of CTD-induced L-O2 cells were significantly enhanced.ConclusionThe molecular mechanism of CTD-induced toxicity in mouse liver and L-O2 cells is mainly through DDIT4/mTOR signaling pathway activation, leading to an increase in autophagy and apoptosis levels.

Abstract Background Acute coronary syndrome due to coronary artery embolism in the setting of ascending aortic thrombus is an uncommon condition, even rarer when there is no aortic pathology such as aneurysm, severe atherosclerosis, aortic dissection, or thrombophilia (whether inherited or acquired). Case presentation We report a case of a 58-year-old male presented with acute chest pain, electrocardiogram showing non-ST-elevation acute coronary syndrome. The computed tomography angiography of coronary artery revealed a mural thrombus in the proximal part of ascending aorta, located above the left coronary artery ostium, without any aortic pathologies. With the exception of hypertension and cigarette smoking, no other risk factors were identified in this patient that may increase the risk of thrombosis. Given the life-threatening risk of interventional therapy and surgery, the patient determinedly opted for anticoagulant and dual antiplatelet therapy. Then he experienced the reoccurrence of chest pain after 6-day treatment, progressed to anterior and inferior ST-segment elevation myocardial infarction. Coronary artery embolism originating from the ascending aortic thrombus was suspected. Considering the hemodynamic instability of the patient, the medical treatment was continued and bridged to warfarin and aspirin after discharge. Follow-up computed tomography angiography at 6 months showed no obstruction in coronary artery and complete resolution of the thrombus. No thromboembolic events occurred henceforward. Conclusions Acute coronary syndrome could be a manifestation of secondary coronary embolism due to ascending aortic thrombus. Currently, there is no standardized guideline for the treatment of aortic mural thrombus, individualized treatment is recommended. When surgical therapy is not applicable for the patient, anticoagulation and dual antiplatelet treatment are alternative treatments that may successfully lead to the resolution of the aortic thrombus.

Zhenzhu Wu,1 Jie Li,1 Peipei Fang,1 Chenwei Pan,1 Yi Chen2 1Department of Infectious Disease, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, People’s Republic of China; 2Department of Gastroenterology, Wenzhou People’s Hospital, Wenzhou, Zhejiang, 325000, People’s Republic of ChinaCorrespondence: Yi Chen; Zhenzhu Wu, Email alivefish1993@qq.com; 15003890524@163.comBackground: The prevalence of pyogenic liver abscess (PLA) is increasing worldwide. However, evaluation on its economic burden is still lack.Methods: A retrospective study that included all patients identified PLA from 2017 to 2020 was conducted. Clinical information and hospital costs were collected through the electronic medical records. We evaluated the economic burden using disability-adjusted life years (DALYs). Differences in socioeconomic burdens between Klebsiella pneumoniae-caused liver abscesses (KPLA) and non-Klebsiella pneumoniae-caused liver abscesses (non-KPLA) were compared.Results: We found 327 patients identified PLA in the study, including 146 with KPLA and 181 with non-KPLA. The demographic characteristics, median hospital stay, severity, and in-hospital mortality were similar between the two groups. The median total in-hospital cost was higher in the non-KPLA than in the KPLA group, although no statistical difference was found ($3607.2 vs $3424.6; P = 0.446). The median DALY loss was significantly higher in the KPLA than in the non-KPLA group [1.49 (0.97– 2.30) vs 1.27 (0.87– 1.89); P = 0.033)], and male patients presented a higher average DALY loss than female patients. KPLA had a substantially greater median indirect economic loss than the non-KPLA group [$1442.8 (915.9– 17,221.5) vs $1232.5 (764.6– 15,473.0); P = 0.028], and indirect economic loss exhibited a significant increase from 2017 to 2020 in patients with PLA. No differences were found in the socioeconomic burden between the two groups [$8019.6 (4200.3– 21,832.1) vs $7436.4 (4023.2– 19,063.9); P = 0.172].Conclusion: The economic burden of PLA is significant, particularly in patients with KP. Patients with KPLA experienced increased DALY loss and indirect economic loss than non-KPLA. PLA must be prioritized as the indirect economic burden rises annually.Keywords: pyogenic liver abscess, Klebsiella pneumoniae, socioeconomic burden, disability-adjusted life years

Dunling Xia,1 Zongqing Lu,1 Shuai Li,1 Pu Fang,1 Chun Yang,2 Xiaoyan He,3 Qinghai You,1 Gengyun Sun1 1Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Emergency Intensive Care Unit, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3School of Life Sciences, Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Qinghai You; Gengyun Sun, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Sanli’an Street, Shushan District, Hefei, Anhui Province, 230032, People’s Republic of China, Tel +86 551 6292 2913, Fax +86 551 6292 2752, Email amormor@126.com; sungengy@126.comIntroduction: Acute lung injury (ALI) and its most severe form acute respiratory distress syndrome (ARDS) are commonly occurring devastating conditions that seriously threaten the respiratory system in critically ill patients. The current treatments improve oxygenation in patients with ALI/ARDS in the short term, but do not relieve the clinical mortality of patients with ARDS.Purpose: To develop the novel drug delivery systems that can enhance the therapeutic efficacy of ALI/ARDS and impede adverse effects of drugs.Methods: Based on the key pathophysiological process of ARDS that is the disruption of the pulmonary endothelial barrier, bilirubin (Br) and atorvastatin (As) were encapsulated into an intelligent reactive oxygen species (ROS)-responsive nanocarrier DSPE-TK-PEG (DPTP) to form nanoparticles (BA@DPTP) in which the thioketal bonds could be triggered by high ROS levels in the ALI tissues.Results: BA@DPTP could accumulate in inflammatory pulmonary sites through passive targeting strategy and intelligently release Br and As only in the inflammatory tissue via ROS-responsive bond, thereby enhancing the drugs effectiveness and markedly reducing side effects. BA@DPTP effectively inhibited NF-κB signaling and NLRP3/caspase-1/GSDMD-dependent pyroptosis in mouse pulmonary microvascular endothelial cells. BA@DPTP not only protected mice with lipopolysaccharide-induced ALI and retained the integrity of the pulmonary structure, but also reduced ALI-related mortality.Conclusion: This study combined existing drugs with nano-targeting strategies to develop a novel drug-targeting platform for the efficient treatment of ALI/ARDS.Keywords: acute lung injury, acute respiratory distress syndrome, reactive oxygen species-responsiveness, nanoparticles, bilirubin, atorvastatin

Background Osteoarthritis (OA) is a common chronic joint disease that significantly affects an individual’s quality-of-life and frailty has become one of the common complications in OA patients as the disease progresses. The relationship between dietary patterns is not clear.Methods All participants are from the National Health and Nutrition Examination Survey (NHANES) and have been diagnosed with OA. The dietary inflammation index (DII) is calculated based on the dietary intake reported by the participants. Logistic regression analysis is used to investigate the relationship between DII and frailty. Restricted cubic splines are utilised to explore their nonlinear relationship. Mediation analysis is conducted to explore the role of inflammation in this relationship.Results A total of 2,530 OA patients were included in the study, with an average age of 64.46 (12.67) years. After adjusting for covariates, for each one standard deviation increase in DII, the risk of frailty increased by 15% (OR = 1.15, 95% CI = 1.03–1.28). Compared to patients with DII < –1, patients with DII > 1 had a significantly higher risk of frailty (OR = 1.50, 95% CI = 1.05-2.14).Conclusions The findings of this study indicate a positive association between DII and the risk of frailty in OA patients. These results underscore the potential impact of dietary interventions in improving the quality-of-life for OA patients.

BackgroundPrenatal anxiety and depression exert a significant influence on the physiological and psychological health outcomes of both expectant mothers and their infants. The aim of this study was to explore the intrinsic relationships between maternal anxiety, depression in early pregnancy, and their influencing factors. The findings of this study provide scientific basis for developing targeted preventive interventions.MethodsThe study involved 887 expectant mothers in the early stages of pregnancy residing in Changsha City from March to August 2022. The sociodemographic characteristics, health and lifestyle factors, and pregnancy-related factors of participants were collected. The Edinburgh Postnatal Depression Scale and the Self-Rating Anxiety Scale were used to assess depression and anxiety, respectively. Chi-square tests and multivariate logistic regression models using SPSS 26.0 were used to assess factors impacting early pregnancy anxiety and depression. Amos 23.0 was used to construct a path model to determine the potential pathways of the influencing factors.ResultsIn early pregnancy, the prevalence of depression and anxiety were 17.4% and 15.8%, respectively. Path analysis showed that early pregnancy anxiety and illness during pregnancy had a direct effect on early pregnancy depression. Anxiety had the greatest overall impact on early pregnancy depression. Education, maternal comorbidities, symptoms of pregnancy, electronic device usage time, work stress, active smoking in the 6 months before pregnancy, and sleep quality were found to solely exert indirect effects on early pregnancy depression. Sleep quality had the greatest overall impact on early pregnancy anxiety. Active smoking in the 6 months before pregnancy, sleep quality, and work stress only had a direct impact on early pregnancy anxiety. Additionally, electronic device usage duration and monthly per capita household income exclusively indirectly impacted symptoms of early pregnancy anxiety.ConclusionThe study highlights the importance of targeted interventions in early screening. Avoiding excessive use of electronic devices and active smoking in the 6 months before pregnancy, alleviating work stress and symptoms of pregnancy, increasing education levels and monthly per capita household income, improving sleep quality, and actively preventing illnesses during pregnancy and maternal comorbidities might reduce anxiety and depression in early pregnancy.

BackgroundPulmonary hypertension (PH) is a progressive disease affecting the lung vasculature that is characterized by sustained vasoconstriction and leads to vascular remodeling. The lung microbiome contributes to PH progression, but the function of the gut microbiome and the correlation between the gut microbiome and metabolome remain unclear. We have analyzed whether chronic hypoxia-induced PH alters the rat fecal microbiota.PurposeWe explored hypoxia-induced pulmonary hypertension model rats to find out the characteristic changes of intestinal microorganisms and metabolites of hypoxia-induced pulmonary hypertension, and provide a theoretical basis for clinical treatment.MethodsIn the current study, a chronic hypoxia-induced PH rat model was used to investigate the role of the gut microbiome and metabolome as a potential mechanism contributing to the occurrence and development of PH. 16S ribosomal ribonucleic acid (16S rRNA), short-chain fatty acid (SCFA) measurements, mass spectrometry (MS) metabolomics analysis and metatranscriptome were performed to analyze stool samples. The datasets were analyzed individually and integrated for combined analysis using bioinformatics approaches.ResultsOur results suggest that the gut microbiome and metabolome of chronic hypoxia-induced PH rats are distinct from those of normoxic rats and may thus aid in the search for new therapeutic or diagnostic paradigms for PH.ConclusionThe gut microbiome and metabolome are altered as a result of chronic hypoxia-induced PH. This imbalanced bacterial ecosystem might play a pathophysiological role in PH by altering homeostasis.

Renal angiomyolipoma is a benign mesenchymal tumor that can be divided into classical and other subtypes. Angiomyolipoma with epithelial cysts (AMLEC) is an extremely rare non classical subtype. AMLEC without fat component is even rarer. We report a case of AMLEC without fat in a 29-year-old man who was provisionally diagnosed with cystic renal carcinoma by ultrasonography, abdominal enhanced CT and MRI. He had no complaints, or personal or family history of TSC, or other malignancies. Based on imaging findings, robot-assisted laparoscopic nephron-sparing partial nephrectomy through a retroperitoneal approach was performed for the purpose of both diagnosis and treatment. We diagnosed AMLEC after considering the differential diagnosis of other cystic renal neoplasms, such as cystic renal carcinoma, multilocular cystic renal cell neoplasm of low malignant potential, adult cystic nephroma and mixed epithelium and stromal tumor. Meanwhile, the whole-exon sequencing (WES) results showed insert-splicing mutation in the 21st exon and 20th exon of the TSC1 gene. No treatments were performed after the operation and no evidence of recurrence or metastasis at regular follow-up.

Objective: Invasive lung adenocarcinoma（ILA） with micropapillary (MPP)/solid (SOL) components has a poor prognosis. Preoperative identification is essential for decision-making for subsequent treatment. This study aims to construct and evaluate a super-resolution（SR） enhanced radiomics model designed to predict the presence of MPP/SOL components preoperatively to provide more accurate and individualized treatment planning. Methods: Between March 2018 and November 2023, patients who underwent curative intent ILA resection were included in the study. We implemented a deep transfer learning network on CT images to improve their resolution, resulting in the acquisition of preoperative super-resolution CT (SR-CT) images. Models were developed using radiomic features extracted from CT and SR-CT images. These models employed a range of classifiers, including Logistic Regression (LR), Support Vector Machines (SVM), k-Nearest Neighbors (KNN), Random Forest, Extra Trees, Extreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LightGBM), and Multilayer Perceptron (MLP). The diagnostic performance of the models was assessed by measuring the area under the curve (AUC). Result: A total of 245 patients were recruited, of which 109 (44.5 %) were diagnosed with ILA with MPP/SOL components. In the analysis of CT images, the SVM model exhibited outstanding effectiveness, recording AUC scores of 0.864 in the training group and 0.761 in the testing group. When this SVM approach was used to develop a radiomics model with SR-CT images, it recorded AUCs of 0.904 in the training and 0.819 in the test cohorts. The calibration curves indicated a high goodness of fit, while decision curve analysis (DCA) highlighted the model's clinical utility. Conclusion: The study successfully constructed and evaluated a deep learning（DL）-enhanced SR-CT radiomics model. This model outperformed conventional CT radiomics models in predicting MPP/SOL patterns in ILA. Continued research and broader validation are necessary to fully harness and refine the clinical potential of radiomics when combined with SR reconstruction technology.

Konjac (Amorphophallus konjac) is a horticultural plant with high nutritional and medicinal values. Soft rot is a severe disease in production of konjac and it is also the main factor restricting the development of the konjac industry. It has been reported that the soft rot of konjac is mainly caused by pathogenic bacteria (mainly including Pectobacterium aroidearum, P. carotovorum subsp. carotovorum, P. chrysanthemi and Enterobacter sp.), and there is rare reports on pathogenic fungi that cause konjac soft rot. In order to clarify the pathogenic types and infection characteristics of the soft rot in Qujing City, Yunnan Province, the diseased corms were collected for fungal isolation by tissue isolation methods. The isolated fungi were identified by morphological and molecular identification methods based on ITS and LSU sequence analyses, and pathogenicity was determined according to Koch's rule. The infection characteristic was analyzed by mixed inoculation using the identified pathogenic fungi and the pathogenic bacteria of konjac soft rot. The results were as follows: (1) Three species of Fusarium spp. (Fusarium concentricum, F. oxysporum and F. ambrosium), one species of Mucor sp., one species of Rhizopus sp., one species of Penicillium sp. and one species of Clonostachys sp. were identified. (2) Statistics analysis found that Fusarium concentricum had the highest relative abundance (45.45%). (3) Koch postulates tests showed that inoculation with F. concentricum caused obvious soft rot symptoms of konjac corms within three days. (4) In addition, mixed Pectobacterium aroidearum and Fusarium concentricum together inoculation promoted the disease development, and the weight of rotten tissue was significantly higher than that of single inoculation using F. concentricum or Pectobacterium aroidearum. Overall, these results indicate that konjac soft rot may be caused by a combination of fungus and bacterium infection. The results provide a theoretical reference for the prevention and management of konjac soft rot.

The urban-rural fringe is located between the central urban built-up area and the rural hinterland, which is a transition zone for land use, economic development, and population structure. It is the most dynamic area between urban and rural areas and has become the focus of academic research in terms of geography, sociology, and urban planning. Boundary definition is the most fundamental and primary task for urban research and is particularly important for the spatial definition of the urban-rural fringe. However, a literature review reveals that an unclear spatial definition hinders in-depth scientific research on the urban-rural fringe. The absence of a spatial scope also results in a lack of targeted spatial governance policies attuned to the unique characteristics of urban, non-urban, rural, and both urban and rural areas. Existing policy instruments that exclusively focus on urban or rural areas face significant challenges in fringe regions. Recently, the establishment of a national land spatial planning system has created favorable conditions for studying the spatial definition of urban-rural junction areas. The simultaneous implementation of Territorial and Spatial Planning surveys as part of the construction of this planning system also provides technical support for accurately defining these junction areas. High precision "three adjustments" data allows for an accurate representation of the current state of urban and rural land use, enabling the precise identification of the physical geographical extent of cities. In the context of this study, a reasonable and widely accepted method for spatially defining the urban-rural fringe is essential. To address these issues, this study proposes a spatial definition method based on the urban entity regions identified in three land spatial planning surveys. The approach relies on mature territorial planning technology and addresses three key questions: indicators, thresholds, and units for defining the urban-rural fringe. 1) These indicators were derived from the precise identification of physical urban areas by the Ministry of Natural Resources of the People's Republic of China. The research units were administrative villages and neighborhood committees from previous government policies. It can effectively connect with the territorial spatial planning technology system; 2) Adopt the 25% to 75% ideal value and cluster analysis method recognized based on a comprehensive review of relevant literature and practices in spatially defining the urban-rural fringe domestically and internationally. At the end of the paper, Guangzhou is taken as a typical case study to test the effectiveness of the proposed method in defining the spatial boundaries of the urban-rural fringe. It was determined that a threshold of 10%-75% is reasonable for the spatial definition of the urban-rural fringe in Guangzhou. 3) Through the literature review and practice of government on the spatial definition of urban-rural fringe, as well as the urban-rural fringe identification and examination in Guangzhou. This study proposes a definitive approach based on the physical urban areas of territorial and spatial planning. Finally, accurate measurement indicators, clear research units and highly operable definition methods has an effective integration into the process of Territorial and Spatial Planning, which could provide a solid foundation for further spatial research and the implementation of effective governance strategies.

Virtual reality (VR)-based rehabilitation training holds great potential for post-stroke motor recovery. Existing VR-based motor imagery (MI) paradigms mostly focus on the first-person perspective, and the benefit of the third-person perspective (3PP) remains to be further exploited. The 3PP is advantageous for movements involving the back or those with a large range because of its field coverage. Some movements are easier to imagine from the 3PP. However, the 3PP training efficiency may be unsatisfactory, which may be attributed to the difficulty encountered when generating a strong sense of ownership (SOO). In this work, we attempt to enhance a visual-guided 3PP MI in stroke patients by eliciting the SOO over a virtual avatar with VR. We propose to achieve this by inducing the so-called out-of-body experience (OBE), which is a full-body illusion (FBI) that people misperceive a 3PP virtual body as his/her own (i.e., generating the SOO to the virtual body). Electroencephalography signals of 13 stroke patients are recorded while MI of the affected upper limb is being performed. The proposed paradigm is evaluated by comparing event-related desynchronization (ERD) with a control paradigm without FBI induction. The results show that the proposed paradigm leads to a significantly larger ERD during MI, indicating a bilateral activation pattern consistent with that in previous studies. In conclusion, 3PP MI can be enhanced in stroke patients by eliciting the SOO through induction of the “OBE” FBI. This study offers more possibilities for virtual rehabilitation in stroke patients and can further facilitate VR application in rehabilitation.

Visual guided motor imagery (MI) is commonly used in stroke rehabilitation, eliciting event-related desynchronization (ERD) in EEG. Previous studies found that immersion level and visuo-tactile stimulation could modulate ERD during visual guided MI, and both of two factors could also improve sense of ownership (SOO) over target limb (or body). Additionally, the relationship was also reported between the performance of MI and SOO. This study aims to investigate whether immersion and visuo-tactile stimulation affect visual guided MI through the SOO over virtual body in stroke patients. Nineteen stroke patients were recruited. The experiment included two phases (i.e., SOO induction and visual guided MI with SOO) that was manipulated across four conditions in a within-subject design: ${2}\times {2}$ , i.e., immersion (VR, 2D monitor display) $\times $ multisensory stimulation (visuo-tactile stimulation, observation without tactile stimulation). Results found peaks ERD amplitude during MI were significantly higher in stronger SOO conditions than weaker SOO conditions. Interestingly, the ERD during visual guided MI under the condition of vision only in VR and visuo-tactile stimulation in 2D monitor are similar, which indicates that SOO may be an important factor behind this phenomenon (due to the similar SOO between these two conditions). A moderate correlation was also found between SOO scores and peaks ERD amplitude during MI. This study discussed the possible factor underlying the effects of immersion and multisensory stimulation on visual guided MI in post-stroke patients, identifying the effect of SOO in this process, and could be referred in future studies for coming up with better MI paradigms for stroke rehabilitation.

Introduction: Ji-Ni-De-Xie (JNDX) is a traditional herbal preparation in China. It is widely used to treat type 2 diabetes mellitus (T2DM) in traditional Tibetan medicine system. However, its antidiabetic mechanisms have not been elucidated. The aim of this study is to elucidate the underlying mechanism of JNDX on bile acids (BAs) metabolism and FXR/FGF15 signaling pathway in T2DM rats.Methods: High-performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-QQQ-MS) and UPLC-Q-Exactive Orbitrap MS technology were used to identify the constituents in JNDX. High-fat diet (HFD) combined with streptozotocin (45 mg∙kg−1) (STZ) was used to establish a T2DM rat model, and the levels of fasting blood-glucose (FBG), glycosylated serum protein (GSP), homeostasis model assessment of insulin resistance (HOMA-IR), LPS, TNF-α, IL-1β, IL-6, TG, TC, LDL-C, HDL-C, and insulin sensitivity index (ISI) were measured to evaluate the anti-diabetic activity of JNDX. In addition, metagenomic analysis was performed to detect changes in gut microbiota. The metabolic profile of BAs was analyzed by HPLC-QQQ-MS. Moreover, the protein and mRNA expressions of FXR and FGF15 in the colon and the protein expressions of FGF15 and CYP7A1 in the liver of T2DM rats were measured by western blot and RT-qPCR.Results: A total of 12 constituents were identified by HPLC-QQQ-MS in JNDX. Furthermore, 45 chemical components in serum were identified from JNDX via UPLC-Q-Exactive Orbitrap MS technology, including 22 prototype components and 23 metabolites. Using a T2DM rat model, we found that JNDX (0.083, 0.165 and 0.33 g/kg) reduced the levels of FBG, GSP, HOMA-IR, LPS, TNF-α, IL-1β, IL-6, TG, TC, and LDL-C, and increased ISI and HDL-C levels in T2DM rats. Metagenomic results demonstrated that JNDX treatment effectively improved gut microbiota dysbiosis, including altering some bacteria (e.g., Streptococcus and Bacteroides) associated with BAs metabolism. Additionally, JNDX improved BAs disorder in T2DM rats, especially significantly increasing cholic acid (CA) levels and decreasing ursodeoxycholic acid (UDCA) levels. Moreover, the protein and mRNA expressions of FXR and FGF15 of T2DM rats were significantly increased, while the expression of CYP7A1 protein in the liver was markedly inhibited by JNDX.Discussion: JNDX can effectively improve insulin resistance, hyperglycemia, hyperlipidemia, and inflammation in T2DM rats. The mechanism is related to its regulation of BAs metabolism and activation of FXR/FGF15 signaling pathway.

Background CD276 (B7-H3), a pivotal immune checkpoint, facilitates tumorigenicity, invasiveness, and metastasis by escaping immune surveillance in a variety of tumors; however, the underlying mechanisms facilitating immune escape in esophageal squamous cell carcinoma (ESCC) remain enigmatic.Methods We investigated the expression of CD276 in ESCC tissues from patients by using immunohistochemistry (IHC) assays. In vivo, we established a 4-nitroquinoline 1-oxide (4NQO)-induced CD276 knockout (CD276wKO) and K14cre; CD276 conditional knockout (CD276cKO) mouse model of ESCC to study the functional role of CD276 in ESCC. Furthermore, we used the 4NQO-induced mouse model to evaluate the effects of anti-CXCL1 antibodies, anti-Ly6G antibodies, anti-NK1.1 antibodies, and GSK484 inhibitors on tumor growth. Moreover, IHC, flow cytometry, and immunofluorescence techniques were employed to measure immune cell proportions in ESCC. In addition, we conducted single-cell RNA sequencing analysis to examine the alterations in tumor microenvironment following CD276 depletion.Results In this study, we elucidate that CD276 is markedly upregulated in ESCC, correlating with poor prognosis. In vivo, our results indicate that depletion of CD276 inhibits tumorigenesis and progression of ESCC. Furthermore, conditional knockout of CD276 in epithelial cells engenders a significant downregulation of CXCL1, consequently reducing the formation of neutrophil extracellular trap networks (NETs) via the CXCL1–CXCR2 signaling axis, while simultaneously augmenting natural killer (NK) cells. In addition, overexpression of CD276 promotes tumorigenesis via increasing NETs’ formation and reducing NK cells in vivo.Conclusions This study successfully elucidates the functional role of CD276 in ESCC. Our comprehensive analysis uncovers the significant role of CD276 in modulating immune surveillance mechanisms in ESCC, thereby suggesting that targeting CD276 might serve as a potential therapeutic approach for ESCC treatment.

Multiple Sclerosis (MS) is an immune-mediated condition that persistently harms the central nervous system. While existing treatments can slow its course, a cure remains elusive. Stem cell therapy has gained attention as a promising approach, offering new perspectives with its regenerative and immunomodulatory properties. This article reviews the application of stem cells in MS, encompassing various stem cell types, therapeutic potential mechanisms, preclinical explorations, clinical research advancements, safety profiles of clinical applications, as well as limitations and challenges, aiming to provide new insights into the treatment research for MS.

Abstract Objectives The recommended treatment for limited‐stage small‐cell lung cancer (LS‐SCLC) is a combination of thoracic radiotherapy (TRT) and etoposide plus cisplatin (EP) chemotherapy, typically administered over 4–6 cycles. Nonetheless, the optimal duration of chemotherapy is still not determined. This study aimed to compare the outcomes of patients with LS‐SCLC who received either 6 cycles or 4–5 cycles of EP chemotherapy combined with TRT. Materials and Methods In this retrospective analysis, we utilized data from our prior prospective trial to analyze the outcomes of 265 LS‐SCLC patients who received 4–6 courses of EP combined with concurrent accelerated hyperfractionated TRT between 2002 and 2017. Patients were categorized into two groups depending on their number of chemotherapy cycles: 6 or 4–5 cycles. To assess overall survival (OS) and progression‐free survival (PFS), we employed the Kaplan–Meier method after conducting propensity score matching (PSM). Results Among the 265 LS‐SCLC patients, 60 (22.6%) received 6 cycles of EP chemotherapy, while 205 (77.4%) underwent 4–5 cycles. Following PSM (53 patients for each group), the patients in the 6 cycles group exhibited a significant improvement in OS and PFS in comparison to those in the 4–5 cycles group [median OS: 29.8 months (95% confidence interval [CI], 23.6–53.1 months) vs. 22.7 months (95% CI, 20.8–29.1 months), respectively, p = 0.019; median PFS: 17.9 months (95% CI, 13.7–30.5 months) vs. 12.0 months (95% CI, 9.8–14.2 months), respectively, p = 0.006]. The two‐year and five‐year OS rates were 60.38% and 29.87% in the 6 cycles group, whereas 47.17% and 15.72% in the 4–5 cycles group, respectively. Conclusion Patients diagnosed with LS‐SCLC who were treated with EP regimen chemotherapy combined with TRT exhibited notably enhanced survival when administered 6 cycles of chemotherapy, as compared to those who underwent only 4–5 cycles.

This study examines the effectiveness of classroom-based student writing tutors with discipline-specific backgrounds as adjunct collaborators in supporting non-native English-speaking writing teachers in the disciplines. In this qualitative study, the participants’ perceptions of this collaborative instructional model were evaluated through a thematic analysis of semi-structured interviews with the participating students, in-class writing tutors, and writing instructors from two discipline-specific writing courses. The findings highlighted the perceived benefits of this collaborative teaching with discipline-specific tutors and their involvement as the “pedagogical bridge” to overcome language teachers’ insufficiency of disciplinary content knowledge. The findings also pointed to pedagogical challenges concerning writing variations within the same discipline and students’ need for linguistic knowledge rather than discipline-specific content knowledge. Based on these findings, this study concludes with a discussion of the pedagogical implications for the effective training of discipline-based tutor collaboration and the future implementation of discipline-based writing curricula across disciplines.

Abstract Background Many studies have shown that coronary angiography (CAG) and percutaneous coronary intervention (PCI) via distal radial access (DRA) are safe and effective. Safety and efficacy of neuroangiography and neurointerventions via DRA are unknown. Purpose Search the literatures on neuroangiography and neurointerventions via DRA and conduct a systematic review and meta-analysis. Methods PubMed, Embase and Cochrane were searched from inception to November 10, 2022. After literature screening, data extraction and assessment of literature quality, random effects model was used for meta-analysis. Results A total of 236 literatures were retrieved, and 17 literatures including 1163 patients were finally included for meta-analysis.The pooled access success rate was 0.96 (95% confidence interval, 0.94–0.98), and the heterogeneity was obvious (I2 = 55.5%). The pooled access-related complications incidence rate was 0.03 (95% confidence interval, 0.02–0.05), and the heterogeneity was not obvious (I2 = 15.8%). Conclusion Neuroangiography and neurointerventions via DRA may be safe and effective. DRA is an alternative access for neuroangiography and neurointerventions.

Abstract A high recurrence rate and easy metastasis are two prominent clinical features of hepatocellular carcinoma (HCC), which is also the most common cause of cancer-related death. However, the molecular pathogenesis of HCC remains unclear. Soluble resistance-related calcium-binding protein (Sorcin) is highly expressed in a variety of tumor cell lines and multidrug-resistant cell lines and participates in the malignant progression of tumors by regulating apoptosis. Pyroptosis is also a form of programmed cell death that plays a crucial role in exerting tumor suppression function and evoking anti-tumor immune responses. However, there is no consensus that Sorcin promotes HCC progression by regulating pyroptosis. Our study manifested that Sorcin was considerably upregulated, whereas pyroptosis-associated proteins were significantly decreased in HCC tissues and cells. Sorcin silencing attenuated the proliferation, migration, and invasion of HCC cells. Knockdown of Sorcin activates pyroptosis, and overexpression of Sorcin inhibits pyroptosis, yet has no significant effect on apoptosis, ferroptosis, and autophagy in HCC cells. Furthermore, coimmunoprecipitation and immunofluorescence assays revealed that Sorcin interacted with NLRP3 inflammasome to regulate pyroptosis in HCC cells. Then, the NLRP3 inhibitor MCC950 inhibited the activation of Sorcin knockdown-induced pyroptosis and reversed the effect of Sorcin silencing-induced weakening of malignant biological behavior in HCC. Similarly, suppression of Caspase-1 reversed the inhibitory effect of Sorcin knockdown on the malignant progression of HCC via knockdown of Caspase-1 or the inhibitor VX765. Consistent with the in vitro results, the nude mouse experiment showed that Sorcin knockdown inhibited the growth of HCC by activating pyroptosis, while Caspase-1 knockdown partially restored the growth inhibition caused by Sorcin knockdown. Collectively, high Sorcin expression in HCC negatively regulates pyroptosis by interacting with the NLRP3 inflammasome to promote HCC proliferation, migration, and invasion. The results of this study provide a scientific basis for Sorcin as a new biomarker and potential therapeutic target for HCC.

Dunmin She,1,2,&ast; Wei Xu,3,&ast; Jing Liu,4,&ast; Zikai Zhang,5 Ping Fang,3 Ran Li,3 Dehong Kong,3 Miao Xuan,3 Qi Liu,3 Mo Yuan Pan,6 Yan Wang,1,2 Ying Xue3 1Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 2Department of Endocrinology, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 3Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 4Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 5Department of Oncology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 6The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Xue, Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, No. 389, Xincun Road, Shanghai, People’s Republic of China, Tel +86-21-66111061, Email doxy0622@163.com Yan Wang, Clinical Medical College, Yangzhou University, No. 98, Nantong West Road, Yangzhou, Jiangsu Province, People’s Republic of China, Email yzyan1972@126.comPurpose: Metabolic syndrome (MetS) is a rising global concern with an increasing prevalence. This study aimed to evaluate the relationship between serum uric acid to creatinine ratio (SUA/Cr) and MetS in adults with overweight/obesity in China.Patients and Methods: We conducted a cross-sectional study comprising 4699 participants with overweight/obesity who underwent physical examinations. Their serum levels of various components, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), fasting plasma glucose (FPG), creatinine (Cr), and uric acid (UA) were measured. Renal function-normalized SUA was calculated using SUA/Cr. Logistic regression analysis was employed to investigate the association between SUA/Cr and MetS in adults with overweight/obesity.Results: SUA/Cr levels were lower in non-MetS participants (OR: 2.159, 95% CI: 1.82 to 2.56; p < 0.001), and tended to rise with the increasing number of MetS components. Additionally, elevated SUA/Cr levels were associated with a higher risk of hypertension, hyperglycemia, and dyslipidemia.Conclusion: SUA/Cr levels were significantly associated with MetS and its components in Chinese adults with overweight/obesity.Keywords: metabolic syndrome, serum uric acid to creatinine ratio, overweight/obesity

To overcome the dependency of strategies utilizing cell‐free DNA (cfDNA) on tissue sampling, the emergence of sequencing panels for non‐invasive mutation screening was promoted. However, cfDNA sequencing with panels still suffers from either inaccuracy or omission, and novel approaches for accurately screening tumor mutations solely based on plasma without gene panel restriction are urgently needed. We performed unique molecular identifier (UMI) target sequencing on plasma samples and peripheral blood mononuclear cells (PBMCs) from 85 hepatocellular carcinoma (HCC) patients receiving surgical resection, which were divided into an exploration dataset (20 patients) or an evaluation dataset (65 patients). Plasma mutations were identified in pre‐operative plasma, and the mutation variant frequency change (MVFC) between post‐ and pre‐operative plasma was then calculated. In the exploration dataset, we observed that plasma mutations with MVFC

Ecosystem services are an essential foundation for sustainable human development. In view of the severe soil erosion on the Loess Plateau (LP), it is important to explore the spatial and temporal characteristics of the supply-demand balance of soil conservation services (SCSs). In this study, the soil conservation ecosystem service supply-demand ratio was innovatively proposed to quantitatively assess the supply and demand balance of soil conservation. First, the InVEST model was used to spatially quantify the supply (soil retention) and demand (soil erosion) of soil conservation services (SCS) in the LP from 2005 to 2020. Meanwhile, the spatial variation characteristics of supply-demand matching were analyzed. Second, to predict the soil conservation ecosystem service supply-demand in the future, the InVEST-PLUS model was used to simulate the supply-demand balance under multiple scenarios in 2030. The natural development (NDS), ecological protection (EPS) and economic development scenarios (EDS) were coupled with shared socioeconomic pathways (SSPs) and representative concentration pathways (RCPs). The results showed that: (1) from 2005 to 2020, the annual average soil erosion modulus of LP increased by 60.58 (t/(hm²·a)); soil retention per unit area increased by 12.89 t/hm2; both increased from northwest to southeast, and the spatial matching pattern of supply-demand was mainly low-low and shifted to low-high each year; and (2) based on the LULC of LP simulated by the PLUS model, the kappa coefficient and overall accuracy were 86.29% and 91.14%, respectively. A total of 19.8% and 22.97% of the built-up land was expanded under the NDS and EDS scenarios, respectively, and a total of 17,515.65 km2 of forestland and grassland was expanded under the EPS scenario; (3) 2030. NDS-SSP245, 2030. EPS-SSP126 and 2030. EDS-SSP585 scenarios, moderate and high surpluses accounted for 11.40%, 14.34% and 10.80% of the total surplus area, respectively; compared to 2020, the high deficit increased by 49.67%, 43.29% and 56.65% respectively. The study provided innovations for the coupling degree of future ecosystem services simulated by the InVEST-PLUS model.

Compared with the variables separation method and integral-transform method, Green’s function method is much more applicable and thus of great practical significance. Based on the general steps of Green’s function method, a new method is originally raised to get Green’s function in oil and gas flow problems through underground formations. After that, the transient pressure solution is get for flow in a spherical reservoir by using this method. This case enlarged the application of Greenʼs method function, and this work can also be a good foundation for the solution of more and more complicated flow problems in oil and gas reservoirs.

Graphene was first employed to improve the mechanical properties of Nb/Nb5Si3 composite, which is a critical candidate for the next-generation of high-temperature structural materials for aero-engines. Microstructures and mechanical properties of graphene reinforced Nb/Nb5Si3 composites with interfacial nano-Nb4C3 phase were systematically investigated. The graphene reinforced Nb/Nb5Si3 composite with outstanding room temperature fracture toughness and compressive strength was fabricated successfully via spark plasma sintering. The microstructure of this composite changes from laminated morphology to uniformly distributed equiaxed microstructure, with the increase of fabrication temperature from 1450 °C to 1550 °C. The high compressive strength of graphene reinforced Nb/Nb5Si3 composites is attributed to the load transfer of graphene, and this load transfer efficiency is strengthened due to the anchoring effect of the interfacial nano-scale Nb4C3 phase. The high fracture toughness of this composite is attributed to the pull-out of graphene, as well as the crack deflection and crack bridging induced by graphene. The laminated architecture is also beneficial to improve fracture toughness because it can promote the minor deflection of cracks. The superior combination of strength and toughness of graphene reinforced Nb/Nb5Si3 composites validates that our design strategy can successfully break through the strength-toughness trade-off. This study is expected to offer a new strategy and theoretical basis for the development of Nb/Nb5Si3 composites with outstanding mechanical properties.

Wei Xu,1,&ast; Zikai Zhang,2,&ast; Kerong Hu,1,&ast; Ping Fang,1 Ran Li,1 Dehong Kong,1 Miao Xuan,1 Yang Yue,3 Dunmin She,4,5 Ying Xue1 1Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Department of Oncology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 3School of Mathematics and Statistics, University of Melbourne, Melbourne, Australia; 4Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 5Department of Endocrinology, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Xue, Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, No. 389, Xincun Road, Shanghai, People’s Republic of China, Tel +86-21-66111061, Email doxy0622@163.com Dunmin She, Clinical Medical College, Yangzhou University, No. 98, Nantong West Road, Yangzhou, Jiangsu, People’s Republic of China, Email sdm1979@126.comPurpose: The objective of this study was to employ machine learning (ML) models utilizing non-invasive factors to achieve early and low-cost identification of MetS in a large physical examination population.Patients and Methods: The study enrolled 9171 participants who underwent physical examinations at Northern Jiangsu People’s Hospital in 2009 and 2019, to determine MetS based on criteria established by the Chinese Diabetes Society. Non-invasive characteristics such as gender, age, body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were collected and used as input variables to train and evaluate ML models for MetS identification. Several ML models were used for MetS identification, including logistic regression (LR), k-nearest neighbors algorithm (k-NN), naive bayesian (NB), decision tree (DT), random forest (RF), artificial neural network (ANN), and support vector machine (SVM).Results: Our ML models all showed good performance in the 10-fold cross-validation except for the SVM model. In the external validation, the NB model exhibited the best performance with an AUC of 0.976, accuracy of 0.923, sensitivity of 98.32%, and specificity of 91.32%.Conclusion: This study proposed a new non-invasive method for early and low-cost identification of MetS by using ML models. This approach has the potential to serve as a highly sensitive, convenient, and cost-effective tool for large-scale MetS screening.Keywords: metabolic syndrome, machine learning methods, non-invasive method, naive Bayesian

Wanyi Chen,1,&ast; Po-Han Fang,2,&ast; Bin Zheng,3 Yue Liang,1 Yiwen Mao,1 Xuefeng Jiang,1 Qionglan Tang4 1Department of Obstetrics and Gynecology, the First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 2International School, Jinan University, Guangzhou, People’s Republic of China; 3Guangdong Research Center for Organoid Engineering and Technology, Guangzhou, People’s Republic of China; 4Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qionglan Tang, Email qionglantang@126.comAbstract: So far, ovarian cancer has still been the most lethal gynecological malignancy. The chemotherapy and targeted medication are the mainstay for the recurrent ovarian cancer treatment. About 70% of the advanced-stage cases will relapse. Ascites-derived organoid is a pre-clinical model for the precise prediction of the therapeutic effectiveness for the ovarian cancer: it can be used to assess the drug sensitivity, to guide individualized precise treatment, and to improve advanced stage as well as recurrent ovarian cancer patient’ survival and prognosis. Until now, there has been no report concerning the establishment of the organoid out of the patient’s ascites and the concurrent usage of drug sensitivity test to guide the individualized precise treatment for the ovarian cancer. Here, we report a case of recurrent ovarian cancer of a 59-year-old female patient whose CA125 at its peak increased to 4523.4 U/mL. Then, patient’s own ovarian cancer organoid was constructed from the ascites by the abdominocentesis; concurrently, medication sensitivity test was performed on the organoid to guide individualized precise treatment. After the treatment, CA125 decreased to 33.7 U/mL, and the patient’s condition relieved effectively. This is the first published case report using ascites-derived organoid and the drug sensitivity test thereof to guide the precise treatment of recurrent ovarian cancer.Keywords: ascites-derived organoid, ovarian cancer organoid, recurrent ovarian cancer, drug sensitivity test, precise treatment

Panpan Fang,1,&ast; Kaijie Gao,1 Junmei Yang,1 Tiewei Li,1 Weihua Gong,1 Qianqian Sun,1 Yingyuan Wang2,&ast; 1Zhengzhou Key Laboratory of Children’s Infection and Immunity, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, People’s Republic of China; 2Department of Neonatal Intensive Care Unit, Children’s Hospital Affiliated to Zhengzhou University, Henan Children’s Hospital, Zhengzhou Children’s Hospital, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Panpan Fang; Yingyuan Wang, Email fang_panpan@163.com; yingyuanxse@163.comIntroduction: Sepsis is the most severe infectious disease with the highest mortality rate, particularly among neonates admitted to the neonatal intensive care unit (NICU). This study retrospectively analyzed the epidemiology, antibiotic resistance profiles, and prevalence of multidrug-resistant (MDR) bacteria isolated from blood or cerebrospinal fluid (CSF) cultures in order to evaluate the appropriateness of initial empirical therapy for neonatal sepsis.Methods: A retrospective study was conducted in the NICU from January 1, 2015, to December 31, 2022. Microbiological data from patients admitted to the NICU were anonymously extracted from the Laboratory of Microbiology database. Neonatal sepsis was classified into two types: early-onset sepsis (EOS), which occurs within the first 72 hours of life, and late-onset sepsis (LOS) for those begins later.Results: A total of 679 bacterial strains, 543 from blood and 136 from CSF, were detected in 631 neonates. Among these, 378 isolates (55.67%) were Gram-positive bacteria, and 301 isolates (44.33%) were Gram-negative bacteria. The most frequently isolated pathogens were Coagulase-negative staphylococci (CoNS) (36.52%), followed by Klebsiella pneumoniae (20.47%) and Escherichia coli (13.84%). In EOS, 121 strains were found, CoNS represented the majority (33.88%), followed by Klebsiella pneumoniae (23.97%) and Escherichia coli (8.26%). Early-onset septicemia exhibited 67 (55.37%) MDR bacteria. In LOS, 558 strains were isolated, CoNS represented the majority of pathogens (37.10%), followed by Klebsiella pneumoniae (19.71%) and Escherichia coli (15.05%). Late-onset septicemia showed 332 (59.50%) MDR bacteria. High rates of MDR were found in CoNS (76.21%), carbapenem-resistant Klebsiella pneumoniae (66.91%), and MRSA (33.33%).Conclusion: The study revealed an alarming prevalence of MDR strains isolated from neonatal sepsis, emphasizing the necessity of finding effective prevention and treatment measures. Colistin can be used for MDR Gram-negative bacteria, while vancomycin and teicoplanin can be considered treatment therapies for staphylococcal infections.Keywords: MDR, EOS, LOS, sepsis, bacterial strains

Abstract Lung cancer, with non‐small cell lung cancer (NSCLC) being the main subtype, is the leading cause of cancer death worldwide, which is mainly due to the cancer metastasis. Glutathione peroxidase 2 (GPX2), an antioxidant enzyme, is involved in tumor progression and metastasis. Nevertheless, the role of GPX2 in NSCLC metastasis has not been clarified. In this study, we found that GPX2 expression was elevated in NSCLC tissues and high GPX2 expression was correlated with poor prognosis in patients with NSCLC. In addtion, GPX2 expression was related to the patient's clinicopathological features, including lymph node metastasis, tumor size, and TNM stage. Overexpression of GPX2 promoted epithelial–mesenchymal transition (EMT), migration, and invasion of NSCLC cells in vitro. Knockdown of GPX2 showed the opposite effects in vitro and inhibited the metastasis of NSCLC cells in nude mice. Furthermore, GPX2 reduced reactive oxygen species (ROS) accumulation and activated the PI3K/AKT/mTOR/Snail signaling axis. Therefore, our results indicate that GPX2 promotes EMT and metastasis of NSCLC cells by activating the PI3K/AKT/mTOR/Snail signaling axis via the removal of ROS. GPX2 may be an effective diagnostic and prognostic biomarker for NSCLC.

We investigated the effects of the complex cultivation of Salvia miltiorrhiza on microbial communities, secretions, yield, and active ingredients, and the mechanism of action between microbial communities, secretions, and S. miltiorrhiza growth and development. Neither maize nor soybean was suitable to grow with S. miltiorrhiza, but sesame significantly increased salvinone content, the active ingredient of S. miltiorrhiza, and Tanshinone IIA, Tanshinone I, and Cryptotanshinone increased by 27.06%, 22.76%, and 26.41%, respectively, which increased the abundance and number of microbial communities in S. miltiorrhiza roots. 16S rRNA results showed that the most abundant bacterial phyla were Proteobacteria and Acidobacteriota, and their number increased with compound planting of sesame and S. miltiorrhiza. Salvia inter-root secretions affected the microbial community and Salvia growth and development, and lipids and lipid-like molecules significantly reduced Salvia yield and active ingredients. Overall, different plant secretions can lead to differences in the natural environment and Salvia root growth and development, and the composite planting of sesame with Salvia can improve inter-root microbial communities, enhance Salvia quality, and make fuller use of land resources.

Background: According to statistics, about one-fifth of the world's elderly people suffer from sleep disorders, and the problem of sleep disorders in the elderly is extremely serious, and this problem is one of the important causes of chronic diseases such as hypertension, hyperlipidemia, diabetes mellitus, and coronary heart disease in the elderly. The positive effect of Tai Chi exercise therapy on sleep problems has been confirmed, but at present, the effect of the specific duration of Tai Chi exercise on the improvement of elderly people with moderate to severe sleep disorders varies. Objective: META analysis was used to investigate and find that long-term Tai Chi exercise therapy has the best effect on improving sleep in elderly patients with moderate to severe sleep disorders. Methods: META analysis was performed using Revman 5.3 after searching Web of science, Pubmed, Scopus, The Cochroae Library, OVID, CBM, CNKI, VIP, and other databases, and then filtering and extracting. Results: A total of seven papers were included. Meta-analysis showed that tai chi exercise was more effective in improving sleep problems in elderly patients with sleep disorders compared to the control group, and the difference was significant. This was demonstrated by a decrease in the global Pittsburgh Sleep Quality Index (PSQI) score [SMD = −0.66, 95 % CI (−0.91, −0.41), P

ABSTRACTLong non-coding RNAs (LncRNAs) have been found to play a regulatory role in the pathophysiology of vascular remodeling-associated illnesses through the lncRNA-microRNA (miRNA) regulation axis. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is thought to be involved in proliferation, migration, apoptosis, and calcification of vascular smooth muscle cells (VSMCs). The purpose of this study was to investigate the regulatory role of MALAT1 on vascular remodeling in hypertension. Our data indicate that the expression of MALAT1 is significantly upregulated in hypertensive aortic smooth muscle. Knockdown of MALAT1 inhibited the proliferation, migration, and phenotypic transition of VSMCs induced by Ang II. Bioinformatics analysis was used to predict the complementary binding of miR-145-5p to the 3’-untranslated region of MALAT1. Besides, the expressions of MALAT1 and miR-145-5p were negatively correlated, while luciferase reporter assays and RNA immunoprecipitation assay validated the interaction between miR-145-5p and MALAT1. The proliferation, migration and phenotypic transformation of VSMCs induced by overexpression of MALAT1 were reversed in the presence of miR-145-5p. Furthermore, we verified that miR-145-5p could directly target and bind to hexokinase 2 (HK2) mRNA, and that HK2 expression was negatively correlated with miR-145-5p in VSMCs. Knockdown of HK2 significantly inhibited the effects of overexpression of MALAT1 on Ang II-induced VSMCs proliferation, migration and phenotypic transformation. Taken together, the MALAT1/miR-145-5p/HK2 axis may play a critical regulatory role in the vascular remodeling of VSMCs in hypertension.

ABSTRACTObjective Endothelial dysfunction is a critical initiating factor in the development of hypertension and related complications. Follistatin-like 1 (FSTL1) can promote endothelial cell function and stimulates revascularization in response to ischemic insult. However, it is unclear whether FSTL1 has an effect on ameliorating endothelial dysfunction in spontaneously hypertensive rats (SHRs).Methods Wistar Kyoto (WKY) and SHRs were treated with a tail vein injection of vehicle (1 mL/day) or recombinant FSTL1 (100 μg/kg body weight/day) for 4 weeks. Blood pressure was measured by tail-cuff plethysmograph, and vascular reactivity in mesenteric arteries was measured using wire myography.Results We found that treatment with FSTL1 reversed impaired endothelium-dependent relaxation (EDR) in mesenteric arteries and lowered blood pressure of SHRs. Decreased AMP-activated protein kinase (AMPK) phosphorylation, elevated endoplasmic reticulum (ER) stress markers, increased reactive oxygen species (ROS), and reduction of nitric oxide (NO) production in mesenteric arteries of SHRs were also reversed by FSTL1 treatment. Ex vivo treatment with FSTL1 improved the impaired EDR in mesenteric arteries from SHRs and reversed tunicamycin (ER stress inducer)-induced ER stress and the impairment of EDR in mesenteric arteries from WKY rats. The effects of FSTL1 were abolished by cotreatment of compound C (AMPK inhibitor).Conclusions These results suggest that FSTL1 prevents endothelial dysfunction in mesenteric arteries of SHRs through inhibiting ER stress and ROS and increasing NO production via activation of AMPK signaling.

ABSTRACTBackground The vitamin D level in the blood is associated with the incidence of hypertension. The present study investigated whether or not calcitriol, an active form of vitamin D, reverses age-related hypertension.Methods Young (3-month-old) and aged (12-month-old) C57BL/6 male mice were administered with or without calcitriol at 150 ng/kg per day by oral gavage for 8 weeks. Blood pressure was measured by tail-cuff plethysmography and telemetry, and superoxide production in renal tissue was assessed by fluorescence imaging, and the protein expression of AP1/AT1R signaling pathway was examined by Western blot.Results We showed that 24-hour renal sodium excretion was impaired and blood pressure was increased in aged mice, which was related to the enhancement of renal AT1R expression and function. In addition, the expression of transcription factor AP1 (a dimer of c-Fos and c-Jun) and the binding of AP1 to the AT1R promoter region was significantly enhanced, accompanied by decreased nuclear translocation of Nrf2, abnormal mitochondrial function including decreased ATP production, NAD+/NADH ratio and mtDNA copy numbers, and increased reactive oxygen species. Calcitriol increased 24-hour urinary sodium excretion and reduced blood pressure in aged mice. Mechanically, calcitriol increased the nuclear translocation of Nrf2, improved mitochondrial function, reduced AP1 binding ability to AT1R promoter, which reversed enhanced AT1R expression and function, and lowered blood pressure in aged mice.Conclusions Our findings indicated that calcitriol reversed age-related hypertension via downregulating renal AP1/AT1R pathway through regulating mitochondrial function. Thus, calcitriol may be a valuable therapeutic strategy for age-related hypertension.

Pressure in arteries is difficult to measure non-invasively. Although computational fluid dynamics (CFD) provides high-precision numerical solutions according to the basic physical equations of fluid mechanics, it relies on precise boundary conditions and complex preprocessing, which limits its real-time application. Machine learning algorithms have wide applications in hemodynamic research due to their powerful learning ability and fast calculation speed. Therefore, we proposed a novel method for pressure estimation based on physics-informed neural network (PINN). An ideal aortic arch model was established according to the geometric parameters from human aorta, and we performed CFD simulation with two-way fluid-solid coupling. The simulation results, including the space-time coordinates, the velocity and pressure field, were obtained as the dataset for the training and validation of PINN. Nondimensional Navier-Stokes equations and continuity equation were employed for the loss function of PINN, to calculate the velocity and relative pressure field. Post-processing was proposed to fit the absolute pressure of the aorta according to the linear relationship between relative pressure, elastic modulus and displacement of the vessel wall. Additionally, we explored the sensitivity of the PINN to the vascular elasticity, blood viscosity and blood velocity. The velocity and pressure field predicted by PINN yielded good consistency with the simulated values. In the interested region of the aorta, the relative errors of maximum and average absolute pressure were 7.33% and 5.71%, respectively. The relative pressure field was found most sensitive to blood velocity, followed by blood viscosity and vascular elasticity. This study has proposed a method for intra-vascular pressure estimation, which has potential significance in the diagnosis of cardiovascular diseases.

Using hourly data from automatic observation stations in Guizhou Province， the China Meteorological Administration Land Data Assimilation System （CLDAS） temperature and relative humidity products have been evaluated and linearly corrected in 2019.The results show that the CLDAS temperature products have a good consistency with the observations， the CLDAS relative humidity products are systematically lower than the observations and using in-situ observations to correct the CLDAS temperature and relative humidity products significantly improves the usability of the products.The mean error （ME） of the whole year CLDAS temperature products in Guizhou Province is 0.2985 ℃， the root mean square error （RMSE） is 1.5578 ℃， and the correlation coefficient （COR） is 0.9822.The annual root mean square error of the temperature products in 12.4% stations exceeds 2 ℃。From 00:00 to 23:00（Beijing Time）， the ME of the temperature products firstly decreases and then increases， while the RMSE has the maximum value around noon.After the correction， both the absolute value of the ME and the RMSE decrease， the COR increases and the RMSE of the whole year CLDAS temperature products is significantly reduced to 1.2369 ℃.When correcting grid products， the smaller the effective distance， the better the corrected effect.The ME of the whole year CLDAS relative humidity products in Guizhou Province is -4.501 %， the RMSE is 9.021 %， the COR is 0.863， while the COR during the nighttime is 0.711.The ME and COR of the relative humidity products reach the maximum around noon， while a maximum of the RMSE exists around dusk and a minimum around dawn.Linear correction has a positive effect on the CLDAS relative humidity products.The RMSE of the whole year CLDAS relative humidity products decreases by 2.317 % and the COR increases by 0.104 during the nighttime after the linear correction conducts.It is shown that the correction has a better improvement on the CLDAS relative humidity products at night.

Ping Fang,1 Zhengqin Ye,1 Ran Li,1 Dunmin She,2 Guannan Zong,1 Liya Zhang,1 Ying Xue,1 Keqin Zhang1 1Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, People’s Republic of China; 2Department of Endocrinology, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, 225001, People’s Republic of ChinaCorrespondence: Ying Xue; Keqin Zhang, Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, No. 389, Xincun Road, Shanghai, 200065, People’s Republic of China, Tel +86-21-66111061, Email doxy0622@163.com; 13621798084@126.comPurpose: Our aims were to investigate the pathogenesis of diabetic cardiomyopathy (DCM) and to explore the protective effect of glucagon-like peptide-1 receptor agonist (GLP-1RA) on DCM.Methods: After 12 weeks of treatment with exenatide-loaded microspheres, a long-acting GLP-1RA, in DCM mice, cardiac structure and function were evaluated by plasma B-type natriuretic peptide (BNP), echocardiography, H&E, oil red and Sirius staining. The expression of glucagon-like peptide-1 receptor in mouse heart tissue was determined by immunofluorescence staining. The label-free proteomic analysis of cardiac proteins was conducted among control, DCM and DM+GLP-1RA groups. Then, quantitative real-time PCR, Western blotting and dual-luciferase reporter assay were performed to verify the regulation of target protein by the upstream microRNA (miRNA).Results: GLP-1RA treatment obviously improved serum BNP, myocardial fibrosis, lipid deposition of the myocardium and echocardiography parameters in DCM mice. Sarcolemmal membrane-associated protein (SLMAP) was one of 61 differentially expressed cardiac proteins found in three groups by proteomic analysis. Up-regulation of microRNA-29b-3p (miR-29b-3p) and down-regulation of SLMAP were found in the ventricular myocardium of GLP-1RA-treated DCM mice. SLMAP was a target of miR-29b-3p, while GLP-1RA regulated SLMAP expression through miR-29b-3p. Furthermore, inhibition of glucagon-like peptide-1 receptor (GLP-1R) in cardiomyocytes reversed the effects of GLP-1RA on miR-29b/SLMAP.Conclusion: SLMAP may play roles in the pathogenesis of DCM and may be a target of GLP-1RA in protecting against DCM. After binding to myocardial GLP-1R, GLP-1RA can regulate the expression of myocardial SLMAP through miR-29b-3p.Keywords: diabetic cardiomyopathy, microRNA-29b-3p, proteomics, sarcolemmal membrane-associated protein, glucagon-like peptide-1 receptor agonist