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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.

The present study was conducted to evaluate the effect of lysolecithin supplementation in a low-energy diet on growth performance, nutrient digestibility and liver lipid metabolism of yellow-feather broilers. A total of 900 one-day-old male broilers were randomly divided into five treatment groups with 6 replicates. The dietary treatments were followed as control group (CON, basal diet), low energy group (LE, reduced 0.25 MJ/kg of metabolisable energy than basal diet), and experimental groups supplemented with 500, 750, or 1000 g/T of lysolecithin (LPL500, LPL750, and LPL1000) in LE diet. The results showed that LE treatment significantly increased the feed to gain ratio (F/G) of broilers during the whole period compared to CON group. Compared with the LE group, lysolecithin addition reduced the F/G of broiler over the entire period and significantly increased the digestibility of ether extract on 21 d and the VH/CD ratio of the jejunum and ileum over the whole period. Lysolecithin supplementation also increased chymotrypsin activity on 21 d and lipase activity on 52 d in duodenum and apolipoprotein A4 (APOA4) expression in liver tissue on 52 d compared with LE treatment. In conclusion, lysolecithin could alleviate the growth retardation caused by low ME diet through improving lipase and chymotrypsin activity, intestinal morphology, nutrients digestibility and absorption.

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).

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.

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.

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.

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.

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

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.

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.

Conclusion: UC-MSCs inhibit autophagy and improve sperm quality in AS rats through the AKT/mTOR pathway, highlighting a new idea for the treatment of AS.

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

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.

Abstract Background There is still no consensus on the optimal time of oocyte–sperm co-incubation during in vitro fertilization and embryo transfer (IVF-ET). The aim of this meta-analysis was to compare the effects of brief (1-6 h) and long (16-24 h) gametes co-incubation time on IVF outcomes. Methods The study protocol was registered online through PROSPERO (CRD42022337503) and PRISMA guidelines were followed in the present study. The following databases were searched from inception to May 2022 for randomized controlled trials (RCTs): PubMed, Embase, Cochrane library, Web of Science, using search terms related to IVF, gametes, time of co-incubation and reproductive outcome measure. Studies comparing outcomes of brief co-incubation to that of long co-incubation during IVF, and reporting primary outcome (live birth rate), secondary outcomes (clinical pregnancy rate; ongoing pregnancy rate; miscarriage rate; normal fertilization rate; polyspermy rate; top-quality embryo rate; implantation rate) were searched. A total of 11 studies were included in the meta-analysis. Combined odds ratio (OR) and 95% confidence interval (CI) were calculated for the data. Statistical heterogeneity analysis between studies was assessed by Cochran Q and I2 statistic with a significant threshold of P

Chemical modifications are a specific and efficient way to regulate the function of biological macromolecules. Among them, RNA molecules exhibit a variety of modifications that play important regulatory roles in various biological processes. More than 170 modifications have been identified in RNA molecules, among which the most common internal modifications include N6-methyladenine (m6A), n1-methyladenosine (m1A), 5-methylcytosine (m5C), and 7-methylguanine nucleotide (m7G). The most widely affected RNA modification is m6A, whose writers, readers, and erasers all have regulatory effects on RNA localization, splicing, translation, and degradation. These functions, in turn, affect RNA functionality and disease development. RNA modifications, especially m6A, play a unique role in renal cell carcinoma disease. In this manuscript, we will focus on the biological roles of m6A in renal diseases such as acute kidney injury, chronic kidney disease, lupus nephritis, diabetic kidney disease, and renal cancer.

The wide application of emerging advanced technologies causes significant changes in the development trend of the employment market. The lack of flexible and easy-to-implement analysis methods challenges general maritime education practitioners to understand the developing trends. This research proposed the improved Apriori algorithm to explore employment preference by identifying the association rule of the employability indicators and the employment status. The candidate generation methods are optimised based on the questionnaire design to generate fewer candidates. The minimum support value is automatically generated to reduce the reliance on analysis expertise and improve accuracy. To validate the algorithm, a questionnaire for the maritime graduate is used to collect employment data to test the efficiency and capability of the improved algorithm. The computation time for different data set sizes shows that the improvement could improve the algorithm's effectiveness. The algorithm also successfully identifies significant employment preference that certain employment types emphasise specific employability skills, such as responsibility and core professional skills. The results suggest that the improved A algorithm could reduce the computing burden and identify the employment preference from questionnaire data. This research provides easy-to-use and flexible analysis tools, which could reduce the computing expertise required for education practitioners.

This paper presents a novel teleoperation system using Electroencephalogram (EEG) to control the motion of a wheeled mobile robot (WMR). Different from the other traditional motion controlling method, the WMR is braked with the EEG classification results. Furthermore, the EEG will be induced by using the online BMI (Brain Machine Interface) system, and adopting the non-intrusion induced mode SSVEP (steady state visually evoked potentials). Then, user's motion intention can be recognized by canonical correlation analysis (CCA) classifier, which will be converted into motion commands of the WMR. Finally, the teleoperation technique is utilized to manage the information of the movement scene and adjust the control instructions based on the real-time information. Bezier curve is used to parameterize the path planning of the robot, and the trajectory can be adjusted in real time by EEG recognition results. A motion controller based on error model is proposed to track the planned trajectory by using velocity feedback control, providing excellent track tracking performance. Finally, the feasibility and performance of the proposed teleoperation brain-controlled WMR system are verified using demonstration experiments.

Abstract CircRNAs have been reported to play crucial roles in tumor progression and recurrence, showing potential as biomarkers in cancer. However, the global abundance of circRNA and their involvement in hepatocellular carcinoma (HCC) development have not been fully explored. Whole transcriptome sequencing was performed on tumor and peritumor from 60 patients with HCC to quantify the expression of circRNAs, and the global circRNA abundance was calculated by circRNA index (CRI). Gene‐set enrichment analysis and weighted gene co‐expression network analysis were used to reveal the biological signaling pathways associated with the global circRNA abundance. The correlation between the global circRNA abundance and the infiltration level of CD8+ T cells was explored by immunohistochemical assays. Small interfering RNA was used to knock down the pre–messenger RNA spliceosome in HCC cell lines to verify the regulation of spliceosome in global circRNA abundance. We found that dysregulation of global circRNA abundance in both tumor and peritumor could lead to worse prognosis. The immunohistochemical assay further revealed that the dysregulation of global circRNA abundance in both tumor and peritumor would obstruct the CD8+ T cells from invading into the tumor, which might explain its correlation with HCC prognosis. We also demonstrated that the spliceosome genes were the main factors to regulate the global circRNA abundance in HCC, and these results were also confirmed by knockdown experiments. Conclusion: This study revealed the association between the global circRNA abundance and patients' prognosis and its underlying mechanism.

Abstract Background Hepatocellular carcinoma (HCC) is one of the most malignant solid tumors worldwide. Recent evidence shows that the stimulator of interferon genes (STING) pathway is essential for anti-tumor immunity via inducing the production of downstream inflammatory cytokines. However, its impact on the prognosis and tumor microenvironment of HCC was still limited known. Methods We obtained gene expression profiles of HCC from GEO, TCGA, and ICGC databases, and immune-related genes (IRGs) from the ImmPort database. Multivariate Cox regression was performed to identify independent prognostic factors. Nomogram was established to predict survival probability for individual patients. Kaplan–Meier curve was used to evaluate the survival difference. Afterward, ESTIMATE, TISCH, and TIMER databases were combined to assess the immune cell infiltration. Furthermore, the qPCR, western blotting, and immunohistochemistry were done to evaluate gene expression, and in vitro cell models were built to determine cell migratory ability. Results We found that gene markers of NLRC3, STING1, TBK1, TRIM21, and XRCC6 within STING pathway were independent prognostic factors in HCC patients. Underlying the finding, a predictive nomogram was constructed in TCGA-training cohort and further validated in TCGA-all and ICGC datasets, showing credible performance. Experimentally, up-regulated TBK1 promotes the ability of HCC cell migration. Next, the survival-related immune-related co-expressed gene signatures (IRCGS) (VAV1, RHOA, and ZC3HAV1) were determined in HCC cohorts and their expression was verified in human HCC cells and clinical samples. Furthermore, survival-related IRCGS was associated with the infiltration of various immune cell subtypes in HCC, the transcriptional expression of prominent immune checkpoints, and immunotherapeutic response. Conclusion Collectively, we constructed a novel prognostic nomogram model for predicting the survival probability of individual HCC patients. Moreover, an immune-related prognostic gene signature was determined. Both might function as potential therapeutic targets for HCC treatment in the future.

Background: Tumor immune microenvironment (TIME) is crucial for tumor initiation, progression, and metastasis; however, its relationship with lung adenocarcinoma (LUAD) is unknown. Traditional predictive models screen for biomarkers that are too general and infrequently associated with immune genes. Methods: RNA sequencing data of LUAD patients and immune-related gene sets were retrieved from public databases. Using the common genes shared by The Cancer Genome Atlas (TCGA) and Immunology Database and Analysis Portal (ImmPort), differential gene expression analysis, survival analysis, Lasso regression analysis, and univariate and multivariate Cox regression analyses were performed to generate a novel risk score model. LUAD cohort in International Cancer Genome Consortium (ICGC), GSE68465 cohort in Gene Expression Omnibus (GEO) and an immunohistochemical assay were used to validate the key genes constructed risk score. The LUAD-related prognosis, clinical indicators, immune infiltrate characteristics, response to immunotherapy, and response to chemotherapeutic agents in different risk groups were evaluated by CIBERSORT, ImmuCellAI, pRRophetic and other tools. Results: The risk score model was constructed using CD79a molecule (CD79A), Dickkopf WNT signaling pathway inhibitor 1 (DKK1), and vascular endothelial growth factor C (VEGFC). High risk score was identified as a negative predictor for overall survival (OS) in subgroup analyses with tumor stage, TNM classification, therapy outcome, and ESTIMATE scores (P

ObjectiveTo evaluate the predictive value of tumor regression grade assessed by MRI (mr-TRG) after neoadjuvant chemoradiotherapy (neo-CRT) for postoperative pathological TRG (pTRG) and prognosis in patients with locally advanced rectal adenocarcinoma (LARC).Materials and methodsThis was a retrospective study from a single center experience. The patients who were diagnosed with LARC and received neo-CRT in our department between January 2016 and July 2021 were enrolled. The agreement between mrTRG and pTRG was assessed with the weighted κ test. Overall survival (OS), progress-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were calculated by Kaplan-Meier analysis and log-rank test.ResultsFrom January 2016 to July 2021, 121 LARC patients received neo-CRT in our department. Among them, 54 patients had complete clinical data, including MRI of pre- and post-neo-CRT, postoperative tumor samples, and follow-up. The median follow-up time was 34.6 months (range: 4.4-70.6 months). The estimated 3-year OS, PFS, LRFS and DMFS were 78.5%, 70.7%, 89.0%, and 75.2%, respectively. The median time from the completion of neo-CRT to preoperative MRI and surgery was 7.1 weeks and 9.7 weeks, respectively. Out of 54 patients, 5 patients achieved mrTRG1 (9.3%), 37 achieved mrTRG2 (68.5%), 8 achieved mrTRG3 (14.8%), 4 achieved mrTRG4 (7.4%), and no patient achieved mrTRG5 after neo-CRT. Regarding pTRG, 12 patients achieved pTRG0 (22.2%), 10 achieved pTRG1 (18.5%), 26 achieved pTRG2 (48.1%), and 6 achieved pTRG3 (11.1%). The agreement between three-tier mrTRG (mrTRG1 vs. mrTRG2-3 vs. mrTRG4-5) and pTRG (pTRG0 vs. pTRG1-2 vs. pTRG3) was fair (weighted kappa=0.287). In a dichotomous classification, the agreement between mrTRG(mrTRG1 vs. mrTRG2-5)and pTRG(pTRG0 vs. pTRG1-3) also resulted in fair agreement (weighted kappa=0.391). The sensitivity, specificity, positive, and negative predictive values of favorable mrTRG (mrTRG 1-2) for pathological complete response (PCR) were 75.0%, 21.4%, 21.4%, and 75.0%, respectively. In univariate analysis, favorable mrTRG (mrTRG1-2) and downstaging N were significantly associated with better OS, while favorable mrTRG (mrTRG1-2), downstaging T, and downstaging N were significantly associated with superior PFS (p

Abstract Objective Early identification of diabetic retinopathy (DR) is key to prioritizing therapy and preventing permanent blindness. This study aims to propose a machine learning model for DR early diagnosis using metabolomics and clinical indicators. Methods From 2017 to 2018, 950 participants were enrolled from two affiliated hospitals of Wenzhou Medical University and Anhui Medical University. A total of 69 matched blocks including healthy volunteers, type 2 diabetes, and DR patients were obtained from a propensity score matching-based metabolomics study. UPLC-ESI-MS/MS system was utilized for serum metabolic fingerprint data. CART decision trees (DT) were used to identify the potential biomarkers. Finally, the nomogram model was developed using the multivariable conditional logistic regression models. The calibration curve, Hosmer–Lemeshow test, receiver operating characteristic curve, and decision curve analysis were applied to evaluate the performance of this predictive model. Results The mean age of enrolled subjects was 56.7 years with a standard deviation of 9.2, and 61.4% were males. Based on the DT model, 2-pyrrolidone completely separated healthy controls from diabetic patients, and thiamine triphosphate (ThTP) might be a principal metabolite for DR detection. The developed nomogram model (including diabetes duration, systolic blood pressure and ThTP) shows an excellent quality of classification, with AUCs (95% CI) of 0.99 (0.97–1.00) and 0.99 (0.95–1.00) in training and testing sets, respectively. Furthermore, the predictive model also has a reasonable degree of calibration. Conclusions The nomogram presents an accurate and favorable prediction for DR detection. Further research with larger study populations is needed to confirm our findings.

Abstract In atrial fibrillation (AF) patients, complex electrograms during sinus rhythm (C-EGMs) could be pathological or not. We aimed to demonstrate whether local pacing was helpful to discern pathological C-EGMs. 126 persistent AF patients and 27 patients with left-side accessory pathway (LAP) underwent left atrial mapping during sinus rhythm. If C-EGMs were detected, local pacing was performed. If the electrograms turned normal, we defined them as non-fixed C-EGMs, otherwise as fixed C-EGMs. No difference was detected in the incidence and proportion of non-fixed C-EGMs between AF patients and LAP patients (101/126 vs. 19/27, P = 0.26; 9.1 ± 6.0% vs. 7.7 ± 5.7%, P = 0.28). However, the incidence and proportion of fixed C-EGMs were higher in persistent AF patients (87/126 vs. 1/27, P

ObjectiveTo investigate the prognosis of patients with LS-SCLC who responded to chest chemoradiotherapy but did not receive PCI.MethodsA retrospective analysis was conducted on LS-SCLC patients who had achieved complete remission (CR) or partial remission (PR) after definitive chemoradiotherapy but did not receive PCI. The survival rates were calculated using Kaplan–Meier method. The prognosis was analyzed using Cox proportional hazard regression model. The main endpoint was OS.ResultsOf the 500 patients with LS-SCLC admitted between June 2002 and January 2018, 327 achieved CR or PR after definitive chest chemoradiotherapy, 103 did not receive PCI, and 63 of them developed brain metastases (BM). The 1-year and 3-year OS rates in PCI group were 87.5% and 42.3% respectively, versus 70.4% and 20.9% for non-PCI group(P=0.002). The median survival time after BM was 8.7 months (range: 0.3-48.7), and 3-year OS rate was 15.0%, the median survival time of patients without BM was 20.1 months (range: 2.9-79.4), and 3-year OS was 33.4% (P=0.014). Patients with BM were subsequently treated with palliative therapy. Multivariate analysis showed that compared with no treatment, brain radiotherapy alone (HR: 0.131, 95%CI: 0.035-0.491, P=0.003) and radiotherapy combined with chemotherapy (HR: 0.039, 95%CI: 0.008-0.194, P

Context: Hepatic fibrosis is a progressive condition, often attributed to metabolic disorders, which may promote cirrhosis and liver cancer. Ganlong capsules derived from Periplaneta Americana have been shown to have a therapeutic effect on liver fibrosis but little is known about the molecular mechanisms involved.Objective: To investigate the metabolic modulations produced by Ganlong capsules in liver fibrosis.Methods: A carbon tetrachloride- (CCl4) treated rat model of liver fibrosis was constructed and Ganlong capsules administered. Levels of serum liver enzymes and pathological changes to the liver were evaluated. Non-targeted metabolomics of liver, serum and urine were used to investigate metabolic regulatory mechanisms.Results:Ganlong capsules reduced serum levels of liver enzymes and improved pathological changes in the rat model of fibrosis. Non-targeted metabolomics showed that Ganlong capsules ameliorated pathways of glycerophospholipid, linoleic acid, pyrimidine, glycine, butyric acid, valine, serine, threonine and arachidonic acid metabolism and biosynthesis of leucine and isoleucine. Such pathways influence the development of CCl4-induced liver fibrosis.Conclusion:Ganlong capsules had an anti-fibrotic hepatoprotective effect and regulated lipid, butyric acid, amino acid and arachidonic acid metabolism.

Background Tai Chi (Bafa Wubu) is a new type of simplified Tai Chi widely practiced by Tai Chi enthusiasts that has developed and perfected simplified Tai Chi movement and enriched Tai Chi practice methods. When practicing, Tai Chi athletes and enthusiasts can choose the Bafa Wubu movements to practice according to their physical conditions. The purpose of this article is to discuss the mechanism by which Bafa Wubu promotes lower extremity exercise from the perspective of exercise biomechanics. Objectives This article aims to explore the scientific training methods and technical characteristics of Bafa Wubu, and its contribution to comprehensive exercise of the lower extremities, by analyzing the biomechanical characteristics of the lower extremities of participants who practice Bafa Wubu at different levels and by comparing their ground reaction force, lower limb joints, and muscles during Bafa Wubu. Methods A total of 16 male participants were recruited and divided into an amateur group (N = 8) and a professional group (N = 8). The data were collected by a BTS 3D infrared-based motion capture system, and Kistler 3D force plate. The lower extremity joint forces and muscle strength were calculated by anybody simulation software with inverse dynamics. Results During elbowing and leaning sideways with steps sideways (ELS), the ground reaction force of the professional group was significantly higher than that of the amateur group in the sagittal, vertical, and frontal axes (P < 0.01). While stepping forward, backward, and sideways, the professional group’s joints loading at the hip, knee, and ankle was always higher in the vertical direction (P < 0.01). Furthermore, during warding off with steps forward (WOF), laying with steps forward (LF), and rolling back with steps backward (RBB), hip joint loading increased in the med–lat direction. During actions with steps backward and sideways, the professional group’s ankle flexion/extension torque and hip abduction/rotation torque were significantly larger than those of the amateur group (P < 0.01). Different actions in Bafa Wubu activate muscles to different degrees, whereas the iliacus is mainly responsible for stabilizing postures when practitioners perform standing knee lifting motions. Conclusions Professional groups who have been practicing Tai Chi (Bafa Wubu) for a long time have higher ground reaction force, and the force on the three joints of the lower extremities is different for various movements, which has positive significance for exercising the joints of the lower extremities. In addition, various motions activate muscles of different types at different levels. For amateurs to practice different movements to stimulate the muscles, targeted areas of practice promote the lower extremity muscles’ synergistic force. In summary, the muscles and joints of the lower extremity can obtain comprehensive and balanced exercise through Bafa Wubu.

Abstract Background Hepatocellular carcinoma (HCC) is the most common pathological type of liver cancer. Valosin-containing protein (VCP) is a member of the AAA-ATPase family associated with multiple molecular functions and involved in tumor metastasis and prognosis. However, the role of VCP in HCC progression is still unclear. Methods We examined the expression of VCP in HCC using the RNA sequencing and microarray data from public databases and measured it in clinical samples and cell lines by western blot, and immunohistochemistry (IHC). We also evaluated the correlation between VCP and clinical features. The VCP-interacting proteins were identified by co-immunoprecipitation combined with mass spectrometry (CoIP/MS). The underlying molecular mechanisms were investigated using in vitro and in vivo models of HCC. Results We found that VCP expression is significantly increased in tumor tissues and is associated with advanced TNM stages and poorer prognosis in HCC patients. In vitro analyses revealed that VCP overexpression promoted HCC cell proliferation, migration, and invasion via PI3K/AKT/mTOR pathway activation. Conversely, VCP knockdown resulted in the reverse phenotypes. In vivo studies indicated that up-regulated VCP expression accelerated tumor growth in a subcutaneous HCC model. The D1 domain of VCP and A box of HMGB1 were identified as the critical regions for their interaction, and D1 area was required for the tumor-promoting effects induced by VCP expression. VCP enhanced the protein stability of HMGB1 by decreasing its degradation via ubiquitin–proteasome process. Inhibition of HMGB1 markedly attenuated VCP-mediated HCC progression and downstream activation of PI3K/AKT/mTOR signals. Conclusion Collectively, these findings demonstrate that VCP is a potential prognostic biomarker in HCC and exhibits oncogenic roles via PI3K/AKT/mTOR pathway activation. HMGB1 played an essential role in VCP-mediated HCC progression, indicating that VCP and HMGB1 are potential therapeutic targets in human HCC.

Transarterial chemoembolization (TACE) is the most commonly used treatment for advanced hepatocellular carcinoma (HCC), but still lacks accurate real‐time biomarkers for monitoring its therapeutic efficacy. Here, we explored whether copy number profiling of circulating free DNA (cfDNA) could be utilized to predict responses and prognosis in HCC patients with TACE treatment. In total, 266 plasma cfDNA samples were collected from 64 HCC patients, 57 liver cirrhosis (LC) patients and 32 healthy volunteers. We performed low‐depth whole‐genome sequencing (LD‐WGS) on cfDNA samples to conduct copy number variant (CNV) analysis and tumour fraction (TFx) quantification. Then, the correlation between TFx/CNVs and therapeutic efficacy, treatment outcomes and lipiodol deposition were explored. The change in TFx during TACE treatment was associated with patients' tumour burden, and could accurately and earlier predict treatment response and prognosis, providing an alternative strategy other than mRECIST. Meanwhile, the chromosomal 16q/NQO1 amplification indicated worse therapeutic response; in patients who underwent multiple TACE sessions, TFx change during their first TACE treatment reflected the long‐term survival; additionally, the copy number amplification of chromosome 1q, 3p, 6p, 8q, 10p, 12q, 18p or 18q affected lipiodol deposition. Overall, we have provided a new liquid biopsy approach for future TACE management of HCC patients.

Although previous studies demonstrate that trehalose can help maintain glucose homeostasis in healthy humans, its role and joint effect with gl utamate on diabetic retinopathy (DR) remain unclear. We aimed to comprehensively quantify the associations of trehalose and glutamate with DR. This study included 69 pair s of DR and matched type 2 diabetic (T2D) patients. Serum trehalose and glutamate were d etermined via ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry system. Covariates were collected by a standardized questionnai re, clinical examinations and laboratory assessments. Individual and joint association of trehalose and glutamate with DR were quantified by multiple conditional logistic regress ion models. The adjusted odds of DR averagely decreased by 86% (odds ratio (OR): 0.14; 9 5% CI: 0.06, 0.33) with per interquartile range increase of trehalose. Comparing with the l owest quartile, adjusted OR (95% CI) were 0.20 (0.05, 0.83), 0.14 (0.03, 0.63) and 0.01 (

Abstract The authors investigate and demonstrate an all‐optical hybrid fiber‐free space optical (FSO)‐fiber communication system based on optical code division multiple access (OCDMA). Under different turbulence effects, the interception probability and interception distance are used as security metrics, and optimal parameters are obtained when the system meets the requirements of reliability and security simultaneously. The interception probability increases with the enhancement of turbulence effect, and decreases as the number of interfering users increases. In the case of strong turbulence, the maximum interception probability is 4.14 × 10−4. The authors design and build a 10 Gb/s all‐optical hybrid fiber‐FSO‐fiber CDMA communication system. It is shown that, under the soft‐decision forward‐error‐correction threshold of 2 × 10−2, this scheme can guarantee physical layer security in the second 20‐km optical fiber link under different turbulence conditions, while the interception distance is 8 km in the first optical fiber link. Under the hard‐decision forward‐error‐correction threshold of 3.38 × 10−3, the whole system can ensure the physical layer security.

Abstract N6-methyladenosine (m6A) is one of the most important epigenetic regulation of RNAs, such as lncRNAs. However, the underlying regulatory mechanism of m6A in diabetic cardiomyopathy (DCM) is very limited. In this study, we sought to define the role of METTL14-mediated m6A modification in pyroptosis and DCM progression. DCM rat model was established and qRT-PCR, western blot, and immunohistochemistry (IHC) were used to detect the expression of METTL14 and TINCR. Gain-and-loss functional experiments were performed to define the role of METTL14-TINCR-NLRP3 axis in pyroptosis and DCM. RNA pulldown and RNA immunoprecipitation (RIP) assays were carried out to verify the underlying interaction. Our results showed that pyroptosis was tightly involved in DCM progression. METTL14 was downregulated in cardiomyocytes and hear tissues of DCM rat tissues. Functionally, METTL14 suppressed pyroptosis and DCM via downregulating lncRNA TINCR, which further decreased the expression of key pyroptosis-related protein, NLRP3. Mechanistically, METTL14 increased m6A methylation level of TINCR gene, resulting in its downregulation. Moreover, the m6A reader protein YTHDF2 was essential for m6A methylation and mediated the degradation of TINCR. Finally, TINCR positively regulated NLRP3 by increasing its mRNA stability. To conclude, our work revealed the novel role of METTL14-mediated m6A methylation and lncRNA regulation in pyroptosis and DCM, which could help extend our understanding the epigenetic regulation of pyroptosis in DCM progression.

AimsThis study aimed to examine and compare different psychological intervention effects on the quality of life (QoL) and remission rates of patients with acute leukemia receiving chemotherapy.MethodsA total of 180 participants were randomly divided into a cognitive intervention group, a progressive muscle relaxation (PMR) group, a cognitive intervention plus PMR group, and a usual care control group. QoL via the Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 and remission rate were assessed at baseline and immediate post-intervention. A Generalized Linear Mixed Model was used for statistical analysis. Cost-effectiveness analysis with the value of the Incremental Cost-effectiveness Ratio was conducted to realize the economic evaluation of psychological interventions.ResultsThe total score of QoL and its most dimensions were significantly improved for participants in the intervention groups compared with the control group. The cognitive intervention plus PMR intervention was the most effective concerning QoL with cost-effectiveness. No significant improvements were indicated in participants’ remission rates among the groups.ConclusionThe cognitive intervention plus PMR intervention is the most effective in improving QoL with cost-effectiveness among patients with acute leukemia receiving chemotherapy. More rigorous randomized controlled trials with multiple follow-up points are suggested to clarify the psychological interventions on remission rates in this population.

According to average nucleotide identity (ANI) analysis of the complete genomes, strain 24S4–2 isolated from Antarctica is considered as a potential novel Arthrobacter species. Arthrobacter sp. 24S4–2 could grow and produce ammonium in nitrate or nitrite or even nitrogen free medium. Strain 24S4–2 was discovered to accumulate nitrate/nitrite and subsequently convert nitrate to nitrite intracellularly when incubated in a nitrate/nitrite medium. In nitrogen-free medium, strain 24S4–2 not only reduced the accumulated nitrite for growth, but also secreted ammonia to the extracellular under aerobic condition, which was thought to be linked to nitrite reductase genes nirB, nirD, and nasA by the transcriptome and RT-qPCR analysis. A membrane-like vesicle structure was detected in the cell of strain 24S4–2 by transmission electron microscopy, which was thought to be the site of intracellular nitrogen supply accumulation and conversion. This spatial and temporal conversion process of nitrogen source helps the strain maintain development in the absence of nitrogen supply or a harsh environment, which is part of its adaption strategy to the Antarctic environment. This process may also play an important ecological role, that other bacteria in the environment would benefit from its extracellular nitrogen source secretion and nitrite consumption characteristics.

IntroductionThe passive immunity of newborn piglets is mainly derived from immunoglobulin G (IgG) in breast milk, and the incomplete transfer of passive immune is considered to be an important cause of piglet death. This study was conducted to investigate the effect of early intestinal flora colonization on IgG uptake and its possible mechanism.MethodsThe newborn piglets and IPEC-J2 cells were used to investigate the possible factors and regulatory mechanisms affecting intestinal IgG uptake. In vivo, all 40 piglets were euthanized on postnatal d 0, 1, 3, and 7, with 10 piglets per time. The blood sample, gastric contents, jejunal contents and mucosa were collected for analysis. In vitro, IPEC-J2 cells transwell culture system was used to establish the IgG transporter model to explore the specific regulatory mechanism of IgG transport.ResultsOur results demonstrated that the intestinal IgG uptake was positively correlated with the expression of Neonatal Fc receptor (FcRn). With the increase of age, the intestinal flora of newborn piglets was gradually enriched. The function of intestinal genes also changes with the colonization of intestinal flora. We found that the expression trend of TLR2, TLR4 and NF-κB (P65) in intestine was consistent with that of FcRn. Furthermore, the in vitro results demonstrate that the NF-κB signaling pathway is involved in regulating FcRn-mediated IgG transmembrane transport.DiscussionEarly flora colonization affects intestinal IgG uptake in piglets, which may be mediated by NF-κB-FcRn pathway.