A data-driven intravoxel mean diffusivities distribution approach for molecular classifications and MIB-1 prediction of gliomas.

BACKGROUND: Measuring non-parametric intravoxel mean diffusivity distributions (MDDs) using magnetic resonance imaging (MRI) is a sensitive method for detecting intracellular diffusivity changes during physiological alterations. Histological and molecular glioma classifications are essential for prognosis and treatment, with distinct water diffusion dynamics among subtypes. PURPOSE: We developed a data-driven approach using a fully connected network (FCN) to enhance the speed and stability of calculating MDDs across varying SNRs, enable tumor microstructural mapping, and test its reliability in identifying MIB-1 labeling index (LI) levels and molecular status of gliomas. METHODS: An FCN was trained to learn the mapping between the simulated diffusion decay curves and the ground truth MDDs. We performed 5 000 000 simulation curves with various diffusivity components and random SNR ∈ [ 30 , 300 ] $ \in [ {30,\ 300} ]$ . Eighty percent of simulation curves were used for the FCN training, 10% for validation, and the others were external tests for the FCN performance evaluation. In vivo data were collected to evaluate its clinical reliability. One hundred one patients (44 years ± $ \pm $ 14, 67 men) with gliomas and six healthy controls underwent a 3.0 T MRI examination with a spin echo-echo planar imaging (SE-EPI) diffusion-weighted imaging (DWI) sequence. The trained FCN was employed to calculate MDDs of each brain voxel by voxel. We used the Fuzzy C-means algorithm to cluster the MDDs of tumor voxels, facilitating the characterization of distinct glioma tissues. Quantitative assessments were conducted through sectional integrals of the MDDs, demarcated by six bands to derive signal fractions ( f n , n = 1 - 6 ${{f}_n},\ n = 1 -6$ ) and diffusivities of the maximum peaks ( D p e a k ${{D}_{peak}}$ ). Cosine similarity scores (CSS) were used for MDD similarity. ANOVA and Mann-Whitney U test were used for difference analysis. Logistic regression and area under the receiver operator characteristic curve (AUC) were used for classification evaluation. RESULTS: The simulation results showed that the FCN-based MDD approach (FCN-MDD) achieved higher CSS than non-negative least squares-based MDD (NNLS-MDD). For in vivo data, the spectra of ET and NET obtained by FCN-MDD are more distinguishable than NNLS-MDD. Fraction maps delineate the characteristics of different tumor tissues (enhancing and non-enhancing tumor, edema, and necrosis). f 3 , f 4 , D p e a k ${{f}_3},\ {{f}_4},{{D}_{peak}}$ showed a positive and negative correlation with MIB-1 respectively ( r = 0.568 , r = - 0.521 , r = - 0.654 $r = 0.568,\ r = - 0.521,\ r = - 0.654$ , all p < 0.001 $p < 0.001$ ). The AUC of D p e a k ${{D}_{peak}}$ for predicting MIB-1 LI levels was 0.900 (95% CI, 0.826-0.974), versus 0.781 (0.677-0.886) of ADC. The highest AUC of isocitrate dehydrogenase (IDH) mutation status, assessed by a logistic regression model ( f 1 + f 3 ${{f}_1} + {{f}_3}$ ) was 0.873 (95% CI, 0.802-0.944). CONCLUSION: The proposed FCN-MDD method was more robust to variations in SNR and less reliant on empirically set regularization values than the NNLS-MDD method. FCN-MDD also enabled qualitative and quantitative evaluation of the composition of gliomas.

Tibial cortex transverse transport surgery improves wound healing in patients with severe type 2 DFUs by activating a systemic immune response: a cross-sectional study.

BACKGROUND: Tibial cortex transverse transport (TTT) surgery has become an ideal treatment for patients with type 2 severe diabetic foot ulcerations (DFUs) while conventional treatments are ineffective. Based on our clinical practice experience, the protective immune response from TTT surgery may play a role against infections to promote wound healing in patients with DFUs. Therefore, this research aimed to systematically study the specific clinical efficacy and the mechanism of TTT surgery. MATERIALS AND METHODS: Between June 2022 and September 2023, 68 patients with type 2 severe DFUs were enrolled and therapized by TTT surgery in this cross-sectional and experimental study. Major clinical outcomes including limb salvage rate and antibiotics usage rate were investigated. Ten clinical characteristics and laboratory features of glucose metabolism and kidney function were statistically analyzed. Blood samples from 6 key time points of TTT surgery were collected for label-free proteomics and clinical immune biomarker analysis. Besides, tissue samples from 3 key time points were for spatially resolved metabolomics and transcriptomics analysis, as well as applied to validate the key TTT-regulated molecules by RT-qPCR. RESULTS: Notably, 64.7% of patients did not use antibiotics during the entire TTT surgery. TTT surgery can achieve a high limb salvage rate of 92.6% in patients with unilateral or bilateral DFUs. Pathway analysis of a total of 252 differentially expressed proteins (DEPs) from the proteomic revealed that the immune response induced by TTT surgery at different stages was first comprehensively verified through multi-omics combined with immune biomarker analysis. The function of upward transport was activating the systemic immune response, and wound healing occurs with downward transport. The spatial metabolic characteristics of skin tissue from patients with DFUs indicated downregulated levels of stearoylcarnitine and the glycerophospholipid metabolism pathway in skin tissue from patients with severe DFUs. Finally, the expressions of PRNP (prion protein) to activate the immune response, PLCB3 (PLCB3, phospholipase C beta 3) and VE-cadherin to play roles in neovascularization, and PPDPF (pancreatic progenitor cell differentiation and proliferation factor), LAMC2 (laminin subunit gamma 2) and SPRR2G (small proline rich protein 2G) to facilitate the developmental process mainly keratinocyte differentiation were statistically significant in skin tissues through transcriptomic and RT-qPCR analysis. CONCLUSION: Tibial cortex transverse transport (TTT) surgery demonstrates favorable outcomes for patients with severe type 2 DFUs by activating a systemic immune response, contributing to anti-infection, ulcer recurrence, and the limb salvage rate for unilateral or bilateral DFUs. The specific clinical immune responses, candidate proteins, genes, and metabolic characteristics provide directions for in-depth mechanistic research on TTT surgery. Further research and public awareness are needed to optimize TTT surgery in patients with severe type 2 DFUs.

Neutrophil extracellular traps promote erectile dysfunction in rats with diabetes mellitus by enhancing NLRP3-mediated pyroptosis.

Erectile dysfunction (ED) is the most prevalent consequences in men with diabetes mellitus (DM). Recent studies demonstrates that neutrophil extracellular traps (NETs) play important roles in DM and its complications. Nevertheless, whether NETs are involved in ED remains unknown. This work intended to explore the role and mechanisms of NETs in ED in the context of DM. Here, we observed that NET generation and pyroptosis were promoted in DM rats with ED compared with controls. Mechanistically, NETs facilitated NLRP3 inflammasome activation and subsequently triggered pyroptosis under high glucose stress, ultimately leading to ED. Intriguingly, DNase I (a NET degrading agent) alleviated ED and corpus cavernosum injury in DM rats. Overall, NETs might induce ED in DM by promoting NLRP3-mediated pyroptosis in the corpus cavernosum.

Bacterial composition and physicochemical characteristics of sorghum based on environmental factors in different regions of China.

The fermentation process for Jiang-flavored baijiu using sorghum as the raw material involves a variety of microorganisms. However, the specific physicochemical characteristics of sorghum and microbial composition on its surface have not been fully elucidated. We aimed to perform a comprehensive comparative analysis of the variations in physicochemical properties and surface microflora in waxy sorghum samples from three prominent production regions in China (Renhuai, Jinsha, and Duyun). Multivariate statistical assessments were conducted that incorporated local soil and climate variables. The results showed that Cyanobacteria, unclassified bacteria, Proteobacteria, Firmicutes, and Bacteroidota were the dominant bacteria in these regions. These bacteria were associated with ethyl acetate, ethyl caprylate, ethyl lactate, and butyl groups, which synergistically produce flavorful compounds. The surface bacterial communities were affected by soil total phosphorus, altitude, diurnal temperature range, monthly mean temperature, precipitation, and effective accumulated temperature. The findings of this study provide a new perspective on microorganisms related to Jiang-flavored baijiu and can help establish a reference for the stability of liquor quality.

Deep learning for intracranial aneurysm segmentation using CT angiography.

OBJECTIVE: This study aimed to employ a two-stage deep learning method to accurately detect small aneurysms (4-10 mm in size) in computed tomography angiography (CTA) images. Methods: This study included 956 patients from 6 hospitals and a public dataset obtained with 6 CT scanners from different manufacturers. The proposed method consists of two components: a lightweight and fast head region selection (HRS) algorithm and an adaptive 3D nnU-Net network, which is used as the main architecture for segmenting aneurysms. Segments generated by the deep neural network were compared with expert-generated manual segmentation results and assessed using Dice scores. Results: The area under the curve (AUC) exceeded 79% across all datasets. In particular, the precision and AUC reached 85.2% and 87.6%, respectively, on certain datasets. The experimental results demonstrated the promising performance of this approach, which reduced the inference time by more than 50% compared to direct inference without HRS. Conclusion: Compared with a model without HRS, the deep learning approach we developed can accurately segment aneurysms by automatically localizing brain regions and can accelerate aneurysm inference by more than 50%. Keywords: Deep Learning, CT Angiography, Aneurisms.

A bibliometric analysis from 2013 to 2024 reveals research hotspots and trends in the connection between atrial fibrillation and cryoballoon: An observational study.

Using bibliometric analysis, this study attempted to provide an overview of the current state of research and key findings regarding the relationship between atrial fibrillation (AF) and cryoballoons in general. We gathered the literature from the Web of Science (WOS) database covering the last 11 years (2013-2024) pertaining to AF and cryoballoons, and we used Citespace to evaluate the mapping of knowledge. The findings demonstrated that there were 1986 articles concerning AF and cryoballoons, with a faster growth after 2018. The United States, Vrije Universiteit Brussel, and Chierchia, Gian-Battista are the nation, organization, and writer with the highest number of publications. Kuck KH (2016) is the most frequently mentioned reference as well (488). We know that Vrije Universiteit Brusse in the Belgium has emerged as 1 of this discipline's leading research forces based on a 10-year bibliometric investigation. Prominent universities and developed nations form the finest alliances for research on cryoballoons and AF.

PKM2/Hif-1α signal suppression involved in therapeutics of pulmonary fibrosis with microcystin-RR but not with pirfenidone.

To date there are only pirfenidone (PFD) and nintedanib to be given conditional recommendation in idiopathic pulmonary fibrosis (IPF) therapies with slowing disease progression, but neither has prospectively shown a reduced mortality. It is one of the urgent topics to find effective drugs for pulmonary fibrosis in medicine. Previous studies have demonstrated that microcystin-RR (MC-RR) effectively alleviates bleomycin-induced pulmonary fibrosis, but the mechanism has not been fully elucidated yet. We further conducted a comparison of therapeutic effect on the model animals of pulmonary fibrosis between MC-RR and PFD with histopathology and the expression of the molecular markers involved in differentiation, proliferation and metabolism of myofibroblasts, a major effector cell of tissue fibrosis. The levels of the enzyme molecules for maintaining the stability of interstitial structure were also evaluated. Our results showed that MC-RR and PFD effectively alleviated pulmonary fibrosis in model mice with a decreased signaling and marker molecules associated with myofibroblast differentiation and lung fibrotic lesion. In the meantime, both MC-RR and PFD treatment are beneficial to restore molecular dynamics of interstitial tissue and maintain the stability of interstitial architecture. Unexpectedly, MC-RR, rather than PFD, showed a significant effect on inhibiting PKM2-HIF-1α signaling and reducing the level of p-STAT3. Additionally, MC-RR showed a better inhibition effect on FGFR1 expression. Given that PKM2-HIF-1α and activated STAT3 molecular present a critical role in promoting the proliferation of myofibroblasts, MC-RR as a new strategy for IPF treatment has potential advantage over PFD.

Outcomes of Anterior Lateral Approach and Gerdy's Tubercle Osteotomy for Tibial Plateau Fractures Involving the Posterior Lateral Condyle: A Retrospective Study of 20 Patients.

BACKGROUND The objective of this investigation was to assess the effectiveness of using T-shaped steel plates through the anterior lateral approach and Gerdy's tubercle osteotomy for treating posterior lateral tibial plateau fractures. MATERIAL AND METHODS A retrospective analysis was conducted on clinical data from 20 patients, aged on average 53.9±10.36 years, who were admitted for tibial plateau fractures involving the posterior lateral condyle between January 2019 and October 2022. The fixation and reduction of the posterior lateral bone block were performed using the anterior lateral approach combined with Gerdy's tubercle osteotomy to address the posterior lateral tibial plateau fracture. Post-surgery assessment was conducted using the Hospital for Special Surgery (HSS) knee combined score. RESULTS During the 12-24 (14.2±1.7) month postoperative period, we conducted 20 surgeries. Within 9 to 12 weeks, fracture healing transpired without any complications such as incision infection, nerve injury, or fracture displacement being detected. Assessment of knee joint function at the final follow-up was conducted using the HSS knee combined score, with results indicating 16 cases rated as excellent, 3 cases as good, and 1 case as fair. CONCLUSIONS In tibial plateau fractures impacting the posterior lateral condyle, the anterior lateral approach, combined with Gerdy's tubercle osteotomy, allows for direct exposure and manipulation of the posterior lateral bone block fracture. Using a T-shaped support plate and a lateral locking plate provides a reliable method for fracture fixation, aiding in convenient surgical positioning and intraoperative fluoroscopy. The treatment approach effectively manages fractures located on the posterior lateral aspect of the tibial plateau.

EBV promotes TCR-T-cell therapy resistance by inducing CD163+M2 macrophage polarization and MMP9 secretion.

BACKGROUND: Epstein-Barr virus (EBV) is a double-stranded DNA oncogenic virus. Several types of solid tumors, such as nasopharyngeal carcinoma, EBV-associated gastric carcinoma, and lymphoepithelioma-like carcinoma of the lung, have been linked to EBV infection. Currently, several TCR-T-cell therapies for EBV-associated tumors are in clinical trials, but due to the suppressive immune microenvironment of solid tumors, the clinical application of TCR-T-cell therapy for EBV-associated solid tumors is limited. Figuring out the mechanism by which EBV participates in the formation of the tumor immunosuppressive microenvironment will help T cells or TCR-T cells break through the limitation and exert stronger antitumor potential. METHODS: Flow cytometry was used for analyzing macrophage differentiation phenotypes induced by EBV-infected and EBV-uninfected tumors, as well as the function of T cells co-cultured with these macrophages. Xenograft model in mice was used to explore the effects of M2 macrophages, TCR-T cells, and matrix metalloprotein 9 (MMP9) inhibitors on the growth of EBV-infected tumors. RESULTS: EBV-positive tumors exhibited an exhaustion profile of T cells, despite the presence of a large T-cell infiltration. EBV-infected tumors recruited a large number of mononuclear macrophages with CCL5 and induced CD163+M2 macrophages polarization through the secretion of CSF1 and the promotion of autocrine IL10 production by mononuclear macrophages. Massive secretion of MMP9 by this group of CD163+M2 macrophages induced by EBV infection was an important factor contributing to T-cell exhaustion and TCR-T-cell therapy resistance in EBV-positive tumors, and the use of MMP9 inhibitors improved the function of T cells cocultured with M2 macrophages. Finally, the combination of an MMP9 inhibitor with TCR-T cells targeting EBV-positive tumors significantly inhibited the growth of xenografts in mice. CONCLUSIONS: MMP9 inhibitors improve TCR-T cell function suppressed by EBV-induced M2 macrophages. TCR-T-cell therapy combined with MMP9 inhibitors was an effective therapeutic strategy for EBV-positive solid tumors.

Intermediate open state of CD4-bound HIV-1 env heterotrimers in asia CRFs.

The HIV-1 envelope glycoprotein (Env) plays crucial role in viral infection by facilitating viral attachment to host cells and inducing fusion of the virus with the host cell membrane. This fusion allows the HIV-1 viral genome to enter the target cell then triggering various stages of the viral life cycle. The native Env directly interacts with the main receptor CD4 and the co-receptor (CCR5 or CXCR4) in human cell membrane then induces membrane fusion. The elucidation of the structure of Env with CD4 and co-receptors in different HIV-1 subtypes is essential for the understanding of the mechanism of virus entry. Here we report the Cryo-EM structure of the CD4-bound HIV-1 heterotrimeric Env from Asia prevalent CRF07_BC CH119 strain. In this structure, the binding of three CD4 molecules with Env induced extensively conformational changes in gp120, resulting in the transformation of the Env from close state to intermediate open state. Additionally, the conformational shift of V1/V2 loops of the heterotrimeric Env allosterically expose the V3 loop and promoting the further interactions with co-receptor CCR5 or CXCR4. These findings not only illustrate the structural complexity and plasticity of HIV-1 Env but also give new insights how the biological trimeric Env initialize the immune recognition and membrane fusion.

Synergistic effect and molecular mechanism of nicotinamide and UM171 in ex vivo expansion of long-term hematopoietic stem cells.

Introduction: Several approaches to expand human hematopoietic stem cells (HSCs) have been reported, but the ability of these methods to expand long-term hematopoietic stem cells (LT-HSCs) remains to be improved, which limits the application of HSCs-based therapies. Methods: CD34+ cells were purified from umbilical cord blood using MacsCD34 beads, and then cultured for 12 d in a serum-free medium. Flow cytometry was used to detect phenotype, cell cycle distribution, and apoptosis of the cultured cells. Colony-forming cell (CFC) assays can evaluate multi-lineage differentiation potential of HSCs. Real-time polymerase chain reaction was employed to detect the expression of genes related to self-renewal programs and antioxidant activity. DCFH-DA probes were used to evaluate intracellular production of reactive oxygen species (ROS). Determination of the effect of different culture conditions on the balance of cytokine by cytometric bead array. Results: Here, we show a combination, Nicotinamide (NAM) combined with pyrimidoindole derivative UM171, can massively expand LT-HSCs ex vivo, and the expanded cells maintained the capability of self-renewal and multilineage differentiation. Additionally, our data indicated that UM171 promoted self-renewal of HSCs by inducing HSCs entry into the cell cycle and activating Notch and Wnt pathways, but the infinite occurrence of this process may lead to mitochondrial metabolism disorder and differentiation of HSCs. NAM kept HSCs in their primitive and dormant states by reducing intracellular ROS levels and upregulating the expression of stemness related genes, so we believed that NAM can act as a brake to control the above process. Conclusions: The discovery of the synergistic effect of NAM and UM171 for expanding LT-HSCs provides a new strategy in solving the clinical issue of limited numbers of HSCs.

Estimating pathological prognostic factors in epithelial ovarian cancers using apparent diffusion coefficients of functional tumor volume.

PURPOSE: To assess the utility of apparent diffusion coefficients (ADCs) of whole tumor volume (WTV) and functional tumor volume (FTV) in determining the pathologicalprognostic factors in epithelial ovarian cancers (EOCs). METHODS: A total of 155 consecutive patients who were diagnosed with EOC between January 2017 and August 2022 and underwent both conventional magnetic resonance imaging and diffusion-weighted imaging were assessed in this study. The maximum, minimum, and mean ADC values of the whole tumor (ADCwmax, ADCwmin, and ADCwmean, respectively) and functional tumor (ADCfmax, ADCfmin, and ADCfmean, respectively) as well as the WTV and FTV were derived from the ADC maps. The univariate and multivariate logistic regression analyses and receiver operating characteristic curve (ROC) analysis were used to assess the correlation between these ADC values and the pathological prognostic factors, namely subtypes, lymph node metastasis (LNM), Ki-67 index, and p53 expression. RESULTS: The ADCfmean value was significantly lower in type II EOC, LNM-positive, and high-Ki-67 index groups compared to the type I EOC, LNM-negative, and low-Ki-67 index groups (p ≤ 0.001). Similarly, the ADCwmean and ADCfmean values were lower in the mutant-p53 group compared to the wild-type-p53 group (p ≤ 0.001). Additionally, the ADCfmean showed the highest area under the ROC curve (AUC) for evaluating type II EOC (0.725), LNM-positive (0.782), and high-Ki-67 index (0.688) samples among the given ROC curves, while both ADCwmean and ADCfmean showed high AUCs for assessing p53 expression (0.694 and 0.678, respectively). CONCLUSION: The FTV-derived ADC values, especially ADCfmean, can be used to assess preoperative prognostic factors in EOCs.

Development of real-time recombinase polymerase amplification (RPA) and RPA combined with lateral flow dipstick (LFD) assays for the rapid and sensitive detection of cyprinid herpesvirus 3.

In this issue, we established rapid, cost-effective, and simple detection methods including recombines polymerase amplification with lateral flow dipstick (RPA-LFD) and real-time RPA for cyprinid herpesvirus 3(CyHV-3), and evaluated their sensitivity, specificity, and applicability, the real-time RPA method could achieve sensitive diagnosis of CyHV-3 within 1.3 copies per reaction, respectively. The real-time RPA method is 10-fold more sensitive than RPA-LFD method. The exact number of CyHV-3 can be calculated in each sample by real-time RPA. The sera from koi also can be tested in these methods. In addition, no cross-reaction was observed with other related pathogens, including carp oedema virus (CEV), spring viraemia of carp virus (SVCV), cyprinid herpesvirus 1(CyHV-1), cyprinid herpesvirus 2(CyHV-2), type I grass carp reovirus (GCRV-I), type II GCRV (GCRV-II), type III GCRV (GCRV-III), and Aeromonas hydrophila.

Nonlinear association of triglyceride-glucose index with hyperuricemia in US adults: a cross-sectional study.

BACKGROUND: Despite abundant evidence on the epidemiological risk factors of metabolic diseases related to hyperuricemia, there is still insufficient evidence regarding the nonlinear relationship between triglyceride-glucose (TyG) index and hyperuricemia. Thus, the purpose of this research is to clarify the nonlinear connection between TyG and hyperuricemia. METHODS: From 2011 to 2018, a cross-sectional study was carried out using data from the National Health and Nutrition Examination Survey (NHANES). This study had 8572 participants in all. TyG was computed as Ln [triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The outcome variable was hyperuricemia. The association between TyG and hyperuricemia was examined using weighted multiple logistic regression, subgroup analysis, generalized additive models, smooth fitting curves, and two-piecewise linear regression models. RESULTS: In the regression model adjusting for all confounding variables, the OR (95% CI) for the association between TyG and hyperuricemia was 2.34 (1.70, 3.21). There is a nonlinear and reverse U-shaped association between TyG and hyperuricemia, with a inflection point of 9.69. The OR (95% CI) before the inflection point was 2.64 (2.12, 3.28), and after the inflection point was 0.32 (0.11, 0.98). The interaction in gender, BMI, hypertension, and diabetes analysis was statistically significant. CONCLUSION: Additional prospective studies are required to corroborate the current findings, which indicate a strong positive connection between TyG and hyperuricemia among adults in the United States.

Metabolites of traditional Chinese medicine targeting PI3K/AKT signaling pathway for hypoglycemic effect in type 2 diabetes.

Type 2 diabetes mellitus is a chronic metabolic disease characterized by insulin resistance, with high morbidity and mortality worldwide. Due to the tightly intertwined connection between the insulin resistance pathway and the PI3K/AKT signaling pathway, regulating the PI3K/AKT pathway and its associated targets is essential for hypoglycemia and the prevention of type 2 diabetes mellitus. In recent years, metabolites isolated from traditional Chinese medicine has received more attention and acceptance for its superior bioactivity, high safety, and fewer side effects. Meanwhile, numerous in vivo and in vitro studies have revealed that the metabolites present in traditional Chinese medicine possess better bioactivities in regulating the balance of glucose metabolism, ameliorating insulin resistance, and preventing type 2 diabetes mellitus via the PI3K/AKT signaling pathway. In this article, we reviewed the literature related to the metabolites of traditional Chinese medicine improving IR and possessing therapeutic potential for type 2 diabetes mellitus by targeting the PI3K/AKT signaling pathway, focusing on the hypoglycemic mechanism of the metabolites of traditional Chinese medicine in type 2 diabetes mellitus and elaborating on the significant role of the PI3K/AKT signaling pathway in type 2 diabetes mellitus. In order to provide reference for clinical prevention and treatment of type 2 diabetes mellitus.

The characterization of the mitochondrial genome of Graptemys ouachitensis.

Graptemys ouachitensis (CAGLE, 1953) belongs to the Graptemys genus, the Emydidae family, and the Testudines order. This study involved sequencing the complete mitochondrial genome (mitogenome) of G. ouachitensis using next-generation sequencing, and analyzing the essential characteristics, and phylogenetic relationship. The results revealed that the G. ouachitensis mitogenome was 16,674 bp in length (A: 34.1%, C: 26.0%, G: 13.0%, T: 26.9%) and included 22 tRNAs, 13 protein-coding genes, two ribosomal RNA genes, and a non-coding control region (GenBank accession: NC071766). The genome composition of G. ouachitensis presented a slight A + T bias (61.0%) and exhibited a positive AT skew (0.118) and a negative GC skew (-0.333). A phylogenetic analysis based on the complete mitogenome indicated that the G. ouachitensis was more closely associated with Malaclemys terrapin than the other eight known Emydidae species. Thus, our findings present a novel mitogenome at the species level. This study introduces the first complete mitogenome of G. ouachitensis, providing valuable molecular information for phylogenetic and conservation genetics analyses of G. ouachitensis.

Neutrophils impaired by anti-galectin-3 antibodies elicit inflammation of endothelial cells to aggregate the development of lupus cutaneous vasculitis.

OBJECTIVES: To investigate whether the interplay of anti-galectin-3 antibodies (anti-Gal3 Abs) with neutrophils contributes to the development of lupus cutaneous vasculitis. METHODS: Enzyme-linked immunosorbent assay was used to determine the serum level of anti-Gal3 Abs in lupus patients. Flow cytometry, quantitative PCR and western blot were performed to investigate the expression of cell surface receptors, proinflammatory cytokines and signalling molecules in neutrophils stimulated by serum from lupus patients or healthy controls (HCs) or anti-Gal3 Ab, respectively. Immunofluorescence was performed to visualise the formation of neutrophil extracellular traps (NETs). Human umbilical vein endothelial cells were co-cultured with the supernatants from neutrophils stimulated by anti-Gal3 Ab, and cytokine production was measured at mRNA and protein levels. Immunohistochemistry was adopted to reveal the distribution of Gal3, cytokines and myeloperoxidase within lupus skin lesions. REULTS: Serum levels of anti-Gal3 Abs were negatively correlated with peripheral counts of neutrophils. Anti-Gal3 Abs positive sera from SLE patients accelerated neutrophil death, altered cell phenotype and promoted formation of NETs with the involvement of p38 MAPK pathway. Supernatants collected from neutrophils co-cultured with anti-Gal3 Ab provoked endothelial cells to produce cytokines such as IL-1, ICAM-1, SELE and particularly IL-6. Consistently, IL-6 was higher in SLE patients with anti-Gal3 Ab positive sera and enriched in the area of vascular inflammation together with enhanced expression of Gal3 protein and infiltration of neutrophils. CONCLUSIONS: Overall, these findings suggested that neutrophils were crucial mediators in anti-Gal3 Ab induced lupus cutaneous vasculitis.

The Use of Real-World Evidence for Regulatory Decisions in China.

There is a growing demand for the use of high-quality real-world evidence (RWE) to support regulatory decision-making worldwide and in China, which highlights the need for conducting literature reviews to evaluate the available data and evidence. This study aims to review the use of RWE in Chinese regulatory decisions and to summarize relevant regulatory and methodological considerations to inform the future use of RWE in China. We identified policy documents, technical guidance documents, and cases on official Chinese government websites and extracted their contents separately. We consulted experts from the National Medical Products Administration (NMPA) and academic institutes and searched case-related articles for enrichment. We also searched and included articles related to the use of RWE/Real-world data in Chinese regulatory decisions. Six trial versions of technical guidance documents, 7 case studies, and 40 articles related to the Chinese regulatory decisions were included in this study. Based on the technical guidance, data quality, and appropriate study design and statistical analysis are the main concerns for RWE generation. The cases and articles related to regulatory decisions revealed 9 main concerns, including data sources and applicability, data quality, strength of existing evidence, appropriate study design and statistical analysis, regulated and transparent process for analysis and evidence generation, product safety and efficacy, product characteristics and clinical needs, ethical considerations and data security, and communicate adequately with regulatory authorities. Among these concerns, data issues are central. Preliminary attempts have been made by the NMPA to promote the use of RWE, but substantial challenges still remain.

Rapid identification of lactic acid bacteria at species/subspecies level via ensemble learning of Ramanomes.

Rapid and accurate identification of lactic acid bacteria (LAB) species would greatly improve the screening rate for functional LAB. Although many conventional and molecular methods have proven efficient and reliable, LAB identification using these methods has generally been slow and tedious. Single-cell Raman spectroscopy (SCRS) provides the phenotypic profile of a single cell and can be performed by Raman spectroscopy (which directly detects vibrations of chemical bonds through inelastic scattering by a laser light) using an individual live cell. Recently, owing to its affordability, non-invasiveness, and label-free features, the Ramanome has emerged as a potential technique for fast bacterial detection. Here, we established a reference Ramanome database consisting of SCRS data from 1,650 cells from nine LAB species/subspecies and conducted further analysis using machine learning approaches, which have high efficiency and accuracy. We chose the ensemble meta-classifier (EMC), which is suitable for solving multi-classification problems, to perform in-depth mining and analysis of the Ramanome data. To optimize the accuracy and efficiency of the machine learning algorithm, we compared nine classifiers: LDA, SVM, RF, XGBoost, KNN, PLS-DA, CNN, LSTM, and EMC. EMC achieved the highest average prediction accuracy of 97.3% for recognizing LAB at the species/subspecies level. In summary, Ramanomes, with the integration of EMC, have promising potential for fast LAB species/subspecies identification in laboratories and may thus be further developed and sharpened for the direct identification and prediction of LAB species from fermented food.

The correlation of obesity status with serum 25-hydroxyvitamin D in US Asian adults: NHANES 2011-2018.

BACKGROUND: There is a correlation between obesity and 25-hydroxyvitamin D (25OHD) that tends to be negative. However, this relationship varies among different races. In this study, Asian adults with and without obesity were compared in terms of their levels of 25OHD. METHODS: We carried out a cross-sectional analysis on 2664 non-Hispanic Asian adults who participated in the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2018. To examine the connection between obese status, body mass index (BMI), waist circumference (WC) and weight, and 25OHD, we ran multivariate linear regression models and multivariate logistic regression models. RESULTS: After adjusting for all confounding factors, obesity status shows a significant positive correlation with vitamin D deficiency (model 3: OR = 2.318, 95% CI:1.317, 4.082). This positive correlation remains significant in males (males: OR = 2.713, 95% CI: -13.398, 5.217). In all three models, a negative association was observed between obesity status and 25OHD (model 1: ß = -4.535, 95% CI: -6.987, -2.083; model 2 ß = -4.249, 95% CI: -6.549, -2.039; model 3 ß = -1.734, 95% CI: -7.285, 3.816). After controlling for covariates, there was a significant negative correlation between WC and 25OHD when stratified by gender and obesity status in both males with and without obesity (males with obesity: ß = -1.461, 95% CI: -2.485, -0.436; males without obesity: ß = -0.855. 95% CI: -1.499, -0.210). In males with obesity, there was a very strong positive connection between body weight and 25OHD (ß = 0.912, 95% CI: 0.227, 1.597). In addition, neither gender's obese individuals showed a significant link between BMI and 25OHD. CONCLUSION: This study demonstrated a positive correlation between obesity and vitamin D deficiency and a negative correlation between obesity and 25OHD in Asian American adults. Additionally, among male obese individuals, there was a significant negative correlation between WC and 25OHD, an observation that needs to be validated in further prospective studies.