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Background At present, there are few studies on the stability of warfarin anticoagulation therapy. The main evaluation method is SAMe-TT2R2 score, but it has obvious limitations and is not applicable to non-white population. Previous studies have shown that platelet distribution width (PDW) and left atrial diameter (LAD) are closely related to time within therapeutic range (TTR). Whether they can be incorporated into the existing scoring system and improved is worthy of clinical reflection. Objective To explore the predictive value of modified SAMe-T-PDW2-LAD2 score for the percentage of TTR of common international normalized ratio (INR) for the stability of warfarin anticoagulation therapy. Methods A total of 164 patients with persistent nonvalvular atrial fibrillation who were treated with warfarin anticoagulation in Jiujiang NO.1 People's Hospital from January 2021 to June 2023 were selected as the research objects. TTR≥65% was defined as high quality anticoagulation. TTR

Introduction: Previous studies highlighted the association between the triglyceride–glucose (TyG) index and cardiovascular events in patients with diabetes. However, whether diabetes affects TyG-cardiovascular diseases (CVD) is still unclear. This study aimed to evaluate the association between the TyG index and CVD risk, stratified by diabetes status, as well as the potential modifying effect of diabetic status. Methods/design: The PubMed, Cochrane Library, and Embase databases were searched for studies on the associations between the TyG index and cardiovascular events and mortality in patients with and without diabetes from inception to December 2, 2024. The random effects model was employed to pool the effect sizes. Results: A total of 50 cohort studies (7,239,790 participants) were included. The mean age of participants was 31.46 years (diabetes mellitus [DM]: 65.18; non-DM: 31.23), and 40.66% of participants were female (DM: 36.07%; non-DM: 40.70%). The associations between the TyG index and cardiovascular events (HR: 1.72 vs. 1.55, P = 0.55), major adverse cardiovascular and cerebrovascular events (HR: 2.02 vs. 1.91, P = 0.84), stroke (HR: 1.46 vs. 1.39, P = 0.77) and cardiovascular death (HR: 1.85 vs. 1.60, P = 0.56) were similar among DM and non-DM individuals. However, the associations between the TyG index and ischemic heart disease (IHD) (HR: 2.20 vs. 1.57, P = 0.03) as well as all-cause mortality (HR: 1.94 vs. 1.24, P = 0.01) were stronger in DM patients than in non-DM patients. Conclusion: TyG index showed association with cardiovascular events, mortality, and all-cause mortality independent of diabetic status, with low to moderate certainty. The associations for IHD and all-cause death were stronger in diabetic patients than in individuals without diabetes. Future studies should explore the role of diabetes in the TyG index-associated CVD outcomes and mortality. [ABSTRACT FROM AUTHOR]

Background: Ischemic heart disease (IHD) may share biological mechanisms with cancer, including ovarian cancer, through pathways such as chronic inflammation and oxidative stress. However, the relationship between IHD and ovarian cancer subtypes remains unclear. This study used Mendelian randomization (MR) to explore potential causal associations. Methods: A two-sample MR analysis was conducted using genetic instruments for IHD from large-scale genome-wide association studies (GWAS). The inverse-variance weighted (IVW) method was used as the primary analysis, supported by MR-Egger, weighted median, and MR-PRESSO for sensitivity analyses. Results: No significant association was found between IHD and overall ovarian cancer risk (OR = 0.97, 95% CI 0.92–1.03, P = 0.378). However, IHD was linked to a reduced risk of endometrioid ovarian cancer (OR = 0.86, 95% CI 0.76–0.98, P = 0.027). No associations were observed for serous, mucinous, or clear cell ovarian cancers. Sensitivity analyses confirmed robust findings. Conclusions: IHD may confer a protective effect against endometrioid ovarian cancer but does not influence overall ovarian cancer risk. These findings highlight the need for further research into subtype-specific mechanisms. [ABSTRACT FROM AUTHOR]

Backgrounds: The role of O-GlcNAc transferase (OGT)-induced O-linked N-acetylglucosaminylation (O-GlcNAcylation) has been reported in multiple human diseases. However, its specific functions in osteoarthritis (OA) progression remain undetermined. Objective: This study focused on the target proteins of OGT-induced O-GlcNAcylation in OA and the specific functional mechanism. Methods: The levels of total O-GlcNAc and OGT were measured in both in vitro and in vivo OA models using western blot. The effects of OGT knockout on OA progression were detected through Safranin O staining, immunohistochemical staining and OARSI score evaluation. The effects of OGT silencing on LPS-induced chondrocyte injury were assessed by performing loss-of function assays. Co-immunoprecipitation (co-IP) was conducted to verify the effect of OGT-induced O-GlcNAcylation on the interaction between NEK7 and NLRP3. The role of OGT in modulating the O-GlcNAcylation and phosphorylation levels of NEK7 was analysed using western blot. Results: The OGT-indued O-GlcNAcylation level was increased in both in vitro and in vivo OA models. Knockout of OGT mitigated OA progression in model mice. Additionally, silencing of OGT suppressed LPS-induced chondrocyte pyroptosis. Moreover, silencing of OGT inhibited the O-GlcNAcylation and enhanced the phosphorylation of NEK7 at S260 site, thereby blocking the binding of NEK7 with NLRP3. Conclusion: OGT-induced NEK7 O-GlcNAcylation promotes OA progression by promoting chondrocyte pyroptosis via the suppressing interaction between NEK7 and NLRP3. [ABSTRACT FROM AUTHOR]

People use a combination of language and gestures to convey intentions, making the generation of natural co-speech gestures a challenging task. In audio-driven gesture generation, relying solely on features extracted from raw audio waveforms limits the model's ability to fully learn the joint distribution between audio and gestures. To address this limitation, we integrated key features from both raw audio waveforms and Mel-spectrograms. Specifically, we employed cascaded 1D convolutions to extract features from the audio waveform and a two-stage attention mechanism to capture features from the Mel-spectrogram. The fused features were then input into a Transformer with cross-dimension attention for sequence modeling, which mitigated accumulated non-autoregressive errors and reduced redundant information. We developed a diffusion model-based Audio to Diffusion Gesture (A2DG) generation pipeline capable of producing high-quality and diverse gestures. Our method demonstrated superior performance in extensive experiments compared to established baselines. Regarding the TED Gesture and TED Expressive datasets, the Fréchet Gesture Distance (FGD) performance improved by 16.8 and 56%, respectively. Additionally, a user study validated that the co-speech gestures generated by our method are more vivid and realistic. [ABSTRACT FROM AUTHOR]

Author(s): Ping Zhou [sup.1] , Yang She [sup.1] [sup.2] [sup.3] , Na Dong [sup.4] , Peng Li [sup.1] , Huabin He [sup.1] , Alessio Borio [sup.5] , Qingcui Wu [sup.1] [...], Immune recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors often activates proinflammatory NF-[kappa]B signalling.sup.1. Recent studies indicate that the bacterial metabolite d-glycero-[beta]-d-manno-heptose 1,7-bisphosphate (HBP) can activate NF-[kappa]B signalling in host cytosol.sup.2-4, but it is unclear whether HBP is a genuine PAMP and the cognate pattern recognition receptor has not been identified. Here we combined a transposon screen in Yersinia pseudotuberculosis with biochemical analyses and identified ADP-[beta]-d-manno-heptose (ADP-Hep), which mediates type III secretion system-dependent NF-[kappa]B activation and cytokine expression. ADP-Hep, but not other heptose metabolites, could enter host cytosol to activate NF-[kappa]B. A CRISPR-Cas9 screen showed that activation of NF-[kappa]B by ADP-Hep involves an ALPK1 (alpha-kinase 1)-TIFA (TRAF-interacting protein with forkhead-associated domain) axis. ADP-Hep directly binds the N-terminal domain of ALPK1, stimulating its kinase domain to phosphorylate and activate TIFA. The crystal structure of the N-terminal domain of ALPK1 and ADP-Hep in complex revealed the atomic mechanism of this ligand-receptor recognition process. HBP was transformed by host adenylyltransferases into ADP-heptose 7-P, which could activate ALPK1 to a lesser extent than ADP-Hep. ADP-Hep (but not HBP) alone or during bacterial infection induced Alpk1-dependent inflammation in mice. Our findings identify ALPK1 and ADP-Hep as a pattern recognition receptor and an effective immunomodulator, respectively.The bacterial metabolite ADP-heptose activates NF-[kappa]B in host cells via alpha-kinase 1 and the TIFA-TRAF signalling pathway.

Author(s): Yupeng Wang [1, 2]; Wenqing Gao [1, 2]; Xuyan Shi [1, 2]; Jingjin Ding [2, 3]; Wang Liu [2]; Huabin He [2]; Kun Wang [2]; Feng Shao (corresponding author) [...]

Background: Hypertrophic cardiomyopathy (HCM) is a genetic disorder characterized by left ventricular hypertrophy that can lead to heart failure, arrhythmias, and sudden cardiac death. Despite extensive research, the molecular mechanisms underlying HCM are not fully understood, and effective treatments remain limited. By leveraging bioinformatics and experimental validation, this study aims to identify key genes and pathways involved in HCM, uncover novel drug candidates, and provide new insights into its pathogenesis and potential therapeutic strategies., Methods: Commonly upregulated and downregulated genes in hypertrophic cardiomyopathy (HCM) were identified using Gene Expression Omnibus (GEO) datasets, including three mRNA profiling datasets and one miRNA expression dataset. Enrichment analysis and hub-gene exploration were performed using interaction networks and consistent miRNA-mRNA matches. Potential drugs for HCM were screened. HCM cellular and animal models were established using isoproterenol. Key unstudied differentially expressed genes (DEGs) were validated. Animals were treated with novel potential drugs, and improvements in HCM were assessed via ultrasound metrics. Hematoxylin and eosin (H&E) staining was used to assess myocardial fibrosis. Immunohistochemistry was employed to detect DEGs in cellular experiments., Result: We discovered 145 key upregulated and 149 downregulated DEGs associated with HCM development, among which there are eight core upregulated and seven core downregulated genes. There are 30 upregulated and six downregulated miRNAs. Between the six downregulated miRNAs and 1291 matched miRNAs (against eight core upregulated DEGs), there is one common miRNA, miR-1469. Using the CTD database, drugs that impact the expression/abundance/methylation/metabolic process of core DEGs (after the exclusion of toxic drugs) included acetaminophen, propylthiouracil, methapyrilene, triptolide, tretinoin, etc. In the HCM cell model, only ATRNL1 and WNT9A were significantly increased. In the HCM animal model, propylthiouracil, miR-1469, and triptolide demonstrated varying degrees of therapeutic effects on HCM. Propylthiouracil, but not miR-1469 or triptolide, significantly inhibited the expression of ATRNL1 in the HCM model, and all three drugs suppressed WNT9A expression., Conclusion: We identified several novel genes in HCM development, among which ATRNL1 and WNT9A were validated by cell and animal models. A deficiency of hsa-miR-1469 may be a mechanism behind HCM development. Novel medications for HCM treatment include propylthiouracil and triptolide., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Liao, Chen, Qin, Hu, Xiao, Wang and Yang.)

BRASH syndrome is a vicious cycle of hyperkalemia and bradycardia and is an under-recognized life-threatening clinical diagnosis. It is usually initiated by hypovolemia or hyperkalemia. We report here on the case of a 92-year-old man with hypertension and heart failure who presented to the emergency department with weakness following diarrhea. He was on amlodipine, benazepril, metoprolol, furosemide and spironolactone. The patient's blood pressure was 88/53 mmHg and the serum creatinine was 241 μmol/L. Within 2 h, the patient's heart rate decreased from 58 beats per minute to 26 beats per minute, and serum potassium levels gradually increased from 6.07 mmol/L to 7.3 mmol/L. The electrocardiogram showed a junctional escape rhythm with accidental sinus capture. The diagnosis of BRASH syndrome was made based on clinical symptoms, a biochemical profile and the results of an electrocardiogram. The patient was rapidly stabilized with the administration of intravenous calcium gluconate, dextrose and insulin, 5% sodium bicarbonate, 0.9% sodium chloride, furosemide, and oral zirconium cyclosilicate. Sinus rhythm at a heart rate of 75 bpm was detected 5 h later, along with normal serum potassium levels. After 2 weeks, kidney function returned to normal. Clinicians should be alert to patients with hyperkalemia and maintain a high index of suspicion for BRASH syndrome. Timely diagnosis and comprehensive intervention are critical for better outcomes in managing patients with BRASH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lei, Cao, Yuan, Xiong and He.)

Target tracking is an important research in the field of computer vision. Despite the rapid development of technology, difficulties still remain in balancing the overall performance for target occlusion, motion blur, etc . To address the above issue, we propose an improved kernel correlation filter tracking algorithm with adaptive occlusion judgement and model updating strategy (called Aojmus) to achieve robust target tracking. Firstly, the algorithm fuses color-naming (CN) and histogram of gradients (HOG) features as a feature extraction scheme and introduces a scale filter to estimate the target scale, which reduces tracking error caused by the variations of target features and scales. Secondly, the Aojmus introduces four evaluation indicators and a double thresholding mechanism to determine whether the target is occluded and the degree of occlusion respectively. The four evaluation results are weighted and fused to a final value. Finally, the updating strategy of the model is adaptively adjusted based on the weighted fusion value and the result of the scale estimation. Experimental evaluations on the OTB-2015 dataset are conducted to compare the performance of the Aojmus algorithm with four other comparable algorithms in terms of tracking precision, success rate, and speed. The experimental results show that the proposed Aojmus algorithm outperforms all the algorithms compared in terms of tracking precision. The Aojmus also exhibits excellent performance on attributes such as target occlusion and motion blur in terms of success rate. In addition, the processing speed reaches 74.85 fps, which also demonstrates good real-time performance., Competing Interests: The authors declare that they have no competing interests., (© 2023 Cai et al.)

Objective: To explore suitable treatment strategies for patients with coronary heart disease and atrial fibrillation after percutaneous coronary intervention (PCI) via systematically analyzing and comparing the clinical efficacy of dual antithrombotic therapy (DAT) and triple antithrombotic therapy (TAT)., Methods: Pubmed, Embase and Cochrane Library databases were searched. The literature from the database establishment to August 2022 was reviewed by 2 researchers separately according to the inclusion and exclusion criteria and the method recommended by the Cochrane Collaboration. The data was extracted for quality assessment. The primary endpoints of the study were safety endpoints and efficacy endpoints, the former includes major bleeding events and the latter includes mortality, myocardial infarction, stent thrombosis and stroke. RevMan5.4 software was used for meta-analysis., Results: There were 11 studies were included for the meta-analysis, 5 observational studies and 6 randomized controlled trials. The number of patients included was 2,4032, of which 13818 (57.5%) received DAT and 9483 (39.5%) received TAT. Our analyses indicated that compared with TAT treatment, DAT significantly reduced the incidence of major bleeding (OR=0.71, 95% CI [0.61, 0.83], P<0.0001) and the incidence of minor bleeding (OR=0.61, 95% CI [0.50, 0.75], P<0.00001). Subgroup analysis showed that DAT with novel oral anticoagulants (NOACs) reduced major bleeding (OR=0.64, 95% CI [0.54, 0.76], P<0.00001) and the incidence of minor bleeding (OR=0.56, 95% CI [0.45, 0.69], P<0.00001), but DAT with vitamin K antagonists (VKAs) was not significantly different from TAT in major bleeding (OR=1.20, 95% CI [0.82, 1.75], P=0.35) and minor bleeding (OR=1.15, 95% CI [0.64, 2.05], P=0.64)., Conclusions: DAT with NOACs has a higher safety profile against bleeding in patients with atrial fibrillation after PCI. DAT with VKAs was similar to TAT in terms of antithrombotic effect and incidence of bleeding., Competing Interests: None., (AJTR Copyright © 2022.)

Objective To investigate the effect of oxidative stress preconditioning on the oxidative stress-induced damage of bone marrow mesenchymal stem cells (BMSCs). Methods BMSCs were isolated and cultured by density gradient centrifugation combined with adherence method. The cells were divided into three groups: control group (control medium), oxidative damage group (treated with 1000 μmol/L H 2 O 2 for 24 hours), and preconditioning group (preincubated with 50 μmol/L H 2 O 2 for 8 hours before treatment with 1000 μmol/L H 2 O 2 for 24 hours). DCFH-DA staining was used to analyze the level of reactive oxygen species (ROS). Mitochondrial membrane potential was measured by JC-1 staining. DNA damage was detected by TUNEL. Malondialdehyde (MDA) content was detected by thiobarbituric acid (TBA) method, and superoxide dismutase (SOD) activity was detected by water soluble tetrazolium-1 (WST-1) assay. CCK-8 assay was used to detect cell viability and flow cytometry to detect cell apoptosis. Results Compared with the oxidative damage group, the preconditioning group had reduced ROS level, reduced DNA damage, higher mitochondrial membrane potential, significantly decreased MDA content, increased SOD activity, increased cell viability, and significantly decreased apoptosis. Conclusion Oxidative stress preconditioning can enhance the anti-oxidative stress ability of BMSCs and promote its survival under oxidative stress.

Objective To investigate the effect of miR-125b on the aerobic glycolysis of osteosarcoma HOS cells and its underlying mechanism. Methods Real-time quantitative PCR was performed to detect the expression of miR-125b in HOSB normal human osteoblast cells and HOS osteosarcoma cells. The glucose uptake rate was assessed with 3 H-2 deoxyglucose ( 3 H-2DG) and lactate production was tested with the kits to observe the effect of miR-125b-mimics on the aerobic glycolysis of osteosarcoma HOS cells. Hexokinase-2 (HK2) protein was detected by Western blot analysis. Dual luciferase reporter gene assay was used to determine whether HK2 was the direct target of miR-125b. Results Compared with HOSB normal human osteoblast cells, the expression of miR-125b was significantly lower in HOS cells. The glucose uptake and lactate production were downregulated in HOS cells transfected with miR-125b-mimics. Aerobic glycolysis of HOS cells was markedly inhibited. Protein level of HK2 was significantly inhibited in HOS cells transfected with miR-125b-mimics. Luciferase assay indicated that HK2 was the direct target of miR-125b. Conclusion miR-125b is down-regulated in HOS cells, and it inhibits the aerobic glycolysis of HOS cells by directly regulating the expression of HK2.