Assessing the clinical diagnostic value of anti-Müllerian hormone in polycystic ovarian syndrome and its correlation with clinical and metabolism indicators.

BACKGROUND: This study investigated the association between Anti-Müllerian Hormone (AMH) and relevant metabolic parameters and assessed its predictive value in the clinical diagnosis of polycystic ovarian syndrome (PCOS). METHODS: A total of 421 women aged 20-37 years were allocated to the PCOS (n = 168) and control (n = 253) groups, and their metabolic and hormonal parameters were compared. Spearman correlation analysis was conducted to investigate associations, binary logistic regression was used to determine PCOS risk factors, and receiver operating characteristic (ROC) curves were generated to evaluate the predictive value of AMH in diagnosing PCOS. RESULTS: The PCOS group demonstrated significantly higher blood lipid, luteinizing hormone (LH), and AMH levels than the control group. Glucose and lipid metabolism and hormonal disorders in the PCOS group were more significant than in the control group among individuals with and without obesity. LH, TSTO, and AMH were identified as independent risk factors for PCOS. AMH along with LH, and antral follicle count demonstrated a high predictive value for diagnosing PCOS. CONCLUSION: AMH exhibited robust diagnostic use for identifying PCOS and could be considered a marker for screening PCOS to improve PCOS diagnostic accuracy. Attention should be paid to the effect of glucose and lipid metabolism on the hormonal and related parameters of PCOS populations.

Clinical value of endoscopic ultrasound sound speed in differential diagnosis of pancreatic solid lesion and prognosis of pancreatic cancer.

BACKGROUND: Differential diagnosis of pancreatic solid lesion (PSL) and prognosis of pancreatic cancer (PC) is a clinical challenge. We aimed to explore the differential diagnostic value of sound speed (SS) obtained from endoscopic ultrasonography (EUS) in PSL and the prognostic value of SS in PC. METHODS: Patients with PSL in The Third Xiangya Hospital of Central South University from March 2019 to October 2019 were prospectively enrolled, who obtained SS from PSL. Patients were divided into the PC group and the pancreatic benign lesion (PBL) group. SS1 is the SS of lesions and SS2 is the SS of normal tissues adjacent to lesions. Ratio1 is equal to SS1 divided by SS2 of PSL (ratio1 = SS1/SS2). RESULTS: Eighty patients were enrolled (24 PBL patients, 56 PC patients). SS1 and ratio1 in PC group were higher compared with PBL group (SS1:1568.00 vs. 1550.00, Z = -2.066, p = 0.039; ratio1: 1.0110 vs. 1.0051, Z = -3.391, p = 0.001). The SS1 in PC (Z = -6.503, p < 0.001) was higher compared to SS2. In the nonsurgical group of PC, low ratio1 predicted high overall survival (OS) (7.000 months vs. 4.000 months; p = 0.039). In the surgical group of PC, low SS1 was associated with low median OS (4.000 months vs. 12.000 months; p = 0.033). CONCLUSIONS: SS plays a vital role in distinguishing between PBL and PC. Higher SS1 and ratio1 obtained by EUS are more related to PC than PBL. In PC patients, high SS1 may predict pancreatic lesions. In the nonsurgical group of PC, low ratio1 may predict high OS. However, in the surgical group of PC, low SS1 may predict low OS.

A Vascular Feature Detection and Matching Method Based on Dual-Branch Fusion and Structure Enhancement.

How to obtain internal cavity features and perform image matching is a great challenge for laparoscopic 3D reconstruction. This paper proposes a method for detecting and associating vascular features based on dual-branch weighted fusion vascular structure enhancement. Our proposed method is divided into three stages, including analyzing various types of minimally invasive surgery (MIS) images and designing a universal preprocessing framework to make our method generalized. We propose a Gaussian weighted fusion vascular structure enhancement algorithm using the dual-branch Frangi measure and MFAT (multiscale fractional anisotropic tensor) to address the structural measurement differences and uneven responses between venous vessels and microvessels, providing effective structural information for vascular feature extraction. We extract vascular features through dual-circle detection based on branch point characteristics, and introduce NMS (non-maximum suppression) to reduce feature point redundancy. We also calculate the ZSSD (zero sum of squared differences) and perform feature matching on the neighboring blocks of feature points extracted from the front and back frames. The experimental results show that the proposed method has an average accuracy and repeatability score of 0.7149 and 0.5612 in the Vivo data set, respectively. By evaluating the quantity, repeatability, and accuracy of feature detection, our method has more advantages and robustness than the existing methods.

OsGLP8-7 interacts with OsPRX111 to detoxify excess copper in rice.

Lignin is a phenolic biopolymer generated from phenylpropanoid pathway in the secondary cell wall and is required for defense of plants against various stress. Although the fact of stress-induced lignin deposition has been clearly demonstrated, it remains largely elusive how the formation of lignin is promoted under Cu stress. The present study showed that OsGLP8-7, an extracellular glycoprotein of rice (Oryza sativa L.), plays an important function against Cu stress. The loss function of OsGLP8-7 results in Cu sensitivity whereas overexpression of OsGLP8-7 scavenges Cu-induced superoxide anion (O2•-). OsGLP8-7 interacts with apoplastic peroxidase111 (OsPRX111) and elevates OsPRX111 stability when exposed to excess Cu. In OsGLP8-7 overexpressing (OE) lines, the retention of Cu within cell wall limiting Cu uptake into cytoplasm is attributed to the enhanced lignification required for Cu tolerance. Exogenous application of a lignin inhibitor can impair the Cu tolerance of transgenic Arabidopsis lines overexpressing OsGLP8-7. In addition, co-expression of OsGLP8-7 and OsPRX111 genes in tobacco leaves leads to an improved lignin deposition compared to leaves expressing each gene individually or the empty vector. Taken together, our findings provided the convincing evidences that the interaction between OsGLP8-7 and OsPRX111 facilitates effectively lignin polymerization, thereby contributing to Cu tolerance in rice.

Structural insights into IMP2 dimerization and RNA binding.

IGF2BP2 (IMP2) is an RNA-binding protein that contributes to cancer tumorigenesis and metabolic disorders. Structural studies focused on individual IMP2 domains have provided important mechanistic insights into IMP2 function; however, structural information on full-length IMP2 is lacking but necessary to understand how to target IMP2 activity in drug discovery. In this study, we investigated the behavior of full-length IMP2 and the influence of RNA binding using biophysical and structural methods including mass photometry, hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS), and small angle x-ray scattering (SAXS). We found that full-length IMP2 forms multiple oligomeric states but predominantly adopts a dimeric conformation. Molecular models derived from SAXS data suggest the dimer is formed in a head-to-tail orientation by the KH34 and RRM1 domains. Upon RNA binding, IMP2 forms a pseudo-symmetric dimer different from its apo/RNA-free state, with the KH12 domains of each IMP2 molecule forming the dimer interface. We also found that the formation of IMP2 oligomeric species, which includes dimers and higher-order oligomers, is sensitive to ionic strength and RNA binding. Our findings provide the first insight into the structural properties of full-length IMP2, which may lead to novel opportunities for disrupting its function with more effective IMP2 inhibitors.

Sphingosylphosphorylcholine alleviates pressure overload-induced myocardial remodeling in mice via inhibiting CaM-JNK/p38 signaling pathway.

Apoptosis plays a critical role in the development of heart failure, and sphingosylphosphorylcholine (SPC) is a bioactive sphingolipid naturally occurring in blood plasma. Some studies have shown that SPC inhibits hypoxia-induced apoptosis in myofibroblasts, the crucial non-muscle cells in the heart. Calmodulin (CaM) is a known SPC receptor. In this study we investigated the role of CaM in cardiomyocyte apoptosis in heart failure and the associated signaling pathways. Pressure overload was induced in mice by trans-aortic constriction (TAC) surgery. TAC mice were administered SPC (10 µM·kg-1·d-1) for 4 weeks post-surgery. We showed that SPC administration significantly improved survival rate and cardiac hypertrophy, and inhibited cardiac fibrosis in TAC mice. In neonatal mouse cardiomyocytes, treatment with SPC (10 µM) significantly inhibited Ang II-induced cardiomyocyte hypertrophy, fibroblast-to-myofibroblast transition and cell apoptosis accompanied by reduced Bax and phosphorylation levels of CaM, JNK and p38, as well as upregulated Bcl-2, a cardiomyocyte-protective protein. Thapsigargin (TG) could enhance CaM functions by increasing Ca2+ levels in cytoplasm. TG (3 µM) annulled the protective effect of SPC against Ang II-induced cardiomyocyte apoptosis. Furthermore, we demonstrated that SPC-mediated inhibition of cardiomyocyte apoptosis involved the regulation of p38 and JNK phosphorylation, which was downstream of CaM. These results offer new evidence for SPC regulation of cardiomyocyte apoptosis, potentially providing a new therapeutic target for cardiac remodeling following stress overload.

Long-term stable and efficient degradation of ornidazole with minimized by-product formation by a biological sulfidogenic process based on elemental sulfur.

Conventional biological treatment processes cannot efficiently and completely degrade nitroimidazole antibiotics, due to the formation of highly antibacterial and carcinogenic nitroreduction by-products. This study investigated the removal of a typical nitroimidazole antibiotic (ornidazole) during wastewater treatment by a biological sulfidogenic process based on elemental sulfur (S0-BSP). Efficient and stable ornidazole degradation and organic carbon mineralization were simultaneously achieved by the S0-BSP in a 798-day bench-scale trial. Over 99.8 % of ornidazole (200‒500 µg/L) was removed with the removal rates of up to 0.59 g/(m3·d). Meanwhile, the efficiencies of organic carbon mineralization and sulfide production were hardly impacted by the dosed ornidazole, and their rates were maintained at 0.15 kg C/(m3·d) and 0.49 kg S/(m3·d), respectively. The genera associated with ornidazole degradation were identified (e.g., Sedimentibacter, Trichococcus, and Longilinea), and their abundances increased significantly. Microbial degradation of ornidazole proceeded by several functional genes, such as dehalogenases, cysteine synthase, and dioxygenases, mainly through dechlorination, denitration, N-heterocyclic ring cleavage, and oxidation. More importantly, the nucleophilic substitution of nitro group mediated by in-situ formed reducing sulfur species (e.g., sulfide, polysulfides, and cysteine hydropolysulfides), instead of nitroreduction, enhanced the complete ornidazole degradation and minimized the formation of carcinogenic and antibacterial nitroreduction by-products. The findings suggest that S0-BSP can be a promising approach to treat wastewater containing multiple contaminants, such as emerging organic pollutants, organic carbon, nitrate, and heavy metals.

Go big and go home: A bulky extension makes promiscuous ligands settle down.

Synthetic ligands often show undesired polypharmacology, affecting the function of multiple targets. In this issue of Structure, Huber et al. developed a PXR-specific agonist based on a promiscuous ligand. Their structure-guided approach exploited the malleability of the PXR ligand-binding pocket, which unlike other nuclear receptors could accommodate bulkier ligands.

A Novel Evaluation Method for SLAM-Based 3D Reconstruction of Lumen Panoramas.

Laparoscopy is employed in conventional minimally invasive surgery to inspect internal cavities by viewing two-dimensional images on a monitor. This method has a limited field of view and provides insufficient information for surgeons, increasing surgical complexity. Utilizing simultaneous localization and mapping (SLAM) technology to reconstruct laparoscopic scenes can offer more comprehensive and intuitive visual feedback. Moreover, the precision of the reconstructed models is a crucial factor for further applications of surgical assistance systems. However, challenges such as data scarcity and scale uncertainty hinder effective assessment of the accuracy of endoscopic monocular SLAM reconstructions. Therefore, this paper proposes a technique that incorporates existing knowledge from calibration objects to supplement metric information and resolve scale ambiguity issues, and it quantifies the endoscopic reconstruction accuracy based on local alignment metrics. The experimental results demonstrate that the reconstructed models restore realistic scales and enable error analysis for laparoscopic SLAM reconstruction systems. This suggests that for the evaluation of monocular SLAM three-dimensional (3D) reconstruction accuracy in minimally invasive surgery scenarios, our proposed scheme for recovering scale factors is viable, and our evaluation outcomes can serve as criteria for measuring reconstruction precision.

Compilation and evaluation of gastrointestinal endoscopy satisfaction scale. / æ¶ˆåŒ–å† é•œè¯Šç–—æ»¡æ„åº¦é‡è¡¨çš„ç¼–åˆ¶åŠè¯„ä»·.

OBJECTIVES: Gastrointestinal endoscopy plays an important role in the diagnosis and treatment of gastrointestinal diseases. The satisfaction degree of gastrointestinal endoscopy can directly affect the patient's compliance and further impact the treating effect. At present, there is no scale to evaluate the satisfaction degree of gastrointestinal endoscopy in China. This study aims to develop a satisfaction scale of gastrointestinal endoscopy suitable for national conditions and to evaluate its reliability and validity, which provides a tool for clinic to evaluate patients' satisfaction with gastrointestinal endoscopy. METHODS: The original gastrointestinal endoscopy satisfaction scale was compiled by literature review, consulting senior endoscopists and experts. Through the first round of survey about 120 patients, the original scale was analyzed and modified according to the results to get the gastrointestinal endoscopy satisfaction scale (formal scale). The formal scale was used to conduct the second round of survey about 200 patients. The reliability and validity of the scale were analyzed and evaluated according to the survey results. RESULTS: The reliability of the original scale was good but the validity was poor. The formal scale had 2 dimensions and 10 items, the Cronbach's alpha and split-half reliability were 0.889 and 0.823. The structure validity index χ2/df was 2.513, root mean square error of approximation (RMSEA) was 0.094, goodness of fit index (GFI) was 0.914, adjusted goodness of fit index (AGFI) was 0.861, comparative fit index (CFI) was 0.946, normed fit index (NFI) was 0.915. The aggregate validity was general, the discriminative validity was good, and the direct score of patients was strongly correlated with the total score of the scale. CONCLUSIONS: The gastrointestinal endoscopy satisfaction scale has good reliability and validity, which can be used as a tool to evaluate patients' satisfaction with gastrointestinal endoscopy in China.

ELK3 Targeting AEG1 Promotes Migration and Invasion of Ovarian Cancer Cells under Hypoxia.

Ovarian cancer (OC) is one of the most common tumors in female reproductive organs with a five-year survival rate of less than 45%. Metastasis is a crucial contributor to OC development. ETS transcription factor (ELK3), as a transcriptional factor, have been involved in multiple tumor development. However, its role in OC remains elusive. In this study, we observed high expression of ELK3 and AEG1 in human OC tissues. OVCAR-3 and SKOV3 cells were treated with hypoxia to mimic tumor microenvironment in vivo. We found that the expression of ELK3 was significantly increased in cells under hypoxia compared with normoxia. ELK3 knockdown inhibited cell migration and invasion abilities under hypoxia. Moreover, ELK3 knockdown decreased ß-catenin expression and inhibited the activation of Wnt/ß-catenin pathway in SKOV3 cells under hypoxia. Astrocyte-elevated gene-1 (AEG1) has been reported to promote OC progression. Our results showed that the mRNA level of AEG1 was decreased when ELK3 knockdown under hypoxia. Dural luciferase assay confirmed that ELK3 bound to gene AEG1 promoter (-2005-+15) and enhanced its transcriptional activity under hypoxia. Overexpression of AEG1 increased the migration and invasion abilities of SKOV3 cell with ELK3 knockdown. In the absence of ELK3, the activation of ß-catenin was recovered by AEG1 overexpression. To sum up, we conclude that ELK3 promotes AEG1 expression by binding to its promoter. ELK3 could promote migration and invasion of OC cells by targeting AEG1, which provides a potential basis for therapeutic approaches to OC.

Loss of USP22 alleviates cardiac hypertrophy induced by pressure overload through HiF1-α-TAK1 signaling pathway.

Ubiquitin-specific protease 22 (USP22) is a member of the ubiquitin specific protease family (ubiquitin-specific protease, USPs), the largest subfamily of deubiquitinating enzymes, and plays an important role in the treatment of tumors. USP22 is also expressed in the heart. However, the role of USP22 in heart disease remains unclear. In this study, we found that USP22 was elevated in hypertrophic mouse hearts and in angiotensin II (Ang II)-induced cardiomyocytes. The inhibition of USP22 expression with adenovirus significantly rescued hypertrophic phenotype and cardiac dysfunction induced by pressure overloaded. Consistent with in vivo study, silencing by USP22 shRNA expression in vitro had similar results. Molecular analysis revealed that transforming growth factor-ß-activating protein 1 (TAK1)-(JNK1/2)/P38 signaling pathway and HIF-1α was activated in the Ang II-induced hypertrophic cardiomyocytes, whereas HIF-1α expression was decreased after the inhibition of USP22. Inhibition of HIF-1α expression reduces TAK1 expression. Co-immunoprecipitation and ubiquitination studies revealed the regulatory mechanism between USP22 and HIF1α.Under hypertrophic stress conditions, USP22 enhances the stability of HIF-1α through its deubiquitination activity, which further activates the TAK1-(JNK1/2)/P38 signaling pathway to lead to cardiac hypertrophy. Inhibition of HIF-1α expression further potentiates the in vivo pathological effects caused by USP22 deficiency. In summary, this study suggests that USP22, through HIF-1α-TAK1-(JNK1/2)/P38 signaling pathway, may be potential targets for inhibiting pathological cardiac hypertrophy induced by pressure overload.

Effects of visceral adipose tissue on anti-tumour necrosis factor-α in Crohn's disease.

Background: It remains unclear whether visceral adipose tissue (VAT) can predict the response of patients with Crohn's disease (CD) to anti-tumour necrosis factor-α (anti-TNF-α) therapy. Objectives: This study aimed to investigate whether VAT predicts the efficacy of infliximab (IFX) for different sites of CD and its relationship with serum TNF-α levels and IFX serum trough concentration. Design: This is a multicentre retrospective study. Methods: Patients with CD treated with IFX from January 2014 to January 2021 were included. The perimeter of the visceral adipose area was obtained by a Computed Tomography (CT) scan. Participants were classified according to the lesion site (L1, L2, and L3) and visceral fat area. The participants were divided into colon-uninvolved non-visceral obesity (L1-VATL), colon-uninvolved visceral obesity (L1-VATH), colon-involved non-visceral obesity (L2 + L3-VATL), and colon involved visceral obesity (L2 + L3-VATH) groups. The end points of this study were set as disease remission status at 6 and 12 months. Results: The final cohort included 140 patients. Regarding efficacy at 6 and 12 months, there was a significant difference between L1-VATL (73.8% versus 36.8%, p = 0.006) and L1-VATH (81.0% versus 47.4%, p = 0.008) groups. In the analysis of serum TNF-α levels and IFX serum trough concentrations, there was a significant difference between L1-VATL and L1-VATH (59.5 pg/mL versus 236.0 pg/mL, pTNF-α = 0.006), (10.0 µg/mL versus 0.4 µg/mL, pIFX = 0.000), and L1-VATH and L2 + L3-VATH (78.7 pg/mL versus 118.6 pg/mL, pTNF-α = 0.031), (0.4 µg/mL versus 6.40 µg/mL, pIFX = 0.017). Conclusion: In L1 patients, the VAT level predicted the efficacy of IFX, with high VAT values indicating poor efficacy. The VAT level may be a useful radiological marker to predict the efficacy of IFX in patients with various types of CD.

Effect of lead, calcium, iron, zinc, copper and magnesium on anemia in children with BLLs ≥ 100 µg/L.

OBJECTIVE: Adverse effects of lead exposure on children's health have been demonstrated. While studies have examined the relationship between iron status and low-level lead exposure in children with blood lead levels (BLLs) < 100 µg/L, few have investigated the association between blood lead and other trace elements and anemia in children with BLLs ≥ 100 µg/L. This study aimed to assess the levels of lead, iron, copper, zinc, magnesium, and calcium in children aged 0-14 with BLLs≥ 100 µg/L between 2009 and 2021, and to examine the relationship between blood lead, trace elements and anemia. METHODS: A total of 11,541 children with BLLs ≥ 100 µg/L were included in this study. Venous blood samples were collected to measure blood lead levels, hemoglobin levels, and trace element levels. According to the World Health Organization standard, outpatients with hemoglobin levels < 110 g / L were defined as having anemia. RESULTS: The study results found that high BLLs and blood calcium had a negative influence on Hb with odds ratios (95% confidence interval) of 1.411(1.208, 1.649) and 1.219(1.043, 1.424). High blood iron had a positive influence on Hb with odds ratios of 0.421(0.355, 0.499). CONCLUSION: The results suggest that the risk of anemia rose significantly with higher BLLs, blood copper, and blood calcium levels, and decreases considerably with higher blood iron levels.

METTL13 promotes nasopharyngeal carcinoma progression through regulating the ZEB1/TPT1 axis.

BACKGROUND: Globally, nasopharyngeal carcinoma (NPC) is a prevalent and deadly malignancy. Despite the role of methyltransferase like 13 (METTL13) having been highlighted in a majority of human cancers, its function and mechanism in NPC is indistinct. METHODS: The expression level of METTL13 in NPC cell lines and normal cells was detected using a quantitative real-time polymerase chain reaction. Gain- and loss-of function experiments were conducted. Cell counting kit-8, 5-ethynyl-2'-deoxyuridine, wound-healing, Transwell and tube formation assays, respectively, appraised the proliferative, migratory, invasive and angiogenic cellular responses. Corresponding protein expression was measured by western blotting. A chromatin immunoprecipitation assay was applied to verify the association between ZEB1 and the TPT1 promoter. Eventually, to substantiate the critical role of METTL13 in NPC, the establishment of an in vivo tumorigenesis model was accomplished. RESULTS: METTL13 possessed fortified expression in NPC cells. METTL13 silencing markedly suppressed NPC cellular phenotypes in vitro, including proliferative, migratory, invasive and angiogenic events, as well as hindered tumorigenesis in vivo. Additionally, METTL13 positively regulated ZEB1, whereas ZEB1 could bind to TPT1 promoter and transcriptionally regulate TPT1. TPT1 was also found to be upregulated in NPC cells. TPT1 silencing suppressed NPC cellular phenotypes in vitro. TPT1 overexpression partly weakened the anti-tumor effect of METTL13 in NPC. CONCLUSIONS: In summary, METTL13 up-regulated ZEB1, which facilitated the transcriptional activation of TPT1, ultimately promoting NPC growth and metastasis, providing a potential therapeutic strategy for NPC treatment.

Towards precision medicine based on a continuous deep learning optimization and ensemble approach.

We developed a continuous learning system (CLS) based on deep learning and optimization and ensemble approach, and conducted a retrospective data simulated prospective study using ultrasound images of breast masses for precise diagnoses. We extracted 629 breast masses and 2235 images from 561 cases in the institution to train the model in six stages to diagnose benign and malignant tumors, pathological types, and diseases. We randomly selected 180 out of 3098 cases from two external institutions. The CLS was tested with seven independent datasets and compared with 21 physicians, and the system's diagnostic ability exceeded 20 physicians by training stage six. The optimal integrated method we developed is expected accurately diagnose breast masses. This method can also be extended to the intelligent diagnosis of masses in other organs. Overall, our findings have potential value in further promoting the application of AI diagnosis in precision medicine.

FTO-dependent m6A modification of Plpp3 in circSCMH1-regulated vascular repair and functional recovery following stroke.

Vascular repair is considered a key restorative measure to improve long-term outcomes after ischemic stroke. N6-methyladenosine (m6A), the most prevalent internal modification in eukaryotic mRNAs, functionally mediates vascular repair. However, whether circular RNA SCMH1 (circSCMH1) promotes vascular repair by m6A methylation after stroke remains to be elucidated. Here, we identify the role of circSCMH1 in promoting vascular repair in peri-infarct cortex of male mice and male monkeys after photothrombotic (PT) stroke, and attenuating the ischemia-induced m6A methylation in peri-infarct cortex of male mice after PT stroke. Mechanically, circSCMH1 increased the translocation of ubiquitination-modified fat mass and obesity-associated protein (FTO) into nucleus of endothelial cells (ECs), leading to m6A demethylation of phospholipid phosphatase 3 (Plpp3) mRNA and subsequently the increase of Plpp3 expression in ECs. Our data demonstrate that circSCMH1 enhances vascular repair via FTO-regulated m6A methylation after stroke, providing insights into the mechanism of circSCMH1 in promoting stroke recovery.

Cardiac-Specific Overexpression of Caveolin-1 in Rats With Ischemic Cardiomyopathy Improves Arrhythmogenicity and Cardiac Remodelling.

BACKGROUND: Ischemic cardiomyopathy (ICM) is associated with electrical and structural remodelling, leading to arrhythmias. Caveolin-1 (Cav1) is a membrane protein involved in the pathogenesis of ischemic injury. Cav1 deficiency has been associated with arrhythmogenicity. The current study aimed to determine how Cav1 overexpression inhibits arrhythmias and cardiac remodelling in ICM. METHODS: ICM was modelled using left anterior descending (LAD) artery ligation for 4 weeks. Cardiac-specific Cav1 overexpression in ICM on arrhythmias, excitation-contraction coupling, and cardiac remodelling were investigated using the intramyocardial injection of an adeno-associated virus serotype 9 (AAV-9) system, carrying a specific sequence expressing Cav1 (AAVCav1) under the cardiac troponin T (cTnT) promoter. RESULTS: Cav1 overexpression decreased susceptibility to arrhythmias by upregulating gap junction connexin 43 (CX43) and reducing spontaneous irregular proarrhythmogenic Ca2+ waves in ventricular cardiomyocytes. It also alleviated ischemic injury-induced contractility weakness by improving Ca2+ cycling through normalizing Ca2+-handling protein levels and improving Ca2+ homeostasis. Masson stain and immunoblotting revealed that the deposition of excessive fibrosis was attenuated by Cav1 overexpression, inhibiting the transforming growth factor-ß (TGF-ß)/Smad2 signalling pathway. Coimmunoprecipitation assays demonstrated that the interaction between Cav1 and cSrc modulated CX43 expression and Ca2+-handling protein levels. CONCLUSIONS: Cardiac-specific overexpression of Cav1 attenuated ventricular arrhythmia, improved Ca2+ cycling, and attenuated cardiac remodelling. These effects were attributed to modulation of CX43, normalized Ca2+-handling protein levels, improved Ca2+ homeostasis, and attenuated cardiac fibrosis.

Development and evaluation of acceptance scale for artificial intelligence in digestive endoscopy by subjects. / å—æ£€è€ å¯¹æ¶ˆåŒ–å† é•œäººå·¥æ™ºèƒ½æŽ¥å—åº¦é‡è¡¨çš„ç¼–åˆ¶åŠè¯„ä»·.

OBJECTIVES: Digestive endoscopy is an important diagnostic and therapeutic tool for digestive system diseases. The artificial intelligence (AI)-assisted system in endoscopy (hereinafter referred to as AI in digestive endoscopy) has broad application prospects in the field of digestive endoscopy. The trust and acceptance of endoscopic subjects are the cornerstone of the research, application, and promotion of AI in digestive endoscopy. Currently, the tools for measuring the acceptance of AI in digestive endoscopy by subjects are limited at home and abroad. This study aims to develop a scale for measuring the acceptance of AI in digestive endoscopy by subjects, then to evaluate its reliability and validity. METHODS: By conducting literature research, an item pool and dimensions were constructed, and a preliminary scale was constructed using Delphi method. Through the first stage of the survey on the subjects, the reliability and validity of the scale were tested, and the revised scale was used for the second stage of survey on the subjects to further verify the structural validity of the scale. RESULTS: The acceptance scale for AI in digestive endoscopy included 11 items in 3 dimensions: accuracy, ethics, benefit and willingness. In the first stage of the survey, 351 valid questionnaires were collected, and the Cronbach's α was 0.864. The correlation coefficient between the total score of the scale and the score of the test item was 0.636, and the Kaiser-Meyer-Olkin (KMO) value in exploratory factor analysis was 0.788. In the second stage of the survey, 335 valid questionnaires were collected, and in confirmatory factor analysis, the χ2/df was 3.774, while the root mean squared error of approximation (RMSEA) was 0.091. CONCLUSIONS: Acceptance scale for AI in digestive endoscopy by subjects developed in this study has good reliability and validity.

Recent advances in the activation and regulation of the cGAS-STING pathway.

The cGAS-STING pathway is responsible for cytoplasmic double-stranded DNA (dsDNA) -triggered innate immunity and involved in the pathology of various diseases including infection, autoimmune diseases, neurodegeneration and cancer. Understanding the activation and regulatory mechanisms of this pathway is critical to develop therapeutic strategies toward these diseases. Here, we review the signal transduction, cellular functions and regulations of cGAS and STING, particularly highlighting the latest understandings on the activation of cGAS by dsDNA and/or Manganese (Mn2+), STING trafficking, sulfated glycosaminoglycans (sGAGs)-induced STING polymerization and activation, and also regulation of the cGAS-STING pathway by different biocondensates formed via phase separation of proteins from host cells and viruses.