HINT2 protects against pressure overload-induced cardiac remodelling through mitochondrial pathways.

Histidine triad nucleotide-binding protein 2 (HINT2) is an enzyme found in mitochondria that functions as a nucleotide hydrolase and transferase. Prior studies have demonstrated that HINT2 plays a crucial role in ischemic heart disease, but its importance in cardiac remodelling remains unknown. Therefore, the current study intends to determine the role of HINT2 in cardiac remodelling. HINT2 expression levels were found to be lower in failing hearts and hypertrophy cardiomyocytes. The mice that overexpressed HINT2 exhibited reduced myocyte hypertrophy and cardiac dysfunction in response to stress. In contrast, the deficiency of HINT2 in the heart of mice resulted in a worsening hypertrophic phenotype. Further analysis indicated that upregulated genes were predominantly associated with the oxidative phosphorylation and mitochondrial complex I pathways in HINT2-overexpressed mice after aortic banding (AB) treatment. This suggests that HINT2 increases the expression of NADH dehydrogenase (ubiquinone) flavoprotein (NDUF) genes. In cellular studies, rotenone was used to disrupt mitochondrial complex I, and the protective effect of HINT2 overexpression was nullified. Lastly, we predicted that thyroid hormone receptor beta might regulate HINT2 transcriptional activity. To conclusion, the current study showcased that HINT2 alleviates pressure overload-induced cardiac remodelling by influencing the activity and assembly of mitochondrial complex I. Thus, targeting HINT2 could be a novel therapeutic strategy for reducing cardiac remodelling.

BMP2-ERK-ATF4 Axis-Based 6-methoxybenzofuran Compound I-9 Acts as Candidate Drug for Bone Formation and Anti-Osteoporosis.

As the global population ages, the number of patients with osteoporosis is rapidly rising. The existing first-line clinical drugs are bone resorption inhibitors that have difficulty restoring the bone mass of elderly patients to the safe range. The range and period of use of existing peptides and monoclonal antibodies are limited, and small-molecule bone formation-promoting drugs are urgently required. We established an I-9 synthesis route with high yield, simple operation, and low cost that was suitable for future large-scale production. I-9 administration promoted bone formation and increased bone mass in mice with low bone mass in an aged C57 mouse model. Our findings revealed a hitherto undescribed pathway involving the BMP2-ERK-ATF4 axis that promotes osteoblast differentiation; I-9 has favorable biosafety in mice. This study systematically investigated the efficacy, safety, and mechanism of I-9 for treating osteoporosis and positions this drug for preclinical research in the future. Thus, this study has promoted the development of small-molecule bone-promoting drugs.

CircZfp609 contributes to cerebral infarction via sponging miR-145a-5p to regulate BACH1.

BACKGROUND: Circular RNAs (circRNA) have been reported to be involved in the progression of cerebral infarction. The purpose of this study was to reveal the role and potential molecular mechanism of circZfp609 (mmu_circ_0001797) in cerebral infarction. METHODS: C57BL/6J mice was used to construct middle cerebral artery occlusion (MCAO) mice model, and primary mouse astrocytes were treated with oxygen-glucose deprivation/reperfusion (OGD/R) process. The circZfp609, microRNA (miR)-145a-5p and BTB and CNC homology 1 (BACH1) expression levels were detected by quantitative real-time PCR. Cell proliferation and apoptosis were assessed by cell counting kit 8 assay, EdU assay and flow cytometry. Western blot analysis was used to measure protein levels, and ELISA assay was utilized to detect the levels of inflammation factors. Lactate dehydrogenase (LDH) level was measured by LDH Assay Kit. Dual-luciferase reporter assay, RIP assay and RNA pull-down assay were used to evaluate RNA interaction. RESULTS: CircZfp609 was upregulated in MCAO mice and OGD/R-induced astrocytes. Knockdown of circZfp609 promoted cell proliferation, while suppressed apoptosis and inflammation in OGD/R-induced astrocytes. CircZfp609 served as a sponge for miR-145a-5p, and miR-145a-5p inhibitor reversed the regulation of circZfp609 knockdown on OGD/R-induced astrocyte injury. BACH1 was a target of miR-145a-5p, and its overexpression abolished the inhibition effect of miR-145a-5p on OGD/R-induced astrocyte injury. Besides, circZfp609 downregulation also relieved the brain injury of MCAO mice through miR-145a-5p/BACH1 axis. CONCLUSION: Our data showed that circZfp609 might promote cerebral infarction by regulating the miR-145a-5p/BACH1 pathway.

Down-Regulated microRNA-192-5p Protects Against Hypoxic-Ischemic Brain Damage via Regulation of YAP1-Mediated Hippo Signaling Pathway.

Hypoxic-ischemic brain damage (HIBD) is a familiar neurological disorder. Emerging reports manifest that microRNAs (miRs) are related to the progression of HIBD. The goal of this study is to explore the mechanism of miR-192-5p in HIBD via regulation of Yes-associated protein 1 (YAP1)-mediated Hippo signaling pathway. The miR-192-5p, YAP1, and Hippo pathway-related factors Phospho (p)-Triaminoguanidinium azide (TAZ) in hippocampal tissues and neurons were detected. The regulatory relationship between miR-192-5p and YAP1 was verified. Neonatal hypoxic ischemia and oxygen-glucose deprivation (OGD) were used to simulate HIBD in vivo and in vitro. The neurobehavioral impairment, neuronal damage and vascular endothelial growth factor (VEGF) expression of neonatal rats in each group were detected. The viability, apoptosis and VEGF expression of hippocampal neurons in each group were also examined. MiR-192-5p expression was elevated while YAP1 expression was reduced in hippocampal tissues of HIBD rats in vivo and OGD neurons in vitro. MiR-192-5p had a targeting relation with YAP1. Suppressed miR-192-5p or overexpressed YAP1 in HIBD rats alleviated neurobehavioral impairment and neuronal damage, and decreased the expression levels of p-TAZ and VEGF expression in vivo. Reduced miR-192-5p or augmented YAP1 decelerated the neuron apoptosis, decreased the p-TAZ level and VEGF level and promoted cell viability of OGD hippocampal neurons in vitro. The study highlights that inhibited miR-192-5p protects against HIBD via regulation of YAP1 and Hippo signaling pathway, which is beneficial for HIBD treatment.

Structure-Based Virtual Screening towards the Discovery of Novel ULK1 Inhibitors with Anti-HCC Activities.

There is an urgent need to develop new effective therapies for HCC. Our previous study identified ULK1 as the potential target for HCC therapy and screened the compound XST-14 as a specific inhibitor of ULK1 to suppress HCC progression. However, the poor manufacturability of XST-14 impeded the process of its clinical translation. In this study, we first generated pharmacophore models of ULK1 based on the X-ray structure of UKL1 in complex with ligands. We then screened the Specs chemical library for potential UKL1 inhibitors. By molecular docking, we screened out the 19 compounds through structure-based virtual screening. Through CCK8 activity screening on HCC cells, we found that ZZY-19 displayed obvious cell killing effects on HCC cells. SPR assay indicated that ZZY-19 had a higher binding affinity for ULK1 than XST-14. Moreover, ZZY-19 induced the effects of anti-proliferation, anti-invasion and anti-migration in HCC cells. Mechanistically, ZZY-19 induces autophagy inhibition by reducing the expression of ULK1 on HCC cells. Especially, the combination of ZZY-19 with sorafenib synergistically suppresses the progression of HCC in vivo. Taken together, ZZY-19 was a potential candidate compound that targeted ULK1 and possessed promising anti-HCC activities by inhibiting autophagy.

GenCLiP 3: mining human genes' functions and regulatory networks from PubMed based on co-occurrences and natural language processing.

SUMMARY: We present a web server, GenCLiP 3, which is an updated version of GenCLiP 2.0 to enhance analysis of human gene functions and regulatory networks, with the following improvements: i) accurate recognition of molecular interactions with polarity and directionality from the entire PubMed database; ii) support for Boolean search to customize multiple-term search and to quickly retrieve function related genes; iii) strengthened association between gene and keyword by a new scoring method; and iv) daily updates following literature release at PubMed FTP. AVAILABILITY: The server is freely available for academic use at: http://ci.smu.edu.cn/genclip3/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Combination treatment of perifosine and valsartan showed more efficiency in protecting against pressure overload induced mouse heart failure.

The optimum strategy for heart failure (HF) treatment has yet to be elucidated. This study intended to test the benefit of a combination of valsartan (VAL) and perifosine (PER), a specific AKT inhibitor, in protecting against pressure overload induced mouse HF. Mouse were subjected to aortic banding (AB) surgery to establish HF models and then were given vehicle (HF), VAL (50 mg/kg/d), PER (30 mg/kg/d) or combination of VAL and PER for 4 weeks. Mouse with sham surgery treated with VEH were used for control (VEH). VAL or PER treatment could significantly alleviate mouse heart weight, attenuate cardiac fibrosis and improve cardiac function. The combination treatment of VAL and PER presented much better benefit compared with VAL or PER group respectively. PER treatment significantly inhibited AKT/GSK3ß/mTORC1 signaling. Besides the classic AT1 inhibition, VAL treatment significantly inhibited MAPK (ERK1/2) signaling. Furthermore, VAL and PER treatment could markedly prevent neonatal rat cardiomyocyte hypertrophy and the activation of neonatal rat cardiac fibroblast. Combination of VAL and PER also presented superior beneficial effects than single treatment of VAL or PER in vitro experiments respectively. This study presented that the combination of valsartan and PER may be a potential treatment for HF prevention.

Two New Indole Alkaloids from Toad Venom of Bufo bufo gargarizans.

Two new indole alkaloids, Bufotenidine B (2) and Bufocarboline A (6), along with seven known indole alkaloids (1, 3-5, and 7-9) and three organic acids (10-12), were isolated from the water extract of toad venom. The structures of the new alkaloids were elucidated by extensive spectroscopic methods. The absolute configurations of 4, 6, and 8 were determined for the first time by electronic circular dichroism (ECD) calculations. The cytotoxic activity of all compounds was tested against human malignant melanoma cells A375 by the MTT method, and no antitumor activity was observed.

Electron tomography simulator with realistic 3D phantom for evaluation of acquisition, alignment and reconstruction methods.

Because of the significance of electron microscope tomography in the investigation of biological structure at nanometer scales, ongoing improvement efforts have been continuous over recent years. This is particularly true in the case of software developments. Nevertheless, verification of improvements delivered by new algorithms and software remains difficult. Current analysis tools do not provide adaptable and consistent methods for quality assessment. This is particularly true with images of biological samples, due to image complexity, variability, low contrast and noise. We report an electron tomography (ET) simulator with accurate ray optics modeling of image formation that includes curvilinear trajectories through the sample, warping of the sample and noise. As a demonstration of the utility of our approach, we have concentrated on providing verification of the class of reconstruction methods applicable to wide field images of stained plastic-embedded samples. Accordingly, we have also constructed digital phantoms derived from serial block face scanning electron microscope images. These phantoms are also easily modified to include alignment features to test alignment algorithms. The combination of more realistic phantoms with more faithful simulations facilitates objective comparison of acquisition parameters, alignment and reconstruction algorithms and their range of applicability. With proper phantoms, this approach can also be modified to include more complex optical models, including distance-dependent blurring and phase contrast functions, such as may occur in cryotomography.

Expression and clinical implication of S100A12 in gastric carcinoma.

S100 protein family has been implicated in multiple stages of tumorigenesis and progression in which S100A12 is one of the subtypes. However, the role of S100A12 in gastric carcinoma (GC) has not been elucidated yet. This study was aimed to investigate the expression of S100A12 in GC tissues and evaluate the clinical significance of S100A12 in GC patients. S100A12 protein was detected in 207 GC and 52 paired non-cancerous mucosal tissues by immunohistochemistry, while messenger RNA (mRNA) was investigated by Oncomine database analysis. Moreover, survival analysis was performed and the correlation between S100A12 and ubiquitin-specific protease 10 (USP10) and p53 was determined. As for tumor cells, the expression of S100A12 protein and mRNA in GC was proved to be lower than that in non-cancerous mucosa tissues (p < 0.05). Clinicopathological analysis showed that S100A12 protein was negatively associated with tumor size (p = 0.004), depth of invasion (p = 0.022), tumor node metastasis (TNM) stage (p = 0.018), Lauren classification (p < 0.000), and cell differentiation (p < 0.000). In contrast, a positive correlation was found between S100A12 and USP10 protein (p < 0.000). However, no relationship was detected between S100A12 and p53. Moreover, the survival analysis indicated that S100A12 protein was a favorable factor of prognosis of GC (p < 0.05). Although the expression of S100A12 in the stromal cells was detected higher than that in the tumor cells, no relationship between S100A12 protein in stromal cells and the clinicopathological features described above was found (p > 0.05). Our findings suggested that low expression of S100A12 might be served as a new marker in the tumorigenesis and progression of GC.

Potent in vitro synergism of fusidic acid (FA) and berberine chloride (BBR) against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA).

It was found in the present study that combined use of fusidic acid (FA) and berberine chloride (BBR) offered an in vitro synergistic action against 7 of the 30 clinical methicillin-resistant Staphylococcus aureus (MRSA) strains, with a fractional inhibitory concentration (FIC) index ranging from 0.5 to 0.19. This synergistic effect was most pronounced on MRSA 4806, an FA-resistant isolate, with a minimum inhibitory concentration (MIC) value of 1,024 µg/ml. The time-kill curve experiment showed that FA plus BBR yielded a 4.2 log10 c.f.u./ml reduction in the number of MRSA 4806 bacteria after 24-h incubation as compared with BBR alone. Viable count analysis showed that FA plus BBR produced a 3.0 log10 c.f.u./ml decrease in biofilm formation and a 1.5 log10 c.f.u./ml decrease in mature biofilm in viable cell density as compared with BBR alone. In addition, phase contrast micrographs confirmed that biofilm formation was significantly inhibited and mature biofilm was obviously destructed when FA was used in combination with BBR. These results provide evidence that combined use of FA and BBR may prove to be a promising clinical therapeutic strategy against MRSA.

Global research of artificial intelligence in eyelid diseases: A bibliometric analysis.

Purpose: To generate an overview of global research on artificial intelligence (AI) in eyelid diseases using a bibliometric approach. Methods: All publications related to AI in eyelid diseases from 1900 to 2023 were retrieved from the Web of Science (WoS) Core Collection database. After manual screening, 98 publications published between 2000 and 2023 were finally included. We analyzed the annual trend of publication and citation count, productivity and co-authorship of countries/territories and institutions, research domain, source journal, co-occurrence and evolution of the keywords and co-citation and clustering of the references, using the analytic tool of the WoS, VOSviewer, Wordcloud Python package and CiteSpace. Results: By analyzing a total of 98 relevant publications, we detected that this field had continuously developed over the past two decades and had entered a phase of rapid development in the last three years. Among these countries/territories and institutions contributing to this field, China was the most productive country and had the most institutions with high productivity, while USA was the most active in collaborating with others. The most popular research domains was Ophthalmology and the most productive journals were Ocular Surface. The co-occurrence network of keywords could be classified into 3 clusters respectively concerned about blepharoptosis, meibomian gland dysfunction and blepharospasm. The evolution of research hotspots is from clinical features to clinical scenarios and from image processing to deep learning. In the clustering analysis of co-cited reference network, cluster "0# deep learning" was the largest and latest, and cluster "#5 meibomian glands visibility assessment" existed for the longest time. Conclusions: Although the research of AI in eyelid diseases has rapidly developed in the last three years, there are still gaps in this area. Our findings provide researchers with a better understanding of the development of the field and a reference for future research directions.

Multidimensional quantitative characterization of periocular morphology: distinguishing esotropia from epicanthus by deep learning network.

Background: Prominent epicanthus could not only diminish the eyes' aesthetics but may be deceptive for its typical appearance of pseudo-esotropia. This study aims to apply a deep learning model to characterize the periocular morphology for preliminary identification. Methods: This prospective study consecutively included 300 subjects visiting the ophthalmology department in a tertiary referral hospital. Children aged 7-18 years with simple epicanthus or concomitant esotropia and healthy volunteers who were age- and gender-matched were eligible for inclusion. Multiple metrics were extracted automatically and manually from facial images to characterize the periocular morphology and binocular symmetry. The dice coefficient (Dice), intraclass correlation coefficient (ICC), and Bland-Altman biases were calculated to evaluate their consistency. The receiver operating characteristic (ROC) curve determined the cut-off values of symmetry indexes (SIs) for distinguishing concomitant esotropia subjects from epicanthus ones. Results: The Dice for eyelid and cornea segmentation were 0.949 and 0.944, respectively. The ICCs of the two measurements ranged from 0.898 to 0.983. Biases ranged from 0.16 to 0.74 mm. The periocular morphology of epicanthus eyes was significantly different from the normal ones, including palpebral fissure width (21.41±1.53 vs. 24.45±1.82 mm; P<0.01), and palpebral fissure height (8.91±1.37 vs. 9.60±1.25 mm; P<0.01). The ROC analysis yielded an area under the curve of 0.971 [95% confidence interval (CI): 0.950-0.991] with SI for distinguishing esotropia subjects. Its optimal cut-off value was 1.296 with 0.920 sensitivity and 0.910 specificity. Conclusions: Our study established a standard deep learning system for characterizing the periocular morphology of epicanthus and esotropia eyes with great accuracy. This objective method could be generalized to other periocular morphological assessments for clinical care.

Hawthorn with "homology of medicine and food": a review of anticancer effects and mechanisms.

Over the past few years, there has been a gradual increase in the incidence of cancer, affecting individuals at younger ages. With its refractory nature and substantial fatality rate, cancer presents a notable peril to human existence and wellbeing. Hawthorn, a medicinal food homology plant belonging to the Crataegus genus in the Rosaceae family, holds great value in various applications. Due to its long history of medicinal use, notable effects, and high safety profile, hawthorn has garnered considerable attention and plays a crucial role in cancer treatment. Through the integration of modern network pharmacology technology and traditional Chinese medicine (TCM), a range of anticancer active ingredients in hawthorn have been predicted, identified, and analyzed. Studies have shown that ingredients such as vitexin, isoorientin, ursolic acid, and maslinic acid, along with hawthorn extracts, can effectively modulate cancer-related signaling pathways and manifest anticancer properties via diverse mechanisms. This review employs network pharmacology to excavate the potential anticancer properties of hawthorn. By systematically integrating literature across databases such as PubMed and CNKI, the review explores the bioactive ingredients with anticancer effects, underlying mechanisms and pathways, the synergistic effects of drug combinations, advancements in novel drug delivery systems, and ongoing clinical trials concerning hawthorn's anticancer properties. Furthermore, the review highlights the preventive health benefits of hawthorn in cancer prevention, offering valuable insights for clinical cancer treatment and the development of TCM with anticancer properties that can be used for both medicinal and edible purposes.

Response of Human Retinal Microvascular Endothelial Cells to Influenza A (H1N1) Infection and the Underlying Molecular Mechanism.

Purpose: Whether H1N1 infection-associated ocular manifestations result from direct viral infections or systemic complications remains unclear. This study aimed to comprehensively elucidate the underlying causes and mechanism. Method: TCID50 assays was performed at 24, 48, and 72 hours to verify the infection of H1N1 in human retinal microvascular endothelial cells (HRMECs). The changes in gene expression profiles of HRMECs at 24, 48, and 72 hours were characterized using RNA sequencing technology. Differentially expressed genes (DEGs) were validated using real-time quantitative polymerase chain reaction and Western blotting. CCK-8 assay and scratch assay were performed to evaluate whether there was a potential improvement of proliferation and migration in H1N1-infected cells after oseltamivir intervention. Results: H1N1 can infect and replicate within HRMECs, leading to cell rounding and detachment. After H1N1 infection of HRMECs, 2562 DEGs were identified, including 1748 upregulated ones and 814 downregulated ones. These DEGs primarily involved in processes such as inflammation and immune response, cytokine-cytokine receptor interaction, signal transduction regulation, and cell adhesion. The elevated expression levels of CXCL10, CXCL11, CCL5, TLR3, C3, IFNB1, IFNG, STAT1, HLA, and TNFSF10 after H1N1 infection were reduced by oseltamivir intervention, reaching levels comparable to those in the uninfected group. The impaired cell proliferation and migration after H1N1 infection was improved by oseltamivir intervention. Conclusions: This study confirmed that H1N1 can infect HRMECs, leading to the upregulation of chemokines, which may cause inflammation and destruction of the blood-retina barrier. Moreover, early oseltamivir administration may reduce retinal inflammation and hemorrhage in patients infected with H1N1.

Substituted indole derivatives as UNC-51-like kinase 1 inhibitors: Design, synthesis and anti-hepatocellular carcinoma activity.

The five-year survival rate for patients with hepatocellular carcinoma (HCC) is only 20 %, highlighting the urgent need to identify new therapeutic targets and develop potential therapeutic options to improve patient prognosis. One promising approach is inhibiting autophagy as a strategy for HCC treatment. In this study, we established a virtual docking conformation of the autophagy promoter ULK1 binding XST-14 derivatives. Based on this conformation, we designed and synthesized four series of derivatives. By evaluating their affinity and anti-HCC effects, we confirmed that these compounds exert anti-HCC activity by inhibiting ULK1. The structure-activity relationship was summarized, with derivative A4 showing 10 times higher activity than XST-14 and superior efficacy to sorafenib against HCC. A4 has excellent effect on reducing tumor growth and enhancing sorafenib activity in HepG2 and HCCLM3 cells. Moreover, we verified the therapeutic effect of A4 in sorafenib-resistant HCC cells both in vivo and in vitro. These results suggest that inhibiting ULK1 to regulate autophagy may become a new treatment method for HCC and that A4 will be used as a lead drug for HCC in further research. Overall, A4 shows good drug safety and efficacy, offering hope for prolonging the survival of HCC patients.

Banxia-Shengjiang drug pair inhibits gastric cancer development and progression by improving body immunity.

To investigate the mechanism of action of Banxia-Shengjiang drug pair on the inhibition of gastric cancer (GC) using network pharmacology and bioinformatics techniques. The action targets of the Banxia (Pinellia ternata (Thunb.) Makino) -Shengjiang (Zingiber officinale Roscoe) drug pair obtained from the TCMSP database were intersected with differentially expressed genes (DEGs) and GC-related genes, and the intersected genes were analyzed for pathway enrichment to identify the signaling pathways and core target genes. Subsequently, the core target genes were analyzed for clinical relevance gene mutation analysis, methylation analysis, immune infiltration analysis and immune cell analysis. Finally, by constructing the PPI network of hub genes and corresponding active ingredients, the key active ingredients of the Banxia-Shengjiang drug pair were screened for molecular docking with the hub genes. In this study, a total of 557 target genes of Banxia-Shengjiang pairs, 7754 GC-related genes and 1799 DEGs in GC were screened. Five hub genes were screened, which were PTGS2, MMP9, PPARG, MMP2, and CXCR4. The pathway enrichment analyses showed that the intersecting genes were associated with RAS/MAPK signaling pathway. In addition, the clinical correlation analysis showed that hub genes were differentially expressed in GC and was closely associated with immune infiltration and immunotherapy. The results of single nucleotide variation (SNV) and copy number variation (CNV) indicated that mutations in the hub genes were associated with the survival of gastric cancer patients. Finally, the PPI network and molecular docking results showed that PTGS2 and MMP9 were potentially important targets for the inhibition of GC by Banxia-Shengjiang drug pair, while cavidine was an important active ingredient for the inhibition of GC by Banxia-Shengjiang drug pair. Banxia-Shengjiang drug pair may regulate the immune function and inhibit GC by modulating the expression of core target genes such as RAS/MAPK signaling pathway, PTGS2 and MMP9.

Design and synthesis of dabigatran etexilate derivatives with inhibiting thrombin activity for hepatocellular carcinoma treatment.

Hepatocellular carcinoma (HCC) is one of the most fatal solid malignancies worldwide. Evidence suggests that thrombin stimulates tumor progression via fibrin formation and platelet activation. Meanwhile, we also found a correlation between thrombin and HCC through bioinformatics analysis. Dabigatran is a selective, direct thrombin inhibitor that reversibly binds to thrombin. Dabigatran was used as the lead agent in this study, and 19 dabigatran derivatives were designed and synthesized based on docking mode. The thrombin-inhibitory activity of the derivative AX-2 was slightly better than that of dabigatran. BX-2, a prodrug of AX-2, showed a fairly strong inhibitory effect on thrombin-induced platelet aggregation, and effectively antagonized proliferation of HCC tumor cells induced by thrombin at the cellular level. Furthermore, BX-2 reduced tumor volume, weight, lung metastasis, and secondary tumor occurrence in nude mouse models. BX-2 combined with sorafenib increased sorafenib efficacy. This study lays the foundation for discovering new anti-HCC mechanism based on thrombin. BX-2 can be used as an anti-HCC drug lead for further research.

CircSEC11A knockdown alleviates oxidative stress and apoptosis and promotes cell proliferation and angiogenesis by regulating miR-29a-3p/SEMA3A axis in OGD-induced human brain microvascular endothelial cells (HBMECs).

BACKGROUND: Circular RNA (circRNA) has been found to play an important role in the progression of many diseases, including ischemic stroke. However, the regulatory mechanism of circSEC11A in ischemic stroke progression need to further investigation. METHODS: Human brain microvascular endothelial cells (HBMECs) were stimulated by oxygen glucose deprivation (OGD). CircSEC11A, SEC11A mRNA and miR (microRNA)-29a-3p were quantified by quantitative real-time PCR (qRT-PCR). SEMA3A, BAX and BCL2 protein level was quantified by western blot. Oxidative stress, cell proliferation, angiogenesis and apoptosis abilities were gauged by oxidative stress assay kit, 5-Ethynyl-2'-Deoxyuridine (EdU) staining, tube formation assay and flow cytometry assays, respectively. Direct relationship between miR-29a-3p and circSEC11A or SEMA3A was validated by dual-luciferase reporter assay, RIP assay and RNA pull-down assay. RESULTS: CircSEC11A was upregulated in OGD-induced HBMECs. OGD promoted the oxidative stress and apoptosis and inhibited cell proliferation and angiogenesis, while circSEC11A knockdown relieved the effects. CircSEC11A functioned as the sponge for miR-29a-3p, and miR-29a-3p inhibitor reversed the effects of si-circSEC11A on OGD-induced HBMECs oxidative injuries. Moreover, SEMA3A served as the target gene of miR-29a-3p. MiR-29a-3p inhibition ameliorated OGD-induced HBMECs oxidative injuries, while SEMA3A overexpression rescued the impacts of miR-29a-3p mimic. CONCLUSION: CircSEC11A promoted the malignant progression in OGD-induced HBMECs through the mediation of miR-29a-3p/SEMA3A axis. This study has provided the new insight into the underlying application of circSEC11A in cell model of ischemic stroke.

Global research of artificial intelligence in strabismus: a bibliometric analysis.

Purpose: To analyze the global publications on artificial intelligence (AI) in strabismus using a bibliometric approach. Methods: The Web of Science Core Collection (WoSCC) database was used to retrieve all of the publications on AI in strabismus from 2002 to 2023. We analyzed the publication and citation trend and identified highly-cited articles, prolific countries, institutions, authors and journals, relevant research domains and keywords. VOSviewer (software) and Bibliometrix (package) were used for data analysis and visualization. Results: By analyzing a total of 146 relevant publications, this study found an overall increasing trend in the number of annual publications and citations in the last decade. USA was the most productive country with the closest international cooperation. The top 3 research domains were Ophthalmology, Engineering Biomedical and Optics. Journal of AAPOS was the most productive journal in this field. The keywords analysis showed that "deep learning" and "machine learning" may be the hotspots in the future. Conclusion: In recent years, research on the application of AI in strabismus has made remarkable progress. The future trends will be toward optimized technology and algorithms. Our findings help researchers better understand the development of this field and provide valuable clues for future research directions.