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Rationale: Ischemic heart disease remains a primary threat to human health, while its precise etiopathogenesis is still unclear. TBC domain family member 15 (TBC1D15) is a RAB7 GTPase-activating protein participating in the regulation of mitochondrial dynamics. This study was designed to explore the role of TBC1D15 in acute myocardial infarction (MI)-induced cardiac injury and the possible mechanism(s) involved. Methods: Mitochondria-lysosome interaction was evaluated using transmission electron microscopy and live cell time-lapse imaging. Mitophagy flux was measured by fluorescence and western blotting. Adult mice were transfected with adenoviral TBC1D15 through intra-myocardium injection prior to a 3-day MI procedure. Cardiac morphology and function were evaluated at the levels of whole-heart, cardiomyocytes, intracellular organelles and cell signaling transduction. Results: Our results revealed downregulated level of TBC1D15, reduced systolic function, overt infarct area and myocardial interstitial fibrosis, elevated cardiomyocyte apoptosis and mitochondrial damage 3 days after MI. Overexpression of TBC1D15 restored cardiac systolic function, alleviated infarct area and myocardial interstitial fibrosis, reduced cardiomyocyte apoptosis and mitochondrial damage although TBC1D15 itself did not exert any myocardial effect in the absence of MI. Further examination revealed that 3-day MI-induced accumulation of damaged mitochondria was associated with blockade of mitochondrial clearance because of enlarged defective lysosomes and subsequent interrupted mitophagy flux, which were attenuated by TBC1D15 overexpression. Mechanistic studies showed that 3-day MI provoked abnormal mitochondria-lysosome contacts, leading to lysosomal enlargement and subsequently disabled lysosomal clearance of damaged mitochondria. TBC1D15 loosened the abnormal mitochondria-lysosome contacts through both the Fis1 binding and the RAB7 GAPase-activating domain of TBC1D15, as TBC1D15-dependent beneficial responses were reversed by interference with either of these two domains both in vitro and in vivo. Conclusions: Our findings indicated a pivotal role of TBC1D15 in acute MI-induced cardiac anomalies through Fis1/RAB7 regulated mitochondria-lysosome contacts and subsequent lysosome-dependent mitophagy flux activation, which may provide a new target in the clinical treatment of acute MI.

Accumulating evidence suggests that sexual minorities experience elevated levels of depressive symptoms compared to heterosexuals in Western countries. Still, little is known about whether there is any difference in depressive symptoms between sexual minority men and heterosexual men in China. This study investigated the differences in depressive symptoms and social support between 302 Chinese sexual minority men and 249 heterosexual men. The association between depressive symptoms, social support and sexual orientation was also explored. Our results indicated that Chinese sexual minority men have more depressive symptoms and perceived lower social support than heterosexual men. Overall, sexual orientation and social support both predicted depressive symptoms. Different from previous Western studies, in our results, social support fully mediates but does not moderate the relationship between sexual orientation and depressive symptoms in Chinese men. The current findings suggest that social support has a significant impact on depressive symptoms among Chinese sexual minority men, highlighting the unique role of social support in understanding depressive symptoms among Chinese sexual minority men. Providing more social support, as well as promoting accepting and positive environments, may lead to better adjustment in this population in China.

Various physical information can be leaked while the encryption algorithm is running in the device. Side-channel analysis exploits these leakages to recover keys. Due to the sensitivity of deep learning to the data features, the efficiency and accuracy of side channel analysis are effectively improved with the application of deep learning algorithms. However, a considerable part of existing reserches are based on traditional neural networks. The effectiveness of key recovery is improved by increasing the size of the network. However, the computational complexity of the algorithm increases accordingly. Problems such as overfitting, low training efficiency, and low feature extraction ability also occur. In this paper, we construct an improved lightweight convolutional neural network based on the feature fusion network. The new network and the traditional neural networks are respectively applied to the side-channel analysis for comparative experiments. The results show that the new network has faster convergence, better robustness and higher accuracy. No overfitting has occurred. A heatmap visualization method was introduced for analysis. The new network has higher heat value and more concentration in the key interval. Side-channel analysis based on feature fusion network has better performance, compared with the ones based on traditional neural networks.

YAP is a transcriptional co-activator with critical roles in tumorigenesis. However, its upstream regulatory mechanism, especially how its mRNA stability is regulated, remains to be further studied. Here, we validated that YAP expression was higher in lung adenocarcinoma (LUAD) tissues compared to adjacent normal tissues, and found that YAP m5C modification occurred in its 328–331 3′ UTR region under the promotion NSUN2 and ALYREF, and increased the stability of YAP mRNA. This m5C modification also inhibited miR-582-3p binding and m6A modification in the nearby region. In addition, YAP m5C modification enhanced the exosome secretion effect, which was caused by two YAP-dependent transcription factors, Mycn and SOX10, and then stimulating the transcription of seven downstream exosome-promoting genes. Furthermore, we found that YAP m5C modification and its exosome-secretion-promoting function contributed to the malignant phenotype and AZD9291 (a third-generation EGFR-TKI) resistance of LUAD cells. Collectively, YAP is promoted by its m5C modification, and blocking YAP m5C modification will be helpful for future LUAD treatment.Briefly, YAP 3′UTR is m5C modified under the promotion of NSUN2 and ALYREF, and this modification increases YAP mRNA stability and inhibits nearby m6A modification and miR-582-3p binding. Furthermore, YAP stimulates seven exosome biogenesis, transport and release-related genes including HRS, PLD2, RAB2B, RAB27A, RAB27B, VAMP and ATG7 in a Mycn- and SOX10-dependent manner.

Objective This study aimed to preliminarily investigate the feasibility, safety, and early clinical outcomes of minimally invasive left ventricular assist device (LVAD) implantation with concomitant cardiac procedures. Methods We retrospectively analyzed the clinical data of three consecutive male patients with end-stage heart failure who underwent minimally invasive LVAD implantation at our center between August and November 2024. Two patients received the CorHeart 6 LVAD, while one received the CH-VAD LVAD. Two patients underwent concomitant procedures (patent foramen ovale closure or left atrial appendage occlusion) during the LVAD implantation. Results All procedures were successfully completed without intraoperative mortality or conversion to sternotomy. Cardiopulmonary bypass time ranged from 121 to 214 min. Postoperative echocardiography demonstrated reduced ventricular dimensions, improved ejection fraction, and resolution of significant valvular regurgitation in all patients. The duration of mechanical ventilation ranged from 1 to 5 days, and the ICU stay ranged from 3 to 7 days. No mortality, pump thrombosis, stroke, or reoperation for bleeding occurred. One patient experienced transient postoperative arrhythmia, which resolved with medical management. Conclusion This initial experience suggests that minimally invasive LVAD implantation via left thoracotomy, with concomitant cardiac procedures, is technically feasible and safe in selected patients with end-stage heart failure. This strategy was associated with encouraging early outcomes and provides early clinical data on the minimally invasive application of devices such as the CorHeart 6 to the international LVAD community. Key findings The minimally invasive LVAD implantation for the treatment of advanced heart failure highlight its safety and effectiveness. What is known and what is new? The clinical application of LVADs in the field of heart failure has shown rapid growth. Traditional open-chest surgery has been the standard approach for LVAD implantation, but it is associated with significant surgical trauma and longer recovery times. The minimally invasive LVAD implantation reduces operative time and blood loss. And it has a lower incidence of postoperative complications, such as infections and respiratory issues. Additionally, our patients reported faster recovery and improved quality of life, with shorter hospital stays and quicker return to normal activities. These findings suggest that minimally invasive LVAD implantation not only offers technical advantages but also significant clinical benefits for patients with advanced heart failure. What is the implication, and what should change now? Minimally invasive implantation of LVAD can improve symptoms, reduce complications, lower the risk of perioperative right heart failure, and enhance early survival rates.

This study aimed to investigate the influence of pine pollen (PP) on hepatocellular carcinoma (HCC) behavior in vitro and in vivo and explore its mechanism of action by focusing on the phosphatidylinositol 3-kinase/protein serine-threonine kinase (PI3K/AKT) signaling pathway and α-Enolase (ENO1) gene expression. We performed a bioinformatics analysis of ENO1. HCC cells overexpressing ENO1 were developed by lentivirus transfection. Cell proliferation, invasion, and migration were assessed using the cell cytotoxicity kit-8 assay, transwell assay, cell scratch test, and ENO1 inhibiting proliferation experiment. Protein expression was analyzed using Western blot. The in vivo effects of PP on HCC xenografts were also assessed in mice. The serum of nude mice in each group was analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and AST/ALT. The tumor blocks of nude mice were weighed, and proteins were extracted for Western blot. Compared to normal cells, the phosphorylation of ENO1 at the S27 site was most significant in HCC cells and was closely related to cell proliferation. In vitro, the PP solution inhibited the proliferation, invasion, and migration of ENO1 overexpressing cells compared with empty-vector-transfected cells. In mice bearing HCC, PP injection inhibited the overexpression of ENO1, affected serum ALT, AST, and AST/ALT levels, and reduced tumor weight. However, the expression of proliferation-related proteins in tumors overexpressing ENO1 was higher than in empty transfected tumors. PP inhibits HCC by regulating the expression of ENO1 and MBP-1 and suppressing the PI3K/AKT pathway by inhibiting C-MYC and erb-B2 receptor tyrosine kinase 2.

Background Wound healing is impaired in patients with diabetes due to the multifactorial etiology of the disease, which limits the therapeutic efficacy of various approaches. This study hypothesizes that the combination of adipose-derived stem cells (ADSCs) and platelet-rich plasma (PRP) might achieve optimally efficient diabetic wound healing. Methods ADSCs were isolated from the adipose tissues of Sprague-Dawley (SD) rats. PRP was prepared by using a two-step centrifugation technique. A diabetic wound model was established on the backs of SD rats to evaluate the effect of ADSCs incorporated into PRP. Hematoxylin and eosin staining, immunofluorescence, and immunohistochemistry were performed to observe the changes in neovascularization. ELISA and Western blot were utilized to detect the angiogenesis-related protein expression levels. The proliferation of endothelial cells was assessed by the MTS assay. Results ADSCs incorporated into PRP induced a higher wound closure rate than ADSCs, PRP, and negative control. The expression levels of VEGF, p-STAT3, and SDF-1 in the ADSC+PRP group were higher than those in the other groups. Moreover, the proliferation of endothelial cells was strongly stimulated by treatment with the combination of ADSC-conditioned medium (ADSC-CM) and PRP. Conclusions PRP enhanced diabetic wound healing induced by ADSCs, and its promoting effect involved neovascularization.

This article, drawing on recent research on Language Other than English (LOTE) programs in China’s universities, examines the impact of multilingual education policy on the professional development of LOTE teachers. We argue for the mediating roles of LOTE programs as they carry the influence of education policy on teacher development. In other words, LOTE programs may influence the way in which education policy impacts teacher development. Specifically, LOTE programs seem to play three mediating roles: (1) How education policy is perceived and understood by the program designer or/and coordinator impacts how LOTE teachers who engage in the program are influenced, (2) how educational resources are allocated to teachers teaching in the LOTE program impacts teachers’ professional development, (3) how teachers actually position themselves in the LOTE program as opposed to their identities positioned by education policy and the university administration impacts their professional development. In a word, the influence of multilingual education policy on the professional development of LOTE teachers may be mediated by such meso- and micro-level factors as administration, resource, and identity work.

Soil moisture (SM) retrieved from satellite and spaceborn sensors provides useful parameters for earth system models (ESMs). The Climate Change Initiative (CCI) SM products released by the European Space Agency have been widely used in many humid/semi-humid climatic regions due to their relatively long-term record. However, the performance of these products in cold and arid regions, such as the Qinghai-Tibetan Plateau (QTP), is largely unknown, necessitating urgent evaluation and calibration in these areas. In this work, we evaluated the reliability and improved the accuracy of the active-passive combined CCI products (CCI-C) using in-situ measured SM contents (SMC) under different underlying surface conditions. First, some conventional models were used to investigate the relationship between the CCI-C and the in-situ observed SMC, yielding similar fitting performances. Next, the random forest method and multiple linear regression were used to contrast the conventional models to calibrate and validate the CCI-C SM product based on the in-situ observed SMC, and the random forest method was found to have the highest accuracy. However, calibration of the CCI-C SM data with the best-performed random forest method based on different spatial zonation methods, e.g., by climate, topography, land cover, and vegetation, resulted in distinct spatial patterns of SM. Compared to a widely-used satellite SM product, namely the Soil Moisture Active Passive (SMAP) SM dataset, the calibrated CCI-C SM data based on climatic and vegetation zonation were larger but had similar spatial patterns. This study also points to the value of the calibrated CCI-C SM product to support land surface studies on the QTP.

Pectins are complex polysaccharides that are widely found in plant cells and have a variety of bioactivities. However, the high molecular weights (Mw) and complex structures of natural pectins mean that they are difficult for organisms to absorb and utilize, limiting their beneficial effects. The modification of pectins is considered to be an effective method for improving the structural characteristics and promoting the bioactivities of pectins, and even adding new bioactivities to natural pectins. This article reviews the modification methods, including chemical, physical, and enzymatic methods, for natural pectins from the perspective of their basic information, influencing factors, and product identification. Furthermore, the changes caused by modifications to the bioactivities of pectins are elucidated, including their anti-coagulant, anti-oxidant, anti-tumor, immunomodulatory, anti-inflammatory, hypoglycemic, and anti-bacterial activities and the ability to regulate the intestinal environment. Finally, suggestions and perspectives regarding the development of pectin modification are provided.