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Highlights Cetyltrimethylammonium cations can shield the repelling force on anions to attract more anions into electric double layer region during lithium plating process, facilitating the formation of inorganic-rich solid-state electrolyte interphase (SEI). An inorganic-rich (N/F-containing species) structure of SEI can be evidenced by the in-depth analysis. The cycling lifetime of Li||Li symmetric cell in the designed electrolyte can be extended from 500 to 1300 h. Moreover, full cells with a high cathode mass loading of >10 mg cm-2 can be stably cycled over 180 cycles.

Abstract Background Telomere length has long been recognized as a valuable biomarker of aging and is inversely correlated with chronological age. Various lifestyle factors have been implicated in telomere shortening or preservation; however, the association between lifestyle factors and telomere length remains controversial. To address this issue, we conducted a Mendelian randomization (MR) analysis to investigate the potential causal associations between multiple lifestyle factors and telomere length. Methods Independent genetic variants strongly associated with lifestyle factors (tobacco smoking, sleep duration, insomnia, and physical activity) were selected as instrumental variables from corresponding genome-wide association studies (GWASs). Summary-level data for telomere length was obtained from a GWAS comprising 472,174 European ancestries. Univariable and multivariable MR analyses were performed to assess the relationships. Results The genetic liability to lifetime smoking was robustly associated with shorter telomere length (odd ratio [OR]: 0.882; 95% confidence interval [CI]: 0.847–0.918). Genetically predicted insomnia was also linked to shorter telomere length (OR: 0.972; 95% CI: 0.959–0.985), while no significant association was observed between sleep duration and telomere length. Furthermore, a suggestive association was found between moderate-to-vigorous physical activity and longer telomere length (OR: 1.680; 95% CI: 1.115–2.531). In multivariable MR analyses, adjusting for potential mediators such as body mass index, type 2 diabetes, alcohol consumption, and alcohol use disorder, the associations of lifetime smoking and insomnia with telomere length remained robust. Conclusion Our findings suggest that smoking and insomnia may contribute to telomere shortening, while physical activity may play a role in telomere length maintenance. These findings underscore the importance of managing positive risk factors and adopting a healthy lifestyle to promote telomere health.

Abstract Background It is very common for patients with newly diagnosed lung masses to have heart disease. However, papillary fibroelastomas (PFEs) of the tricuspid valve (TV) combined with lung cancer are rarely reported. It is thus unclear whether a two-stage surgery or concomitant surgery is optimal. Case presentation We report the case of a 73-year-old Chinese male who was diagnosed with PFEs on the TV by transthoracic echocardiography (TTE) examination while being evaluated to undergo video-assisted thoracic surgery (VATS) for a right lower lung nodule. We resected both the PFEs and the lung nodule via right minithoracotomy. The surgery was uneventful, and histopathology reports confirmed PFEs of the TV and moderately to poorly differentiated squamous cell carcinoma. The patient recovered uneventfully, and there was no sign of tumor recurrence during 15 months of follow-up. Conclusions We suggest that after careful evaluation, concomitant minimally invasive radical resection of primary lung cancer after cardiac PFE removal is an acceptable and safe treatment strategy and should be performed as soon as possible.

Abstract Background Heart failure (HF) seriously threatens human health worldwide. However, the pathological mechanisms underlying HF are still not fully clear. Results In this study, we performed proteomics and transcriptomics analyses on samples from human HF patients and healthy donors to obtain an overview of the detailed changes in protein and mRNA expression that occur during HF. We found substantial differences in protein expression changes between the atria and ventricles of myocardial tissues from patients with HF. Interestingly, the metabolic state of ventricular tissues was altered in HF samples, and inflammatory pathways were activated in atrial tissues. Through analysis of differentially expressed genes in HF samples, we found that several glutathione S-transferase (GST) family members, especially glutathione S-transferase M2-2 (GSTM2), were decreased in all the ventricular samples. Furthermore, GSTM2 overexpression effectively relieved the progression of cardiac hypertrophy in a transverse aortic constriction (TAC) surgery-induced HF mouse model. Moreover, we found that GSTM2 attenuated DNA damage and extrachromosomal circular DNA (eccDNA) production in cardiomyocytes, thereby ameliorating interferon-I-stimulated macrophage inflammation in heart tissues. Conclusions Our study establishes a proteomic and transcriptomic map of human HF tissues, highlights the functional importance of GSTM2 in HF progression, and provides a novel therapeutic target for HF.

Abstract Background Redo heart surgery has become increasingly common but involves additional high surgical risk, especially redo surgery after coronary artery bypass grafting (CABG). Case presentation In this study, we report the case of a 57-year-old Chinese male with left atrium myxoma who had previously undergone CABG. Common surgical methods usually include aortic cross-clamping, administering cold cardioplegia perfusion to protect the myocardium, opening the heart, and then removing the tumor. However, for patients with previous CABG, redo thoracotomy and ascending aortic cross-clamping present a greater risk of damage to the grafted vessels. In this study, we chose a right lateral mini-thoracotomy incision and hypothermia-induced ventricular fibrillation to minimize damage and avoid any adverse effects on the bridge vasculature. The patient recovered uneventfully and was discharged seven days after surgery. Conclusions For patients with previous CABG, minimally invasive right thoracotomy under perfused ventricular fibrillation with hypothermia is safe and reliable and can prevent potential damage to the ascending aorta and graft.

Abstract Background Growing evidence suggests that various reproductive factors, including early menarche, early menopause, and age at first birth, may increase the risk of developing cardiovascular disease (CVD) later in life. However, the associations between reproductive factors and CVDs are inconsistent and controversial. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis to explore the potential links between age at first sex (AFS) and age at first birth (AFB) and several CVDs. Methods We obtained summary statistics for exposure from the largest genome-wide association studies of AFS and AFB. To serve as instrumental variables, we selected 259 SNPs associated with AFS and 81 SNPs associated with AFB at the genome-wide significance level. We employed a random-effects inverse-variance weighted method to pool estimates, and conducted multivariable MR analysis to determine the direct association between AFS and AFB with CVDs, while accounting for the effects of confounders. Results The genetic liability to later AFS was associated with decreased risks of heart failure (odd ratio [OR] 0.700; 95% confidence interval [CI] 0.639–0.767; p = 2.23 × 10−14), coronary artery disease (OR 0.728; 95% CI 0.657–0.808; p = 1.82 × 10−9), myocardial infarction (OR 0.731; 95% CI 0.657–0.813; p = 8.33 × 10−9), stroke (OR 0.747; 95% CI 0.684–0.816; p = 6.89 × 10−11), and atrial fibrillation (OR 0.871; 95% CI 0.806–0.941; p = 4.48 × 10−4). The genetic liability to later AFB was also associated with decreased risks of CVDs, including myocardial infarction (OR 0.895; 95% CI 0.852–0.940; p = 8.66 × 10−6), coronary heart disease (OR 0.901; 95% CI 0.860–0.943; p = 9.02 × 10−6), heart failure (OR 0.925; 95% CI 0.891–0.961; p = 5.32 × 10−5), and atrial fibrillation (OR 0.944; 95% CI 0.911–0.978; p = 0.001). However, no association was found between AFB and stroke. The associations remained independent from the effects of AFS and AFB on potential confounders, including smoking, alcohol intake, body mass index, and depression. Mediation analysis suggested that education attainment partly mediates the link from AFS and AFB to CVD outcomes. Conclusion Our results observed a causal relationship between later AFS, AFB and lower CVDs risk; it emphasizes the importance of providing sex education since early sex and birth may have undesirable effects. Cardiovascular risk stratification that considers reproductive factors may help address CVD risk.

Abstract Background CD34+ cells have been used to treat the patients with heart failure, but the outcome is variable. It is of great significance to scrutinize the fate and the mechanism of CD34+ cell differentiation in vivo during heart failure and explore its intervention strategy. Methods We performed single-cell RNA sequencing (scRNA-seq) of the total non-cardiomyocytes and enriched Cd34-tdTomato+ lineage cells in the murine (male Cd34-CreERT2; Rosa26-tdTomato mice) pressure overload model (transverse aortic constriction, TAC), and total non-cardiomyocytes from human adult hearts. Then, in order to determine the origin of CD34+ cell that plays a role in myocardial fibrosis, bone marrow transplantation model was performed. Furthermore, to further clarify the role of CD34 + cells in myocardial remodeling in response to TAC injury, we generated Cd34-CreERT2; Rosa26-eGFP-DTA (Cre/DTA) mice. Results By analyzing the transcriptomes of 59,505 single cells from the mouse heart and 22,537 single cells from the human heart, we illustrated the dynamics of cell landscape during the progression of heart hypertrophy, including CD34+ cells, fibroblasts, endothelial and immune cells. By combining genetic lineage tracing and bone marrow transplantation models, we demonstrated that non-bone-marrow-derived CD34+ cells give rise to fibroblasts and endothelial cells, while bone-marrow-derived CD34+ cell turned into immune cells only in response to pressure overload. Interestingly, partial depletion of CD34+ cells alleviated the severity of myocardial fibrosis with a significant improvement of cardiac function in Cd34-CreERT2; Rosa26-eGFP-DTA model. Similar changes of non-cardiomyocyte composition and cellular heterogeneity of heart failure were also observed in human patient with heart failure. Furthermore, immunostaining showed a double labeling of CD34 and fibroblast markers in human heart tissue. Mechanistically, our single-cell pseudotime analysis of scRNA-seq data and in vitro cell culture study revealed that Wnt-β-catenin and TGFβ1/Smad pathways are critical in regulating CD34+ cell differentiation toward fibroblasts. Conclusions Our study provides a cellular landscape of CD34+ cell-derived cells in the hypertrophy heart of human and animal models, indicating that non-bone-marrow-derived CD34+ cells differentiating into fibroblasts largely account for cardiac fibrosis. These findings may provide novel insights for the pathogenesis of cardiac fibrosis and have further potential therapeutic implications for the heart failure.

Cropland abandonment is crucial in agricultural management and has a profound impact on crop yield and food security. In recent years, many cropland abandonment identification methods based on remote sensing observation data have been proposed, but most of these methods are based on coarse-resolution images and use traditional machine learning methods for simple identification. To this end, we perform abandonment recognition on high-resolution remote sensing images. According to the texture features of the abandoned land, we combine the method of statistical texture learning and propose a new deep learning framework called pyramid scene parsing network-statistical texture learning (PSPNet-STL). The model integrates high-level semantic feature extraction and deep mining of low-level texture features to identify cropland abandonment. First, we labeled the abandoned cropland area and built the high-resolution abandoned cropland (HRAC) dataset, a high-resolution cropland abandonment dataset. Second, we improved PSPNet by fusing statistical texture learning modules to learn multiple texture information on low-level feature maps and combined high-level semantic features for cropland abandonment recognition. Experiments are performed on the HRAC dataset. Compared with other methods, the proposed model has the best performance on this dataset, both in terms of accuracy and visualization, proving that deep mining of low-level statistical texture features is beneficial for crop abandonment recognition.

Exosomes, as potent intercellular communication tools, have garnered significant attention due to their unique cargo-carrying capabilities, which enable them to influence diverse physiological and pathological functions. Extensive research has illuminated the biogenesis, secretion, and functions of exosomes. These vesicles are secreted by cells in different states, exerting either protective or harmful biological functions. Emerging evidence highlights their role in cardiovascular disease (CVD) by mediating comprehensive interactions among diverse cell types. This review delves into the significant impacts of exosomes on CVD under stress and disease conditions, including coronary artery disease (CAD), myocardial infarction, heart failure, and other cardiomyopathies. Focusing on the cellular signaling and mechanisms, we explore how exosomes mediate multifaceted interactions, particularly contributing to endothelial dysfunction, oxidative stress, and apoptosis in CVD pathogenesis. Additionally, exosomes show great promise as biomarkers, reflecting differential expressions of NcRNAs (miRNAs, lncRNAs, and circRNAs), and as therapeutic carriers for targeted CVD treatment. However, the specific regulatory mechanisms governing exosomes in CVD remain incomplete, necessitating further exploration of their characteristics and roles in various CVD-related contexts. This comprehensive review aims to provide novel insights into the biological implications of exosomes in CVD and offer innovative perspectives on the diagnosis and treatment of CVD.

Iron impurities are believed to act as deep acceptors that can compensate for the n-type conductivity in as-grown Ga2O3, but several scientific issues, such as the site occupation of the Fe heteroatom and the complexes of Fe-doped β-Ga2O3 with native defects, are still lacking. In this paper, based on first-principle density functional theory calculations with the generalized gradient approximation approach, the controversy regarding the preferential Fe incorporation on the Ga site in the β-Ga2O3 crystal has been addressed, and our result demonstrates that Fe dopant is energetically favored on the octahedrally coordinated Ga site. The structural stabilities are confirmed by the formation energy calculations, the phonon dispersion relationships, and the strain-dependent analyses. The thermodynamic transition level Fe3+/Fe2+ is located at 0.52 eV below the conduction band minimum, which is consistent with Ingebrigtsen’s theoretical conclusion, but slightly smaller than some experimental values between 0.78 eV and 1.2 eV. In order to provide direct guidance for material synthesis and property design in Fe-doped β-Ga2O3, the defect formation energies, charge transitional levels, and optical properties of the defective complexes with different kinds of native defects are investigated. Our results show that VGa and Oi can be easily formed for the Fe-doped β-Ga2O3 crystals under O-rich conditions, where the +3 charge state FeGaGai and −2 charge state FeGaOi are energetically favorable when the Fermi level approaches the valence and conduction band edges, respectively. Optical absorption shows that the complexes of FeGaGai and FeGaVGa can significantly enhance the optical absorption in the visible-infrared region, while the energy-loss function in the β-Ga2O3 material is almost negligible after the extra introduction of various intrinsic defects.

Abstract Background Pathological cardiac hypertrophy is a major contributor of heart failure (HF), which seriously threatens human’s health world widely. Deregulation of m6A RNA methylation, and m6A methyltransferases and de-methyltransferases have been demonstrated to act essential roles in cardiac hypertrophy and HF. Here, we studied the potential roles and its underlying mechanisms of m6A Reader YTHDF proteins in HF. In this study, we constructed HF mouse model by transverse aortic constriction surgery. Primary cardiomyocytes were isolated and stimulated with isoproterenol (ISO) or phenylephrine (PHE) to induce myocardial hypertrophy. Results Through single-cell RNA-seq analysis, immunofluorescent staining, HE staining, Western blotting, and real time-PCR detections, we found that YTHDF2 mRNA and protein level, but not YTHDF1 or YTHDF3, was significantly increased during HF development. YTHDF2 overexpression could efficiently alleviate cardiac hypertrophy. Furthermore, through immunoprecipitation accompanied with mass spectrometry analysis, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, we found that ISO stimulation did not evidently affect YTHDF2-interacting proteins. However, ISO or PHE stimulation significantly increased YTHDF2 protein interacting with Myh7 (beta-myosin heavy chain) mRNA, an important cardiac hypertrophy marker, in an m6A-dependent manner. Knockdown of Myh7 or deletion of the YTH domain of YTHDF2 reversed the protective effects of YTHDF2 on cardiac hypertrophy. Finally, we found that ISO or PHE stimulation promoted YTHDF2 protein expression through enhancing Ythdf2 mRNA stability in an m6A-dependent manner in cardiomyocytes. Conclusions Overall, our results indicate that the m6A Reader YTHDF2 suppresses cardiac hypertrophy via Myh7 mRNA decoy in an m6A-dependent manner. This study highlights the functional importance of YTHDF2-dependent cardiac m6A mRNA regulation during cardiac hypertrophy, and provides a novel mechanistic insight into the therapeutic mechanisms of YTHDF2.

Cingulin, a cytoplasmic element of tight junctions (TJs), is involved in maintenance of the integrity of epithelial and endothelial cells. However, the role of cingulin in the development of auditory organs remains unclear. Zebrafish is popular as a model organism for hearing research. Using the whole mount in situ hybridization (WISH) experiment, we detected the expression of cingulin b in the posterior lateral line system (PLLs) of zebrafish. We traced the early development progress of zebrafish PLLs from 36 hpf to 72 hpf, and found that inhibition of cingulin b by target morpholinos resulted in severe developmental obstruction, including decreased number of neuromasts, reduced proliferative cells in the primordium, and repressed hair cell differentiation in the neuromasts. To examine the potential mechanism of cingulin b in the development of zebrafish PLL neuromasts, we performed RNA-seq analysis to compare the differently expressed genes (DEGs) between cingulin b knockdown samples and the controls. The KEGG enrichment analysis revealed that MAPK signaling pathway and cellular senescence were the key pathways with most DEGs in cingulin b-MO morphants compared to the Control-MO embryos. Furthermore, quantitative RT-PCR analysis confirmed the findings by RNA-seq that the transcript levels of cell cycle negative regulators such as tp53 and cdkn1a, were remarkably upregulated after inhibition of cingulin b. Our results therefore indicated an important role of cingulin b in the development of auditory organs, and MAPK signaling pathway was inhibited while cellular senescence pathway was activated after downregulation of cingulin b. We bring forward new insights of cingulin by exploring its function in auditory system.

Kif15, a kinesin family member, is powerful in the formation of bipolar spindles. There is emerging evidence indicating that Kif15 plays vital roles in influencing the growth of axons and interference with the progression of the tumor. However, the function of Kif15 in the auditory organs remains unknown. The Western blotting test was used to examine the effect of Kif15 downregulation by specific morpholino targeting Kif15 (Kif15-MO). The development of the inner ear and posterior lateral line (PLL) system in zebrafish was under continuous observation from spawns to 96 h postfertilization (hpf) to investigate the potential role of Kif15 in the auditory and vestibular system. We uncovered that Kif15 inhibition induced otic organ deformities in zebrafish, including malformed semicircular canals, abnormal number and location of otoliths, and reduced number of hair cells (HCs) both in utricle and saccule. Furthermore, a remarkable reduction in the number of PLL neuromasts was also explored in Kif15-MO morphants compared to the normal larvae. We also detected notably reduced activity in locomotion after Kif15 was knocked down. Additionally, we performed rescue experiments with co-injection of Kif15 mRNA and found that the Kif15 splicing MO-induced deformities in otic vesicle and PLL of zebrafish were successfully rescued, and the severely reduced locomotor activity caused by Kif15-MO was partially rescued compared to the control-MO (Con-MO) embryos. Our findings uncover that Kif15 is essential in the early development of auditory and vestibular organs using zebrafish as models.

Abstract Heart diseases caused by structure and function degradation is troubling millions of people all over the world. With the extension of human lifespan, the demand for heart valve replacement is rapidly increasing. However, the currently used prostheses of heart valve in clinic such as mechanical and tissue valves all have serious limitations over long‐term stability after implanting. Therefore, novel artificial heart valves with outstanding durability and low degradation risk are still in great demands, despite of numerous studies in the literature. The sophisticated, multiscale structure of native heart valve is believed to be the key to its mechanical and biological durability during long‐term cyclic motion. In this review, we discussed the complex structure of the native heart valve as well as their contributions to the valve's cyclic work. In addition, representative and state of the art studies of biomimetic heart valves inspired by the natural valve are also introduced. Based on these, the structural and functional design of future novel biomimetic heart valves are proposed.

Aim: The structural and electrical changes in the atrium, also known as atrial remodeling, are the main characteristics of atrial fibrillation (AF). Fibroblast growth factor 21 (Fgf21) is an important endocrine factor, which has been shown to play an important role in cardiovascular diseases. However, the effects of Fgf21 on atrial remodeling have not been addressed yet. The purpose of the present study is to evaluate the effects of Fgf21 on atrial remodeling.Methods and Results: Adult mice were treated with Ang II, and randomly administrated with or without Fgf21 for 2 weeks. The susceptibility to AF was assessed by electrical stimulation and optical mapping techniques. Here, we found that Fgf21 administration attenuated the inducibility of atrial fibrillation/atrial tachycardia (AF/AT), improved epicardial conduction velocity in the mice atria. Mechanistically, Fgf21 protected against atrial fibrosis and reduced oxidative stress of the atria. Consistently, in vitro study also demonstrated that Fgf21 blocked the upregulation of collagen by Tgf-β in fibroblasts and attenuated tachypacing-induced oxidative stress including reactive oxygen species (ROS), Tgf-β, and ox-CaMKII in atrial myocytes. We further found that Fgf21 attenuated oxidative stress by inducing antioxidant genes, such as SOD2 and UCP3. Fgf21 also improved tachypacing-induced myofibril degradation, downregulation of L-type calcium channel, and upregulation of p-RyR2, which implicated protective effects of Fgf21 on structural and electrical remodeling in the atria. Moreover, Nrf2 was identified as a downstream of Fgf21 and partly mediated Fgf21-induced antioxidant gene expression in atrial myocytes.Conclusion: Fgf21 administration effectively suppressed atrial remodeling by reducing oxidative stress, which provides a novel therapeutic insight for AF.

Background: Previous observational studies have reported an association between psychiatric traits and cardiovascular diseases (CVDs). In this two-sample Mendelian randomization (MR) study, we aimed to investigate the causality between psychiatric traits and CVDs.Methods: Single-nucleotide polymorphisms (SNPs) associated with autism spectrum disorder (ASD), neuroticism, and subjective well-being at genome-wide significance (P < 1 × 10−8) were identified from genome-wide association studies. Summary-level data of the outcomes, including coronary artery disease (CAD), myocardial infarction (MI), atrial fibrillation (AF), and heart failure (HF), were obtained from several largest datasets. The inverse-variance weighted (IVW) method was used as our main analyses to conduct this MR study. Sensitivity analyses included the weighted median, the MR-robust adjusted profile score (MR-RAPS), and the MR pleiotropy residual sum and outlier (MR-PRESSO) method. Repeated MR analyses using a more relaxed threshold (P < 1 × 10−6) for instruments selection and multivariable MR analyses were also applied to evaluate the robustness of results.Results: The MR analyses showed that genetic predisposition to ASD was associated with a higher risk of AF [odds ratio (OR), 1.109; 95% confidence interval (CI), 1.023–1.201; P = 0.011] and HF (OR, 1.138; 95% CI, 1.036–1.251; P = 0.007). Neuroticism was casually associated with an increased risk of AF (OR, 1.201; 95% CI, 1.037–1.392; P = 0.015), whereas subjective well-being had a protective effect on HF (OR, 0.732; 95% CI, 0.574–0.933; P = 0.012). No other causal association between psychiatric traits and CVDs was observed. Consistent results were obtained in sensitivity analyses.Conclusion: This study provided evidence of causal associations of ASD with a higher risk of AF and HF. Besides, neuroticism was casually associated with an increased risk of AF, and subjective well-being was associated with a decreased risk of HF.

Abstract Background The treatment strategy for aortic valve and lung cancer patients includes concomitant or two-stage procedures. Conventional simultaneous operations are usually performed under the median sternotomy. Case presentation A 72-year-old man was admitted to our hospital after experiencing chest tightness after activity for two months. Aortic valve regurgitation had been confirmed when squamous cell carcinoma of the lung was discovered. The therapeutic strategy for these patients is controversial. Considering the potential risk of tumour metastasis and the risk of cardiopulmonary bypass (CPB), we recommended concomitant transcatheter aortic valve implantation (TAVI) and a lobectomy. A trans-apical TAVI with left-sided intercostal thoracotomy was successfully performed, followed by an immediate video-assisted thoracoscopic surgery (VATS) lobectomy and selective lymph node dissection. Conclusions We suggest that a one-stage surgery of pulmonary resection following TAVI is an acceptable and safe choice after careful evaluation and should be performed as soon as possible in response to lung cancer in elderly patients with aortic valve disease.

Abstract Background Cardiac radiofrequency ablation is a popular treatment for arrhythmias. However, it does have some complications, some of which are severe, even fatally. And there were limited reports on cardiac internal perforation after radiofrequency catheter ablation (RFCA) that required a surgical repair. Case presentation A 47-year-old male was admitted to our hospital due to chest congestion for 4 months. He received a radiofrequency catheter ablation (RFCA) 9 months prior to admission. On admission, an echocardiogram showed an abnormal perforation between the left ventricle and the left atrium with moderate mitral valve regurgitation. We therefore performed a mitral valve replacement (MVR) and fixed the abnormal atrial-ventricular breakage via median sternotomy. Conclusions Cardiac perforation is a severe complication of cardiac RFCA, operators should be extremely cautious to minimize radiofrequency associated perforations. Such a challenging and complex procedure should be deliberately considered by doctors and patients before implementation.

Objective Colorectal cancer (CRC) is the most common cancer worldwide. Patient outcomes following recurrence of CRC are very poor. Therefore, identifying the risk of CRC recurrence at an early stage would improve patient care. Accumulating evidence shows that autophagy plays an active role in tumorigenesis, recurrence, and metastasis. Methods We used machine learning algorithms and two regression models, univariable Cox proportion and least absolute shrinkage and selection operator (LASSO), to identify 26 autophagy-related genes (ARGs) related to CRC recurrence. Results By functional annotation, these ARGs were shown to be enriched in necroptosis and apoptosis pathways. Protein–protein interactions identified SQSTM1 , CASP8 , HSP80AB1 , FADD , and MAPK9 as core genes in CRC autophagy. Of 26 ARGs, BAX and PARP1 were regarded as having the most significant predictive ability of CRC recurrence, with prediction accuracy of 71.1%. Conclusion These results shed light on prediction of CRC recurrence by ARGs. Stratification of patients into recurrence risk groups by testing ARGs would be a valuable tool for early detection of CRC recurrence.

Chemosensory proteins (CSPs) are a class of transporters in arthropods. Deeper research on CSPs showed that CSPs may be involved in some physiological processes beyond chemoreception, such as insect resistance to pesticides. We identified two upregulated CSPs in two resistant strains of Aphis gossypii Glover. To understand their role in the resistance of aphids to pesticides, we performed the functional verification of CSP1 and CSP4 in vivo and in vitro. Results showed that the sensitivity of the thiamethoxam-resistant strain to thiamethoxam increased significantly with the silencing of CSP1 and CSP4 by RNAi (RNA interference), and the sensitivity of the spirotetramat-resistant strain to spirotetramat increased significantly with the silencing of CSP4. Transgenic Drosophila melanogaster expressing CSPs exhibited stronger resistance to thiamethoxam, spirotetramat, and alpha-cypermethrin than the control did. In the bioassay of transgenic Drosophila, CSPs showed different tolerance mechanisms for different pesticides, and the overexpressed CSPs may play a role in processes other than resistance to pesticides. In brief, the present results prove that CSPs are related to the resistance of cotton aphids to insecticides.

Adult rats treated concomitantly with insulin and human chorionic gonadotropin exhibit endocrine, metabolic, and reproductive abnormalities that are very similar to those observed in polycystic ovary syndrome (PCOS) patients. In this study, we used this rat model to assess the effects of metformin on PCOS-related uterine dysfunction. In addition to reducing androgen levels, improving insulin sensitivity, and correcting the reproductive cycle, metformin treatment induced morphological changes in the PCOS-like uterus. At the molecular and cellular levels, metformin normalized the androgen receptor-mediated transcriptional program and restored epithelial–stromal interactions. In contrast to glucose transport, uterine inflammatory gene expression was suppressed through the PI3K–Akt–NFκB network, but without affecting apoptosis. These effects appeared to be independent of AMPK subunit and autophagy-related protein regulation. We found that when metformin treatment partially restored implantation, several implantation-related genes were normalized in the PCOS-like rat uterus. These results improve our understanding of how metformin rescues the disruption of the implantation process due to the uterine defects that result from hyperandrogenism and insulin resistance. Our data provide insights into the molecular and functional clues that might help explain, at least in part, the potential therapeutic options of metformin in PCOS patients with uterine dysfunction.

With the key words of skilled worker training, evaluation, innovation, mobility and motivation, three sets of relevant survey questionnaires were designed for skilled workers, managers and enterprises, and they were used in more than ten enterprises in Hubei. In the questionnaire data statistics, according to the principle of "single-question compliance", data that does not meet the requirements of the topic selection is eliminated. Based on high-quality development and manufacturing in Hubei Province, this article summarizes and puts forward the problems that exist in the training process and the improvement of skills of manufacturing skilled workers in Hubei Province under the background of big data through the analysis of effective data and field investigations. Thinking about the corresponding countermeasures from the legal level.

Studying the interaction between demand forecasting and train stop planning is important, as it ensures the sustainable development of high-speed rail (HSR). Forecasting the demand for high-speed rail (HSR), which refers to modal choice or modal split in this paper, is the first step in high-speed rail (HSR) planning. Given the travel demand and the number of train trips on each route, the train stop planning problem (TSPP) of line planning involves determining the stations at which each train trip stops, i.e., the stop-schedule of each train trip, so that the demand can be satisfied. To integrate and formulate the two problems, i.e., the modal choice problem (MCP) and train stop planning problem (TSPP), a nonlinear model is presented with the objective of maximizing the total demand captured by a high-speed rail system. To solve the model, a heuristic iterative algorithm is developed. To study the relationship between the demand and the service, the Beijing−Shanghai high-speed rail (HSR) corridor in China is selected. The empirical analysis indicates that combining modal choice and train stop planning should be considered for the sustainable design of high-speed rail (HSR) train services. Furthermore, the model simulates the impact of the number of stops on its mode share by reflecting changes in travelers’ behaviors according to HSR train stop planning, and it also provides a theoretical basis for the evaluation of the adaptability of the service network to travel demand.

Adenosine deaminases acting on RNA (ADAR) are enzymes that regulate RNA metabolism through post-transcriptional mechanisms. ADAR1 is involved in a variety of pathological conditions including inflammation, cancer, and the host defense against viral infections. However, the role of ADAR1p150 in vascular disease remains unclear. In this study, we examined the expression of ADAR1p150 and its role in viral myocarditis (VMC) in a mouse model. VMC mouse cardiomyocytes showed significantly higher expression of ADAR1p150 compared to the control samples. Coimmunoprecipitation verified that ADAR1p150 forms a complex with Dicer in VMC. miRNA-222, which is involved in many cardiac diseases, is highly expressed in cardiomyocytes in VMC. In addition, the expression of miRNA-222 was promoted by ADAR1p150/Dicer. Among the target genes of miRNA-222, the expression of phosphatase-and-tensin (PTEN) protein was significantly reduced in VMC. By using a bioinformatics tool, we found a potential binding site of miRNA-222 on the PTEN gene’s 3′-UTR, suggesting that miRNA-222 might play a regulatory role. In cultured cells, miR-222 suppressed PTEN expression. Our findings suggest that ADAR1p150 plays a key role in complexing with Dicer and promoting the expression of miRNA-222, the latter of which suppresses the expression of the target gene PTEN during VMC. Our work reveals a previously unknown role of ADAR1p150 in gene expression in VMC.

Viral myocarditis (VMC) is a life-threatening disease that leads to heart failure or cardiac arrhythmia. A large number of researches have revealed that mircroRNAs (miRNAs) participate in the pathological processes of VMC. We previously reported that miR-1 repressed the expression of gap junction protein α1 (GJA1) in VMC. In this study, miR-19b was found to be significantly upregulated using the microarray analysis in a mouse model of VMC, and overexpression of miR-19b led to irregular beating pattern in human cardiomyocytes derived from the induced pluripotent stem cells (hiPSCs-CMs). The upregulation of miR-19b was associated with decreased GJA1 in vivo. Furthermore, a miR-19b inhibitor increased, while its mimics suppressed the expression of GJA1 in HL-1 cells. When GJA1 was overexpressed, the miR-19b mimics-mediated irregular beating was reversed in hiPSCs-CMs. In addition, the effect of miR-19b on GJA1 was enhanced by miR-1 in a dose-dependent manner. These data suggest miR-19b contributes to irregular beating through regulation of GJA1 by cooperating with miR-1. Based on the present and our previous studies, it could be indicated that miR-19b and miR-1 might be critically involved in cardiac arrhythmia associated with VMC.