Mid-term outcomes of endoscopic vein harvesting in coronary artery bypass grafting: a retrospective cohort study.

OBJECTIVES: Endoscopic vein harvesting (EVH) is an alternative technique to obtain the saphenous vein for coronary artery bypass grafting (CABG) surgery. We aimed to evaluate the early and mid-term outcomes of patients with EVH in CABG. METHODS: This cohort study included consecutive isolated CABG patients in Nanjing First Hospital from July 2020 to December 2022 using propensity score matching methods. Patients were classified to EVH group and open vein harvesting (OVH) group according to the vein harvesting methods. The primary outcome was the all-cause death, and the secondary outcomes were major adverse cardiovascular events (MACEs) including cardiovascular death, heart failure, myocardial infarction and revascularization and asymptomatic survival in the follow-up. RESULTS: Totally 1247 patients were included in the study with 849 in OVH group and 398 in EVH group. Patients with EVH were more female, diabetes, higher body mass index, more multi-vessel and left main diseases. 308 pairs were formed after the matching. There was no significant difference in the rates of in-hospital death (EVH vs. OVH, 2.3% vs. 1.3%, P = 0.543). During the 3 years follow-up, EVH grafts were considered not inferior to OVH grafts, no differences were found in all-cause death [8.5% vs. 5.0%, hazard ratio (HR) 1.565, 95% confidence interval (CI): 0.77-3.17, P = 0.21], MACEs (8.1% vs. 7.1%, HR 1.165, 95CI: 0.51-2.69, P = 0.71) and asymptomatic survival (66.7% vs. 72.5%, HR 1.117, 95%CI: 0.65-1.92, P = 0.68). CONCLUSIONS: EVH grafts were considered comparable to OVH grafts in patients following CABG in the 3 years follow-up.

Generalist and topologically central avian frugivores promote plant invasion unequally across land-bridge islands.

Seed dispersal by frugivorous birds facilitates plant invasions, but it is poorly known how invasive plants integrate into native communities in fragmented landscapes. We surveyed plant-frugivore interactions, including an invasive plant (Phytolacca americana), on 22 artificial land-bridge islands (fragmented forests) in the Thousand Island Lake, China. Focusing on frugivory interactions that may lead to seed dispersal, we built ecological networks of studied islands both at the local island (community) and at landscape (metacommunity) levels. On islands with P. americana, we found that P. americana impacted local avian frugivory networks more on islands with species-poor plant communities and on isolated islands. Moreover, as P. americana interacted mainly with local core birds (generalists), this indicates reduced seed dispersal of native plants on invaded islands. At the landscape level, P. americana had established strong interactions with generalist birds that largely maintain seed-dispersal functions across islands, as revealed by their topologically central roles both in the regional plant-bird trophic network and in the spatial metanetwork. This indicates that generalist frugivorous birds may have facilitated the dispersal of P. americana across islands, making P. americana well integrated into the plant-frugivore mutualistic metacommunity. Taken together, our study demonstrates that the impact of plant invasion is context-dependent and that generalist native frugivores with high dispersal potential may accelerate plant invasion in fragmented landscapes. These findings highlight the importance of taking the functional roles of animal mutualists and habitat fragmentation into account when managing plant invasions and their impact on native communities.

Short-Term Mortality Among Pediatric Patients With Heart Diseases Undergoing Veno-Arterial Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation serves as a crucial mechanical circulatory support for pediatric patients with severe heart diseases, but the mortality rate remains high. The objective of this study was to assess the short-term mortality in these patients. METHODS AND RESULTS: We systematically searched PubMed, Embase, and Cochrane Library for observational studies that evaluated the short-term mortality of pediatric patients undergoing veno-arterial extracorporeal membrane oxygenation. To estimate short-term mortality, we used random-effects meta-analysis. Furthermore, we conducted meta-regression and binomial regression analyses to investigate the risk factors associated with the outcome of interest. We systematically reviewed 28 eligible references encompassing a total of 1736 patients. The pooled analysis demonstrated a short-term mortality (defined as in-hospital or 30-day mortality) of 45.6% (95% CI, 38.7%-52.4%). We found a significant difference (P<0.001) in mortality rates between acute fulminant myocarditis and congenital heart disease, with acute fulminant myocarditis exhibiting a lower mortality rate. Our findings revealed a negative correlation between older age and weight and short-term mortality in patients undergoing veno-arterial extracorporeal membrane oxygenation. Male sex, bleeding, renal damage, and central cannulation were associated with an increased risk of short-term mortality. CONCLUSIONS: The short-term mortality among pediatric patients undergoing veno-arterial extracorporeal membrane oxygenation for severe heart diseases was 45.6%. Patients with acute fulminant myocarditis exhibited more favorable survival rates compared with those with congenital heart disease. Several risk factors, including male sex, bleeding, renal damage, and central cannulation contributed to an increased risk of short-term mortality. Conversely, older age and greater weight appeared to be protective factors.

Comparative transcriptome profiling reveals RNA splicing alterations and biological function in patients exposed to occupational noise.

Genetic factors play an important role in susceptibility to noise-induced hearing loss (NIHL). Alternative splicing (AS) is an essential mechanism affecting gene expression associated with disease pathogenesis at the post-transcriptional level, but has rarely been studied in NIHL. To explore the role of AS in the development of NIHL, we performed a comprehensive analysis of RNA splicing alterations by comparing the RNA-seq data from blood samples from NIHL patients and subjects with normal hearing who were exposed to the same noise environment. A total of 356 differentially expressed genes, including 23 transcription factors, were identified between the two groups. Of particular note was the identification of 56 aberrant alternative splicing events generated by 41 differentially expressed genes between the two groups, with exon skipping events accounting for 54% of all the differentially alternative splicing (DAS) events. The results of functional enrichment analysis showed that these intersecting DAS genes and differentially expressed genes were significantly enriched in autophagy and mitochondria-related pathways. Together, our findings provide insights into the role of AS events in susceptibility and pathogenesis of NIHL.

The safety and efficacy of emergency stenting during bridging therapy: A Single-Center Retrospective Study.

INTRODUCTION: To investigated the safety and efficacy of emergency stenting for patients with ischemic stroke treated with bridging therapy. METHODS: Patients with onset of stroke who underwent bridging therapy were included in the two groups with emergency stenting (ESG) and without stenting (NSG). To avoid the bias due to confounding variables, subjects were further assigned in two groups using 1:1 propensity score matching (PSM). The safety outcomes include the incidence of intracranial hemorrhage (ICH), parenchymal hemorrhage type 2 (PH2), symptomatic intracranial hemorrhage (sICH), fatal hemorrhage, and mortality. The efficacy outcomes include successful recanalization, three-month favorable outcome (modified Rankin Scale [mRS]: 0-2). RESULTS: 175 patients treated with bridging therapy were included in this study, with 52 patients in the ES group and 123 patients in the groups without ES, and with 30 patients in each group after PSM. No significant differences in the incidences of ICH, PH2, sICH, fatal hemorrhage, and mortality were found between the two groups with ES and without ES before and after PSM (P>0.05 for all groups). The analysis without PSM showed that the group with ES had a higher rate of successful recanalization (98.1% vs. 81.6%，P=0.041) than the group without ES, but no significant difference was seen (96.6% vs. 93.3%，P=0.554) between the two groups after PSM. There was no difference in favorable outcome between the two groups before and after matching as well (P>0.05). CONCLUSIONS: It is safe and effective for patients with onset of ischemic stroke to receive emergency stenting during bridging therapy, without increasing the risk of hemorrhagic transformation and mortality.

Aided diagnosis of thyroid nodules based on an all-optical diffraction neural network.

Background: Thyroid cancer is the most common malignancy in the endocrine system, with its early manifestation being the presence of thyroid nodules. With the advantages of convenience, noninvasiveness, and a lack of radiation, ultrasound is currently the first-line screening tool for the clinical diagnosis of thyroid nodules. The use of artificial intelligence to assist diagnosis is an emerging technology. This paper proposes the use optical neural networks for potential application in the auxiliary diagnosis of thyroid nodules. Methods: Ultrasound images obtained from January 2013 to December 2018 at the Institute and Hospital of Oncology, Tianjin Medical University, were included in a dataset. Patients who consecutively underwent thyroid ultrasound diagnosis and follow-up procedures were included. We developed an all-optical diffraction neural network to assist in the diagnosis of thyroid nodules. The network is composed of 5 diffraction layers and 1 detection plane. The input image is placed 10 mm away from the first diffraction layer. The input of the diffractive neural network is light at a wavelength of 632.8 nm, and the output of this network is determined by the amplitude and light intensity obtained from the detection region. Results: The all-optical neural network was used to assist in the diagnosis of thyroid nodules. In the classification task of benign and malignant thyroid nodules, the accuracy of classification on the test set was 97.79%, with an area under the curve value of 99.8%. In the task of detecting thyroid nodules, we first trained the model to determine whether any nodules were present and achieved an accuracy of 84.92% on the test set. Conclusions: Our study demonstrates the potential of all-optical neural networks in the field of medical image processing. The performance of the models based on optical neural networks is comparable to other widely used network models in the field of image classification.

Pulmonary Nodule Detection and Classification Using All-Optical Deep Diffractive Neural Network.

A deep diffractive neural network (D2NN) is a fast optical computing structure that has been widely used in image classification, logical operations, and other fields. Computed tomography (CT) imaging is a reliable method for detecting and analyzing pulmonary nodules. In this paper, we propose using an all-optical D2NN for pulmonary nodule detection and classification based on CT imaging for lung cancer. The network was trained based on the LIDC-IDRI dataset, and the performance was evaluated on a test set. For pulmonary nodule detection, the existence of nodules scanned from CT images were estimated with two-class classification based on the network, achieving a recall rate of 91.08% from the test set. For pulmonary nodule classification, benign and malignant nodules were also classified with two-class classification with an accuracy of 76.77% and an area under the curve (AUC) value of 0.8292. Our numerical simulations show the possibility of using optical neural networks for fast medical image processing and aided diagnosis.

Long divergent haplotypes introgressed from wild sheep are associated with distinct morphological and adaptive characteristics in domestic sheep.

The worldwide sheep population comprises more than 1000 breeds. Together, these exhibit a considerable morphological diversity, which has not been extensively investigated at the molecular level. Here, we analyze whole-genome sequencing individuals of 1,098 domestic sheep from 154 breeds, and 69 wild sheep from seven Ovis species. On average, we detected 6.8%, 1.0% and 0.2% introgressed sequence in domestic sheep originating from Iranian mouflon, urial and argali, respectively, with rare introgressions from other wild species. Interestingly, several introgressed haplotypes contributed to the morphological differentiations across sheep breeds, such as a RXFP2 haplotype from Iranian mouflon conferring the spiral horn trait, a MSRB3 haplotype from argali strongly associated with ear morphology, and a VPS13B haplotype probably originating from urial and mouflon possibly associated with facial traits. Our results reveal that introgression events from wild Ovis species contributed to the high rate of morphological differentiation in sheep breeds, but also to individual variation within breeds. We propose that long divergent haplotypes are a ubiquitous source of phenotypic variation that allows adaptation to a variable environment, and that these remain intact in the receiving population probably due to reduced recombination.

Design and characterization of a high-resolution multiple-SNP capture array by target sequencing for sheep.

The efficiency of molecular breeding largely depends on inexpensive genotyping arrays. In this study, we aimed to develop an ovine high-resolution multiple-single-nucleotide polymorphism (SNP) capture array, based on genotyping by target sequencing (GBTS) system with capture-in-solution (liquid chip) technology. All the markers were from 40K captured regions, including genes located within selective sweep regions, breed-specific regions, quantitative trait loci (QTL), and the potential functional SNPs on the sheep genome. The results showed that a total of 210K high-quality SNPs were identified in the 40K regions, indicating a high average capture ratio (99.7%) for the target genomic regions. Using genotyped data (n = 317) from liquid chip technology, we further performed genome-wide association studies (GWAS) to detect the genetic loci affecting sheep hair types and teat number. A single significant association signal for hair types was identified on 6.7-7.1 Mb of chromosome 25. The IRF2BP2 gene (chr25: 7,067,974-7,071,785), which is located within this genomic region, has been previously known to be involved in hair/wool traits in sheep. The results further showed a new candidate region around 26.4 Mb of chromosome 13, between the ARHGAP21 and KIAA1217 genes, that was significantly related to teat number in sheep. The haplotype patterns of this region also showed differences in animals with 2, 3, or 4 teats. Advances in using the high-accuracy and low-cost liquid chip are expected to accelerate sheep genomic and breeding studies in the coming years.

Large-scale genotyping platforms are valuable tools for animal selection and breeding programs. The bead chip has been widely used in both research and commercial applications for a long time. A highly efficient and economical genotyping platform has been developed recently. In the present study, by combining the advantages of resequencing and bead chips, we developed a high-resolution capture array based on target sequencing with capture-in-solution technology (liquid chip), including updated functional probes according to the latest research. We further evaluated this approach by using 317 individuals and found that 210K single-nucleotide polymorphisms can be accurately genotyped, confirming the ratio of the captured regions compared with the designed rations is around 99.7%. Genome-wide association studies conducted using this chip suggested IRF2BP2 gene may be involved in hair types and ARHGAP21-KIAA1217 locus may be related to teats number. The liquid chip with high accuracy and low cost can be widely used in genome-wide association studies and genome selection, supporting efforts in molecular breeding and genetic improvement of sheep.

Estrogen receptor α regulates phenotypic switching and proliferation of vascular smooth muscle cells through the NRF1-OMI-mitophagy signaling pathway under simulated microgravity.

Vascular remodeling during microgravity exposure results in postflight cardiovascular deconditioning and orthostatic intolerance in astronauts. To clarify the underlying mechanism, we investigated whether estrogen receptor α (ERα)-NRF1-OMI-mitophagy signaling was involved in the dedifferentiation and proliferation of vascular smooth muscle cells (VSMCs) under simulated microgravity. Phenotypic markers, mtDNA copy number and mitochondrial biogenesis, mitochondrial dynamics and mitophagy in rat thoracic artery smooth muscle cells were examined. Four-week hindlimb unweighting (HU) was used to simulate microgravity in rats and 10% serum was used to induce VSMCs dedifferentiation in vitro. The effects of ERα-NRF1-OMI signaling on mitophagy, phenotypic switching and proliferation of VSMCs, and cerebrovascular remodeling in HU rats were studied by genetic manipulation and chronic drug intervention. We found that ERα is positively associated with contractile phenotype switching but inversely correlated with synthetic phenotype switching and proliferation of VSMCs both in vivo and in vitro. During the dedifferentiation process of VSMCs, reduced mtDNA copy number, disturbed mitochondrial biogenesis and respiration, and perturbed fission-fusion-mitophagy signaling were detected, which were reversed by ERα overexpression. Mechanistically, the ERα downstream protein OMI preserved the mitochondrial Parkin level by increasing its protein stability, thereby protecting mitophagy. In line with this, we found that activating ERα signaling by propyl pyrazole triol (PPT) could alleviate the synthetic phenotype switching and proliferation of HU rat cerebral VSMCs by reestablishing fission-fusion-mitophagy hemostasis. The current study clarified a novel mechanism by which inhibited ERα-NRF1-OMI-mitophagy signaling resulted in synthetic phenotype switching and proliferation of VSMCs and cerebrovascular remodeling under simulated microgravity.

Identification of hub biomarkers and immune cell infiltration characteristics of polymyositis by bioinformatics analysis.

Background: Polymyositis (PM) is an acquirable muscle disease with proximal muscle involvement of the extremities as the main manifestation; it is a category of idiopathic inflammatory myopathy. This study aimed to identify the key biomarkers of PM, while elucidating PM-associated immune cell infiltration and immune-related pathways. Methods: The gene microarray data related to PM were downloaded from the Gene Expression Omnibus database. The analyses using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) networks were performed on differentially expressed genes (DEGs). The hub genes of PM were identified using weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) algorithm, and the diagnostic accuracy of hub markers for PM was assessed using the receiver operating characteristic curve. In addition, the level of infiltration of 28 immune cells in PM and their interrelationship with hub genes were analyzed using single-sample GSEA. Results: A total of 420 DEGs were identified. The biological functions and signaling pathways closely associated with PM were inflammatory and immune processes. A series of four expression modules were obtained by WGCNA analysis, with the turquoise module having the highest correlation with PM; 196 crossover genes were obtained by combining DEGs. Subsequently, six hub genes were finally identified as the potential biomarkers of PM using LASSO algorithm and validation set verification analysis. In the immune cell infiltration analysis, the infiltration of T lymphocytes and subpopulations, dendritic cells, macrophages, and natural killer cells was more significant in the PM. Conclusion: We identified the hub genes closely related to PM using WGCNA combined with LASSO algorithm, which helped clarify the molecular mechanism of PM development and might have great significance for finding new immunotherapeutic targets, and disease prevention and treatment.

Potential of immune-related genes as promising biomarkers for premature coronary heart disease through high throughput sequencing and integrated bioinformatics analysis.

Background: Coronary heart disease (CHD) is the most common progressive disease that is difficult to diagnose and predict in the young asymptomatic period. Our study explored a mechanistic understanding of the genetic effects of premature CHD (PCHD) and provided potential biomarkers and treatment targets for further research through high throughput sequencing and integrated bioinformatics analysis. Methods: High throughput sequencing was performed among recruited patients with PCHD and young healthy individuals, and CHD-related microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by using R software. Enrichment analysis and CIBERSORT were performed to explore the enriched pathways of DEGs and the characteristics of infiltrating immune cells. Hub genes identified by protein-protein interaction (PPI) networks were used to construct the competitive endogenous RNA (ceRNA) networks. Potential drugs were predicted by using the Drug Gene Interaction Database (DGIdb). Results: A total of 35 DEGs were identified from the sequencing dataset and GEO database by the Venn Diagram. Enrichment analysis indicated that DEGs are mostly enriched in excessive immune activation pathways and signal transduction. CIBERSORT exhibited that resting memory CD4 T cells and neutrophils were more abundant, and M2 macrophages, CD8 T cells, and naïve CD4 T cells were relatively scarce in patients with PCHD. After the identification of 10 hub gens, three ceRNA networks of CD83, CXCL8, and NR4A2 were constructed by data retrieval and validation. In addition, CXCL8 might interact most with multiple chemical compounds mainly consisting of anti-inflammatory drugs. Conclusions: The immune dysfunction mainly contributes to the pathogenesis of PCHD, and three ceRNA networks of CD83, CXCL8, and NR4A2 may be potential candidate biomarkers for early diagnosis and treatment targets of PCHD.

Pathogenesis of premature coronary artery disease: Focus on risk factors and genetic variants.

The development of premature coronary artery disease (PCAD) is dependent on both genetic predisposition and traditional risk factors. Strategies for unraveling the genetic basis of PCAD have evolved with the advent of modern technologies. Genome-wide association studies (GWASs) have identified a considerable number of common genetic variants that are associated with PCAD. Most of these genetic variants are attributable to lipid and blood pressure-related single-nucleotide polymorphisms (SNPs). The genetic variants that predispose individuals to developing PCAD may depend on race and ethnicity. Some characteristic genetic variants have been identified in Chinese populations. Although translating this genetic knowledge into clinical applications is still challenging, these genetic variants can be used for CAD phenotype identification, genetic prediction and therapy. In this article we will provide a comprehensive review of genetic variants detected by GWASs that are predicted to contribute to the development of PCAD. We will highlight recent findings regarding CAD-related genetic variants in Chinese populations and discuss the potential clinical utility of genetic variants for preventing and managing PCAD.

Anti-inflammatory Therapies for Coronary Heart Disease: A Systematic Review and Meta-Analysis.

Background: Anti-inflammatory therapy has been proposed as a promising treatment for coronary heart disease (CHD) that could reduce residual inflammation risk (RIR) and therefore major adverse cardiovascular events. We implemented a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the clinical benefits of anti-inflammatory agents in patients with CHD based on secondary cardiovascular prevention. Methods: We systemically searched the PubMed, Embase, and Cochrane Library databases for RCTs (published between Jan 1, 1950, and June 1, 2021; no language restrictions) that focused on anti-inflammatory therapy for coronary heart disease. Our primary end points of interest were a composite of all-cause death, recurrent myocardial infarction and stroke. We processed pooled data using a random-effects model. Results: Of 1497 selected studies, 18 studies with 67,449 participants met our inclusion criteria and were included in the present meta-analysis. Comparing anti-inflammatory agents with placebo, there was no significant decrease in risk of primary end points, secondary end points, all-cause mortality, cardiac mortality, recurrent myocardial infarction, stroke or revascularization. Further subgroup analysis indicated that anti-inflammatory agents led to a significant reduction in secondary end points (OR 0.87, CI 0.77-0.99; P = 0.03), recurrent myocardial infarction (OR 0.86, CI 0.78-0.95; P = 0.003) and revascularization (OR 0.81, CI 0.70-0.92; P = 0.001) in patients with stable CHD compared with placebo. Moreover, stable CHD patients had a lower propensity for recurrent myocardial infarction than acute coronary syndrome (ACS) patients when using anti-inflammatory agents (P = 0.03). The colchicine subgroup analysis showed that colchicine yielded a promising reduction in the primary end points (OR 0.81, CI 0.70-0.95; P = 0.009) compared with placebo. Anti-inflammatory agents were associated with a higher risk of infection (OR 1.13, CI 1.03-1.23; P = 0.007) and negligible effects on cancers (OR 0.98, CI 0.90-1.06; P = 0.61). Conclusion: Anti-inflammatory agents appear to have beneficial effects in reducing the risk of recurrent myocardial infarction in patients with stable CHD, albeit at the cost of increased infection. Notably, colchicine demonstrates a promising cardioprotective effect with a lower incidence of major cardiovascular events and thus is a potential therapeutic strategy for stable CHD patients. Systematic Review Registration: PROSPERO, identifier CRD42021245514.

GGVD: A goat genome variation database for tracking the dynamic evolutionary process of selective signatures and ancient introgressions.

Understanding the evolutionary history and adaptive process depends on the knowledge that we can acquire from both ancient and modern genomic data. With the availability of a deluge of whole-genome sequencing data from ancient and modern goat samples, a user-friendly database making efficient reuse of these important resources is needed. Here, we use the genomes of 208 modern domestic goats, 24 bezoars, 46 wild ibexes, and 82 ancient goats to present a comprehensive goat genome variation database (GGVD). GGVD hosts a total of ∼41.44 million SNPs, ∼5.14 million indels, 6,193 selected loci, and 112 introgression regions. Users can freely visualize the frequency of genomic variations in geographical maps, selective sweeps in interactive tables, Manhattan plots, or line charts, as well as the heatmap patterns of the SNP genotype. Ancient data can be shown in haplotypes to track the state of genetic variants of selection and introgression events in the early, middle, and late stages. For facilitating access to sequence features, the UCSC Genome Browser, BLAT, BLAST, LiftOver, and pcadapt are also integrated into GGVD. GGVD will be a convenient tool for population genetic studies and molecular marker designing in goat breeding programs, and it is publicly available at http://animal.nwsuaf.edu.cn/GoatVar.

Military medical research on internal diseases in modern warfare: new concepts, demands, challenges, and opportunities.

Battlefield internal medicine aims at the treatment of combatants and noncombatants with various internal diseases on the battlefield. The military medical research on battlefield internal diseases focuses on the pathogenesis, clinical management, and prevention of internal diseases under military war conditions. In both wartime and peacetime, the soldiers suffer from more internal diseases than surgical wounds. With the introduction of high-tech weapons, including chemical, physical, and biological agents, a large number of special internal illnesses and casualties will appear in future wars. The battles often occur in special environments, such as high or low temperatures, plateau or polar areas, and micro- or hyper-gravity. The current theories of battlefield internal medicine are mainly derived from wars decades ago and cannot meet the needs of military medical support under the conditions of modern warfare. Therefore, the military medical research on battlefield internal medicine should be based on contemporary military situations, focus on the purpose of treating battlefield internal diseases, and adhere to the actual needs of the troops in peacetime and wartime. We should investigate the pathogenesis of battlefield internal diseases and explore the threats that may arise in future wars to ensure the advancement of battlefield internal medicine. This review highlights new concepts, demands, challenges, and opportunities for the further development of military medical research on battlefield internal medicine.

Targeting PTEN to regulate autophagy and promote the repair of injured neurons.

The effects of autophagy on neuronal damage can be positive or detrimental negative. Through establishing a model of fetal rat cortical neuron hydraulic shock injury, dipotassium bisperoxo (picolinoto) oxovanadate (V) [bpv(pic)] was used to inhibit PTEN at different time points post-injury and autophagy level after neuronal injury was assessed. Neurons were divided into several intervention groups according to the time point at which bpv(pic) was used to inhibit autophagy, normal neurons and injuried neurons were set as two control groups. Growth of neurons in each group was assessed through immunofluorescence staining. Expression of the autophagy-related proteins LC3-II and LC3-I was analyzed by western blot. Expression of PTEN, mTOR and Beclin-1 was detected by RT-PCR. The number of autophagosomes in the normal group, injury control group and 24 h, 36 h intervention groups were assessed by electron microscope. We found that autophagy was enhanced after neuronal injury and that the levels of LC3-II was significantly reduced by bpv (pic) intervention. The growth of the injury control groups was worse than normal groups, while improved through bpv(pic) intervention at 24 h and 30 h after injured. Western blot analysis showed that the LC3-II and LC3-II/LC3-I ratios of cells increased post-injury, and autophagy induction was evident by electron microscopy. These effects were confirmed by RT-PCR analysis. Taken together, these data suggest that autophagy is activated after injury in neurons while can be inhibited by bpv(pic) administration and then promote the repair of injured neurons.

Immune and Inflammation in Acute Coronary Syndrome: Molecular Mechanisms and Therapeutic Implications.

Acute coronary syndrome (ACS) is a major cause of acute death worldwide. Both innate and adaptive immunity regulate atherosclerosis progression, plaque stability, and thrombus formation. Immune and inflammation dysfunction have been indicated in the pathogenesis of ACS. The imbalance in the proatherogenic and antiatherogenic immune networks promotes the transition of plaques from a stable to unstable state and results in the occurrence of acute coronary events. The residual inflammatory risk (RIR) has received increasing attention in recent years, and lowering RIR has been expected to improve the outcomes of ACS patients. The CANTOS, COLCOT, and LoDoCo trials verified the benefits of reducing cardiovascular events using anti-inflammation therapies; however, most of the other studies focusing on lowering RIR produced negative or contradicting results. Therefore, restoring the balance in autoimmune regulation is essential because proatherogenic and antiatherogenic immunomodulatory effects are equally important in the complex human immune network. In this review, we summarized the recent evidence of the roles of proatherogenic and antiatherogenic immune networks in the pathogenesis of ACS and discussed how immune and inflammation contribute to atherosclerosis progression, plaque instability, and adverse cardiovascular events. We also provide a "from bench to bedside" perspective of a novel and promising personalized strategy in RIR intervention and therapeutic approaches for the treatment of ACS.

Comparative Transcriptome Profiling Analysis Uncovers Novel Heterosis-Related Candidate Genes Associated with Muscular Endurance in Mules.

Heterosis has been widely exploited in animal and plant breeding programs to enhance the productive traits of hybrid progeny from two breeds or species. However, its underlying genetic mechanisms remain enigmatic. Transcriptome profiling analysis can be used as a method for exploring the mechanism of heterosis. Here, we performed genome-wide gene expression and alternative splicing (AS) analyses in different tissues (muscle, brain, and skin) from crosses between donkeys and horses. Our results indicated that 86.1% of the differentially expressed genes (DEGs) and 87.2% of the differential alternative splicing (DAS) genes showed over-dominance and dominance in muscle. Further analysis showed that the "muscle contraction" pathway was significantly enriched for both the DEGs and DAS genes in mule muscle tissue. Taken together, these DEGs and DAS genes could provide an index for future studies of the genetic and molecular mechanism of heterosis in the hybrids of donkey and horse.