Genetically predicted lipid traits mediate the association between folic acid and atherosclerosis.

Atherosclerosis (AS) is one of the most common causes of death from cardiovascular disease, and low folic acid (FA) levels have been reported to be strongly associated with an increased risk of AS. We aimed to obtain causal estimates of the association between FA and AS and to quantify the mediating role of known modifiable risk factors. Based on the largest genome-wide association study (GWAS) from the IEU Open GWAS Project for all human studies, we conducted a two-sample Mendelian randomization (MR) study of genetically predicted FA and AS. A two-step MR design was then used to assess the causal mediating effect of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) on the relationship between FA and AS. This MR analysis showed that genetically determined FA levels [IVW: Odds Ratio (OR) = 0.623, 95% CI 0.421-0.924, P = 0.018] were associated with a reduced risk of AS. Inverse variance weighted (IVW) MR analysis also showed that genetically predicted FA was positively correlated with HDL-C levels (OR = 1.358, 95% CI 1.029-1.792, P = 0.031) and negatively correlated with LDL-C (OR = 0.956, 95% CI 0.920-0.994, P = 0.023) and TG levels (OR = 0.929, 95% CI 0.886-0.974, P = 0.003). LDL-C, HDL-C, and TG mediate 3.00%, 6.80%, and 4.40%, respectively, of the total impact of FA on AS. The combined effect of these three factors accounts for 13.04% of the total effect. Sensitivity analysis verifies the stability and reliability of the results. These results support a potential causal protective effect of FA on AS, with considerable mediation through many modifiable risk factors. Thus, interventions on levels of LDL-C, HDL-C, and TG have the potential to substantially reduce the burden of AS caused by low FA.

Diagnostic Performance of Noninvasive Coronary Computed Tomography Angiography-Derived FFR for Coronary Lesion-Specific Ischemia Based on Deep Learning Analysis.

Background: The noninvasive computed tomography angiography-derived fractional flow reserve (CT-FFR) can be used to diagnose coronary ischemia. With advancements in associated software, the diagnostic capability of CT-FFR may have evolved. This study evaluates the effectiveness of a novel deep learning-based software in predicting coronary ischemia through CT-FFR. Methods: In this prospective study, 138 subjects with suspected or confirmed coronary artery disease were assessed. Following indication of 30%-90% stenosis on coronary computed tomography (CT) angiography, participants underwent invasive coronary angiography and fractional flow reserve (FFR) measurement. The diagnostic performance of the CT-FFR was determined using the FFR as the reference standard. Results: With a threshold of 0.80, the CT-FFR displayed an impressive diagnostic accuracy, sensitivity, specificity, area under the receiver operating characteristic curve (AUC), positive predictive value (PPV), and negative predictive value (NPV) of 97.1%, 96.2%, 97.7%, 0.98, 96.2%, and 97.7%, respectively. At a 0.75 threshold, the CT-FFR showed a diagnostic accuracy, sensitivity, specificity, AUC, PPV, and NPV of 84.1%, 78.8%, 85.7%, 0.95, 63.4%, and 92.8%, respectively. The Bland-Altman analysis revealed a direct correlation between the CT-FFR and FFR (p < 0.001), without systematic differences (p = 0.085). Conclusions: The CT-FFR, empowered by novel deep learning software, demonstrates a strong correlation with the FFR, offering high clinical diagnostic accuracy for coronary ischemia. The results underline the potential of modern computational approaches in enhancing noninvasive coronary assessment.

Exploring the role of CBLB in acute myocardial infarction: transcriptomic, microbiomic, and metabolomic analyses.

BACKGROUND: Specific alterations in gut microbiota and metabolites have been linked to AMI, with CBLB potentially playing an essential role. However, the precise interactions remain understudied, creating a significant gap in our understanding. This study aims to address this by exploring these interactions in CBLB-intervened AMI mice using transcriptome sequencing, 16 S rDNA, and non-targeted metabolite analysis. METHODS: To probe the therapeutic potential and mechanistic underpinnings of CBLB overexpression in AMI, we utilized an integrative multi-omics strategy encompassing transcriptomics, metabolomics, and 16s rDNA sequencing. We selected these particular methods as they facilitate a holistic comprehension of the intricate interplay between the host and its microbiota, and the potential effects on the host's metabolic and gene expression profiles. The uniqueness of our investigation stems from utilizing a multi-omics approach to illuminate the role of CBLB in AMI, an approach yet unreported to the best of our knowledge. Our experimental protocol encompassed transfection of CBLB lentivirus-packaged vectors into 293T cells, followed by subsequent intervention in AMI mice. Subsequently, we conducted pathological staining, fecal 16s rDNA sequencing, and serum non-targeted metabolome sequencing. We applied differential expression analysis to discern differentially expressed genes (DEGs), differential metabolites, and differential microbiota. We performed protein-protein interaction analysis to identify core genes, and conducted correlation studies to clarify the relationships amongst these core genes, paramount metabolites, and key microbiota. RESULTS: Following the intervention of CBLB in AMI, we observed a significant decrease in inflammatory cell infiltration and collagen fiber formation in the infarcted region of mice hearts. We identified key changes in microbiota, metabolites, and DEGs that were associated with this intervention. The findings revealed that CBLB has a significant correlation with DEGs, differential metabolites and microbiota, respectively. This suggests it could play a pivotal role in the regulation of AMI. CONCLUSION: This study confirmed the potential of differentially expressed genes, metabolites, and microbiota in AMI regulation post-CBLB intervention. Our findings lay groundwork for future exploration of CBLB's role in AMI, suggesting potential therapeutic applications and novel research directions in AMI treatment strategies.

Diagnostic performance of the quantitative flow ratio and CT-FFR for coronary lesion-specific ischemia.

Fractional flow reserve (FFR) has become the gold standard for evaluating coronary lesion-specific ischemia. However, FFR is an invasive method that may cause possible complications in the coronary artery and requires expensive equipment, which limits its use. Promising noninvasive diagnostic methods, such as computed tomography angiography-derived FFR (CT-FFR) and the quantitative flow ratio (QFR), have been proposed. In this study, we evaluated the diagnostic performance of the QFR and CT-FFR in predicting coronary lesion-specific ischemia, with the FFR serving as the reference standard. Patients with suspected or known coronary artery disease who underwent coronary CT angiography revealing 30-90% diameter stenosis in the main coronary artery (≥ 2.0 mm reference diameter) were enrolled. The FFR was measured during invasive coronary angiography (within 15 days after coronary CT angiography). An FFR ≤ 0.8 was the reference standard for coronary lesion-specific ischemia. A total of 103 vessels from 92 consecutive patients (aged 59.8 ± 9.2 years; 60.9% were men) were evaluated. The diagnostic performance of a QFR ≤ 0.80 for predicting coronary lesion-specific ischemia demonstrated good diagnostic accuracy, sensitivity, and specificity (92.2%, 87.2%, and 96.4%, respectively), with an area under the receiver operating characteristic curve (AUC) of 0.987 (P < 0.0001). The diagnostic performance of a CT-FFR ≤ 0.80 for predicting coronary lesion-specific ischemia also demonstrated good diagnostic accuracy, sensitivity, and specificity (96.1%, 95.7%, and 96.4%, respectively), with an AUC of 0.967 (P < 0.0001). However, there was no significant difference in the AUC between a QFR ≤ 0.80 and a CT-FFR ≤ 0.80 for predicting coronary lesion-specific ischemia (P = 0.319). There was an excellent correlation between the QFR and FFR (r = 0.856, P < 0.0001). The CT-FFR and FFR also showed a good direct correlation (r = 0.816, P < 0.0001). The QFR and CT-FFR are strongly correlated with the FFR and can provide excellent clinical diagnostic performance for coronary lesion-specific ischemia detection.

Identification of necroptosis-related diagnostic biomarkers in coronary heart disease.

Background: The implication of necroptosis in cardiovascular disease was already recognized. However, the molecular mechanism of necroptosis has not been extensively studied in coronary heart disease (CHD). Methods: The differentially expressed genes (DEGs) between CHD and control samples were acquired in the GSE20681 dataset downloaded from the GEO database. Key necroptosis-related DEGs were captured and ascertained by bioinformatics analysis techniques, including weighted gene co-expression network analysis (WGCNA) and two machine learning algorithms, while single-gene gene set enrichment analysis (GSEA) revealed their molecular mechanisms. The diagnostic biomarkers were selected via receiver operating characteristic (ROC) analysis. Moreover, an analysis of immune elements infiltration degree was carried out. Authentication of pivotal gene expression at the mRNA level was investigated in vitro utilizing quantitative real-time PCR (qRT-PCR). Results: A total of 94 DE-NRGs were recognized here, among which, FAM166B, NEFL, POLDIP3, PRSS37, and ZNF594 were authenticated as necroptosis-related biomarkers, and the linear regression model based on them presented an acceptable ability to different sample types. Following regulatory analysis, the ascertained biomarkers were markedly abundant in functions pertinent to blood circulation, calcium ion homeostasis, and the MAPK/cAMP/Ras signaling pathway. Single-sample GSEA exhibited that APC co-stimulation and CCR were more abundant, and aDCs and B cells were relatively scarce in CHD patients. Consistent findings from bioinformatics and qRT-PCR analyses confirmed the upregulation of NEFL and the downregulation of FAM166B, POLDIP3, and PRSS37 in CHD. Conclusion: Our current investigation identified 5 necroptosis-related genes that could be diagnostic markers for CHD and brought a novel comprehension of the latent molecular mechanisms of necroptosis in CHD.

Ultrafast universal fabrication of configurable porous silicone-based elastomers by Joule heating chemistry.

Silicone-based elastomers (SEs) have been extensively applied in numerous cutting-edge areas, including flexible electronics, biomedicine, 5G smart devices, mechanics, optics, soft robotics, etc. However, traditional strategies for the synthesis of polymer elastomers, such as bulk polymerization, suspension polymerization, solution polymerization, and emulsion polymerization, are inevitably restricted by long-time usage, organic solvent additives, high energy consumption, and environmental pollution. Here, we propose a Joule heating chemistry method for ultrafast universal fabrication of SEs with configurable porous structures and tunable components (e.g., graphene, Ag, graphene oxide, TiO2, ZnO, Fe3O4, V2O5, MoS2, BN, g-C3N4, BaCO3, CuI, BaTiO3, polyvinylidene fluoride, cellulose, styrene-butadiene rubber, montmorillonite, and EuDySrAlSiOx) within seconds by only employing H2O as the solvent. The intrinsic dynamics of the in situ polymerization and porosity creation of these SEs have been widely investigated. Notably, a flexible capacitive sensor made from as-fabricated silicone-based elastomers exhibits a wide pressure range, fast responses, long-term durability, extreme operating temperatures, and outstanding applicability in various media, and a wireless human-machine interaction system used for rescue activities in extreme conditions is established, which paves the way for more polymer-based material synthesis and wider applications.

miR-200a-3p overexpression alleviates diabetic cardiomyopathy injury in mice by regulating autophagy through the FOXO3/Mst1/Sirt3/AMPK axis.

Objective: Hyperglycemia and insulin resistance or deficiency are characteristic features of diabetes. Diabetes is accompanied by cardiomyocyte hypertrophy, fibrosis and ventricular remodeling, and eventually heart failure. In this study, we established a diabetic cardiomyopathy (DCM) mouse model to explore the role and mechanism of miR-200a-3p in DCM. Methods: We used db/db mice to simulate the animal model of DCM and the expression of miR-200a-3p was then examined by RT-qPCR. Tail vein injection of mice was done with rAAV-miR-200a-3p for 8 weeks, and cardiac function was assessed by cardiac ultrasound. The levels of myocardial tissue injury, fibrosis, inflammation, apoptosis and autophagy in mice were detected by histological staining, TUNEL and other molecular biological experiments. Results: miR-200a-3p expression levels were significantly decreased in the myocardium of DCM mice. Diabetic mice developed cardiac dysfunction and presented pathological changes such as myocardial injury, myocardial interstitial fibrosis, cardiomyocyte apoptosis, autophagy, and inflammation. Overexpression of miR-200a-3p expression significantly ameliorated diabetes induced-cardiac dysfunction and myocardial injury, myocardial interstitial fibrosis, cardiomyocyte apoptosis, and inflammation, and enhanced autophagy. Mechanistically, miR-200a-3p interacted with FOXO3 to promote Mst1 expression and reduce Sirt3 and p-AMPK expression. Conclusion: In type 2 diabetes, increased miR-200a-3p expression enhanced autophagy and participated in the pathogenic process of cardiomyopathy throug7 Mst1/Sirt3/AMPK axis regulation by its target gene FOXO3. This conclusion provides clues for the search of new gene targeted therapeutic approaches for diabetic cardiomyopathy.

Multi-omics analysis identifies potential mechanisms by which high glucose accelerates macrophage foaming.

Atherosclerotic morbidity is significantly higher in the diabetic population. Hyperglycemia, a typical feature of diabetes, has been proven to accelerate foam cell formation. However, the molecular mechanisms behind this process remain unclear. In this study, LPS and IFN-γ were used to convert THP-1-derived macrophages into M1 macrophages, which were then activated with ox-LDL in either high glucose or normal condition. We identified lipids within macrophages by Oil red O staining and total cholesterol detection. The genes involved in lipid absorption, efflux, inflammation, and metabolism were analyzed using qRT-PCR. The mechanisms of high glucose-induced foam cell formation were further investigated through metabolomics and transcriptomics analysis. We discovered that high glucose speed up lipid accumulation in macrophages (both lipid droplets and total cholesterol increased), diminished lipid efflux (ABCG1 down-regulation), and aggravated inflammation (IL1B and TNF up-regulation). Following multi-omics analysis, it was determined that glucose altered the metabolic and transcriptional profiles of macrophages, identifying 392 differently expressed metabolites and 293 differentially expressed genes, respectively. Joint pathway analysis suggested that glucose predominantly disrupted the glycerolipid, glycerophospholipid, and arachidonic acid metabolic pathways in macrophages. High glucose in the glyceride metabolic pathway, for instance, suppressed the transcription of triglyceride hydrolase (LIPG and LPL), causing cells to deposit excess triglycerides into lipid droplets and encouraging foam cell formation. More importantly, high glucose triggered the accumulation of pro-atherosclerotic lipids (7-ketocholesterol, lysophosphatidylcholine, and glycerophosphatidylcholine). In conclusion, this work elucidated mechanisms of glucose-induced foam cell formation via a multi-omics approach.

Integrated analysis of miRNA-mRNA regulatory network and functional verification of miR-338-3p in coronary heart disease.

Coronary heart disease is a cardiovascular disease with high morbidity and mortality. Although great progress has been made in treatment, the prognosis is still very poor. Therefore, this project aims to screen potential diagnostic markers and therapeutic targets related to the progression of coronary heart disease. A total of 94 overlapping differentially expressed mRNAs and 70 differentially expressed miRNAs were identified from GSE20681, GSE12288, GSE49823, and GSE105449. Through a series of bioinformatics methods and experiment, we obtained 5 core miRNA-mRNA regulatory pairs, and selected miR-338-3p/RPS23 for functional analysis. Moreover, we found that RPS23 directly targets miR-338-3p by dual luciferase assay, western, and qPCR. And the expression of miR-338-3p and RPS23 is negatively correlated. The AUC value of miR-338-3p is 0.847. Downregulation of miR-338-3p can significantly inhibit the proliferation and migration of HUVEC. On the contrary, overexpression of miR-338-3p promoted the proliferation and migration of HUVEC. In addition, the interference of RPS23 expression can reverse the regulation of miR-338-3p on HUVEC proliferation. In conclusion, miR-338-3p/RPS23 may be involved in the progression of coronary heart disease, and miR-338-3p may be a diagnostic biomarker and therapeutic target for coronary heart disease.

Efficacy and safety of drug-coated balloon combined with cutting balloon for side branch of true coronary bifurcation lesions: Study protocol for a multicenter, prospective, randomized controlled trial.

Background: Coronary bifurcation lesions are common of percutaneous coronary intervention (PCI), and the optimal interventional therapy strategy is still a matter of debate and remains a challenge for interventional cardiologists. The provisional stenting technique is still a preferred method for most bifurcation lesions, but restenosis of the side branch (SB) occurs in approximately 17-19% of cases. Therefore, the dilemma of reducing SB restenosis still exists, and further research on strategies to reduce restenosis for SB is necessary. Drug-coated balloon (DCB) can reduce clinical events in small vessel disease and in-stent restenosis. The efficacy and safety of DCB for SB of true coronary bifurcation lesions have not been fully investigated. A randomized comparison of DCB combined with cutting balloon angioplasty vs. cutting balloon angioplasty for SB has never been published. Methods and design: The purpose of this study is to explore the superiority of DCB combined with cutting balloon vs. cutting balloon angioplasty for SB after main vessel (MV) drug-eluting stent implantation of true coronary bifurcation lesions. This study is a multicenter, prospective, randomized controlled trial including 140 patients with true coronary bifurcation lesions. Patients will be randomized in a 1:1 manner to receive either DCB combined with cutting balloon or cutting balloon angioplasty for SB after MV drug-eluting stent implantation. The primary endpoint is the evaluation of late lumen loss (LLL) of SB at the 9-month follow-up. The secondary endpoints include procedural success during initial hospitalization, LLL of MV at the 9-month follow-up, binary angiographic restenosis in MV and SB at the 9-month follow-up, the proportion of patients with a final post-PCI quantitative flow ratio result ≤ 0.80 for SB at the 9-month follow-up, and major adverse cardiac events during the 24-month follow-up. Conclusions: This clinical trial will provide evidence as to whether DCB combined with cutting balloon for SB of true coronary bifurcation lesions is a superior treatment approach. Trial Registration Number: ChiCTR2000040475. Dissemination: The results of this clinical trial will be published in a peer-reviewed journal.

The Alteration of HDL in Patients with AMI Inhibited Angiogenesis by Blocking ERK1/2 Activation.

Objective: High-density lipoprotein (HDL) was found vasoprotective, but numbers of patients with acute myocardial infarction (AMI) have normal or even high levels of pathological HDL (pHDL). So, we investigate the mechanism of pHDL in AMI patients on angiogenesis. Methods: HDL with normal levels from healthy subjects (nHDL, control group, n = 20) and patients with AMI (pHDL, experimental groups, n = 30) were obtained by super high speed centrifugation. Then, effects of HDL on proliferation, migration, angiogenesis, and expression of ERK1/2 and its phosphorylation in human umbilical vein endothelial cells (HUVEC) with or without PD98059 (inhibitor of ERK1/2) preincubation were detected. Results: Compared with the control group (nHDL), HDL from the experimental group (pHDL) significantly inhibited the phosphorylation of ERK1/2, proliferation, migration, and angiogenesis of HUVEC (P < 0.05), while these effects of HDL could substantially be blocked by preincubation of PD98059 (P < 0.05). Conclusion: HDL in AMI patients affects angiogenesis by inhibiting ERK1/2 activation free from HDL levels.

Artificial Intelligence Assisted Topographic Mapping System for Endoscopic Submucosal Dissection Specimens.

Background: Endoscopic submucosal dissection (ESD), a minimally invasive surgery used to treat early gastrointestinal malignancies, has been widely embraced around the world. The gross reconstruction of ESD specimens can facilitate a more precise pathological diagnosis and allow endoscopists to explore lesions thoroughly. The traditional method of mapping is time-consuming and inaccurate. We aim to design a topographic mapping system via artificial intelligence to perform the job automatically. Methods: The topographic mapping system was built using computer vision techniques. We enrolled 23 ESD cases at the Peking Union Medical College Hospital from September to November 2019. The reconstruction maps were created for each case using both the traditional approach and the system. Results: Using the system, the time saved per case ranges from 34 to 3,336 s. Two approaches revealed no significant variations in the shape, size, or tumor area. Conclusion: We developed an AI-assisted system that would help pathologists complete the ESD topographic mapping process rapidly and accurately.

Association of dietary cholesterol and dyslipidemia in Chinese health examinees.

BACKGROUND: The association between dietary cholesterol consumption and dyslipidemia is still in controversy. The study aims to evaluate whether dietary cholesterol intake associated with dyslipidemia and its components in Chinese health examinees. METHODS: A large-scale cross-sectional study was conducted among health examinees of in Shaanxi province. Totally of 8358 participants (3677 male and 4681 female) were included. Dietary cholesterol intake was assessed by validated food frequency questionnaire. Multivariable regression and restricted cubic spline models were used to capture the linear and non-linear association between dietary cholesterol and dyslipidemia. RESULTS: A total of 2429 (29.1%) subjects were newly diagnosed of dyslipidemia, the prevalence was 29.2% in male and 27.7% in female. Mean intake of dietary cholesterol was 213.7 mg/day. After adjusting for all potential confounders including demographics information and lifestyles, higher cholesterol consumption was related to lower risk of dyslipidemia, the ORs (95% CIs) across Q2 to Q4 group were 0.87 (0.60-1.26), 0.80 (0.55-1.18) and 0.61 (0.41-0.91) in female. With further controlling for nutrients principal components, a null association was observed between dietary cholesterol and dyslipidemia and serum lipids, regardless of gender. Results of restricted cubic splines showed that the risk of dyslipidemia decreased slowly until around 300 mg/day in men and 200 mg/day in women, although the non-linear association was not significant. CONCLUSIONS: The study suggested that dietary cholesterol consumption was not associated with dyslipidemia or serum lipids in Chinese health examinees, although a decreased risk was observed before the threshold points.

Vascular damage effect of circulating microparticles in patients with ACS is aggravated by type 2 diabetes.

As a common factor of both type 2 diabetes mellitus (T2DM) and acute coronary syndrome (ACS), circulating microparticles (MPs) may provide a link between these two diseases. The present study compared the content and function of MPs from patients with ACS with or without T2DM. MPs from healthy subjects (n=20), patients with ACS (n=24), patients with T2DM (n=20) and patients with combined ACS and T2DM (n=24) were obtained. After incubating rat thoracic tissue with MPs, the effect of MPs on endothelial­dependent vasodilatation, expression of caveolin­1 and endothelial nitric oxide synthase (eNOS), phosphorylation of eNOS at the S1177 and T495 sites and its association with heat shock protein 90 (Hsp90), and the generation of NO and superoxide anion (O2˙­) were determined. MP concentrations were higher in patients with T2DM and patients with ACS with or without T2DM than in healthy subjects. Moreover, MPs from patients with T2DM or ACS led to impairment in endothelial­dependent vasodilatation, decreased expression of NO, as well as eNOS and its phosphorylation at Ser1177 and association with Hsp90, but increased eNOS phosphorylation at T495, caveolin­1 expression and O2˙­ generation. These effects were strengthened by MPs from patients with ACS combined with T2DM. T2DM not only increased MP content but also resulted in greater vascular impairment effects in ACS. These results may provide novel insight into the treatment of patients with ACS and T2DM.

3D Printed Flexible Strain Sensors: From Printing to Devices and Signals.

The revolutionary and pioneering advancements of flexible electronics provide the boundless potential to become one of the leading trends in the exploitation of wearable devices and electronic skin. Working as substantial intermediates for the collection of external mechanical signals, flexible strain sensors that get intensive attention are regarded as indispensable components in flexible integrated electronic systems. Compared with conventional preparation methods including complicated lithography and transfer printing, 3D printing technology is utilized to manufacture various flexible strain sensors owing to the low processing cost, superior fabrication accuracy, and satisfactory production efficiency. Herein, up-to-date flexible strain sensors fabricated via 3D printing are highlighted, focusing on different printing methods based on photocuring and materials extrusion, including Digital Light Processing (DLP), fused deposition modeling (FDM), and direct ink writing (DIW). Sensing mechanisms of 3D printed strain sensors are also discussed. Furthermore, the existing bottlenecks and future prospects are provided for further progressing research.

[Rosmarinic acid inhibits high glucose-induced cardiomyocyte hypertrophy by activating Parkin-mediated mitophagy].

OBJECTIVE: To evaluate the effect of rosmarinic acid (RA) on mitophagy and hypertrophy of cardiomyocytes exposed to high glucose (HG). METHODS: Rat cardiomyocytes (H9c2) exposed to HG (25 mmol/L) were treated with 50 µmol/L RA or with both RA treatment and Parkin siRNA transfection, with the cells cultured in normal glucose (5.5 mmol/L) and HG as the controls. The expressions of PINK1, Parkin and LC3II/LC3I in the cells were detected by Western blotting. The formation of mitochondrial autophagosomes was observed by transmission electron microscope. Flow cytometry was employed to detect the level of reactive oxygen species (ROS) and apoptotic rate of the cells. The activities of respiratory chain complex enzymes were measured by spectrophotometry. Fluorescence enzyme labeling and 3H-leucine labeling were used for determining the level of membrane potential and protein synthesis rate, respectively. The cell surface area was observed by light microscopy. RESULTS: RA treatment significantly increased the expression levels of PINK1, Parkin and LC3-II/I (P < 0.05), promoted the formation of mitochondrail autophagosome, inhibited the production of reactive oxygen species (P < 0.05), restored the activities of mitochondrial respiratory chain complex enzymes and mitochondrial membrane potential (P < 0.05), inhibited apoptosis (P < 0.05), and reduced the cell surface area and protein synthesis rate of H9c2 cells induced by HG exposure (P < 0.05). The protective effects of RA against HG-induced oxidative stress and cardiomyocyte hypertrophy was obviously blocked by inhibition of mitophagy mediated by transfection with Parkin siRNA (P < 0.05). CONCLUSIONS: RA can protect rat cardiomyocytes against oxidative stress injury and cardiomyocyte hypertrophy induced by HG by activating Parkin-mediated mitophagy.

Neural Stem Cells Direct Axon Guidance via Their Radial Fiber Scaffold.

Neural stem cells directly or indirectly generate all neurons and macroglial cells and guide migrating neurons by using a palisade-like scaffold made of their radial fibers. Here, we describe an unexpected role for the radial fiber scaffold in directing corticospinal and other axons at the junction between the striatum and globus pallidus. The maintenance of this scaffold, and consequently axon pathfinding, is dependent on the expression of an atypical RHO-GTPase, RND3/RHOE, together with its binding partner ARHGAP35/P190A, a RHO GTPase-activating protein, in the radial glia-like neural stem cells within the ventricular zone of the medial ganglionic eminence. This role is independent of RND3 and ARHGAP35 expression in corticospinal neurons, where they regulate dendritic spine formation, axon elongation, and pontine midline crossing in a FEZF2-dependent manner. The prevalence of neural stem cell scaffolds and their expression of RND3 and ARHGAP35 suggests that these observations might be broadly relevant for axon guidance and neural circuit formation.

Metallic Sandwiched-Aerogel Hybrids Enabling Flexible and Stretchable Intelligent Sensor.

Flexible strain sensors have been widely investigated with their rapid development in human-machine interfaces, soft robots, and medical care monitoring. Here, we report a new in situ catalytic strategy toward the fabrication of metallic aerogel hybrids, which are composed of vanadium nitride (VN) nanosheets decorated with well-defined vertically aligned carbon nanotube arrays (VN/CNTs) for the first time. In this architecture, the two-dimensional VN nanosheets as the main bone structure are favorable for the flexible devices due to their excellent structural compatibility during the repetitive deforming process. In addition, the sandwiched aerogel hybrids form highly conductive 3D network, affording outstanding sensitivity for the strain-responsive behaviors. Further, the VN/CNTs-based flexible strain sensors are successfully fabricated, showing a high gauge factor of 386 within a small strain of 10%, fast response, and extraordinary durability. The monitoring of physical signals and an actual real-time human-machine controlling system based on the sensors are also presented.

Signal transducer and activator of transcription 3 promotes the Warburg effect possibly by inducing pyruvate kinase M2 phosphorylation in liver precancerous lesions.

BACKGROUND: Study shows that signal transducer and activator of transcription 3 (STAT3) can increase the Warburg effect by stimulating hexokinase 2 in breast cancer and upregulate lactate dehydrogenase A and pyruvate dehydrogenase kinase 1 in myeloma. STAT3 and pyruvate kinase M2 (PKM2) can also be activated and enhance the Warburg effect in hepatocellular carcinoma. Precancerous lesions are critical to human and rodent hepatocarcinogenesis. However, the underlying molecular mechanism for the development of liver precancerous lesions remains unknown. We hypothesized that STAT3 promotes the Warburg effect possibly by upregulating p-PKM2 in liver precancerous lesions in rats. AIM: To investigate the mechanism of the Warburg effect in liver precancerous lesions in rats. METHODS: A model of liver precancerous lesions was established by a modified Solt-Farber method. The liver pathological changes were observed by HE staining and immunohistochemistry. The transformation of WB-F344 cells induced with N-methyl-N'-nitro-N-nitrosoguanidine and hydrogen peroxide was evaluated by the soft agar assay and aneuploidy. The levels of glucose and lactate in the tissue and culture medium were detected with a spectrophotometer. The protein levels of glutathione S-transferase-π, proliferating cell nuclear antigen (PCNA), STAT3, and PKM2 were examined by Western blot and immunofluorescence. RESULTS: We found that the Warburg effect was increased in liver precancerous lesions in rats. PKM2 and p-STAT3 were upregulated in activated oval cells in liver precancerous lesions in rats. The Warburg effect, p-PKM2, and p-STAT3 expression were also increased in transformed WB-F344 cells. STAT3 activation promoted the clonal formation rate, aneuploidy, alpha-fetoprotein expression, PCNA expression, G1/S phase transition, the Warburg effect, PKM2 phosphorylation, and nuclear translocation in transformed WB-F344 cells. Moreover, the Warburg effect was inhibited by stattic, a specific inhibitor of STAT3, and further reduced in transformed WB-F344 cells after the intervention for PKM2. CONCLUSION: The Warburg effect is initiated in liver precancerous lesions in rats. STAT3 activation promotes the Warburg effect by enhancing the phosphorylation of PKM2 in transformed WB-F344 cells.

Factors Influencing Stent Restenosis After Percutaneous Coronary Intervention in Patients with Coronary Heart Disease: A Clinical Trial Based on 1-Year Follow-Up.

BACKGROUND This study observed the incidence of in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) and discusses the risk factors of ISR based on clinical data, coronary angiography, and stent features, to provide a theoretical basis for the prevention and treatment of ISR. MATERIAL AND METHODS We selected 1132 cases who received stent implantation at the Shaanxi People's Hospital from June 2014 to June 2016 and were followed up by coronary angiography within 1 year. Based on coronary angiography, the cases were divided into ISR and non-ISR groups. ISR was defined as a reduction in lumen diameter by over 50% after PCI. The ISR group consisted of 93 cases and the non-ISR group consisted of 1039 cases. Medical history, biochemical indicators, features of coronary artery lesions, and stent status were analyzed retrospectively. Risk factors of ISR were identified by univariate and multivariate logistic regression analyses. RESULTS Among 1132 cases, 93 cases had ISR, with the overall incidence of 8.21%. Univariate and multivariate logistic regression analyses indicated that postoperative hypersensitive C-reactive protein (hs-CRP) levels (OR=2.309, 1.579-3.375 mg/L), postoperative homocysteine (HCY) levels (OR=2.202, 1.268-3.826 µmol/L), history of diabetes (OR=1.955,1.272-3.003), coronary bifurcation lesions (OR=3.785, 2.246-6.377), and stent length (OR=1.269, 1.179-1.365 mm) were independent risk factors of ISR after PCI (P<0.05). CONCLUSIONS Elevated hs-CRP and HCY levels after PCI, history of diabetes, coronary bifurcation lesions, and greater stent length were associated with a higher risk of ISR. Patients with a higher risk of ISR should receive routine follow-up and intense medication management after PCI to control the risk factors and to reduce ISR.