Identification and exploration of aging-related subtypes and distinctive role of SERPINE1 in heart failure based on single-cell and bulk RNA sequencing data.

Aging is a major risk factor for heart failure (HF) and is the leading cause of death worldwide. Currently, the nature of the relationship between aging and HF is not entirely clear. Herein, this study aimed to explore new diagnostic biomarkers, molecular typing and therapeutic strategies for HF by investigating the biological significance of aging-related genes in HF. A total of 157 differentially expressed genes (DEGs) were screened totally between HF and normal samples, and functional enrichment analysis of DEGs revealed the strong association of HF progression with aging, immune processes and metabolism. Six HF-specific aging-related genes were further identified, and a diagnostic model was developed and validated for good diagnostic efficacy. In addition, we collected blood samples from 10 normal controls and 10 HF patients for RT-qPCR analysis to verify the bioinformation. We also identified two aging-associated subtypes with distinctly different immune infiltration and metabolic microenvironment. Further single-cell sequencing analysis conducted in the study identified SERPINE1 as a key gene in HF. The distinctive role of SERPINE1 fibroblasts was revealed, including three main findings: (I) fibroblasts had a higher proportion and expression of SERPINE1 levels in HF; (II) the ligand-receptor pair MDK-LRP1 made the most contributions in high interactions with other cell types in SERPINE1 fibroblasts; and (III) SERPINE1 fibroblasts were associated with the interaction of extracellular matrix and receptor and may be regulated by the transcription factor EGR1. In conclusion, this study highlights the importance of aging-related genes in diagnosing HF and regulating immune infiltration. We also identified different HF subtypes and a potentially crucial gene, which may provide a better understanding of the molecular-level mechanisms of aging-related HF and aid in developing effective therapeutic strategies.

Tetrahedral Occupied V Ions Enabling Reversible Three-Electron Redox of Cr3+ /Cr6+ in Layered Cathode Materials for Potassium-Ion Batteries.

Reversible three-electron redox of Cr3+ /Cr6+ in layered cathode materials for rechargeable batteries is very attractive in layered cathode materials, which leads to high capacity and energy density for rechargeable batteries. However, the poor reversibility and Cr-ion migration make it very challenging. In this work, by introducing V ions into tetrahedral sites of layer-structured NaCrO2 , reversible three-electron redox of Cr3+ /Cr6+ is realized successfully in NaCr0.92 V0.05 O2 (NCV05) cathode for potassium-ion batteries with a cut-off voltage of 4.0 V. V ions can weaken the attraction of Cr to electrons, leading to enhanced valence change of Cr ions. On the other hand, V in tetrahedral sites can facilitate the reversible migration of Cr between octahedral and tetrahedral sites via coulombic repulsion to realize the reversible redox between Cr3+ and Cr6+ during charge and discharge processes. In addition, V ions can inhibit the phase transition from O3 phase to O'3 phase during the charge process by adjusting the crystal lattices. As a result, the NaCr0.92 V0.05 O2 cathode exhibits a high reversible capacity of 130 mAh g-1 with promising cycle stability and rate capability. The strategy opens new opportunity for developing high-capacity cathode materials for potassium-ion batteries.

Hepatic Krüppel-like factor 14 regulates lipid metabolism in nonalcoholic steatohepatitis mice.

Excessive lipid accumulation is a critical characteristic in the development of nonalcoholic steatohepatitis (NASH). The underlying molecular mechanism, however, is unclear. In this study, we explored whether and how Krüppel-like factor 14 (KLF14) affects hepatic lipid metabolism in NASH. KLF14 expression was detected in NASH patients and mice fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Adeno-associated viruses and adenoviruses were used to alter hepatic KLF14 expression in vivo or in vitro to investigate how KLF14 functions in lipid regulation. The molecular mechanisms were explored using RNA-seq, luciferase reporter, and ChIP assays. The fatty liver phenotype was analyzed histopathologically, and serum and hepatocyte biochemical parameters were measured. The NASH mouse model developed quickly in C57BL/6J mice fed a CDAHFD for 8 weeks. We found that KLF14 expression was decreased in NASH patients and CDAHFD mice. Oleic acid and palmitic acid treatment also reduced KLF14 levels in hepatocytes. KLF14 knockdown downregulated the genes involved in fatty acid oxidation, promoting the progression of hepatic steatosis. In contrast, hepatic KLF14 overexpression alleviated lipid accumulation and oxidative stress in CDAHFD mice. These effects resulted from direct activation of the PPARα signaling pathway. PPARα inhibition diminished the KLF14 overexpression-reduced protective effects against steatosis in OA&PA-treated MPHs and AAV-KLF14-infected CDAHFD mice. These data reveal that hepatic KLF14 regulates lipid accumulation and oxidative stress through the KLF14-PPARα pathway as NASH progresses. KLF14 may be a novel therapeutic target for hepatic steatosis.

Direct Regulation of Alternative Splicing by SMAD3 through PCBP1 Is Essential to the Tumor-Promoting Role of TGF-ß.

In advanced stages of cancers, TGF-ß promotes tumor progression in conjunction with inputs from receptor tyrosine kinase pathways. However, mechanisms that underpin the signaling cooperation and convert TGF-ß from a potent growth inhibitor to a tumor promoter are not fully understood. We report here that TGF-ß directly regulates alternative splicing of cancer stem cell marker CD44 through a phosphorylated T179 of SMAD3-mediated interaction with RNA-binding protein PCBP1. We show that TGF-ß and EGF respectively induce SMAD3 and PCBP1 to colocalize in SC35-positive nuclear speckles, and the two proteins interact in the variable exon region of CD44 pre-mRNA to inhibit spliceosome assembly in favor of expressing the mesenchymal isoform CD44s over the epithelial isoform CD44E. We further show that the SMAD3-mediated alternative splicing is essential to the tumor-promoting role of TGF-ß and has a global influence on protein products of genes instrumental to epithelial-to-mesenchymal transition and metastasis.

Ultrasound-guided stellate ganglion block benefits the postoperative recovery of patients undergoing laparoscopic colorectal surgery: a single-center, double-blinded, randomized controlled clinical trial.

BACKGROUND: With the increasing prevalence of colorectal cancer (CRC), optimizing perioperative management is of paramount importance. This study investigates the potential of stellate ganglion block (SGB), known for its stress response-mediating effects, in improving postoperative recovery. We postulate that preoperative SGB may enhance the postoperative recovery of patients undergoing laparoscopic CRC surgery. METHODS: We conducted a randomized controlled trial of 57 patients undergoing laparoscopic colorectal cancer surgery at a single center. Patients, aged 18-70 years, were randomly assigned to receive either preoperative SGB or standard care. SGB group patients received 10 mL of 0.2% ropivacaine under ultrasound guidance prior to surgery. Primary outcome was time to flatus, with secondary outcomes encompassing time to defecation, lying in bed time, visual analog scale (VAS) pain score, hospital stays, patient costs, intraoperative and postoperative complications, and 3-year mortality. A per-protocol analysis was used. RESULTS: Twenty-nine patients in the SGB group and 28 patients in the control group were analyzed. The SGB group exhibited a significantly shorter time to flatus (mean [SD] hour, 20.52 [9.18] vs. 27.93 [11.69]; p = 0.012), accompanied by decreased plasma cortisol levels (mean [SD], postoperatively, 4.01 [3.42] vs 7.75 [3.13], p = 0.02). Notably, postoperative pain was effectively managed, evident by lower VAS scores at 6 h post-surgery in SGB-treated patients (mean [SD], 4.70 [0.91] vs 5.35 [1.32]; p = 0.040). Furthermore, patients in the SGB group experienced reduced hospital stay length (mean [SD], day, 6.61 [1.57] vs 8.72 [5.13], p = 0.042). CONCLUSIONS: Preoperative SGB emerges as a promising approach to enhance the postoperative recovery of patients undergoing laparoscopic CRC surgery. CLINICAL TRIAL REGISTRATION: ChiCTR1900028404, Principal investigator: Xia Feng, Date of registration: 12/20/2019.

Ultrafast X-ray scattering offers a structural view of excited-state charge transfer.

Intramolecular charge transfer and the associated changes in molecular structure in N,N'-dimethylpiperazine are tracked using femtosecond gas-phase X-ray scattering. The molecules are optically excited to the 3p state at 200 nm. Following rapid relaxation to the 3s state, distinct charge-localized and charge-delocalized species related by charge transfer are observed. The experiment determines the molecular structure of the two species, with the redistribution of electron density accounted for by a scattering correction factor. The initially dominant charge-localized state has a weakened carbon-carbon bond and reorients one methyl group compared with the ground state. Subsequent charge transfer to the charge-delocalized state elongates the carbon-carbon bond further, creating an extended 1.634 Å bond, and also reorients the second methyl group. At the same time, the bond lengths between the nitrogen and the ring-carbon atoms contract from an average of 1.505 to 1.465 Å. The experiment determines the overall charge transfer time constant for approaching the equilibrium between charge-localized and charge-delocalized species to 3.0 ps.

PIEZO mediates a protective mechanism for nematode Caenorhabditis elegans in response to nanoplastics caused dopaminergic neurotoxicity at environmentally relevant concentrations.

Studies have probed nanoplastic toxicity on environmental organisms, but the regulatory role of animal PIEZO-type mechanosensitive ion channel component (PIEZO) remains unclear. Herein, we identified the sole PIEZO in Caenorhabditis elegans (C. elegans), utilizing amino acid homology analysis and Trans-Membrane prediction using Hidden Markov Models (TMHMM). In C. elegans, RNAi knockdown of pezo-1 had no impact on lifespan, body length, lethality, locomotion behaviors, or oxidative response (P > 0.05). However, exposure to 15 µg/L nanopolystyrene in the pezo-1 RNAi group resulted in severe locomotion changes: head trashes (P < 0.01), body bends (P < 0.05), forward turns (P < 0.05), backward turns (P < 0.01), and impaired sensory perception, including abnormal chemotaxis to NaCl (P < 0.01) and diacetyl (P < 0.01), as well as aversive responses (P < 0.05) to nanopolystyrene compared to the wild-type group. Dopaminergic neuron damage explains these behaviors, with GST-4 (P < 0.01) and SKN-1/Nrf2 (P < 0.01) activation mitigating nanoplastic-induced damage. Our results emphasize that even at the environmentally relevant concentrations (ERC), nanoplastics can impact neurotoxicity-related endpoints, with PIEZO mediating the regulation of oxidative and antioxidative systems in response to these effects. PIEZO may be applied for assessing the neurotoxicity or oxidative stress induced by other environmental toxicants besides nanoplastics.

Impaired fertility in 4930590J08Rik mutant male mice is associated with defective sperm energy metabolism.

Testis-specifically expressed genes are important for male reproduction according to their unique expression patterns. However, the functions of most of these genes in reproduction are unclear. Here, we showed that mouse 4930590J08Rik was a testis-specifically expressed gene. 4930590J08Rik knockout mice exhibited a delay in the first wave of spermatogenesis and a reduction of cauda epididymal sperm. Furthermore, knockout spermatozoa exhibited defective acrosome reactions and decreased progressive motility, which led to impaired in vivo fertilization. Transcriptome analysis of testes revealed that most of the differentially expressed genes in knockout testes were associated with metabolic processes. 4930590J08Rik knockout sperm exhibited oxidative phosphorylation deficiency and were highly dependent on increased anaerobic glycolysis to compensate for ATP demands. Taken together, the 4930590J08Rik-disrupted mouse partially mimics the phenotypes of human asthenospermia and oligozoospermia, which provides a new model for further understanding the pathogenesis of idiopathic male infertility.

Alpha-lipoic Acid Protects Against Chronic Alcohol Consumption-induced Cardiac Damage by the Aldehyde Dehydrogenase 2-associated PINK/Parkin Pathway.

ABSTRACT: Chronic alcohol intake contributes to high mortality rates due to ethanol-induced cardiac hypertrophy and contractile dysfunction, which are accompanied by increased oxidative stress and disrupted mitophagy. Alpha-lipoic acid (α-LA), a well-known antioxidant, has been shown to protect against cardiac hypertrophy and inflammation. However, little is known about its role and mechanism in the treatment of alcoholic cardiomyopathy. Here, we evaluated the role of α-LA in alcohol-induced cardiac damage by feeding mice a 4.8% (v/v) alcohol diet with or without α-LA for 6 w. Our results suggested that chronic alcohol consumption increased mortality, blood alcohol concentrations, and serum aldehyde levels, but a-LA attenuated the elevations in mortality and aldehydes. Chronic alcohol intake also induced cardiac dysfunction, including enlarged left ventricles, reduced left ventricular ejection fraction, enhanced cardiomyocyte size, and increased serum levels of brain natriuretic peptide, lactate dehydrogenase, and creatine kinase myocardial isoenzyme. Moreover, alcohol intake led to the accumulation of collagen fiber and mitochondrial dysfunction, the effects of which were alleviated by α-LA. In addition, α-LA intake also prevented the increase in reactive oxygen species production and the decrease in mitochondrial number that were observed after alcohol consumption. Chronic alcohol exposure activated PINK1/Parkin-mediated mitophagy. These effects were diminished by α-LA intake by the activation of aldehyde dehydrogenase 2. Our data indicated that α-LA helps protect cardiac cells against the effects of chronic alcohol intake, likely by inhibiting PINK1/Parkin-related mitophagy through the activation of aldehyde dehydrogenase 2.

Fe-N hollow mesoporous carbon spheres with high oxidase-like activity for sensitive detection of alkaline phosphatase.

Due to the vital role of alkaline phosphatase (ALP) in clinical diagnoses and biomedical research, a sensitive and selective detection method for ALP activity is of considerable importance. Herein, a facile and sensitive colorimetric assay for the detection of ALP activity was developed based on Fe-N hollow mesoporous carbon spheres (Fe-N HMCS). Fe-N HMCS were synthesized by a practical one-pot method with aminophenol/formaldehyde (APF) resin as the carbon/nitrogen precursor, silica as the template and iron phthalocyanine (FePC) as the iron source. Thanks to the highly dispersed Fe-N active sites, Fe-N HMCS exhibited exceptional oxidase-like activity. In the presence of dissolved oxygen, Fe-N HMCS were able to effectively convert colorless 3,3',5,5'-tetramethylbenzidine (TMB) into oxidized TMB (oxTMB) with blue color, while the reducing agent of ascorbic acid (AA) inhibited the color reaction. Based on this fact, an indirect and sensitive colorimetric sensing method was developed to detect alkaline phosphatase (ALP) with the assistance of the substrate L-ascorbate 2-phosphate (AAP). This ALP biosensor exhibited a linear range of 1-30 U L-1 and a limit of detection (LOD) of 0.42 U L-1 in standard solutions. In addition, this method was applied to detect ALP activity in human serum with satisfactory results. This work offers a positive reference for the reasonable excavation of transition metal-N carbon compounds in ALP-extended sensing applications.

Regulating the Electronic Structure of Ni Sites in Ni(OH)2 by Ce Doping and Cu(OH)2 Coupling to Boost 5-Hydroxymethylfurfural Oxidation Performance.

Biomass is a sustainable and renewable resource that can be converted into valuable chemicals, reducing the demand for fossil energy. 5-Hydroxymethylfurfural (HMF), as an important biomass platform molecule, can be converted to high-value-added 2,5-furandicarboxylic acid (FDCA) via a green and renewable electrocatalytic oxidation route under mild reaction conditions, but efficient electrocatalysts are still lacking. Herein, we rationally fabricate a novel self-supported electrocatalyst of core-shell-structured copper hydroxide nanowires@cerium-doped nickel hydroxide nanosheets composite nanowires on a copper mesh (CuH_NWs@Ce:NiH_NSs/Cu) for electrocatalytically oxidizing HMF to FDCA. The integrated configuration of composite nanowires with rich interstitial spaces between them facilitates fast mass/electron transfer, improved conductivity, and complete exposure of active sites. The doping of Ce ions in nickel hydroxide nanosheets (NiH_NSs) and the coupling of copper hydroxide nanowires (CuH_NWs) regulate the electronic structure of the Ni active sites and optimize the adsorption strength of the active sites to the reactant, meanwhile promoting the generation of strong oxidation agents of Ni3+ species, thereby resulting in improved electrocatalytic activity. Consequently, the optimal CuH_NWs@Ce:NiH_NSs/Cu electrocatalyst is able to achieve a HMF conversion of 98.5% with a FDCA yield of 97.9% and a Faradaic efficiency of 98.0% at a low constant potential of 1.45 V versus reversible hydrogen electrode. Meanwhile, no activity attenuation can be found after 15 successive cycling tests. Such electrocatalytic performance suppresses most of the reported Cu-based and Ni-based electrocatalysts. This work highlights the importance of structure and doping engineering strategies for the rational fabrication of high-performance electrocatalysts for biomass upgrading.

Seroprevalence of coxsackievirus A6 and enterovirus A71 infection in humans: a systematic review and meta-analysis.

Hand, foot, and mouth disease (HFMD) is a common infectious disease in children. Enterovirus A71 (EV-A71) is one of the main pathogens, and coxsackievirus A6 (CVA6) has gradually become the dominant pathogen of HFMD in recent years. This study was conducted mainly to assess the serological prevalence of EV-A71 and CVA6 antibodies in people of different ages, sexes, and regions through a systematic review and meta-analysis. A comprehensive study was performed based on the EV-A71 and CVA6 serological literature published before May 2022. Heterogeneity analysis (Cochrane's Q test and the I2 statistic) and random effect models were adopted. Subgroup and meta-regression analyses were used to identify potential sources of heterogeneity in the data, and all analysis was performed using STATA version 16.0. This study included 71 studies involving 55,176 people from 13 countries that met the inclusion criteria. The serological prevalence of EV-A71 antibody in different studies was 4.31-88.8%, and that of CVA6 antibody was 40.8-80.9%. Meta-analysis results showed that the serum positive rate for EV-A71 antibody was 45.9% (95% CI: 37.6-54.1%). The rate in the Chinese population was 47.8% (95% CI: 42.4-53.2%), and in the other countries, it was 38% (95% CI: 23-55%). The serum positive rate for CVA6 antibody was 58.3% (95% CI: 46.5-70.2%). The rate in the Chinese population was 49.1% (95% CI: 38.3-59.9%), and in the other countries, it was 68% (95% CI: 51-83%). Subgroup analysis was also conducted. The seroprevalence of EV-A71 and CVA6 antibodies is related to age rather than gender or region. The rates of EV-A71 and CVA6 seropositivity are considerably lower in children younger than five years of age. However, the rates gradually increase with age. The findings of this study suggest that children under five years of age may be susceptible to EV-A71 and CVA6. Thus, safety education and vaccination should be strengthened accordingly. This study provides a basis for understanding the risk factors for EV-A71 and CVA6 infection in China and for deciding how to formulate standard preventive measures to prevent the spread of the virus.

Integrating scRNA-seq to explore novel macrophage infiltration-associated biomarkers for diagnosis of heart failure.

OBJECTIVE: Inflammation and immune cells are closely intertwined mechanisms that contribute to the progression of heart failure (HF). Nonetheless, there is a paucity of information regarding the distinct features of dysregulated immune cells and efficient diagnostic biomarkers linked with HF. This study aims to explore diagnostic biomarkers related to immune cells in HF to gain new insights into the underlying molecular mechanisms of HF and to provide novel perspectives for the detection and treatment of HF. METHOD: The CIBERSORT method was employed to quantify 22 types of immune cells in HF and normal subjects from publicly available GEO databases (GSE3586, GSE42955, GSE57338, and GSE79962). Machine learning methods were utilized to screen for important cell types. Single-cell RNA sequencing (GSE145154) was further utilized to identify important cell types and hub genes. WGCNA was employed to screen for immune cell-related genes and ultimately diagnostic models were constructed and evaluated. To validate these predictive results, blood samples were collected from 40 normal controls and 40 HF patients for RT-qPCR analysis. Lastly, key cell clusters were divided into high and low biomarker expression groups to identify transcription factors that may affect biomarkers. RESULTS: The study found a noticeable difference in immune environment between HF and normal subjects. Macrophages were identified as key immune cells by machine learning. Single-cell analysis further showed that macrophages differed dramatically between HF and normal subjects. This study revealed the existence of five subsets of macrophages that have different differentiation states. Based on module genes most relevant to macrophages, macrophage differentiation-related genes (MDRGs), and DEGs in HF and normal subjects from GEO datasets, four genes (CD163, RNASE2, LYVE1, and VSIG4) were identified as valid diagnostic markers for HF. Ultimately, a diagnostic model containing two hub genes was constructed and then validated with a validation dataset and clinical samples. In addition, key transcription factors driving or maintaining the biomarkers expression programs were identified. CONCLUSION: The analytical results and diagnostic model of this study can assist clinicians in identifying high-risk individuals, thereby aiding in guiding treatment decisions for patients with HF.

The severity and infection of acute pancreatitis may increase the risk of bleeding in patients undergoing EUS-guided drainage and endoscopic necrosectomy: a large retrospective cohort.

BACKGROUND: There has been great progress in the use of endoscopic ultrasound (EUS)-guided drainage in acute pancreatitis patients using a novel lumen-apposing metal stent (LAMS) in the last decade, but some patients experience bleeding. Our research analyzed the preprocedural risk factors for bleeding. METHODS: From July 13, 2016 to June 23, 2021, we retrospectively analyzed all patients who received endoscopic drainage by the LAMS in our hospital. Univariate and multivariate statistical analyses were used to identify the independent risk factors. We plotted ROC curves based on the independent risk factors. RESULTS: A total of 205 patients were analyzed and 5 patients were excluded. A total of 200 patients were included in our research. Thirty (15%) patients presented with bleeding. In the multivariate analysis, computed tomography severity index score (CTSI) score [odds ratio (OR), 2.66; 95% CI: 1.31-5.38; P = 0.007], positive blood cultures [odds ratio (OR), 5.35; 95% CI: 1.31-21.9; P = 0.02], and Acute Physiology and Chronic Health Evaluation II (APACHE II) score [odds ratio (OR), 1.14; 95% CI: 1. 01-1.29; P = 0.045] were associated with bleeding. The area under the ROC curve of the combined predictive indicator was 0.79. CONCLUSION: Bleeding in endoscopic drainage by the LAMS is significantly associated with the CTSI score, positive blood cultures, and APACHE II score. This result could help clinicians make more appropriate choices.

Inhibition of Cyclophilin A-Metalloproteinase-9 Pathway Alleviates the Development of Neuropathic Pain by Promoting Repair of the Blood-Spinal Cord Barrier.

BACKGROUND: Dysfunction of the blood-spinal cord barrier (BSCB) contributes to the occurrence and development of neuropathic pain (NP). Previous studies revealed that the activation of cyclophilin A (CypA)-metalloproteinase-9 (MMP9) signaling pathway can disrupt the integrity of the blood-brain barrier (BBB) and aggravate neuroinflammatory responses. However, the roles of CypA-MMP9 signaling pathway on BSCB in NP have not been studied. This study aimed to investigate the effect of CypA on the structure and function of the BSCB and pain behaviors in mice with NP. METHODS: We first created the mouse chronic constriction injury (CCI) model, and they were then intraperitoneally injected with the CypA inhibitor cyclosporine A (CsA) or vehicle. Pain behaviors, the structure and function of the BSCB, the involvement of the CypA-MMP9 signaling pathway, microglia activation, and expression levels of proinflammatory factors in mice were examined. RESULTS: CCI mice presented mechanical allodynia and thermal hyperalgesia, impaired permeability of the BSCB, downregulated tight junction proteins, activated CypA-MMP9 signaling pathway, microglia activation, and upregulated proinflammatory factors, which were significantly alleviated by inhibition of CypA. CONCLUSIONS: Collectively, the CypA-MMP9 signaling pathway is responsible for CCI-induced NP in mice by impairing the structure and function of the BSCB, and activating microglia and inflammatory responses.

Identification of Three Cuproptosis-specific Expressed Genes as Diagnostic Biomarkers and Therapeutic Targets for Atherosclerosis.

Atherosclerosis is a chronic, inflammatory disease characterized by a lipid-driven infiltration of inflammatory cells in large and medium arteries and is considered to be a major underlying cause of cardiovascular diseases. Cuproptosis, a novel form of cell death, is highly linked to mitochondrial metabolism and mediated by protein lipoylation. However, the clinical implication of cuproptosis-related genes (CRGs) in atherosclerosis remains unclear. In this study, genes collected from the GEO database intersected with CRGs were identified in atherosclerosis. GSEA, GO and KEGG pathway enrichment analyses were performed for functional annotation. Through the random forest algorithm and the construction of a protein-protein interaction (PPI) network, eight selected genes (LOXL2, SLC31A1, ATP7A, SLC31A2, COA6, UBE2D1, CP and SOD1) and a vital cuproptosis-related gene FDX1 were then further validated. Two independent datasets (GSE28829 (N = 29), GSE100927 (N = 104)) were collected to construct the signature of CRGs for validation in atherosclerosis. Consistently, the atherosclerosis plaques showed significantly higher expression of SLC31A1, SLC31A2 and lower expression of SOD1 than the normal intimae. The area under the curve (AUC) of SLC31A1, SLC31A2 and SOD1 performed well for the diagnostic validation in the two datasets. In conclusion, the cuproptosis-related gene signature could serve as a potential diagnostic biomarker for atherosclerosis and may offer novel insights into the treatment of cardiovascular diseases. Based on the hub genes, a competing endogenous RNA (ceRNA) network of lncRNA-miRNA-mRNA and a transcription factor regulation network were ultimately constructed to explore the possible regulatory mechanism in atherosclerosis.

Prevalence and clinical characteristics of sleep-disordered breathing in patients with heart failure of different left ventricular ejection fractions.

PURPOSES: The prevalence of sleep-disordered breathing (SDB) is high in patients with heart failure (HF), while the prevalence of SDB in HF with different left ventricular ejection fractions (LVEF) has rarely been reported. We aimed to explore the prevalence and clinical characteristics of SDB in patients with HF having different LVEF. METHODS: Patients with stable HF were consecutively enrolled. All patients underwent portable overnight cardiorespiratory polygraphy and echocardiography. According to their LVEF, the patients were divided into the HFrEF (HF with reduced EF, EF < 40%), HFmrEF (HF with mid-range EF, 40 ≤ EF < 50), and HFpEF groups (HF with preserved EF, EF ≥ 50%). The prevalence and clinical data of SDB among the 3 groups were then compared. RESULTS: A total of 252 patients, including 134 men, were enrolled in the study. The prevalence of SDB in patients with HF was 70%. Obstructive sleep apnea (OSA) was diagnosed in 48% and central sleep apnea (CSA) in 22%. The prevalence of SDB in the HFrEE, HFmrEF, and HFpEF groups was 86%, 86%, and 62%, respectively (P = 0.001). The prevalence of OSA among the 3 groups was 42%, 47%, and 49%, respectively (P = 0.708), while the prevalence of CSA among the 3 groups was 44%, 40%, and 13% (P < 0.001). Logistic regression analysis revealed that age and BMI were independent risk factors for OSA in patients with HF, while LVEF and smoking were independent risk factors for CSA in patients with HF. Correlational analyses revealed that LVEF was negatively correlated with apnea-hypopnea index (AHI) (r = -0.309, P < 0.001) and central apnea index (CAI) ( r = -0.558, P < 0.001), while there was no significant correlation with obstructive apnea index (OAI). The ROC curve revealed that LVEF could predict the occurrence of CSA and SDB, with AUC = 0.683 (95%CI 0.600-0.767, P < 0.001) and AUC = 0.630 (95%CI 0.559-0.702, P = 0.001), but not of OSA. CONCLUSIONS: SDB was highly common in HF, and the prevalence of SDB was different in HF with different LVEF, mainly due to the difference in cardiac functions. The prevalence and severity of SDB in HFrEF and HFmrEF were significantly higher than those in HFpEF, which was mainly related to the increase in CSA. When HFmrEF was similar to HFrEF in cardiac functions, the prevalence, type, and severity of SDB were similar between the two groups. Changes in LVEF had a significant impact on CAI, but not on OAI. LVEF can predict the occurrence of CSA and SDB to a certain extent.

Toll-interacting protein participates in immunity and development of the lepidopteran insect Antheraea pernyi.

Toll-interacting protein (Tollip) participates in multiple biological processes. However, the biological functions of Tollip proteins in insects remain to be further explored. Here, the genomic sequence of tollip gene from Antheraea pernyi (named Ap-Tollip) was identified with a length of 15,060 bp, including eight exons and seven introns. The predicted Ap-Tollip protein contained conserved C2 and CUE domains and was highly homologous to those tollips from invertebrates. Ap-Tollip was highly expressed in fat body compared with other determined tissues. As far as the developmental stages were concerned, the highest expression level was found at the 14th day in eggs or the 3rd day of the 1st instar. Ap-Tollip was also obviously regulated by lipopolysaccharide, polycytidylic acid or 20E in different tissues. In addition, the interaction between Ap-Tollip and ubiquitin was confirmed by western blotting and pull-down assay. RNAi of Ap-Tollip significantly affected the expression levels of apoptosis and autophagy-related genes. These results indicated that Ap-Tollip was involved in immunity and development of A. pernyi.

Molecular insights into plant desiccation tolerance: transcriptomics, proteomics and targeted metabolite profiling in Craterostigma plantagineum.

The resurrection plant Craterostigma plantagineum possesses an extraordinary capacity to survive long-term desiccation. To enhance our understanding of this phenomenon, complementary transcriptome, soluble proteome and targeted metabolite profiling was carried out on leaves collected from different stages during a dehydration and rehydration cycle. A total of 7348 contigs, 611 proteins and 39 metabolites were differentially abundant across the different sampling points. Dynamic changes in transcript, protein and metabolite levels revealed a unique signature characterizing each stage. An overall low correlation between transcript and protein abundance suggests a prominent role for post-transcriptional modification in metabolic reprogramming to prepare plants for desiccation and recovery. The integrative analysis of all three data sets was performed with an emphasis on photosynthesis, photorespiration, energy metabolism and amino acid metabolism. The results revealed a set of precise changes that modulate primary metabolism to confer plasticity to metabolic pathways, thus optimizing plant performance under stress. The maintenance of cyclic electron flow and photorespiration, and the switch from C3 to crassulacean acid metabolism photosynthesis, may contribute to partially sustain photosynthesis and minimize oxidative damage during dehydration. Transcripts with a delayed translation, ATP-independent bypasses, alternative respiratory pathway and 4-aminobutyric acid shunt may all play a role in energy management, together conferring bioenergetic advantages to meet energy demands upon rehydration. This study provides a high-resolution map of the changes occurring in primary metabolism during dehydration and rehydration and enriches our understanding of the molecular mechanisms underpinning plant desiccation tolerance. The data sets provided here will ultimately inspire biotechnological strategies for drought tolerance improvement in crops.

Upregulation of key genes Eln and Tgfb3 were associated with the severity of cardiac hypertrophy.

BACKGROUND: Hypertension-induced cardiac hypertrophy is one of the most common pre-conditions that accompanies heart failure. This study aimed to identify the key pathogenic genes in the disease process. METHODS: GSE18224 was re-analyzed and differentially expressed genes (DEGs) were obtained. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were carried out. Networks of transcription factor (TF)-mRNA, microRNA (miRNA)-mRNA and Protein-Protein interaction (PPI) were constructed, and a key module was further screened out from PPI network. GSE36074 dataset and our transverse aortic constriction (TAC) mouse model were used to validate gene expression in the module. Finally, the correlation between the genes and biomarkers of cardiac hypertrophy were evaluated. RESULTS: Totally, there were 348 DEGs in GSE18224, which were mainly enriched in biological processes including collagen fibril organization, cellular response to transforming growth factor-beta stimulus and were involved in ECM-receptor interaction and Oxytocin signaling pathway. There were 387 miRNAs targeted by 257 DEGs, while 177 TFs targeted 71 DEGs. The PPI network contained 222 nodes and 770 edges, with 18 genes screened out into the module. After validation, 8 genes, which were also significantly upregulated in the GSE36074 dataset, were selected from the 18 DEGs. 2 of the 8 DEGs, including Eln and Tgfb3 were significantly upregulated in our mouse model of myocardial hypertrophy. Finally, the expression of Eln and Tgfb3 were found to be positively correlated with the level of the disease biomarkers. CONCLUSIONS: Upregulated key genes Eln and Tgfb3 were positively correlated with the severity of cardiac hypertrophy, which may provide potential therapeutic targets for the disease.