Daratumumab and venetoclax combined with CAGE for late R/R T-ALL/LBL patients: Single-arm, open-label, phase I study.

The prognosis of patients diagnosed with relapsed or refractory (R/R) T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) has consistently been unsatisfactory, with limited treatment options. As reports, the CAG regimen can serve as a salvage treatment for R/R T-ALL/LBL, but there remains a subset of patients who do not benefit from it. Recent studies have indicated that daratumumab (Dara) and venetoclax (Ven) may offer promising therapeutic benefits for T-ALL/LBL. In light of these findings, we conducted a safety and efficacy evaluation of the enhanced treatment regimen, combining Dara and Ven with aclarubicin, cytarabine, granulocyte colony-stimulating factor, and etoposide (CAGE), in patients suffering from R/R T-ALL/LBL. The participants in this phase I trial were patients with R/R T-ALL/LBL who fail to standard treatment regimens. During each 28-day cycle, the patients were treated by Dara, Ven, cytarabine, aclarubicin, granulocyte colony-stimulating factor, etoposide. The primary endpoint of this study was the rate of remission. This report presents the prospective outcomes of 21 patients who received the salvage therapy of Dara and Ven combined with the CAGE regimen (Dara + Ven + CAGE). The objective remission rate (ORR) was determined to be 57.1%, while the complete remission (CR) rate was 47.6%. Notably, patients with the early T-cell precursor (ETP) subtype exhibited a significantly higher remission rate in the bone marrow compared to non-ETP patients (100% vs. 44.4%, p = 0.044). The Dara + Ven + CAGE regimen demonstrated a favorable remission rate in patients with R/R T-ALL/LBL. Moreover, the treatment was well-tolerated.

Transcriptome and Gene Co-Expression Network Analysis Identifying Differentially Expressed Genes and Signal Pathways Involved in the Height Development of Banana (Musa spp.).

Plant height is an important and valuable agronomic trait associated with yield and resistance to abiotic and biotic stresses. Dwarfism has positive effects on plant development and field management, especially for tall monocotyledon banana (Musa spp.). However, several key genes and their regulation mechanism of controlling plant height during banana development are unclear. In the present study, the popular cultivar 'Brazilian banana' ('BX') and its dwarf mutant ('RK') were selected to identify plant height-related genes by comparing the phenotypic and transcriptomic data. Banana seedlings with 3-4 leaves were planted in the greenhouse and field. We found that the third and fourth weeks are the key period of plant height development of the selected cultivars. A total of 4563 and 10507 differentially expressed genes (DEGs) were identified in the third and fourth weeks, respectively. Twenty modules were produced by the weighted gene co-expression network analysis (WGCNA). Eight modules were positively correlated with the plant height, and twelve other modules were negatively correlated. Combining with the analysis of DEGs and WGCNA, 13 genes in the signaling pathway of gibberellic acid (GA) and 7 genes in the signaling pathway of indole acetic acid (IAA) were identified. Hub genes related to plant height development were obtained in light of the significantly different expression levels (|log2FC| ≥ 1) at the critical stages. Moreover, GA3 treatment significantly induced the transcription expressions of the selected candidate genes, suggesting that GA signaling could play a key role in plant height development of banana. It provides an important gene resource for the regulation mechanism of banana plant development and assisted breeding of ideal plant architecture.

Stable Long Cycling of Small Molecular Organic Acid Electrode Materials Enabled by Nonflammable Eutectic Electrolyte.

Small molecule organic acids as electrode materials possess the advantages of high theoretical capacity, low cost, and good processability. However, these electrode materials suffer from poor cycling stability due to the inevitable dissolution of organic molecules in the electrolytes. Here, a eutectic mixture of lithium bis(trifluoromethanesulfonyl)imide and N-methylamine is employed as a eutectic electrolyte in Li-ion batteries with small molecule organic acids as electrodes. To enhance the cycling stability of the electrolyte, fluoroethylene carbonate is used as an additive. The electrolyte exhibits nonflammability, high ionic conductivity, and good electrochemical stability. Molecular dynamics simulations and density functional theory are performed to further investigate the solvation chemistry of the eutectic electrolyte. The well-designed eutectic electrolyte inhibits the dissolution of terephthalic acid effectively and displays superior performance with a capacity retention of ≈84% after 2000 cycles at a high current density of 1 A g-1 . It also enables stable cycling of more than 900 cycles at a high current density of 2 A g-1 at 60 °C. This study provides a strategy to enhance the cycling stability and safety of Li-ion batteries with organic electrode materials.

Association between inflammation markers and all-cause mortality in critical ill patients with atrial fibrillation: Analysis of the Multi-Parameter Intelligent Monitoring in Intensive Care (MIMIC-IV) database.

Background: Inflammation is related to cardiovascular disease. Among the many inflammatory markers, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII) were considered as novel predictors for atherosclerosis outcomes. We aimed to investigate the impact of these inflammatory markers on the prognosis of patients with atrial fibrillation (AF). Methods: We obtained data on AF patients from the Medical Information Mart for Intensive Care (MIMIC)-IV database. These patients were classified into two groups based on their survival status within 30 days. Then, they were divided into three groups based on the tertile of baseline NLR, PLR, and SII, respectively. We comprehensively explored the relationship between those inflammatory indicators and all-cause mortality in patients with AF by Kaplan-Meier analysis, multivariate Cox regression analysis, receiver operating characteristic (ROC) analyses, restricted cubic spline regression (RCS), and subgroup analysis. Results: A total of 4562 patients with AF were included. Statistically significant differences were found between survivor and non-survivor groups for NLR, PLR and SII. Patients in the high tertile of the NLR had a higher mortality rate than those in the low and intermediate tertiles, as did patients in the PLR and the SII. NLR, PLR and SII were independently associated with increased risk of all-cause mortality. RCS showed that the 30-day and 365-day risk of death were linearly associated with increases in NLR, PLR, and SII, respectively. Conclusion: NLR, PLR, and SII have the potential to be used as indicators for stratifying the risk of mortality in critically ill patients with AF.

Response of microbial community composition and function to land use in mining soils of Xikuang Mountain in Hunan.

Nine land types in the northern mining area (BKQ) (mining land, smelting land, living area), the old mining area (LKQ) (whole-ore heap, wasteland, grassland), and southern mining area (NKQ) (grassland, shrubs, farmland) of Xikuang Mountain were chosen to explore the composition and functions of soil bacterial communities under different habitats around mining areas. The composition and functions of soil bacterial communities were compared among the sampling sites using 16S rRNA high-throughput sequencing and metagenomic sequencing. α diversity analysis showed the soil bacterial diversity and abundance in the old mining area were significantly higher than those in the northern mining area. ß diversity analysis demonstrated that the soil bacterial community composition was highly similar among different vegetation coverages in the southern mining area. Microbial community function analysis showed the annotated KEGG function pathways and eggNOG function composition were consistent between the grassland of the old mining area and the grassland of the southern mining area. This study uncovers the soil bacterial community composition and functions among different habitats in the mining areas of Xikuang Mountain and will underlie soil ecosystem restoration in different habitats under heavy metal pollution around the mining areas there.

Unique Electron-Transfer-Mediated Electrochemiluminescence of AuPt Bimetallic Nanoclusters and the Application in Cancer Immunoassay.

Noble Metal nanoclusters (NCs) are promising electrochemiluminescence (ECL) emitters due to their amazing optical properties and excellent biocompatibility. They have been widely used in the detection of ions, pollutant molecules, biomolecules, etc. Herein, we found that glutathione-capped AuPt bimetallic NCs (GSH-AuPt NCs) emitted strong anodic ECL signals with triethylamine as co-reactants which had no fluorescence (FL) response. Due to the synergistic effect of bimetallic structures, the ECL signals of AuPt NCs were 6.8 and 94 times higher than those of monometallic Au and Pt NCs, respectively. The electric and optical properties of GSH-AuPt NCs differed from those of Au and Pt NCs completely. An electron-transfer mediated ECL mechanism was proposed. The excited electrons may be neutralized by Pt(II) in GSH-Pt and GSH-AuPt NCs, resulting in the vanished FL. Furthermore, abundant TEA radicals formed on the anode contributed electrons to the highest unoccupied molecular orbital of GSH-Au2.5Pt NCs and Pt(II), booming intense ECL signals. Because of the ligand effect and ensemble effect, bimetallic AuPt NCs exhibited much stronger ECL than GSH-Au NCs. A sandwich-type immunoassay for alpha fetoprotein (AFP) cancer biomarkers was fabricated with GSH-AuPt NCs as signal tags, which displayed a wide linear range from 0.01 to 1000 ng·mL-1 and a limit of detection (LOD) down to 1.0 pg·mL-1 at 3S/N. Compared to previous ECL AFP immunoassays, this method not only had a wider linear range but also a lower LOD. The recoveries of AFP in human serum were around 108%, providing a wonderful strategy for fast, sensitive, and accurate cancer diagnosis.

Molten salt synthesis of NiCo-NiCo2O4@C nanotubes as anode materials for Li-ion batteries.

The construction of carbon-encapsulated transition metal nanotube structures is a preferred method that can effectively slow down volume expansion, improve cycling stability and enhance the electrical conductivity of the reactive sites of lithium-ion batteries. In this study, nanotubes of carbon-coated NiCo-NiCo2O4 nanoparticles (NC-NCO@C) were prepared by a one-step molten salt method at high temperature using Ni and Co as catalytic centers and sodium acetate as carbon source. We used NC-NCO@C-2 nanotubes as anode materials for lithium-ion batteries(LIBs), which exhibited excellent lithium storage performance and good stability, with a specific capacity of 616.26 mAh g-1 after 1000 cycles at a high current density of 1 A g-1. In addition, NC-NCO@C-2 were used as anodes in lithium-ion full cells and LiFePO4 (LFP) was used as the cathode. The NC-NCO@C-2//LFP full-cell exhibits high capacity and good cycling stability, with a capacity of 100.7 mAh g-1 after 100 cycles and a capacity retention rate of 92%. The construction of NC, NCO, and carbon ternary complexes was found to activate and promote the reversible conversion of certain inorganic components at the solid electrolyte interfaces (SEI), which effectively reduced the volume change during cycling, increased the electrical conductivity, and improved the cycling stability of the electrode. The proposed one-step molten salt synthesis of Carbon-coated metals complexes with excellent compatibility characteristics, is expected to solve the problem of volume change in transition metals, which is encountered in LIBs applications.

The Comparison of Long-Term Outcome Between Patients with Single and Multiple Coronary Chronic Total Occlusions After Percutaneous Coronary Intervention.

BACKGROUND: Rapid advancements in percutaneous coronary intervention (PCI) have improved the outcome of chronic coronary total occlusions (CTOs); however, data regarding the difference in long-term outcomes in stable coronary artery disease (CAD) patients with single and multiple CTOs who underwent PCI are scarce. This study aimed to compare the long-term outcomes of patients with multiple CTOs and single CTO after PCI. METHODS: This study cohort included stable CAD patients who were diagnosed with CTO and treated with PCI from a single center. The primary endpoint was all-cause death. RESULTS: We retrospectively reviewed 670 consecutive patients with CTO-PCI. Among them, 539 patients had a single CTO, and 131 (19.7%) patients had multiple (at least two) CTOs. CTO revascularization was achieved in 470 (70.1%) patients. After a median follow-up duration of 33.7 months, the cumulative all-cause mortality (p = 0.037) and cardiac mortality (p = 0.003) were higher in patients with multiple CTOs than in those with a single CTO. In the multivariable model, multiple CTOs and left ventricular ejection fraction (LVEF) less than 40% were independent predictors for cardiac death (adjusted hazard ratio (HR) 2.53; P = 0.013 and adjusted HR 3.95; P < 0.001), while age older than 65 and LVEF less than 40% were independent predictors for all-cause death in CTO-PCI patients (adjusted hazard ratio (HR) 1.84; P = 0.035 and adjusted HR 2.54; P = 0.001). CONCLUSION: In CTO-PCI patients, long-term survival was associated with multiple CTOs, age and LVEF, but not with CTO revascularization.

Refinement of CHADS2 and CHA2DS2-VASc scores predict left atrial thrombus or spontaneous echo contrast in nonvalvular atrial fibrillation patients.

OBJECTIVE: To investigate the risk factors of left atrial thrombus (LAT)/spontaneous echo contrast (SEC) in patients with nonvalvular atrial fibrillation (AF). METHODS: This retrospective study analysed the data from consecutive patients with nonvalvular AF that underwent transoesophageal echocardiography. Logistic regression analysis was performed to identify risk factors of LAT/SEC. Receiver operating characteristic curve analysis was undertaken compare the new scales with CHADS2 and CHA2DS2-VASc scores. RESULTS: A total of 558 patients with AF were included in the study. LAT/SEC was detected in 137 (24.6%) patients. The independent risk factors of LAT/SEC beyond CHADS2 or CHA2DS2-VASc scores included non-paroxysmal AF and left atrial diameter >37.5 mm. These two variables were added into the CHADS2 or CHA2DS2-VASc score to build new scales. Areas under the curve for the new scales based on CHADS2 and CHA2DS2-VASc scores were significantly higher than the CHADS2 or CHA2DS2-VASc score both in the overall study cohort and in patients at a high risk of thromboembolism. CONCLUSIONS: Non-paroxysmal AF and increased left atrial diameter beyond the CHADS2 or CHA2DS2-VASc score were independent risk factors of LAT/SEC and may help to improve the current risk stratification, especially for patients with nonvalvular AF at a high risk of thromboembolism.

Sex differences in global disability-adjusted life years due to ischemic stroke: findings from global burden of diseases study 2019.

To investigate the sex differences in disability-adjusted life years (DALYs) due to ischemic stroke (IS) by year, location and age. We extracted sex-specific data on DALYs number, age-standardized DALYs rate (ASDR) and all-age DALYs rate of IS by year, location and age from the Global Burden of Diseases study 2019. The estimated annual percentage changes (EAPC) were calculated to evaluate the temporal trend of ASDR. For both sexes, although the ASDR of IS slightly decreased from 1990 to 2019, there has been an 60.3% increase in DALYs number worldwide. Sex difference in DALYs number (men minus women) decreased from - 2.83 million in 1990 to 0.14 million in 2019, while the men to women's ASDR ratio slightly increased from 1.10 in 1990 to 1.21 in 2019. The sex differences in IS DALYs showed remarkable regional variation. The largest sex differences in DALYs number and ASDR were in China and Vietnam. Middle-aged men had a higher IS DALYs than their age-matched counterparts. High systolic blood pressure accounted for the highest DALYs number in 2019, but the top three attributable risk factors that had the greatest sex differences were tobacco, dietary risk, and alcohol use. Sex differences in IS DALYs varied by year, location and age, mostly attributed to the disproportion of cardiovascular risk factors between sexes. Considering the population growth and aging, it is necessary to monitor the sex difference in IS DALYs in different populations and thus provide evidence for local administration to improve current preventive and management strategies of IS.

Safe and Stable Lithium Metal Batteries Enabled by an Amide-Based Electrolyte.

HIGHLIGHTS: A novel amide-based nonflammable electrolyte is proposed. The formation mechanism and solvation chemistry are investigated by molecular dynamics simulations and density functional theory. An inorganic/organic-rich solid electrolyte interphase with an abundance of LiF, Li3N and Li-N-C is in situ formed, leading to spherical lithium deposition. The amide-based electrolyte can enable stable cycling performance at room temperature and 60 ℃. The formation of lithium dendrites and the safety hazards arising from flammable liquid electrolytes have seriously hindered the development of high-energy-density lithium metal batteries. Herein, an emerging amide-based electrolyte is proposed, containing LiTFSI and butyrolactam in different molar ratios. 1,1,2,2-Tetrafluoroethyl-2,2,3,3-tetrafluoropropylether and fluoroethylene carbonate are introduced into the amide-based electrolyte as counter solvent and additives. The well-designed amide-based electrolyte possesses nonflammability, high ionic conductivity, high thermal stability and electrochemical stability (> 4.7 V). Besides, an inorganic/organic-rich solid electrolyte interphase with an abundance of LiF, Li3N and Li-N-C is in situ formed, leading to spherical lithium deposition. The formation mechanism and solvation chemistry of amide-based electrolyte are further investigated by molecular dynamics simulations and density functional theory. When applied in Li metal batteries with LiFePO4 and LiMn2O4 cathode, the amide-based electrolyte can enable stable cycling performance at room temperature and 60 ℃. This study provides a new insight into the development of amide-based electrolytes for lithium metal batteries.

Distribution Characteristics of Soil Viruses Under Different Precipitation Gradients on the Qinghai-Tibet Plateau.

Viruses are extremely abundant in the soil environment and have potential roles in impacting on microbial population, evolution, and nutrient biogeochemical cycles. However, how environment and climate changes affect soil viruses is still poorly understood. Here, a metagenomic approach was used to investigate the distribution, diversity, and potential biogeochemical impacts of DNA viruses in 12 grassland soils under three precipitation gradients on the Qinghai-Tibet Plateau, which is one of the most sensitive areas to climate change. A total of 557 viral operational taxonomic units were obtained, spanning 152 viral families from the 30 metagenomes. Both virus-like particles (VLPs) and microbial abundance increased with average annual precipitation. A significant positive correlation of VLP counts was observed with soil water content, total carbon, total nitrogen, soil organic matter, and total phosphorus. Among these biological and abiotic factors, SWC mainly contributed to the variability in VLP abundance. The order Caudovirales (70.1% of the identified viral order) was the predominant viral type in soils from the Qinghai-Tibet Plateau, with the Siphoviridae family being the most abundant. Remarkably, abundant auxiliary carbohydrate-active enzyme (CAZyme) genes represented by glycoside hydrolases were identified, indicating that soil viruses may play a potential role in the carbon cycle on the Qinghai-Tibet Plateau. There were more diverse hosts and abundant CAZyme genes in soil with moderate precipitation. Our study provides a strong evidence that changes in precipitation impact not only viral abundance and virus-host interactions in soil but also the viral functional potential, especially carbon cycling.

Antifungal Mechanism of Metabolites from Newly Isolated Streptomyces sp. Y1-14 against Banana Fusarium Wilt Disease Using Metabolomics.

Banana Fusarium wilt caused by Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) is one of the most destructive banana diseases in the world, which limits the development of the banana industry. Compared with traditional physical and chemical practices, biological control becomes a promising safe and efficient strategy. In this study, strain Y1-14 with strong antagonistic activity against Foc TR4 was isolated from the rhizosphere soil of a banana plantation, where no disease symptom was detected for more than ten years. The strain was identified as Streptomyces according to the morphological, physiological, and biochemical characteristics and the phylogenetic tree of 16S rRNA. Streptomyces sp. Y1-14 also showed a broad-spectrum antifungal activity against the selected 12 plant pathogenic fungi. Its extracts inhibited the growth and spore germination of Foc TR4 by destroying the integrity of the cell membrane and the ultrastructure of mycelia. Twenty-three compounds were identified by gas chromatography-mass spectrometry (GC-MS). The antifungal mechanism was investigated further by metabolomic analysis. Strain Y1-14 extracts significantly affect the carbohydrate metabolism pathway of Foc TR4 by disrupting energy metabolism.

Transient complete atrioventricular block and ST-segment elevation induced by coronary vasospasm due to iatrogenic hyperkalemia: a case report.

BACKGROUND: Hyperkalemia and acute coronary syndrome are not only all responsible for syncope related to complete atrioventricular block, but also share parts of electrocardiogram manifestations. Additionally, they influence each other. CASE PRESENTATION: A 32-year-old Chinese man presented with severe hypokalemia (1.63 mmol/l) at midnight in the emergency room. He developed unexpected rebound hyperkalemia (7.76 mmol/l) after 18 hours of oral and intravenous potassium chloride supplementation at a concentration of about 10 g/day and a rate of 10 mmol/hour. Subsequently, the patient complained of chest discomfort and dyspnea, followed by syncope for several minutes, approximately 2 hours after potassium reduction treatment had been started. The instant electrocardiogram showed complete atrioventricular block and elevated ST segment in the inferolateral leads, which resolved 15 minutes later, before hyperkalemia was corrected. Combined with mild coronary stenosis and negative myocardial injury markers, transient complete atrioventricular block induced by coronary vasospasm due to iatrogenic hyperkalemia was diagnosed. Normal urine potassium excretion, acid-base state, and other examinations made the diagnosis of hypokalemic periodic paralysis possible. CONCLUSIONS: Hyperkalemia may provoke acute coronary syndrome, and early coronary angiography is an effective strategy for identifying the direct cause of acute complete atrioventricular block.

G604S-HERG mutation in LQT2 leads to autophagy via the UPR-related pathway.

Congenital long QT syndrome (LQTS) is a heart channel disease associated with fatal ventricular arrhythmias or cardiac arrest. Human ether-a-go-go-related gene (HERG) mutation is one of the main causes in type 2 LQTS since it may lead to abundant immature HERG channel protein accumulate in the endoplasmic reticulum (ER). In our study, we have successfully constructed the G604S-HERG mutation in HEK293 cells and demonstrated that the immature HERG protein on ER via Western blot and immunofluorescence. Herein we found that unfolded protein reaction (UPR) process has been activated in order to counter this endoplasmic reticulum stress (ERS) since the main sensors got upregulated. Meanwhile, autophagy was also observed in this process and verified by Western blot and transmission electron microscopy. To explore the relationship underlying autophagy and UPR in the condition of ERS, we found that PERK-EIF2a-CHOP axis was activated. Our findings provides insight for G604S-HERG mutation in type 2 LQTS.

Atrioventricular block can be used as a risk predictor of clinical atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia, with its incidence making up nearly one-third of all hospital admissions. Atrioventricular block (AVB) is a conduction abnormality along the atrioventricular node or the His-Purkinje system. The relationship between atrioventricular conduction block and AF is controversial. HYPOTHESIS: This study is designed to observe whether there is a correlation between AVB and AF, and which type of AVB has the most obvious correlation with AF. METHODS: This study retrospectively reviewed 1345 patients. We classified the AVB according to the AVB classification criteria. One hundred and two patients were excluded, and the final total sample size was 1243 patients, including 679 patients in the AF group (378, 55.7% males) and 564 patients in the non-AF group (287, 50.8% males). AF group and non-AF group were compared to observe the relationship between AVB and AF. RESULTS: The I AVB have a relative statistical risk of 1.927 (95% confidence interval [CI]: 1.160-3.203, P < 0.05) with the occurrence of AF. II AVB occupied the largest proportion, accounting for 67 cases (9.87%), and the statistical risk of II AVB in AF is 16.845 (95% CI: 6.099-46.524, P < 0.000). III AVB has a comparative statistical risk of 17.599 (95% CI: 4.212-73.541, P < 0.000). CONCLUSIONS: The three types of AVB in the AF group were significantly higher than that in the non-AF group. II AVB has the highest incidence rate compared with other types of AVB in the AF group. AVB can be used as a risk factor for AF occurrence.

Human ether­à­go­go­related gene mutation L539fs/47­hERG leads to cell apoptosis through the endoplasmic reticulum stress pathway.

Congenital long QT syndrome (LQTS) is a cardiac channelopathy that often results in fatal arrhythmias. LQTS mutations not only lead to abnormal myocardial electrical activities but are associated with heart contraction abnormalities, cardiomyopathy and congenital heart defects. In vivo and in vitro studies have found that LQTS mutations are associated with cardiomyocyte apoptosis, cardiac developmental disorders and even embryonic mortality. Cardiac delayed rectifier potassium channel dysfunction due to the human ether­à­go­go­related gene (hERG) mutation causes congenital LQTS type 2. The majority of LQTS 2 mutations are characterized by mutant protein accumulation in the endoplasmic reticulum (ER). Unfolded or misfolded protein retention in the ER causes an unfolded protein reaction, which is characteristic of ER stress (ERS). Therefore, the present study hypothesized that LQTS mutations can cause cardiac structural abnormalities via ERS­mediated cardiomyocyte apoptosis. To test this hypothesis, 293 cells were transiently transfected with an L539fs/47­hERG plasmid to generate an LQTS 2 model. L539fs/47­hERG is an LQTS 2 mutation, which consists of a 19­bp deletion at 1619­1637 and a point mutation at 1692. Using confocal laser scanning microscopy analysis, it was verified that the L539fs/47­hERG protein was retained in the ER. Hoechst 33342 apoptosis staining indicated that apoptosis was increased in the L539fs/47­hERG­transfected cells, and this be reversed by treatment with 4­phenyl butyric acid. Western blot analysis revealed increased expression levels of the ERS chaperone glucose regulated protein 78 and pro­apoptotic ERS­induced factors, including protein kinase R­like endoplasmic reticulum kinase, eukaryotic translation­initiation factor­2α and C/EBP homologous protein, in the L539fs/47­hERG­transfected cells. The B­cell lymphoma (Bcl­2)­associated X protein/Bcl­2 ratio and caspase­12 were also increased in the mutated cells. These results demonstrate that L539fs/47­hERG induces cell apoptosis and the potential molecular mechanism involves the activation of ERS and ERS­mediated cell apoptosis.

Hollow core-shell structured Cu2O@Cu1.8S spheres as novel electrode for enzyme free glucose sensing.

This study reports a novel hollow Cu2O@Cu1.8S material used as a catalyst for enzyme free glucose detection. Cu2O@Cu1.8S is successfully synthesized by a facile in-situ growth method. The obtained Cu2O@Cu1.8S exhibits a hollow structure with a Cu1.8S rich surface. Compared to Cu2O spheres, electrochemical results reveal that the Cu2O@Cu1.8S material exhibits a much higher catalytic activity toward glucose oxidation due to synergistic effect between Cu2O and Cu1.8S. The as-prepared Cu2O@Cu1.8S produces a high sensitivity, a fast sensing response, a wide linear range in concentrations of 1-1000 µM, and an excellent selectivity, thus prove to be a promising catalyst for enzyme free glucose detection.

Small RNA-sequencing identified the potential roles of neuron differentiation and MAPK signaling pathway in dilated cardiomyopathy.

Dilated cardiomyopathy is a severe disease characterized by ventricular enlargement and subsequent cardiac dysfunction. MiRNAs plays multiple roles in cardiovascular disease. However, diagnosis values and therapeutic effects of miRNAs in dilated cardiomyopathy are yet poorly understood. In the present study, small RNA-sequencing was employed to identify dysregulated circulating miRNAs in DCM patients compared with healthy controls. A total of 48 dysregulated miRNAs were detected, and 7198 mRNAs, the intersection of predicted mRNAs from both Miranda database and RNAhybrid database, were identified as the target mRNAs of these dysregulated miRNAs. Bioinformatics analysis was performed to identify the potential effects of these dysregulated miRNAs in dilated cardiomyopathy. GO analysis and GO-Tree analysis disclosed that neuron differentiation was potentially the core biological process associated with dilated cardiomyopathy. KEGG analysis and Pathway-Act network showed that mitogen-activated protein kinase (MAPK) signaling pathway was the hub pathway in dilated cardiomyopathy. The dysregulated miRNAs and related target mRNAs in neuron differentiation process and MAPK signaling pathway were also presented in the study. In conclusion, forty-eight dysregulated miRNAs were identified by small RNA-sequencing. Bioinformatics analysis suggested these miRNAs might be involved in the pathogenesis of dilated cardiomyopathy via regulating neuron differentiation process and MAPK signaling pathway.

RNA sequencing discloses the genome­wide profile of long noncoding RNAs in dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a common type of non­ischemic cardiomyopathy, of which the underlying mechanisms have not yet been fully elucidated. Long noncoding RNAs (lncRNAs) have been reported to serve crucial physiological roles in various cardiac diseases. However, the genome­wide expression profile of lncRNAs remains to be elucidated in DCM. In the present study, a case­control study was performed to identify expression deviations in circulating lncRNAs between patients with DCM and controls by RNA sequencing. Partial dysregulated lncRNAs were validated by reverse transcription­polymerase chain reaction. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and lncRNA­messenger RNA (mRNA) co­expression network analyses were employed to probe potential functions of these dysregulated lncRNAs in DCM. Comparison between 8 DCM and 8 control samples demonstrated that there were alterations in the expression levels of 988 lncRNAs and 1,418 mRNAs in total. The dysregulated lncRNAs were found to be mainly associated with system development, organ morphogenesis and metabolic regulation in terms of 'biological processes'. Furthermore, the analysis revealed that the gap junction pathway, phagosome, and dilated and hypertrophic cardiomyopathy pathways may serve crucial roles in the development of DCM. The lncRNA­mRNA co­expression network also suggested that the target genes of the lncRNAs were different in patients with DCM as compared with those in the controls. In conclusion, the present study revealed the genome­wide profile of circulating lncRNAs in DCM by RNA sequencing, and explored the potential functions of these lncRNAs in DCM using bioinformatics analysis. These findings provide a theoretical foundation for future studies of lncRNAs in DCM.