lncRNA Oip5-as1 inhibits excessive mitochondrial fission in myocardial ischemia/reperfusion injury by modulating DRP1 phosphorylation.

BACKGROUND: Aberrant mitochondrial fission, a critical pathological event underlying myocardial ischemia/reperfusion (MI/R) injury, has emerged as a potential therapeutic target. The long non-coding RNA (lncRNA) Oip5-as1 is increasingly recognized for its regulatory roles, particularly in MI/R injury. However, its precise mechanistic role in modulating mitochondrial dynamics remains elusive. This study aims to elucidate the mechanistic role of Oip5-as1 in regulating mitochondrial fission and evaluate its therapeutic potential against MI/R injury. METHODS: To simulate in vitro MI/R injury, HL-1 cardiomyocytes were subjected to hypoxia/reoxygenation (H/R). Lentiviral vectors were employed to achieve overexpression or knockdown of Oip5-as1 in HL-1 cells by expressing Oip5-as1 or shRNA targeting Oip5-as1, respectively. The impact of Oip5-as1 on mitochondrial dynamics in HL-1 cells was assessed using CCK-8 assay, flow cytometry, immunofluorescence staining, and biochemical assays. MI/R injury was induced in mice by ligating the left anterior descending coronary artery. Conditional knockout mice for Oip5-as1 were generated using the CRISPR/Cas9 genome editing technology, while overexpression of Oip5-as1 in mice was achieved via intramyocardial administration of AAV9 vectors. In mice, the role of Oip5-as1 was evaluated through echocardiographic assessment, histopathological staining, and transmission electron microscopy. Furthermore, Western blotting, RNA pull-down, RNA immunoprecipitation, and co-immunoprecipitation assays were conducted to investigate Oip5-as1's underlying mechanisms. RESULTS: The expression levels of Oip5-as1 are significantly decreased in MI/R-injured HL-1 cells and myocardium. In HL-1 cells undergoing H/R injury, overexpression of Oip5-as1 attenuated excessive mitochondrial fission, preserved mitochondrial functionality, and reduced cellular apoptosis, while knockdown of Oip5-as1 exhibited the opposite effects. Furthermore, in a mouse model of MI/R injury, overexpression of Oip5-as1 diminished mitochondrial fission, myocardial infarct size and improved cardiac function. However, knockout of Oip5-as1 exacerbated myocardial injury and cardiac dysfunction, which were significantly reversed by treatment with a mitochondrial division inhibitor-1 (Mdivi-1). Mechanistically, Oip5-as1 selectively interacts with AKAP1 and CaN proteins, inhibiting CaN activation and subsequent DRP1 dephosphorylation at Ser637, thereby constraining DRP1's translocation to the mitochondria and its involvement in mitochondrial fission. CONCLUSIONS: Our study underscores the pivotal role of Oip5-as1 in mitigating excessive mitochondrial fission during MI/R injury. The findings not only enhance our comprehension of the molecular mechanisms underlying MI/R injury but also identify Oip5-as1 as a potential therapeutic target for ameliorating MI/R injury.

Highly Effective Hybrid Copper(I) Iodide Cluster Emitter with Negative Thermal Quenched Phosphorescence for X-Ray Imaging.

The low efficiency triplet emission of hybrid copper(I) iodide clusters is a critical obstacle to their further practical optoelectronic application. Herein, we present an efficient hybrid copper(I) iodide cluster emitter (DBA)4 Cu4 I4 , where the cooperation of excited state structure reorganization and the metallophilicity interaction enables ultra-bright triplet yellow-orange emission with a photoluminescence quantum yield over 94.9 %, and the phonon-assisted de-trapping process of exciton induces the negative thermal quenching effect at 80-300 K. We also investigate the potential of this emitter for X-ray imaging. The (DBA)4 Cu4 I4 wafer demonstrates a light yield higher than 104  photons MeV-1 and a high spatial resolution of ≈5.0 lp mm-1 , showing great potential in practical X-ray imaging applications. Our new copper(I) iodide cluster emitter can serve as a model for investigating the thermodynamic mechanism of photoluminescence in hybrid copper(I) halide phosphorescence materials.

Halogen Bonding: A New Platform for Achieving Multi-Stimuli-Responsive Persistent Phosphorescence.

Monotonous luminescence has always been a major factor limiting the application of organic room-temperature phosphorescence (RTP) materials. Enhancing and regulating the intermolecular interactions between the host and guest is an effective strategy to achieve excellent phosphorescence performance. In this study, intermolecular halogen bonding (CN⋅⋅⋅Br) was introduced into the host-guest RTP system. The interaction promoted intersystem crossing and stabilized the triplet excitons, thus helping to achieve strong phosphorescence emission. In addition, the weak intermolecular interaction of halogen bonding is sensitive to external stimuli such as heat, mechanical force, and X-rays. Therefore, the triplet excitons were easily quenched and colorimetric multi-stimuli responsive behaviors were realized, which greatly enriched the luminescence functionality of the RTP materials. This method provides a new platform for the future design of responsive RTP materials based on weak intermolecular interactions between the host and guest molecules.

Effect of intracoronary agents on the no-reflow phenomenon during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction: a network meta-analysis.

BACKGROUND: Despite the restoration of epicardial flow after primary percutaneous coronary intervention (PPCI), myocardial reperfusion remains impaired in a significant proportion of patients. We performed a network meta-analysis to assess the effect of 7 intracoronary agents (adenosine, anisodamine, diltiazem, nicorandil, nitroprusside, urapidil, and verapamil) on the no-reflow phenomenon in patients with ST-elevation myocardial infarction (STEMI) undergoing PPCI. METHODS: Database searches were conducted to identify randomized controlled trials (RCTs) comparing the 7 agents with each other or with standard PPCI. Outcome measures included thrombolysis in myocardial infarction flow grade (TFG), ST-segment resolution (STR), left ventricular ejection fraction (LVEF), major adverse cardiovascular events (MACEs), and adverse events. RESULTS: Forty-one RCTs involving 4069 patients were analyzed. The addition of anisodamine to standard PPCI for STEMI was associated with improved post-procedural TFG, more occurrences of STR, and improvement of LVEF. The cardioprotective effect of anisodamine conferred a MACE-free survival benefit. Additionally, nitroprusside was regarded as efficient in improving coronary flow and clinical outcomes. Compared with standard care, adenosine, nicorandil, and verapamil improved coronary flow but had no corresponding benefits regarding cardiac function and clinical outcomes. The ranking probability for the 7 treatment drugs showed that anisodamine consistently ranked the highest in efficacy outcomes (TFG < 3, STR, LVEF, and MACEs). No severe adverse events, such as hypotension and malignant arrhythmia, were observed in patients treated with anisodamine. Network meta-regression analysis showed that age, the time to reperfusion, and study follow-up did not affect the treatment effects. CONCLUSIONS: The intracoronary administration of anisodamine appears to improve myocardial reperfusion, cardiac function, and clinical outcomes in patients with STEMI undergoing PPCI. Given the limited quality and quantity of the included studies, more rigorous RCTs are needed to verify the role of this inexpensive and well-tolerated regimen.

Genome-wide identification of cucumber green mottle mosaic virus-responsive microRNAs in watermelon.

Cucumber green mottle mosaic virus (CGMMV) is a damaging pathogen that attacks crop plants belonging to the family Cucurbitaceae. Little is known about the regulatory role of microRNAs (miRNAs) in response to CGMMV infection. To identify CGMMV-responsive miRNAs, two sRNA libraries from mock-inoculated and CGMMV-infected watermelon leaves were constructed and sequenced using Solexa sequencing technology. In total, 471 previously known and 1,809 novel miRNAs were obtained, of which 377 known and 246 novel miRNAs were found to be differentially expressed during CGMMV infection. The target genes for the CGMMV-responsive known miRNAs are active in diverse biological processes, including cell wall modulation, plant hormone signaling, defense-related protein induction, primary and secondary metabolism, regulation of virus replication, and intracellular transport. The expression patterns of some CGMMV-responsive miRNAs and their corresponding targets were confirmed by RT-qPCR. One target gene for miR156a-5p was verified by 5'-RNA-ligase-mediated rapid amplification of cDNA ends (5'-RLM-RACE) analysis. The results of this study provide further insights into the miRNA-mediated regulatory network involved in the response to viral infection in watermelon and other cucurbit crops.

GhCFE1A, a dynamic linker between the ER network and actin cytoskeleton, plays an important role in cotton fibre cell initiation and elongation.

Fibre cell initiation and elongation is critical for cotton fibre development. However, little is known about the regulation of initiation and elongation during fibre cell development. Here, the regulatory role of a novel protein GhCFE1A was uncovered. GhCFE1A is preferentially expressed at initiation and rapid elongation stages during fibre development; in addition, much higher expression of GhCFE1A was detected at the fibre initiation stage in fibreless cotton mutants than in the fibre-bearing TM-1 wild-type. Importantly, overexpression of GhCFE1A in cotton not only delayed fibre cell elongation but also significantly reduced the density of lint and fuzz fibre initials and stem trichomes. Yeast two-hybrid assay showed that GhCFE1A interacted with several actin proteins, and the interaction was further confirmed by co-sedimentation assay. Interestingly, a subcellular localization assay showed that GhCFE1A resided on the cortical endoplasmic reticulum (ER) network and co-localized with actin cables. Moreover, the density of F-actin filaments was shown to be reduced in GhCFE1A-overexpressing fibres at the rapid elongation stage compared with the wild-type control. Taken together, the results demonstrate that GhCFE1A probably functions as a dynamic linker between the actin cytoskeleton and the ER network, and plays an important role in fibre cell initiation and elongation during cotton fibre development.

[A meta-analysis of randomized controlled trials comparing left with right radial approach for coronary angiography].

OBJECTIVE: To compare the efficacy between left radial approach (LRA) and right radial approach (RRA) for coronary angiography (CAG). METHODS: The following databases were searched, including PubMed, Embase, Web of science, Cochrane Library, CBM, VIP, Wanfang databases and CNKI, from creation of database to January 2013. Two reviewers extracted data independently, according to inclusive criteria, exclusion criteria and methods of Cochrane Collaboration. Statistical analysis was performed using Review Manager Software (RevMan 5.1). RESULTS: Eleven trials with 5 442 patients were included in the systematic review. The results of meta-analysis showed that when compared with RRA, LRA did not increase the failure rate of the procedures (OR = 1.04, 95%CI 0.80-1.35, P > 0.05) and amount of contrast medium (mean difference = 2.39, 95%CI -0.30-5.08), P > 0.05). However, LRA was superior to RRA in reducing fluoroscopy time (standardized mean difference = 0.15, 95%CI 0.06-0.24, P < 0.01). In addition, the incidence of severe tortuosity of subclavian artery was significantly lower with LRA (OR = 4.65, 95%CI 1.98-10.88, P < 0.01). CONCLUSIONS: Based on the current evidence, LRA shares similar safety with RRA for CAG and is superior to RRA in certain respects. LRA can thus be used either as an alternative approach or routine approach for CAG.

First-principles study on the effect of torsional deformation on WSe2 as an anode material for calcium ion batteries.

CONTEXT: In this paper, the effects of torsional deformation on the electronic properties of intrinsic WSe2 system and Ca-adsorbed WSe2 system were systematically studied by first-principles method. The results show that Ca can be stably adsorbed on the vacancy (H site) of WSe2 surface in all deformation systems, and the adsorption energy of the system without deformation is the highest. Intrinsic WSe2 is a semiconductor with a direct band gap of 1.53 eV. The torsional deformation makes WSe2 change from a direct band gap semiconductor to an indirect band gap semiconductor and finally to a metal property. The adsorption of Ca makes the conduction band of WSe2 move down and increases the number of peaks in the conduction band region. The new density of state peaks are mainly derived from the contribution of W-d, Se-p, and d orbitals of adsorbed atoms in each adsorption system. Mulliken charge analysis shows that Ca transfers most of the valence electrons to the substrate, and the torsional deformation changes the amount of transferred charge. The twist deformation reduces the diffusion barrier of Ca on WSe2 surface from 0.20 to 0.14 eV. The above results provide a basis for the improved application of WSe2 in ion batteries. METHODS: In this study, all the first-principles calculations are based on Materials Studio 8.0 software package. The generalized gradient approximation (GGA) functional Perdew-Burke-Ernzerhof (PBE) is used for the electron exchange correlation interactions in all systems. The optimization algorithm uses Broyden-Fletcher-Goldfarb-Shanno (BFGS) to optimize the model structure and calculate the energy. The measured cutoff energy is optimized to 450 eV, and the radius of the vacuum layer in the Z-axis direction is 20 Å. The K-point of 7 × 7 × 1 is selected by Monkhorst-Pack method. The structural optimization criterion is selected, the convergence radius of the force is 0.01 eV/Å, and the displacement radius between atoms is within 0.001 Å distance. The energy convergence radius of each atom is less than 1.0 × 10-6 eV/atom.

Insights into research on myocardial ischemia/reperfusion injury from 2012 to 2021: a bibliometric analysis.

BACKGROUND: Numerous studies on myocardial ischemia/reperfusion (MI/R) injury have been undertaken in recent years. Hotspots and developmental trends in MI/R research are being rapidly updated. However, there has been no bibliometric analysis that systematically evaluates existing literature on MI/R injury. Our study explores developments in MI/R research over the past decade, and provides a reference for future research. MATERIALS AND METHODS: Both experimental and clinical publications on MI/R injury from 2012 to 2021 were retrieved from the Web of Science Core Collection database. The CiteSpace and VOSviewer tools were used to perform a bibliometric analysis. RESULTS: A total of 8419 papers were analyzed. The number of annual publications demonstrated an overall upward trend, rising from 629 publications in 2012 to 1024 publications in 2021. China, the USA, Germany, England, and Italy were the top five contributors to MI/R studies. The Fourth Military Medical University in China contributed the most publications (188, 2.23%), while the University College London in England cooperated the most with relevant research institutions. Derek J Hausenloy (University College London), Derek M Yellon (University College London), and Gerd Heusch (University of Essen Medical School) were the top three most active and influential scholars according to the H-index. Among the top 10 journals with the most publications, Basic Research in Cardiology had the highest impact factors. The top three co-cited journals were Circulation, Circulation Research, and Cardiovascular Research. According to a co-cited reference analysis, MI/R research can be divided across 10 major subfields of mitophagy, cardioprotection, inflammation, remote ischemic preconditioning, long non-coding RNA, melatonin, postconditioning, mitochondria, microvascular obstruction, and ferroptosis. After 2018, the keywords with strongest citation bursts included extracellular vesicles, long non-coding RNA, cell proliferation, microRNA, mitochondrial quality control, mitophagy, biomarker, and mitochondrial biogenesis. CONCLUSIONS: The present study reveals the influential authors, cooperating institutions, and main research foci in the field of MI/R injury in the past decade. The latest hotspots are a more in-depth insight into the molecular mechanisms underlying MI/R injury, such as mitochondrial quality control, non-coding RNAs, cell proliferation, and extracellular vesicles.

Unexplained Left Ventricular Hypertrophy Diagnosed as a Cardiac Variant of Late-Onset Fabry Disease: A Case Report.

The cardiac variant of Fabry disease (FD) has high rates of missed diagnosis and misdiagnosis due to the lack of systemic symptoms. Here, we report a case of a 68-year-old female with delayed-onset FD presenting as concentric left ventricular hypertrophy (LVH) with right bundle branch block, atrial fibrillation, and diastolic dysfunction, which was first presented with coronary artery spasm. Early cardiac-specific signs are crucial for diagnosing this disease due to the lack of extracardiac indications and the late onset of symptoms. This case raises a new red flag that patients with unexplained LVH and its atypical electrocardiographic (ECG) manifestations accompanied by diastolic dysfunction should be considered for FD. We also recommend further refinement of examinations associated with Fabry disease, which will contribute to the early diagnosis and treatment of the disease.

Titanate nanotubes as a promising absorbent for high effective radioactive uranium ions uptake.

In this study, titanate nanotubes with a layered structure were investigated for the uptake of radioactive uranium ions for the first time. The nanotubes have been successfully prepared with a reaction of Ti metal nanopowders and NaOH mixed solution by a novel and effective ultrasonic-assisted hydrothermal method. As the absorbent of radioactive ions, they have the ability to selectively adsorb radioactive U ions from water via ion exchange process and subsequently immobilize these ions in the nanotube sorbents without the need of further treatment after absorption. Sorption induces considerable deformation of the layer structures, resulting in the structures changing from the nanotubes to sheets and having the ability of permanent entrapment of the radioactive cations in these as-grown sheets. Our results have proved that titanate nanotubes can be used as a promising absorbent for the removal of nuclear leaking water at the first time.

Improvement of Al2O3 on the multi-pollutant control performance of NOx and chlorobenzene in vanadia-based catalysts.

We compared the influences of Al2O3 and SiO2 on a traditional V2O5-MoO3/TiO2 for the simultaneous removal of NOx and chlorobenzene (CB). The Al2O3 doping catalyst considerably broadens the active temperature window with higher NOx reduction and CB oxidation efficiencies than the SiO2 doping one and the V2O5-MoO3/TiO2. Furthermore, its resistance to SO2 was preserved and the quantities of polychlorinated byproducts also decreased. The increase in activity at low temperatures could be due to the promotion of vanadia reducibility via interactions between V2O5 and Al2O3. Moreover, the high temperature activity could be due to the additional surface acidities provided by Al2O3, in which the Lewis acid sites played the predominant role in both NH3 adsorptions and CB de-chlorination compared to the Brønsted acid sites. Finally, we proposed that Al2O3 is an effective addition for vanadia-based catalyst in NOx and CB simultaneous removal from stationary sources.

Case report: A case of isolated cardiac sarcoidosis diagnosed by multimodal imaging and endomyocardial biopsy.

Due to its low incidence, isolated cardiac sarcoidosis (ICS) is often missed or misdiagnosed. Herein, we describe a case of ICS in a 52-year-old male patient. Advanced imaging, including cardiac magnetic resonance (CMR) and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET), could not only screen high-risk patients for establishing diagnosis, but also guide endomyocardial biopsy (EMB) for improving cardiac disease detection rate. This case highlights the importance of multimodal imaging for screening and necessity of EMB for diagnosis.

PM2.5-Induced Programmed Myocardial Cell Death via mPTP Opening Results in Deteriorated Cardiac Function in HFpEF Mice.

PM2.5 exposure can induce or exacerbate heart failure and is associated with an increased risk of heart failure hospitalization and mortality; however, the underlying mechanisms remain unclear. This study focuses on the potential mechanisms underlying PM2.5 induction of cardiomyocyte programmed necrosis as well as its promotion of cardiac function impairment in a mouse model of heart failure with preserved ejection fraction (HFpEF). HFpEF mice were exposed to concentrated ambient PM2.5 (CAP) (CAP group) or filtered air (FA) (FA group) for 6 weeks. Changes in myocardial pathology and cardiac function were documented for comparisons between the two groups. In vitro experiments were performed to measure oxidative stress and mitochondrial permeability transition pore (mPTP) dynamics in H9C2 cells following 24 h exposure to PM2.5. Additionally, co-immunoprecipitation was conducted to detect p53 and cyclophilin D (CypD) interactions. The results showed exposure to CAP promoted cardiac function impairment in HFpEF mice. Myocardial pathology analysis and in vitro experiments demonstrated that PM2.5 led to mitochondrial damage in cardiomyocytes and, eventually, their necrosis. Moreover, our experiments also suggested that PM2.5 increases mitochondrial reactive oxygen species (ROS), induces DNA oxidative damage, and decreases the inner mitochondrial membrane potential (ΔΨm). This indicates the presence of mPTP opening. Co-immunoprecipitation results showed a p53/CypD interaction in the myocardial tissue of HFpEF mice in the CAP group. Inhibition of CypD by cyclosporin A was found to reverse PM2.5-induced mPTP opening and H9C2 cell death. In conclusion, PM2.5 induces mPTP opening to stimulate mitochondria-mediated programmed necrosis of cardiomyocytes, and it might exacerbate cardiac function impairment in HFpEF mice.

All-Inorganic Manganese-Based CsMnCl3 Nanocrystals for X-Ray Imaging.

Lead-based halide perovskite nanomaterials with excellent optical properties have aroused great attention in the fields of solar cells, light-emitting diodes, lasing, X-ray imaging, etc. However, the toxicity of lead prompts researchers to develop alternatives to cut down the usage of lead. Herein, all-inorganic manganese-based perovskite derivatives, CsMnCl3 nanocrystals (NCs), with uniform size and morphology have been synthesized successfully via a modified hot-injection method. These NCs have a direct bandgap of 4.08 eV and a broadband emission centered at 660 nm. Through introducing modicum lead (1%) into the CsMnCl3 NCs, the photoluminescence intensity greatly improves, and the quantum yield (PLQY) increases from 0.7% to 21%. Furthermore, the CsMnCl3 :1%Pb NCs feature high-efficiency of X-ray absorption and radioluminescence, which make these NCs promising candidates for X-ray imaging.

Genetic Mapping and Identification of the Candidate Genes for Mottled Rind in Cucumis melo L.

The rind appearance of melon is one of the most vital commercial quality traits which determines the preferences and behavior of consumers toward the consumption of melon. In this study, we constructed an F2 population derived from SC (mottled rind) and MG (non-mottled rind) lines for mapping the mottled rind gene(s) in melon. Genetic analysis showed that there were two dominant genes (CmMt1 and CmMt2) with evidence of epistasis controlling the mottled rind. Meanwhile, the phenotypic segregation ratio implied that the immature rind color had an epistatic effect on the mottled rind, which was regulated by CmAPRR2. A Kompetitive Allele-Specific PCR (KASP) DNA marker (CmAPRR2 SNP(G/T) ) was developed and shown to co-segregate with rind color, confirming that CmAPRR2 was CmMt1. Using bulked segregant analysis sequencing and KASP assays, CmMt2 was fine-mapped to an interval of 40.6 kb with six predicted genes. Functional annotation, expression analysis, and sequence variation analyses confirmed that AtCPSFL1 homolog, MELO3C026282, was the most likely candidate gene for CmMt2. Moreover, pigment content measurement and transmission electron microscopy analysis demonstrated that CmMt2 might participate in the development of chloroplast, which, in turn, decreases the accumulation of chlorophyll. These results provide insight into the molecular mechanism underlying rind appearance and reveal valuable information for marker-assisted selection breeding in melon.

Effects of SGLT-2 inhibitors on health-related quality of life and exercise capacity in heart failure patients with reduced ejection fraction: A systematic review and meta-analysis.

OBJECTIVE: Improving health-related quality of life (HRQoL) and exercise capacity is an important goal of treatment in heart failure (HF). However, evidence for the effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on the improvement of HRQoL and exercise capacity seems to be conflicted. We performed a systematic review and meta-analysis to evaluate the effects of SGLT-2 inhibitors on HRQL and exercise capacity in patients with heart failure and reduced ejection fraction (HFrEF). METHODS: All studies (up to March 20, 2021) evaluating the effects of SGLT-2 inhibitors on HRQoL and exercise capacity in patients with HFrEF were initially searched from four electronic search engines: PubMed, Web of Science, Cochrane Library, and SinoMed. All statistical analyses were performed with RevMan 5.4. RESULTS: We included 9 articles describing 7 trials with 9428 patients. SGLT-2 inhibitors group exhibited significant improvement in HRQoL assessed by Kansas City Cardiomyopathy Questionnaires (KCCQ) (MD: 2.13, 95% CI: 1.11 to 3.14, p < 0.001) and the rate of KCCQ-overall summary score improvement≥5 points (RR 1.15, 95%CI 1.08 to 1.21, P < 0.001) compared with placebo. No significant difference was observed in exercise capacity assessed by 6-min walk test distance between SGLT-2 inhibitors and placebo (MD 24.45, 95%CI -22.82 to 71.72, P = 0.31). CONCLUSIONS: Our meta-analysis demonstrates that SGLT-2 inhibitors significantly improve HRQoL, and supports the concept that SGLT-2 inhibitors do not significantly improve exercise capacity in patients with HFrEF. Studies with larger sample sizes and longer follow-up duration are needed to determine whether the treatment with SGLT-2 inhibitors may improve exercise ability. PROSPERO: CRD42021248346.

Location of the beta 4 transmembrane helices in the BK potassium channel.

Large-conductance, voltage- and Ca(2+)-gated potassium (BK) channels control excitability in a number of cell types. BK channels are composed of alpha subunits, which contain the voltage-sensor domains and the Ca(2+)- sensor domains and form the pore, and often one of four types of beta subunits, which modulate the channel in a cell-specific manner. beta 4 is expressed in neurons throughout the brain. Deletion of beta 4 in mice causes temporal lobe epilepsy. Compared with channels composed of alpha alone, channels composed of alpha and beta 4 activate and deactivate more slowly. We inferred the locations of the two beta 4 transmembrane (TM) helices TM1 and TM2 relative to the seven alpha TM helices, S0-S6, from the extent of disulfide bond formation between cysteines substituted in the extracellular flanks of these TM helices. We found that beta 4 TM2 is close to alpha S0 and that beta 4 TM1 is close to both alpha S1 and S2. At least at their extracellular ends, TM1 and TM2 are not close to S3-S6. In six of eight of the most highly crosslinked cysteine pairs, four crosslinks from TM2 to S0 and one each from TM1 to S1 and S2 had small effects on the V(50) and on the rates of activation and deactivation. That disulfide crosslinking caused only small functional perturbations is consistent with the proximity of the extracellular ends of TM2 to S0 and of TM1 to S1 and to S2, in both the open and closed states.

Combined treatment with valsartan and fluvastatin to delay disease progression in nonpermanent atrial fibrillation with hypertension: A clinical trial.

BACKGROUND: Atrial fibrillation (AF) is a complex cardiac arrhythmia in clinical practice with increasing incidence. However, the effects of statins on patients with AF are not quite clear. HYPOTHESIS: To investigate the protective effect of calcium channel blocker (CCB) and valsartan combined fluvastatin on hypertension (HTN) patients with nonpermanent AF. METHODS: In three and a half years, 189 cases of patients diagnosed as HTN combining nonpermanent AF by eight medical centers, were recruited and randomly assigned to four groups with varied treatments: CCB group; CCB + statin group; valsartan group; and valsartan + statin group. The four groups were followed up for 24 months. The 7-day Holter ultrasound echocardiography (UCG) and biochemical indexes were completed at preset time nodes respectively. RESULTS: After 24 months of follow-up, 178 patients completed the study. Compared with CCB group, the blood lipid level, inflammatory index, ultrasonic index and electrocardiographic measurement results of CCB + statin group, valsartan group and valsartan + statin group were improved in different degrees and had statistical significance (P < .05 or P < .01). Furthermore, the improvement trend of CCB + statin group and valsartan + statin group was more obvious. CONCLUSIONS: The results indicated that valsartan can reduce AF load and recurrence rate, and delay the progression of nonpermanent AF to permanent AF in multiple ways, and the effect of combination of valsartan and fluvastatin is more significant. These results provide a new direction for the integrated upstream control strategy of AF.

lncRNA Oip5-as1 attenuates myocardial ischaemia/reperfusion injury by sponging miR-29a to activate the SIRT1/AMPK/PGC1α pathway.

OBJECTIVES: Myocardial ischaemia/reperfusion (MI/R) injury is associated with adverse cardiovascular outcomes after acute myocardial infarction. However, the molecular mechanisms underlying MI/R injury are unclear. This study investigated the role of long non-coding RNA (lncRNA) Oip5-as1 in regulating mitochondria-mediated apoptosis during MI/R injury. MATERIALS AND METHODS: Sprague-Dawley rats were subjected to MI/R induced by ligation of the left anterior descending coronary artery followed by reperfusion. H9c2 cells were incubated under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions to mimic in vivo MI/R. RT-qPCR and Western blot were used to evaluate gene and protein levels. CCK-8 assay, biochemical assay and flow cytometric analysis were performed to assess the function of Oip5-as1. The dual-luciferase gene reporter assay and RIP assay were conducted as needed. RESULTS: Oip5-as1 expression was downregulated in the hearts of rats with MI/R and in H9c2 cells treated with OGD/R. Oip5-as1 overexpression alleviated reactive oxygen species-driven mitochondrial injury and consequently decreased apoptosis in MI/R rats and H9c2 cells exposed to OGD/R. Mechanistically, Oip5-as1 acted as a competing endogenous RNA of miR-29a and thus decreased its expression. Inhibition of miR-29a reduced the oxidative stress and cytotoxicity induced by OGD/R. Overexpression of miR-29a reversed the anti-apoptotic effect of Oip5-as1 in H9c2 cells treated with OGD/R. Further experiments identified SIRT1 as a downstream target of miR-29a. Oip5-as1 upregulated SIRT1 expression and activated the AMPK/PGC1α pathway by targeting miR-29a, thus reducing the apoptosis triggered by OGD/R. However, these effects were reversed by a selective SIRT1 inhibitor, EX527. CONCLUSIONS: Oip5-as1 suppresses miR-29a leading to activation of the SIRT1/AMPK/PGC1α pathway, which attenuates mitochondria-mediated apoptosis during MI/R injury. Our findings thus provide new insights into the molecular mechanisms of MI/R injury.