IP3R1-mediated MAMs formation contributes to mechanical trauma-induced hepatic injury and the protective effect of melatonin.

INTRODUCTION: There is a high morbidity and mortality rate in mechanical trauma (MT)-induced hepatic injury. Currently, the molecular mechanisms underlying liver MT are largely unclear. Exploring the underlying mechanisms and developing safe and effective medicines to alleviate MT-induced hepatic injury is an urgent requirement. The aim of this study was to reveal the role of mitochondria-associated ER membranes (MAMs) in post-traumatic liver injury, and ascertain whether melatonin protects against MT-induced hepatic injury by regulating MAMs. METHODS: Hepatic mechanical injury was established in Sprague-Dawley rats and primary hepatocytes. A variety of experimental methods were employed to assess the effects of melatonin on hepatic injury, apoptosis, MAMs formation, mitochondrial function and signaling pathways. RESULTS: Significant increase of IP3R1 expression and MAMs formation were observed in MT-induced hepatic injury. Melatonin treatment at the dose of 30 mg/kg inhibited IP3R1-mediated MAMs and attenuated MT-induced liver injury in vivo. In vitro, primary hepatocytes cultured in 20% trauma serum (TS) for 12 h showed upregulated IP3R1 expression, increased MAMs formation and cell injury, which were suppressed by melatonin (100 µmol/L) treatment. Consequently, melatonin suppressed mitochondrial calcium overload, increased mitochondrial membrane potential and improved mitochondrial function under traumatic condition. Melatonin's inhibitory effects on MAMs formation and mitochondrial calcium overload were blunted when IP3R1 was overexpressed. Mechanistically, melatonin bound to its receptor (MR) and increased the expression of phosphorylated ERK1/2, which interacted with FoxO1 and inhibited the activation of FoxO1 that bound to the IP3R1 promoter to inhibit MAMs formation. CONCLUSION: Melatonin prevents the formation of MAMs via the MR-ERK1/2-FoxO1-IP3R1 pathway, thereby alleviating the development of MT-induced liver injury. Melatonin-modulated MAMs may be a promising therapeutic therapy for traumatic hepatic injury.

Engineering dual-crystal configurations in perovskite oxides boosts electrocatalysis of lithium-oxygen batteries.

Sculpting crystal configurations can vastly affect the charge and orbital states of electrocatalysts, fundamentally determining the catalytic activity of lithium-oxygen (Li-O2) batteries. However, the crucial role of crystal configurations in determining the electronic states has usually been neglected and needs to be further examined. Herein, we introduce orthorhombic and trigonal system into 0.5La0.6Sr0.4MnO3-0.5LaMn0.6Co0.4O3 (LSMCO) by selectively incorporating Sr and Co cations into the LaMnO3 framework during the sol-gel process, which is used to explore the relationship among crystal structure, electronic states and catalytic performance. Based on both experimental and theoretical calculations, the dual-crystal configurations induce strong lattice distortion, which promotes MnO6 octahedra vibration and shortened MnO bonds. Furthermore, the suppressed Jahn-Teller distortion weakens the orbital arrangement and accelerates the charge delocalization, leading to the conversion of Mn3+ to Mn4+ and optimized electronic states. Ultimately, this resulted in optimized Mn 3d and O 2p orbital hybridization and activated lattice oxygen function, leading to a significant improvement in electrocatalytic activity. The LSMCO catalyzed Li-O2 battery achieves enhanced discharge capacity of 14498.7 mAh/g and cycling stability of 258 cycles. This work highlights the significance of inner structure and presents a feasible strategy for engineering crystal configurations to boost electrocatalysis of Li-O2 batteries.

Scalable fabrication of ultra-fine lithiophilic nanoparticles encapsulated in soft buffered hosts for long-life anode-free Li2S-based cells.

Minimizing the amount of metallic lithium (Li) to zero excess to achieve an anode-free configuration can help achieve safer, higher energy density, and more economical Li metal batteries. Nevertheless, removal of excess Li creates challenges for long-term cycling performance in Li metal batteries due to the lithiophobic copper foils as anodic current collectors. Here, we improve the long-term cycling performance of anode-free Li metal batteries by modifying the anode-free configuration. Specifically, a lithiophilic Au nanoparticle-anchored reduced graphene oxide (Au/rGO) film is used as an anodic modifier to reduce the Li nucleation overpotential and inhibit dendrite growth by forming a lithiophilic LixAu alloy and solid solution, which is convincingly evidenced by density functional theory calculations and experimentally. Meanwhile, the flexible rGO film can also act as a buffer layer to endure the volume expansion during repeated Li plating/stripping processes. In addition, the Au/rGO film promotes a homogeneous distribution of the electric field over the entire anodic surface, thus ensuring a uniform deposition of Li during the electrodeposition process, which is convincingly evidenced by finite element simulations. As expected, the Li||Au/rGO-Li half-cell shows a highly stable long-term cycling performance for at least 500 cycles at 0.5 mA cm-2 and 0.5 mA h cm-2. A Li2S-based anode-free full cell allows achieving a stable operation life of up to 200 cycles with a capacity retention of 63.3%. This work provides a simple and scalable fabrication method to achieve anode-free Li2S-based cells with high anodic interface stability and a long lifetime.

Artificial bi-functional layers promoting Zn2+ desolvation and homogeneous deposition for reversible zinc metal anodes.

Rechargeable aqueous zinc-ion hybrid supercapacitors (ZHSs) are drawing extensive attention because of their cost-effectiveness and diminished safety hazards. Nevertheless, large-scale application of ZHSs has been hindered by the severe side reactions and rampant dendrites growth on the surface of Zn metal anodes. Herein, we propose a three-dimensional organic-inorganic composite frame material as an artificial bi-functional layer coated on the zinc foil, featuring nitrogenous functional groups with zincophilicity (abbreviated as NCFM@Zn). The nitrogen (N) site's strong adsorption capacity and synergistic effect of the sub-nanopore size promote rapid desolvation of zinc ions and reduce side reactions, while also prolonging galvanized nucleation's Sand's time and allowing for even nucleation. Moreover, the uniform distribution of N on the layer results in homogeneous zinc ions flux and supports consistent zinc plating while inhibiting dendrites generation. As a result of this unique artificial bi-functional layer, symmetric Zn cells can survive 2500 h at 2.5 mA cm-2. High-areal-capacity zinc||activated carbon hybrid supercapacitors also demonstrate 20,000 cycles at high Coulombic efficiency, thus highlighting the utter convenience and potential of this strategy for modifying rechargeable metal hybrid supercapacitor surfaces.

N, F-enriched inorganic/organic composite interphases to stabilize lithium metal anodes for long-life anode-free cells.

The practical application of lithium metal batteries is considered to be one of the most promising successors for lithium-ion batteries due to their ability to meet the high-energy storage demands of modern society. However, their application is still hindered by the unstable solid electrolyte interphase (SEI) and uncontrollable dendrite growth. In this study, we propose a robust composite SEI (C-SEI) that consists of a fluorine doped boron nitride (F-BN) inner layer and an organic polyvinyl alcohol (PVA) outer layer. Both theoretical calculations and experimental results demonstrate that the F-BN inner layer induces the formation of favourable components (LiF and Li3N) at the interface, promoting rapid ionic transport and inhibiting electrolyte decomposition. The PVA outer layer acts as a flexible buffer in the C-SEI, ensuring the structural integrity of the inorganic inner layer during lithium plating and stripping. The C-SEI modified lithium anode shows a dendrite-free performance and stable cycle over 1200 h, with an ultralow overpotential (15 mV) at 1 mA cm-2 in this study. This novel approach also enhances the stability of capacity retention rate by 62.3% after 100 cycles even in anode-free full cells (C-SEI@Cu||LFP). Our findings suggest a feasible strategy for addressing the instability inherent in SEI, showing great prospects for the practical application of lithium metal batteries.

Chromium-doped inverse spinel electrocatalysts with optimal orbital occupancy for facilitating reaction kinetics of lithium-oxygen batteries.

Tailored electrocatalysts that can modulate their electronic structure are highly desirable to facilitate the reaction kinetics of oxygen evolution reaction (OER) and oxidation reduction reaction (ORR) in lithium-oxygen batteries (LOB). Although octahedron predominant inverse spinels (e.g., CoFe2O4) have been proposed as promising candidates for catalytic reactions, their performance has remained unsatisfactory. Herein, the chromium (Cr) doped CoFe2O4 nanoflowers (Cr-CoFe2O4) are elaborately constructed on nickel foam as a bifunctional electrocatalyst that drastically improves the performance of LOB. The results show that the partially oxidized Cr6+ stabilizes the cobalt (Co) sites at high-valence and regulates the electronic structure of Co sites, facilitating the oxygen redox kinetics of LOB due to their strong electron-withdrawing capability. Moreover, DFT calculations and ultraviolet photoelectron spectrometer (UPS) results consistently demonstrate that Cr doping optimizes the eg electron filling state of the active octahedral Co sites, significantly improves the covalency of Co-O bonds, and enhances the degree of Co 3d-O 2p hybrids. As a result, Cr-CoFe2O4 catalyzed LOB can achieve low overpotential (0.48 V), high discharge capacity (22030 mA h g-1) and long-term cycling durability (over 500 cycles at 300 mA g-1). This work promotes the oxygen redox reaction and accelerates the electron transfer between Co ions and oxygen-containing intermediates, highlighting the potential of Cr-CoFe2O4 nanoflowers as bifunctional electrocatalysts for LOB.

Ischemia/reperfusion-induced MiD51 upregulation recruits Drp1 to mitochondria and contributes to myocardial injury.

The translocation of Drp1 from the cytosol to mitochondria leads to Drp1 activation and mitochondrial fission in myocardial ischemia/reperfusion (MI/R). However, the molecular mechanism underlying mitochondrial Drp1 translocation remains poorly understood. Mitochondrial Drp1 recruitment relies on 4 binding partners including MiD49, MiD51, Mff and Fis1. This study was to elucidate which one facilitate mitochondrial Drp1 translocation and its role in MI/R injury. MI/R was induced by ligating the left anterior descending coronary artery for 30 min and subsequent reperfusion for 3 h. Primary neonatal cardiomyocytes were subjected to hypoxia for 2 h and reoxygenation for 4 h. SiRNA or Adeno-associated virus (AAV) expressing shRNA was used to knock down the key binding partner in vitro or in vivo respectively. The expression of MiD51 rather than other binding partners (MiD49, Mff or Fis1) was increased after MI/R. MiD51 knockdown inhibited hypoxia/reoxygenation (H/R) or ischemia/reperfusion (I/R)-induced mitochondrial Drp1 translocation. SiRNA-induced knockdown of MiD51 suppressed mitochondrial oxidative stress, improved mitochondrial function and alleviate cellular injury in H/R cardiomyocytes. AAV-mediated knockdown of MiD51 reduced myocardial injury and improved cardiac function in the I/R hearts, while mitochondrial Drp1 translocation and cardiac function were not affected by MiD51 knockdown in the hearts without I/R. MiD51 is identified as the binding partner that promotes mitochondrial Drp1 translocation and contributes to MI/R injury. Inhibition of MiD51 may be a potential therapeutic target to alleviate MI/R injury.

Air-Stable Protective Layers for Lithium Anode Achieving Safe Lithium Metal Batteries.

With markedly expansive demand in energy storage devices, rechargeable batteries will concentrate on achieving the high energy density and adequate security, especially under harsh operating conditions. Considering the high capacity (3860 mA h g-1 ) and low electrochemical potential (-3.04 V vs the standard hydrogen electrode), lithium metal is identified as one of the most promising anode materials, which has sparked a research boom. However, the intrinsically high reactivity triggers a repeating fracture/reconstruction process of the solid electrolyte interphase, side reactions with electrolyte and lithium dendrites, detrimental to the electrochemical performance of lithium metal batteries (LMBs). Even worse, when exposed to air, lithium metal will suffer severe atmospheric corrosion, especially the reaction with moisture, leading to grievous safety hazards. To settle these troubles, constructing air-stable protective layers (ASPLs) is an effective solution. In this review, besides the necessity of ASPLs is highlighted, the modified design criteria, focusing on enhancing chemical/mechanical stability and controlling ion flux, are proposed. Correspondingly, current research progress is comprehensively summarized and discussed. Finally, the perspectives of developing applicable lithium metal anodes (LMAs) are put forward. This review guides the direction for the practical use of LMAs, further pushing the evolution of safe and stable LMBs.

Band engineering in heterostructure catalysts to achieve High-Performance Lithium-Oxygen batteries.

The electronic structure of cathode catalysts dominates the electrochemistry reaction kinetics in lithium-oxygen batteries. However, conventional catalysts perform inferior intrinsic activity due to the low d-band level of the active sites makes it difficult to bond with the reaction intermediates, which results in poor electrochemical performance of lithium-oxygen batteries. Herein, NiFe2O4/MoS2 heterostructures are elaborately constructed to reach an electronic state balance for the active sites, which realizes the upper shift of the d-band level and enhanced adsorption of intermediates. Density functional theory calculation suggests that the d-band center of Fe active sites on the heterostructure moves toward the Fermi level, demonstrating the heterointerface engineering endows Fe active sites with high d-band level by the transfer and balance of electron. As a proof of concept, lithium-oxygen battery catalyzed by NiFe2O4/MoS2 exhibits a large specific capacity of 21526 mA h g-1 and an extended cycle performance for 268 cycles. Moreover, NiFe2O4/MoS2 with strong adsorption to intermediates promotes the uniform growth of discharge products, which is favor of the reversible decomposition during cycling. This work presents the energy band regulation of the active sites in heterostructure catalysts has great feasibility for enhancing catalytic activities.

Rhein ameliorates transverse aortic constriction-induced cardiac hypertrophy via regulating STAT3 and p38 MAPK signaling pathways.

The progression from compensatory hypertrophy to heart failure is difficult to reverse, in part due to extracellular matrix fibrosis and continuous activation of abnormal signaling pathways. Although the anthraquinone rhein has been examined for its many biological properties, it is not clear whether it has therapeutic value in the treatment of cardiac hypertrophy and heart failure. In this study, we report for the first time that rhein can ameliorate transverse aortic constriction (TAC)-induced cardiac hypertrophy and other cardiac damage in vivo and in vitro. In addition, rhein can reduce cardiac hypertrophy by attenuating atrial natriuretic peptide, brain natriuretic peptide, and ß-MHC expression; cardiac fibrosis; and ERK phosphorylation and transport into the nucleus. Furthermore, the inhibitory effect of rhein on myocardial hypertrophy was similar to that of specific inhibitors of STAT3 and ERK signaling. In addition, rhein at therapeutic doses had no significant adverse effects or toxicity on liver and kidney function. We conclude that rhein reduces TAC-induced cardiac hypertrophy via targeted inhibition of the molecular function of ERK and downregulates STAT3 and p38 MAPK signaling. Therefore, rhein might be a novel and effective agent for treating cardiac hypertrophy and other cardiovascular diseases.

Injectable selenium-containing polymeric hydrogel formulation for effective treatment of myocardial infarction.

Myocardial infarction (MI) is a serious threat to people's life and health, which is significantly hindered by effective treatment formulations. Interestingly, our recent endeavour of designing selenium-containing polymeric hydrogel has been experimentally proved to be helpful in combating inflammatory responses and treating MI. The design was inspired by selenium with anti-inflammatory and anti-fibrosis activities, and the formulation could also serve as a support of myocardial tissue upon the failure of this function. In details, an injectable selenium-containing polymeric hydrogel, namely, poly[di-(1-hydroxylyndecyl) selenide/polypropylene glycol/polyethylene glycol urethane] [poly(DH-SE/PEG/PPG urethane)], was synthesised by combining a thermosensitive PPG block, DH-Se (which has oxidation-reduction properties), and hydrophilic PEG segments. Based on the established mouse model of MI, this formulation was experimentally validated to effectively promote the recovery of cardiac function. At the same time, we confirmed by enzyme-linked immunosorbent assay, Masson staining and Western blotting that this formulation could inhibit inflammation and fibrosis, so as to significantly improve left ventricular remodelling. In summary, a selenium-containing polymeric hydrogel formulation analysed in the current study could be a promising therapeutic formulation, which can provide new strategies towards the effective treatment of myocardial infarction or even other inflammatory diseases.

Inhibition of GSDMD Activates Poly(ADP-ribosyl)ation and Promotes Myocardial Ischemia-Reperfusion Injury.

The precise control of cardiomyocyte viability is imperative to combat myocardial ischemia-reperfusion injury (I/R), in which apoptosis and pyroptosis putatively contribute to the process. Recent researches indicated that GSDMD is involved in I/R as an executive protein of pyroptosis. However, its effect on other forms of cell death is unclear. We identified that GSDMD and GSDMD-N levels were significantly upregulated in the I/R myocardium of mice. Knockout of GSDMD conferred the resistance of the hearts to reperfusion injury in the acute phase of I/R but aggravated reperfusion injury in the chronic phase of I/R. Mechanistically, GSDMD deficiency induced the activation of PARylation and the consumption of NAD+ and ATP, leading to cardiomyocyte apoptosis. Moreover, PJ34, a putative PARP-1 inhibitor, reduced the myocardial injury caused by GSDMD deficiency. Our results reveal a novel action modality of GSDMD in the regulation of cardiomyocyte death; inhibition of GSDMD activates PARylation, suggesting the multidirectional role of GSDMD in I/R and providing a new theory for clinical treatment.

Interfacial Electron Redistribution of Hydrangea-like NiO@Ni2 P Heterogeneous Microspheres with Dual-Phase Synergy for High-Performance Lithium-Oxygen Battery.

Lithium-oxygen batteries (LOBs) with ultra-high theoretical energy density (≈3500 Wh kg-1 ) are considered as the most promising energy storage systems. However, the sluggish kinetics during the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) can induce large voltage hysteresis, inferior roundtrip efficiency and unsatisfactory cyclic stability. Herein, hydrangea-like NiO@Ni2 P heterogeneous microspheres are elaborately designed as high-efficiency oxygen electrodes for LOBs. Benefitting from the interfacial electron redistribution on NiO@Ni2 P heterostructure, the electronic structure can be modulated to ameliorate the chemisorption of the intermediates, which is confirmed by density functional theory (DFT) calculations and experimental characterizations. In addition, the interpenetration of the PO bond at the NiO@Ni2 P heterointerface leads to the internal doping effect, thereby boosting electron transfer to further improve ORR and OER activities. As a result, the NiO@Ni2 P electrode shows a low overpotential of only 0.69 V, high specific capacity of 18254.1 mA h g-1 and superior long-term cycling stability of over 1400 h. The exploration of novel bifunctional electrocatalyst in this work provides a new solution for the practical application of LOBs.

Synergy of cobalt vacancies and iron doping in cobalt selenide to promote oxygen electrode reactions in lithium-oxygen batteries.

Electronic structural engineering plays a key role in the design of high-efficiency catalysts. Here, to achieve optimal electronic states, introduction of exotic Fe dopant and Co vacancy into CoSe2 nanosheet (denoted as Fe-CoSe2-VCo) is presented. The obtained Fe-CoSe2-VCo demonstrates excellent catalytic activity as compared to CoSe2. Experimental results and density functional theory (DFT) calculations confirm that Fe dopant and Co defects cause significant electron delocalization, which reduces the adsorption energy of LiO2 intermediate on the catalyst surface, thereby obviously improving the electrocatalytic activity of Fe-CoSe2-VCo towards oxygen redox reactions. Moreover, the synergistic effect between Co vacancy and Fe dopant is able to optimize the microscopic electronic structure of Co ion, further reducing the energy barrier of oxygen electrode reactions on Fe-CoSe2-VCo. And the lithium-oxygen batteries (LOBs) based on Fe-CoSe2-VCo electrodes demonstrate a high Coulombic efficiency (CE) of about 72.66%, a large discharge capacity of about 13723 mA h g-1, and an excellent cycling life of about 1338 h. In general, the electronic structure modulation strategy with the reasonable introduction of vacancy and dopant is expected to inspire the design of highly efficient catalysts for various electrochemical systems.

Adjusting the d-band center of metallic sites in NiFe-based Bimetal-organic frameworks via tensile strain to achieve High-performance oxygen electrode catalysts for Lithium-oxygen batteries.

Developing effective electrocatalyst and fundamentally understanding the corresponding working mechanism are both urgently desired to overcome the current challenges facing lithium-oxygen batteries (LOBs). Herein, a series of NiFe-based bimetal-organic frameworks (NiFe-MOFs) with certain internal tensile strain are fabricated via a simple organic linker scission strategy, and served as cathode catalysts for LOBs. The introduced tensile strain broadens the inherent interatomic distances, leading to an upshifted d-band center of metallic sites and thus the enhancement of the adsorption strength of catalysts surface towards intermediates, which is contributed to rationally regulate the crystallinity of discharge product Li2O2. As a result, the uniformly distributed amorphous film-like Li2O2 tightly deposits on the surface of strain-regulated MOF, resulting in excellent electrochemical performance of LOBs, including a large discharge capacity of 12317.4 mAh g-1 at 100 mA g-1 and extended long-term cyclability of 357 cycles. This work presents a novel insight in adjusting the adsorption strength of cathode catalysts towards intermediates via introducing tensile strain in catalysts, which is a pragmatic strategy for improving the performance of LOBs.

Exercise ameliorates insulin resistance and improves ASK1-mediated insulin signalling in obese rats.

Increasing evidence reveals that physical exercise is an efficient therapeutical approach in the treatment of insulin resistance (IR) and related metabolic diseases. However, the potential beneficial effects of exercise on insulin resistance and its underlying mechanisms remain unclear. Recent findings elucidated the negative role of ASK1 in repressing the glucose uptake through JNK1-IRS1-Akt signalling in liver. Thus, a detailed investigation of the effect of ASK1-mediated insulin signalling on exercise-mediated improvement of insulin sensitivity and its underlying mechanism was implemented in this study. Using a high-fat diet-induced IR rat model of chronic or acute swimming exercise training, we here showed that body weight and visceral fat mass were significantly reduced after chronic exercise. Moreover, chronic exercise reduced serum FFAs levels and hepatic triglyceride content. Both chronic and acute exercise promoted glucose tolerance and insulin sensitivity. Meanwhile, both chronic and acute exercise decreased ASK1 phosphorylation and improved JNK1-IRS1-Akt signalling. Furthermore, exercise training decreased CFLAR, CREG and TRAF1 protein levels in liver of obese rats, which are positive regulator of ASK1 activity. These results suggested that swimming exercise demonstrated to be an effective ameliorator of IR through the regulation of ASK1-mediated insulin signalling and therefore, could present a prospective therapeutic mean towards the treatment of IR and several metabolic diseases based on IR, containing NAFLD and type Ⅱ diabetes.

Rationalizing Surface Electronic Configuration of Ni-Fe LDO by Introducing Cationic Nickel Vacancies as Highly Efficient Electrocatalysts for Lithium-Oxygen Batteries.

Cationic defect engineering is an effective strategy to optimize the electronic structure of active sites and boost the oxygen electrode reactions in lithium-oxygen batteries (LOBs). Herein, Ni-Fe layered double oxides enriched with cationic nickel vacancies (Ni-Fe LDO-VNi ) are first designed and studied as the electrocatalysts for LOBs. Based on the density functional theory calculation, the existence of nickel vacancy in Ni-Fe LDO-VNi significantly improves its intrinsic affinity toward intermediates, thereby fundamentally optimizing the formation and decomposition pathway of Li2 O2 . In addition, the number of eg electrons on each nickel site is 1.19 for Ni-Fe LDO-VNi , which is much closer to 1 than 1.49 for Ni-Fe LDO. The near-unity occupation of eg orbital enhances the covalency of transition metal-oxygen bonds and thus improves the electrocatalytic activity of Ni-Fe LDO-VNi toward oxygen electrode reactions. The experimental results show that the LOBs with Ni-Fe LDO-VNi electrode deliver low overpotentials of 0.11/0.29 V during the oxygen reduction reaction/oxygen evolution reaction, respectively, large specific capacities of 13 933 mA h g-1 and superior cycling stability of over 826 h. This study provides a novel approach to optimize the electrocatalytic activity of LDO through reasonable defect engineering.

Genetic Characteristics and Transcriptional Regulation of Sodium Channel Related Genes in Chinese Patients With Brugada Syndrome.

Objective: To investigate the genetic characteristics and transcriptional regulation of the SCN5A gene of Brugada syndrome (BrS) patients in China. Methods: Using PubMed, Medline, China National Knowledge Internet (CNKI), and Wanfang Database, Chinese patients with BrS who underwent SCN5A gene testing were studied. Results: A total of 27 suitable studies involving Chinese BrS patients who underwent the SCN5A gene test were included. A total of 55 SCN5A gene mutations/variations were reported in Chinese BrS patients, including 10 from southern China and 45 from northern China. Mutations/variations of BrS patients from southern China mostly occurred in the regions of the α-subunit of Nav1.5, including DIII (Domain III), DIV, DIII-DIV, C-terminus regions, and the 3'UTR region. Furthermore, we analyzed the post-transcriptional modifications (PTMs) throughout the Nav1.5 protein encoded by SCN5A and found that the PTM changes happened in 72.7% of BrS patients from southern China and 26.7% from northern China. Conclusions: SCN5A mutations/variations of BrS patients in southern China mostly occurred in the DIII-DIV to C-terminus region and the 3'-UTR region of the SCN5A gene, different from northern China. PTM changes were consistent with the mutation/variation distribution of SCN5A, which might be involved in the regulation of the pathogenesis of BrS patients.

Adjusting the Covalency of Metal-Oxygen Bonds in LaCoO3 by Sr and Fe Cation Codoping to Achieve Highly Efficient Electrocatalysts for Aprotic Lithium-Oxygen Batteries.

Developing high-efficiency dual-functional catalysts to promote oxygen electrode reactions is critical for achieving high-performance aprotic lithium-oxygen (Li-O2) batteries. Herein, Sr and Fe cation-codoped LaCoO3 perovskite (La0.8Sr0.2Co0.8Fe0.2O3-σ, LSCFO) porous nanoparticles are fabricated as promising electrocatalysts for Li-O2 cells. The results demonstrate that the LSCFO-based Li-O2 batteries exhibit an extremely low overpotential of 0.32 V, ultrahigh specific capacity of 26 833 mA h g-1, and superior long-term cycling stability (200 cycles at 300 mA g-1). These prominent performances can be partially attributed to the existence of abundant coordination unsaturated sites caused by oxygen vacancies in LSCFO. Most importantly, density functional theory (DFT) calculations reveal that codoping of Sr and Fe cations in LaCoO3 results in the increased covalency of Co 3d-O 2p bonds and the transition of Co3+ from an ordinary low-spin state to an intermediate-spin state, eventually resulting in the transformation from nonconductor LCO to metallic LSCFO. In addition, based on the theoretical calculations, it is found that the inherent adsorption capability of LSCFO toward the LiO2 intermediate is reduced due to the increased covalency of Co 3d-O 2p bonds, leading to the formation of large granule-like Li2O2, which can be effectively decomposed on the LSCFO surface during the charging process. Notably, this work demonstrates a unique insight into the design of advanced perovskite oxide catalysts via adjusting the covalency of transition-metal-oxygen bonds for high-performance metal-air batteries.