Discovery of 1,2,4-Triazole-3-thione Derivatives as Potent and Selective DCN1 Inhibitors for Pathological Cardiac Fibrosis and Remodeling.

DCN1, a critical co-E3 ligase during the neddylation process, is overactivated in many diseases, such as cancers, heart failure as well as fibrotic diseases, and has been regarded as a new target for drug development. Herein, we designed and synthesized a new class of 1,2,4-triazole-3-thione-based DCN1 inhibitors based the hit HD1 identified from high-throughput screening and optimized through numerous structure-activity-relationship (SAR) explorations. HD2 (IC50= 2.96 nM) was finally identified and represented a highly potent and selective DCN1 inhibitor with favorable PK properties and low toxicity. Amazingly, HD2 effectively relieved Ang II/TGFß-induced cardiac fibroblast activation in vitro, and reduced ISO-induced cardiac fibrosis as well as remodeling in vivo, which was linked to the inhibition of cullin 3 neddylation and its substrate Nrf2 accumulation. Our findings unveil a novel 1,2,4-triazole-3-thione-based derivative HD2, which can be recognized as a promising lead compound targeting DCN1 for cardiac fibrosis and remodeling.

HAX-1 interferes in assembly of NLRP3-ASC to block microglial pyroptosis in cerebral I/R injury.

Acute cerebral ischemia has a high rate of disability and death. Although timely recanalization therapy may rescue the ischemic brain tissue, cerebral ischemia-reperfusion injury has been shown to limit the therapeutic effects of vascular recanalization. Protein HAX-1 has been reported as a pro-survival protein that plays an important role in various disorders, particularly in association with the nervous system. However, the effects and mechanisms of HAX-1 in cerebral IR injury have yet to be elucidated. So, we aimed to investigate the effect of HAX-1 on microglial pyroptosis and explore its potential neuroprotective effects in ischemia-reperfusion injury. Our results show that the expression of HAX-1 decreased after cerebral IR injury, accompanied by an increase in pyroptosis pathway activation. In addition, HAX-1 could inhibit microglial pyroptosis both in vivo and in vitro and reduce the release of inflammatory mediators. The above neuroprotective effects might be partially mediated by inhibiting of interaction of NLRP3 and ASC through competitive binding, followed by the attenuation of NLRP3 inflammasome formation. In conclusion, Our findings support that HAX-1 exhibits a protective role in cerebral I/R injury, and further study on HAX-1 expression regulation will contribute to cerebral infarction therapy.

Structural regulation of asphalt-based hard carbon microcrystals based on liquid-phase crosslinking to enhance sodium storage.

Air-oxidation is an effective strategy to obtain promising carbon materials from asphalt for sodium-ion batteries. However, this method would generate a vast amount of gaseous pollutant, which pose challenges for recycling. Herein, a simple, cost-effective and environmentally friendly liquid-phase oxidation method is proposed. The oxygen-containing functional groups (-NO2) are introduced into asphalt, which effectively prevents the melting of asphalt and rearrangement of carbon layers during subsequent carbonization process. As a result, a carbon material with notable disorder degree, large interlayer spacing and abundant closed pores, is prepared. The as-prepared product demonstrates an impressive initial Coulombic efficiency of 88.3 % and an enhanced specific capacity of 317.0 mA h g-1, which is 2.6 times that of the pristine product. Moreover, when assembled with a Na3.32Fe2.34(P2O7)2 cathode, the full-cell delivers a high reversible capacity of 271.7 mA h g-1 at 30 mA g-1 with superb cycle life. This study offers a novel oxidation strategy and provides a solution for producing highly disordered carbon anodes from soft carbon precursors.

Critical Roles of Polycomb Repressive Complexes in Transcription and Cancer.

Polycomp group (PcG) proteins are members of highly conserved multiprotein complexes, recognized as gene transcriptional repressors during development and shown to play a role in various physiological and pathological processes. PcG proteins consist of two Polycomb repressive complexes (PRCs) with different enzymatic activities: Polycomb repressive complexes 1 (PRC1), a ubiquitin ligase, and Polycomb repressive complexes 2 (PRC2), a histone methyltransferase. Traditionally, PRCs have been described to be associated with transcriptional repression of homeotic genes, as well as gene transcription activating effects. Particularly in cancer, PRCs have been found to misregulate gene expression, not only depending on the function of the whole PRCs, but also through their separate subunits. In this review, we focused especially on the recent findings in the transcriptional regulation of PRCs, the oncogenic and tumor-suppressive roles of PcG proteins, and the research progress of inhibitors targeting PRCs.

Discovery of Novel Pyrazole-Based KDM5B Inhibitor TK-129 and Its Protective Effects on Myocardial Remodeling and Fibrosis.

Lysine-specific demethylase 5B (KDM5B) has been recognized as a potential drug target for cardiovascular diseases. In this work, we first found that the KDM5B level was increased in mouse hearts after transverse aortic constriction (TAC) and in Ang II-induced activated cardiac fibroblasts. Structure-based design and further optimizations led to the discovery of highly potent pyrazole-based KDM5B inhibitor TK-129 (IC50 = 0.044 µM). TK-129 reduced Ang II-induced activation of cardiac fibroblasts in vitro, exhibited good PK profile (F = 42.37%), and reduced isoprenaline-induced myocardial remodeling and fibrosis in vivo. Mechanistically, we found that KDM5B up-regulation in cardiac fibroblast activation was associated with the activation of Wnt-related pathway. The protective effects of TK-129 were associated with its KDM5B inhibition and blocking KDM5B-related Wnt pathway activation. Taken together, TK-129 may represent a novel KDM5-targeting lead compound for cardiac remodeling and fibrosis.

Recent Advances of Pore Structure in Disordered Carbons for Sodium Storage: A Mini Review.

Disordered carbons as the most promising anode materials for sodium ion batteries (SIBs) have attracted much attention, due to the widely-distributed sources and potentially high output voltage when applied in full cells owing to the almost lowest voltage plateau. The complex microstructure makes the sodium storage mechanism of disordered carbons controversial. Recently, many studies show that the plateau region of disordered carbons are closely related to the embedment of sodium ion/semimetal in nanopores. In this regard, the classification, characterization and construction of nanopores are exhaustively discussed in this review. In addition, perspectives about the controllable construction of nanopores are presented in the last section, aiming to catch out more valuable studies include not only the construction of closed pores to enhance capacity but also the design of carbon materials to understand Na storage mechanism.

Hollow carbon spheres loaded with NiSe2 nanoplates as multifunctional SeS2 hosts for Li-SeS2 batteries.

Selenium sulfide as a new alternative cathode material can effectively address the inferior electronic conductivity of sulfur, which is the main cause for poor electrochemical reactivity of conventional lithium-sulfur batteries (Li-S batteries). Therefore, in this work, hollow carbon spheres loaded with NiSe2 nanoplates were prepared as SeS2 hosts for Li-SeS2 batteries. The unique micro-mesoporous hollow carbon spheres not only provide channels for the diffusion of SeS2, but also afford spaces for alleviating the volume expansion of the active substance. Besides, the external polar NiSe2 nanoplates increase active sites for capturing polysulfides or polyselenides during the charge/discharge process. Meanwhile, the excellent electronic conductivity of NiSe2 can accelerate the catalytic reaction on the surface, thus reducing the loss of soluble intermediate products and finally suppressing the "shuttle effect". These extraordinary features of the as-proposed cathode offer many superiorities in electrochemical performances in terms of a high initial discharge capacity of 1139 mA h g-1 at a current rate of 0.1C and an excellent cycling life of up to 1000 cycles at 1C.

Efficient Anchoring of Polysulfides Based on Self-Assembled Ti3C2Tx Nanosheet-Connected Hollow Co(OH)2 Nanotubes for Lithium-Sulfur Batteries.

Designing sulfur host materials with unique functions such as physical constraint or chemical catalysis to suppress the shuttle effect and promote the fast conversion of polysulfides is a prerequisite for lithium-sulfur batteries (LSBs). Herein, we construct hollow Co(OH)2 nanotubes connected by Ti3C2Tx nanosheets (denoted as Co(OH)2@Ti3C2Tx) as host materials for sulfur through a simple self-assembly method at room temperature. The large void spaces of Co(OH)2 nanotubes not only confine higher sulfur loading but also mitigate the volumetric expansion in the process of lithiation. Moreover, the conductive Ti3C2Tx layers facilitate fast electron transfer and catalyze the transition of sulfur based on the terminations on the surface. Combining those two materials can also act as an efficient polysulfide anchor to enable outstanding electrochemical performance. The Co(OH)2@Ti3C2Tx@S cathode presents a high discharge capacity of 1400 mAh g-1 at 0.1C and long-cycling stability at 1C for 500 cycles. Moreover, the obtained capacity of Li2S precipitation and the dissolution capacity reach 193.3 and 291.1 mAh g-1, respectively. Consequently, this work demonstrates a facile strategy to design multifunctional materials that effectively confine the polysulfides and enhance the performance of LSBs.

A Fe3N/carbon composite electrocatalyst for effective polysulfides regulation in room-temperature Na-S batteries.

The practical application of room-temperature Na-S batteries is hindered by the low sulfur utilization, inadequate rate capability and poor cycling performance. To circumvent these issues, here, we propose an electrocatalyst composite material comprising of N-doped nanocarbon and Fe3N. The multilayered porous network of the carbon accommodates large amounts of sulfur, decreases the detrimental effect of volume expansion, and stabilizes the electrodes structure during cycling. Experimental and theoretical results testify the Fe3N affinity to sodium polysulfides via Na-N and Fe-S bonds, leading to strong adsorption and fast dissociation of sodium polysulfides. With a sulfur content of 85 wt.%, the positive electrode tested at room-temperature in non-aqueous Na metal coin cell configuration delivers a reversible capacity of about 1165 mA h g-1 at 167.5 mA g-1, satisfactory rate capability and stable capacity of about 696 mA h g-1 for 2800 cycles at 8375 mA g-1.

A facilely-synthesized polyanionic cathode with impressive long-term cycling stability for sodium-ion batteries.

In this work, nanoflower-like Na0.5VOPO4·2H2O with a large interlayer distance of 6.5295 Å is synthesized via a simple chemical precipitation method at room temperature. It is the first time that the potential of the Na0.5VOPO4·2H2O electrode as a cathode material for SIBs has been investigated, and it exhibits a high specific capacity (127 mA h g-1 at 0.2C), outstanding long-term cycling stability and superior reaction kinetics.

Efficient Catalytic Conversion of Polysulfides by Biomimetic Design of "Branch-Leaf" Electrode for High-Energy Sodium-Sulfur Batteries.

Rechargeable room temperature sodium-sulfur (RT Na-S) batteries are seriously limited by low sulfur utilization and sluggish electrochemical reaction activity of polysulfide intermediates. Herein, a 3D "branch-leaf" biomimetic design proposed for high performance Na-S batteries, where the leaves constructed from Co nanoparticles on carbon nanofibers (CNF) are fully to expose the active sites of Co. The CNF network acts as conductive "branches" to ensure adequate electron and electrolyte supply for the Co leaves. As an effective electrocatalytic battery system, the 3D "branch-leaf" conductive network with abundant active sites and voids can effectively trap polysulfides and provide plentiful electron/ions pathways for electrochemical reaction. DFT calculation reveals that the Co nanoparticles can induce the formation of a unique Co-S-Na molecular layer on the Co surface, which can enable a fast reduction reaction of the polysulfides. Therefore, the prepared "branch-leaf" CNF-L@Co/S electrode exhibits a high initial specific capacity of 1201 mAh g-1 at 0.1 C and superior rate performance.

Myofibroblast Deficiency of LSD1 Alleviates TAC-Induced Heart Failure.

[Figure: see text].

Gelation of organic liquid electrolyte to achieve superior sodium-ion full-cells.

The irreversible consumption of active sodium in sodium-ion full-cells (SIFCs) becomes particularly serious due to the existence of unavoidable interface or side reaction, which has become the key to restrict the development of high-performance sodium-ion batteries (SIBs). Interface design and electrolyte optimization have been proved to be effective strategies to improve or solve this problem. In this work, on the basis of traditional organic liquid electrolytes, a novel gel polymer electrolyte with high ionic conductivity (1.13 × 10-3 S cm-1) and wide electrochemical stability window (~4.7 V) was designed and synthesized using bacterial cellulose film as precursor. Compared with the liquid electrolyte, the obtained electrolyte can endow better sodium storage performance in both half- and full-cells. When coupled with sodium hexacyanoferrate cathode and hard carbon anode, a capacity of 94.2 mA h g-1 can be obtained with a capacity retention of 75% after 100 cycles at a current density of 100 mA g-1, while those of with conventional liquid electrolyte can deliver a capacity of 99.0 mA h g-1 but only accompany 58% capacity retention under the same conditions. Significantly, when the current density increases to 800 mA g-1, their capacity difference reaches 23.4 mA h g-1.

Suppressed shuttling effect of polysulfides using three-dimensional nickel hydroxide polyhedrons for advanced lithium-sulfur batteries.

In this work, controlled-size hollow polyhedron assembled by crumpled nickel hydroxide (Ni(OH)2) nanosheets from silicon dioxide (SiO2)-covered zeolitic imidazole framework-67 (ZIF-67@SiO2) is prepared via a template-sacrificed method. It is found that SiO2 plays an essential role in keeping intact polyhedrons and suppressing particle growth. Benefiting from structural and compositional advantages, the Ni(OH)2@S electrode exhibits high specific capacity, excellent rate performance, and stable cycle life at 1C with a small capacity decay of 0.067% per cycle. The Ni(OH)2 hollow polyhedrons can accommodate the volume expansion to maintain the integrity of the electrode and suppress the shuttling effect of polysulfides via abundant hydroxyl groups. Hence, this strategy is beneficial to anticipate the material for large-scale applications.

Multi-step Controllable Catalysis Method for the Defense of Sodium Polysulfide Dissolution in Room-Temperature Na-S Batteries.

Room-temperature (RT) sodium-sulfur batteries hold great promise for the development of efficient, low-cost, and environmentally friendly energy storage systems. Nevertheless, the dissolution of long-chain polysulfides is a huge obstacle. In this work, a composite cathode which integrates Ni/Co bimetal nanoparticles as the catalyst and carbon spheres with abundant channels as the host is prepared for RT Na-S batteries. Moreover, a valuable strategy to reduce the dissolution of polysulfides by accurately regulating the two-step reaction kinetics of polysulfide transformation (from Na2S to long-chain polysulfides and then from polysulfides to sulfur) is presented. Through adjusting the ratio of Ni and Co, the optimal cathode with a Ni/Co ratio of 1:2 can retard the first conversion of Na2S to polysulfides and simultaneously accelerate the subsequent transformation of polysulfides to sulfur. In this case, the soluble polysulfides can immediately transform to solid sulfur as soon as it appears, thus avoiding the shuttle of polysulfides. The galvanostatic intermittent titration method and in situ Raman are employed to supervise the transformation of polysulfides during the discharge/charge process. As a result, the composite shows excellent performance as the cathode of RT liquid/quasi-solid-state Na-S batteries in terms of specific capacities, rate capability, and cycle stability.

Low-operating temperature quasi-solid-state potassium-ion battery based on commercial materials.

Quasi-solid-state potassium-ion batteries (QSPIBs) are regarded as one of the most promising safety-enhanced energy storage devices. Herein, a facile method for preparing a potassium-ion composite electrolyte membrane on a large scale is presented for the first time. The as-synthesized membrane displays excellent electrochemical stability, good mechanical flexibility, and high ionic conductivity (9.31 × 10-5 S cm-1 at 25 °C). Furthermore, QSPIBs prepared with this membrane and commercial raw material-based electrodes show superior electrochemical performance even at low temperatures (99.7 mAh g-1 at -20 °C for half QSPIBs and 90.7 mAh g-1 at -15 °C for full QSPIBs), and a promising rate performance (115.6 mAh g-1 for half QSPIBs and 90.9 mAh g-1 for full QSPIBs at 800 mA g-1). The reaction mechanism and structure evolution of a 3,4,9,10-perylene-tetracarboxylicacid-dianhydride (PTCDA) cathode is also systematically studied. The promising characteristics of the prepared low-cost quasi-solid-state potassium-ion batteries in this work open up new possibilities for safer and more durable batteries and a wide range of practical applications in the electronics industry.

Nickel Hollow Spheres Concatenated by Nitrogen-Doped Carbon Fibers for Enhancing Electrochemical Kinetics of Sodium-Sulfur Batteries.

The high energy density of room temperature (RT) sodium-sulfur batteries (Na-S) usually rely on the efficient conversion of polysulfide to sodium sulfide during discharging and sulfur recovery during charging, which is the rate-determining step in the electrochemical reaction process of Na-S batteries. In this work, a 3D network (Ni-NCFs) host composed by nitrogen-doped carbon fibers (NCFs) and Ni hollow spheres is synthesized by electrospinning. In this novel design, each Ni hollow unit not only can buffer the volume fluctuation of S during cycling, but also can improve the conductivity of the cathode along the carbon fibers. Meanwhile, the result reveals that a small amount of Ni is polarized during the sulfur-loading process forming a polar Ni-S bond. Furthermore, combining with the nitrogen-doped carbon fibers, the Ni-NCFs composite can effectively adsorb soluble polysulfide intermediate, which further facilitates the catalysis of the Ni unit for the redox of sodium polysulfide. In addition, the in situ Raman is employed to supervise the variation of polysulfide during the charging and discharging process. As expected, the freestanding S@Ni-NCFs cathode exhibits outstanding rate capability and excellent cycle performance.

Slope-Dominated Carbon Anode with High Specific Capacity and Superior Rate Capability for High Safety Na-Ion Batteries.

The comprehensive performance of carbon anodes for Na-ion batteries (NIBs) is largely restricted by their inferior rate capability and safety issues. Herein, a slope-dominated carbon anode is achieved at a low temperature of 800 °C, which delivers a high reversible capacity of 263 mA h g-1 at 0.15C with an impressive initial Coulombic efficiency (ICE) of 80 %. When paired with the NaNi1/3 Fe1/3 Mn1/3 O2 cathode, the reversible capacity at 6C is still 75 % of that at 0.15C, and 73 % of the capacity is retained after 1000 cycles at 3C. The enhanced Na storage performance could be attributed to the unique microstructure with randomly oriented short carbon layers and the relatively higher defect concentration. Given its robustness, such a low-temperature carbonization strategy could also be applicable to other precursors and provide a new opportunity to design slope-dominated carbon anodes for high safety, low-cost NIBs with excellent ICE and superior rate capability.

Advanced Nanostructured Anode Materials for Sodium-Ion Batteries.

Sodium-ion batteries (NIBs), due to the advantages of low cost and relatively high safety, have attracted widespread attention all over the world, making them a promising candidate for large-scale energy storage systems. However, the inherent lower energy density to lithium-ion batteries is the issue that should be further investigated and optimized. Toward the grid-level energy storage applications, designing and discovering appropriate anode materials for NIBs are of great concern. Although many efforts on the improvements and innovations are achieved, several challenges still limit the current requirements of the large-scale application, including low energy/power densities, moderate cycle performance, and the low initial Coulombic efficiency. Advanced nanostructured strategies for anode materials can significantly improve ion or electron transport kinetic performance enhancing the electrochemical properties of battery systems. Herein, this Review intends to provide a comprehensive summary on the progress of nanostructured anode materials for NIBs, where representative examples and corresponding storage mechanisms are discussed. Meanwhile, the potential directions to obtain high-performance anode materials of NIBs are also proposed, which provide references for the further development of advanced anode materials for NIBs.

Superior Na-Storage Performance of Low-Temperature-Synthesized Na3(VO(1-x)PO4)2F(1+2x) (0≤x≤1) Nanoparticles for Na-Ion Batteries.

Na-ion batteries are becoming comparable to Li-ion batteries because of their similar chemical characteristics and abundant sources of sodium. However, the materials production should be cost-effective in order to meet the demand for large-scale application. Here, a series of nanosized high-performance cathode materials, Na3(VO(1-x)PO4)2F(1+2x) (0≤x≤1), has been synthesized by a solvothermal low-temperature (60-120 °C) strategy without the use of organic ligands or surfactants. The as-synthesized Na3(VOPO4)2F nanoparticles show the best Na-storage performance reported so far in terms of both high rate capability (up to 10 C rate) and long cycle stability over 1200 cycles. To the best of our knowledge, the current developed synthetic strategy for Na3(VO(1-x)PO4)2F(1+2x) is by far one of the least expensive and energy-consuming methods, much superior to the conventional high-temperature solid-state method.