Ultrafine CoRu alloy nanoclusters densely anchored on Nitrogen-Doped graphene nanotubes for a highly efficient hydrogen evolution reaction.

Designing highly efficient and stable electrocatalysts for hydrogen evolution reactions (HER) is essential to the production of green and renewable hydrogen. Metal-organic framework (MOF) precursor strategies are promising for the design of excellent electrocatalysts because of their porous architectures and adjustable compositions. In this study, a hydrogen-bonded organic framework (HOF) nanowire was developed as a precursor and template for the controllable and scalable synthesis of CoRu-MOF nanotubes. After calcination in Ar, the CoRu-MOF nanotubes were converted into N-doped graphene (NG) nanotubes with ultrafine CoRu nanoclusters (hereon called Co-xRu@NG-T; x  = 0, 5, 10, 15, 25 representing the Ru content of 0-0.25 mmol; T = 400 °C to 700 °C) that were densely encapsulated and isolated on the shell. Taking advantage of the synergistic effects of the porous, one-dimensional hollow structure and ultrafine CoRu nanoclusters, the optimized Co-15Ru@NG-500 catalyst demonstrated superior catalytic performance for HERs in alkaline electrolytes with an overpotential of only 30 mV at 10 mA cm-2 and robust durability for 2000 cycles, which outperforms many typical catalytic materials, such as commercial Pt/C. This work introduces a novel high-efficiency and cost-effective HER catalyst for application in commercial water-splitting electrolysis.

Intrabasal Plane Defect Formation in NiFe Layered Double Hydroxides Enabling Efficient Electrochemical Water Oxidation.

Defect engineering has proven to be one of the most effective approaches for the design of high-performance electrocatalysts. Current methods to create defects typically follow a top-down strategy, cutting down the pristine materials into fragmented pieces with surface defects yet also heavily destroying the framework of materials that imposes restrictions on the further improvements in catalytic activity. Herein, we describe a bottom-up strategy to prepare free-standing NiFe layered double hydroxide (LDH) nanoplatelets with abundant internal defects by controlling their growth behavior in acidic conditions. Our best-performing nanoplatelets exhibited the lowest overpotential of 241 mV and the lowest Tafel slope of 43 mV/dec for the oxygen evolution reaction (OER) process, superior to the pristine LDHs and other reference cation-defective LDHs obtained by traditional etching methods. Using both material characterization and density functional theory (DFT) simulation has enabled us to develop relationships between the structure and electrochemical properties of these catalysts, suggesting that the enhanced electrocatalytic activity of nanoplatelets mainly results from their defect-abundant structure and stable layered framework with enhanced exposure of the (001) surface.

Synthesis and chemiluminescent characteristics of two new acridinium esters.

Two new acridinium esters with a 2-(succinimidyloxycarbonyl)ethyl side arm, namely, 9-(2,6-dibromophenoxycarbonyl)-10-methyl-2-(2-(succinimidyloxycarbonyl)ethyl)acridinium trifluoromethanesulfonate and 9-(4-(2-(succinimidyloxycarbonyl)ethyl)phenoxycarbonyl)-2,7-dimethoxy-10-methylacridinium triflate, have been produced and characterized. The chemiluminescent properties and hydrolytic stabilities of the new acridinium esters have been investigated.

Three-way contact analysis characterizes the higher order organization of the Tcra locus.

The generation of highly diverse antigen receptors in T and B lymphocytes relies on V(D)J recombination. The enhancer Eα has been implicated in regulating the accessibility of Vα and Jα genes through long-range interactions during rearrangements of the T-cell antigen receptor gene Tcra. However, direct evidence for Eα physically mediating the interaction of Vα and Jα genes is still lacking. In this study, we utilized the 3C-HTGTS assay, a chromatin interaction technique based on 3C, to analyze the higher order chromatin structure of the Tcra locus. Our analysis revealed the presence of sufficient information in the 3C-HTGTS data to detect multiway contacts. Three-way contact analysis of the Tcra locus demonstrated the co-occurrence of the proximal Jα genes, Vα genes and Eα in CD4+CD8+ double-positive thymocytes. Notably, the INT2-TEAp loop emerged as a prominent structure likely to be responsible for bringing the proximal Jα genes and the Vα genes into proximity. Moreover, the enhancer Eα utilizes this loop to establish physical proximity with the proximal Vα gene region. This study provides insights into the higher order chromatin structure of the Tcra locus, shedding light on the spatial organization of chromatin and its impact on V(D)J recombination.

Synthesis, structure elucidation, and chemiluminescent activity of new 9-substituted 10-(ω-(succinimidyloxycarbonyl)alkyl)acridinium esters.

Several new acridinium esters 2-9 having their central acridinium ring bearing a 9-(2,5-dimethylphenoxycarbonyl), 9-(2,6-bis(trifluoromethyl)phenoxycarbonyl) or 9-(2,6-dinitrophenoxycarbonyl) group, and a 10-methyl, 10-(3-(succinimidyloxycarbonyl)propyl), 10-(5-(succinimidyloxycarbonyl)pentyl), or 10-(10-(succinimidyloxycarbonyl)decyl) group, have been synthesized and their chemiluminescent properties have been tested. The 2,5-dimethylphenyl acridinium esters emit light slowly (glow) when treated with alkaline hydrogen peroxide, while the 2,6-dinitrophenyl and 2,6-bis(trifluoromethyl)phenyl esters emit light rapidly (flash). The substituent at the 10 position affects the hydrolytic stabilities of the compounds.

Chromatin organizer SATB1 controls the cell identity of CD4+ CD8+ double-positive thymocytes by regulating the activity of super-enhancers.

CD4+ and CD8+ double-positive (DP) thymocytes play a crucial role in T cell development in the thymus. DP cells rearrange the T cell receptor gene Tcra to generate T cell receptors with TCRß. DP cells differentiate into CD4 or CD8 single-positive (SP) thymocytes, regulatory T cells, or invariant nature kill T cells (iNKT) in response to TCR signaling. Chromatin organizer SATB1 is highly expressed in DP cells and is essential in regulating Tcra rearrangement and differentiation of DP cells. Here we explored the mechanism of SATB1 orchestrating gene expression in DP cells. Single-cell RNA sequencing shows that Satb1 deletion changes the cell identity of DP thymocytes and down-regulates genes specifically and highly expressed in DP cells. Super-enhancers regulate the expressions of DP-specific genes, and our Hi-C data show that SATB1 deficiency in thymocytes reduces super-enhancer activity by specifically decreasing interactions among super-enhancers and between super-enhancers and promoters. Our results reveal that SATB1 plays a critical role in thymocyte development to promote the establishment of DP cell identity by globally regulating super-enhancers of DP cells at the chromatin architectural level.

Preparation of a novel group of chemiluminescent N-substituted acridinium esters.

Several novel N-substituted acridinium esters 7-16 containing a 10-methyl, 10-dodecyl, or 10-(ω-[succinimidyloxycarbonyl]alkyl) group have been synthesized and their chemiluminescent properties have been tested. Their chemiluminescent efficiencies and hydrolytic stabilities have been found to be affected by the characteristics of the group on the nitrogen atom. Dibromo-substituted leaving groups slightly accelerate the chemiluminescence process.

Impact of Visit-to-Visit Triglyceride-Glucose Index Variability on the Risk of Cardiovascular Disease in the Elderly.

Background: The aging population is increasingly susceptible to cardiovascular disease (CVD). Visit-to-visit variability in glucose and lipid levels both contributed to CVD risk independent of their mean values. However, whether variability in the triglyceride-glucose (TyG) index is a risk factor for CVD remains unknown. Research Design and Methods. In this retrospective study of electronic health records, 27,520 participants aged over 60 years were enrolled. The visit-to-visit variability of TyG index was calculated from annual health examination data and defined as average real variability (ARV), standard deviation (SD), or the coefficient of variability (CV). CVD events were identified from the chronic disease registry or follow-up database and included myocardial infarction, angina, coronary, and stroke. Multivariate Cox regression was used to examine the correlation between TyG variability and incident CVD. Results: Over a median follow-up of 6.2 years, there were 2,178 CVD events. When participants were divided into four quartiles according to their TyG variability, after adjusting for established CVD risk factors, subjects in the top quartile had (HR = 1.18, 95% CI 1.05-1.34, P=0.005) significantly higher CVD risk than those in the bottom quartile. The association remained significant in overweight individuals or those without diabetes (P < 0.005 and P < 0.01, respectively). Conclusions: High variability in TyG was significantly associated with elevated CVD risk in the elderly, independent of average TyG and other risk factors. Close monitoring variability in TyG might be informative to identify old individuals at high risk of CVD.

"Tree-Trunk" Design for Flexible Quasi-Solid-State Electrolytes with Hierarchical Ion-Channels Enabling Ultralong-Life Lithium-Metal Batteries.

The construction of robust (quasi)-solid-state electrolyte (SSE) for flexible lithium-metal batteries is desirable but extremely challenging. Herein, a novel, flexible, and robust quasi-solid-state electrolyte (QSSE) with a "tree-trunk" design is reported for ultralong-life lithium-metal batteries (LMBs). An in-situ-grown metal-organic framework (MOF) layer covers the cellulose-based framework to form hierarchical ion-channels, enabling rapid ionic transfer kinetics and excellent durability. A conductivity of 1.36 × 10-3  S cm-1 , a transference number of 0.72, an electrochemical window of 5.26 V, and a good rate performance are achieved. The flexible LMBs fabricated with as-designed QSSEs deliver areal capacity of up to 3.1 mAh cm-2 at the initial cycle with high mass loading of 14.8 mg cm-2 in Li-NCM811 cells and can retain ≈80% capacity retention after 300 cycles. An ultralong-life of 3000 cycles (6000 h) is also achieved in Li-LiFePO4 cells. This work presents a promising route in constructing a flexible QSSE toward ultralong-life LMBs, and also provides a design rationale for material and structure development in the area of energy storage and conversion.

Bioinspired Tough Solid-State Electrolyte for Flexible Ultralong-Life Zinc-Air Battery.

Manufacturing advanced solid-state electrolytes (SSEs) for flexible rechargeable batteries becomes increasingly important but remains grand challenge. The sophisticated structure of robust animal dermis and good water-retention of plant cell in nature grant germane inspirations for designing high-performance SSEs. Herein, tough bioinspired SSEs with intrinsic hydroxide ion (OH- ) conduction are constructed by in situ formation of OH- conductive ionomer network within a hollow-polymeric-microcapsule-decorated hydrogel polymer network. By virtue of the bioinspired design and dynamic dual-penetrating network structure, the bioinspired SSEs simultaneously obtain mechanical robustness with 1800% stretchability, good water uptake of 107 g g-1 and water retention, and superhigh ion conductivity of 215 mS cm-1 . The nanostructure of bioinspired SSE and related ion-conduction mechanism are revealed and visualized by molecular dynamics simulation, where plenty of compact and superfast ion-transport channels are constructed, contributing to superhigh ion conductivity. As a result, the flexible solid-state zinc-air batteries assembled with bioinspired SSEs witness high power density of 148 mW cm-2 , specific capacity of 758 mAh g-1 and ultralong cycling stability of 320 h as well as outstanding flexibility. The bioinspired methodology and deep insight of ion-conduction mechanism will shed light on the design of advanced SSEs for flexible energy conversion and storage systems.

Achieve Stable Lithium Metal Anode by Sulfurized-Polyacrylonitrile Modified Separator for High-Performance Lithium Batteries.

To develop a high-energy-density lithium battery, there still are several severe challenges for Li metal anode: low Coulombic efficiency caused by its high chemical reactivity, Li dendrite formation, and "dead" Li accumulation during repeated plating/stripping processes. Especially, lithium dendrite growth imposes inferior cycling stability and serious safety issues. Herein, we propose a facile but effective strategy to suppress lithium dendrite growth through an artificial inorganic-polymer protective layer derived from sulfurized polyacrylonitrile on a polyethylene separator. Benefiting from the lithiated sulfurized polyacrylonitrile and poly(acrylic acid), the flexible and ion-conductive protective layer could regulate Li+ flux and facilitate dendrite-free lithium deposition. Consequently, lithium metal with the meritorious protective layer can achieve a long-term cycling with negligible overpotential rise in Li-Li symmetric cells, even at a high areal capacity of 5 mAh cm-2. Remarkably, such a protective layer enables stable cycling performance of Li-S cell with a high areal capacity (∼9 mAh cm-2). This work provides a valuable exploration strategy for potential industrial applications of high-performance lithium metal batteries.

Promotional effect of ZrO2 and WO3 on bimetallic Pt-Pd diesel oxidation catalyst.

Diesel oxidation catalysts Pt-Pd-(y)ZrO2-(z)WO3/CeZrOx-Al2O3 with total Pt & Pd loading of only 0.68 wt.% were prepared and investigated for oxidation activity and stability of CO, C3H6, and NO. Introduction of ZrO2 greatly improved low-temperature activities and retained stability especially for CO and C3H6 oxidation after treated at 800 °C. With the optimal loading amount of 6 wt% ZrO2, 2 wt% WO3 was introduced to the system and showed higher activity. Reaction temperature for 50% CO and C3H6 conversion declined to 160 and 181 °C, and the maximal NO conversion increased to 50%. By using XRD, TEM, CO chemisorption, XPS, and H2-TPR analysis, it was found that ZrO2 could inhibit aggregation of Pt and Pd, improve metal dispersion, and increase surface-chemisorbed oxygen after high-temperature treatment, accounting for promoted performance. Also, there were more reducible oxide species in ZrO2-doped catalysts. ZrO2 could induce reduction of noble metal oxides and surface ceria by weakening Pt-O-Ce interaction, which increased the ability to dissociate H2 and spillover effect of dissociated hydrogen to ceria. Doping WO3 increased metal dispersion of fresh samples and brought more Pt0 species that were active sites for oxidation reactions. Thus, ZrO2 and WO3 could be effective additives for oxidation catalysts to synergistically improve their activities and thermal stability.

Macrophage NFATc3 prevents foam cell formation and atherosclerosis: evidence and mechanisms.

AIMS: Our previous study demonstrated that Ca2+ influx through the Orai1 store-operated Ca2+ channel in macrophages contributes to foam cell formation and atherosclerosis via the calcineurin-ASK1 pathway, not the classical calcineurin-nuclear factor of activated T-cell (NFAT) pathway. Moreover, up-regulation of NFATc3 in macrophages inhibits foam cell formation, suggesting that macrophage NFATc3 is a negative regulator of atherogenesis. Hence, this study investigated the precise role of macrophage NFATc3 in atherogenesis. METHODS AND RESULTS: Macrophage-specific NFATc3 knockout mice were generated to determine the effect of NFATc3 on atherosclerosis in a mouse model of adeno-associated virus-mutant PCSK9-induced atherosclerosis. NFATc3 expression was decreased in macrophages within human and mouse atherosclerotic lesions. Moreover, NFATc3 levels in peripheral blood mononuclear cells from atherosclerotic patients were negatively associated with plaque instability. Furthermore, macrophage-specific ablation of NFATc3 in mice led to the atherosclerotic plaque formation, whereas macrophage-specific NFATc3 transgenic mice exhibited the opposite phenotype. NFATc3 deficiency in macrophages promoted foam cell formation by potentiating SR-A- and CD36-meditated lipid uptake. NFATc3 directly targeted and transcriptionally up-regulated miR-204 levels. Mature miR-204-5p suppressed SR-A expression via canonical regulation. Unexpectedly, miR-204-3p localized in the nucleus and inhibited CD36 transcription. Restoration of miR-204 abolished the proatherogenic phenotype observed in the macrophage-specific NFATc3 knockout mice, and blockade of miR-204 function reversed the beneficial effects of NFATc3 in macrophages. CONCLUSION: Macrophage NFATc3 up-regulates miR-204 to reduce SR-A and CD36 levels, thereby preventing foam cell formation and atherosclerosis, indicating that the NFATc3/miR-204 axis may be a potential therapeutic target against atherosclerosis.

Phase separation of Epstein-Barr virus EBNA2 protein reorganizes chromatin topology for epigenetic regulation.

Epstein-Barr virus nuclear antigen 2 (EBNA2) is a transactivator of viral and cellular gene expression, which plays a critical role in the Epstein-Barr virus-associated diseases. It was reported that EBNA2 regulates gene expression by reorganizing chromatin and manipulating epigenetics. Recent studies showed that liquid-liquid phase separation plays an essential role in epigenetic and transcriptional regulation. Here we show that EBNA2 reorganized chromatin topology to form accessible chromatin domains (ACDs) of the host genome by phase separation. The N-terminal region of EBNA2, which is necessary for phase separation, is sufficient to induce ACDs. The C-terminal domain of EBNA2 promotes the acetylation of accessible chromatin regions by recruiting histone acetylase p300 to ACDs. According to these observations, we proposed a model of EBNA2 reorganizing chromatin topology for its acetylation through phase separation to explain the mechanism of EBNA2 hijacking the host genome by controlling its epigenetics.

Downregulation by CNNM2 of ATP5MD expression in the 10q24.32 schizophrenia-associated locus involved in impaired ATP production and neurodevelopment.

Genome-wide association studies (GWAS) have accelerated the discovery of numerous genetic variants associated with schizophrenia. However, most risk variants show a small effect size (odds ratio (OR) <1.2), suggesting that more functional risk variants remain to be identified. Here, we employed region-based multi-marker analysis of genomic annotation (MAGMA) to identify additional risk loci containing variants with large OR value from Psychiatry Genomics Consortium (PGC2) schizophrenia GWAS data and then employed summary-data-based mendelian randomization (SMR) to prioritize schizophrenia susceptibility genes. The top-ranked susceptibility gene ATP5MD, encoding an ATP synthase membrane subunit, is observed to be downregulated in schizophrenia by the risk allele of CNNM2-rs1926032 in the schizophrenia-associated 10q24.32 locus. The Atp5md knockout (KO) in mice was associated with abnormal startle reflex and gait, and ATP5MD knockdown (KD) in human induced pluripotent stem cell-derived neurons disrupted the neural development and mitochondrial respiration and ATP production. Moreover, CNNM2-rs1926032 KO could induce downregulation of ATP5MD expression and disruptions of mitochondrial respiration and ATP production. This study constitutes an important mechanistic component that links schizophrenia-associated CNNM2 regions to disruption in energy adenosine system modulation and neuronal function by long-distance chromatin domain downregulation of ATP5MD. This pathogenic mechanism provides therapeutic implications for schizophrenia.

The role of chromatin organizer Satb1 in shaping TCR repertoire in adult thymus.

T cells recognize the universe of foreign antigens with a diverse repertoire of T cell receptors generated by V(D)J recombination. Special AT-rich binding protein 1 (Satb1) is a chromatin organizer that plays an essential role in T cell development. Previous study has shown that Satb1 regulates the re-induction of recombinase Rag1 and Rag2 in CD4+CD8+ thymocytes, affecting the secondary rearrangement of the Tcra gene. Here, we detected the repertoires of four TCR genes, Tcrd, Tcrg, Tcrb, and Tcra, in the adult thymus, and explored the role of the Satb1 in shaping the TCR repertoires. We observed a strong bias in the V and J gene usages of the Tcrd and Tcrg repertoires in WT and Satb1-deleted thymocytes. Satb1 deletion had few effects on the V(D)J rearrangement and repertoire of the Tcrg, Tcrd, and Tcrb genes. The Tcra repertoire was severely impaired in Satb1-deleted thymocytes, while the primary rearrangement was relatively normal. We also found the CDR3 length of TCRα chain was significantly longer in Satb1-deleted thymocytes, which can be explained by the strong bias of the proximal Jα usage. Our results showed that Satb1 plays an essential role in shaping TCR repertoires in αß T cells.

Faradaic Electrodes Open a New Era for Capacitive Deionization.

Capacitive deionization (CDI) is an emerging desalination technology for effective removal of ionic species from aqueous solutions. Compared to conventional CDI, which is based on carbon electrodes and struggles with high salinity streams due to a limited salt removal capacity by ion electrosorption and excessive co-ion expulsion, the emerging Faradaic electrodes provide unique opportunities to upgrade the CDI performance, i.e., achieving much higher salt removal capacities and energy-efficient desalination for high salinity streams, due to the Faradaic reaction for ion capture. This article presents a comprehensive overview on the current developments of Faradaic electrode materials for CDI. Here, the fundamentals of Faradaic electrode-based CDI are first introduced in detail, including novel CDI cell architectures, key CDI performance metrics, ion capture mechanisms, and the design principles of Faradaic electrode materials. Three main categories of Faradaic electrode materials are summarized and discussed regarding their crystal structure, physicochemical characteristics, and desalination performance. In particular, the ion capture mechanisms in Faradaic electrode materials are highlighted to obtain a better understanding of the CDI process. Moreover, novel tailored applications, including selective ion removal and contaminant removal, are specifically introduced. Finally, the remaining challenges and research directions are also outlined to provide guidelines for future research.

A review of composite solid-state electrolytes for lithium batteries: fundamentals, key materials and advanced structures.

All-solid-state lithium ion batteries (ASSLBs) are considered next-generation devices for energy storage due to their advantages in safety and potentially high energy density. As the key component in ASSLBs, solid-state electrolytes (SSEs) with non-flammability and good adaptability to lithium metal anodes have attracted extensive attention in recent years. Among the current SSEs, composite solid-state electrolytes (CSSEs) with multiple phases have greater flexibility to customize and combine the advantages of single-phase electrolytes, which have been widely investigated recently and regarded as promising candidates for commercial ASSLBs. Based on existing investigations, herein, we present a comprehensive overview of the recent developments in CSSEs. Initially, we introduce the historical development from solid-state ionic conductors to CSSEs, and then summarize the fundamentals including mechanisms of lithium ion transport, key evaluation parameters, design principles, and key materials. Four main types of advanced structures for CSSEs are classified and highlighted according to the recent progress. Moreover, advanced characterization and computational simulation techniques including machine learning are reviewed for the first time, and the main challenges and perspectives of CSSEs are also provided for their future development.

A role of the CTCF binding site at enhancer Eα in the dynamic chromatin organization of the Tcra-Tcrd locus.

The regulation of T cell receptor Tcra gene rearrangement has been extensively studied. The enhancer Eα plays an essential role in Tcra rearrangement by establishing a recombination centre in the Jα array and a chromatin hub for interactions between Vα and Jα genes. But the mechanism of the Eα and its downstream CTCF binding site (here named EACBE) in dynamic chromatin regulation is unknown. The Hi-C data showed that the EACBE is located at the sub-TAD boundary which separates the Tcra-Tcrd locus and the downstream region including the Dad1 gene. The EACBE is required for long-distance regulation of the Eα on the proximal Vα genes, and its deletion impaired the Tcra rearrangement. We also noticed that the EACBE and Eα regulate the genes in the downstream sub-TAD via asymmetric chromatin extrusion. This study provides a new insight into the role of CTCF binding sites at TAD boundaries in gene regulation.

Deep-Breathing Honeycomb-like Co-Nx-C Nanopolyhedron Bifunctional Oxygen Electrocatalysts for Rechargeable Zn-Air Batteries.

Metal organic framework (MOF) derivatives have been extensively used as bifunctional oxygen electrocatalysts. However, the utilization of active sites is still not satisfactory owing to the sluggish mass transport within their narrow pore channels. Herein, interconnected macroporous channels were constructed inside MOFs-derived Co-Nx-C electrocatalyst to unblock the mass transfer barrier. The as-synthesized electrocatalyst exhibits a honeycomb-like morphology with highly exposed Co-Nx-C active sites on carbon frame. Owing to the interconnected ordered macropores throughout the electrocatalyst, these active sites can smoothly "exhale/inhale" reactants and products, enhancing the accessibility of active sites and the reaction kinetics. As a result, the honeycomb-like Co-Nx-C displayed a potential difference of 0.773 V between the oxygen evolution reaction potential at 10 mA cm-2 and the oxygen reduction reaction half-wave potential, much lower than that of bulk-Co-Nx-C (0.842 V). The rational modification on porosity makes such honeycomb-like MOF derivative an excellent bifunctional oxygen electrocatalyst in rechargeable Zn-air batteries.