Regulation of Protein Conformation Enables Cell-Selective Targeting of Virus-Mimicking Nanoparticles for siRNA Therapy of Glioblastoma.

Orthotopic glioblastoma (GBM) has an aggressive growth pattern and complex pathogenesis, becoming one of the most common and deadly tumors of the central nervous system (CNS). The emergence of RNA therapies offers promise for the treatment of GBM. However, the efficient and precise delivery of RNA drugs to specific tumor cells in the brain with high cellular heterogeneity remains ongoing. Here, a strategy is proposed to regulate protein conformation through lipid nanoenvironments to custom-design virus-mimicking nanoparticles (VMNs) with excellent selective cell targeting capabilities, leading to efficient and precise delivery of small interfering RNA for effective treatment of GBM. The optimized VMNs not only retain the ability to cross the blood-brain barrier and release the RNA by lysosomal escape like natural viruses but also ensure precise enrichment in the GBM area. This study lays the conceptual foundation for the custom design of VMNs with superior cell-selective targeting capabilities and opens up the possibility of RNA therapies for the efficient treatment of GBM and CNS tumors.

Hydrophobic substrate binding pocket remodeling of echinocandin B deacylase based on multi-dimensional rational design.

Actinoplanes utahensis deacylase (AAC)-catalyzed deacylation of echinocandin B (ECB) is a promising method for the synthesis of anidulafungin, the newest of the echinocandin antifungal agents. However, the low activity of AAC significantly limits its practical application. In this work, we have devised a multi-dimensional rational design strategy for AAC, conducting separate analyses on the substrate-binding pocket's volume, curvature, and length. Furthermore, we quantitatively analyzed substrate properties, particularly on hydrophilic and hydrophobic. Accordingly, we tailored the linoleic acid-binding pocket of AAC to accommodate the extended long lipid chain of ECB. By fine-tuning the key residues, the resulting AAC mutants can accommodate the ECB lipid chain with a lower curvature binding pocket. The D53A/I55F/G57M/F154L/Q661L mutant (MT) displayed 331 % higher catalytic efficiency than the wild-type (WT) enzyme. The MT product conversion was 94.6 %, reaching the highest reported level. Utilizing a multi-dimensional rational design for a customized mutation strategy of the substrate-binding pocket is an effective approach to enhance the catalytic efficiency of enzymes in handling complicated substrates.

Cellular ATP redistribution achieved by deleting Tgparp improves lignocellulose utilization of Trichoderma under heat stress.

BACKGROUND: Thermotolerance is widely acknowledged as a pivotal factor for fungal survival across diverse habitats. Heat stress induces a cascade of disruptions in various life processes, especially in the acquisition of carbon sources, while the mechanisms by which filamentous fungi adapt to heat stress and maintain carbon sources are still not fully understood. RESULTS: Using Trichoderma guizhouense, a representative beneficial microorganism for plants, we discover that heat stress severely inhibits the lignocellulases secretion, affecting carbon source utilization efficiency. Proteomic results at different temperatures suggest that proteins involved in the poly ADP-ribosylation pathway (TgPARP and TgADPRase) may play pivotal roles in thermal adaptation and lignocellulose utilization. TgPARP is induced by heat stress, while the deletion of Tgparp significantly improves the lignocellulose utilization capacity and lignocellulases secretion in T. guizhouense. Simultaneously, the absence of Tgparp prevents the excessive depletion of ATP and NAD+, enhances the protective role of mitochondrial membrane potential (MMP), and elevates the expression levels of the unfolded protein response (UPR)-related regulatory factor Tgire. Further investigations reveal that a stable MMP can establish energy homeostasis, allocating more ATP within the endoplasmic reticulum (ER) to reduce protein accumulation in the ER, thereby enhancing the lignocellulases secretion in T. guizhouense under heat stress. CONCLUSIONS: Overall, these findings underscored the significance of Tgparp as pivotal regulators in lignocellulose utilization under heat stress and provided further insights into the molecular mechanism of filamentous fungi in utilizing lignocellulose.

BmNPV p35 regulates apoptosis in Bombyx mori via a novel target of interaction with the BmVDAC2-BmRACK1 complex.

Voltage-dependent anion channel 2 (VDAC2) is an important channel protein that plays a crucial role in the host response to viral infection. The receptor for activated C kinase 1 (RACK1) is also a key host factor involved in viral replication. Our previous research revealed that Bombyx mori VDAC2 (BmVDAC2) and B. mori RACK1 (BmRACK1) may interact with Bombyx mori nucleopolyhedrovirus (BmNPV), though the specific molecular mechanism remains unclear. In this study, the interaction between BmVDAC2 and BmRACK1 in the mitochondria was determined by various methods. We found that BmNPV p35 interacts directly with BmVDAC2 rather than BmRACK1. BmNPV infection significantly reduced the expression of BmVDAC2, and activated the mitochondrial apoptosis pathway. Overexpression of BmVDAC2 in BmN cells inhibited BmNPV-induced cytochrome c (cyto c) release, decrease in mitochondrial membrane potential as well as apoptosis. Additionally, the inhibition of cyto c release by BmVDAC2 requires the involvement of BmRACK1 and protein kinase C. Interestingly, overexpression of p35 inhibited cyto c release during mitochondrial apoptosis in a RACK1 and VDAC2-dependent manner. Even the mutant p35, which loses Caspase inhibitory activity, could still bind to VDAC2 and inhibit cyto c release. In summary, our results indicated that BmNPV p35 interacts with the VDAC2-RACK1 complex to regulate apoptosis by inhibiting cyto c release. These findings confirm the interaction between BmVDAC2 and BmRACK1, the interaction between p35 and the VDAC2-RACK1 complex, and a novel target that BmNPV p35 regulates apoptosis in Bombyx mori via interaction with the BmVDAC2-BmRACK1 complex. The result provide an initial exploration of the function of this interaction in the BmNPV-induced mitochondrial apoptosis pathway.

Methionine inducing carbohydrate esterase secretion of Trichoderma harzianum enhances the accessibility of substrate glycosidic bonds.

BACKGROUND: The conversion of plant biomass into biochemicals is a promising way to alleviate energy shortage, which depends on efficient microbial saccharification and cellular metabolism. Trichoderma spp. have plentiful CAZymes systems that can utilize all-components of lignocellulose. Acetylation of polysaccharides causes nanostructure densification and hydrophobicity enhancement, which is an obstacle for glycoside hydrolases to hydrolyze glycosidic bonds. The improvement of deacetylation ability can effectively release the potential for polysaccharide degradation. RESULTS: Ammonium sulfate addition facilitated the deacetylation of xylan by inducing the up-regulation of multiple carbohydrate esterases (CE3/CE4/CE15/CE16) of Trichoderma harzianum. Mainly, the pathway of ammonium-sulfate's cellular assimilates inducing up-regulation of the deacetylase gene (Thce3) was revealed. The intracellular metabolite changes were revealed through metabonomic analysis. Whole genome bisulfite sequencing identified a novel differentially methylated region (DMR) that existed in the ThgsfR2 promoter, and the DMR was closely related to lignocellulolytic response. ThGsfR2 was identified as a negative regulatory factor of Thce3, and methylation in ThgsfR2 promoter released the expression of Thce3. The up-regulation of CEs facilitated the substrate deacetylation. CONCLUSION: Ammonium sulfate increased the polysaccharide deacetylation capacity by inducing the up-regulation of multiple carbohydrate esterases of T. harzianum, which removed the spatial barrier of the glycosidic bond and improved hydrophilicity, and ultimately increased the accessibility of glycosidic bond to glycoside hydrolases.

Experimental Study of a Superabsorbent Polymer Hydrogel in an Alkali Environment and Its Effects on the Mechanical and Shrinkage Properties of Cement Mortars.

As internal curing self-healing agents in concrete repair, the basic properties of superabsorbent polymers (SAPs), such as water absorption and release properties, are generally affected by several factors, including temperature and humidity solution properties and SAP particle size, which regulate the curing effect and the durability of cementitious composites. This study aimed to investigate the water retention capacities of SAPs in an alkaline environment over extended periods by incorporating liquid sodium silicate (SS) into SAP-water mixtures and examining the influence of temperature. The influence of SAP particle size on mortar's water absorption capacity and mechanical behavior was investigated. Two mixing techniques for SAPs (dry and pre-wetting) were employed to assess the influence of SAP on cement mortars' slump, mechanical properties, and cracking resistance. Four types of SAPs (SAP-a, SAP-b, SAP-c, and SAP-d), based on the molecular chains and particle size, were mixed with SS to study their water absorption over 30 days. The results showed that SAPs exhibit rapid water absorption within the first 30 min, exceeding 85% before reaching a saturation point, and the chemical and temperature variations in the water significantly affected water absorption and desorption. The filtration results revealed that SAP-d exhibited the slowest water release rate, retaining water for considerably longer than the other three types of SAPs. The mechanical properties of SAP mortar were reduced due to the addition of an SAP and the improved cracking resistance of the cement mortars.

Security Enhancement for Deep Reinforcement Learning-Based Strategy in Energy-Efficient Wireless Sensor Networks.

Energy efficiency and security issues are the main concerns in wireless sensor networks (WSNs) because of limited energy resources and the broadcast nature of wireless communication. Therefore, how to improve the energy efficiency of WSNs while enhancing security performance has attracted widespread attention. In order to solve this problem, this paper proposes a new deep reinforcement learning (DRL)-based strategy, i.e., DeepNR strategy, to enhance the energy efficiency and security performance of WSN. Specifically, the proposed DeepNR strategy approximates the Q-value by designing a deep neural network (DNN) to adaptively learn the state information. It also designs DRL-based multi-level decision-making to learn and optimize the data transmission paths in real time, which eventually achieves accurate prediction and decision-making of the network. To further enhance security performance, the DeepNR strategy includes a defense mechanism that responds to detected attacks in real time to ensure the normal operation of the network. In addition, DeepNR adaptively adjusts its strategy to cope with changing network environments and attack patterns through deep learning models. Experimental results show that the proposed DeepNR outperforms the conventional methods, demonstrating a remarkable 30% improvement in network lifespan, a 25% increase in network data throughput, and a 20% enhancement in security measures.

Gilteritinib combined with venetoclax and azacitidine for relapsed acute myeloid leukemia cocurrent with pure red cell aplasia after allogeneic hematopoietic stem cell transplantation: a case report.

Pure red cell aplasia (PRCA) is a rare bone marrow (BM) disorder characterized by ineffective erythropoiesis, reduced reticulocyte count, normocytic anemia, and the absence of erythroid precursors. Here, we present a rare instance of PRCA occurring after ABO-matched allo-HSCT in a refractory/relapsed acute myeloid leukemia (R/R AML) patient. In this case, the patient received a combination treatment of Gilteritinib, Venetoclax, and Azacitidine. Remarkably, this treatment not only reduced myeloblasts but also facilitated the restoration of erythroid hematopoiesis.

Constructing a Titanium Silicon Molecular Sieve-Based Z-Scheme Heterojunction with Enhanced Photocatalytic Activity.

Titanium silicon molecular sieve (TS-1) is an oxidation catalyst that possesses a long lifetime of charge transfer excited state, high Ti utilization efficiency, large specific surface area, and good adsorption property; therefore, TS-1 acts as a Ti-based photocatalyst candidate. In this work, TS-1 coupled Bi2MoO6 (TS-1/BMO) photocatalysts were fabricated via a facile hydrothermal route. Interestingly, the optimized TS-1/BMO-1.0 catalyst exhibited a decent photodegradation property toward tetracycline hydrochloride (85.49% in 120 min) under the irradiation of full spectrum light, which were 4.38 and 1.76 times compared to TS-1 and BMO, respectively. The enhanced photodegradation property of the TS-1/BMO-1.0 catalyst could be attributed to the reinforced light-harvesting capacity of the photocatalyst, high charge mobility, and suitable band structure for tetracycline hydrochloride degradation. In addition, the mechanism of photocatalytic degradation of tetracycline hydrochloride by the TS-1/BMO-1.0 catalyst was reasonably proposed based on the band structure, trapping, and ESR tests. This research provided feasible ideas for the design and construction of high-efficiency photocatalysts for contaminant degradation.

Metabolic control of adaptive ß-cell proliferation by the protein deacetylase SIRT2.

Selective and controlled expansion of endogenous ß-cells has been pursued as a potential therapy for diabetes. Ideally, such therapies would preserve feedback control of ß-cell proliferation to avoid excessive ß-cell expansion and an increased risk of hypoglycemia. Here, we identified a regulator of ß-cell proliferation whose inactivation results in controlled ß-cell expansion: the protein deacetylase Sirtuin 2 (SIRT2). Sirt2 deletion in ß-cells of mice increased ß-cell proliferation during hyperglycemia with little effect in homeostatic conditions, indicating preservation of feedback control of ß-cell mass. SIRT2 restrains proliferation of human islet ß-cells cultured in glucose concentrations above the glycemic set point, demonstrating conserved SIRT2 function. Analysis of acetylated proteins in islets treated with a SIRT2 inhibitor revealed that SIRT2 deacetylates enzymes involved in oxidative phosphorylation, dampening the adaptive increase in oxygen consumption during hyperglycemia. At the transcriptomic level, Sirt2 inactivation has context-dependent effects on ß-cells, with Sirt2 controlling how ß-cells interpret hyperglycemia as a stress. Finally, we provide proof-of-principle that systemic administration of a GLP1-coupled Sirt2-targeting antisense oligonucleotide achieves ß-cell selective Sirt2 inactivation and stimulates ß-cell proliferation under hyperglycemic conditions. Overall, these studies identify a therapeutic strategy for increasing ß-cell mass in diabetes without circumventing feedback control of ß-cell proliferation.

Prevalence and network analysis of internet addiction, depression and their associations with sleep quality among commercial airline pilots: A national survey in China.

OBJECTIVE: Airline pilots are members of a unique occupational group that is often confronted with sleep routine disruptions, yet relatively few studies have examined their mental health status. This study assessed the prevalence and network structure of internet addiction, depression and sleep quality problems in commercial airline pilots. METHOD: A total of 7055 airline pilots were included in analyses. Internet addiction and depression were measured with the Internet Addiction Test (IAT) and 9-item Patient Health Questionnaire (PHQ-9), respectively. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). The network model was constructed based on an Ising model and its association with sleep quality was evaluated using a flow procedure. RESULTS: Internet addiction, depression and sleep quality were common among airline pilots. The prevalence of internet addiction was 8.0 % (95 % CI: 7.3-8.6 %), while the rates of depression and poor sleep quality were 23.3 % (95 % CI: 22.3-24.2 %) and 33.0 % (95 % CI: 31.9-34.1 %), respectively. In the depression and internet addiction network model, "Fatigue" (PHQ4; Expected Influence (EI): 2.04) and "Depressed/moody/nervous only while being offline" (IAT20; EI: 1.76) were most central symptoms while "Fatigue" (PHQ4; Bridge EI: 1.30) was also the most important bridge symptom. The flow network model of sleep quality with internet addiction and depression showed that "Appetite" (PHQ5) had the strongest positive association with poor sleep quality. CONCLUSION: Internet addiction, depression and sleep quality were common among airline pilots and warrant regular screening and timely treatment. Strategies to improve sleep hygiene may be useful in preventing onsets or exacerbations in depression and internet addiction among airline pilots.

DiffModeler: Large Macromolecular Structure Modeling in Low-Resolution Cryo-EM Maps Using Diffusion Model.

Cryogenic electron microscopy (cryo-EM) has now been widely used for determining multi-chain protein complexes. However, modeling a complex structure is challenging particularly when the map resolution is low, typically in the intermediate resolution range of 5 to 10 Å. Within this resolution range, even accurate structure fitting is difficult, let alone de novo modeling. To address this challenge, here we present DiffModeler, a fully automated method for modeling protein complex structures. DiffModeler employs a diffusion model for backbone tracing and integrates AlphaFold2-predicted single-chain structures for structure fitting. Extensive testing on cryo-EM maps at intermediate resolutions demonstrates the exceptional accuracy of DiffModeler in structure modeling, achieving an average TM-Score of 0.92, surpassing existing methodologies significantly. Notably, DiffModeler successfully modeled a protein complex composed of 47 chains and 13,462 residues, achieving a high TM-Score of 0.94. Further benchmarking at low resolutions (10-20 Å confirms its versatility, demonstrating plausible performance. Moreover, when coupled with CryoREAD, DiffModeler excels in constructing protein-DNA/RNA complex structures for near-atomic resolution maps (0-5 Å), showcasing state-of-the-art performance with average TM-Scores of 0.88 and 0.91 across two datasets.

Mental health status among children and adolescents in one-child and multichild families: a meta-analysis of comparative studies.

PURPOSE OF REVIEW: Controversy remains about the difference in mental health status among children and adolescents between one-child and multichild families in China. Thus, we conducted a meta-analysis of studies comparing mental health status between both groups and explored their potential moderating factors. RECENT FINDINGS: Totally, 113 eligible studies encompassing 237 899 participants (one-child families: 83 125; multichild families: 154 774) were included. The pooled SMD of SCL-90 total score was -0.115 [95% confidence interval (95% CI): -0.152; -0.078; I2  = 86.9%]. Specifically, children and adolescents from one-child families exhibited lower scores in terms of somatization (SMD = -0.056; 95% CI: -0.087; -0.026), obsessive-compulsive symptoms (SMD = -0.116; 95% CI: -0.154; -0.079), interpersonal sensitivity (SMD = -0.140; 95% CI: -0.171; -0.109), depression (SMD = -0.123; 95% CI: -0.159; -0.088); anxiety (SMD = -0.121; 95% CI: -0.151; -0.092); phobic anxiety (SMD = -0.124; 95% CI: -0.166; -0.081); paranoid ideation (SMD = -0.040; 95% CI: -0.070; -0.009); and psychoticism (SMD = -0.119; 95% CI: -0.148; -0.089). Study publication year was significantly associated with differences in mental health status between both groups ( P  = 0.015). SUMMARY: Children and adolescents from one-child families had better mental health status compared to those from multichild families in China. Future studies should investigate the underlying factors contributing to such mental health differences, and the potential interventions that could address these mental health problems.

Hydrolytic endonucleolytic ribozyme (HYER) is programmable for sequence-specific DNA cleavage.

Ribozymes are catalytic RNAs with diverse functions including self-splicing and polymerization. This work aims to discover natural ribozymes that behave as hydrolytic and sequence-specific DNA endonucleases, which could be repurposed as DNA manipulation tools. Focused on bacterial group II-C introns, we found that many systems without intron-encoded protein propagate multiple copies in their resident genomes. These introns, named HYdrolytic Endonucleolytic Ribozymes (HYERs), cleaved RNA, single-stranded DNA, bubbled double-stranded DNA (dsDNA), and plasmids in vitro. HYER1 generated dsDNA breaks in the mammalian genome. Cryo-electron microscopy analysis revealed a homodimer structure for HYER1, where each monomer contains a Mg2+-dependent hydrolysis pocket and captures DNA complementary to the target recognition site (TRS). Rational designs including TRS extension, recruiting sequence insertion, and heterodimerization yielded engineered HYERs showing improved specificity and flexibility for DNA manipulation.

The Effects and Toxicity of Different Pyrene Concentrations on Escherichia coli Using Transcriptomic Analysis.

Pyrene is a pollutant in the environment and affects the health of living organisms. It is important to understand microbial-mediated pyrene resistance and the related molecular mechanisms due to its toxicity and biodegradability. Due to the unclear response mechanisms of bacteria to PAHs, this study detected the transcriptional changes in Escherichia coli under different pyrene concentrations using transcriptome sequencing technology. Global transcriptome analysis showed that the number of differentially expressed genes (DEGs) in multiple metabolic pathways increased with increasing concentrations of pyrene. In addition, the effects and toxicity of pyrene on Escherichia coli mainly included the up-regulation and inhibition of genes related to carbohydrate metabolism, membrane transport, sulfate reduction, various oxidoreductases, and multidrug efflux pumps. Moreover, we also constructed an association network between significantly differentially expressed sRNAs and key genes and determined the regulatory relationship and key genes of Escherichia coli under pyrene stress. Our study utilized pyrene as an exogenous stress substance to investigate the possible pathways of the bacterial stress response. In addition, this study provides a reference for other related research and serves as a foundation for future research.

THE IMPACT OF ROUTINE CARDIAC TROPONIN I-BASED CARDIOTOXICITY SCREENING ON CLINICAL OUTCOMES IN PATIENTS ON CANCER IMMUNOTHERAPY.

Purpose: Immune checkpoint inhibitors (ICI) used as cancer therapy have been associated with a range of cardiac immune-related adverse events (irAEs), including fulminant myocarditis with a high case fatality rate. Early detection through cardiotoxicity screening by biomarker monitoring can lead to prompt intervention and improved patient outcomes. In this study, we investigate the association between cardiotoxicity screening with routine serial troponin I monitoring in asymptomatic patients receiving ICI, cardiovascular adverse event (CV AE) detection, and overall survival (OS). Methods: We instituted a standardized troponin I screening protocol at baseline and with each ICI dose (every 2-4 weeks) in all patients receiving ICI at our center starting Jan 2019. We subsequently collected data in 825 patients receiving ICI at our institution from January 2018 to October 2021. Of these patients, 428 underwent cardiotoxicity screening with serial troponin I monitoring during ICI administration (Jan 2019-Oct 2021) and 397 patients were unmonitored (Jan 2018-Dec 2018). We followed patients for nine months following their first dose of ICI and compared outcomes of CV AEs and OS between monitored and unmonitored patients. Additionally, we investigated rates of CV AEs, all-cause mortality, and oncologic time-to-treatment failure (TTF) between patients with an elevated troponin I value during the monitoring period versus patients without elevated troponin I. Results: We found a lower rate of severe (grades 4-5) CV AEs, resulting in critical illness or death, in patients who underwent troponin monitoring (0.5%) compared to patients who did not undergo monitoring (1.8%), (HR 0.17, 95% CI 0.02-0.79, p = 0.04). There was no difference in overall CV AEs (grades 3-5) or OS between monitored and unmonitored patients. In the entire cohort, patients with at least one elevated troponin I during the follow up period, during routine monitoring or unmonitored, had a higher risk of overall CV AEs (HR 10.96, 95% CI 4.65-25.85, p<0.001) as well as overall mortality (HR 2.67, 95% CI 1.69 - 4.10, p<0.001) compared to those without elevated troponin. Oncologic time-to-treatment failure (TTF) was not significantly different in a sub-cohort of monitored vs. unmonitored patients. Conclusions: Patients undergoing cardiotoxicity screening with troponin I monitoring during ICI therapy had a lower rate of severe (grade 4-5) CV AEs compared patients who were not screened. Troponin I elevation in screened and unscreened patients was significantly associated with increased CV AEs as well as increased mortality. Troponin I monitoring did not impact oncologic time-to-treatment-failure in a sub-cohort analysis of patients treated with ICI. These results provide preliminary evidence for clinical utility of cardiotoxicity screening with troponin I monitoring in patients receiving ICI therapy.

Additive manufacturing of dental ceramics in prosthodontics: The status quo and the future.

PURPOSE: This review aims to summarize the available technologies, material categories, and prosthodontic applications of additive manufacturing (AM) dental ceramics, evaluate the achievable accuracy and mechanical properties in comparison with current mainstream computer-aided design/computer-aided manufacturing (CAD/CAM) subtractive manufacturing (SM) methods, and discuss future prospects and directions. STUDY SELECTION: This paper is based on the latest reviews, state-of-the-art research, and existing ISO standards on AM technologies and prosthodontic applications of dental ceramics. PubMed, Web of Science, and ScienceDirect were amongst the sources searched for narrative reviews. RESULTS: Relatively few AM technologies are available and their applications are limited to crowns and fixed partial dentures. Although the accuracy and strength of AM dental ceramics are comparable to those of SM, they have the limitations of relatively inferior curved surface accuracy and low strength reliability. Furthermore, functionally graded additive manufacturing (FGAM), a potential direction for AM, enables the realization of biomimetic structures, such as natural teeth; however, specific studies are currently lacking. CONCLUSIONS: AM dental ceramics are not sufficiently developed for large-scale clinical applications. However, with additional research, it may be possible for AM to replace SM as the mainstream manufacturing technology for ceramic restorations.

Emerging electrospinning platform toward nanoparticle to single atom transformation for steering selectivity in ammonia synthesis.

The rising top-down synthetic methodologies for transition metal single-atom catalysts (SACs) require controlled movement of metal atoms through the substrates; however, their direct transportation towards the ideal carrier remains a huge challenge. Herein, we showed a "top down" strategy for Co nanoparticles (NPs) to Co SA transformation by employing electrospun carbon nanofibers (CNFs) as atom carriers. Under high-temperature conditions, the Co atoms migrate from the surfaces of Co NPs and are then anchored by the surrounding carbon to form a Co-C3O1 coordination structure. The synthesized Co SAs/CNF electrocatalyst exhibits excellent electrocatalytic nitrate reduction reaction (NO3RR) activity with an NH3 yield of 0.79 mmol h-1 cm-2 and Faraday efficiency (FE) of 91.3% at -0.7 V vs. RHE in 0.1 M KNO3 and 0.1 M K2SO4 electrolytes. The in situ electrochemical characterization suggests that the NOH pathway is preferred by Co SAs/CNFs, and *NO hydrogenation and deoxygenation easily occur on Co SAs due to the small adsorption energy between Co SAs and *NO, as calculated by theoretical calculations. It is revealed that a small energy barrier (0.45 eV) for the rate determining step (RDS) ranges from *NO to *NOH and a strong capability for inhibiting hydrogen evolution (HER) significantly promotes the NH3 selectivity and activity of Co SAs/CNFs.

Engineering a Dynamic Solvent-Phobic Liquid Electrolyte Interphase for Long-Life Lithium Metal Batteries.

The heterogeneity, species diversity, and poor mechanical stability of solid electrolyte interphases (SEIs) in conventional carbonate electrolytes result in the irreversible exhaustion of lithium (Li) and electrolytes during cycling, hindering the practical applications of Li metal batteries (LMBs). Herein, this work proposes a solvent-phobic dynamic liquid electrolyte interphase (DLEI) on a Li metal (Li-PFbTHF (perfluoro-butyltetrahydrofuran)) surface that selectively transports salt and induces salt-derived SEI formation. The solvent-phobic DLEI with C-F-rich groups dramatically reduces the side reactions between Li, carbonate solvents, and humid air, forming a LiF/Li3PO4-rich SEI. In situ electrochemical impedance spectroscopy and Ab-initio molecular dynamics demonstrate that DLEI effectively stabilizes the interface between Li metal and the carbonate electrolyte. Specifically, the LiFePO4||Li-PFbTHF cells deliver 80.4% capacity retention after 1000 cycles at 1.0 C, excellent rate capacity (108.2 mAh g-1 at 5.0 C), and 90.2% capacity retention after 550 cycles at 1.0 C in full-cells (negative/positive (N/P) ratio of 8) with high LiFePO4 loadings (15.6 mg cm-2) in carbonate electrolyte. In addition, the 0.55 Ah pouch cell of 252.0 Wh kg-1 delivers stable cycling. Hence, this study provides an effective strategy for controlling salt-derived SEI to improve the cycling performances of carbonate-based LMBs.

Immune checkpoints in cardiac physiology and pathology: therapeutic targets for heart failure.

Immune checkpoint molecules are physiological regulators of the adaptive immune response. Immune checkpoint inhibitors (ICIs), such as monoclonal antibodies targeting programmed cell death protein 1 or cytotoxic T lymphocyte-associated protein 4, have revolutionized cancer treatment and their clinical use is increasing. However, ICIs can cause various immune-related adverse events, including acute and chronic cardiotoxicity. Of these cardiovascular complications, ICI-induced acute fulminant myocarditis is the most studied, although emerging clinical and preclinical data are uncovering the importance of other ICI-related chronic cardiovascular complications, such as accelerated atherosclerosis and non-myocarditis-related heart failure. These complications could be more difficult to diagnose, given that they might only be present alongside other comorbidities. The occurrence of these complications suggests a potential role of immune checkpoint molecules in maintaining cardiovascular homeostasis, and disruption of physiological immune checkpoint signalling might thus lead to cardiac pathologies, including heart failure. Although inflammation is a long-known contributor to the development of heart failure, the therapeutic targeting of pro-inflammatory pathways has not been successful thus far. The increasingly recognized role of immune checkpoint molecules in the failing heart highlights their potential use as immunotherapeutic targets for heart failure. In this Review, we summarize the available data on ICI-induced cardiac dysfunction and heart failure, and discuss how immune checkpoint signalling is altered in the failing heart. Furthermore, we describe how pharmacological targeting of immune checkpoints could be used to treat heart failure.