Genetic Deletion of Galectin-3 Inhibits Pancreatic Cancer Progression and Enhances the Efficacy of Immunotherapy.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) has a desmoplastic tumor stroma and immunosuppressive microenvironment. Galectin-3 (GAL3) is enriched in PDAC, highly expressed by cancer cells and myeloid cells. However, the functional roles of GAL3 in the PDAC microenvironment remain elusive. METHODS: We generated a novel transgenic mouse model (LSL-KrasG12D/+;Trp53loxP/loxP;Pdx1-Cre;Lgals3-/- [KPPC;Lgals3-/-]) that allows the genetic depletion of GAL3 from both cancer cells and myeloid cells in spontaneous PDAC formation. Single-cell RNA-sequencing analysis was used to identify the alterations in the tumor microenvironment upon GAL3 depletion. We investigated both the cancer cell-intrinsic function and immunosuppressive function of GAL3. We also evaluated the therapeutic efficacy of GAL3 inhibition in combination with immunotherapy. RESULTS: Genetic deletion of GAL3 significantly inhibited the spontaneous pancreatic tumor progression and prolonged the survival of KPPC;Lgals3-/- mice. Single-cell analysis revealed that genetic deletion of GAL3 altered the phenotypes of immune cells, cancer cells, and other cell populations. GAL3 deletion significantly enriched the antitumor myeloid cell subpopulation with high major histocompatibility complex class II expression. We also identified that GAL3 depletion resulted in CXCL12 upregulation, which could act as a potential compensating mechanism on GAL3 deficiency. Combined inhibition of the CXCL12-CXCR4 axis and GAL3 enhanced the efficacy of anti-PD-1 immunotherapy, leading to significantly inhibited PDAC progression. In addition, deletion of GAL3 also inhibited the basal/mesenchymal-like phenotype of pancreatic cancer cells. CONCLUSIONS: GAL3 promotes PDAC progression and immunosuppression via both cancer cell-intrinsic and immune-related mechanisms. Combined treatment targeting GAL3, CXCL12-CXCR4 axis, and PD-1 represents a novel therapeutic strategy for PDAC.

Differentiation of Type 17 Mucosal-Associated Invariant T Cells in Circulation Contributes to the Severity of Sepsis.

Mucosal-associated invariant T (MAIT) cells are essential in defending against infection. Sepsis is a systemic inflammatory response to infection and a leading cause of death. The relationship between the overall competency of the host immune response and disease severity is not fully elucidated. This study identified a higher proportion of circulating MAIT17 with expression of IL-17A and retinoic acid receptor-related orphan receptor γt in patients with sepsis. The proportion of MAIT17 was correlated with the severity of sepsis. Single-cell RNA-sequencing analysis revealed an enhanced expression of lactate dehydrogenase A (LDHA) in MAIT17 in patients with sepsis. Cell-culture experiments demonstrated that phosphoinositide 3-kinase-LDHA signaling was required for retinoic acid receptor-related orphan receptor γt expression in MAIT17. Finally, the elevated levels of plasma IL-18 promoted the differentiation of circulating MAIT17 cells in sepsis. In summary, this study reveals a new role of circulating MAIT17 in promoting sepsis severity and suggests the phosphoinositide 3-kinase-LDHA signaling as a driving force in MAIT17 responses.

The CsDof1.8-CsLIPOXYGENASE09 module regulates C9 aroma production in cucumber.

Nine-carbon aldehydes and their relative alcohols (C9 aromas) are the main aroma compounds of cucumber (Cucumis sativus L.) fruits and provide a unique cucumber-like note. However, the key regulators of C9 aroma accumulation in cucumber fruit are poorly characterized. Based on C9 aroma dynamic analysis and transcriptome analysis during fruit development of two different cucumber inbred lines, Q16 and Q24, Lipoxygenase09 (CsLOX09) was identified as a candidate gene for C9 aroma accumulation. Additionally, Q24 with higher CsLOX09 expression accumulated more C9 aromas than Q16. To verify the function of CsLOX09, Cslox09 homozygote knockout lines were created. C9 aroma content decreased by 80.79%-99.16% in these mutants compared to the wild type. To further explore the reasons for the difference in CsLOX09 expression between Q16 and Q24 fruits, a co-expression network was constructed by integrating the C9 aroma-associated metabolism and transcriptomic data. Eighteen candidate transcription factors were highly correlated with the expression of CsLOX09. DNA binding with One Finger 1.8 (CsDof1.8) was confirmed to bind directly to the A/TAAAG motif of the CsLOX09 promoter through dual-luciferase, yeast one-hybrid, chromatin immunoprecipitation-qPCR and electrophoretic mobility shift assays. Furthermore, C9 aroma content and CsLOX09 expression were significantly increased in the CsDof1.8 overexpression lines. Overall, these data elucidate the metabolic regulation of C9 aromas in cucumber and provide a foundation for facilitating the regulation of flavor in cucumber breeding.

The synthesis and application of crystalline-amorphous hybrid materials.

Crystalline-amorphous hybrid materials (CA-HMs) possess the merits of both pure crystalline and amorphous phases. Abundant dangling bonds, unsaturated coordination atoms, and isotropic structural features in the amorphous phase, as well as relatively high electronic conductivity and thermodynamic structural stability of the crystalline phase simultaneously take effect in CA-HMs. Furthermore, the atomic and bandgap mismatch at the CA-HM interface can introduce more defects as extra active sites, reservoirs for promoted catalytic and electrochemical performance, and induce built-in electric field for facile charge carrier transport. Motivated by these intriguing features, herein, we provide a comprehensive overview of CA-HMs on various aspects-from synthetic methods to multiple applications. Typical characteristics of CA-HMs are discussed at the beginning, followed by representative synthetic strategies of CA-HMs, including hydrothermal/solvothermal methods, deposition techniques, thermal adjustment, and templating methods. Diverse applications of CA-HMs, such as electrocatalysis, batteries, supercapacitors, mechanics, optoelectronics, and thermoelectrics along with underlying structure-property mechanisms are carefully elucidated. Finally, challenges and perspectives of CA-HMs are proposed with an aim to provide insights into the future development of CA-HMs.

Biomaterials with cancer cell-specific cytotoxicity: challenges and perspectives.

Significant advances have been made in materials for biomedical applications, including tissue engineering, bioimaging, cancer treatment, etc. In the past few decades, nanostructure-mediated therapeutic strategies have been developed to improve drug delivery, targeted therapy, and diagnosis, maximizing therapeutic effectiveness while reducing systemic toxicity and side effects by exploiting the complicated interactions between the materials and the cell and tissue microenvironments. This review briefly introduces the differences between the cells and tissues of tumour or normal cells. We summarize recent advances in tumour microenvironment-mediated therapeutic strategies using nanostructured materials. We then comprehensively discuss strategies for fabricating nanostructures with cancer cell-specific cytotoxicity by precisely controlling their composition, particle size, shape, structure, surface functionalization, and external energy stimulation. Finally, we present perspectives on the challenges and future opportunities of nanotechnology-based toxicity strategies in tumour therapy.

KLHL21 suppresses gastric tumourigenesis via maintaining STAT3 signalling equilibrium in stomach homoeostasis.

OBJECTIVE: Precancerous metaplasia transition to dysplasia poses a risk for subsequent intestinal-type gastric adenocarcinoma. However, the molecular basis underlying the transformation from metaplastic to cancerous cells remains poorly understood. DESIGN: An integrated analysis of genes associated with metaplasia, dysplasia was conducted, verified and characterised in the gastric tissues of patients by single-cell RNA sequencing and immunostaining. Multiple mouse models, including homozygous conditional knockout Klhl21-floxed mice, were generated to investigate the role of Klhl21 deletion in stemness, DNA damage and tumour formation. Mass-spectrometry-based proteomics and ribosome sequencing were used to elucidate the underlying molecular mechanisms. RESULTS: Kelch-like protein 21 (KLHL21) expression progressively decreased in metaplasia, dysplasia and cancer. Genetic deletion of Klhl21 enhances the rapid proliferation of Mist1+ cells and their descendant cells. Klhl21 loss during metaplasia facilitates the recruitment of damaged cells into the cell cycle via STAT3 signalling. Increased STAT3 activity was confirmed in cancer cells lacking KLHL21, boosting self-renewal and tumourigenicity. Mechanistically, the loss of KLHL21 promotes PIK3CB mRNA translation by stabilising the PABPC1-eIF4G complex, subsequently causing STAT3 activation. Pharmacological STAT3 inhibition by TTI-101 elicited anticancer effects, effectively impeding the transition from metaplasia to dysplasia. In patients with gastric cancer, low levels of KLHL21 had a shorter survival rate and a worse response to adjuvant chemotherapy. CONCLUSIONS: Our findings highlighted that KLHL21 loss triggers STAT3 reactivation through PABPC1-mediated PIK3CB translational activation, and targeting STAT3 can reverse preneoplastic metaplasia in KLHL21-deficient stomachs.

Natural killer cell-related anti-tumour adoptive cell immunotherapy.

Chimeric antigen receptor- (CAR-)modified T cells have been successfully used to treat blood cancer. With the improved research on anti-tumour adoptive cell therapy, researchers have focused on immune cells other than T lymphocytes. Natural killer (NK) cells have received widespread attention as barriers to natural immunity. Compared to T lymphocyte-related adoptive cell therapy, the use of NK cells to treat tumours does not cause graft-versus-host disease, significantly improving immunity. Moreover, NK cells have more sources than T cells, and the related modified cells are less expensive. NK cells function through several pathways in anti-tumour mechanisms. Currently, many anti-tumour clinical trials have used NK cell-related adoptive cell therapies. In this review, we have summarized the recent progress in NK cell-related adoptive cellular immunotherapy for tumour treatment and propose the current challenges faced by CAR-NK cell therapy.

Superoxide dismutase 1-modified dental pulp stem cells alleviate high-altitude pulmonary edema by inhibiting oxidative stress through the Nrf2/HO-1 pathway.

High-altitude pulmonary edema (HAPE) is a deadly form of altitude sickness, and there is no effective treatment for HAPE. Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cell isolated from dental pulp tissues and possess various functions, such as anti-inflammatory and anti-oxidative stress. DPSCs have been used to treat a variety of diseases, but there are no studies on treating HAPE. In this study, Sprague-Dawley rats were exposed to acute low-pressure hypoxia to establish the HAPE model, and SOD1-modified DPSCs (DPSCsHiSOD1) were administered through the tail vein. Pulmonary arterial pressure, lung water content (LWC), total lung protein content of bronchoalveolar lavage fluid (BALF) and lung homogenates, oxidative stress, and inflammatory indicators were detected to evaluate the effects of DPSCsHiSOD1 on HAPE. Rat type II alveolar epithelial cells (RLE-6TN) were used to investigate the effects and mechanism of DPSCsHiSOD1 on hypoxia injury. We found that DPSCs could treat HAPE, and the effect was better than that of dexamethasone treatment. SOD1 modification could enhance the function of DPSCs in improving the structure of lung tissue, decreasing pulmonary arterial pressure and LWC, and reducing the total lung protein content of BALF and lung homogenates, through anti-oxidative stress and anti-inflammatory effects. Furthermore, we found that DPSCsHiSOD1 could protect RLE-6TN from hypoxic injury by reducing the accumulation of reactive oxygen species (ROS) and activating the Nrf2/HO-1 pathway. Our findings confirm that SOD1 modification could enhance the anti-oxidative stress ability of DPSCs through the Nrf2/HO-1 signalling pathway. DPSCs, especially DPSCsHiSOD1, could be a potential treatment for HAPE. Schematic diagram of the antioxidant stress mechanism of DPSCs in the treatment of high-altitude pulmonary edema. DPSCs can alleviate oxidative stress by releasing superoxide dismutase 1, thereby reducing ROS production and activating the Nrf2/HO-1 signalling pathway to ameliorate lung cell injury in HAPE.

Reshaping the Primary Cell Wall: Dual Effects on Plant Resistance to Ralstonia solanacearum and Heat Stress Response.

Temperature elevation drastically affects plant defense responses to Ralstonia solanacearum and inhibits the major source of resistance in Arabidopsis thaliana, which is mediated by the receptor pair RRS1-R/RPS4. In this study, we refined a previous genome-wide association (GWA) mapping analysis by using a local score approach and detected the primary cell wall CESA3 gene as a major gene involved in plant response to R. solanacearum at both 27°C and an elevated temperature, 30°C. We functionally validated CESA3 as a susceptibility gene involved in resistance to R. solanacearum at both 27 and 30°C through a reverse genetic approach. We provide evidence that the cesa3mre1 mutant enhances resistance to bacterial disease and that resistance is associated with an alteration of root cell morphology conserved at elevated temperatures. However, even by forcing the entry of the bacterium to bypass the primary cell wall barrier, the cesa3mre1 mutant still showed enhanced resistance to R. solanacearum with delayed onset of bacterial wilt symptoms. We demonstrated that the cesa3mre1 mutant had constitutive expression of the defense-related gene VSP1, which is upregulated at elevated temperatures, and that during infection, its expression level is maintained higher than in the wild-type Col-0. In conclusion, this study reveals that alteration of the primary cell wall by mutating the cellulose synthase subunit CESA3 contributes to enhanced resistance to R. solanacearum, remaining effective under heat stress. We expect that these results will help to identify robust genetic sources of resistance to R. solanacearum in the context of global warming. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Omicron breakthrough infections after triple-dose inactivated COVID-19 vaccination: A comprehensive analysis of antibody and T-cell responses.

This study longitudinally evaluated the immune response in individuals over a year after receiving three doses of an inactivated SARS-CoV-2 vaccine, focusing on reactions to Omicron breakthrough infections. From 63 blood samples of 37 subjects, results showed that the third booster enhanced the antibody response against Alpha, Beta, and Delta VOCs but was less effective against Omicron. Although antibody titres decreased post-vaccination, SARS-CoV-2-specific T-cell responses, both CD4+ and CD8+, remained stable. Omicron breakthrough infections significantly improved neutralization against various VOCs, including Omicron. However, the boost in antibodies against WT, Alpha, Beta, and Delta variants was more pronounced. Regarding T cells, breakthrough infection predominantly boosted the CD8+ T-cell response, and the intensity of the spike protein-specific T-cell response was roughly comparable between WT and Omicron BA.5.

Role of H2O in Catalytic Conversion of C1 Molecules.

Due to their role in controlling global climate change, the selective conversion of C1 molecules such as CH4, CO, and CO2 has attracted widespread attention. Typically, H2O competes with the reactant molecules to adsorb on the active sites and therefore inhibits the reaction or causes catalyst deactivation. However, H2O can also participate in the catalytic conversion of C1 molecules as a reactant or a promoter. Herein, we provide a perspective on recent progress in the mechanistic studies of H2O-mediated conversion of C1 molecules. We aim to provide an in-depth and systematic understanding of H2O as a promoter, a proton-transfer agent, an oxidant, a direct source of hydrogen or oxygen, and its influence on the catalytic activity, selectivity, and stability. We also summarize strategies for modifying catalysts or catalytic microenvironments by chemical or physical means to optimize the positive effects and minimize the negative effects of H2O on the reactions of C1 molecules. Finally, we discuss challenges and opportunities in catalyst design, characterization techniques, and theoretical modeling of the H2O-mediated catalytic conversion of C1 molecules.

JAK/STAT in leukemia: a clinical update.

Over the past three decades, considerable efforts have been expended on understanding the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in leukemia, following the identification of the JAK2V617F mutation in myeloproliferative neoplasms (MPNs). The aim of this review is to summarize the latest progress in our understanding of the involvement of the JAK/STAT signaling pathway in the development of leukemia. We also attempt to provide insights into the current use of JAK/STAT inhibitors in leukemia therapy and explore pertinent clinical trials in this field.

Chimeric antigen receptor-modified macrophages ameliorate liver fibrosis in preclinical models.

BACKGROUND & AIMS: Treatments directly targeting fibrosis remain limited. Given the unique intrinsic features of macrophages and their capacity to engraft in the liver, we genetically engineered bone marrow-derived macrophages with a chimeric antigen receptor (CAR) to direct their phagocytic activity against hepatic stellate cells (HSCs) in multiple mouse models. This study aimed to demonstrate the therapeutic efficacy of CAR macrophages (CAR-Ms) in mouse models of fibrosis and cirrhosis and to elucidate the underlying mechanisms. METHODS: uPAR expression was studied in patients with fibrosis/cirrhosis and in murine models of liver fibrosis, including mice treated with carbon tetrachloride, a 5-diethoxycarbonyl-1, 4-dihydrocollidine diet, or a high-fat/cholesterol/fructose diet. The safety and efficacy of CAR-Ms were evaluated in vitro and in vivo. RESULTS: Adoptive transfer of CAR-Ms resulted in a significant reduction in liver fibrosis and the restoration of function in murine models of liver fibrosis. CAR-Ms modulated the hepatic immune microenvironment to recruit and modify the activation of endogenous immune cells to drive fibrosis regression. These CAR-Ms were able to recruit and present antigens to T cells and mount specific antifibrotic T-cell responses to reduce fibroblasts and liver fibrosis in mice. CONCLUSION: Collectively, our findings demonstrate the potential of using macrophages as a platform for CAR technology to provide an effective treatment option for liver fibrosis. CAR-Ms might be developed for treatment of patients with liver fibrosis. IMPACT AND IMPLICATIONS: Liver fibrosis is an incurable condition that afflicts millions of people globally. Despite the clear clinical need, therapies for liver fibrosis are limited. Our findings provide the first preclinical evidence that chimeric antigen receptor (CAR)-macrophages (CAR-Ms) targeting uPAR can attenuate liver fibrosis and cirrhosis. We show that macrophages expressing this uPAR CAR exert a direct antifibrotic effect and elicit a specific T-cell response that augments the immune response against liver fibrosis. These findings demonstrate the potential of using CAR-Ms as an effective cell-based therapy for the treatment of liver fibrosis.

Targeting EFHD2 inhibits interferon-γ signaling and ameliorates non-alcoholic steatohepatitis.

BACKGROUND & AIMS: The precise pathomechanisms underlying the development of non-alcoholic steatohepatitis (NASH, also known as metabolic dysfunction-associated steatohepatitis [MASH]) remain incompletely understood. In this study, we investigated the potential role of EF-hand domain family member D2 (EFHD2), a novel molecule specific to immune cells, in the pathogenesis of NASH. METHODS: Hepatic EFHD2 expression was characterized in patients with NASH and two diet-induced NASH mouse models. Single-cell RNA sequencing (scRNA-seq) and double-immunohistochemistry were employed to explore EFHD2 expression patterns in NASH livers. The effects of global and myeloid-specific EFHD2 deletion on NASH and NASH-related hepatocellular carcinoma were assessed. Molecular mechanisms underlying EFHD2 function were investigated, while chemical and genetic investigations were performed to assess its potential as a therapeutic target. RESULTS: EFHD2 expression was significantly elevated in hepatic macrophages/monocytes in both patients with NASH and mice. Deletion of EFHD2, either globally or specifically in myeloid cells, improved hepatic steatosis, reduced immune cell infiltration, inhibited lipid peroxidation-induced ferroptosis, and attenuated fibrosis in NASH. Additionally, it hindered the development of NASH-related hepatocellular carcinoma. Specifically, deletion of myeloid EFHD2 prevented the replacement of TIM4+ resident Kupffer cells by infiltrated monocytes and reversed the decreases in patrolling monocytes and CD4+/CD8+ T cell ratio in NASH. Mechanistically, our investigation revealed that EFHD2 in myeloid cells interacts with cytosolic YWHAZ (14-3-3ζ), facilitating the translocation of IFNγR2 (interferon-γ receptor-2) onto the plasma membrane. This interaction mediates interferon-γ signaling, which triggers immune and inflammatory responses in macrophages during NASH. Finally, a novel stapled α-helical peptide targeting EFHD2 was shown to be effective in protecting against NASH pathology in mice. CONCLUSION: Our study reveals a pivotal immunomodulatory and inflammatory role of EFHD2 in NASH, underscoring EFHD2 as a promising druggable target for NASH treatment. IMPACT AND IMPLICATIONS: Non-alcoholic steatohepatitis (NASH) represents an advanced stage of non-alcoholic fatty liver disease (NAFLD); however, not all patients with NAFLD progress to NASH. A key challenge is identifying the factors that trigger inflammation, which propels the transition from simple fatty liver to NASH. Our research pinpointed EFHD2 as a pivotal driver of NASH, orchestrating the over-activation of interferon-γ signaling within the liver during NASH progression. A stapled peptide designed to target EFHD2 exhibited therapeutic promise in NASH mice. These findings support the potential of EFHD2 as a therapeutic target in NASH.

Development of a Colorimetric and SERS Dual-Signal Platform via dCas9-Mediated Chain Assembly of Bifunctional Au@Pt Nanozymes for Ultrasensitive and Robust Salmonella Assay.

Timely screening for harmful pathogens is a great challenge in emergencies where traditional culture methods suffer from long assay time and alternative methods are limited by poor accuracy and low robustness. Herein, we present a dCas9-mediated colorimetric and surface-enhanced Raman scattering (SERS) dual-signal platform (dCas9-CSD) to address this challenge. Strategically, the platform used dCas9 to accurately recognize the repetitive sequences in amplicons produced by loop-mediated isothermal amplification (LAMP), forming nucleic acid frameworks that assemble numerous bifunctional gold-platinum (Au@Pt) nanozymes into chains on the surface of streptavidin-magnetic beads (SA-MB). The collected Au@Pt converted colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB (oxTMB) via its Pt shell and then enhanced the Raman signal of oxTMB by its Au core. Therefore, the presence of Salmonella could be dexterously converted into cross-validated colorimetric and SERS signals, providing more reliable conclusions. Notably, dCas9-mediated secondary recognition of amplicons reduced background signal caused by nontarget amplification, and two-round signal amplification consisting of LAMP reaction and Au@Pt catalysis greatly improved the sensitivity. With this design, Salmonella as low as 1 CFU/mL could be detected within 50 min by colorimetric and SERS modes. The robustness of dCas9-CSD was further confirmed by various real samples such as lake water, cabbage, milk, orange juice, beer, and eggs. This work provides a promising point-of-need tool for pathogen detection.

Five years of change in adult twins: longitudinal changes of genetic and environmental influence on epigenetic clocks.

BACKGROUND: Epigenetic clocks were known as promising biomarkers of aging, including original clocks trained by individual CpG sites and principal component (PC) clocks trained by PCs of CpG sites. The effects of genetic and environmental factors on epigenetic clocks are still unclear, especially for PC clocks. METHODS: We constructed univariate twin models in 477 same-sex twin pairs from the Chinese National Twin Registry (CNTR) to estimate the heritability of five epigenetic clocks (GrimAge, PhenoAge, DunedinPACE, PCGrimAge, and PCPhenoAge). Besides, we investigated the longitudinal changes of genetic and environmental influences on epigenetic clocks across 5 years in 134 same-sex twin pairs. RESULTS: Heritability of epigenetic clocks ranged from 0.45 to 0.70, and those for PC clocks were higher than those for original clocks. For five epigenetic clocks, the longitudinal stability was moderate to high and was largely due to genetic effects. The genetic correlations between baseline and follow-up epigenetic clocks were moderate to high. Special unique environmental factors emerged both at baseline and at follow-up. PC clocks showed higher longitudinal stability and unique environmental correlations than original clocks. CONCLUSIONS: For five epigenetic clocks, they have the potential to identify aging interventions. High longitudinal stability is mainly due to genetic factors, and changes of epigenetic clocks over time are primarily due to changes in unique environmental factors. Given the disparities in genetic and environmental factors as well as longitudinal stability between PC and original clocks, the results of studies with original clocks need to be further verified with PC clocks.

Redox-Responsive AIEgen Diselenide-Covalent Organic Framework Composites Targeting Hepatic Macrophages for Treatment of Drug-induced Liver Injury.

The escalating misuse of antipyretic and analgesic drugs, alongside the rising incidents of acute drug-induced liver injury, underscores the need for a precisely targeted drug delivery system. Herein, two isoreticular covalent organic frameworks (Se-COF and Se-BCOF) are developed by Schiff-base condensation of emissive tetraphenylethylene and diselenide-bridged monomers. Leveraging the specific affinity of macrophages for mannose, the first precise targeting of these COFs to liver macrophages is achieved. The correlation is also explored between the therapeutic effects of COFs and the NLRP3/ASC/Caspase-1 signaling pathway. Utilizing this innovative delivery vehicle, the synergistic delivery of matrine and berberine are accomplished, compounds extracted from traditional Chinese medicine. This approach not only demonstrated the synergistic effects of the drugs but also mitigated their toxicity. Notably, berberine, through phosphorylation of JNK and up-regulation of nuclear Nrf-2 and its downstream gene Mn-SOD expression, simultaneously countered excessive ROS and suppressed the activation of the NLRP3/ASC/Caspase-1 signaling pathway in injured liver tissues. This multifaceted approach proved highly effective in safeguarding against acute drug-induced liver injury, ultimately restoring liver health to normalcy. These findings present a novel and promising strategy for the treatment of acute drug-induced liver injury.

Low-Temperature and Fast-Charge Sodium Metal Batteries.

Low-temperature operation of sodium metal batteries (SMBs) at the high rate faces challenges of unstable solid electrolyte interphase (SEI), Na dendrite growth, and sluggish Na+ transfer kinetics, causing a largely capacity curtailment. Herein, low-temperature and fast-charge SMBs are successfully constructed by synergetic design of the electrolyte and electrode. The optimized weak-solvation dual-salt electrolyte enables high Na plating/stripping reversibility and the formation of NaF-rich SEI layer to stabilize sodium metal. Moreover, an integrated copper sulfide electrode is in situ fabricated by directly chemical sulfuration of copper current collector with micro-sized sulfur particles, which significantly improves the electronic conductivity and Na+ diffusion, knocking down the kinetic barriers. Consequently, this SMB achieves the reversible capacity of 202.8 mAh g-1 at -20 °C and 1 C (1 C = 558 mA g-1). Even at -40 °C, a high capacity of 230.0 mAh g-1 can still be delivered at 0.2 C. This study is encouraging for further exploration of cryogenic alkali metal batteries, and enriches the electrode material for low-temperature energy storage.

Ti─O─C Bonding at 2D Heterointerfaces of 3D Composites for Fast Sodium Ion Storage at High Mass Loading Level.

3D composite electrodes have shown extraordinary promise as high mass loading electrode materials for sodium ion batteries (SIBs). However, they usually show poor rate performance due to the sluggish Na+ kinetics at the heterointerfaces of the composites. Here, a 3D MXene-reduced holey graphene oxide (MXene-RHGO) composite electrode with Ti─O─C bonding at 2D heterointerfaces of MXene and RHGO is developed. Density functional theory (DFT) calculations reveal the built-in electric fields (BIEFs) are enhanced by the formation of bridged interfacial Ti─O─C bonding, that lead to not only faster diffusion of Na+ at the heterointerfaces but also faster adsorption and migration of Na+ on the MXene surfaces. As a result, the 3D composite electrodes show impressive properties for fast Na+ storage. Under high current density of 10 mA cm-2, the 3D MXene-RHGO composite electrodes with high mass loading of 10 mg cm-2 achieve a strikingly high and stable areal capacity of 3 mAh cm-2, which is same as commercial LIBs and greatly exceeds that of most reported SIBs electrode materials. The work shows that rationally designed bonding at the heterointerfaces represents an effective strategy for promoting high mass loading 3D composites electrode materials forward toward practical SIBs applications.

Localized High-Concentration Sulfone Electrolytes with High-Voltage Stability and Flame Retardancy for Ni-Rich Lithium Metal Batteries.

The localized high-concentration electrolyte (LHCE) propels the advanced high-voltage battery system. Sulfone-based LHCE is a transformative direction compatible with high energy density and high safety. In this work, the application of lithium bis(trifluoromethanesulphonyl)imide and lithium bis(fluorosulfonyl)imide (LiFSI) in the LHCE system constructed from sulfolane and 1,1,2,2-tetrafluoroethyl-2,2,3,3-tetrafluoropropyl ether (TTE) is investigated. The addition of diluent causes an increase of contact ion pairs and ionic aggregates in the solvation cluster and an acceptable quantity of free solvent molecules. A small amount of LiFSI as an additive can synergistically decompose with TTE on the cathode and participate in the construction of both electrode interfaces. The designed electrolyte helps the Ni-rich system to cycle firmly at a high voltage of 4.5 V. Even with high mass load and lean electrolyte, it can keep a reversible specific capacity of 91.5% after 50 cycles. The constructed sulfone-based electrolyte system exhibits excellent thermal stability far beyond the commercial electrolytes. Further exploration of in-situ gelation has led to a quick conversion of the designed liquid electrolyte to the gel state, accompanied by preserved stability, which provides a direction for the synergistic development of LHCE with gel electrolytes.