University of South China

In this critical review, metal oxides-based materials for electrochemical supercapacitor (ES) electrodes are reviewed in detail together with a brief review of carbon materials and conducting polymers. Their advantages, disadvantages, and performance in ES electrodes are discussed through extensive analysis of the literature, and new trends in material development are also reviewed. Two important future research directions are indicated and summarized, based on results published in the literature: the development of composite and nanostructured ES materials to overcome the major challenge posed by the low energy density of ES (476 references).

As an essential micronutrient, copper is required for a wide range of physiological processes in virtually all cell types. Because the accumulation of intracellular copper can induce oxidative stress and perturbing cellular function, copper homeostasis is tightly regulated. Recent studies identified a novel copper-dependent form of cell death called cuproptosis, which is distinct from all other known pathways underlying cell death. Cuproptosis occurs via copper binding to lipoylated enzymes in the tricarboxylic acid (TCA) cycle, which leads to subsequent protein aggregation, proteotoxic stress, and ultimately cell death. Here, we summarize our current knowledge regarding copper metabolism, copper-related disease, the characteristics of cuproptosis, and the mechanisms that regulate cuproptosis. In addition, we discuss the implications of cuproptosis in the pathogenesis of various disease conditions, including Wilson's disease, neurodegenerative diseases, and cancer, and we discuss the therapeutic potential of targeting cuproptosis.

Abstract The overlapping metabolic reprogramming of cancer and immune cells is a putative determinant of the antitumor immune response in cancer. Increased evidence suggests that cancer metabolism not only plays a crucial role in cancer signaling for sustaining tumorigenesis and survival, but also has wider implications in the regulation of antitumor immune response through both the release of metabolites and affecting the expression of immune molecules, such as lactate, PGE 2 , arginine, etc. Actually, this energetic interplay between tumor and immune cells leads to metabolic competition in the tumor ecosystem, limiting nutrient availability and leading to microenvironmental acidosis, which hinders immune cell function. More interestingly, metabolic reprogramming is also indispensable in the process of maintaining self and body homeostasis by various types of immune cells. At present, more and more studies pointed out that immune cell would undergo metabolic reprogramming during the process of proliferation, differentiation, and execution of effector functions, which is essential to the immune response. Herein, we discuss how metabolic reprogramming of cancer cells and immune cells regulate antitumor immune response and the possible approaches to targeting metabolic pathways in the context of anticancer immunotherapy. We also describe hypothetical combination treatments between immunotherapy and metabolic intervening that could be used to better unleash the potential of anticancer therapies.

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We study the process ${e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}J/\ensuremath{\psi}$ at a center-of-mass energy of 4.260 GeV using a $525\text{ }\text{ }{\mathrm{pb}}^{\ensuremath{-}1}$ data sample collected with the BESIII detector operating at the Beijing Electron Positron Collider. The Born cross section is measured to be $(62.9\ifmmode\pm\else\textpm\fi{}1.9\ifmmode\pm\else\textpm\fi{}3.7)\text{ }\text{ }\mathrm{pb}$, consistent with the production of the $Y(4260)$. We observe a structure at around $3.9\text{ }\text{ }\mathrm{GeV}/{c}^{2}$ in the ${\ensuremath{\pi}}^{\ifmmode\pm\else\textpm\fi{}}J/\ensuremath{\psi}$ mass spectrum, which we refer to as the ${Z}_{c}(3900)$. If interpreted as a new particle, it is unusual in that it carries an electric charge and couples to charmonium. A fit to the ${\ensuremath{\pi}}^{\ifmmode\pm\else\textpm\fi{}}J/\ensuremath{\psi}$ invariant mass spectrum, neglecting interference, results in a mass of $(3899.0\ifmmode\pm\else\textpm\fi{}3.6\ifmmode\pm\else\textpm\fi{}4.9)\text{ }\text{ }\mathrm{MeV}/{c}^{2}$ and a width of $(46\ifmmode\pm\else\textpm\fi{}10\ifmmode\pm\else\textpm\fi{}20)\text{ }\text{ }\mathrm{MeV}$. Its production ratio is measured to be $R=(\ensuremath{\sigma}\mathbf{(}{e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}{\ensuremath{\pi}}^{\ifmmode\pm\else\textpm\fi{}}{Z}_{c}(3900{)}^{\ensuremath{\mp}}\ensuremath{\rightarrow}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}J/\ensuremath{\psi}\mathbf{)}/\ensuremath{\sigma}({e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}J/\ensuremath{\psi}))=(21.5\ifmmode\pm\else\textpm\fi{}3.3\ifmmode\pm\else\textpm\fi{}7.5)%$. In all measurements the first errors are statistical and the second are systematic.

Atherosclerosis is a chronic disease characterized by the deposition of excessive cholesterol in the arterial intima. Macrophage foam cells play a critical role in the occurrence and development of atherosclerosis. The generation of these cells is associated with imbalance of cholesterol influx, esterification and efflux. CD36 and scavenger receptor class A (SR-A) are mainly responsible for uptake of lipoprotein-derived cholesterol by macrophages. Acyl coenzyme A:cholesterol acyltransferase-1 (ACAT1) and neutral cholesteryl ester hydrolase (nCEH) regulate cholesterol esterification. ATP-binding cassette transporters A1(ABCA1), ABCG1 and scavenger receptor BI (SR-BI) play crucial roles in macrophage cholesterol export. When inflow and esterification of cholesterol increase and/or its outflow decrease, the macrophages are ultimately transformed into lipid-laden foam cells, the prototypical cells in the atherosclerotic plaque. The aim of this review is to describe what is known about the mechanisms of cholesterol uptake, esterification and release in macrophages. An increased understanding of the process of macrophage foam cell formation will help to develop novel therapeutic interventions for atherosclerosis.

Abstract Restructuring-induced catalytic activity is an intriguing phenomenon of fundamental importance to rational design of high-performance catalyst materials. We study three copper-complex materials for electrocatalytic carbon dioxide reduction. Among them, the copper(II) phthalocyanine exhibits by far the highest activity for yielding methane with a Faradaic efficiency of 66% and a partial current density of 13 mA cm −2 at the potential of – 1.06 V versus the reversible hydrogen electrode. Utilizing in-situ and operando X-ray absorption spectroscopy, we find that under the working conditions copper(II) phthalocyanine undergoes reversible structural and oxidation state changes to form ~ 2 nm metallic copper clusters, which catalyzes the carbon dioxide-to-methane conversion. Density functional calculations rationalize the restructuring behavior and attribute the reversibility to the strong divalent metal ion–ligand coordination in the copper(II) phthalocyanine molecular structure and the small size of the generated copper clusters under the reaction conditions.

Ferroptosis is an iron-dependent form of non-apoptotic cell death characterized by excessive lipid peroxidation and associated with a plethora of pathological conditions in the liver. Emerging evidence supports the notion that dysregulated metabolic pathways and impaired iron homeostasis play a role in the progression of liver disease via ferroptosis. Although the molecular mechanisms by which ferroptosis causes disease are poorly understood, several ferroptosis-associated genes and pathways have been implicated in liver disease. Here, we review the physiological role of the liver in processing nutrients, our current understanding of iron metabolism, the characteristics of ferroptosis, and the mechanisms that regulate ferroptosis. In addition, we summarize the role of ferroptosis in the pathogenesis of liver disease, including liver injury, non-alcoholic steatohepatitis, liver fibrosis, liver cirrhosis, and hepatocellular carcinoma. Finally, we discuss the therapeutic potential of targeting ferroptosis for managing liver disease.

As an emerging star of 2D nanomaterials, 2D transition metal carbides and nitrides, named MXenes, present a large potential in various research areas owing to their intrinsic multilayer structure and intriguing physico-chemical properties. However, the fabrication and application of functional MXene-based devices still remain challenging as they are prone to oxidative degradation under ambient environment. Within this review, the preparation methods of MXenes focusing on the recent investigations on their thermal structure-stability relationships in inert, oxidizing, and aqueous environments are systematically introduced. Moreover, the key factors that affect the oxidation of MXenes, such as, atmosphere, temperature, composition, microstructure, and aqueous environment, are reviewed. Based on different scenarios, strategies for avoiding or delaying the oxidation of MXenes are proposed to encourage the utilization of MXenes in complicated environments, especially at high temperature. Furthermore, the chemistry of MXene-derived oxides is analyzed, which can offer perspectives on the further design and fabrication of novel 2D composites with the unique structures of MXenes being preserved.

Ferroptosis is a kind of regulated cell death (RCD) caused by the redox state disorder of intracellular microenvironment controlled by glutathione (GSH) peroxidase 4 (GPX4), which is inhibited by iron chelators and lipophilic antioxidants. In addition to classical regulatory mechanisms, new regulatory factors for ferroptosis have been discovered in recent years, such as the P53 pathway, the activating transcription factor (ATF)3/4 pathway, Beclin 1 (BECN1) pathway, and some non-coding RNA. Ferroptosis is closely related to cancer treatment, neurodegenerative diseases, ischemia-reperfusion of organ, neurotoxicity, and others, in particular, in the field of neurodegenerative diseases treatment has aroused people's interest. The nuclear factor E2 related factor 2 (Nrf2/NFE2L2) has been proved to play a key role in neurodegenerative disease treatment and ferroptosis regulation. Ferroptosis promotes the progression of neurodegenerative diseases, while the expression of Nrf2 and its target genes (Ho-1, Nqo-1, and Trx) has been declined with aging; therefore, there is still insufficient evidence for ferroptosis and Nrf2 regulatory networks in the field of neurodegenerative diseases. In this review, we will provide a brief overview of ferroptosis regulatory mechanisms, as well as an emphasis on the mechanism of Nrf2 regulating ferroptosis. We also highlight the role of ferroptosis and Nrf2 during the process of neurodegenerative diseases and investigate a theoretical basis for further research on the relationship between Nrf2 and ferroptosis in the process of neurodegenerative diseases treatment.

Here, an integrated cascade nanozyme with a formulation of Pt@PCN222-Mn is developed to eliminate excessive reactive oxygen species (ROS). This nanozyme mimics superoxide dismutase by incorporation of a Mn-[5,10,15,20-tetrakis(4-carboxyphenyl)porphyrinato]-based metal-organic framework compound capable of transforming oxygen radicals to hydrogen peroxide. The second mimicked functionality is that of catalase by incorporation of Pt nanoparticles, which catalyze hydrogen peroxide disproportionation to water and oxygen. Both in vitro and in vivo experimental measurements reveal the synergistic ROS-scavenging capacity of such an integrated cascade nanozyme. Two forms of inflammatory bowel disease (IBD; i.e., ulcerative colitis and Crohn's disease) can be effectively relieved by treatment with the cascade nanozyme. This study not only provides a new method for constructing enzyme-like cascade systems but also illustrates their efficient therapeutic promise in the treatment of in vivo IBDs.

Importance: Sorafenib is the first-line treatment for hepatocellular carcinoma with portal vein invasion; however, it has shown unsatisfactory survival benefit. Sorafenib plus hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown promising results for these patients in a previous phase 2 study. Objective: To investigate the efficacy and safety of sorafenib plus HAIC compared with sorafenib for hepatocellular carcinoma with portal vein invasion. Design, Setting, and Participants: This randomized, open-label clinical trial enrolled 818 screened patients. Of the 818 participants, 247 with hepatocellular carcinoma and portal vein invasion were randomly assigned (1:1) via a computer-generated sequence to receive sorafenib plus HAIC or sorafenib. This trial was conducted at 5 hospitals in China and enrolled patients from April 1, 2016, to October 10, 2017, with a follow-up period of 10 months. Interventions: Randomization to receive 400 mg sorafenib twice daily (sorafenib group) or 400 mg sorafenib twice daily plus HAIC (SoraHAIC group) (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2400 mg/m2 for 46 hours, every 3 weeks). Main Outcomes and Measures: The primary endpoint was overall survival by intention-to-treat analysis. Safety was assessed in patients who received at least 1 dose of study treatment. Results: For 247 patients (median age, 49 years; range, 18-75 years; 223 men and 24 women), median overall survival was 13.37 months (95% CI, 10.27-16.46) in the SoraHAIC group vs 7.13 months (95% CI, 6.28-7.98) in the sorafenib group (hazard ratio [HR], 0.35; 95% CI, 0.26-0.48; P < .001). The SoraHAIC group showed a higher response rate than the sorafenib group (51 [40.8%] vs 3 [2.46%]; P < .001), and a longer median progression-free survival (7.03 [95% CI, 6.05-8.02] vs 2.6 [95% CI, 2.15-3.05] months; P < .001). Grade 3/4 adverse events that were more frequent in the SoraHAIC group than in the sorafenib group included neutropenia (12 [9.68%] vs 3 [2.48%]), thrombocytopenia (16 [12.9%] vs 6 [4.96%]), and vomiting (8 [6.45%] vs 1 [0.83%]). Conclusions and Relevance: Sorafenib plus HAIC of FOLFOX improved overall survival and had acceptable toxic effects compared with sorafenib in patients with hepatocellular carcinoma and portal vein invasion. Trial Registration: ClinicalTrials.gov identifier: NCT02774187.

Breast cancer is the second leading cause of death for women worldwide. The heterogeneity of this disease presents a big challenge in its therapeutic management. However, recent advances in molecular biology and immunology enable to develop highly targeted therapies for many forms of breast cancer. The primary objective of targeted therapy is to inhibit a specific target/molecule that supports tumor progression. Ak strain transforming, cyclin-dependent kinases, poly (ADP-ribose) polymerase, and different growth factors have emerged as potential therapeutic targets for specific breast cancer subtypes. Many targeted drugs are currently undergoing clinical trials, and some have already received the FDA approval as monotherapy or in combination with other drugs for the treatment of different forms of breast cancer. However, the targeted drugs have yet to achieve therapeutic promise against triple-negative breast cancer (TNBC). In this aspect, immune therapy has come up as a promising therapeutic approach specifically for TNBC patients. Different immunotherapeutic modalities including immune-checkpoint blockade, vaccination, and adoptive cell transfer have been extensively studied in the clinical setting of breast cancer, especially in TNBC patients. The FDA has already approved some immune-checkpoint blockers in combination with chemotherapeutic drugs to treat TNBC and several trials are ongoing. This review provides an overview of clinical developments and recent advancements in targeted therapies and immunotherapies for breast cancer treatment. The successes, challenges, and prospects were critically discussed to portray their profound prospects.

Cardiac function is determined by the dynamic equilibrium of various cell types and the extracellular matrix that composes the heart. Cardiovascular diseases (CVDs), especially atherosclerosis and myocardial infarction, are often accompanied by cell death and acute/chronic inflammatory reactions. Caspase-dependent pyroptosis is characterized by the activation of pathways leading to the activation of NOD-like receptors, especially the NLRP3 inflammasome and its downstream effector inflammatory factors interleukin (IL)-1β and IL-18. Many studies in the past decade have investigated the role of pyroptosis in CVDs. The findings of these studies have led to the development of therapeutic approaches based on the regulation of pyroptosis, and some of these approaches are in clinical trials. This review summarizes the molecular mechanisms, regulation and cellular effects of pyroptosis briefly and then discusses the current pyroptosis studies in CVD research.

Alzheimer's disease (AD) and Parkinson's disease (PD) are two typical neurodegenerative diseases that increased with aging. With the emergence of aging population, the health problem and economic burden caused by the two diseases also increase. Phosphatidylinositol 3-kinases/protein kinase B (PI3K/AKT) signaling pathway regulates signal transduction and biological processes such as cell proliferation, apoptosis and metabolism. According to reports, it regulates neurotoxicity and mediates the survival of neurons through different substrates such as forkhead box protein Os (FoxOs), glycogen synthase kinase-3β (GSK-3β), and caspase-9. Accumulating evidences indicate that some natural products can play a neuroprotective role by activating PI3K/AKT pathway, providing an effective resource for the discovery of potential therapeutic drugs. This article reviews the relationship between AKT signaling pathway and AD and PD, and discusses the potential natural products based on the PI3K/AKT signaling pathway to treat two diseases in recent years, hoping to provide guidance and reference for this field. Further development of Chinese herbal medicine is needed to treat these two diseases.

We study ${e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}{h}_{c}$ at center-of-mass energies from 3.90 to 4.42 GeV by using data samples collected with the BESIII detector operating at the Beijing Electron Positron Collider. The Born cross sections are measured at 13 energies and are found to be of the same order of magnitude as those of ${e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}{\ensuremath{\pi}}^{+}{\ensuremath{\pi}}^{\ensuremath{-}}J/\ensuremath{\psi}$ but with a different line shape. In the ${\ensuremath{\pi}}^{\ifmmode\pm\else\textpm\fi{}}{h}_{c}$ mass spectrum, a distinct structure, referred to as ${Z}_{c}(4020)$, is observed at $4.02\text{ }\text{ }\mathrm{GeV}/{c}^{2}$. The ${Z}_{c}(4020)$ carries an electric charge and couples to charmonium. A fit to the ${\ensuremath{\pi}}^{\ifmmode\pm\else\textpm\fi{}}{h}_{c}$ invariant mass spectrum, neglecting possible interferences, results in a mass of $(4022.9\ifmmode\pm\else\textpm\fi{}0.8\ifmmode\pm\else\textpm\fi{}2.7)\text{ }\text{ }\mathrm{MeV}/{c}^{2}$ and a width of $(7.9\ifmmode\pm\else\textpm\fi{}2.7\ifmmode\pm\else\textpm\fi{}2.6)\text{ }\text{ }\mathrm{MeV}$ for the ${Z}_{c}(4020)$, where the first errors are statistical and the second systematic. The difference between the parameters of this structure and the ${Z}_{c}(4025)$ observed in the ${D}^{*}{\overline{D}}^{*}$ final state is within $1.5\ensuremath{\sigma}$, but whether they are the same state needs further investigation. No significant ${Z}_{c}(3900)$ signal is observed, and upper limits on the ${Z}_{c}(3900)$ production cross sections in ${\ensuremath{\pi}}^{\ifmmode\pm\else\textpm\fi{}}{h}_{c}$ at center-of-mass energies of 4.23 and 4.26 GeV are set.

Abstract Proton exchange membrane fuel cells convert hydrogen and oxygen into electricity without emissions. The high cost and low durability of Pt-based electrocatalysts for the oxygen reduction reaction hinder their wide application, and the development of non-precious metal electrocatalysts is limited by their low performance. Here we design a hybrid electrocatalyst that consists of atomically dispersed Pt and Fe single atoms and Pt–Fe alloy nanoparticles. Its Pt mass activity is 3.7 times higher than that of commercial Pt/C in a fuel cell. More importantly, the fuel cell with a low Pt loading in the cathode (0.015 mg Pt cm −2 ) shows an excellent durability, with a 97% activity retention after 100,000 cycles and no noticeable current drop at 0.6 V for over 200 hours. These results highlight the importance of the synergistic effects among active sites in hybrid electrocatalysts and provide an alternative way to design more active and durable low-Pt electrocatalysts for electrochemical devices.

Anti-Siglec15 immunotherapy might be suitable for BLCA treatment as Siglec15 correlates with a non-inflamed TME in BLCA. Siglec15 could also predict the molecular subtype and the response to several treatment options.

Mesenchymal stem cells (MSC) derived from bone marrow can potentially reduce the acute inflammatory response in spinal cord injury (SCI) and thus promote functional recovery. However, the precise mechanisms through which transplanted MSC attenuate inflammation after SCI are still unclear. The present study was designed to investigate the effects of MSC transplantation with a special focus on their effect on macrophage activation after SCI. Rats were subjected to T9-T10 SCI by contusion, then treated 3 days later with transplantation of 1.0×10(6) PKH26-labeled MSC into the contusion epicenter. The transplanted MSC migrated within the injured spinal cord without differentiating into glial or neuronal elements. MSC transplantation was associated with marked changes in the SCI environment, with significant increases in IL-4 and IL-13 levels, and reductions in TNF-α and IL-6 levels. This was associated simultaneously with increased numbers of alternatively activated macrophages (M2 phenotype: arginase-1- or CD206-positive), and decreased numbers of classically activated macrophages (M1 phenotype: iNOS- or CD16/32-positive). These changes were associated with functional locomotion recovery in the MSC-transplanted group, which correlated with preserved axons, less scar tissue formation, and increased myelin sparing. Our results suggested that acute transplantation of MSC after SCI modified the inflammatory environment by shifting the macrophage phenotype from M1 to M2, and that this may reduce the effects of the inhibitory scar tissue in the subacute/chronic phase after injury to provide a permissive environment for axonal extension and functional recovery.

Blood-brain barrier (BBB) disruption occurs early enough to be within the thrombolytic time window, and this early ischemic BBB damage is closely associated with hemorrhagic transformation and thus emerging as a promising target for reducing the hemorrhagic complications of thrombolytic stroke therapy. However, the mechanisms underlying early ischemic BBB damage remain poorly understood. Here, we investigated the early molecular events of ischemic BBB damage using in vitro oxygen-glucose deprivation (OGD) and in vivo rat middle cerebral artery occlusion (MCAO) models. Exposure of bEND3 monolayer to OGD for 2 h significantly increased its permeability to FITC-labeled dextran and promoted the secretion of metalloproteinase-2 and -9 (MMP-2/9) and cytosolic translocation of caveolin-1 (Cav-1). This same OGD treatment also led to rapid degradation of tight junction protein occludin and dissociation of claudin-5 from the cytoskeleton, which contributed to OGD-induced endothelial barrier disruption. Using selective MMP-2/9 inhibitor SB-3CT (2-[[(4-phenoxyphenyl)sulfonyl]methyl]-thiirane) or their neutralizing antibodies or Cav-1 siRNA, we found that MMP-2 was the major enzyme mediating OGD-induced occludin degradation, while Cav-1 was responsible for claudin-5 redistribution. The interaction between Cav-1 and claudin-5 was further confirmed by coimmunoprecipitation. Consistent with these in vitro findings, we observed fluorescence tracer extravasation, increased gelatinolytic activity, and elevated interstitial MMP-2 levels in ischemic subcortical tissue after 2 h MCAO. Moreover, occludin protein loss and claudin-5 redistribution were detected in ischemic cerebromicrovessels. These data indicate that cerebral ischemia initiates two rapid parallel processes, MMP-2-mediated occludin degradation and Cav-1-mediated claudin-5 redistribution, to cause BBB disruption at early stroke stages relevant to acute thrombolysis.