Integration of STING activation and COX-2 inhibition via steric-hindrance effect tuned nanoreactors for cancer chemoimmunotherapy.

Integrating immunotherapy with nanomaterials-based chemotherapy presents a promising avenue for amplifying antitumor outcomes. Nevertheless, the suppressive tumor immune microenvironment (TIME) and the upregulation of cyclooxygenase-2 (COX-2) induced by chemotherapy can hinder the efficacy of the chemoimmunotherapy. This study presents a TIME-reshaping strategy by developing a steric-hindrance effect tuned zinc-based metal-organic framework (MOF), designated as CZFNPs. This nanoreactor is engineered by in situ loading of the COX-2 inhibitor, C-phycocyanin (CPC), into the framework building blocks, while simultaneously weakening the stability of the MOF. Consequently, CZFNPs achieve rapid pH-responsive release of zinc ions (Zn2+) and CPC upon specific transport to tumor cells overexpressing folate receptors. Accordingly, Zn2+ can induce reactive oxygen species (ROS)-mediated cytotoxicity therapy while synchronize with mitochondrial DNA (mtDNA) release, which stimulates mtDNA/cGAS-STING pathway-mediated innate immunity. The CPC suppresses the chemotherapy-induced overexpression of COX-2, thus cooperatively reprogramming the suppressive TIME and boosting the antitumor immune response. In xenograft tumor models, the CZFNPs system effectively modulates STING and COX-2 expression, converting "cold" tumors into "hot" tumors, thereby resulting in ≈ 4-fold tumor regression relative to ZIF-8 treatment alone. This approach offers a potent strategy for enhancing the efficacy of combined nanomaterial-based chemotherapy and immunotherapy.

Discovery of cinnamamide/ester triazole hybrids as potential treatment for Alzheimer's disease.

Developing multitargeted ligands as promising therapeutics for Alzheimer's disease (AD) has been considered important. Herein, a novel class of cinnamamide/ester-triazole hybrids with multifaceted effects on AD was developed based on the multitarget-directed ligands strategy. Thirty-seven cinnamamide/ester-triazole hybrids were synthesized, with most exhibiting significant inhibitory activity against Aß-induced toxicity at a single concentration in vitro. The most optimal hybrid compound 4j inhibited copper-induced Aß toxicity in AD cells. its action was superior to that of donepezil and memantine. It also moderately inhibited intracellular AChE activity and presented favorable bioavailability and blood-brain barrier penetration with low toxicity in vivo. Of note, it ameliorated cognitive impairment, neuronal degeneration, and Aß deposition in Aß1-42-injured mice. Mechanistically, the compound regulated APP processing by promoting the ADAM10-associated nonamyloidogenic signaling and inhibiting the BACE1-mediated amyloidogenic pathway. Moreover, it suppressed intracellular AChE activity and tau phosphorylation. Therefore, compound 4j may be a promising multitargeted active molecule against AD.

Disulfiram downregulates ferredoxin 1 to maintain copper homeostasis and inhibit inflammation in cerebral ischemia/reperfusion injury.

In the current study, we aimed to investigate whether disulfiram (DSF) exerts a neuroprotective role in cerebral ischemiareperfusion (CI-RI) injury by modulating ferredoxin 1 (FDX1) to regulate copper ion (Cu) levels and inhibiting inflammatory responses. To simulate CI-RI, a transient middle cerebral artery occlusion (tMCAO) model in C57/BL6 mice was employed. Mice were administered with or without DSF before and after tMCAO. Changes in infarct volume after tMCAO were observed using TTC staining. Nissl staining and hematoxylin-eosin (he) staining were used to observe the morphological changes of nerve cells at the microscopic level. The inhibitory effect of DSF on initial inflammation was verified by TUNEL assay, apoptosis-related protein detection and iron concentration detection. FDX1 is the main regulatory protein of copper death, and the occurrence of copper death will lead to the increase of HSP70 stress and inflammatory response. Cuproptosis-related proteins and downstream inflammatory factors were detected by western blotting, immunofluorescence staining, and immunohistochemistry. The content of copper ions was detected using a specific kit, while electron microscopy was employed to examine mitochondrial changes. We found that DSF reduced the cerebral infarction volume, regulated the expression of cuproptosis-related proteins, and modulated copper content through down regulation of FDX1 expression. Moreover, DSF inhibited the HSP70/TLR-4/NLRP3 signaling pathway. Collectively, DSF could regulate Cu homeostasis by inhibiting FDX1, acting on the HSP70/TLR4/NLRP3 pathway to alleviate CI/RI. Accordingly, DSF could mitigate inflammatory responses and safeguard mitochondrial integrity, yielding novel therapeutic targets and mechanisms for the clinical management of ischemia-reperfusion injury.

Covalent Bonding of Salen Metal Complexes with Pyrene Chromophores to Porous Polymers for Photocatalytic Hydrogen Evolution.

The development of low-cost and efficient photocatalysts to achieve water splitting to hydrogen (H2) is highly desirable but remains challenging. Herein, we design and synthesize two porous polymers (Co-Salen-P and Fe-Salen-P) by covalent bonding of salen metal complexes and pyrene chromophores for photocatalytic H2 evolution. The catalytic results demonstrate that the two polymers exhibit excellent catalytic performance for H2 generation in the absence of additional noble-metal photosensitizers and cocatalysts. Particularly, the H2 generation rate of Co-Salen-P reaches as high as 542.5 µmol g-1 h-1, which is not only 6 times higher than that of Fe-Salen-P but also higher than a large amount of reported Pt-assisted photocatalytic systems. Systematic studies show that Co-Salen-P displays faster charge separation and transfer efficiencies, thereby accounting for the significantly improved photocatalytic activity. This study provides a facile and efficient way to fabricate high-performance photocatalysts for H2 production.

Controllable silver release for efficient treatment of drug-resistant bacterial-infected wounds.

The use of traditional Ag-based antibacterial agents is usually accompanied by uncontrollable silver release, which makes it difficult to find a balance between antibacterial performance and biosafety. Herein, we prepared a core-shell system of ZIF-8-derived amorphous carbon-coated Ag nanoparticles (Ag@C) as an ideal research model to reveal the synergistic effect and structure-activity relationship of the structural transformation of carbon shell and Ag core on the regulation of silver release behavior. It is found that Ag@C prepared at 600 °C (AC6) exhibits the best ion release kinetics due to the combination of relatively simple shell structure and lower crystallinity of Ag core, thereby exerting stronger antibacterial properties (> 99.999%) at trace doses (20 µg mL-1) compared with most other Ag-based materials. Meanwhile, the carbon shell prevents the metal Ag from being directly exposed to the organism and thus endows AC6 with excellent biocompatibility. In animal experiments, AC6 can effectively promote wound healing by inactivating drug-resistant bacteria while regulating the expression of TNF-α and CD31. This work provides theoretical support for the scientific design and clinical application of controllable ion-releasing antibacterial agents.

Validation of the China mortality prediction model in trauma based on the ICD-10-CM codes.

The China mortality prediction model in trauma, based on the International Classification of Diseases, Tenth Revision, Clinical Modification lexicon (CMPMIT-ICD-10), is a novel model for predicting outcomes in patients who experienced trauma. This model has not yet been validated using data acquired from patients at other trauma centers in China. This retrospective study used data retrieved from the Peking University People's Hospital discharge database and included all patients admitted for trauma between 2012 and 2022 for model validation. Model performance was categorized into discrimination and calibration. In total, 23,299 patients were included in this study, with an overall mortality rate of 1.2%. CMPMIT-ICD-10 showed good discrimination and calibration, with an area under the curve of 0.84 (95% confidence interval: 0.82-0.87) and a Brier score of 0.02. The performance of the CMPMIT-ICD-10 during validation was satisfactory, and the application of the model will be scaled up in future studies.

Unveiling the role of proton concentration in dinuclear metal complexes for boosting photocatalytic CO2 reduction.

The reaction kinetics of photocatalytic CO2 reduction is highly dependent on the transfer rate of electrons and protons to the CO2 molecules adsorbed on catalytic centers. Studies on uncovering the proton effect in catalysts on photocatalytic activity of CO2 reduction are significant but rarely reported. In this paper, we, from the molecular level, revealed that the photocatalytic activity of CO2 reduction is closely related to the proton availability in catalysts. Specifically, four dinuclear Co(II) complexes based on Robson-type ligands with different number of carboxylic groups (-nCOOH; n = 0, 2, 4, 6) were designed and synthesized. All these complexes show photocatalytic activity for CO2 reduction to CO in a water-containing system upon visible-light illumination. Interestingly, the CO yields increase positively with the increase of the carboxylic-group number in dinuclear Co(II) complexes. The one containing -6COOH shows the best photocatalytic activity for CO2 reduction to CO, with the TON value reaching as high as 10,294. The value is 1.8, 3.4, and 7.8 times higher than those containing -4COOH, -2COOH, and -0COOH, respectively. The high TON value also makes the dinuclear Co(II) complex with -6COOH outstanding among reported homogeneous molecular catalysts for photocatalytic CO2 reduction. Control experiments and density functional theory calculation indicated that more carboxylic groups in the catalyst endow the catalyst with more proton relays, thus accelerating the proton transfer and boosting the photocatalytic CO2 reduction. This study, at a molecular level, elucidates that more carboxylic groups in catalysts are beneficial for boosting the reaction kinetics of photocatalytic CO2 reduction.

MyD88 Inhibition Attenuates Cerebral Ischemia-reperfusion Injury by Regulating the Inflammatory Response and Reducing Blood-brain Barrier Damage.

Myeloid differentiation primary response gene 88 (MyD88), a downstream molecule directly linked to Toll-like receptor (TLRs) and IL1 receptor, has been implicated in ischemia-reperfusion injury across various organs. However, its role in cerebral ischemia-reperfusion injury (CIRI) remains unclear. Five transient middle cerebral artery occlusion (tMCAO) microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. We screened these datasets for differentially expressed genes (DEGs) using the GSE35338 and GSE58720 datasets and performed weighted gene co-expression network analysis (WGCNA) using the GSE30655, GSE28731, and GSE32529 datasets to identify the core module related to tMCAO. A protein-protein interaction (PPI) network was constructed using the intersecting DEGs and genes in the core module. Finally, we identified Myd88 was the core gene. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) validated that TNFα, IL17, and MyD88 signaling pathways were significantly enriched in tMCAO. Subsequently, we investigated the mechanistic role of MyD88 in the tMCAO model using male C57BL/6 mice. MyD88 expression increased significantly 24 h after reperfusion. After intraperitoneal administration of TJ-M2010-5, a MyD88-specific inhibitor, during reperfusion, the infarction volumes in the mice were ameliorated. TJ-M2010-5 inhibits the activation of microglia and astrocytes. Moreover, it attenuates the upregulation of inflammatory cytokines TNFα, IL17, and MMP9 while preserving the expression level of ZO1 after tMCAO, thereby safeguarding against blood-brain barrier (BBB) disruption. Finally, our findings suggest that MyD88 regulates the IRAK4/IRF5 signaling pathway associated with microglial activation. MyD88 participates in CIRI by regulating the inflammatory response and BBB damage following tMCAO.

Novel peripheral blood mononuclear cell mRNA signature for IFN-beta therapy responsiveness prediction in multiple sclerosis.

Interferon-beta (IFN-ß) is one of the classical drugs for immunomodulatory therapy in relapsing-remitting multiple sclerosis (RRMS) patients, but the drug responsiveness of different patients varies. Currently, there is no valid model to predict IFN-ß responsiveness. This research attempted to develop an IFN-ß responsiveness prediction model based on mRNA expression in RRMS patient peripheral blood mononuclear cells. Peripheral blood mononuclear cell mRNA expression datasets including 50 RRMS patients receiving IFN-ß treatment were obtained from GEO. Among the datasets, 24 cases from GSE24427 were included in a training set, and 18 and 9 cases from GSE19285 and GSE33464, respectively, were adopted as two independent test sets. In the training set, blood samples were collected immediately before first, second, month 1, 12, and 24 IFN-ß injection, and the mRNA expression data at four time points, namely, two days, one month, one year and two years after the onset of IFN-ß treatment, were compared with pre-treatment data to identify IFN-stimulated genes (ISGs). The ISGs at the one-month time point were used to construct the drug responsiveness prediction model. Next, the drug responsiveness model was verified in the two independent test sets to examine the performance of the model in predicting drug responsiveness. Finally, we used CIBERSORTx to estimate the content of cell subtypes in samples and evaluated whether differences in the proportions of cell subtypes were related to differences in IFN-ß responsiveness. Among the four time points, one month was the time point when the training set GSE24427 and test set GSE33464 had the highest number of ISGs. Functional analysis showed that these one-month ISGs were enriched in biological functions such as the innate immune response, type-I interferon signalling pathway, and other IFN-ß-associated functions. Based on these ISGs, we obtained a four-factor prediction model for IFN-ß responsiveness including MX1, MX2, XAF1, and LAMP3. In addition, the model demonstrated favourable predictive performance within the training set and two external test sets. A higher proportion of activated NK cells and lower naive CD4/total CD4 ratio might indicate better drug responsiveness. This research developed a polygene-based biomarker model that could predict RRMS patient IFN-ß responsiveness in the early treatment period. This model could probably help doctors screen out patients who would not benefit from IFN-ß treatment early and determine whether a current treatment plan should be continued.

NRF2 activation ameliorates blood-brain barrier injury after cerebral ischemic stroke by regulating ferroptosis and inflammation.

Arterial occlusion-induced ischemic stroke (IS) is a highly frequent stroke subtype. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that modulates antioxidant genes. Its role in IS is still unelucidated. The current study focused on constructing a transient middle cerebral artery occlusion (tMCAO) model for investigating the NRF2-related mechanism underlying cerebral ischemia/reperfusion (I/R) injury. Each male C57BL/6 mouse was injected with/with no specific NRF2 activator post-tMCAO. Changes in blood-brain barrier (BBB)-associated molecule levels were analyzed using western-blotting, PCR, immunohistochemistry, and immunofluorescence analysis. NRF2 levels within cerebral I/R model decreased at 24-h post-ischemia. NRF2 activation improved brain edema, infarct volume, and neurological deficits after MCAO/R. Similarly, sulforaphane (SFN) prevented the down-regulated tight junction proteins occludin and zonula occludens 1 (ZO-1) and reduced the up-regulated aquaporin 4 (AQP4) and matrix metalloproteinase 9 (MMP9) after tMCAO. Collectively, NRF2 exerted a critical effect on preserving BBB integrity modulating ferroptosis and inflammation. Because NRF2 is related to BBB injury regulation following cerebral I/R, this provides a potential therapeutic target and throws light on the underlying mechanism for clinically treating IS.

Electronic Modulation in Homonuclear Dual-Atomic Catalysts for Enhanced CO2 Electroreduction.

Homonuclear dual-atomic catalysts showcase unique electronic modulation due to their dual metal centres, providing new direction in development of efficient catalysts for CO2 electroreduction. This article highlights a few cutting-edge homonuclear dual-atomic catalysts, focusing on their inherent advantages in efficient and selective CO2 electroreduction, to spotlight the potential application of dual-atomic catalysts in CO2 electroreduction.

Boosting CO2 Photoreduction to Formate or CO with High Selectivity over a Covalent Organic Framework Covalently Anchored on Graphene Oxide.

Covalent organic frameworks (COFs) have been widely studied in photocatalytic CO2 reduction reaction (CO2 RR). However, pristine COFs usually exhibit low catalytic efficiency owing to the fast recombination of photogenerated electrons and holes. In this study, we fabricated a stable COF-based composite (GO-COF-366-Co) by covalently anchoring COF-366-Co on the surface of graphene oxide (GO) for the photocatalytic CO2 reduction. Interestingly, in absolute acetonitrile (CH3 CN), GO-COF-366-Co shows a high selectivity of 94.4 % for the photoreduction of CO2 to formate, with a formate yield of 15.8 mmol/g, which is approximately four times higher than that using the pristine COF-366-Co. By contrast, in CH3 CN/H2 O (v : v=4 : 1), the main product for the photocatalytic CO2 reduction over GO-COF-366-Co is CO (96.1 %), with a CO yield as high as 52.2 mmol/g, which is also approximately four times higher than that using the pristine COF-366-Co. Photoelectrochemical experiments demonstrate the covalent bonding of COF-366-Co and GO to form the GO-COF-366-Co composite facilitates charge separation and transfer significantly, thereby accounting for the enhanced catalytic activity. In addition, theoretical calculations and in situ Fourier transform infrared spectroscopy reveal H2 O can stabilize the *COOH intermediate to further form a *CO intermediate via O-H(aq)⋅⋅⋅O(*COOH) hydrogen bonding, thus explaining the regulated photocatalytic performance.

A Nano-Autophagy Inhibitor Triggering Reciprocal Feedback Control of Cholesterol Depletion for Solid Tumor Therapy.

Solid tumors are characterized by enhanced metabolism of lipid, particularly cholesterol, inspiring the exploration of metabolic therapy through cholesterol oxidase (COD)-mediated cholesterol deprivation. However, the therapeutic efficacy of COD is limited due to the hypoxic tumor microenvironment and the protective autophagy triggered by cholesterol deprivation. Herein, a combination therapy for metabolically treating solid tumors through COD in conjunction with molybdenum oxide nanodots (MONDs), which serve as both potent oxygen generators and autophagy inhibitors, is reported. MONDs convert H2 O2 (arising from COD-mediated cholesterol oxidation) into O2 , which is then recycled by COD to form reciprocal feedback for cholesterol depletion. Concurrently, MONDs can overcome autophagy-induced therapeutic resistance frequently occurring in conventional nutrient deprivation therapy by activating AKT/mTOR pathway phosphorylation. Combination therapy in the xenograft model results in an ≈5-fold increase in therapeutic efficiency as compared with COD treatment alone. This functionally cooperative metabolic coupling strategy holds great promise as a novel polytherapy approach that will benefit patients with solid tumors.

An Analysis of Respiratory Muscle Paralysis of Adult Patients in Guillain-Barré Syndrome: A Retrospective Analysis.

Respiratory muscle paralysis is known as a very common complication of Guillain-Barré syndrome (GBS). However, most research has focused on its later stages rather than its earlier stages, including the prognosis of patients with this condition, or factors that act as early predictors of risk. Therefore, our study aimed to identify early predictors of respiratory muscle paralysis in patients with GBS and determine the short-term prognosis of such patients. We recruited 455 GBS patients (age ≥ 18) who had been hospitalized in the First Affiliated Hospital of Harbin Medical University between 2016 and 2021, retrospectively. We recorded clinical and laboratory data and used linear and logistic regression analysis to investigate the relationship between early clinical, examination results, and subsequent respiratory muscle paralysis. Among the 455 patients, 129 were assigned to a respiratory muscle paralysis group and 326 were assigned to a non-respiratory muscle paralysis group. Compared with the non-affected group, the time from onset to admission was shorter (p = 0.0003), and the Medical Research Council (MRC) score at admission and discharge was smaller in the affected group (p < 0.0001). Compared with the non-affected group, the affected group had higher Hughes and Erasmus GBS Respiratory Insufficiency Score (EGRIS) scores at admission and longer hospital stays (p < 0.0001). Patients in the affected group were more likely to have bulbar palsy and lung infections (p < 0.0001). To conclude, bulbar palsy, a higher EGRIS score and Hughes score at admission, a lower MRC score, and a shorter time between onset and admission, are all predictive risk factors for respiratory muscle paralysis in patients with GBS. An increase in any of these factors increases the risk of muscle paralysis. Patients with respiratory muscle paralysis have a poorer short-term prognosis than those without respiratory muscle paralysis. Therefore, we should attempt to identify patients with one or more of these characteristics in the early stages of admission, provide ventilation management, and administer IMV treatment if necessary.

Bone marrow mesenchymal stem cell-derived exosomal miR-193b-5p reduces pyroptosis after ischemic stroke by targeting AIM2.

BACKGROUND: Ischemic stroke represents a major factor causing global morbidity and death. Bone marrow mesenchymal stem cell (BMSC)-derived exosomes (Exos) have important effects on treating ischemic stroke. Here, we investigated the therapeutic mechanism by which BMSC-derived exosomal miR-193b-5p affects ischemic stroke. METHODS: luciferase assay was performed to evaluate the regulatory relationship of miR-193b-5p with absent in melanoma 2 (AIM2). Additionally, an oxygen-glucose deprivation/reperfusion (OGD/R) model was constructed for the in vitro assay, while a middle cerebral artery occlusion (MCAO) model was developed for the in vivo assay. After exosome therapy, lactate dehydrogenase and MTT assays were conducted to detect cytotoxicity and cell viability, while PCR, ELISA, western blotting assay, and immunofluorescence staining were performed to detect changes in the levels of pyroptosis-related molecules. TTC staining and TUNEL assays were performed to assess cerebral ischemia/reperfusion (I/R) injury. RESULTS: In the luciferase assay, miR-193b-5p showed direct binding to the 3'-untranslated region of AIM2. In both in vivo and in vitro assays, the injected exosomes could access the sites of ischemic injury and could be internalized. In the in vitro assay, compared to normal BMSC-Exos, miR-193b-5p-overexpressing BMSC-Exos showed greater effects on increasing cell viability and attenuating cytotoxicity; AIM2, GSDMD-N, and cleaved caspase-1 levels; and IL-1ß/IL-18 generation. In the in vivo assay, compared to normal BMSC-Exos, miR-193b-5p-overexpressing BMSC-Exos showed greater effects on decreasing the levels of these pyroptosis-related molecules and infarct volume. CONCLUSION: BMSC-Exos attenuate the cerebral I/R injury in vivo and in vitro by inhibiting AIM2 pathway-mediated pyroptosis through miR-193b-5p delivery.

Water-Etched Approach to Hierarchically Porous Metal-Organic Frameworks with High Stability.

The development of hierarchically porous metal-organic frameworks (MOFs) with high stability is desirable to expand their applications but remains challenging. Herein, an anionic sodalite-type microporous MOF (Yb-TTCA; TTCA3- = triphenylene-2,6,10-tricarboxylate) was synthesized, which shows outstanding catalytic activities for the cycloaddition of CO2 into cyclic carbonates. Moreover, the microporous Yb-TTCA can be transformed into a hierarchical micro- and mesoporous Yb-TTCA by water treatment with the mesopore sizes of 2 to 12 nm. The hierarchically porous Yb-TTCA (HP-Yb-TTCA) not only exhibits a high thermal stability up to 500 °C but also shows a high chemical stability in aqueous solutions with pH values ranging from 2 to 12. In addition, the HP-Yb-TTCA displays enhanced performance for the removal of organic dyes in comparison with microporous Yb-TTCA. This work provides a facile way to construct hierarchically porous MOF materials.

Single-cell analysis reveals novel clonally expanded monocytes associated with IL1ß-IL1R2 pair in acute inflammatory demyelinating polyneuropathy.

Guillain-Barré syndrome (GBS) is an autoimmune disorder wherein the composition and gene expression patterns of peripheral blood immune cells change significantly. It is triggered by antigens with similar epitopes to Schwann cells that stimulate a maladaptive immune response against peripheral nerves. However, an atlas for peripheral blood immune cells in patients with GBS has not yet been constructed. This is a monocentric, prospective study. We collected 5 acute inflammatory demyelinating polyneuropathy (AIDP) patients and 3 healthy controls hospitalized in the First Affiliated Hospital of Harbin Medical University from December 2020 to May 2021, 3 AIDP patients were in the peak stage and 2 were in the convalescent stage. We performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from these patients. Furthermore, we performed cell clustering, cell annotation, cell-cell communication, differentially expressed genes (DEGs) identification and pseudotime trajectory analysis. Our study identified a novel clonally expanded CD14+ CD163+ monocyte subtype in the peripheral blood of patients with AIDP, and it was enriched in cellular response to IL1 and chemokine signaling pathways. Furthermore, we observed increased IL1ß-IL1R2 cell-cell communication between CD14+ and CD16+ monocytes. In short, by analyzing the single-cell landscape of the PBMCs in patients with AIDP we hope to widen our understanding of the composition of peripheral immune cells in patients with GBS and provide a theoretical basis for future studies.

Dinuclear metal synergistic catalysis for energy conversion.

Catalysts featuring dinuclear metal sites are regarded as superior systems compared with their counterparts with mononuclear metal sites. The dinuclear metal sites in catalysts with appropriate spatial separations and geometric configurations can confer the dinuclear metal synergistic catalysis (DMSC) effect, and thus boost the catalytic performance, in particular for reactions involving multiple reactants, intermediates and products. In this review, we summarize the related reports on the design and synthesis of both homogeneous and heterogeneous dinuclear metal catalysts, and their applications in energy conversion reactions, including photo-/electro-catalytic hydrogen evolution reaction (HER), oxygen evolution reaction (OER), oxygen reduction reaction (ORR), CO2 reduction reaction (CO2RR), and N2 reduction reaction (N2RR). Particularly, we focus on the analysis of the relationship between the catalyst structure and catalytic performances, where the design principles are presented. Finally, we discuss the challenges in the design and preparation of dinuclear metal catalysts with the DMSC effect and present a perspective on the future development of dinuclear metal catalysts in energy conversion. This review aims to comprehensively summarize the up-to-date research progress on the synthesis and energy-related application of dinuclear metal catalysts and provide guidance for designing energy-conversion catalysts with superior performances.

Annexin A protein family: Focusing on the occurrence, progression and treatment of cancer.

The annexin A (ANXA) protein family is a well-known tissue-specific multigene family that encodes Ca2+ phospholipid-binding proteins. A considerable amount of literature is available on the abnormal expression of ANXA proteins in various malignant diseases, including cancer, atherosclerosis and diabetes. As critical regulatory molecules in cancer, ANXA proteins play an essential role in cancer progression, proliferation, invasion and metastasis. Recent studies about their structure, biological properties and functions in different types of cancers are briefly summarised in this review. We further discuss the use of ANXA as new class of targets in the clinical diagnosis and treatment of cancer.

Photosystem II Inspired NiFe-Based Electrocatalysts for Efficient Water Oxidation via Second Coordination Sphere Effect.

The mismatched fast-electron-slow-proton process in the electrocatalytic oxygen evolution reaction (OER) severely restricts the catalytic efficiency. To overcome these issues, accelerating the proton transfer and elucidating the kinetic mechanism are highly sought after. Herein, inspired by photosystem II, we develop a family of OER electrocatalysts with FeO6 /NiO6 units and carboxylate anions (TA2- ) in the first and second coordination sphere, respectively. Benefiting from the synergistic effect of the metal units and TA2- , the optimized catalyst delivers superior activity with a low overpotential of 270 mV at 200 mA cm-2 and excellent cycling stability over 300 h. A proton-transfer-promotion mechanism is proposed by in situ Raman, catalytic tests, and theoretical calculations. The TA2- (proton acceptor) can mediate proton transfer pathways by preferentially accepting protons, which optimizes the O-H adsorption/activation process and reduces the kinetic barrier for O-O bond formation.