Biomimetic Design of a Dynamic M-O-V Pyramid Electron Bridge for Enhanced Nitrogen Electroreduction.

Electrochemical nitrogen reduction reaction (eNRR) offers a sustainable route for ammonia synthesis; however, current electrocatalysts are limited in achieving optimal performance within narrow potential windows. Herein, inspired by the heliotropism of sunflowers, we present a biomimetic design of Ru-VOH electrocatalyst, featuring a dynamic Ru-O-V pyramid electron bridge for eNRR within a wide potential range. In situ spectroscopy and theoretical investigations unravel the fact that the electrons are donated from Ru to V at lower overpotentials and retrieved at higher overpotentials, maintaining a delicate balance between N2 activation and proton hydrogenation. Moreover, N2 adsorption and activation were found to be enhanced by the Ru-O-V moiety. The catalyst showcases an outstanding Faradaic efficiency of 51.48% at -0.2 V (vs RHE) with an NH3 yield rate exceeding 115 µg h-1 mg-1 across the range of -0.2 to -0.4 V (vs RHE), along with impressive durability of over 100 cycles. This dynamic M-O-V pyramid electron bridge is also applicable to other metals (M = Pt, Rh, and Pd).

Metal-organic framework-derived two-dimensional in-plane Janus catalysts promoting oxygen electroreduction to hydrogen peroxide.

We use MOFs material as precursor to synthesize carbon based two-dimensional (2D) materials loaded with In2 S3 -In2 O3 (In-S-O) nanoparticles. The In-S-O nanoparticles have exhibited Janus architecture composed of two compounds with different crystal structures that are combined in-plane on 2D carbon material surface. The excellent properties of this in-plane Janus material include 2D nanoarchitecture and its Janus properties formed by combining two different crystal structures. It has exhibited excellent electrochemical performances due to its abundant electrochemical active sites and large specific surface area. According to experiments, the electron transfer number of the material for two-electron oxygen reduction is about 2.4, and the hydrogen peroxide yield is 32 mg/h cm2 . In the further test of liquid flow electrolytic cell, the yield can reach up to 172 mg/h cm2 .

Entropy-Driven Direct Air Electrofixation.

According to the principles of chemical thermodynamics, the catalytic activation of small molecules (like N2 in air and CO2 in flue gas) generally exhibits a negative activity dependence on O2 owning to the competitive oxygen reduction reaction (ORR). Nevertheless, some catalysts can show positive activity dependence for N2 electrofixation, an important route to produce ammonia under ambient condition. Here we report that the positive activity dependence on O2 of (Ni0.20Co0.20Fe0.20Mn0.19Mo0.21)3S4 catalyst arises from high-entropy mechanism. Through experimental and theoretical studies, we demonstrate that under the reaction condition in the mixed N2/O2, the adsorption of O2 on high-entropy catalyst contributes to activating N2 molecules characteristic of elongated N≡N bond lengths. As comparison to the low- and medium-entropy counterparts, high entropy can play the second role of attenuating competitive ORR by displaying a negative exponential entropy-ORR activity relationship. Accordingly, benefiting from the O2, the system for direct air electrofixation has demonstrated an ammonia yield rate of 47.70 µg h-1 cm-2, which is even 1.5 times of pure N2 feedstock (31.92 µg h-1 cm-2), overtaking all previous reports for this reaction. We expect the present finding providing an additional dimension to high entropy that leverages systems beyond the constraint of traditional rules.

Less-Coordinated Atomic Copper-Dimer Boosted Carbon-Carbon Coupling During Electrochemical CO2 Reduction.

This work reports a metal-organic framework (MOF) with less-coordinated copper dimers, which displays excellent electrochemical CO2 reduction (eCO2 RR) performance with an advantageous current density of 0.9 A cm-2 and a high Faradaic efficiency of 71% to C2 products. In comparison with MOF with Cu monomers that are present as Cu1 O4 with a coordination number of 3.8 ± 0.2, Cu dimers exist as O3 Cu1 ···Cu2 O2 with a coordination number of 2.8 ± 0.1. In situ characterizations together with theoretical calculations reveal that two *CO intermediates are stably adsorbed on each site of less-coordinated Cu dimers, which favors later dimerization via a key intermediate of *CH2 CHO. The highly unsaturated dual-atomic Cu provides large-quantity and high-quality actives sites for carbon-carbon coupling, achieving the optimal trade-off between activity and selectivity of eCO2 RR to C2 products.

Improved Electrochemical Alkaline Seawater Oxidation over Cobalt Carbonate Hydroxide Nanowire Array by Iron Doping.

Constructing efficient and low-cost oxygen evolution reaction (OER) catalysts operating in seawater is essential for green hydrogen production but remains a great challenge. In this study, we report an iron doped cobalt carbonate hydroxide nanowire array on nickel foam (Fe-CoCH/NF) as a high-efficiency OER electrocatalyst. In alkaline seawater, such Fe-CoCH/NF demands an overpotential of 387 mV to drive 500 mA cm-2, superior to that of CoCH/NF (597 mV). Moreover, it achieves excellent electrochemical and structural stability in alkaline seawater.

Amorphous Co-Mo-P film on nickel foam: a superior bifunctional electrocatalyst for alkaline seawater splitting.

Seawater splitting is a compelling avenue to produce abundant hydrogen, which requires high-performance and cost-effective catalysts. Constructing bimetallic transition metal phosphides is a feasible strategy to meet the challenge. Here, an amorphous Co-Mo-P film supported on nickel foam (Co-Mo-P/NF) electrode is developed with bifunctional properties for both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in alkaline seawater. Corresponding results indicate that the introduction of Mo can improve the active sites and regulate the intrinsic activity. Such a Co-Mo-P/NF behaves with prominent electrocatalytic activity towards both HER and OER, demanding low overpotentials of 193 and 352 mV at 100 mA cm‒2in alkaline seawater, respectively. Furthermore, the assembled electrolyzer demands a pronounced overall seawater splitting activity with a low cell voltage of 1.76 V to deliver 100 mA cm-2presenting excellent durability without obvious attenuation after 24 h continuous stability test. This work expands the horizon to develop transition metal-phosphorus electrocatalysts with robust and efficient activity for overall seawater splitting.

Hypoxic preconditioned MSCs-derived small extracellular vesicles for photoreceptor protection in retinal degeneration.

Photoreceptor apoptosis is an important pathogenesis of retinal degeneration and a primary cause of vision loss with limited treatment methods. Mesenchymal stem/stromal cells-derived small extracellular vesicles (MSC-sEVs) have shown therapeutic value in various ocular disorders. Recent studies have revealed that hypoxic preconditioning can improve the effectiveness of MSC-sEVs in tissue regeneration. However, whether hypoxic preconditioned MSC-sEVs (Hyp-sEVs) exert superior effects on photoreceptor protection relative to normoxic conditioned MSC-sEVs (Nor-sEVs) remains unclear. Here, we reported that Hyp-sEVs further improved retinal structure, recovered retinal function, and suppressed photoreceptor apoptosis in N-methyl-N-nitrosourea (MNU)-induced mouse model compared with Nor-sEVs. Hyp-sEVs also exhibited enhanced anti-apoptotic roles in MNU-provoked 661 W cell injury in vitro. We then analyzed the protein profiles of Nor-sEVs and Hyp-sEVs by LC-MS/MS and found that growth-associated protein 43 (GAP43) was enriched in Hyp-sEVs. The knockdown of GAP43 abolished the retinal therapeutic effects of Hyp-sEVs. Mechanistically, hypoxic stimulation-induced hypoxia-inducible factor-1α (HIF-1α) activation was responsible for preventing tripartite motif-containing protein 25 (TRIM25)-mediated GAP43 ubiquitination and degradation, leading to the upregulation of GAP43 in Hyp-sEVs. Together, our findings uncover the efficacy and mechanism of Hyp-sEVs-based photoreceptor protection and highlight the potential of Hyp-sEVs as optimized therapeutics for retinal degeneration.

Battery-Driven N2 Electrolysis Enabled by High-Entropy Catalysts: From Theoretical Prediction to Prototype Model.

A small-scale standalone device of nitrogen (N2 ) splitting holds great promise for producing ammonia (NH3 ) in a decentralized manner as the compensation or replacement of centralized Haber-Bosch process. However, the design of such a device has been impeded by sluggish kinetics of its half reactions, i.e., cathodic N2 reduction reaction (NRR) and anodic oxygen evolution reaction (OER). Here, it is predicted from density function theory that high-entropy oxides (HEOs) are potential catalysts for promoting NRR and OER, and subsequently develop a facile procedure to synthesize HEOs in the morphology of sea urchin-shaped hollow nanospheres assembled from ultrathin nanosheets. The excellent electrocatalytic activities of HEOs for both NRR (NH3 yield rate: 47.58 µg h-1 mg-1 and Faradaic efficiency (FE): 10.74%) and OER (215 mV @10 mA cm-2 ) are demonstrated. Consequently, a prototype device of N2 electrolysis driven by commercial batteries is constructed, which can operate smoothly and deliver remarkable NH3 yield rate (41.11 µg h-1 mg-1 ) and FE (14.14%). Further mechanism study has attributed the excellent catalytic performances of HEOs to their unique electronic structures originated from multi-metal synergistic effects and entropy increase effects. The work will provide new clues for designing versatile catalysts and devices for large-scale industrialization.

Biomimetic FeMo(Se, Te) as Joint Electron Pool Promoting Nitrogen Electrofixation.

It has been long believed that the FeMoS structure, where Fe is bonded with S, plays a pivotal role as a biomimetic catalyst for electrochemical nitrogen (N2 ) fixation. Nevertheless, the structure of Fe bonded to heavier analogues (Se or Te) has never been explored for N2 electrofixation. Here, we theoretically predict the electronic structure of FeMo(Se, Te) composed of tri-coordinated Fe species with open shells for binding with Se, which forms a joint electron pool for promoting N2 activation. Guided by this interesting prediction, we then demonstrate a two-step procedure to synthesize such structures, which display remarkable N2 electrofixation activities with an ammonia yield of 72.54 µg h-1 mg-1 and a Faradic efficiency of 51.67 % that are more than three times of the FeMoS counterpart. Further mechanism studies have been conducted by density function theory (DFT) simulations. This work provides new clues for designing versatile electrocatalytic materials for large-scale industrialization.

Tuning Coordination Structures of Zn Sites Through Symmetry-Breaking Accelerates Electrocatalysis.

Manipulating the coordination environment of individual active sites in a precise manner remains an important challenge in electrocatalytic reactions. Herein, inspired by theoretical predictions, a facile procedure to synthesize a series of symmetry-breaking zinc metal-organic framework (Zn-MOF) catalysts with well-defined structures is presented. Benefiting from the optimized coordination microenvironment regulated by symmetry-breaking, Zn-N2 S2 -MOF exhibits the best performance of nitrogen (N2 ) reduction reaction (NRR) with NH3 yield rate of 25.07 ± 1.57 µg h-1  cm-2 and Faradaic efficiency of 44.57 ± 2.79% compared with reported Zn-based NRR catalysts. X-ray absorption near-edge structure shows that the symmetry-breaking distorts the coordination environment and modulates the delocalized electrons around the Zn sites, which favors the formation of unpaired low-valence Znδ+ , thereby facilitating the adsorption/activation of N2 . Theoretical calculations elucidate that low-valence Znδ+ in Zn-N2 S2 -MOF can effectively lower the energy barrier of potential determining step, promoting the kinetics and boosting the NRR activity. This work highlights the relationship between the precise coordination environment of metal sites and the catalytic activity, which offers insightful guidance for rationally designing high-efficiency electrocatalysts.

Engineered mesenchymal stem cell-derived small extracellular vesicles for diabetic retinopathy therapy through HIF-1α/EZH2/PGC-1α pathway.

Diabetic retinopathy (DR) is a leading cause of blindness worldwide with limited treatment options. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) hold promise as a cell-free therapy for retinal diseases. In this study, we present evidence that the intravitreal injection of MSC-sEVs improved retinal function and alleviated retinal apoptosis, inflammation, and angiogenesis in both db/db mice and streptozotocin-induced diabetic rats. Mechanistically, hyperglycemia-induced activation of hypoxia-inducible factor-1α (HIF-1α) inhibited the tripartite motif 21 (TRIM21)-mediated ubiquitination and degradation of enhancer of zeste homologue 2 (EZH2), ultimately resulting in the downregulation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) through EZH2-induced methylation modification. The presence of miR-5068 and miR-10228 in MSC-sEVs targeted the HIF-1α/EZH2/PGC-1α pathway. The blockade of miR-5068 and miR-10228 abolished the retinal therapeutic effects of MSC-sEVs. Additionally, we engineered MSC-sEVs with elevated levels of miR-5068 and miR-10228 to enhance retinal repair efficiency. Together, our findings provide novel insights into the mechanism underlying DR progress and highlight the potential of MSC-sEVs, especially engineered MSC-sEVs, as a therapeutic option for DR.

Fabrication of a hierarchical NiTe@NiFe-LDH core-shell array for high-efficiency alkaline seawater oxidation.

Herein, a hierarchical NiTe@NiFe-LDH core-shell array on Ni foam (NiTe@NiFe-LDH/NF) demonstrates its effectiveness for oxygen evolution reaction (OER) in alkaline seawater electrolyte. This NiTe@NiFe-LDH/NF array showcases remarkably low overpotentials of 277 mV and 359 mV for achieving current densities of 100 and 500 mA cm-2, respectively. Also, it shows a low Tafel slope of 68.66 mV dec-1. Notably, the electrocatalyst maintains robust stability over continuous electrolysis for at least 50 h at 100 mA cm-2. The remarkable performance and hierarchical structure advantages of NiTe@NiFe-LDH/NF offer innovative insights for designing efficient seawater oxidation electrocatalysts.

Engineered Extracellular Vesicles as a Targeted Delivery Platform for Precision Therapy.

Extracellular vesicles (EVs)-based cell-free strategy has shown therapeutic potential in tissue regeneration. Due to their important roles in intercellular communications and their natural ability to shield cargos from degradation, EVs are also emerged as novel delivery vehicles for various bioactive molecules and drugs. Accumulating studies have revealed that EVs can be modified to enhance their efficacy and specificity for the treatment of many diseases. Engineered EVs are poised as the next generation of targeted delivery platform in the field of precision therapy. In this review, the unique properties of EVs are overviewed in terms of their biogenesis, contents, surface features and biological functions, and the recent advances in the strategies of engineered EVs construction are summarized. Additionally, we also discuss the potential applications of engineered EVs in targeted therapy of cancer and damaged tissues, and evaluate the opportunities and challenges for translating them into clinical practice.

Exosomal LncRNAs in Gastrointestinal Cancer: Biological Functions and Emerging Clinical Applications.

Due to the lack of specific and effective biomarkers and therapeutic targets, the early diagnosis and treatment of gastrointestinal cancer remain unsatisfactory. As a type of nanosized vesicles derived from living cells, exosomes mediate cell-to-cell communication by transporting bioactive molecules, thus participating in the regulation of many pathophysiological processes. Recent evidence has revealed that several long non-coding RNAs (lncRNAs) are enriched in exosomes. Exosomes-mediated lncRNAs delivery is critically involved in various aspects of gastrointestinal cancer progression, such as tumor proliferation, metastasis, angiogenesis, stemness, immune microenvironment, and drug resistance. Exosomal lncRNAs represent promising candidates to act as the diagnosis biomarkers and anti-tumor targets. This review introduces the major characteristics of exosomes and lncRNAs and describes the biological functions of exosomal lncRNAs in gastrointestinal cancer development. The preclinical studies on using exosomal lncRNAs to monitor and treat gastrointestinal cancer are also discussed, and the opportunities and challenges for translating them into clinical practice are evaluated.

Machine learning and network analysis of the gut microbiome from patients with schizophrenia and non-psychiatric subject controls reveal behavioral risk factors and bacterial interactions.

Recent findings have supported an association between deviations in gut microbiome composition and schizophrenia. However, the extent to which the gut microbiota contributes to schizophrenia remains unclear. Moreover, studies have yet to explore variations in ecological associations among bacterial types in subjects with schizophrenia, which can reveal differences in community interactions and gut stability. We examined the dataset collected by Nguyen et al. (2021) to investigate the similarities and differences in gut microbial constituents between 48 subjects with schizophrenia and 48 matched non-psychiatric comparison cases. We re-analyzed alpha- and beta-diversity differences and completed modified differential abundance analyses and confirmed the findings of Nguyen et al. (2021) that there was little variation in alpha-diversity but significant differences in beta-diversity between individuals with schizophrenia and non-psychiatric subjects. We also conducted mediation analysis, developed a machine learning (ML) model to predict schizophrenia, and completed network analysis to examine community-level interactions among bacterial taxa. Our study offers new insights, suggesting that the gut microbiome mediates the effects between schizophrenia and smoking status, BMI, anxiety score, and depression score. Our differential abundance and network analysis findings suggest that the differential abundance of Lachnospiraceae and Ruminococcaceae taxa fosters a decrease in stabilizing competitive interactions in the gut microbiome of subjects with schizophrenia. Loss of this competition may promote ecological instability and dysbiosis, altering gut-brain axis interactions in these subjects.

Chromium doping enabled improvement in alkaline seawater oxidation over cobalt carbonate hydroxide nanowire array.

The presence of chlorine species in seawater can cause severe anode corrosion, highlighting the critical need for the design of efficient and robust electrocatalysts towards the oxygen evolution reaction (OER) for hydrogen production. Herein, we present a chromium doped cobalt carbonate hydroxide nanowire array on nickel foam (Cr-CoCH/NF) as an effective OER electrocatalyst in seawater. In alkaline conditions, Cr-CoCH/NF exhibits a low overpotential of 450 mV to achieve 500 mA cm-2, surpassing that of CoCH/NF (614 mV). Additionally, it demonstrates 200 h of continuous oxygen evolution testing.

Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Potential Therapy for Diabetes Mellitus and Diabetic Complications.

As a novel cell-free strategy, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) inherit the therapeutic potential of donor cells, and are widely used for the treatment of many diseases. Increasing studies have shown that MSC-EVs transfer various bioactive molecules to create a beneficial microenvironment, thus exerting protective roles in diabetic mellitus (DM) and diabetic complications. To overcome the limitations of natural MSC-EVs such as heterogeneity and insufficient function, several modification methods have been established for constructing engineered MSC-EVs with elevated repairing efficiency. In this review, the PubMed library was searched from inception to August 2022, using a combination of Medical Subject Headings (MeSH) and keywords related to MSC-EVs, DM, and diabetic complications. We provide an overview of the major characteristics of MSC-EVs and summarize the recent advances of MSC-EV-based therapy for hyperglycemia-induced tissue damage with an emphasis on MSC-EV-mediated delivery of functional components. Moreover, the potential applications of engineered MSC-EVs in DM-related diseases therapy are discussed by presenting examples, and the opportunities and challenges for the clinical translation of MSC-EVs, especially engineered MSC-EVs, are evaluated.

Mesenchymal stem cells-derived small extracellular vesicles alleviate diabetic retinopathy by delivering NEDD4.

BACKGROUND: As a leading cause of vision decline and severe blindness in adults, diabetic retinopathy (DR) is characterized by the aggravation of retinal oxidative stress and apoptosis in the early stage. Emerging studies reveal that mesenchymal stem cells-derived small extracellular vesicles (MSC-sEV) treatment represents a promising cell-free approach to alleviate ocular disorders. However, the repairing effects of MSC-sEV in DR remain largely unclear. This study aimed at exploring the role and the underlying mechanism of MSC-sEV in hyperglycemia-induced retinal degeneration. METHODS: In vivo, we used streptozotocin (STZ) to establish diabetic rat model, followed by the intravitreal injection of MSC-sEV to determine the curative effect. The cell viability and antioxidant capacity of retinal pigment epithelium (RPE) cells stimulated with high-glucose (HG) medium after MSC-sEV treatment were analyzed in vitro. By detecting the response of cell signaling pathways in MSC-sEV-treated RPE cells, we explored the functional mechanism of MSC-sEV. Mass spectrometry was performed to reveal the bioactive protein which mediated the role of MSC-sEV. RESULTS: The intravitreal injection of MSC-sEV elicited antioxidant effects and counteracted retinal apoptosis in STZ-induced DR rat model. MSC-sEV treatment also reduced the oxidative level and enhanced the proliferation ability of RPE cells cultured in HG conditions in vitro. Further studies showed that the increased level of phosphatase and tensin homolog (PTEN) inhibited AKT phosphorylation and nuclear factor erythroid 2-related factor 2 (NRF2) expression in RPE cells stimulated with HG medium, which could be reversed by MSC-sEV intervention. Through mass spectrometry, we illustrated that MSC-sEV-delivered neuronal precursor cell-expressed developmentally downregulated 4 (NEDD4) could cause PTEN ubiquitination and degradation, activate AKT signaling and upregulate NRF2 level to prevent DR progress. Moreover, NEDD4 knockdown impaired MSC-sEV-mediated retinal therapeutic effects. CONCLUSIONS: Our findings indicated that MSC-sEV ameliorated DR through NEDD4-induced regulation on PTEN/AKT/NRF2 signaling pathway, thus revealing the efficiency and mechanism of MSC-sEV-based retinal protection and providing new insights into the treatment of DR.

Biomimetic assembly to superplastic metal-organic framework aerogels for hydrogen evolution from seawater electrolysis.

Applications for metal-organic frameworks (MOFs) demand their assembly into three-dimensional (3D) macroscopic architectures. The capability of sustaining structural integrity with considerable deformation is important to allow a monolithic material to work reliably. Nevertheless, it remains a significant challenge to introduce superplasticity in 3D MOF networks. Here, we report a general procedure for synthesizing 3D superplastic MOF aerogels inspired by the hierarchical architecture of natural corks. The resultant MOFs exhibited excellent superplasticity that can recover fully and rapidly to its original dimension after 50% strain compression and unloading for >2000 cycles. The 3D superplastic architecture is achieved by successively assembling one-dimensional (1D) to two-dimensional (2D) and then 3D, in a variety of MOFs with different transition metal active sites (Co-, NiMn-, NiCo-, NiCoMn-) and organic ligands (2-thiophenecarboxylic acid and glutaric acid). Latent applications have been demonstrated for NiMn-MOF aerogels to serve as a new generation of flexible electrocatalysts for hydrogen evolution reaction (HER) from seawater splitting, which requires a low overpotential of 243 mV to achieve a current density of 10 mA·cm-2. Notably, the electrocatalyst remains stable even being deformed, as the overpotential to achieve a current density of 10 mA·cm-2 increases slightly to 270, 264, and 258 mV after one-, two-, and threefold, respectively. In great contrast, traditional MOF powder-electrodes demonstrate significant activity decay under similar conditions. This work opens up enormous opportunities for exploring new applications of MOFs in a freestanding, structurally adaptive, and macroscopic form.

Defect Regulating of Few-Layer Antimonene from Acid-Assisted Exfoliation for Enhanced Electrocatalytic Nitrogen Fixation.

Nitrogen reduction reaction (NRR), as a green and sustainable technology, is far from a practical application due to the lack of efficient electrocatalysts. In this work, we found that antimonene, a group-VA elemental two-dimensional (2D) material, is attractive as an electrocatalyst for NRR. The antimonene here is acquired through chemical exfoliation of antimony (Sb) using H2SO4 for the first time, which simultaneously achieved efficient large-sized exfoliation and created a high density of active edge sites. Moreover, the concentration of defects shows a gradual increasing tendency as the treatment time extends. The obtained antimonene exhibited favorable average ammonia (NH3) yield and Faradaic efficiency as high as 2.08 µg h-1 cm-2 and 14.25% at -0.7 V versus RHE, respectively. Density functional theory calculations prove that the sufficient exposure of edge defects is favorable for reducing the reaction barrier and strengthening the interaction between antimonene and the intermediates of NRR, thus increasing the selectivity and yield rate of NH3. The chemical exfoliation of Sb reported here offers an alternative avenue to engineer the surface structures of group-VA elemental-based catalysts. Investigation of NRR using 2D antimonene can further provide deep insight into the mechanism and principle of NRR over group-VA elemental nanosheets.