Mitochondrial injury induced by a Salmonella genotoxin triggers the proinflammatory senescence-associated secretory phenotype.

Bacterial genotoxins damage host cells by targeting their chromosomal DNA. In the present study, we demonstrate that a genotoxin of Salmonella Typhi, typhoid toxin, triggers the senescence-associated secretory phenotype (SASP) by damaging mitochondrial DNA. The actions of typhoid toxin disrupt mitochondrial DNA integrity, leading to mitochondrial dysfunction and disturbance of redox homeostasis. Consequently, it facilitates the release of damaged mitochondrial DNA into the cytosol, activating type I interferon via the cGAS-STING pathway. We also reveal that the GCN2-mediated integrated stress response plays a role in the upregulation of inflammatory components depending on the STING signaling axis. These SASP factors can propagate the senescence effect on T cells, leading to senescence in these cells. These findings provide insights into how a bacterial genotoxin targets mitochondria to trigger a proinflammatory SASP, highlighting a potential therapeutic target for an anti-toxin intervention.

Constructing regulable supports via non-stoichiometric engineering to stabilize ruthenium nanoparticles for enhanced pH-universal water splitting.

Establishing appropriate metal-support interactions is imperative for acquiring efficient and corrosion-resistant catalysts for water splitting. Herein, the interaction mechanism between Ru nanoparticles and a series of titanium oxides, including TiO, Ti4O7 and TiO2, designed via facile non-stoichiometric engineering is systematically studied. Ti4O7, with the unique band structure, high conductivity and chemical stability, endows with ingenious metal-support interaction through interfacial Ti-O-Ru units, which stabilizes Ru species during OER and triggers hydrogen spillover to accelerate HER kinetics. As expected, Ru/Ti4O7 displays ultralow overpotentials of 8 mV and 150 mV for HER and OER with a long operation of 500 h at 10 mA cm-2 in acidic media, which is expanded in pH-universal environments. Benefitting from the excellent bifunctional performance, the proton exchange membrane and anion exchange membrane electrolyzer assembled with Ru/Ti4O7 achieves superior performance and robust operation. The work paves the way for efficient energy conversion devices.

MSX1+PDGFRAlow limb mesenchyme-like cells as an efficient stem cell source for human cartilage regeneration.

Degenerative bone disorders have a significant impact on global health, and regeneration of articular cartilage remains a challenge. Existing cell therapies using mesenchymal stromal cells (MSCs) have shown limited efficacy, highlighting the necessity for alternative stem cell sources. Here, we have identified and characterized MSX1+ mesenchymal progenitor cells in the developing limb bud with remarkable osteochondral-regenerative and microenvironment-adaptive capabilities. Single-cell sequencing further revealed the presence of two major cell compositions within the MSX1+ cells, where a distinct PDGFRAlow subset retained the strongest osteochondral competency and could efficiently regenerate articular cartilage in vivo. Furthermore, a strategy was developed to generate MSX1+PDGFRAlow limb mesenchyme-like (LML) cells from human pluripotent stem cells that closely resembled their mouse counterparts, which were bipotential in vitro and could directly regenerate damaged cartilage in a mouse injury model. Together, our results indicated that MSX1+PDGFRAlow LML cells might be a prominent stem cell source for human cartilage regeneration.

Polarized Ultrathin BN Induced Dynamic Electron Interactions for Enhancing Acidic Oxygen Evolution.

Developing ruthenium-based heterogeneous catalysts with an efficient and stable interface is essential for enhanced acidic oxygen evolution reaction (OER). Herein, we report a defect-rich ultrathin boron nitride nanosheet support with relatively independent electron donor and acceptor sites, which serves as an electron reservoir and receiving station for RuO2, realizing the rapid supply and reception of electrons. Through precisely controlling the reaction interface, a low OER overpotential of only 180 mV (at 10 mA cm-2) and long-term operational stability (350 h) are achieved, suggesting potential practical applications. In situ characterization and theoretical calculations have validated the existence of a localized electronic recycling between RuO2 and ultrathin BN nanosheets (BNNS). The electron-rich Ru sites accelerate the adsorption of water molecules and the dissociation of intermediates, while the interconnection between the O-terminal and B-terminal edge establishes electronic back-donation, effectively suppressing the over-oxidation of lattice oxygen. This study provides a new perspective for constructing a stable and highly active catalytic interface.

Lewis Acid Driving Asymmetric Interfacial Electron Distribution to Stabilize Active Species for Efficient Neutral Water Oxidation.

Neutral oxygen evolution reaction (OER) with unique reactive environments exhibits extremely slow reaction kinetics, posing significant challenges in the design of catalysts. Herein, a built-in electric field between the tungstate (Ni-FeWO4 ) with adjustable work function and Lewis acid WO3 is elaborately constructed to regulate asymmetric interfacial electron distribution, which promotes electron accumulation of Fe sites in the tungstate. This decelerates the rapid dissolution of Fe under the OER potentials, thereby retaining the active hydroxyl oxide with the optimized OER reaction pathway. Meanwhile, Lewis acid WO3 enhances hydroxyl adsorption near the electrode surface to improve mass transfer. As expected, the optimized Ni-FeWO4 @WO3 /NF self-supporting electrode achieves a low overpotential of 235 mV at 10 mA cm-2 in neutral media and maintains stable operation for 200 h. Furthermore, the membrane electrode assembly constructed by such self-supporting electrode exhibits robust stability for 250 h during neutral seawater electrolysis. This work deepens the understanding of the reconstruction of OER catalysts in neutral environments and paves the way for development of the energy conversion technologies.

Manipulating the Microenvironment of Single Atoms by Switching Support Crystallinity for Industrial Hydrogen Evolution.

Modulating the microenvironment of single-atom catalysts (SACs) is critical to optimizing catalytic activity. Herein, we innovatively propose a strategy to improve the local reaction environment of Ru single atoms by precisely switching the crystallinity of the support from high crystalline and low crystalline, which significantly improves the hydrogen evolution reaction (HER) activity. The Ru single-atom catalyst anchored on low-crystalline nickel hydroxide (Ru-LC-Ni(OH)2 ) reconstructs the distribution balance of the interfacial ions due to the activation effect of metal dangling bonds on the support. Single-site Ru with a low oxidation state induces the aggregation of hydronium ions (H3 O+ ), leading to the formation of a local acidic microenvironment in alkaline media, breaking the pH-dependent HER activity. As a comparison, the Ru single-atom catalyst anchored on high-crystalline nickel hydroxide (Ru-HC-Ni(OH)2 ) exhibits a sluggish Volmer step and a conventional local reaction environment. As expected, Ru-LC-Ni(OH)2 requires low overpotentials of 9 and 136 mV at 10 and 1000 mA cm-2 in alkaline conditions and operates stably at 500 mA cm-2 for 500 h in an alkaline seawater anion exchange membrane (AEM) electrolyzer. This study provides a new perspective for constructing highly active single-atom electrocatalysts.

Switching the Oxygen Evolution Mechanism on Atomically Dispersed Ru for Enhanced Acidic Reaction Kinetics.

Designing stable single-atom electrocatalysts with lower energy barriers is urgent for the acidic oxygen evolution reaction. In particular, the atomic catalysts are highly dependent on the kinetically sluggish acid-base mechanism, limiting the reaction paths of intermediates. Herein, we successfully manipulate the steric localization of Ru single atoms at the Co3O4 surface to improve acidic oxygen evolution by precise control of the anchor sites. The delicate structure design can switch the reaction mechanism from the lattice oxygen mechanism (LOM) to the optimized adsorbate evolution mechanism (AEM). In particular, Ru atoms embedded into cation vacancies reveal an optimized mechanism that activates the proton donor-acceptor function (PDAM), demonstrating a new single-atom catalytic pathway to circumvent the classic scaling relationship. Steric interactions with intermediates at the anchored Ru-O-Co interface played a primary role in optimizing the intermediates' conformation and reducing the energy barrier. As a comparison, Ru atoms confined to the surface sites exhibit a lattice oxygen mechanism for the oxygen evolution process. As a result, the delicate atom control of the spatial position presents a 100-fold increase in mass activity from 36.96 A gRu(ads)-1 to 4012.11 A gRu(anc)-1 at 1.50 V. These findings offer new insights into the precise control of single-atom catalytic behavior.

Valence Oscillation of Ru Active Sites for Efficient and Robust Acidic Water Oxidation.

The continuous oxidation and leachability of active sites in Ru-based catalysts hinder practical application in proton-exchange membrane water electrolyzers (PEMWE). Herein, robust inter-doped tungsten-ruthenium oxide heterostructures [(Ru-W)Ox ] fabricated by sequential rapid oxidation and metal thermomigration processes are proposed to enhance the activity and stability of acidic oxygen evolution reaction (OER). The introduction of high-valent W species induces the valence oscillation of the Ru sites during OER, facilitating the cyclic transition of the active metal oxidation states and maintaining the continuous operation of the active sites. The preferential oxidation of W species and electronic gain of Ru sites in the inter-doped heterostructure significantly stabilize RuOx on WOx substrates beyond the Pourbaix stability limit of bare RuO2 . Furthermore, the asymmetric Ru-O-W active units are generated around the heterostructure interface to adsorb the oxygen intermediates synergistically, enhancing the intrinsic OER activity. Consequently, the inter-doped (Ru-W)Ox heterostructures not only demonstrate an overpotential of 170 mV at 10 mA cm-2 and excellent stability of 300 h in acidic electrolytes but also exhibit the potential for practical applications, as evidenced by the stable operation at 0.5 A cm-2 for 300 h in PEMWE.

Stabilizing Low-Valence Single Atoms by Constructing Metalloid Tungsten Carbide Supports for Efficient Hydrogen Oxidation and Evolution.

Designing novel single-atom catalysts (SACs) supports to modulate the electronic structure is crucial to optimize the catalytic activity, but rather challenging. Herein, a general strategy is proposed to utilize the metalloid properties of supports to trap and stabilize single-atoms with low-valence states. A series of single-atoms supported on the surface of tungsten carbide (M-WCx , M=Ru, Ir, Pd) are rationally developed through a facile pyrolysis method. Benefiting from the metalloid properties of WCx , the single-atoms exhibit weak coordination with surface W and C atoms, resulting in the formation of low-valence active centers similar to metals. The unique metal-metal interaction effectively stabilizes the low-valence single atoms on the WCx surface and improves the electronic orbital energy level distribution of the active sites. As expected, the representative Ru-WCx exhibits superior mass activities of 7.84 and 62.52 A mgRu -1 for the hydrogen oxidation and evolution reactions (HOR/HER), respectively. In-depth mechanistic analysis demonstrates that an ideal dual-sites cooperative mechanism achieves a suitable adsorption balance of Had and OHad , resulting in an energetically favorable Volmer step. This work offers new guidance for the precise construction of highly active SACs.

Dynamic Electronic and Ionic Transport Actuated by Cobalt-Doped MoSe2 /rGO for Superior Potassium-Ion Batteries.

Molybdenum selenium (MoSe2 ) has tremendous potential in potassium-ion batteries (PIBs) due to its large interlayer distance, favorable bandgap, and high theoretical specific capacity. However, the poor conductivity and large K+ insertion/extraction in MoSe2 inevitably leads to sluggish reaction kinetics and poor structural stability. Herein, Coinduced engineering is employed to illuminate high-conductivity electron pathway and mobile ion diffusion of MoSe2 nanosheets anchored on reduced graphene oxide substrate (Co-MoSe2 /rGO). Benefiting from the activated electronic conductivity and ion diffusion kinetics, and an expanded interlayer spacing resulting from Co doping, combined with the interface coupling with highly conductive reduced graphene oxide (rGO) substrate through Mo-C bonding, the Co-MoSe2 /rGO anode demonstrates remarkable reversible capacity, superior rate capability, and stable long-term cyclability for potassium storage, as well as superior energy density and high power density for potassium-ion capacitors. Systematic performance measurement, dynamic analysis, in-situ/ex-situ measurements, and density functional theory (DFT) calculations elucidate the performance-enhancing mechanism of Co-MoSe2 /rGO in view of the electronic and ionic transport kinetics. This work offers deep atomic insights into the fundamental factors of electrodes for potassium-ion batteries/capacitors with superior electrochemical performance.

Coordination engineering of single zinc atoms on hierarchical dual-carbon for high-performance potassium-ion capacitors.

Dual-carbon engineering combines the advantages of graphite and hard carbon, thereby optimizing the potassium storage performance of carbon materials. However, dual-carbon engineering faces challenges balancing specific capacity, capability, and stability. In this study, we present a coordination engineering of Zn-N4 moieties on dual-carbon through additional P doping, which effectively modulates the symmetric charge distribution around the Zn center. Experimental results and theoretical calculations unveil that additional P doping induces an optimized electronic structure of the Zn-N4 moieties, thus enhancing K+ adsorption. A single-atom Zn metal coordinated with nitrogen and phosphorus reduces the K+ diffusion barrier and improves fast K+ migration kinetics. Consequently, Zn-NPC@rGO exhibits high reversible specific capacities, excellent rate capability, and impressive cycling stability, and remarkable power and energy densities for potassium-ion capacitors (PICs). This study provides insights into crucial factors for enhancing potassium storage performance.

Activity-Stability Balance: The Role of Electron Supply Effect of Support in Acidic Oxygen Evolution.

Developing efficient and durable electrocatalysts for the oxygen evolution reaction (OER) in proton exchange membrane (PEM) electrolyzers represents a significant challenge. Herein, the cobalt-ruthenium oxide nano-heterostructures are successfully synthesized on carbon cloth (CoOx /RuOx -CC) for acidic OER through a simple and fast solution combustion strategy. The rapid oxidation process endows CoOx /RuOx -CC with abundant interfacial sites and defect structures, which enhances the number of active sites and the charge transfer at the electrolyte-catalyst interface, promoting the OER kinetics. Moreover, the electron supply effect of the CoOx support allows electrons to transfer from Co to Ru sites during the OER process, which is beneficial to alleviate the ion leaching and over-oxidation of Ru sites, improving the catalyst activity and stability. As a self-supported electrocatalyst, CoOx /RuOx -CC displays an ultralow overpotential of 180 mV at 10 mA cm-2 for OER. Notably, the PEM electrolyzer using CoOx /RuOx -CC as the anode can be operated at 100 mA cm-2 stably for 100 h. Mechanistic analysis shows that the strong catalyst-support interaction is beneficial to redistribute the electronic structure of RuO bond to weaken its covalency, thereby optimizing the binding energy of OER intermediates and lowering the reaction energy barrier.

Tailoring Oxygen Reduction Reaction Kinetics on Perovskite Oxides via Oxygen Vacancies for Low-Temperature and Knittable Zinc-Air Batteries.

High kinetics oxygen reduction reaction (ORR) electrocatalysts under low temperature are critical and highly desired for temperature-tolerant energy conversion and storage devices, but remain insufficiently investigated. Herein, oxygen vacancy-rich porous perovskite oxide (CaMnO3 ) nanofibers coated with reduced graphene oxide coating (V-CMO/rGO) are developed as the air electrode catalyst for low-temperature and knittable Zn-air batteries. V-CMO/rGO exhibits top-level ORR activity among perovskite oxides and shows impressive kinetics under low temperature. Experimental and theoretical calculation results reveal that the synergistic effect between metal atoms and oxygen vacancies, as well as the accelerated kinetics and enhanced electric conductivity and mass transfer over the rGO coated nanofiber 3D network contribute to the enhanced catalytic activity. The desorption of ORR intermediate is promoted by the regulated electron filling. The V-CMO/rGO drives knittable and flexible Zn-air batteries under a low temperature of -40 °C with high peak power density of 56 mW cm-2 and long cycle life of over 80 h. This study provides insight of kinetically active catalyst and facilitates the ZABs application in harsh environment.

Transferability of Alzheimer's disease progression subtypes to an independent population cohort.

In the past, methods to subtype or biotype patients using brain imaging data have been developed. However, it is unclear whether and how these trained machine learning models can be successfully applied to population cohorts to study the genetic and lifestyle factors underpinning these subtypes. This work, using the Subtype and Stage Inference (SuStaIn) algorithm, examines the generalisability of data-driven Alzheimer's disease (AD) progression models. We first compared SuStaIn models trained separately on Alzheimer's disease neuroimaging initiative (ADNI) data and an AD-at-risk population constructed from the UK Biobank dataset. We further applied data harmonization techniques to remove cohort effects. Next, we built SuStaIn models on the harmonized datasets, which were then used to subtype and stage subjects in the other harmonized dataset. The first key finding is that three consistent atrophy subtypes were found in both datasets, which match the previously identified subtype progression patterns in AD: 'typical', 'cortical' and 'subcortical'. Next, the subtype agreement was further supported by high consistency in individuals' subtypes and stage assignment based on the different models: more than 92% of the subjects, with reliable subtype assignment in both ADNI and UK Biobank dataset, were assigned to an identical subtype under the model built on the different datasets. The successful transferability of AD atrophy progression subtypes across cohorts capturing different phases of disease development enabled further investigations of associations between AD atrophy subtypes and risk factors. Our study showed that (1) the average age is highest in the typical subtype and lowest in the subcortical subtype; (2) the typical subtype is associated with statistically more-AD-like cerebrospinal fluid biomarkers values in comparison to the other two subtypes; and (3) in comparison to the subcortical subtype, the cortical subtype subjects are more likely to associate with prescription of cholesterol and high blood pressure medications. In summary, we presented cross-cohort consistent recovery of AD atrophy subtypes, showing how the same subtypes arise even in cohorts capturing substantially different disease phases. Our study opened opportunities for future detailed investigations of atrophy subtypes with a broad range of early risk factors, which will potentially lead to a better understanding of the disease aetiology and the role of lifestyle and behaviour on AD.

UGT76F1 glycosylates an isomer of the C7-necic acid component of pyrrolizidine alkaloids in Arabidopsis thaliana.

Identification of unknown metabolites and their biosynthetic genes is an active research area in plant specialized metabolism. By following a gene-metabolite association from a genome-wide association study of Arabidopsis stem metabolites, we report a previously unknown metabolite, 2-hydroxy-2-(1-hydroxyethyl)pentanoic acid glucoside, and demonstrated that UGT76F1 is responsible for its production in Arabidopsis. The chemical structure of the glucoside was determined by a series of analyses, including tandem MS, acid and base hydrolysis, and NMR spectrometry. T-DNA knockout mutants of UGT76F1 are devoid of the glucoside but accumulate increased levels of the aglycone. 2-hydroxy-2-(1-hydroxyethyl)pentanoic acid is structurally related to the C7-necic acid component of lycopsamine-type pyrrolizidine alkaloids such as trachelantic acid and viridifloric acid. Feeding norvaline greatly enhances the accumulation of 2-hydroxy-2-(1-hydroxyethyl)pentanoic acid glucoside in wild-type but not the UGT76F1 knockout mutant plants, providing evidence for an orthologous C7-necic acid biosynthetic pathway in Arabidopsis despite the apparent lack of pyrrolizidine alkaloids.

A Competitive Panning Method Reveals an Anti-SARS-CoV-2 Nanobody Specific for an RBD-ACE2 Binding Site.

Most neutralizing antibodies neutralize the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by directly blocking the interactions between the spike glycoprotein receptor-binding domain (RBD) and its receptor, human angiotensin-converting enzyme 2 (ACE2). Here, we report a novel nanobody (Nb) identified by an RBD-ACE2 competitive panning method that could specifically bind to the RBD of SARS-CoV-2 with a high affinity (EC50 = 0.03 nM) and successfully block the binding between the RBD and ACE2 recombinant protein. A structural simulation of the RBD-VHH complex also supports a mechanism of the Nb to block the interaction between the RBD and ACE2. A pseudovirus assay of the Nb showed it could neutralize the WT pseudovirus with high potency (IC50 = 0.026 µg/mL). Furthermore, we measured its binding to phages displaying RBDs of different SARS-CoV-2 variants and found that it could bind to recombinant phages displaying the RBD of beta and delta variants. This study also provides a method of phage library competitive panning, which could be useful for directly screening high-affinity antibodies targeting important functional regions.

Air pollution and infant mortality: Evidence from China.

Using a newly assembled prefecture-city level dataset from 2004 to 2015, this paper examines the impact of air pollution on child mortality in China. To identify the causal effect, we exploit ventilation coefficient as the instrument for urban air pollution. We find that a 10 µg/m3 increase in annual PM2.5 concentration causes 163 infant deaths per 100,000 live births per year in a city.

Synergistic Mechanism of Sub-Nanometric Ru Clusters Anchored on Tungsten Oxide Nanowires for High-Efficient Bifunctional Hydrogen Electrocatalysis.

The construction of strong interactions and synergistic effects between small metal clusters and supports offers a great opportunity to achieve high-performance and cost-effective heterogeneous catalysis, however, studies on its applications in electrocatalysis are still insufficient. Herein, it is reported that W18 O49 nanowires supported sub-nanometric Ru clusters (denoted as Ru SNC/W18 O49 NWs) constitute an efficient bifunctional electrocatalyst for hydrogen evolution/oxidation reactions (HER and HOR) under acidic condition. Microstructural analyses, X-ray absorption spectroscopy, and density functional theory (DFT) calculations reveal that the Ru SNCs with an average RuRu coordination number of 4.9 are anchored to the W18 O49 NWs via RuOW bonds at the interface. The strong metal-support interaction leads to the electron-deficient state of Ru SNCs, which enables a modulated RuH strength. Furthermore, the unique proton transport capability of the W18 O49 also provides a potential migration channel for the reaction intermediates. These components collectively enable the remarkable performance of Ru SNC/W18 O49 NWs for hydrogen electrocatalysis with 2.5 times of exchange current density than that of carbon-supported Ru nanoparticles, and even rival the state-of-the-art Pt catalyst. This work provides a new prospect for the development of supported sub-nanometric metal clusters for efficient electrocatalysis.

Ultrafast Combustion Synthesis of Robust and Efficient Electrocatalysts for High-Current-Density Water Oxidation.

The scalable production of inexpensive, efficient, and robust catalysts for oxygen evolution reaction (OER) that can deliver high current densities at low potentials is critical for the industrial implementation of water splitting technology. Herein, a series of metal oxides coupled with Fe2O3 are in situ grown on iron foam massively via an ultrafast combustion approach for a few seconds. Benefiting from the three-dimensional nanosheet array framework and the heterojunction structure, the self-supporting electrodes with abundant active centers can regulate mass transport and electronic structure for prompting OER activity at high current density. The optimized Ni(OH)2/Fe2O3 with robust structure can deliver a high current density of 1000 mA cm-2 at the overpotential as low as 271 mV in 1.0 M KOH for up to 1500 h. Theoretical calculation demonstrates that the strong electronic modulation plays a crucial part in the hybrid by optimizing the adsorption energy of the intermediate, thereby enhancing the efficiency of oxygen evolution. This work proposes a method to construct cheap and robust catalysts for practical application in energy conversion and storage.

Operando X-ray Studies of Ni-Containing Heteropolyvanadate Electrode for High-Energy Lithium-Ion Storage Applications.

Ni-containing heteropolyvanadate, Na6[NiV14O40], was synthesized for the first time to be applied in high-energy lithium storage applications as a negative electrode material. Na6[NiV14O40] can be prepared via a facile solution process that is suitable for low-cost mass production. The as-prepared electrode provided a high capacity of approximately 700 mAh g-1 without degradation for 400 cycles, indicating excellent cycling stability. The mechanism of charge storage was investigated using operando X-ray absorption spectroscopy (XAS), X-ray diffraction (XRD), transition X-ray microscopy (TXM), and density functional theory (DFT) calculations. The results showed that V5+ was reduced to V2+ during lithiation, indicating that Na6[NiV14O40] is an insertion-type material. In addition, Na6[NiV14O40] maintained its amorphous structure with negligible volume expansion/contraction during cycling. Employed as the negative electrode in a lithium-ion battery (LIB), the Na6[NiV14O40]//LiFePO4 full cell had a high energy density of 300 W h kg-1. When applied in a lithium-ion capacitor, the Na6[NiV14O40]//expanded mesocarbon microbead full cell displayed energy densities of 218.5 and 47.9 W h kg-1 at power densities of 175.7 and 7774.2 W kg-1, respectively. These findings reveal that the negative electrode material Na6[NiV14O40] is a promising candidate for Li-ion storage applications.