Modulating Pd e_(g) orbital occupancy in Pd-Au metallic aerogels for efficient carbon dioxide reduction

The electronic structure of electrocatalysts plays a critical role in energy conversion,whereas for an efficient catalyst,it is challenging to modulate the orbitals.Herein,we present a new strategy to modulate the e_(g) orbital occupancy of Pd by constructing composition-controllable Pd-Au metallic aerogels(MAs),optimizing the d-band center of Pd to achieve excellent performance for electrochemical carbon dioxide reduction reaction(CO_(2)RR).Specifically,Pd_(1)Au_(2) MAs achieve almost 100% Faraday efficiency(FE) of CO in the range of-0.40 to-0.80 V vs.reversible hydrogen electrode(RHE),as well as the long-term stability,being one of the best Pd-based materials for CO_(2)RR.The X-ray photoelectron spectroscopy(XPS) results and density functional theory(DFT) calculations demonstrate that the introduction of Au modulates the Pd e_(g) orbital occupancy,which significantly weakens *CO adsorption on Pd,reduces the CO_(2)RR energy barrier and consequently improves the electrocatalytic activity and stability for long-term applications.Our work highlights a new strategy for designing efficient electrocatalysts for CO_(2)RR and beyond.

MOF负载Weel抑制剂实现p53突变胆囊癌的合成致死靶向治疗

Adavosertib(ADA)is a WEE1 inhibitor that exhibits a synthetic lethal effect on p53-mutated gallbladder cancer(GBC).However,drug resistance due to DNA damage response compensation pathways and high toxicity limits further applications.Herein,estrone-targeted ADA-encapsulated metal–organic frameworks(ADA@MOF-EPL)for GBC synthetic lethal treatment by inducing conditional factors are developed.The high expression of estrogen receptors in GBC enables ADA@MOF-EPL to quickly enter and accumulate near the cell nucleus through estrone-mediated endocytosis and release ADA to inhibit WEE1 upon entering the acidic tumor microenvironment.Ultrasound irradiation induces ADA@MOF-EPL to generate reactive oxygen species(ROS),which leads to a further increase in DNA damage,resulting in a higher sensitivity of p53-mutated cancer cells to WEE1 inhibitor and promoting cell death via conditional synthetic lethality.The conditional factor induced by ADA@MOF-EPL further enhances the antitumor efficacy while significantly reducing systemic toxicity.Moreover,ADA@MOF-EPL demonstrates similar antitumor abilities in other p53-mutated solid tumors,revealing its potential as a broad-spectrum antitumor drug.

Heterointerface engineering of assembled CoP_(2) on N-modified carbon as efficient trifunctional electrocatalysts for Zn-Air batteries and overall water splitting

Enhancing catalytic activity through modulating the interaction between N-doped carbon and metal phosphides clusters is an effective approach.Herein,the electronic structure modulation of CoP_(2) supported N-modified carbon(CoP_(2)/NC)has been designed and prepared as efficient electrocatalysts for oxygen reduction reaction(ORR),oxygen evolution reaction(OER),and hydrogen evolution reaction(HER).Notably,CoP_(2)/NC-1 catalyst exhibits impressive performance in alkaline media,with an ORR half-wave potential of 0.84 V,as well as OER and HER overpotentials of 290 and 129 mV(at 10 mA·cm^(−2)),respectively.In addition,CoP_(2)/NC-1 produces a power density as high as 172.9 mW·cm^(−2),and excellent reversibility of 100 h at 20 mA·cm^(−2) in home-made Zn-air batteries.The experimental results demonstrate that the synergistic interactions between N modified carbon substrate and CoP_(2) material significantly enhance the kinetics of ORR,OER,and HER.Density functional theory(DFT)calculations reveal the strong electrons redistribution of CoP_(2) induced by high-density N atoms at the interface,thus optimizing the key intermediates and significantly lower the energy barrier of reactions.These electronic adjustments of CoP_(2) greatly enhance its kinetics of ORR/OER/HER,leading to faster reactions.This study provides profound insights into the specific modification of CoP_(2) by N-doped carbon,enabling the construction of efficient catalysts.

Lattice-distorted Pt wrinkled nanoparticles for highly effective hydrogen electrocatalysis

Modulating Pt surfaces through the introduction of lattice distortion emerges as immensely effective strategy that enhances the kinetics of alkaline hydrogen evolution and oxidation processes.In this study,we fabricated lattice-distorted Pt wrinkled nanoparticles(LD-Pt WNPs)for efficient hydrogen electrocatalysis.The LD-Pt WNPs not only outperform the Pt/C benchmark in hydrogen oxidation reaction,achieving an excellent mass-specific current of 968.5 mA·mg_(Pt)^(-1)(9 times that of Pt/C),but also demonstrate outstanding hydrogen evolution reaction activity with a small overpotential of 58.0 mV.Comprehensive experiments and density functional theory calculations reveal that lattice defects introduce an abundance of unsaturated coordination atoms while modifying the d-band center of Pt.This dual effect optimizes the binding strength of crucial H and OH intermediates,leading to a significant reduction in the energy barrier of the reaction bottleneck,commonly known as the Volmer step.This work unveils a fresh viewpoint on projecting and developing high efficiency electrocatalysts through defect engineering.

Somatostatin-Positive Neurons in the Rostral Zona Incerta Modulate Innate Fear-Induced Defensive Response in Mice

Defensive behaviors induced by innate fear or Pavlovian fear conditioning are crucial for animals to avoid threats and ensure survival.The zona incerta(ZI)has been demonstrated to play important roles in fear learning and fear memory,as well as modulating auditory-induced innate defensive behavior.However,whether the neuronal subtypes in the ZI and specific circuits can mediate the innate fear response is largely unknown.Here,we found that somatostatin(SST)-positive neurons in the rostral ZI of mice were activated by a visual innate fear stimulus.Optogenetic inhibition of SST-positive neurons in the rostral ZI resulted in reduced flight responses to an overhead looming stimulus.Optogenetic activation of SST-positive neurons in the rostral ZI induced fear-like defensive behavior including increased immobility and bradycardia.In addition,we demonstrated that manipulation of the GABAergic projections from SST-positive neurons in the rostral ZI to the downstream nucleus reuniens(Re)mediated fear-like defensive behavior.Retrograde trans-synaptic tracing also revealed looming stimulus-activated neurons in the superior colliculus(SC)that projected to the Re-projecting SST-positive neurons in the rostral ZI(SC-ZIrSST-Re pathway).Together,our study elucidates the function of SST-positive neurons in the rostral ZI and the SC-ZIrSST-Re tri-synaptic circuit in mediating the innate fear response.

Intercalation-Assisted Co-Doped MoS_(2) Nanoflowers for an Efficient Hydrogen Evolution Reaction

2D transition metal disulfides have emerged as promising Pt-alternative electrocatalysts for hydrogen generation.However,the sluggish water dissociation kinetics and limited active sites hinder their performance in alkaline media.Herein,we propose a two-step hydrothermal method to synthesize K intercalation-assisted Codoped MoS_(2) nanoflowers.These nanoflowers exhibit an overpotential of only 67 mV at a current density of 10 mA cm^(-2),which exceeds that of pristine MoS_(2)(143 mV).We demonstrated that the intercalation of K enlarges the interlayer spacing of MoS_(2) nanosheets and facilitates the doping of Co.The incorporation of Co effectively improves the surface charge transfer efficiency of MoS_(2) and accelerates water splitting with an energy barrier of 0.12 eV.This work offers an approach to activate the inert MoS_(2) basal plane by chemical intercalation and atomic doping coengineering.It can be extended to develop other functional materials beyond water splitting.

Phosphorylated TDP-43 Staging of Primary Age-Related Tauopathy

Primary age-related tauopathy(PART) is characterized by tau neurofibrillary tangles(NFTs) in the absence of amyloid plaque pathology. In the present study,we analyzed the distribution patterns of phosphorylated43-kDa TAR DNA-binding protein(pTDP-43) in the brains of patients with PART. Immunohistochemistry and immunofluorescence double-labeling in multiple brain regions was performed on brain tissues from PART,Alzheimer's disease(AD), and aging control cases. We examined the regional distribution patterns of pTDP-43 intraneuronal inclusions in PART with Braak NFT stages[ 0 and B IV, and a Thal phase of 0(no beta-amyloid present). We found four stages which indicated potentially sequential dissemination of pTDP-43 in PART. Stage I was characterized by the presence of pTDP-43 lesions in the amygdala, stage II by such lesions in the hippocampus,stage III by spread of pTDP-43 to the neocortex, and stage IV by pTDP-43 lesions in the putamen, pallidum, and insular cortex. In general, the distribution pattern of pTDP-43 pathology in PART cases was similar to the early TDP-43 stages reported in AD, but tended to be more restricted to the limbic system. However, there were some differences in the distribution patterns of pTDP-43 between PART and AD, especially in the dentate gyrus of the hippocampus. Positive correlations were found in PART between the Braak NFT stage and the pTDP-43 stage and density.

Selective Electrochemical Reduction of Nitrogen to Ammonia by Adjusting the Three-Phase Interface

The electrochemical nitrogen reduction reaction(NRR)provides a sustainable and alternative avenue to the Haber-Bosch process for ammonia(NH_(3))synthesis.Despite the great efforts made on catalysts and electrolytes,unfortunately,current NRR suffers from low selectivity due to the overwhelming competition with the hydrogen evolution reaction(HER).Here,we present an adjusted three-phase interface to enhance nitrogen(N_(2))coverage on a catalyst surface and achieve a record-high Faradic efficiency(FE)up to 97%in aqueous solution.The almost entirely suppressed HER process combined with the enhanced NRR activity,benefiting from the efficient three-interface contact line,is responsible for the excellent selectivity toward NH_(3),as evidenced by the theoretical and experimental results.Our strategy also demonstrates the applicability to other catalysts that feature strong H adsorption ability,to boost the FE for NH_(3) synthesis above 90%and to improve the NRR activity by engineering the catalysts.

Pathological Networks Involving Dysmorphic Neurons in Type ⅡFocal Cortical Dysplasia

Focal cortical dysplasia(FCD)is one of the most common causes of drug-resistant epilepsy.Dysmorphic neurons are the major histopathological feature of typeⅡFCD,but their role in seizure genesis in FCD is unclear.Here we performed whole-cell patch-clamp recording and morphological reconstruction of cortical principal neurons in postsurgical brain tissue from drug-resistant epilepsy patients.Quantitative analyses revealed distinct morphological and electrophysiological characteristics of the upper layer dysmorphic neurons in typeⅡFCD,including an enlarged soma,aberrant dendritic arbors,increased current injection for rheobase action potential firing,and reduced action potential firing frequency.Intriguingly,the upper layer dysmorphic neurons received decreased glutamatergic and increased GABAergic synaptic inputs that were coupled with upregulation of the Na^(+)-K^(+)-Cl^(−)cotransporter.In addition,we found a depolarizing shift of the GABA reversal potential in the CamKⅡ-cre::PTENflox/flox mouse model of drug-resistant epilepsy,suggesting that enhanced GABAergic inputs might depolarize dysmorphic neurons.Thus,imbalance of synaptic excitation and inhibition of dysmorphic neurons may contribute to seizure genesis in typeⅡFCD.

A novel polymer-based nitrocellulose platform for implementing a multiplexed microfluidic paperbased enzyme-linked immunosorbent assay

Nitrocellose(NC)membranes,as porous paper-like substrates with high protein-binding capabilties,are very popular in the field of point-of-care immunoassays.However,generating robust hydrophobic structures in NC membranes to fabricate microfluidic paper-based analytical devices(μPADs)remains a great challenge.At present,the main method relies on an expensive wax printer In addition,NC membranes very easy to adhere during the printing process due to electrostatic adsorption.Herein,we developed a facile,fast and low-cost strategy to fabricateμPADs in NC membranes by screen-printing polyurethane acrylate(PUA)as a barrier material for defning flow channels and reaction zones.Moreover,hydrophobic barriers based on UV-curable PUA can resist various surfactant solutions and organic solvents that are generally used in immunoassays and biochemical reactions.To validate the feasibility of this PUA-based NC membrane for immunoassays in point-of-care testing(POCT),we further designed and assembled a rotational paperbased analytical device for implementing a multiplexed enzyme-linked immunosorbent assay(ELISA)in a simple manner.Using the proposed device under the optimal conditions,alpha fetoprotein(AFP)and carcinoembryonic antigen(CEA)could be identified,with limits of detection of 136 pg/mL and 174 pg/mL,respectively,which are below the threshold values of these two cancer biomarkers for clinical diagnosis.We believe that this reliable device provides a promising plaform for the diagnosis of disease based on ELISA or other related bioassays in limited setings or remote regions.

Visualizing temperature-dependent phase stability in high

High entropy alloys(HEAs)contain near equimolar amounts of five or more elements and are a compelling space for materials design.In the design of HEAs,great emphasis is placed on identifying thermodynamic conditions for single-phase and multi-phase stability regions,but this process is hindered by the difficulty of navigating stability relationships in high-component spaces.Traditional phase diagrams use barycentric coordinates to represent composition axes,which require(N–1)spatial dimensions to represent an N-component system,meaning that HEA systems with N>4 components cannot be readily visualized.Here,we propose forgoing barycentric composition axes in favor of two energy axes:a formation-energy axis and a‘reaction energy’axis.These Inverse Hull Webs offer an information-dense 2D representation that successfully captures complex phase stability relationships in N≥5 component systems.We use our proposed diagrams to visualize the transition of HEA solid-solutions from high-temperature stability to metastability upon quenching,and identify important thermodynamic features that are correlated with the persistence or decomposition of metastable HEAs.