Mitophagy in intracerebral hemorrhage:a new target for therapeutic intervention

Intracerebral hemorrhage is a life-threatening condition with a high fatality rate and severe sequelae.However,there is currently no treatment available for intracerebral hemorrhage,unlike for other stroke subtypes.Recent studies have indicated that mitochondrial dysfunction and mitophagy likely relate to the pathophysiology of intracerebral hemorrhage.Mitophagy,or selective autophagy of mitochondria,is an essential pathway to preserve mitochondrial homeostasis by clearing up damaged mitochondria.Mitophagy markedly contributes to the reduction of secondary brain injury caused by mitochondrial dysfunction after intracerebral hemorrhage.This review provides an overview of the mitochondrial dysfunction that occurs after intracerebral hemorrhage and the underlying mechanisms regarding how mitophagy regulates it,and discusses the new direction of therapeutic strategies targeting mitophagy for intracerebral hemorrhage,aiming to determine the close connection between mitophagy and intracerebral hemorrhage and identify new therapies to modulate mitophagy after intracerebral hemorrhage.In conclusion,although only a small number of drugs modulating mitophagy in intracerebral hemorrhage have been found thus far,most of which are in the preclinical stage and require further investigation,mitophagy is still a very valid and promising therapeutic target for intracerebral hemorrhage in the long run.

The role of snapin in regulation of brain homeostasis

Brain homeostasis refe rs to the normal working state of the brain in a certain period,which is impo rtant for overall health and normal life activities.Currently,there is a lack of effective treatment methods for the adverse consequences caused by brain homeostasis imbalance.Snapin is a protein that assists in the formation of neuronal synapses and plays a crucial role in the normal growth and development of synapses.Recently,many researchers have reported the association between snapin and neurologic and psychiatric disorders,demonstrating that snapin can improve brain homeostasis.Clinical manifestations of brain disease often involve imbalances in brain homeostasis and may lead to neurological and behavioral sequelae.This article aims to explo re the role of snapin in restoring brain homeostasis after injury or diseases,highlighting its significance in maintaining brain homeostasis and treating brain diseases.Additionally,it comprehensively discusses the implications of snapin in other extracerebral diseases such as diabetes and viral infections,with the objective of determining the clinical potential of snapin in maintaining brain homeostasis.

Fine-tuning the activation behaviors of ternary modular cabazitaxel prodrugs for efficient and on-target oral anti-cancer therapy

The disulfide bond plays a crucial role in the design of anti-tumor prodrugs due to its exceptional tumor-specific redox responsiveness. However, premature breaking of disulfide bonds is triggered by small amounts of reducing substances (e.g., ascorbic acid, glutathione, uric acid and tea polyphenols) in the systemic circulation. This may lead to toxicity, particularly in oral prodrugs that require more frequent and high-dose treatments. Fine-tuning the activation kinetics of these prodrugs is a promising prospect for more efficient on-target cancer therapies. In this study, disulfide, steric disulfide, and ester bonds were used to bridge cabazitaxel (CTX) to an intestinal lymph vessel-directed triglyceride (TG) module. Then, synthetic prodrugs were efficiently incorporated into self-nanoemulsifying drug delivery system (corn oil and Maisine CC were used as the oil phase and Cremophor EL as the surfactant). All three prodrugs had excellent gastric stability and intestinal permeability. The oral bioavailability of the disulfide bond-based prodrugs (CTX-(C)S-(C)S-TG and CTX-S-S-TG) was 11.5- and 19.1-fold higher than that of the CTX solution, respectively, demonstrating good oral delivery efficiency. However, the excessive reduction sensitivity of the disulfide bond resulted in lower plasma stability and safety of CTX-S-S-TG than that of CTX-(C)S-(C)S-TG. Moreover, introducing steric hindrance into disulfide bonds could also modulate drug release and cytotoxicity, significantly improving the anti-tumor activity even compared to that of intravenous CTX solution at half dosage while minimizing off-target adverse effects. Our findings provide insights into the design and fine-tuning of different disulfide bond-based linkers, which may help identify oral prodrugs with more potent therapeutic efficacy and safety for cancer therapy.

Bioinspired fish-scale-like magnesium composites strengthened by contextures of continuous titanium fibers:Lessons from nature

Natural fish scales demonstrate outstanding mechanical efficiency owing to their elaborate architectures and thereby may serve as ideal prototypes for the architectural design of man-made materials.Here bioinspired magnesium composites with fish-scale-like orthogonal plywood and double-Bouligand architectures were developed by pressureless infiltration of a magnesium melt into the woven contextures of continuous titanium fibers.The composites exhibit enhanced strength and work-hardening ability compared to those estimated from a simple mixture of their constituents at ambient to elevated temperatures.In particular,the double-Bouligand architecture can effectively deflect cracking paths,alleviate strain localization,and adaptively reorient titanium fibers within the magnesium matrix during the deformation of the composite,representing a successful implementation of the property-optimizing mechanisms in fish scales.The strength of the composites,specifically the effect of their bioinspired architectures,was interpreted based on the adaptation of classical laminate theory.This study may offer a feasible approach for developing new bioinspired metal-matrix composites with improved performance and provide theoretical guidance for their architectural designs.

Residual Feature Attentional Fusion Network for Lightweight Chest CT Image Super-Resolution

The diagnosis of COVID-19 requires chest computed tomography(CT).High-resolution CT images can provide more diagnostic information to help doctors better diagnose the disease,so it is of clinical importance to study super-resolution(SR)algorithms applied to CT images to improve the reso-lution of CT images.However,most of the existing SR algorithms are studied based on natural images,which are not suitable for medical images;and most of these algorithms improve the reconstruction quality by increasing the network depth,which is not suitable for machines with limited resources.To alleviate these issues,we propose a residual feature attentional fusion network for lightweight chest CT image super-resolution(RFAFN).Specifically,we design a contextual feature extraction block(CFEB)that can extract CT image features more efficiently and accurately than ordinary residual blocks.In addition,we propose a feature-weighted cascading strategy(FWCS)based on attentional feature fusion blocks(AFFB)to utilize the high-frequency detail information extracted by CFEB as much as possible via selectively fusing adjacent level feature information.Finally,we suggest a global hierarchical feature fusion strategy(GHFFS),which can utilize the hierarchical features more effectively than dense concatenation by progressively aggregating the feature information at various levels.Numerous experiments show that our method performs better than most of the state-of-the-art(SOTA)methods on the COVID-19 chest CT dataset.In detail,the peak signal-to-noise ratio(PSNR)is 0.11 dB and 0.47 dB higher on CTtest1 and CTtest2 at×3 SR compared to the suboptimal method,but the number of parameters and multi-adds are reduced by 22K and 0.43G,respectively.Our method can better recover chest CT image quality with fewer computational resources and effectively assist in COVID-19.

Engineering the morphology and electronic structure of atomic cobalt-nitrogen-carbon catalyst with highly accessible active sites for enhanced oxygen reduction

The stabilization of non-precious metals as isolated active sites with high loading density over nitrogendoped carbon materials is essential for realizing the industrial application of single atom catalysts.However,achieving high loading of single cobalt active sites with greatly enhanced oxygen reduction reaction(ORR)activity and stability remains challenging.Here,an efficient approach was described to create a single atom cobalt electrocatalyst(Co SAs/NC)which possesses enhanced mesoporosity and specific surface area that greatly favor the mass transportation and exposure of accessible active sites.The electronic structure of the catalyst by the strong metal-support interaction has been elucidated through experimental characterizations and theoretical calculations.Due to dramatically enhanced mass transport and electron transfer endowed by morphology and electronic structure engineering,Co SAs/NC exhibits remarkable ORR performance with excellent activity(onset and half-wave potentials of 1.04 V(RHE)and 0.90 V(RHE),Tafel slope of 69.8 mV dec^(-1)and J_(k) of 18.8 mA cm^(-2)at 0.85 V)and stability(7 mV activity decay after 10,000 cycles).In additio n,the catalyst demonstrates great promise as an alternative to traditional Pt/C catalyst in zinc-air batteries while maintaining high performance in terms of high specific capacity of(796.1 mAh/g_(Zn)),power density(175.4 mW/cm^(2)),and long-term cycling stability(140 h).This study presents a facile approach to design SACs with highly accessible active sites for electrochemical transformations.

Silicon micropillar electrodes of lithiumion batteries used for characterizing electrolyte additives

The 100 crystal-oriented silicon micropillar array platforms were prepared by microfabrication processes for the purpose of electrolyte additive identification. The silicon micropillar array platform was used for the study of fluorinated vinyl carbonate(FEC), vinyl ethylene carbonate(VEC), ethylene sulfite(ES), and vinyl carbonate(VC) electrolyte additives in the LiPF_6 dissolved in a mixture of ethylene carbonate and diethyl carbonate electrolyte system using charge/discharge cycles, electrochemical impedance spectroscopy, cyclic voltammetry, scanning electron microscopy, and x-ray photoelectron spectroscopy. The results show that the silicon pillar morphology displays cross-shaped expansion after lithiation/delithiation, the inorganic lithium salt keeps the silicon pillar morphology intact, and the organic lithium salt content promotes a rougher silicon pillar surface. The presence of poly-(VC) components on the surface of FEC and VC electrodes allows the silicon pillar to accommodate greater volume expansion while remaining intact. This work provides a standard, fast, and effective test method for the performance analysis of electrolyte additives and provides guidance for the development of new electrolyte additives.

Acoustic Emission Recognition Based on a Two-Streams Convolutional Neural Network

The Convolutional Neural Network(CNN)is a widely used deep neural network.Compared with the shallow neural network,the CNN network has better performance and faster computing in some image recognition tasks.It can effectively avoid the problem that network training falls into local extremes.At present,CNN has been applied in many different fields,including fault diagnosis,and it has improved the level and efficiency of fault diagnosis.In this paper,a two-streams convolutional neural network(TCNN)model is proposed.Based on the short-time Fourier transform(STFT)spectral and Mel Frequency Cepstrum Coefficient(MFCC)input characteristics of two-streams acoustic emission(AE)signals,an AE signal processing and classification system is constructed and compared with the traditional recognition methods of AE signals and traditional CNN networks.The experimental results illustrate the effectiveness of the proposed model.Compared with single-stream convolutional neural network and a simple Long Short-Term Memory(LSTM)network,the performance of TCNN which combines spatial and temporal features is greatly improved,and the accuracy rate can reach 100%on the current database,which is 12%higher than that of single-stream neural network.

Frontiers of collaborative intelligence systems

The development of information technology has propelled technological reform in artificial intelligence(AI).To address the needs of diversified and complex applications,AI has been increasingly trending towards intelligent,collaborative,and systematized development across different levels and tasks.Research on intelligent,collaborative and systematized AI can be divided into three levels:micro,meso,and macro.Firstly,the micro-level collaboration is illustrated through the introduction of swarm intelligence collaborative methods related to individuals collaboration and decision variables collaboration.Secondly,the meso-level collaboration is discussed in terms of multi-task collaboration and multi-party collaboration.Thirdly,the macro-level collaboration is primarily in the context of intelligent collaborative systems,such as terrestrial-satellite collaboration,space-air-ground collaboration,space-air-ground-air collaboration,vehicle-road-cloud collaboration and end-edge-cloud collaboration.Finally,this paper provides prospects on the future development of relevant fields from the perspectives of the micro,meso,and macro levels.

Corrigendum to“Bi-continuous Mg-Ti interpenetrating-phase composite as a partially degradable and bioactive implant material”[Journal of Materials Science&Technology 146(2023)211-220]

The authors are very sorry for their carelessness that there are some problems with Fig.3 in the original manuscript.

G protein-coupled receptors(GPCRs):advances in structures,mechanisms,and drug discovery

G protein-coupled receptors(GPCRs),the largest family of human membrane proteins and an important class of drug targets,play a role in maintaining numerous physiological processes.Agonist or antagonist,orthosteric effects or allosteric effects,and biased signaling or balanced signaling,characterize the complexity of GPCR dynamic features.In this study,we first review the structural advancements,activation mechanisms,and functional diversity of GPCRs.We then focus on GPCR drug discovery by revealing the detailed drug-target interactions and the underlying mechanisms of orthosteric drugs approved by the US Food and Drug Administration in the past five years.Particularly,an up-to-date analysis is performed on available GPCR structures complexed with synthetic small-molecule allosteric modulators to elucidate key receptor-ligand interactions and allosteric mechanisms.Finally,we highlight how the widespread GPCR-druggable allosteric sites can guide structure-or mechanism-based drug design and propose prospects of designing bitopic ligands for the future therapeutic potential of targeting this receptor family.

Bi-continuous Mg-Ti interpenetrating-phase composite as a partially degradable and bioactive implant material

Mg(and Mg alloys)and Ti(and Ti alloys)are two important classes of metallic implant materials which are respectively completely degradable and non-degradable after implantation.Making composites composed of them offers the promise for combining their property advantages for bone repair.Here,we present a Mg-Ti composite fabricated by pressureless infiltration of pure Mg melt into 3D printed Ti scaffold,and demonstrate a potential of the composite for use as new partially degradable and bioactive implant materials.The composite has such architecture that the Mg and Ti phases are topologically bicontinuous and mutually interspersed in 3D space,and exhibits several advantages over its constituents,such as higher strengths than as-cast pure Mg and Ti scaffold along with lower Young’s modulus than dense Ti.Additionally,the degradation of Mg phase may induce the formation and ingrowth of new bone tissues into the Ti scaffold to form mechanical interlocking between them;in this process,the Ti scaffold provides constant support and Young’s modulus adaptively decreases toward that of bone.Despite the accelerated corrosion than pure Mg,the composite remains non-cytotoxic and does not cause obvious adverse reactions after implantation as revealed by in vitro and in vivo experiments.This study may offer a new possibility for combining mechanical durability and bioactivity in implant materials,and allow for customized and targeted design of the implant.

Disulfiram enhances the antitumor activity of cisplatin by inhibiting the Fanconi anemia repair pathway

A series of chemotherapeutic drugs that induce DNA damage,such as cisplatin(DDP),are standard clinical treatments for ovarian cancer,testicular cancer,and other diseases that lack effective targeted drug therapy.Drug resistance is one of the main factors limiting their application.Sensitizers can overcome the drug resistance of tumor cells,thereby enhancing the antitumor activity of chemotherapeutic drugs.In this study,we aimed to identify marketable drugs that could be potential chemotherapy sensitizers and explore the underlying mechanisms.We found that the alcohol withdrawal drug disulfiram(DSF)could significantly enhance the antitumor activity of DDP.JC-1 staining,propidium iodide(PI)staining,and western blotting confirmed that the combination of DSF and DDP could enhance the apoptosis of tumor cells.Subsequent RNA sequencing combined with Gene Set Enrichment Analysis(GSEA)pathway enrichment analysis and cell biology studies such as immunofluorescence suggested an underlying mechanism:DSF makes cells more vulnerable to DNA damage by inhibiting the Fanconi anemia(FA)repair pathway,exerting a sensitizing effect to DNA damaging agents including platinum chemotherapy drugs.Thus,our study illustrated the potential mechanism of action of DSF in enhancing the antitumor effect of DDP.This might provide an effective and safe solution for combating DDP resistance in clinical treatment.

Erratum to:Boosting SN38-based oral chemotherapy to combine reduction-bioactivated structured lipid-mimetic prodrug with ascorbic acid

Erratum to Nano Research 2022,15(10):9092-9104 https://doi.org/10.1007/s12274-022-4544-7 Figure 9 was unfortunately mistakenly typeset.This error did not affect any of the conclusions from the published paper.

Development mechanism of internal local corrosion of X80 pipeline steel

The occurrence and development mechanism of internal local corrosion has always been a controversial topic,and especially under flow conditions.In this paper,an improved high shear force loop was experimentally used,and local flow field is induced by simulating corrosion defects on the surface of X80 pipeline steel specimens.The characteristics of corrosion products deposited on the surface of specimens in CO2-saturated NACE solution were investigated by means of electrochemical impedance spectroscopy(EIS),scanning electron microscopy(SEM),X-ray diffraction(XRD),and energy dispersive spectrometry(EDS).The 3D micromorphology of the corrosion test surface after remove the corrosion scale used to measure the size of localized corrosion pit.Under the influence of local defects,the wall shear stress(WSS)and turbulent kinetic energy of local flow fields enhanced significantly,and pressure fluctuations in local flow field were induced.The results showed that the characteristics of surface corrosion products varied with flow velocity.The corrosion scales formed in various regions of specimens with defects exhibited different surface micro-morphologies and chemical compositions.Overall,these data offer new perspectives for better understanding the mechanisms behind local corrosion.

Rational design of palladium single-atoms and clusters supported on silicoaluminophosphate-31 by a photochemical route for chemoselective hydrodeoxygenation of vanillin

Chemoselective hydrodeoxygenation of vanillin is of great importance in converting biomass into high value-added chemicals.Herein,we describe a facile photochemical route to access palladium single atoms and clusters supported on silicoaluminophosphate-31(SAPO-31)as a highly active,chemoselective,and reusable catalyst for hydrodeoxygenation of vanillin.Characterizations by aberration-corrected high-angle annular dark-field scanning transmission electron microscopy,extended X-ray absorption fine structure measurement,and CO-absorbed diffuse reflectance infrared Fourier transform spectroscopy reveal the atomically dispersed palladium single atoms and clusters are loosely bonded and randomly dispersed,without forming strong palladium-palladium metallic bonding,over the SAPO-31 support.This catalyst,with a full metal availability to the reactants,exhibits exceptional catalytic activity(TOF:3,000 h^(−1),Yield:>99%)in the hydrodeoxygenation of vanillin toward 2-methoxy-4-methylphenol(MMP)under mild conditions(1 atm,80°C,30 min),along with excellent stability,scalability(up to 100-fold),and wide substrate scope.The superior catalytic performance can be attributed to the synergistic effect of the positively charged palladium single atoms and fully exposed clusters,as well as the strong metal-support interactions.This work may offer a new avenue for the design and synthesis of fully exposed metal catalysts with targeted functionalities.

Bioinspired tungsten-copper composites with Bouligand-type architectures mimicking fish scales

The microscopic Bouligand-type architectures of fish scales demonstrate a notable efficiency in enhancing the damage tolerance of materials;nevertheless,it is challenging to reproduce in metals.Here bioinspired tungsten-copper composites with different Bouligand-type architectures mimicking fish scales were fabricated by infiltrating a copper melt into woven contextures of tungsten fibers.These composites exhibit a synergetic enhancement in both strength and ductility at room temperature along with an improved resistance to high-temperature oxidization.The strengths were interpreted by adapting the classical laminate theory to incorporate the characteristics of Bouligand-type architectures.In particular,under load the tungsten fibers can reorient adaptively within the copper matrix by their straightening,stretching,interfacial sliding with the matrix,and the cooperative kinking deformation of fiber grids,representing a successful implementation of the optimizing mechanisms of the Bouligand-type architectures to enhance strength and toughness.This study may serve to promote the development of new high-performance tungsten-copper composites for applications,e.g.,as electrical contacts or heat sinks,and offer a viable approach for constructing bioinspired architectures in metallic materials.

Single palladium atoms stabilized byβ-FeOOH nanorod with superior performance for selective hydrogenation of cinnamaldehyde

Atomically dispersed single atom catalysts represent an ideal means of converting less valuable organics into value-added chemicals of interest with high efficiency.Herein,we describe a facile synthetic approach to create defect-containingβ-FeOOH doped with isolated palladium atoms that bond covalently to the nearby oxygen and iron atoms.The presence of singly dispersed palladium atoms is confirmed by spherical aberration correction electron microscopy and extended X-ray absorption fine structure measurements.This single palladium atom catalyst manifests outstanding catalytic efficiency(conversion:99%;selectivity 99%;turnover frequency:2,440 h^(-1))in the selective hydrogenation of cinnamaldehyde to afford hydrocinnamaldehyde.Experimental measurements and density functional theory(DFT)calculations elucidate the high catalytic activity and the strong metal-support interaction stem from the unique coordination environment of the isolated palladium atoms.These findings may pave the way for the facile construction of single atom catalysts in a defect-mediated strategy for efficient organic transformations in heterogeneous catalysis.

Continuous ice-templating of macro-porous materials with uniformly ordered architecture

Ice-templating technique offers a viable means for constructing ordered macro-porous architectures in materials;nevertheless,it is generally limited by a low efficiency for fabrication,large difficulty for manipulation,along with the small dimension,and poor structural uniformity of icetemplated materials.Here,a new approach was exploited for continuous ice-templating of uniformly ordered macro-porous materials based on the establishment of a large,stable temperature gradient with specific bi-directional designs at the freezing front by descending the front toward the cooling medium to accommodate its upward growth.The freezing rate was markedly increased with the dimension of frozen body notably enlarged as compared with the case for conventional static ice-templating technique.The macro-porous architecture of materials,taking zirconia ceramics as an example,was made much finer and more uniform over the entire sample,and exhibited better ordering of alignment and enhanced inter-connectivity between lamellae.This led to an improvement in the compressive strength and its stability along the height direction for ice-templated materials than those made by the static ice-templating technique at a similar porosity.This study may facilitate the scale up of ice-templating techniques and promote the exploitation and application of new high-performance materials.

Boosting SN38-based oral chemotherapy to combine reductionbioactivated structured lipid-mimetic prodrug with ascorbic acid

The reduction-responsive disulfide bonds have been widely used as bioactive linkages to facilitate a rapid release of anticancer drugs into tumor cells.However,the activation can be hindered by the kinetics of the thiol-disulfide exchange reactions.Supplementing with an additional reductant is a promising strategy to further boost drug release.Herein,inspired by the specific absorption mechanism of triglyceride fat,structured lipid-mimetic oral prodrugs of 7-ethyl-10-hydroxycamptothecin(SN38)were designed to improve intestinal permeability and bypass the first-pass effect.SN38 prodrugs were prepared into lipid formulations that could self-emulsify into nano-sized particles after entering the gastrointestinal tract.Surprisingly,we found that the oral bioavailability of the prodrug lipid formulation could be up to 2.69-fold higher than that of the parent SN38,indicating an effective oral delivery.In addition,the reduction-responsive disulfide bond was used as a linker,and ascorbic acid(ASC)was coadministrated to further promote the efficient release of SN38 from the prodrug.ASC enhanced the oral antitumor effect of the reduction-responsive oral prodrug and exhibited good safety.In summary,the combination of a structured lipid-mimetic prodrug and ASC was firstly demonstrated to boost the oral chemotherapy effect of the difficult-for-oral chemotherapeutics.