Dysfunction of synaptic endocytic trafficking in Parkinson's disease

Parkinson's disease is characterized by the selective degeneration of dopamine neurons in the nigrostriatal pathway and dopamine deficiency in the striatum.The precise reasons behind the specific degeneration of these dopamine neurons remain largely elusive.Genetic investigations have identified over 20 causative PARK genes and 90 genomic risk loci associated with both familial and sporadic Parkinson's disease.Notably,several of these genes are linked to the synaptic vesicle recycling process,particularly the clathrinmediated endocytosis pathway.This suggests that impaired synaptic vesicle recycling might represent an early feature of Parkinson's disease,followed by axonal degeneration and the eventual loss of dopamine cell bodies in the midbrain via a"dying back"mechanism.Recently,several new animal and cellular models with Parkinson's disease-linked mutations affecting the endocytic pathway have been created and extensively characterized.These models faithfully recapitulate certain Parkinson's disease-like features at the animal,circuit,and cellular levels,and exhibit defects in synaptic membrane trafficking,further supporting the findings from human genetics and clinical studies.In this review,we will first summarize the cellular and molecular findings from the models of two Parkinson's disease-linked clathrin uncoating proteins:auxilin(DNAJC6/PARK19)and synaptojanin 1(SYNJ1/PARK20).The mouse models carrying these two PARK gene mutations phenocopy each other with specific dopamine terminal pathology and display a potent synergistic effect.Subsequently,we will delve into the involvement of several clathrin-mediated endocytosis-related proteins(GAK,endophilin A1,SAC2/INPP5 F,synaptotagmin-11),identified as Parkinson's disease risk factors through genome-wide association studies,in Parkinson's disease pathogenesis.We will also explore the direct or indirect roles of some common Parkinson's disease-linked proteins(alpha-synuclein(PARK1/4),Parkin(PARK2),and LRRK2(PARK8))in synaptic endocytic trafficking.Additionally,we will discuss the emerging novel functions of these endocytic proteins in downstream membrane traffic pathways,particularly autophagy.Given that synaptic dysfunction is considered as an early event in Parkinson's disease,a deeper understanding of the cellular mechanisms underlying synaptic vesicle endocytic trafficking may unveil novel to rgets for early diagnosis and the development of interventional therapies for Parkinson's disease.Future research should aim to elucidate why generalized synaptic endocytic dysfunction leads to the selective degeneration of nigrostriatal dopamine neurons in Parkinson's disease.

Challenges and Opportunities in Preserving Key Structural Features of 3D-Printed Metal/Covalent Organic Framework

Metal-organic framework(MOF)and covalent organic framework(COF)are a huge group of advanced porous materials exhibiting attractive and tunable microstructural features,such as large surface area,tunable pore size,and functional surfaces,which have significant values in various application areas.The emerging 3D printing technology further provides MOF and COFs(M/COFs)with higher designability of their macrostructure and demonstrates large achievements in their performance by shaping them into advanced 3D monoliths.However,the currently available 3D printing M/COFs strategy faces a major challenge of severe destruction of M/COFs’microstructural features,both during and after 3D printing.It is envisioned that preserving the microstructure of M/COFs in the 3D-printed monolith will bring a great improvement to the related applications.In this overview,the 3D-printed M/COFs are categorized into M/COF-mixed monoliths and M/COF-covered monoliths.Their differences in the properties,applications,and current research states are discussed.The up-to-date advancements in paste/scaffold composition and printing/covering methods to preserve the superior M/COF microstructure during 3D printing are further discussed for the two types of 3D-printed M/COF.Throughout the analysis of the current states of 3D-printed M/COFs,the expected future research direction to achieve a highly preserved microstructure in the 3D monolith is proposed.

Mg/MgO interfaces as efficient hydrogen evolution cathodes causing accelerated corrosion of additive manufactured Mg alloys:A DFT analysis

The corrosion rates of additive-manufactured Mg alloys are higher than their as-cast counterparts,possibly due to increased kinetics for the hydrogen evolution reaction on secondary phases,which may include oxide inclusions.Scanning Kelvin Probe Force Microscopy demonstrated that MgO inclusions could act as cathodes for Mg corrosion,but their low conductivity likely precludes this.However,the density of state calculations through density functional theory using hybrid HSE06 functional revealed overlapping electronic states at the Mg/MgO interface,which facilitates electron transfers and participates in redox reactions.Subsequent determination of the hydrogen absorption energy at the Mg/MgO interface reveals it to be an excellent catalytic site,with HER being found to be a factor of 23x more efficient at the interface than on metallic Mg.The results not only support the plausibility of the Mg/MgO interface being an effective cathode to the adjacent anodic Mg matrix during corrosion but also contribute to the understanding of the enhanced cathodic activities observed during the anodic dissolution of magnesium.

Research progress of ferroptosis regulating lipid peroxidation and metabolism in occurrence and development of primary liver cancer

As a highly aggressive tumor,the pathophysiological mechanism of primary liver cancer has attracted much attention.In recent years,factors such as ferroptosis regulation,lipid peroxidation and metabolic abnormalities have emerged in the study of liver cancer,providing a new perspective for understanding the development of liver cancer.Ferroptosis regulation,lipid peroxidation and metabolic abnormalities play important roles in the occurrence and development of liver cancer.The regulation of ferroptosis is involved in apoptosis and necrosis,affecting cell survival and death.Lipid peroxidation promotes oxidative damage and promotes the invasion of liver cancer cells.Metabolic abnormalities,especially the disorders of glucose and lipid metabolism,directly affect the proliferation and growth of liver cancer cells.Studies of ferroptosis regulation and lipid peroxidation may help to discover new therapeutic targets and improve therapeutic outcomes.The understanding of metabolic abnormalities can provide new ideas for the prevention of liver cancer,and reduce the risk of disease by adjusting the metabolic process.This review focuses on the key roles of ferroptosis regulation,lipid peroxidation and metabolic abnormalities in this process.

Modelling smear effect of vertical drains using a diameter reduction method

Vertical drains are used to accelerate consolidation of clays in ground improvement projects.Smear zones exist around these drains,where permeability is reduced due to soil disturbance caused by the installation process.Hansbo solution is widely used in practice to consider the effects of drain discharge capacity and smear on the consolidation process.In this study,a computationally efficient diameter reduction method(DRM)obtained from the Hansbo solution is proposed to consider the smear effect without the need to model the smear zone physically.Validated by analytical and numerical results,a diameter reduction factor is analytically derived to reduce the diameter of the drain,while achieving similar solutions of pore pressure dissipation profile as the classical full model of the smear zone and drain.With the DRM,the excess pore pressure u obtained from the reduced drain in the original un-disturbed soil zone is accurate enough for practical applications in numerical models.Such performance of DRM is independent of soil material property.Results also show equally accurate performance of DRM under conditions of multi-layered soils and coupled radial-vertical groundwater flow.

Armoring lithium metal anode with soft–rigid gradient interphase toward high-capacity and long-life all-solid-state battery

Solid polymer electrolytes(SPEs)are highly promising for realizing high-capacity,low-cost,and safe Li metal batteries.However,the Li dendritic growth and side reactions between Li and SPEs also plague these systems.Herein,a fluorinated lithium salt coating(FC)with organic-inorganic gradient and soft–rigid feature is introduced on Li surface as an artificial protective layer by the in-situ reaction between Li metal and fluorinated carboxylic acid.The FC layer can improve the interface stability and wettability between Li and SPEs,assist the transport of Li ions,and guide Li nucleation,contributing to a dendrite-free Li deposition and long-lifespan Li metal batteries.The symmetric cell with FC-Li anodes exhibits a high areal capacity of 1 mAh cm^(-2)at 0.5 mA cm^(-2),and an ultra-long lifespan of 2000 h at a current density of 0.1 mA cm^(-2).Moreover,the full cell paired with the LiFePO4 cathode exhibits improved cycling stability,remaining 83.7%capacity after 500 cycles at 1 C.When matching with the S cathode,the FC layer can prevent the shuttle effect,contributing to stable and high-capacity Li–S battery.This work provided a promising way for the construction of stable all-solid-state lithium metal batteries with prolonged lifespan.

Efficacy, patterns of use and cost of Pertuzumab in the treatment of HER2+ metastatic breast cancer in Singapore: The National Cancer Centre Singapore experience

BACKGROUND Pertuzumab is a humanized anti-human epidermal growth factor receptor 2(HER2)monoclonal antibody found in a Phase III clinical trial to significantly improve median survival in HER2 positive metastatic breast cancer(MBC)when used in combination with a taxane and Trastuzumab,and its clinical efficacy has transformed the therapeutic landscape of HER2-positive breast cancer.There are currently few reports on the pattern of use and value of Pertuzumab in real world settings.Our study describes the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC treated in a tertiary cancer centre in Singapore in a predominantly Asian population.AIM To investigate the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC in an Asian population in Singapore.METHODS A retrospective study of 304 HER2-positive MBC patients seen at National Cancer Centre Singapore between 2011-2017 was conducted.Demographic and clinical data were extracted from electronic medical records.Clinical characteristics and billing data of patients who received Pertuzumab were compared with those who did not.RESULTS Thirty-one(62.0%)of the fifty(16.4%)patients who received Pertuzumab as firstline therapy.With a median follow-up of 21.5 mo,there was a statistically significant difference in the median overall survival between Pertuzumab and non-Pertuzumab groups[51.5(95%CI:35.8–60.0)vs 32.9(95%CI:28.1–37.5)mo;P=0.0128].Two(4.88%)patients in the Pertuzumab group experienced grade 3(G3)cardiotoxicity.The median treatment cost incurred for total chemotherapy for the Pertuzumab group was 130456 Singapore Dollars compared to 34523 Singapore Dollars for the non-Pertuzumab group.The median percentage of total chemotherapy costs per patient in the Pertuzumab group spent on Pertuzumab was 50.3%.CONCLUSION This study shows that Pertuzumab use in the treatment of metastatic breast cancer is associated with a significantly better survival and a low incidence of serious cardiotoxicity.However,the proportionate cost of Pertuzumab therapy remains high and further cost-effectiveness studies should be conducted.

Recent advances in fabrication and functions of neuromorphic system based on organic field effect transistor

The development of various artificial electronics and machines would explosively increase the amount of information and data,which need to be processed via in-situ remediation.Bioinspired synapse devices can store and process signals in a parallel way,thus improving fault tolerance and decreasing the power consumption of artificial systems.The organic field effect transistor(OFET)is a promising component for bioinspired neuromorphic systems because it is suitable for large-scale integrated circuits and flexible devices.In this review,the organic semiconductor materials,structures and fabrication,and different artificial sensory perception systems functions based on neuromorphic OFET devices are summarized.Subsequently,a summary and challenges of neuromorphic OFET devices are provided.This review presents a detailed introduction to the recent progress of neuromorphic OFET devices from semiconductor materials to perception systems,which would serve as a reference for the development of neuromorphic systems in future bioinspired electronics.

Comprehensive Survey of the Landscape of Digital Twin Technologies and Their Diverse Applications

The concept of the digital twin,also known colloquially as the DT,is a fundamental principle within Industry 4.0 framework.In recent years,the concept of digital siblings has generated considerable academic and practical interest.However,academia and industry have used a variety of interpretations,and the scientific literature lacks a unified and consistent definition of this term.The purpose of this study is to systematically examine the definitional landscape of the digital twin concept as outlined in scholarly literature,beginning with its origins in the aerospace domain and extending to its contemporary interpretations in the manufacturing industry.Notably,this investigationwill focus on the research conducted on Industry 4.0 and smartmanufacturing,elucidating the diverse applications of digital twins in fields including aerospace,intelligentmanufacturing,intelligent transportation,and intelligent cities,among others.

Dual-channel redox reactions for photocatalytic H_(2)-evolution coupled with photoreforming oxidation of waste materials

Dual-channel redox reaction system is advantageous for photocatalytic hydrogen(H_(2))production when coupled with photoreforming oxidation of waste materials,benefiting both thermodynamically and kinetically.However,existing reviews primarily focus on specific oxidation reactions,such as oxidative organic synthesis and water remediation,often neglecting recent advancements in plastic upgrading,biomass conversion,and H_(2)O_(2)production,and failing to provide an in-depth discussion of catalytic mechanisms.This review addresses these gaps by offering a comprehensive overview of recent advancements in dual-channel redox reactions for photocatalytic H_(2)-evolution and waste photoreforming.It highlights waste-to-wealth design concepts,examines the challenges,advantages and diverse applications of dual-channel photocatalytic reactions,including photoreforming of biomass,alcohol,amine,plastic waste,organic pollutants,and H_(2)O_(2)production.Emphasizing improvement strategies and exploration of catalytic mechanisms,it includes advanced in-situ characterization,spin capture experiments,and DFT calculations.By identifying challenges and future directions in this field,this review provides valuable insights for designing innovative dual-channel photocatalytic systems.

Spatiotemporal characteristics and driving mechanisms of land use/land cover(LULC)changes in the Jinghe River Basin,China

Understanding the trajectories and driving mechanisms behind land use/land cover(LULC)changes is essential for effective watershed planning and management.This study quantified the net change,exchange,total change,and transfer rate of LULC in the Jinghe River Basin(JRB),China using LULC data from 2000 to 2020.Through trajectory analysis,knowledge maps,chord diagrams,and standard deviation ellipse method,we examined the spatiotemporal characteristics of LULC changes.We further established an index system encompassing natural factors(digital elevation model(DEM),slope,aspect,and curvature),socio-economic factors(gross domestic product(GDP)and population),and accessibility factors(distance from railways,distance from highways,distance from water,and distance from residents)to investigate the driving mechanisms of LULC changes using factor detector and interaction detector in the geographical detector(Geodetector).The key findings indicate that from 2000 to 2020,the JRB experienced significant LULC changes,particularly for farmland,forest,and grassland.During the study period,LULC change trajectories were categorized into stable,early-stage,late-stage,repeated,and continuous change types.Besides the stable change type,the late-stage change type predominated the LULC change trajectories,comprising 83.31% of the total change area.The period 2010-2020 witnessed more active LULC changes compared to the period 2000-2010.The LULC changes exhibited a discrete spatial expansion trend during 2000-2020,predominantly extending from southeast to northwest of the JRB.Influential driving factors on LULC changes included slope,GDP,and distance from highways.The interaction detection results imply either bilinear or nonlinear enhancement for any two driving factors impacting the LULC changes from 2000 to 2020.This comprehensive understanding of the spatiotemporal characteristics and driving mechanisms of LULC changes offers valuable insights for the planning and sustainable management of LULC in the JRB.

Data-driven prediction of dimensionless quantities for semi-infinite target penetration by integrating machine-learning and feature selection methods

This study employs a data-driven methodology that embeds the principle of dimensional invariance into an artificial neural network to automatically identify dominant dimensionless quantities in the penetration of rod projectiles into semi-infinite metal targets from experimental measurements.The derived mathematical expressions of dimensionless quantities are simplified by the examination of the exponent matrix and coupling relationships between feature variables.As a physics-based dimension reduction methodology,this way reduces high-dimensional parameter spaces to descriptions involving only a few physically interpretable dimensionless quantities in penetrating cases.Then the relative importance of various dimensionless feature variables on the penetration efficiencies for four impacting conditions is evaluated through feature selection engineering.The results indicate that the selected critical dimensionless feature variables by this synergistic method,without referring to the complex theoretical equations and aiding in the detailed knowledge of penetration mechanics,are in accordance with those reported in the reference.Lastly,the determined dimensionless quantities can be efficiently applied to conduct semi-empirical analysis for the specific penetrating case,and the reliability of regression functions is validated.

Improving the utility of locally differentially private protocols for longitudinal and multidimensional frequency estimates

This paper investigates the problem of collecting multidimensional data throughout time(i.e.,longitudinal studies)for the fundamental task of frequency estimation under Local Differential Privacy(LDP)guarantees.Contrary to frequency estimation of a single attribute,the multidimensional aspect demands particular attention to the privacy budget.Besides,when collecting user statistics longitudinally,privacy progressively degrades.Indeed,the“multiple”settings in combination(i.e.,many attributes and several collections throughout time)impose several challenges,for which this paper proposes the first solution for frequency estimates under LDP.To tackle these issues,we extend the analysis of three state-of-the-art LDP protocols(Generalized Randomized Response–GRR,Optimized Unary Encoding–OUE,and Symmetric Unary Encoding–SUE)for both longitudinal and multidimensional data collections.While the known literature uses OUE and SUE for two rounds of sanitization(a.k.a.memoization),i.e.,L-OUE and L-SUE,respectively,we analytically and experimentally show that starting with OUE and then with SUE provides higher data utility(i.e.,L-OSUE).Also,for attributes with small domain sizes,we propose Longitudinal GRR(L-GRR),which provides higher utility than the other protocols based on unary encoding.Last,we also propose a new solution named Adaptive LDP for LOngitudinal and Multidimensional FREquency Estimates(ALLOMFREE),which randomly samples a single attribute to be sent with the whole privacy budget and adaptively selects the optimal protocol,i.e.,either L-GRR or L-OSUE.As shown in the results,ALLOMFREE consistently and considerably outperforms the state-of-the-art L-SUE and L-OUE protocols in the quality of the frequency estimates.

Electrically-driven ultrafast out-of-equilibrium light emission from hot electrons in suspended graphene/hBN heterostructures

Nanoscale light sources with high speed of electrical modulation and low energy consumption are key components for nanophotonics and optoelectronics.The record-high carrier mobility and ultrafast carrier dynamics of graphene make it promising as an atomically thin light emitter which can be further integrated into arbitrary platforms by van der Waals forces.However,due to the zero bandgap,graphene is difficult to emit light through the interband recombination of carriers like conventional semiconductors.Here,we demonstrate ultrafast thermal light emitters based on suspended graphene/hexagonal boron nitride(Gr/hBN)heterostructures.Electrons in biased graphene are significantly heated up to 2800 K at modest electric fields,emitting bright photons from the near-infrared to the visible spectral range.By eliminating the heat dissipation channel of the substrate,the radiation efficiency of the suspended Gr/hBN device is about two orders of magnitude greater than that of graphene devices supported on SiO2or hBN.Wefurther demonstrate that hot electrons and low-energy acoustic phonons in graphene are weakly coupled to each other and are not in full thermal equilibrium.Direct cooling ofhigh-temperature hot electrons to low-temperature acoustic phonons is enabled by the significant near-field heat transfer at the highly localized Gr/hBN interface,resulting in ultrafast thermal emission with up to 1 GHz bandwidth under electrical excitation.It is found thatsuspending the Gr/hBN heterostructures on the SiO2trenches significantly modifies the light emission due to the formation of the optical cavity and showed a~440%enhancement inintensity at the peak wavelength of 940 nm compared to the black-body thermal radiation.The demonstration of electrically driven ultrafast light emission from suspended Gr/hBNheterostructures sheds the light on applications of graphene heterostructures in photonicintegrated circuits,such as broadband light sources and ultrafast thermo-optic phase modulators.

Sabatier principle guiding the design of cathode catalysts for Li-CO_(2) batteries

The Sabatier principle has been widely used for designing electrocatalysts for energy conversion applications,but it is rarely mentioned in the research of cathode catalyst of Li-CO_(2) batteries.In our work,the"volcanic"relationship between the catalytic activity and the adsorption energy of the catalyst to the intermediates is first demonstrated based on the first-principles calculation,which meets the Sabatier principle and can be used to design the cathode catalysts.The increases in the number of nitrogenvacancy in WN shift the d-band center and increase the interaction with the reactants.The catalytic activity increases first and then decreases with the increase of adsorption energy,which was proved in the experiment.The optimal catalyst for moderate adsorption of intermediate makes the thin LiaCO_(3) distribute evenly.It exhibits a median voltage difference of 0.68 V and an energy efficiency of 84.33%at20μA cm^(-2)with a limited capacity of 200μA h cm^(-2).

Genetic risk stratification of inflammatory bowel disease-associated venous thromboembolism:An Asian perspective

The utilisation of polygenic scoring models may enhance the clinician’s ability to risk stratify an inflammatory bowel disease patient’s individual risk for venous thromboembolism(VTE)and guide the appropriate usage of VTE thromboprophylaxis,yet there is a need to validate such models in ethnically diverse populations.

Amphoteric Supramolecular Nanofiber Separator for High-Performance Sodium-Ion Batteries

The separator is an essential component of sodium-ion batteries(SIBs)to determine their electrochemical performances.However,the separator with high mechanical strength,good electrolyte wettability and excellent electrochemical performance remains an open challenge.Herein,a new separator consisting of amphoteric nanofibers with abundant functional groups was fabricated through supramolecular assembly of natural polymers for SIB.The uniform nanoporous structure,remarkable mechanical properties and abundant functional groups(e.g.-COOH,-NH_(2)and-OH)endow the separator with lower dissolution activation energy and higher ion migration numbers.These metrics enable the separator to lower the barrier for desolvation of Na^(+),accelerate the migration of Na^(+),and generate more stable solid electrolyte interphase(SEI)and cathode electrolyte interphase(CEI).The battery assembled with the amphoteric nanofiber separator shows higher specific capacity and better stability than that assembled with glass fiber(GF)separator.

Regulation of aging by NELF-A and RNA polymerase Ⅱ elongation

Epigenetic regulation of aging:Aging is defined as the gradual decline of physiological function and cellular integrity,causing o rganismal vulnerability to age-onset diseases and morbidity.Studies in different animal models have led to the identification of twelve aging hallmarks that shared several features:its age-associated manifestation.

Correction to“Research progress of ferroptosis regulating lipid peroxidation and metabolism in occurrence of primary liver cancer”

Correction to“Research progress of ferroptosis regulating lipid peroxidation and metabolism in occurrence and development of primary liver cancer”in World J Gastrointest Oncol 2024;16:2335-2349,published by Shu YJ,Lao B,and Qiu YY.In this article,we added the correct citations of images.

Effects of surface chlorine atoms on charge distribution and reaction barriers for photocatalytic CO_(2)reduction

Photocatalytic CO_(2)reduction to produce high value-added carbon-based fuel has been proposed as a promising approach to mitigate global warming issues.However,the conversion efficiency and product selectivity are still low due to the sluggish dynamics of transfer processes involved in proton-assisted multi-electron reactions.Lowering the formation energy barriers of intermediate products is an effective method to enhance the selectivity and productivity of final products.In this study,we aim to regulate the surface electronic structure of Bi_(2)WO_(6)by doping surface chlorine atoms to achieve effective photocatalytic CO_(2)reduction.Surface Cl atoms can enhance the absorption ability of light,affect its energy band structure and promote charge separation.Combined with DFT calculations,it is revealed that surface Cl atoms can not only change the surface charge distribution which affects the competitive adsorption of H_(2)O and CO_(2),but also lower the formation energy barrier of intermediate products to generate more intermediate*COOH,thus facilitating CO production.Overall,this study demonstrates a promising surface halogenation strategy to enhance the photocatalytic CO_(2)reduction activity of a layered structure Bi-based catalyst.