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Nanotechnology-based combinational strategies toward the regulation of myofibroblasts and diseased microenvironment in liver fibrosis and hepatic carcinoma

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Nano Research 2023年第12期16卷 13042-13055页

作者： Fenfen Li ying zhao Guangjun Nie School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China CAS Center for Excellence in Nanoscience National Center for Nanoscience and TechnologyBeijing 101408China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China GBA National Institute for Nanotechnology Innovation Guangzhou 510530China

Liver fibrosis and hepatic carcinoma(HCC)pose a huge challenge worldwide due to the lack of effective treatment options for end-stage liver diseases.According to their functions and roles,hepatic myofibroblasts mainly include nontumoral fibroblasts(mainly activated hepatic stellate cells(HSCs)),which are involved in the wound-healing process of liver fibrosis,and cancer-associated fibroblasts(CAFs)in hepatic HCC.HSCs play a significant role in regulating extracellular matrix(ECM)deposition in progressive liver fibrosis.CAFs can be derived from activated HSCs and differentiate into ECM-producing myofibroblasts.Moreover,growing evidence shows that CAFs are the primary regulators of the HCC microenvironment,releasing growth factors and cytokines and suppressing the antitumor immune response.Combined therapeutic strategies show reduced drug resistance and side effects.Nanotechnology-based combined strategies aim to improve the delivery efficiency of various therapeutic agents with reduced toxicity via multiple mechanisms.In this review,we will discuss recent developments in combinational strategies based on nanotechnology that regulate myofibroblasts and the diseased microenvironment for liver fibrosis and HCC treatment.We will also identify the major challenges that the field is facing and offer some insights for future drug discovery.

关键词： fibroblasts liver fibrosis hepatic carcinoma nanotechnology

A Variance Reducing Stochastic Proximal Method with Acceleration Techniques

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Tsinghua Science and Technology 2023年第6期28卷 999-1008页

作者： Jialin Lei ying Zhang zhao Zhang School of Mathematical Science Zhejiang Normal UniversityJinhua 321004China

We consider a fundamental problem in the field of machine learning—structural risk minimization,which can be represented as the average of a large number of smooth component functions plus a simple and convex(but possibly non-smooth)function.In this paper,we propose a novel proximal variance reducing stochastic method building on the introduced Point-SAGA.Our method achieves two proximal operator calculations by combining the fast Douglas–Rachford splitting and refers to the scheme of the FISTA algorithm in the choice of momentum factors.We show that the objective function value converges to the iteration point at the rate of O(1/k)when each loss function is convex and smooth.In addition,we prove that our method achieves a linear convergence rate for strongly convex and smooth loss functions.Experiments demonstrate the effectiveness of the proposed algorithm,especially when the loss function is ill-conditioned with good acceleration.

关键词： composite optimization Variance Reduction(VR) fast Douglas–Rachford(DR)splitting proximal operator

Phase synchronization and energy balance between neurons

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Frontiers of Information Technology & Electronic Engineering 2022年第9期23卷 1407-1420页

作者： ying XIE zhao YAO Jun MA Department of Physics Lanzhou University of TechnologyLanzhou730050China School of Science Chongqing University of Posts and TelecommunicationsChongqing430065China

A functional neuron has been developed from a simple neural circuit by incorporating a phototube and a thermistor in different branch circuits.The physical field energy is controlled by the photocurrent across the phototube and the channel current across the thermistor.The firing mode of this neuron is controlled synchronously by external temperature and illumination.There is energy diversity when two functional neurons are exposed to different illumination and temperature conditions.As a result,synapse connections can be created and activated in an adaptive way when field energy is exchanged between neurons.We propose two kinds of criteria to discuss the enhancement of synapse connections to neurons.The energy diversity between neurons determines the increase of the coupling intensity and synaptic current for neurons,and the realization of synchronization is helpful in maintaining energy balance between neurons.The first criterion is similar to the saturation gain scheme in that the coupling intensity is increased with a constant step within a certain period until it reaches energy balance or complete synchronization.The second criterion is that the coupling intensity increases exponentially before reaching energy balance.When two neurons become non-identical,phase synchronization can be controlled during the activation of synapse connections to neurons.For two identical neurons,the second criterion for taming synaptic intensity is effective for reaching complete synchronization and energy balance,even in the presence of noise.This indicates that a synapse connection may prefer to enhance its coupling intensity exponentially.These results are helpful in discovering why synapses are awaken and synaptic current becomes time-varying when any neurons are excited by external stimuli.The potential biophysical mechanism is that energy balance is broken and then synapse connections are activated to maintain an adaptive energy balance between the neurons.These results provide guidance for designing and training intellige

关键词： Hamilton energy Coupling synchronization Synapse enhancement Neural circuit

Autophagy in pancreatic cancer

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Journal of Molecular Cell Biology 2021年第11期13卷 786-790页

作者： Congting Guo ying zhao Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China

Macroautophagy(hereafter referred to as autophagy)is a conserved eukaryotic process,in which dysfunctional proteins,organelles,and other macromolecules are wrapped in intracellular vesicles called autophagosomes and delivered to lysosomes for degradation(Mizushima et al.,2008;Mizushima and Komatsu,2011).Autophagy restores cellular energy and recycles cytoplasmic precursors,sustaining cell homeostasis and cell survival(Mizushima et al.,2008;Mizushima and Komatsu,2011).Elevated autophagy can be detected in both cancer cells and surrounding stromal cells in pancreatic cancer(PC),affecting tumor initiation and progression as well(Yang et al.,2011;Endo et al.,2017).The role of autophagy in PC is highly context-dependent.Here,we illustrate the multifactorial role of autophagy in PC,and the significance of autophagy will be emphasized not only in cancer cells but also in the tumor microenvironment.

关键词： al. cancer homeostasis

Comparative architecture in monolithic perovskite/silicon tandem solar cells

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Science China(Physics,Mechanics & Astronomy) 2023年第1期66卷 60-84页

作者： Sayantan Mazumdar ying zhao Xiaodan Zhang Institute of Photoelectronic Thin Film Devices and Technology Renewable Energy Conversion and Storage CenterSolar Energy Conversion CenterNankaiUniversityTianjin 300350China Key Laboratory of Photoelectronic Thin Film Devices and Technology of Tianjin Tianjin 300350China Haihe Laboratory of Sustainable Chemical Transformations Tianjin 300192China Engineering Research Center of Thin Film Photoelectronic Technology of Ministry of Education Tianjin 300350China Collaborative Innovation Center of Chemical Science and Engineering(Tianjin) Tianjin 300072China

Inorganic-organic metal halide perovskite light harvester-based perovskite solar cells(PSCs)with widely tunable bandgap have achieved rapid growth in power conversion efficiency,which exceeds 25%now.It is deliberated that if a semitransparent solar cell made of wider bandgap materials was placed on top of a narrow bandgap materials-based solar cell such as a silicon solar cell,with proper optical and electrical arrangements,the resultant tandem device consisting of two subcells could more effectively utilize the solar spectrum than a single junction solar cell.In a perovskite/silicon tandem solar cell(PSTSC),a semitransparent PSC with a wider bandgap is placed on top of a narrow bandgap silicon solar cell.The PSC efficiently harvests the higher energy photons in the ultraviolet and visible regions of the solar spectrum while the silicon solar cell can convert the photons of the infrared region to power.The PSTSC is proposed as a potential candidate to overcome the Shockley-Queisser limit of single-junction silicon solar cells.Though the theoretical limit of a PSTSC is calculated as~42%,its actual efficiency achieved until now is less than 30%.Therefore,a great scope of research exists in improving the efficiency of PSTSCs.Current issues of stability and upscaling of the device in PSCs are also a matter of concern for PSTSCs.A tandem device consists of multiple parts,and different configurations can be applied,thus tuning the architecture of the device.Altering various parts may result in significant changes in the efficiency of the device.In this review,competing architectures of otherwise comparable devices are compared in terms of photovoltaic properties.Thus,future directions to improve the efficiency of the device based on architecture design are proposed herein.In particular,the influence of the polarity of PSCs and the surface morphology of silicon solar cells(both front and rear)on determining the properties of the PSTSC are discussed.

关键词： tandem solar cell silicon solar cell perovskite perovskite solar cell solar cell architecture polarity of tandem solar cell photoelectrochemical cells photoconduction and photovoltaic effects solar cells and arrays

Formation of local heterogeneity under energy collection in neural networks

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Science China(Technological Sciences) 2023年第2期66卷 439-455页

作者： XIE ying YAO zhao MA Jun Department of Physics Lanzhou University of TechnologyLanzhou 730050China School of Physics and Electronics Central South UniversityChangsha 410083China School of Science Chongqing University of Posts and TelecommunicationsChongqing 430065China

Static distribution of intracellular and extracellular ions can induce the spatial distribution of electric field in the cell,while stochastic diffusion and propagation of ions can generate channel current accompanied by the magnetic field.In fact,the field energy(including magnetic and electric fields)in each cell or neuron can be changed under external stimuli or the deformation of shape.Furthermore,energy pumping occurs,and the synaptic connection is created adaptively to keep energy balance when more neurons are clustered in the same region because of electromagnetic field superposition.For a synchronous and homogeneous network,all neurons keep energy balance with the adjacent neurons,and the network becomes uniform and identical.For cardiac tissue and biological media,local heterogeneity such as sinoatrial node can emit continuous wave front,and target waves are propagated to regulate the neural activities and heartbeat rhythm.In this paper,the Hamilton energy in a simple neuron model is calculated according to the Helmholtz theorem,and more neurons are clustered to build a regular network(chain network and square array).The creation and growth of synapse connection are controlled to pump energy,and local heterogeneity is formed by taming one intrinsic parameter when more energy is accumulated in a few neurons in the network.These results indicate that asymmetrical energy transport will induce the occurrence of heterogeneity in the network,and adaptive synaptic regulation on neurons is activated to keep local energy balance before reaching perfect synchronization.When external stimuli with diversity in intensity are applied,neurons are excited with energy diversity,and possible shape deformation is induced to keep local energy balance.As a result,heterogeneity is developed in a local area.

关键词： energy balance synapse coupling heterogeneity neural network

Unrecognized congenital heart disease in rural school-age children:getting to the root of the problem

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World Journal of Pediatrics 2022年第5期18卷 305-307页

作者： Qu-Ming zhao Guo-ying Huang Pediatric Heart Center Children's Hospital of Fudan UniversityNational Children's Medical Center399 Wan Yuan RoadShanghai 201102China Shanghai Key Laboratory of Birth Defects ShanghaiChina

Congenital heart disease(CHD)is an important contributor to morbidity and mortality in children,and the global burden of this illness has raised unique challenges to the healthcare system[1,2].China is among the countries with the highest burden of this disorder despite having achieved huge advances in cardiac surgery or interventional therapies in CHD during the past two decades[3].Interestingly and unexpected is the lower prevalence rate of CHD reported in China.The prevalence of CHD at live birth is estimated to be 9.4 per 1000 worldwide[4],However,this figure is much lower in China,with only 4.9 per 1000 live births between 2015 and 2019[5].

关键词： mortality congenital raised

Numerical Integrators for Dispersion-Managed KdV Equation

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Communications in Computational Physics 2022年第4期31卷 1180-1214页

作者： ying He Xiaofei zhao School of Mathematics and Statistics Wuhan UniversityWuhan 430072P.R.China Computational Sciences Hubei Key Laboratory Wuhan UniversityWuhan 430072P.R.China

In this paper,we consider the numerics of the dispersion-managed Kortewegde Vries(DM-KdV)equation for describingwave propagations in inhomogeneous media.The DM-KdV equation contains a variable dispersion map with discontinuity,which makes the solution non-smooth in time.We formally analyze the convergence order reduction problems of some popular numerical methods including finite difference and time-splitting for solving the DM-KdV equation,where a necessary constraint on the time step has been identified.Then,two exponential-type dispersionmap integrators up to second order accuracy are derived,which are efficiently incorporatedwith the Fourier pseudospectral discretization in space,and they can converge regardless the discontinuity and the step size.Numerical comparisons show the advantage of the proposed methods with the application to solitary wave dynamics and extension to the fast&strong dispersion-management regime.

关键词： KdV equation dispersion management discontinuous coefficient convergence order finite difference time-splitting exponential integrator pseudospectral method

The complement system and autoimmune diseases

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Chronic Diseases and Translational Medicine 2022年第3期8卷 184-190页

作者： Changhao Jia ying Tan Minghui zhao Laboratory of Renal Disease Department of MedicineRenal DivisionMinistry of Health of ChinaPeking University First HospitalPeking University Institute of NephrologyBeijingChina Peking-Tsinghua Center for Life Sciences BejingChina Centerfor Interdisciplinary Research in Biomedicine Peking UniversityBeijingChina

The complement system plays a key role in the pathogenesis of autoimmune diseases,which usually injures the kidney.More and more studies have shown the pathogenic role and indicated that abnormal activation of the complement system was highly involved in the outbreak of autoimmune diseases.This review mainly introduced recent studies of complement system activation contributing to the pathogenesis of autoimmune diseases,including systemic lupus erythematosus,antiphospholipid syndrome,antineutrophil cytoplasmic antibody-associated vasculitides,and so on.Understanding the pathogenic roles of complement activation in various autoimmune diseases will identify potential novel therapeutic targets on complement systems.

关键词： ANCA-associated vasculitides antiphospholipid syndrome autoimmune disease complement systemic lupus erythematosus