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Electroacupuncture improves cognitive function in a rat model of mild traumatic brain injury by regulating the SIRT-1/PGC-1α/mitochondrial pathway

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Chinese Medical Journal 2024年第6期137卷 711-719页

作者： Bo Jin Yemei Gao yixian Fu Suxin Zhang Ke Zhang Yibing Su Department of Neurosurgery Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China Department of Traditional Chinese Medicine Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing 100029China Department of Cardiology Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Department of Breast Surgical Oncology National Cancer CenterNational Clinical Research Center for CancerCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background:Mild traumatic brain injury(mTBI)is a common neurological trauma that can lead to cognitive impairment.The sirtuin-1(SIRT-1)/peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α)pathway has been reported to have neuroprotective effects in rats with craniocerebral injury.We evaluated potential mechanisms underlying electroacupuncture-mediated recovery of cognitive function after mTBI,focusing on the SIRT-1/PGC-1α/mitochondrial pathway.Methods:We included forty 6-week-old male Sprague-Dawley rats in this study.Rats were randomly divided into four groups:controlled cortical impactor(CCI,n=10),sham operation(sham,n=10),electroacupuncture-treated CCI(CCI+EA,n=10),and electroacupuncture-treated sham(sham+EA,n=10)group.Randomization was performed by assigning a random number to each rat and using a random number table.The mTBI rat model was established using a controllable cortical impactor.Electroacupuncture therapy was performed on the back of rats,by inserting acupuncture needles to the specific acupoints and setting appropriate parameters for treatment.We evaluated spatial learning and memory functions with the Morris water maze test.We performed quantitative real-time polymerase chain reaction(qRT-PCR),western blotting,adenosine triphosphate(ATP)determination,and mitochondrial respiratory chain complex I(MRCC I)determination on rat hippocampal tissue.We analyzed SIRT-1/PGC-1α expression levels and the results of mitochondrial function assays,and compared differences between groups using bilateral Student’s t-tests.Results:Compared with the sham group,SIRT-1/PGC-1α expression was downregulated in the hippocampus of CCI group(P<0.01).Although this expression was upregulated following electroacupuncture,it did not reach the levels observed in the sham group(P<0.05).Compared with the sham group,MRCC I and ATP levels in the CCI group were significantly reduced,and increased after electroacupuncture(P<0.01).In the Morris water maze,electroacupuncture reduced the incubation period of rats and

关键词： Electroacupuncture Cognitive impairment Sirtuin-1 Mild traumatic brain injury SIRT-1/PGC-1α/mitochondrial pathway

Multidimensional autophagy nano-regulator boosts Alzheimer's disease treatment by improving both extra/intraneuronal homeostasis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1380-1399页

作者： yixian Li Peng Yang Ran Meng Shuting Xu Lingling zhou Kang Qian Pengzhen Wang Yunlong Cheng Dongyu Sheng Minjun Xu Tianying Wang Jing Wu Jinxu Cao Qizhi Zhang Key Laboratory of Smart Drug Delivery Ministry of EducationSchool of PharmacyFudan UniversityShanghai 201203China

Intraneuronal dysproteostasis and extraneuronal microenvironmental abnormalities in Alzheimer’s disease(AD)collectively culminate in neuronal deterioration.In the context of AD,autophagy dysfunction,a multi-link obstacle involving autophagy downregulation and lysosome defects in neurons/microglia is highly implicated in intra/extraneuronal pathological processes.Therefore,multidimensional autophagy regulation strategies co-manipulating“autophagy induction”and“lysosome degradation”in dual targets(neuron and microglia)are more reliable for AD treatment.Accordingly,we designed an RP-1 peptide-modified reactive oxygen species(ROS)-responsive micelles(RT-NM)loading rapamycin or gypenoside XVII.Guided by RP-1 peptide,the ligand of receptor for advanced glycation end products(RAGE),RT-NM efficiently targeted neurons and microglia in AD-affected region.This nanocombination therapy activated the whole autophagy-lysosome pathway by autophagy induction(rapamycin)and lysosome improvement(gypenoside XVII),thus enhancing autophagic degradation of neurotoxic aggregates and inflammasomes,and promoting Aβ phagocytosis.Resultantly,it decreased aberrant protein burden,alleviated neuroinflammation,and eventually ameliorated memory defects in 3×Tg-AD transgenic mice.Our research developed a multidimensional autophagy nano-regulator to boost the efficacy of autophagy-centered AD therapy.

关键词： Autophagy-lysosome pathway Alzheimer’s disease Proteostasis Neuroinflammation Multi-target therapy Rapamycin Gypenoside XVII Cascade dual-targeting

Secure state estimation for cyber-physical systems with unknown input sliding mode observer

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Control Theory and Technology 2024年第2期22卷 244-253页

作者： Panpan Zhang Yuwei Ren yixian Fang Ang Liu School of Information Science and Engineering Shandong Normal UniversityJinan250358ShandongChina School of Information Engineering Shandong Management UniversityJinan250357ShandongChina

In recent years, cyber attacks have posed great challenges to the development of cyber-physical systems. It is of great significance to study secure state estimation methods to ensure the safe and stable operation of the system. This paper proposes a secure state estimation for multi-input and multi-output continuous-time linear cyber-physical systems with sparse actuator and sensor attacks. First, for sparse sensor attacks, we propose an adaptive switching mechanism to mitigate the impact of sparse sensor attacks by filtering out their attack modes. Second, an unknown input sliding mode observer is designed to not only observe the system states, sensor attack signals, and measurement noise present in the system but also counteract the effects of sparse actuator attacks through an unknown input matrix. Finally, for the design of an unknown input sliding mode state observer, the feasibility of the observing system is demonstrated by means of Lyapunov functions. Additionally, simulation experiments are conducted to show the effectiveness of this method.

关键词： Sparse attacks Cyber-physical systems Unknown input sliding mode Secure state estimation Adaptive switching mechanism

“Pincer movement”:Reversing cisplatin resistance based on simultaneous glutathione depletion and glutathione S-transferases inhibition by redox-responsive degradable organosilica hybrid nanoparticles

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Acta Pharmaceutica Sinica B 2022年第4期12卷 2074-2088页

作者： Boyi Niu yixian zhou Kaixin Liao Ting Wen Sixian Lao Guilan Quan Xin Pan Chuanbin Wu School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China College of Pharmacy Jinan UniversityGuangzhou 510632China

The therapeutic efficacy of cisplatin has been restricted by drug resistance of cancers.Intracellular glutathione(GSH)detoxification of cisplatin under the catalysis of glutathione S-transferases(GST)plays important roles in the development of cisplatin resistance.Herein,a strategy of“pincer movement”based on simultaneous GSH depletion and GST inhibition is proposed to enhance cisplatin-based chemotherapy.Specifically,a redox-responsive nanomedicine based on disulfide-bridged degradable organosilica hybrid nanoparticles is developed and loaded with cisplatin and ethacrynic acid(EA),a GST inhibitor.Responding to high level of intracellular GSH,the hybrid nanoparticles can be gradually degraded due to the break of disulfide bonds,which further promotes drug release.Meanwhile,the disulfide-mediated GSH depletion and EA-induced GST inhibition cooperatively prevent cellular detoxification of cisplatin and reverse drug resistance.Moreover,the nanomedicine is integrated into microneedles for intralesional drug delivery against cisplatin-resistant melanoma.The in vivo results show that the nanomedicine-loaded microneedles can achieve significant GSH depletion,GST inhibition,and consequent tumor growth suppression.Overall,this research provides a promising strategy for the construction of new-type nanomedicines to overcome cisplatin resistance,which extends the biomedical application of organosilica hybrid nanomaterials and enables more efficient chemotherapy against drug-resistant cancers.

关键词： Cancer therapy Cisplatin Drug resistance Glutathione depletion Glutathione Stransferases Disulfide bonds Organosilica hybrid nanoparticles Ethacrynic acid

Slippery hydrogel with desiccation-tolerant‘skin’for high-precision additive manufacturing

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International Journal of Extreme Manufacturing 2024年第2期6卷 486-500页

作者： Desheng Liu Pan Jiang Yue Hu Yaozhong Lu yixian Wang Jiayu Wu Danli Hu Tao Wu Xiaolong Wang State Key Laboratory of Solid Lubrication Lanzhou Institute of Chemical PhysicsChinese Academy of SciencesLanzhou 730000People’s Republic of China CAS Key Laboratory of Chemistry of Northwestern Plant Resources Lanzhou Institute of Chemical PhysicsChinese Academy of SciencesLanzhou 730000People’s Republic of China Shandong Laboratory of Advanced Materials and Green Manufacturing at Yantai Yantai Zhongke Research Institute of Advanced Materials and Green Chemical EngineeringYantai 264006People’s Republic of China Key Laboratory of Materials-Oriented Chemical Engineering of Xinjiang Uygur Autonomous Region School of Chemistry and Chemical EngineeringShihezi UniversityShihezi 832003People’s Republic of China

Hydrogels inevitably undergo dehydration,structural collapse,and shrinkage deformation due to the uninterrupted evaporation in the atmosphere,thereby losing their flexibility,slipperiness,and manufacturing precision.Here,we propose a novel bioinspired strategy to construct a spontaneously formed‘skin’on the slippery hydrogels by incorporating biological stress metabolites trehalose into the hydrogel network,which can generate robust hydrogen bonding interactions to restrain water evaporation.The contents of trehalose in hydrogel matrix can also regulate the desiccation-tolerance,mechanical properties,and lubricating performance of slippery hydrogels in a wide range.Combining vat photopolymerization three-dimensional printing and trehalose-modified slippery hydrogels enables to achieve the structural hydrogels with high resolution,shape fidelity,and sophisticated architectures,instead of structural collapse and shrinkage deformation caused by dehydration.And thus,this proposed functional hydrogel adapts to manufacture large-scale hydrogels with sophisticated architectures in a long-term process.As a proof-of-concept demonstration,a high-precision and sophisticated slippery hydrogel vascular phantom was easily fabricated to imitate guidewire intervention.Additionally,the proposed protocol is universally applicable to diverse types of hydrogel systems.This strategy opens up a versatile methodology to fabricate dry-resistant slippery hydrogel for functional structures and devices,expanding their high-precision processing and broad applications in the atmosphere.

关键词： slippery hydrogel trehalose desiccation tolerance vat photopolymerization 3D printing hydrogen bonding

Parallel Physics-Informed Neural Networks Method with Regularization Strategies for the Forward-Inverse Problems of the Variable Coefficient Modified KdV Equation

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Journal of Systems Science & Complexity 2024年第2期37卷 511-544页

作者： zhou Huijuan School of Science Shanghai Maritime UniversityShanghai 201306China

This paper mainly introduces the parallel physics-informed neural networks(PPINNs)method with regularization strategies to solve the data-driven forward-inverse problems of the variable coefficient modified Korteweg-de Vries(VC-MKdV)equation.For the forward problem of the VC-MKdV equation,the authors use the traditional PINN method to obtain satisfactory data-driven soliton solutions and provide a detailed analysis of the impact of network width and depth on solving accuracy and speed.Furthermore,the author finds that the traditional PINN method outperforms the one with locally adaptive activation functions in solving the data-driven forward problems of the VC-MKdV equation.As for the data-driven inverse problem of the VC-MKdV equation,the author introduces a parallel neural networks to separately train the solution function and coefficient function,successfully addressing the function discovery problem of the VC-MKdV equation.To further enhance the network’s generalization ability and noise robustness,the author incorporates two regularization strategies into the PPINNs.An amount of numerical experimental data in this paper demonstrates that the PPINNs method can effectively address the function discovery problem of the VC-MKdV equation,and the inclusion of appropriate regularization strategies in the PPINNs can improves its performance.

关键词： Data-driven forward-inverse problems parallel physics-informed neural networks regularization strategies variable coefficient modified KdV equation

A triple-enhanced chemodynamic approach based on glucosepowered hybrid nanoreactors for effective bacteria killing

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Nano Research 2023年第2期16卷 2682-2694页

作者： Jintao Fu yixian zhou Ting Liu Wenhao Wang Yiting Zhao Ying Sun Yiming Zhang Wenxuan Qin Zhongwei Chen Chao Lu Guilan Quan Chuanbin Wu Xin Pan School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China College of Pharmacy Jinan UniversityGuangzhou 511443China

Rapid evolution of multidrug resistance in bacterial pathogens is outpacing the development of new antibiotics,and chemodynamic therapy(CDT)provides an excellent alternative.However,achieving highly efficient CDT is still a great challenge,since the pH in the infection site is close to neutral and the supply of H_(2)O_(2)is inadequate.We herein constructed the antibacterial nanoreactors.Indocyanine green(ICG)and glucose oxidase(GOx)were incorporated into homologous zeolitic imidazolate framework-8(ZIF-8)nanoparticles coating with metal polyphenol network(MPN)composed by Fe^(3+)and tannic acid(TA).The well-designed nanoreactors could simultaneously break the pH and H_(2)O_(2)limitations,and generate hyperthermia under irradiation,thus realizing a triple-enhanced CDT for high-efficiency sterilization.Furthermore,the nanoreactors could combine CDT with photothermal therapy(PTT)and photodynamic therapy(PDT),which not only improved the bactericidal efficiency and broadened the antibacterial spectrum,but also alleviated the antibiotics resistance issues.Remarkably,the proposed nanoreactors achieved a robust in vitro bacterial killing against Gram-positive methicillin-resistant Staphylococcus aureus(MRSA)and Gram-negative Pseudomonas aeruginosa.The nanoreactors achieved an 99.7%MRSA reduction in an MRSA-induced murine abscess model accompanied with negligible toxicity.Overall,this study provides a promising strategy for multiple-enhanced CDT and multimodal combined therapy for pathogenic infections.

关键词： metal-organic frameworks glucose oxidase photothermal therapy photodynamic therapy localized bacterial infection

An Environment‑Tolerant Ion‑Conducting Double‑Network Composite Hydrogel for High‑Performance Flexible Electronic Devices

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Nano-Micro Letters 2024年第5期16卷 352-369页

作者： Wenchao Zhao Haifeng zhou Wenkang Li Manlin Chen Min zhou Long Zhao State Key Laboratory of Advanced Electromagnetic Technology School of Electrical and Electronic EngineeringHuazhong University of Science and TechnologyWuhan 430074People’s Republic of China School of Chemistry and Chemical Engineering Huazhong University of Science and TechnologyWuhan 430074People’s Republic of China

High-performance ion-conducting hydrogels(ICHs)are vital for developing flexible electronic devices.However,the robustness and ion-conducting behavior of ICHs deteriorate at extreme tempera-tures,hampering their use in soft electronics.To resolve these issues,a method involving freeze–thawing and ionizing radiation technology is reported herein for synthesizing a novel double-network(DN)ICH based on a poly(ionic liquid)/MXene/poly(vinyl alcohol)(PMP DN ICH)system.The well-designed ICH exhibits outstanding ionic conductivity(63.89 mS cm^(-1) at 25℃),excellent temperature resistance(-60–80℃),prolonged stability(30 d at ambient temperature),high oxidation resist-ance,remarkable antibacterial activity,decent mechanical performance,and adhesion.Additionally,the ICH performs effectively in a flexible wireless strain sensor,thermal sensor,all-solid-state supercapacitor,and single-electrode triboelectric nanogenerator,thereby highlighting its viability in constructing soft electronic devices.The highly integrated gel structure endows these flexible electronic devices with stable,reliable signal output performance.In particular,the all-solid-state supercapacitor containing the PMP DN ICH electrolyte exhibits a high areal specific capacitance of 253.38 mF cm^(-2)(current density,1 mA cm^(-2))and excellent environmental adaptability.This study paves the way for the design and fabrication of high-performance mul-tifunctional/flexible ICHs for wearable sensing,energy-storage,and energy-harvesting applications.

关键词： Ionic liquids Double-network hydrogels Temperature tolerance Multifunctionality Flexible electronic devices

Perturbation of autophagy pathways in murine alveolar macrophage by 2D TMDCs is chalcogen-dependent

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Journal of Environmental Sciences 2024年第1期135卷 97-107页

作者： Xiaofei zhou Weitao Jin Rui Zhang Xuan Mao Jianbo Jia Hongyu zhou College of Science&Technology Hebei Agricultural UniversityHuanghua 061100China Institute of Environmental Research at Greater Bay Area Key Laboratory for Water Quality and Conservation of the Pearl River DeltaMinistry of EducationGuangzhou UniversityGuangzhou 510006China

Increasing risks of incidental and occupational exposures to two-dimensional transition metal dichalcogenides(2D TMDCs)due to their broad application in various areas raised their public health concerns.While the composition-dependent cytotoxicity of 2D TMDCs has been well-recognized,how the outer chalcogenide atoms and inner transition metal atoms differentially contribute to their perturbation on cell homeostasis at non-lethal doses remains to be identified.In the present work,we compared the autophagy induction and related mechanisms in response to WS_(2),NbS_(2),WSe_(2)and Nb Se_(2)nanosheets exposures in MH-S murine alveolar macrophages.All these 2D TMDCs had comparable physicochemical properties,overall cytotoxicity and capability in triggering autophagy in MH-S cells,but showed outer chalcogen-dependent subcellular localization and activation of autophagy pathways.Specifically,WS_(2)and NbS_(2)nanosheets adhered on the cell surface and internalized in the lysosomes,and triggered m TOR-dependent activation of autophagy.Meanwhile,WSe_(2)and Nb Se_(2)nanosheets had extensive distribution in cytoplasm of MH-S cells and induced autophagy in an m TOR-independent manner.Furthermore,the 2D TMDCs-induced perturbation on autophagy aggravated the cytotoxicity of respirable benzo[a]pyrene.These findings provide a deeper insight into the potential health risk of environmental 2D TMDCs from the perspective of homeostasis perturbation.

关键词： Chalcogen group Autophagy pathway Cell function Endosomal escape Inhalation toxicity