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Aggregate 2024年第1期5卷 130-147页

作者： Yuwei Liu Shuting Xu Qingyang Lyu Yi Huang weiping wang State Key Laboratory of Pharmaceutical Biotechnology The University of Hong KongHong KongChina Department of Pharmacology and Pharmacy Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina Laboratory of Molecular Engineering and Nanomedicine Dr.Li Dak-Sum Research CentreThe University of Hong KongHong KongChina

Nowadays,cancer has become the leading cause of death worldwide,driving the need for effective therapeutics to improve patient prognosis.Photodynamic therapy(PDT)has been widely applied as an antitumor modality,owing to its minimal invasiveness,localized tumor damage,and high safety profile.However,its efficacy is limited by poor stability of photosensitizers,inadequate tumor accumulation,and a complex tumor microenvironment.To overcome these challenges,extensive endeavors have been made to explore the co-assembly of the widely used photosensitizer chlorin e6(Ce6)with various functional small molecules to enhance pharmacodynamic activity.This review provides a comprehensive overview of current studies on Ce6-based nanoparticles for effective PDT and precise delivery of functional molecules.The self-assembly mechanism will be discussed in detail,with a focus on potential strategies for combinational therapy with PDT.

关键词： cancer treatment carrier-free chlorin e6(Ce6) light nanomedicine photodynamic therapy(PDT) selfassembly

Joint Transmit and Reflective Beamforming Design for Active IRS-Aided SWIPT Systems

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Chinese Journal of Electronics 2024年第2期33卷 536-548页

作者： weiping SHI Qingqing WU Di WU Feng SHU Jiangzhou wang School of Electronic and Optical Engineering Nanjing University of Science and Technology Department of Electronic Engineering Shanghai Jiao Tong University School of Information and Communication Engineering Hainan University Department of Automation Shanghai Jiao Tong University School of Engineering University of Kent

To further improve the performance of passive intelligent reflecting surface(IRS)-assisted communication systems and mitigate the serious path loss due to “double-fading ” of IRS-assisted links, an active IRS-aided simultaneous wireless information and power transfer(SWIPT) system is investigated. This paper jointly optimizes the transmit beamforming at the base station(BS) and the phase shifts at the active IRS in order to maximize the power collected by the energy harvesting receiver under both perfect and imperfect channel state information(CSI)states, subject to the signal-to-interference-noise ratio constraint of the information decoding receiver, and the power constraints of the BS/IRS. Under perfect CSI, the alternating optimization algorithm is utilized for obtaining the transmit beamforming at the BS and the phase shifts at the active IRS. For each subproblem, we first transform nonconvex objective function and constraints into convex ones by performing a first-order Taylor expansion. Then, each subproblem is solved by using the interior point method. Given that obtaining perfect CSI is impractical, two robust beamforming designs are proposed for imperfect CSI case. Under the bounded CSI error model, we first transform the non-convex optimization problem into two semidefinite programming subproblems, and then solve each subproblem based on S-procedure and sequential rank-one constraint relaxation(SROCR) techniques. Under the stochastic CSI error model, the alternating optimization method is applied in an iterative manner based on Bernstein-type inequality and SROCR technique. Simulation results show that both robust and non-robust schemes for active IRS-assisted SWIPT systems can achieve extremely superior performance over conventional passive IRS-assisted systems under the same overall power budget.

关键词： Active intelligent reflecting surface Energy harvesting Perfect channel state information Imperfect channel state information Simultaneous wireless information and power transfer

Elastohydrodynamic Lubrication Interface Stiffness and Damping Considering Asperity Lateral Contact

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Acta Mechanica Solida Sinica 2024年第1期37卷 109-123页

作者： Zhiqiang Gao Yu Zhang Xian Wei Yanfang Zhu Lixia Peng weiping Fu Wen wang School of Mechanical and Precision Instrument Engineering Xi'an University of TechnologyXi'an 710048China School of Intelligent Manufacturing Panzhihua UniversityPanzhihua 617000China Material Corrosion and Protection Key Laboratory of Sichuan Province Sichuan University of Light Chemical TechnologyYibin 644002China School of Mechanical Engineering Anyang Institute of TechnologyAnyang 455099China

Elastohydrodynamic lubrication(EHL)point contact occurs between two rough surfaces at the mesoscopic level,while the interaction of rough surfaces involves contact between asperities at the microscale level.In most cases,the contact between asperities within an interface takes the form of lateral contact rather than peak contact.Regions devoid of contact asperities are filled with lubricating oil.However,conventional models often oversimplify lateral contact forms as interactions between asperities and a smooth,rigid plane.These simplifications fail to accurately represent the true contact conditions and can lead to inaccuracies in the analysis of EHL’s contact performance.To address this issue,we have developed a novel EHL interface model comprising two rough surfaces.This model allows us to explore the influence of asperity height,contact angle,and contact azimuth angle on EHL interface performance.

关键词： EHL interface Asperity lateral contact Contact stiffness Damping

Mechanism of nanoparticle aggregation in gas-liquid microfluidic mixing

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Chinese Chemical Letters 2024年第4期35卷 376-381页

作者： Hongxia Li Xiyang wang Du Qiao Jiahao Li weiping Zhu Honglin Li Key Laboratory for Precision&Non-traditional Machining Technology of Ministry of Education Dalian University of TechnologyDalian 116023China Shanghai Key Laboratory of New Drug Design School of PharmacyEast China University of Science and TechnologyShanghai 200237China

Using gas-liquid segmented micromixers to prepare nanoparticles that have a homogeneous particle size, controllable shape, and monodispersity advantages. Although nanoparticle aggregation within a microfluid has been shown to be affected by the shear effect, the shear effect triggering conditions in gasliquid two-phase flow is unclear and the aggregation behavior of nanoparticles under the shear effect is difficult to predict, resulting in uncontrollable physical and chemical properties of nanoparticle aggregates. In this study, a numerical simulation of nanoparticle aggregation in gas-liquid two-phase flow under the shear effect is performed using the CFD-DEM method. Then, the effects of total flow rate,gas-liquid two-phase flow ratio, and particle volume fraction on particle aggregation were analyzed to achieve control of particle aggregation shape and size. Meanwhile, the triggering mechanism of the shear effect and the mechanism of the shear effect on the aggregation of nanoparticles were clarified. The results show that increasing the total flow rate or decreasing the gas-liquid two-phase flow rate ratio can induce the shear effect, which reduces the particle aggregation size and makes the morphology tend to be spherical. Moreover, increasing the particle volume fraction, and total flow rate or decreasing the gas-liquid two-phase flow rate ratio also increases the number of particle collisions and induce interparticle adhesion. Hence, particle adhesion and the shear effect compete with each other and together affect particle aggregation.

关键词： Microfluidic Gas-liquid segmented micromixer Nanoparticle aggregation Shear effect Numerical calculation

Light-responsive nanomedicine for cancer immunotherapy

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药学学报:英文版 2023年第6期13卷 2346-2368页

作者： Weirong Kang Yuwei Liu weiping wang State Key Laboratory of Pharmaceutical Biotechnology the University of Hong KongHong KongChina Department of Pharmacology and Pharmacy Li Ka Shing Faculty of Medicinethe University of Hong KongHong KongChina Laboratory of Molecular Engineering and Nanomedicine Dr.Li Dak-Sum Research Centrethe University of Hong KongHong KongChina

Immunotherapy emerged as a paradigm shift in cancer treatments, which can effectively inhibit cancer progression by activating the immune system. Remarkable clinical outcomes have been achieved through recent advances in cancer immunotherapy, including checkpoint blockades, adoptive cellular therapy, cancer vaccine, and tumor microenvironment modulation. However, extending the application of immunotherapy in cancer patients has been limited by the low response rate and side effects such as autoimmune toxicities. With great progress being made in nanotechnology, nanomedicine has been exploited to overcome biological barriers for drug delivery. Given the spatiotemporal control,light-responsive nanomedicine is of great interest in designing precise modality for cancer immunotherapy. Herein, we summarized current research utilizing light-responsive nanoplatforms to enhance checkpoint blockade immunotherapy, facilitate targeted delivery of cancer vaccines, activate immune cell functions, and modulate tumor microenvironment. The clinical translation potential of those designs is highlighted and challenges for the next breakthrough in cancer immunotherapy are discussed.

关键词： Light-responsive nanoparticles Photodynamic therapy Photothermal therapy Nanomedicine Cancer therapy Immunotherapy Photopharmacology Light-triggered drug release

Multistep continuous flow synthesis of Erlotinib

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Chinese Chemical Letters 2024年第4期35卷 371-375页

作者： Hui Jin Qin Cai Peiwen Liu Yan Chen Derong wang weiping Zhu Yufang Xu Xuhong Qian State Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of Chemical BiologySchool of PharmacyEast China University of Science and TechnologyShanghai 200237China

Erlotinib is an orally administered, highly effective, specific epidermal growth factor receptor tyrosine kinase inhibitor, used to treat non-small cell lung cancer and pancreatic cancer. The traditional synthetic methods for Erlotinib exhibit long reaction time and safety concern. Herein, we describe a novel five-step route for the synthesis of Erlotinib in flow. These five steps comprise etherification, nitration, reduction,addition and cyclization reactions. All steps were optimized and converted to continuous flow process,which drastically reduces the reaction time and considerably improves the process safety as well as the total yield. Enabled by five continuous flow units, Erlotinib is efficiently afforded with an E-factor of 38,an overall yield of 83%, and a total residence time of 25.1 min. Majority steps in this process have been optimized for quantitative conversion, which offers the possibility of telescoping the entire process.

关键词： Erlotinib Continuous flow synthesis Microchannel flow reactor Process optimization Continuous nitration Continuous hydrogenation

Process analytical technologies and self-optimization algorithms in automated pharmaceutical continuous manufacturing

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Chinese Chemical Letters 2024年第3期35卷 87-95页

作者： Peiwen Liu Hui Jin Yan Chen Derong wang Haohui Yan Mingzhao Wu Fang Zhao weiping Zhu State Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of Chemical BiologySchool of PharmacyEast China University of Science and TechnologyShanghai 200237China State Key Laboratory of Chemical Engineering School of Chemical EngineeringEast China University of Science and TechnologyShanghai 200237China Engineering Research Center of Pharmaceutical Process Chemistry Ministry of EducationSchool of PharmacyEast China University of Science and TechnologyShanghai 200237China

The pharmaceutical industry is now paying increased attention to continuous manufacturing.While the revolution to continuous and automated manufacturing is deepening in most of the top pharma companies in the world,the advancement of automated pharmaceutical continuous manufacturing in China is relatively slow due to some key challenges including the lack of knowledge on the related technologies and shortage of qualified personnels.In this review,emphasis is given to two of the crucial technologies in automated pharmaceutical continuous manufacturing,i.e.,process analytical technology(PAT)and self-optimizing algorithm.Research work published in recent 5 years employing advanced PAT tools and self-optimization algorithms is introduced,which represents the great progress that has been made in automated pharmaceutical continuous manufacturing.

关键词： Pharmaceutical continuous manufacturing Automation Process analytical technology Self-optimization algorithm

Fibroblast growth factor 21 inhibits ferroptosis following spinal cord injury by regulating heme oxygenase-1

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Neural Regeneration Research 2024年第7期19卷 1568-1574页

作者： Qi Gu weiping Sha Qun Huang Jin wang Yi Zhu Tianli Xu Zhenhua Xu Qiancheng Zhu Jianfei Ge Shoujin Tian Xiaolong Lin Department of Orthopaedic Surgery Zhangjiagang Hospital Affiliated to Soochow UniversitySuzhouJiangsu ProvinceChina Orthopedics Laboratory The First People’s Hospital of Zhangjiagang CitySuzhouJiangsu ProvinceChina Department of Anesthesiology Zhangjiagang Hospital Affiliated to Soochow UniversitySuzhouJiangsu ProvinceChina

Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury.Fibroblast growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a regulator of iron and reactive oxygen species homeostasis.The relationship between heme oxygenase-1and ferroptosis remains controve rsial.In this study,we used a spinal co rd injury rat model to show that the levels of fibroblast growth factor 21 in spinal co rd tissue decreased after spinal cord injury.In addition,there was a significant aggravation of ferroptosis and a rapid increase in heme oxygenase-1 expression after spinal cord injury.Furthe r,heme oxygenase-1 aggravated fe rroptosis after spinal cord injury,while fibroblast growth factor 21 inhibited fe rroptosis by downregulating heme oxygenase-1.Thus,the activation of fibroblast growth factor 21 may provide a potential treatment for spinal co rd injury.These findings could provide a new potential mechanistic explanation for fibroblast growth factor 21 in the treatment of spinal cord injury.

关键词： ferroptosis fibroblast growth factor 21 functional recovery heme oxygenase-1 lipid peroxidation neuron reactive oxygen species spinal cord injury

Free amino group-directed C(sp^(2))-H arylation ofα-amino-β-aryl esters by palladium catalysis

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Chinese Chemical Letters 2024年第2期35卷 358-360页

作者： Yue Gao Yu Du weiping Su State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhou 350002China Fujian Science & Technology Innovation Laboratory for Optoelectronic Information of China Fuzhou 350108China University of Chinese Academy of Sciences Beijing 100049China

Native amino-directed palladium-catalyzed C(sp^(3))-H activation/functionalization has been developed for modification ofα-amino acids and peptides.Herein a palladium(Ⅱ)-catalyzed C(sp^(2))-H arylation ofα-amino-β-aryl esters has been disclosed,using the native amino as the directing group.A variety of chiralα-amino-β-aryl esters can be functionalized to give the corresponding ortho-substituted mono-and di-arylated products.

关键词： Native amino-directed Palladium catalyst C(sp^(2))-H arylation α-Amino-β-aryl ester Chiralα-amino acid

Histone demethylase Kdm5c regulates osteogenesis and bone formation via PI3K/Akt/HIF1α and Wnt/β-catenin signaling pathways

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Genes & Diseases 2024年第1期11卷 64-66页

作者： Ying Li Lingli Ding Yage Zhang Bingyu Zhou Gene Chi Wai Man Min wang Jinglan Li Yamei Liu weiping Lin Haibin wang Sien Lin Liangliang Xu Key Laboratory of Orthopaedics&Traumatology Lingnan Medical Research CenterThe First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou University of Chinese MedicineGuangzhouGuangdong 510000China Department of Orthopaedics&Traumatology Faculty of MedicineThe Chinese University of Hong KongPrince of Wales HospitalShatinHong Kong SAR 999077China Departments of Diagnostics of Traditional Chinese Medicine Guangzhou University of Chinese MedicineGuangzhouGuangdong 510000China Orthopaedic Research Lab Affiliated Hospital of Guangdong Medical UniversityGuangdong Medical UniversityZhanjiangGuangdong 524001China

Fractures have an extraordinarily negative impact on individuals'quality of life and functional status.Nonunion or disability of fracture is a major health issue with important clinical,social,and economic implications.1 Mesenchymal stem cells(MSCs)play an indispensable role in the initiation of the fracture repair process including the formation of a callus which is replaced by new bone.The use of MSCs in the treatment of fractures is very attractive as they can reduce the time of healing and occurrence of nonunion.

关键词： PI3K/Akt HIF1α healing