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A Tumor Vascular-Targeted Interlocking Trimodal Nanosystem That Induces and Exploits Hypoxia

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A Tumor Vascular-Targeted Interlocking Trimodal Nanosystem T...

Integrated Combination Treatment Using a “Smart” Chemotherapy and MicroRNA Delivery System Improves Outcomes in an Orthotopic Colorectal Cancer Model

首届东方药理论坛暨2018年全国心脑血管药理学术会议、上海市药理学会第十九届学术年会

作者： Luan X Guan YY Liu HJ Lu Q Zhao M Sun D Lovell JF Sun P chen hz Fang C Hongqiao International Institute of Medicine Shanghai Tongren Hospital and Department of Pharmacology and Chemical Biology Institute of Medical SciencesShanghai Jiao Tong University School of Medicine (SJTU-SM) Department of Pharmaceutical Sciences College of PharmacyUniversity of Michigan Department of Pharmacy Ruijin HospitalSJTU-SM Department of Pharmacy Shanghai University of Medicine and Health Sciences Department of Biomedical Engineering University at BuffaloState University of New York Department of General Surgery Shanghai Tongren HospitalSJTU-SM

Vascular-targeted photodynamic therapy(VTP) is a recently approved strategy for treating solid ***,the exacerbated hypoxic stress makes tumor eradication challenging with such a single modality ***,a new graphene oxide(GO)-based nanosystem for rationally designed,interlocking trimodal cancer therapy that enables VTP using photosensitizer verteporfin(VP)(1) with codelivery of banoxantrone dihydrochloride(AQ4 N)(2),a hypoxia-activated prodrug(HAP),and HIF-1α siRNA(siHIF-1α)(3) is *** VTP-induced aggravated hypoxia is highly favorable for AQ4 N activation into AQ4(a topoisomerase II inhibitor) for ***,the hypoxia-induced HIF-la acts as a "hidden brake,"through downregulating CYP450(the dominant HAP-activating reductases),to substantially hinder AQ4 N ***-la is rationally adopted to suppress the HIF-1α expression upon hypoxia and further enhance AQ4 N *** trimodal nanosystem significantly delays the growth of PC-3 tumors in vivo compared to the control nanoparticles carrying VP,AQ4 N,or siHIF-la alone or their pairwise *** multimodal nanoparticle design presents,the first example exploiting VTP to actively induce hypoxia for enhanced HAP *** is also revealed that HAP activation is still insufficient under hypoxia due to the hidden downregulation of the HAP-activating reductases(CYP450),and this can be well overcome by GO nanoparticle-mediated siHIF-la intervention.

关键词： A Tumor Vascular-Targeted Interlocking Trimodal Nanosystem That Induces and Exploits Hypoxia VTP

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Integrated Combination Treatment Using a “Smart” Chemother...

Stepwise Oxidation of Ketene Dithioacetal

首届东方药理论坛暨2018年全国心脑血管药理学术会议、上海市药理学会第十九届学术年会

作者： Liu HJ Luan X Feng HY Dong X Yang SC chen ZJ Cai QY Lu Q Zhang Y Sun P Zhao M chen hz Lovell JF Fang C Hongqiao International Institute of Medicine Shanghai Tongren Hospital and Department of Pharmacology and Chemical Biology Institute of Medical SciencesShanghai Jiao Tong University School of Medicine (SJTU-SM) Department of General Surgery Shanghai Tongren HospitalSJTU-SM Department of Pharmacy Shanghai University of Medicine and Health Sciences Department of Biomedical Engineering University at BuffaloState University of New York

Mesoporous silica nanoparticles(MSN) can load and deliver potentially synergistic anticancer agents such as small molecule cytotoxics(like doxorubicin,DOX) and nucleic acids(like microRNA,miRNA).However,these cargos have different underlying chemical properties so overcoming respective intracellular delivery barriers is a key *** to deliver DOX from MSN frequently employ pH-driven mechanisms that are restricted to the acidic environment of ***,strategies to deliver miRNA make use of approaches that deliberately compromise lysosomal membrane integrity to enable cytosolic delivery of the *** reconcile these two needs(lysosomal delivery of DOX and intracellular delivery of miRNA),a new methodology by "weaving" polyethylenimine on the MSN surface through disulfide bonds to achieve superior delivery of chemotherapy(DOX) and miRNA therapy(using miRNA-145) is ***,an active targeting strategy based on a peptide ligand with affinity to glucose-regulated protein 78(GRP78),a cell surface protein overexpressed in colorectal carcinoma,is *** active targeting approach results in enhanced synergistic antitumor effect both in vitro and in vivo in an orthotopic murine model of colorectal *** together,this work demonstrates the capability and advantages of "smart" MSN delivery systems to deliver anticancer cargo appropriately to targeted cancer cells.

关键词： miRNA Integrated Combination Treatment Using a Smart Chemotherapy and MicroRNA Delivery System Improves Outcomes in an Orthotopic Colorectal Cancer Model

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Chinese Chemical Letters 2001年第10期12卷 865-868页

作者： chen, K Yang, hz Nankai Univ Inst Elementoorgan Chem State Key Lab Elementoorgan Chem Tianjin 300071 Peoples R China

Stepwise oxidation of ketene dithioacetal is found and the different oxidation products changed with the amount of oxidant, temperature and reaction time.

关键词： oxidation reaction ketene dithioacetal hydrogen peroxide

Primary porcine hepatocytes with portal vein serum cultured on microcarriers or in spheroidal aggregates

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World Journal of Gastroenterology 2000年第3期6卷 365-370页

作者： Gao Y Hu hz chen K Yang JZ First Mil Med Univ Zhujiang Hosp Dept Hepatobiliary Surg Guangzhou 510282 Guangdong Provi Peoples R China

AIM To develop a culture mode providingdurable biomaterials with high yields andactivities used in bioartificial *** Hepatocytes were isolated from awhole pig liver by Seglen’s method of orthotopicperfusion with *** culture onmicrocarriers,primary porcine hepatocyteswere inoculated at a concentration of 5×10~7/mLinto the static culture systems containing 2 g/LCytodex-3,then supplemented with 100 mL/Lfetal calf serum(FCS)or 100 mL/L porcineportal vein serum(PPVS)*** aggregate culture hepatocytes wereinoculated into 100 mL siliconized flasks at aconcentration of 5.0×10~6/*** In culture on microcarriershepatocytes tended to aggregate on Cytodex-3obviously after being *** multi-cellular aggregated spheroids could be found inthe two systems 24 h-48 h after hepatocyteswere *** morphological charact-eristics and synthetic functions were maintainedfor 5 wk in FCS culture system and 8 wk in PPVSculture *** spheroidal aggregate cultureabout 80%-90% isolated hepatocytes becameaggregated spheroids 24h after cultured insuspension and mean diameter of the spheroidswas 100μ*** relationship among thehepatocytes resembled that in the liver in *** functions of albumin and urea of the spheroids were twice those of hepatocytescultured on *** As high-yields and high-activitymodes of culture on microcarriers or inspheroidal aggregate culture with portal veinserum are promising to provide biomaterials forbioartificial liver(BAL)efficiently.

关键词： porcine hepatocytes microcarriers cell culture spheroidal aggregate culture portal vein serum

Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

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Neural Regeneration Research 2025年第5期20卷 1483-1494页

作者： Xihang chen Zhifeng chen Menghua Li Weiwei Guo Shuolong Yuan Liangwei Xu Chang Lin Xi Shi Wei chen Shiming Yang Senior Department of Otolaryngology Head and Neck Surgery Chinese PLA General HospitalChinese PLA Medical SchoolBeijingChina State Key Laboratory of Hearing and Balance Science BeijingChina National Clinical Research Center for Otolaryngologic Diseases BeijingChina Key Laboratory of Hearing Science Ministry of EducationBeijingChina Beijing Key Laboratory of Hearing Impairment Prevention and Treatment BeijingChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Otolaryngology Head and Neck Surgery The 940th Hospital of Joint Logistics Support Force of Chinese PLALanzhouGansu ProvinceChina Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikouHainan ProvinceChina Academician Workstation of Hainan University School of Pharmaceutical SciencesYazhou BaySanyaHainan ProvinceChina

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory ***,there are currently no effective pharmacological interventions for patients with noise-induced hearing ***,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory *** established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 *** found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with *** noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k hz frequencies compared with the noise exposure group treated with *** findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell ***,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy *** treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)*** conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing *** findings suggest that inhibiting lysine-specific demethylase 1 is a

关键词： 4-hydroxynonenal apoptosis autophagy cleaved caspase-3 inflammation NOD-like receptor family pyrin domain-containing 3(NLRP3) noise-induced hearing loss oxidative stress Sestrin2 tranylcypromine

Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways

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Neural Regeneration Research 2025年第9期20卷 2706-2726页

作者： Biao Xiao Chaoyang Chu Zhicheng Lin Tianyuan Fang Yuyu Zhou Chuxia Zhang Jianghui Shan Shiyu chen Liping Li Department of Physiology and Pharmacology Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina Ningbo Key Laboratory of Behavioral Neuroscience Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina Key Laboratory of Addiction Research of Zhejiang Province NingboZhejiang ProvinceChina

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's ***,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and ***,nonpharmacological interventions aimed at inducing adult neurogenesis are currently *** individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully *** this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 *** deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease ***,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus *** findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 ***,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice

关键词： acousto-optic stimulation adult neurogenesis Alzheimer's disease amyloid precursor protein/presenilin 1 mice amyloid-beta deposition brain cell apoptosis cognitive impairment depression-like behavior involuntary treadmill exercise olfactory stimulation serum metabolites

THE PERTURBATION SOLUTIONS OF THE FLOW IN A ROTATING CURVED ANNULAR PIPE

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Journal of Hydrodynamics 2001年第1期13卷 75-80页

作者： Zhang Ben-zhao, chen Qian, Zhang Jin-suo, Cui Liang-chen Department of Mechanics, Zhejiang University, Hangzhou, 310027, China[WT5”hz] Dep. of Mechanics Zhejiang Univ. Hangzhou 310027 China

WT5”BZ]In this paper, the flow in a rotating curved annular pipe is examined by a perturbation method. A second order perturbation solution is presented. The characteristics of the secondary flow and the axial flow are studied in detail. The study indicates that the loops of the secondary flow are more complex than those in a curved annular pipe without rotation and its numbers depend on the ratio of the Coriolis force to centrifugal force F. As F≈-1, the secondary flow has eight loops and its intensity reaches the minimum value, and the distribution of the axial flow is like that of the Poiseuille flow. The position of the maximum axial velocity is pushed to either outer bend or inner bend, which is also determined by F. [WT5”hz]

关键词： rotating curved annular pipe secondary flow Coriolis force centrifugal force perturbation solution

Electromagnetic three-dimensional vibration energy harvester based on an oblique cross-spring vibrator structure

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Science China Technological Sciences 2025年第1期 189-206页

作者： Yaohui AN Yimin FAN Kefan XU Yuhao chen Yewei ZHANG Liqun chen School of Science Harbin Institute of Technology College of Aerospace Engineering Shenyang Aerospace University

This paper presents an electromagnetic three-dimensional vibration energy harvesting device that uses an oblique cross-spring vibrator structure to collect low-frequency vibration energy. The oblique cross-spring structure allowed the center vibrator to vibrate in any direction. Together with six-directional coils, this configuration senses and harvests environmental vibrations across all directions and levels. First, the dynamics of the oblique cross-spring vibrator structure were analyzed and a finite element simulation was performed for the magnet arrangement and mode shape of the structure. A prototype is designed,fabricated, and experimentally verified. The results showed that the efficiency of the three-dimensional energy output was higher under the same excitation, which was 2.7 times higher than that of the unidirectional output. The unidirectional output power with load is 0.94 mW at 11 hz under 0.3 g base excitation. The highest total output power of the prototype was 50 mW when it was fixed to the leg at a running speed of 8 km/h. Consequently, the energy harvesting scheme proposed in this study has a considerable low-frequency output effect, which provides a novel means of improving the electrical performance of energy harvesting systems for self-powered IoT and sensor devices.

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Distribution and age-related changes in somatostatinimmunopositive cell in the small intestinal of African ostrich

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Distribution and age-related changes in somatostatinimmunopo...