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Combination of fruquintinib with venetoclax for the treatment of colorectal cancer

Oncology Research 2025年第1期33卷 225-234页

作者： WEI ZHANG WEICHENG WANG RUI WANG XIAO HAN LIJUN ZHU wenjie guo YANHONG GU Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing210029China State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjing210023China Department of Oncology The Affiliated Taizhou People’s Hospital of Nanjing Medical UniversityTaizhou225300China

Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its widespread adverse ***,recognized as the initial inhibitor of B-cell lymphoma protein 2(BCL2),has shown potential in boosting the effectiveness of immunotherapy against *** study investigated the efficacy and mechanisms of fruquintinib combined with venetoclax in treating *** and Materials:We developed a colon cancer mouse model with the CT26 colon cell line to demonstrate fruquintinib and venetoclax’s efficacy against *** we employed various techniques to evaluate different aspects of the experimental *** was used to detect cell proliferation and angiogenesis in tumor *** blot analysis was utilized to examine the occurrence of cell apoptosis,and flow cytometry to quantitate immune cells within the tumor ***,immunofluorescence was employed to measure cytokine ***:The strongest inhibition on tumor growth was achieved by the combination of fruquintinib with venetoclax,as opposed to individual drug *** was found to amplify the impact of fruquintinib,leading to decreased cancer cell proliferation,increased cancer cell apoptosis,lowered angiogenesis,better vascular structure normalization,and improved immune cell ***:Our findings indicate that the addition of venetoclax enhances the impact of fruquintinib on vascular normalization and modulation of the tumor immune *** study presents the justification for utilizing the fruquintinib and venetoclax combination in treating *** holds promise in being assimilated into anticancer medications for CRC.

关键词： Colorectal cancer(CRC) B-cell lymphoma protein 2(BCL2) Venetoclax Vascular endothelial growth factor receptor(VEGFR) Fruquintinib Anti-angiogenesis Immunotherapy

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Stiffeners layout design of thin-walled structures with constraints on multi-fastener joint loads

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Chinese Journal of Aeronautics 2017年第4期30卷 1441-1450页

作者： Jie HOU Jihong ZHU Fei HE Weihong ZHANG wenjie guo Engineering Simulation & Aerospace Computing The Key Laboratory of Contemporary Design and Integrated Manufacturing Technology Northwestern Polytechnieal University Xi'an 710072 China

The purpose of this paper is to present an extended topology optimization method for the stiffeners layout design of aircraft assembled structures. Multi-fastener joint loads and manufacturing constraints are considered simultaneously. On one hand, the joint loads are calculated and constrained within a limited value to avoid the failure of fasteners. On the other hand, the manufacturing constraints of the material distribution in the machining directions of stiffeners are implemented by an improved piecewise interpolation based on a beveled cut-surface. It is proven that the objective function is strictly continuous and differentiable with respect to the piecewise interpolation. The effects of the extended method with two different constraints are highlighted by typical numerical examples. Compared with the standard topology optimization, the final designs have clearly shown the layout of stiffeners and the joint loads have been perfectly constrained to a satisfying level.

关键词： Joint load constraint Manufacturing constraint Stiffeners Thin-walled structures Topology optimization

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Does season regulate heterochronous leaf growth?Mechanisms of petiole-lamina trade-offs in broad-leaved woody plants of the Tianshan Mountains

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Plant Diversity 2024年第6期46卷 755-765页

作者： wenjie guo Lu Gong Yan Luo Qian guo School of Ecology and Environment Xinjiang UniversityWulumuqi830017China

As the core of leaf functional traits,the trade-off relationship between the petiole and lamina expresses the plant's adaptability to the environment in terms of support structure and *** investigated the proportions of allometric growth in the relationship between the petiole and the lamina of broadleaf woody plants in temperate highland Tianshan Mountains montane forests through three dimensions(length,area,and mass),including the length of the lamina(LL)and the length of the petiole(PL),and the area of the lamina(LA)and petiole cross sectional area(PCA)versus the mass of the lamina(LM)and the mass of the petiole(PM),as well as exploring the characteristics of the variance in response to seasonal *** found that the functional traits in all three dimensions showed a clear convergent evolution as the seasons progressed,that is,a“seasonal effect”of increasing and then *** effect of the petioleelamina relationship under spring was minimal in the area dimension;the effects of the threeedimensional relationships of the traits were all highest in summer,and the effect of the petioleelamina relationship was lower in *** also found that petiole traits are simultaneously and multiply affected by lamina traits,with LA and LM having additional effects on the length/mass and area dimensions,*** to tree species,shrub species significantly require more light intensity and support ***-leaved plants would invest more in photoluminescence,increasing leaf light capture efficiency and static load and dynamic *** results suggest that plants have rather complex trade-off mechanisms at the leaf level influencing their ability to adapt to the environment,emphasize the need for leaf-level studies on the relationships between functional traits in plants,and illustrate the importance of the season as a distinct time scale for plant trade-off mechanisms.

关键词： Allometric relationship Functional traits Leaf Season

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Asiatic acid inhibits lung cancer cell growth in vitro and in vivo by destroying mitochondria

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Acta Pharmaceutica Sinica B 2017年第1期7卷 65-72页

作者： Tiancong Wu Ji Geng wenjie guo Jing Gao Xixu Zhu Department of Radiation Oncology Jinling HospitalMedical School of Nanjing University School of Pharmacy Jiangsu University School of Life Science Nanjing University

Asiatic acid(AA), a pentacyclic triterpene found in Centella asiatica, displays significant antiproliferative effects on cancer cells in vitro although the underlying mechanism of this effect remains unknown. This study investigated the efficacy and mechanism of action of AA against lung cancer both in vivo and in vitro. Using the MTT assay, AA was found to induce apoptosis in a dose- and timedependent manner, an effect enhanced by pretreatment with an autophagy inhibitor. It also elevated expression of microtubule-associated protein 1 light chain 3(LC3) and decreased the expression of ***, exposure to AA resulted in collapse of the mitochondrial membrane potential and generation of reactive oxygen species(ROS), suggesting mitochondria are the target of AA. In the mouse lung cancer xenograft model, oral administration of AA significantly inhibited tumor volume and weight accompanied by significant apoptosis of lung cancer cells. In addition, it led to a significant decrease in the expression of proliferating cell nuclear antigen(PCNA). In summary, the results show that AA significantly reduces lung cancer cell growth both in vitro and in vivo and that the associated apoptosis is mediated through mitochondrial damage.

关键词： Asiatic acid Lung cancer Apoptosis Mitochondria Reactive oxygen species

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Case study on stratospheric and mesospheric concentric gravity waves generated by deep convection

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Earth and Planetary Physics 2021年第1期5卷 79-89页

作者： guoChun Shi Xiong Hu ZhiGang Yao wenjie guo MingChen Sun XiaoYan Gong National Space Science Center Chinese Academy of SciencesBeijing 100190China Beijing Institution of Applied Meteorology Beijing 100029China University of Chinese Academy of Sciences Beijing 100049China

Concentric gravity waves(CGWs)in the middle and upper atmosphere show wave-coupling processes between the lower atmosphere and the middle and upper *** this research,we analyzed a case of CGWs detected simultaneously by the AIRS(Atmospheric Infrared Sounder)and the VIIRS/DNB(Day/Night Band of the Visible Infrared Imager Radiometer Suite)in the stratosphere and *** showed that gravity waves(GWs)were generated by the collocated Hurricane Bejisa on the island of *** AIRS data showed arc-like phase fronts of GWs with horizontal wavelengths of 190 and 150 km at 21:08 coordinated universal time(UTC)on 1 January 2014 and at 10:00 UTC on 2 January 2014,whereas the DNB observed arced GWs with horizontal wavelengths of 60 and 150 km in the same geographic regions at 22:24 *** characteristics of CGW parameters in the stratosphere(~40 km)and the mesosphere(~87 km),such as the vertical wavelength,intrinsic frequency,and intrinsic horizontal phase speed,were first derived together with the background winds from ERA5 reanalysis data and Horizontal Wind Model data through the dispersion relationship of GWs and the wind-filtering theory.

关键词： concentric gravity waves wavelength intrinsic frequency phase speed

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Revealing an Invasion Risk of Fish Species in Qingdao Underwater World by Environmental DNA Metabarcoding

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Journal of Ocean University of China 2021年第1期20卷 124-136页

作者： CHEN Jianwei CHEN Zhi LIU Shanshan guo wenjie LI Di MINAMOTO Toshifumi GAO Tianxiang BGI-Qingdao BGI-ShenzhenQingdao 266555China College of Fisheries and Life Science Hainan Tropical Ocean UniversitySanya 572022China China National GeneBank BGI-ShenzhenShenzhen 518120China Qingdao Underwater World Qingdao 266003China Graduate School of Human Development and Environment Kobe UniversityKobe 657-8501Japan Fisheries College Zhejiang Ocean UniversityZhoushan 316022China

Environmental DNA(eDNA)metabarcoding has emerged as a potentially powerful tool to monitor invasive fish *** an alternative(or complementary)tool for biodiversity monitoring,e DNA metabarcoding had been used to detect species in aquariums,which represents an important transit avenue for introducing non-indigenous species with high population *** this study,eDNA metabarcoding as well as morphological characterization were used to reveal the diversity of non-indigenous species in a large aquarium at Qingdao Underwater *** DNA metabarcoding of 14 water samples at five locations from the Big Water Tank detected 24 non-indigenous species and four putative non-indigenous operational taxonomic units(OTUs).In contrast,only 20 non-indigenous species were observed by morphological *** species undetected by morphological characterization,such as Oreochromis niloticus(Linnaeus,1758),are highly adaptable to various environments and/or have invaded preferred regions where they threaten native aquatic *** metabarcoding also detected seven local fishes that were not identified by morphological ***,analysis of OTU diversity among stations and sample replications revealed that eDNA varied within and/or between *** sampling effort as well as negative controls are required to increase the detection rate of species and to eliminate false-positive OTUs.

关键词： eDNA metabarcoding fish diversity non-indigenous sampling effort aquarium

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Effect of lithium or aluminum substitution on the characteristics of graphite for anode of lithium ion batteries

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Rare Metals 2003年第4期22卷 280-284页

作者： guo Huajun, LI Xinhai, WANG Zhixing, PENG wenjie, and guo YongxingCollege of Metallurgical Science and Engineering, Central South University, Changsha 410083, China College of Metallurgical Science and Engineering Central South University Changsha 410083

Modification of graphite for anode of lithium ion batteries is *** of X-ray diffraction shows lithium and aluminum exists as Li compound (CH_3COOLi.2 H_2O) andAl compound (AlD_3) in the graphite, respectiovely. The Brunauer-Emmer-Teller (BET) surface area ofthe modified graphite increases. According to the electrochemical measurements of Li/C cell andprototype Li-ion batteries, the Li-doped graphite has large reversible capacity of 312.2 mA.h/g, lowirreversible capacity of 52.9 mA.h/g, and high initial coulombic efficiency of 85.51 percent. The063448 size prototype battery with Li-doped graphite anode has large discharge capacity of 845 *** good cycling performance. The initial charge/discharge characteristic of Al-doped graphite isclose to those of undoped graphite, but the prototype battery with Al-doped anode shows the bestcycling performance with capacity retention ratio of 94.06 percent at the 200 th cycle.

关键词： Battery graphite dope lithium aluminum

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Andrographolide sulfonate ameliorates lipopolysaccharide-induced acute lung injury in mice by down-regulating MAPK and NF-κB pathways

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Acta Pharmaceutica Sinica B 2016年第3期6卷 205-211页

作者： Shuang Peng Nan Hang Wen Liu wenjie guo Chunhong Jiang Xiaoling Yang Qiang Xu Yang Sun State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University Jiangxi Qingfeng Pharmaceutical Co. Ltd. State Key Laboratory of Innovative Nature Medicine and TCM Injections Jiangxi Qingfeng Pharmaceutical Co. Ltd.

Acute lung injury(ALI) or acute respiratory distress syndrome(ARDS) is a severe, lifethreatening medical condition characterized by widespread inflammation in the lungs, and is a significant source of morbidity and mortality in the patient population. New therapies for the treatment of ALI are desperately needed. In the present study, we examined the effect of andrographolide sulfonate, a water-soluble form of andrographolide(trade name: Xi-Yan-Ping Injection), on lipopolysaccharide(LPS)-induced ALI and inflammation. Andrographolide sulfonate was administered by intraperitoneal injection to mice with LPS-induced ALI. LPS-induced airway inflammatory cell recruitment and lung histological alterations were significantly ameliorated by andrographolide sulfonate. Protein levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid(BALF) and serum were reduced by andrographolide sulfonate administration. m RNA levels of pro-inflammatory cytokines in lung tissue were also suppressed. Moreover, andrographolide sulfonate markedly suppressed the activation of mitogen-activated protein kinase(MAPK) as well as p65 subunit of nuclear factor-κB(NF-κB). In summary, these results suggest that andrographolide sulfonate ameliorated LPS-induced ALI in mice by inhibiting NF-κB and MAPK-mediated inflammatory responses. Our study shows that water-soluble andrographolide sulfonate may represent a new therapeutic approach for treating inflammatory lung disorders.

关键词： Andrographolide sulfonate Lipopolysaccharide Lung injury NF-κB MAPK Mouse

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An improved series expansion method on the multi-frequency analysis of acoustic boundary element

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Chinese Journal of Acoustics 2016年第3期35卷 241-254页

作者： MIAO Yuyue LI Tianyun ZHU Xiang guo wenjie School of Naval Architecture and Ocean Engineering Huazhong University of Science &Technology Hubei Key Laboratory of Naval Architecture & Ocean Engineering Hydrodynamics National Key Laboratory on Ship Vibration & Noise

For the multi-frequency acoustic analysis, a series expansion method has been introduced to reduce the computation time of the frequency-independent parts, but the Runge phenomenon will arise when this method is employed in high frequency band. Therefore, this method is improved by analyzing the application condition and proposing the selection principle of the series truncation number. The argument interval can be adjusted with the wavenumber factor. Therefore, the problem of unstable numeration and poor precision can be solved, and the application scope of this method is expanded. The numerical example of acoustic radiation shows that the improved method is correct for acoustic analysis in wider frequency band with less series truncation number and computation amount.

关键词： An improved series expansion method on the multi-frequency analysis of acoustic boundary element

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Allosterically activating SHP2 by oleanolic acid inhibits STAT3-Th17 axis for ameliorating colitis

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2598-2612页

作者： Jinbo Hu Wen Liu Yi Zou Chenyang Jiao Jiazhen Zhu Qiang Xu Jianjun Zou Yang Sun wenjie guo State Key Laboratory of Pharmaceutical Biotechnology Nanjing Drum Tower HospitalSchool of Life SciencesNanjing UniversityNanjing 210093China Department of Clinical Pharmacology Nanjing First HospitalNanjing Medical UniversityNanjing 210006China Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhou 221004China

Src homology 2 domain-containing tyrosine phosphatase 2(SHP2)is an essential tyrosine phosphatase that is pivotal in regulating various cellular signaling pathways such as cell growth,differentiation,and *** activation of SHP2 has been shown to have a therapeutic effect in colitis and Parkinson's ***,the identification of SHP2 activators and a complete understanding of their mechanism is *** used a two-step screening assay to determine a novel allosteric activator of SHP2 that stabilizes it in an open *** acid was identified as a suitable *** binding to R362,K364,and K366 in the active center of the PTP domain,oleanolic acid maintained the active open state of SHP2,which facilitated the binding between SHP2 and its *** oleanolic acid-activated SHP2 hindered Th17 differentiation by disturbing the interaction between STAT3 and IL-6Rαand inhibiting the activation of ***,via the activation of SHP2 and subsequent attenuation of the STAT3-Th17 axis,oleanolic acid effectively mitigated colitis in *** protective effect was abrogated by SHP2 knockout or administration of the SHP2 inhibitor *** findings underscore the potential of oleanolic acid as a promising therapeutic agent for treating inflammatory bowel diseases.

关键词： Oleanolic acid SHP2 STAT3 Th17 Colitis Allosteric activator

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