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Combination of fruquintinib with venetoclax for the treatment of colorectal cancer

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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 University Nanjing 210029 China. Department of Oncology The Affiliated Taizhou People's Hospital of Nanjing Medical University Taizhou 225300 China. State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University Nanjing 210023 China.

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 reactions. Venetoclax, recognized as the initial inhibitor of B-cell lymphoma protein 2 (BCL2), has shown potential in boosting the effectiveness of immunotherapy against CRC. This study investigated the efficacy and mechanisms of fruquintinib combined with venetoclax in treating CRC.Methods and Materials:We developed a colon cancer mouse model with the CT26 colon cell line to demonstrate fruquintinib and venetoclax's efficacy against tumors. Then we employed various techniques to evaluate different aspects of the experimental outcomes. Immunohistochemistry was used to detect cell proliferation and angiogenesis in tumor tissues. Western blot analysis was utilized to examine the occurrence of cell apoptosis, and flow cytometry to quantitate immune cells within the tumor tissues. Moreover, immunofluorescence was employed to measure cytokine levels.Results:The strongest inhibition on tumor growth was achieved by the combination of fruquintinib with venetoclax, as opposed to individual drug use. Venetoclax 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 infiltration.Conclusion:Our findings indicate that the addition of venetoclax enhances the impact of fruquintinib on vascular normalization and modulation of the tumor immune microenvironment. Our study presents the justification for utilizing the fruquintinib and venetoclax combination in treating CRC. Venetoclax holds promise in being assimilated into anticancer medications for CRC.

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

Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior

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Neural Regeneration Research 2025年第1期20卷 159-173页

作者： Man han Deyang Zeng wei Tan Xingxing Chen Shuyuan Bai Qiong Wu Yushan Chen Zhen wei Yufei Mei Yan Zeng Brain Science and Advanced Technology Institute Wuhan University of Science and TechnologyWuhanHubei ProvinceChina Geriatric Hospital Affiliated to Wuhan University of Science and Technology WuhanHubei ProvinceChina School of Public Health Wuhan University of Science and TechnologyWuhanHubei ProvinceChina

Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral *** studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and *** how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress *** this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of *** focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine *** determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic ***,BDNF might be a biological indicator regulating stress-related processes in various brain regions.

关键词： amygdala chronic mild stress chronic social defeat stress corticolimbic system depression hippocampus medial prefrontal cortex nucleus accumbens social stress models ventral tegmental area

Stiffness-tunable biomaterials provide a good extracellular matrix environment for axon growth and regeneration

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Neural Regeneration Research 2025年第5期20卷 1364-1376页

作者： Ronglin han Lanxin Luo Caiyan wei Yaru Qiao Jiming Xie Xianchao Pan Juan Xing Department of Pathophysiology School of Basic Medical SciencesSouthwest Medical UniversityLuzhouSichuan ProvinceChina Department of Medicinal Chemistry School of PharmacySouthwest Medical UniversityLuzhouSichuan ProvinceChina

Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to providing physical support for cells, the extracellular matrix also conveys critical mechanical stiffness cues. During the development of the nervous system, extracellular matrix stiffness plays a central role in guiding neuronal growth, particularly in the context of axonal extension, which is crucial for the formation of neural networks. In neural tissue engineering, manipulation of biomaterial stiffness is a promising strategy to provide a permissive environment for the repair and regeneration of injured nervous tissue. Recent research has fine-tuned synthetic biomaterials to fabricate scaffolds that closely replicate the stiffness profiles observed in the nervous system. In this review, we highlight the molecular mechanisms by which extracellular matrix stiffness regulates axonal growth and regeneration. We highlight the progress made in the development of stiffness-tunable biomaterials to emulate in vivo extracellular matrix environments, with an emphasis on their application in neural repair and regeneration, along with a discussion of the current limitations and future prospects. The exploration and optimization of the stiffness-tunable biomaterials has the potential to markedly advance the development of neural tissue engineering.

关键词： alginate axon growth biomaterials extracellular matrix neural repair neurons neuroregeneration polyacrylamide polydimethylsiloxane stiffness

基于CodeBERT和Stacking集成学习的补丁正确性验证方法

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计算机科学 2025年第1期52卷 250-258页

作者：韩威姜淑娟周伟中国矿业大学计算机科学与技术学院江苏徐州221116 中国矿业大学矿山数字化教育部工程研究中心江苏徐州221116

近年来,自动程序修复已成为软件工程领域的重要研究课题。然而,现有的自动修复技术大多是基于补丁生成和测试的,在补丁验证环节时间成本很高。此外,由于测试套件的不完备,许多候选补丁虽然能通过测试,但实际上并不正确,从而导致补丁过... 详细信息

近年来,自动程序修复已成为软件工程领域的重要研究课题。然而,现有的自动修复技术大多是基于补丁生成和测试的,在补丁验证环节时间成本很高。此外,由于测试套件的不完备,许多候选补丁虽然能通过测试,但实际上并不正确,从而导致补丁过拟合。为提高补丁验证的效率并缓解补丁过拟合的问题,提出了一种静态的补丁验证方法。该方法首先使用大型预训练模型CodeBERT自动提取缺陷代码片段和补丁代码片段的语义特征,然后使用历史缺陷修复补丁数据训练Stacking集成学习模型,训练之后的模型可以对新的缺陷修复补丁进行有效验证。在Defects4J缺陷数据集相关的1 000个补丁数据上对所提方法的验证能力进行评估。实验结果表明,该方法可以有效地验证补丁的正确性,从而提高补丁验证的效率。

关键词：自动程序修复补丁验证预训练模型集成学习 Defects4J缺陷数据集

Facile synthesis of the dodecahydridododecaborate (B12H122-) from borane Lewis base adducts

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Science China Chemistry 2025年

作者： Yi Jing Xin-Ran Liu Xing-Hua wang Hui han Sha-Sha Liang Xi-Meng Chen Dong-Hui wei Lai-Sheng wang Xue-Nian Chen College of Chemistry Zhengzhou University School of Chemistry and Chemical Engineering Henan Key Laboratory of Boron Chemistry and Advanced MaterialsHenan Normal University Department of Chemistry Brown University

Polyhedral boranes are a class of well-known boron molecular clusters widely used in energy,chemistry,medicine,and materials science because of their unique physical and chemical *** efforts have been made in the past decades to find more effective synthetic methods for this important class of boron ***,existing synthetic methods suffer from low efficiency and low ***,we report a facile one-pot synthesis of[（CH3）3S]2B12H12with moderate yields at mild *** mechanisms for the multi-step chemoselective synthesis of B12H122-without other by-products are elucidated based on theoretical results and our previous *** Lewis base used in B–H bond condensation reaction,which acts as a hydrogen or to balance the newly generated polyhedral borane charges,is proposed and studied in *** current study has led to a more effective and selective synthetic method for B12H122-and has also implicated the syntheses of other new polyhedral boranes.

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Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

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Neural Regeneration Research 2025年第5期20卷 1467-1482页

作者： Wenrui Qu Xiangbing Wu wei Wu Ying wang Yan Sun Lingxiao Deng Melissa Walker Chen Chen Heqiao Dai Qi han Ying Ding Yongzhi Xia George Smith Rui Li Nai-Kui Liu Xiao-Ming Xu Spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA Department of hand Surgery the Second Hospital of Jilin UniversityChangchunJilin ProvinceChina Shriners Hospitals Pediatric Research Center Temple University School of MedicinePhiladelphiaPAUSA Department of Anatomy&Cell Biology Indiana University School of MedicineIndianapolisINUSA

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal *** we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord *** report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal *** Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder ***,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord *** findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

关键词： axonal regrowth bladder function chondroitinase ABC functional recovery glial scar lentivirus migration Schwann cell spinal cord injury transplantation

Mechanism of action of Linggui Zhugan Decoction in treating non-alcoholic fatty liver disease using untargeted metabolomics approach

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Traditional Medicine Research 2025年第2期10卷 65-76页

作者： Huan Pei Ren-Lin Li Xin-Ran Song Qian-Qian Wan Yu-Ming wang han-zhou Li wei-Quan Xu Jia-Bao Liao wei-Bo Wen Jing Miao Huan-Tian Cui School of Basic Medicine Yunnan University of Chinese MedicineKunming 650599China School Clinical Medical College Yunnan University of Chinese MedicineKunming 650599China First School of Clinical Medicine Yunnan University of Chinese MedicineKunming 650599China School of Integrative Chinese and Western Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China Department of Pharmacy Tianjin Second People's HospitalTianjin 300192China

Background:Non-alcoholic fatty liver disease(NAFLD)is a liver disorder characterized by the accumulation and degeneration of fat in the liver cells,a condition that may further deteriorate and lead to cirrhosis and liver *** studies showed that metabolic dysfunction can promote NAFLD *** Zhugan Decoction(LGZGD)has therapeutic effects on *** mechanism of LGZGD still remains *** study was to examine the impact of LGZGD on the metabolic processes involved in the development of ***:A mice model of NAFLD was treated with *** therapeutic potential of LGZGD was evaluated by assessing the activity of transaminases,lipids levels of blood,and pathological changes in the liver of the mice model of ***,this study also evaluated the influence of LGZGD on liver inflammation and oxidative ***:The results of untargeted metabolomics analysis showed that LGZGD reduced the disordered lipid metabolism in NAFLD *** improved the oxidative stress and also reduced the levels of pro-inflammatory cytokines in the *** metabolomics analysis of liver samples revealed that LGZGD treatment improved metabolic disorders,including alanine,aspartate,glutamate,glycerophospholipid metabolism,and citrate *** RT-qPCR and Western blot results showed that LGZGD could regulate the expression of key enzymes in the metabolic pathway of the citrate cycle,including ATP-citrate lyase(ACLY),alanine-glyoxylate aminotransferase-2(AGXT2),phosphatidylethanolamine N-methyltransferase(PEMT),and succinate dehydrogenase(SDH).Conclusion:We found that LGZGD can treat NAFLD by reducing inflammatory responses,inhibiting oxidative stress,regulating alanine,aspartate,glutamate,and glycerophospholipid metabolism,and citrate cycle pathways.

关键词： NAFLD LGZGD untargeted metabolomics glycerophospholipid metabolism citrate cycle

Macroscopic polarization enhancement boosting piezo-photocatalytic performance via Nb-doping on B-site of Bi_(4)Ti_(3)O_(12)nanosheets

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Journal of Advanced Ceramics 2024年第4期13卷 437-446页

作者： Hongjian Yu Xindong wei Min wang Yan Zhang zheng Wu Fan guo jie han School of Chemistry and Chemical Engineering Yangzhou UniversityYangzhou 225002China Engineering Research Center of Ministry of Education for Geological Carbon Storage and Low Carbon Utilization of Resources Beijing Key Laboratory of Materials Utilization of Nonmetallic Minerals and Solid WastesNational Laboratory of Mineral MaterialsSchool of Material Sciences and TechnologyChina University of Geosciences(Beijing)Beijing 100083China School of Environmental and Chemical Engineering Xi’an Key Laboratory of Textile Chemical Engineering AuxiliariesXi'an Polytechnic UniversityXi'an 710048China

The development of a high-performance ferroelectric piezo-photocatalyst is an efficient strategy for advancing sustainability within the environmental and energy ***,a major challenge lies in the creation of a strong polarized electric field that can effectively hinder charge recombination,both within the bulk and on the surface of ***,we synthesize a series of Nb-doped Bi_(4)Ti_(3)O_(12)nanosheets via a facile one-pot hydrothermal method to achieve synergistically enhanced piezo-photocatalytic performance in CO_(2)reduction and pollutant *** optimized doped Bi_(4)Ti_(3)O_(12)demonstrates remarkable efficiency in the conversion of CO_(2)into CO,with a high production rate of 72.7μmol∙g−1∙h−1 without using co-catalysts or any sacrificial agent,surpassing the performance of unmodified Bi_(4)Ti_(3)O_(12)by up to 4.69 ***,our catalyst demonstrates ultra-fast piezo-photocatalytic degradation of organic pollutant Rhodamine B(RhB)at low concentrations and exceptional piezo-photocatalytic activity at high concentrations,outperforming most previously reported state-of-the-art *** systematic corroboration of catalyst characterization and experimental analysis reveals that the synergistic effect arises from the amplified macroscopic polarization induced by lattice distortion caused by the larger Nb ions,thereby improving piezo-photocatalytic *** research thus offers valuable insights into the direct design and fabrication of versatile catalytic systems,with applications spanning CO_(2)valorization and beyond.

关键词： CO_(2)reduction dye degradation piezo-photocatalysis Nb-doped Bi_(4)Ti_(3)O_(12) macroscopic polarization regulation

Combinatorial screening via high-throughput preparation:Thermoelectric performance optimization for n-type Bi-Te-Se film with high average zT>1

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Journal of Materials Science & Technology 2023年第29期160卷 18-27页

作者： Guangyu han wei Zhu Siming guo jie zhou Yutong Liu Yuan Deng School of Materials Science and Engineering Beihang UniversityBeijing 100083China Research Institute for Frontier Science Beihang UniversityBeijing 100083China Key Laboratory of Intelligent Sensing Materials and Chip Integration Technology of Zhejiang Province(2021E10022) Hangzhou Innovation Institute of Beihang UniversityHangzhou 310052China

Thermoelectric materials have drawn extensive interest due to the direct conversion between electricity and heat,however,it is usually a time-consuming process for applying traditional“sequential”meth-ods to grow materials and investigate their properties,especially for thermoelectric films that typically require fine microstructure ***-throughput experimental approaches can effectively accelerate materials development,but the methods for high-throughput screening of the microstructures require further *** this work,a combinatorial high-throughput optimization solution of material properties is proposed for the parallel screening and optimizing of composition and microstructure,which involves two distinctive types of high-throughput fabrication approaches for thin films,along with a new portable multiple discrete masks based high-throughput preparation ***,Bi_(2)Te_(3-x)Se_(x)thin film library with 196 throughputs for locating the optimized composition is obtained in one growth *** addition,another thin film library composed of 31 materials with traceable process parameters is built to further investigate the relationship between microstructure,process,and thermoelectric *** high-throughput screening,the Bi_(2)Te_(2.9)Se_(0.1)film with(00l)orientation is prepared with a peak zT value of 1.303 at 353 K along with a high average zT value of 1.047 in the interval from 313 to 523 *** method can be also extended to the discovery of other functional thin films with a rapid combinatorial screening of the composition and structure to accelerate material optimization.

关键词： High-throughput preparation Thermoelectric performance Bi-Te-Se film Combinatorial screening