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Pyrotinib and chrysin synergistically potentiate autophagy in HER2-positive breast cancer

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Signal Transduction and Targeted Therapy 2024年第1期9卷 295-307页

作者： Xiaoxiao Liu Xing zhang Zhiying Shao Xiaorong Zhong Xin Ding Liang Wu jie chen Ping He yan cheng Kunrui Zhu dan Zheng Jing Jing Ting Luo Institute for Breast Health Medicine Cancer CenterBreast CenterWest China HospitalSichuan University610041 ChengduSichuanChina Department of Radiation Oncology Cancer CenterAffiliated Hospital of Xuzhou Medical UniversityJiangsu Center for the Collaboration and Innovation of Cancer BiotherapyCancer InstituteXuzhou Medical University221000 XuzhouChina Department of Orthopedics Trauma and Reconstructive SurgeryUniversity Hospital RWTH AachenAachen 52074Germany Cancer Institute Xuzhou Medical University221000 XuzhouJiangsuChina Division of Nephrology and Transplantation Department of Internal MedicineUniversity Medical Center Rotterdam Erasmus MCRotterdam 3015 GDThe Netherlands Institute for Breast Health Medicine Department of General SurgeryBreast CenterWest China HospitalSichuan University610041 ChengduSichuanChina Institute for Breast Health Medicine West China HospitalSichuan University610041 ChengduSichuanChina

Human epidermal growth factor receptor 2(HER2)-positive breast cancer(BC)has been the most challenging subtype of BC,consisting of 20%of BC with an apparent correlation with poor *** that pyrotinib,a new HER2 inhibitor,has led to dramatic improvements in prognosis,the efficacy of pyrotinib monotherapy remains largely restricted due to its acquired ***,identifying a new potential antitumor drug in combination with pyrotinib to amplify therapeutic efficacy is a pressing ***,we reported a novel combination of pyrotinib with chrysin and explored its antitumor efficacy and the underlying mechanism in HER2-positive *** determined that pyrotinib combined with chrysin yielded a potent synergistic effect to induce more evident cell cycle arrest,inhibit the proliferation of BT-474 and SK-BR-3 BC cells,and repress in vivo tumor growth in xenograft mice *** may be attributed to enhanced autophagy induced by endoplasmic reticulum ***,the combined treatment of pyrotinib and chrysin induced ubiquitination and glucose-6-phosphate dehydrogenase(G6PD)degradation by upregulating zinc finger and BTB/POZ domain-containing family protein 16(ZBTB16)in tumorigenesis of ***,we identified that miR-16-5p was a potential upstream regulator of ZBTB16,and it showed a significant inverse correlation with *** of miR-16-5p overexpression by restoring ZBTB16 significantly potentiated the overall antitumor efficacy of pyrotinib combined with chrysin against HER2-positive ***,these findings demonstrate that the combined treatment of pyrotinib and chrysin enhances autophagy in HER2-positive BC through an unrecognized miR-16-5p/ZBTB16/G6PD axis.

关键词： HER2 synergistic Together

Comprehensive reutilization of herbal waste:Coproduction of magnolol,honokiol,and β-amyrin from Magnolia officinalis residue

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Green Energy & Environment 2024年第2期9卷 403-412页

作者： Lukun Xiao Anyi Zhao jie Qiu An Liu Sha chen Jinzhu Jiang Jun zhang Cong Guo Jipeng Di Jintang cheng Chang chen Kangxin Hou Aiping zhang yan Liu Caixia Wang Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing100700China School of Pharmacy Shanxi Medical UniversityTaiyuan030001China

Herbal extraction residues(HERs)cause serious environmental pollution and resource *** this study,a novel green route was designed for the comprehensive reutilization of all components in HERs,taking Magnolia officinalis residues(MOR)as an *** reluctant structure of MOR was first destroyed by alkali pretreatment to release the functional ingredients(magnolol and honokiol)originally remaining in MOR and to make MOR more accessible for hydrolysis.A metal–organic frame material MIL-101(Cr)with a maximum absorption capacity of 255.64 mg g^(-1)was synthesized to absorb the released honokiol and magnolol from the pretreated MOR solutions,and 40 g L^(-1)reducing sugars were obtained with 81.8%enzymatic hydrolysis rate at 10%MOR solid ***,382 mg L-1β-amyrin was produced from MOR hydrolysates by an engineered yeast *** total,1 kg honokiol,8 kg magnolol,and 7.64 kg β-amyrin could produce from 1 ton MOR by this cleaner process with a total economic output of 170,700 RMB.

关键词： Magnolia officinalis residues(MOR) Comprehensive utilization Metal-organic frame material Biosynthesis

Single cell analysis unveils B cell-dominated immune subtypes in HNSCC for enhanced prognostic and therapeutic stratification

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International Journal of Oral Science 2024年第3期16卷 448-459页

作者： Kang Li Caihua zhang Ruoxing Zhou Maosheng cheng Rongsong Ling Gan Xiong jieyi Ma yan Zhu Shuang chen jie chen Demeng chen Liang Peng State Key Laboratory of Oncology in South China Department of Oral and Maxillofacial SurgeryInstitute of Precision MedicineCenter for Translational MedicineThe First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina Institute for Advanced Study Shenzhen UniversityShenzhenChina Hospital of Stomatology Guangdong Provincial Key Laboratory of StomatologyGuanghua School of StomatologySun Yat-Sen UniversityGuangzhouChina Senior Department of Oncology The Fifth Medical Center of PLA General HospitalBeijingChina

Head and neck squamous cell carcinoma(HNSCC)is characterized by high recurrence or distant metastases rate and the prognosis is *** is mounting evidence that tumor-infiltrating B cells(TIL-Bs)have a crucial,synergistic role in tumor ***,little is known about the role TIL-Bs play in immune microenvironment and the way TIL-Bs affect the outcome of immune checkpoint *** single-cell RNA sequencing(scRNA-seq)data from the Gene Expression Omnibus(GEO)database,the study identified distinct gene expression patterns in *** samples were categorized into TIL-Bs inhibition and TIL-Bs activation groups using unsupervised *** classification was further validated with TCGA HNSCC data,correlating with patient prognosis,immune cell infiltration,and response to *** found that the B cells activation group exhibited a better prognosis,higher immune cell infiltration,and distinct immune checkpoint levels,including elevated PD-L1.A prognostic model was also developed and validated,highlighting four genes as potential biomarkers for predicting survival outcomes in HNSCC ***,this study provides a foundational approach for B cells-based tumor classification in HNSCC,offering insights into targeted treatment and immunotherapy strategies.

关键词： prognosis elevated offering

Identification of marker genes associated with N6-methyladenosine and autophagy in ulcerative colitis

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World Journal of Clinical Cases 2024年第10期12卷 1750-1765页

作者： Xiao-yan Liu dan Qiao Ya-Li zhang Zi-Xuan Liu You-Lan chen Ren-Ye Que Hong-yan Cao yan-cheng Dai Department of Gastroenterology Shanghai Traditional Chinese Medicine-Integrated HospitalShanghai University of Traditional Chinese MedicineShanghai 200082China Institute of Digestive Diseases Long Hua Hospital Shanghai University of Traditional Chinese MedicineShanghai 200032China Department of Gastroenterology Shu Guang HospitalShanghai University of Traditional Chinese MedicineShanghai 201203China

BACKGROUND Both N6-methyladenosine(m6A)methylation and autophagy are considered relevant to the pathogenesis of ulcerative colitis(UC).However,a systematic exploration of the role of the com-bination of m6A methylation and autophagy in UC remains to be *** To elucidate the autophagy-related genes of m6A with a diagnostic value for *** The correlation between m6A-related genes and autophagy-related genes(ARGs)was ***,gene set enrichment analysis(GSEA)was performed on the characteristic ***,the expression levels of four characteristic genes were verified in dextran sulfate sodium(DSS)-induced colitis in *** GSEA indicated that BAG3,P4HB and TP53INP2 were involved in the inflammatory response and TNF-αsignalling via nuclear factor ***,polymerase chain reaction results showed significantly higher mRNA levels of BAG3 and P4HB and lower mRNA levels of FMR1 and TP53INP2 in the DSS group compared to the control *** This study identified four m6A-ARGs that predict the occurrence of UC,thus providing a scientific reference for further studies on the pathogenesis of UC.

关键词： Ulcerative colitis m6A Autophagy Characteristic genes Immune infiltration

MEIC-global-CO_(2):A new global CO_(2)emission inventory with highly-resolved source category and sub-country information

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Science China Earth Sciences 2024年第2期67卷 450-465页

作者： Ruochong XU dan TONG Qingyang XIAO Xinying QIN Cuihong chen Liu yan Jing cheng Can CUI Hanwen HU Wenyu LIU Xizhe yan Huaxuan WANG Xiaodong LIU Guannan GENG Yu LEI Dabo GUAN Kebin HE Qiang zhang Department of Earth System Science Ministry of Education Key Laboratory for Earth System ModelingInstitute for Global Change StudiesTsinghua UniversityBeijing100084China State Key Joint Laboratory of Environment Simulation and Pollution Control School of EnvironmentTsinghua UniversityBeijing100084China Chinese Academy of Environmental Planning Beijing100041China Institute for Carbon Neutrality Tsinghua UniversityBeijing100084China

CO_(2)emission inventory provides fundamental data for climate research and emission ***,most global CO_(2)emission inventories were developed with energy statistics from International Energy Agency(IEA)and were available at country level with limited source ***,as the first step toward a high-resolution and dynamic updated global CO_(2)emission database,we developed a data-driven approach to construct seamless and highly-resolved energy consumption data cubes for 208 countries/territories,797 sub-country administrative divisions in 29 countries,42 fuel types,and 52 sectors,with the fusion of activity data from 24 international statistics and 65 regional/local *** CO_(2)emissions from fossil fuel combustion and cement production in 1970–2021 were then estimated with highly-resolved source category(1,484 of total)and sub-country information(797 of total).Specifically,73%of global CO_(2)emissions in 2021 were estimated with sub-country information,providing considerably improved spatial resolution for global CO_(2)emission *** the support of detailed information,the dynamics of global CO_(2)emissions across sectors and fuel types were presented,representing the evolution of global economy and progress of climate *** differences of sectoral contribution were found across sub-country administrative divisions within a given country,revealing the uneven distribution of energy and economic structure among different *** estimates were generally consistent with existing databases at aggregated level for global total or large emitters,while large discrepancies were observed for middle and small *** database,named the Multiresolution Emission Inventory model for Climate and air pollution research(MEIC)is publicly available through http://*** with highly-resolved information and timely update,which provides an independent carbon emission accounting data source for climate rese

关键词： CO_(2)emissions Data-driven approach Highly-resolved source category Sub-country information

Loss of monopolar spindle-binding protein 3B expression promotes colorectal cancer malignant behaviors by activation of target of rapamycin kinase/autophagy signaling

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World Journal of Gastroenterology 2024年第26期30卷 3229-3246页

作者： Juan Sun Jin-Xiu zhang Meng-Shi Li Meng-Bin Qin Ruo-Xi cheng Qing-Ru Wu Qiu-Ling chen dan yang Cun Liao Shi-Quan Liu jie-An Huang Department of Gastroenterology The Second Affiliated Hospital of Guangxi Medical UniversityNanning 530007Guangxi Zhuang Autonomous RegionChina Department of Colorectal&Anal Surgery The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina

BACKGROUND Monopolar spindle-binding protein 3B(MOB3B)functions as a signal transducer and altered MOB3B expression is associated with the development of human *** To investigate the role of MOB3B in colorectal cancer(CRC).METHODS This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC *** overexpression and knockdown of MOB3B expression were induced in CRC cell lines,changes in cell viability,migration,invasion,and gene expression were *** cell autophagy was detected using transmission electron microscopy,while nude mouse xenograft experiments were performed to confirm the in-vitro *** MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC *** of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells,whereas knockdown of MOB3B expression had the opposite effects in CRC *** the molecular level,microtubule-associated protein light chain 3 II/I expression was elevated,whereas the expression of matrix metalloproteinase(MMP)2,MMP9,sequestosome 1,and phosphorylated mechanistic target of rapamycin kinase(mTOR)was downregulated in MOB3B-overexpressing RKO *** contrast,the opposite results were observed in tumor cells with MOB3B *** nude mouse data confirmed these in-vitro findings,i.e.,MOB3B expression suppressed CRC cell xenograft growth,whereas knockdown of MOB3B expression promoted the growth of CRC cell *** Loss of MOB3B expression promotes CRC development and malignant behaviors,suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.

关键词： Colorectal cancer Monopolar spindle-binding protein 3B Mechanistic target of rapamycin kinase Autophagy Prognosis

Antigen-induced chimeric antigen receptor multimerization amplifies on-tumor cytotoxicity

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Signal Transduction and Targeted Therapy 2024年第1期9卷 259-270页

作者： yan Sun Xiu-Na yang Shuang-Shuang yang Yi-Zhu Lyu Bing zhang Kai-Wen Liu Na Li Jia-chen Cui Guang-Xiang Huang cheng-Lin Liu jie Xu Jian-Qing Mi Zhu chen Xiao-Hu Fan Sai-Juan chen Shuo chen Shanghai Institute of Hematology National Research Center for Translational MedicineState Key Laboratory of Medical GenomicsRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Department of Hematology Second Hospital of Dalian Medical UniversityDalian 116023China National Facility for Protein Science Shanghai Shanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201210China Legend Biotech China Nanjing 211112China Shanghai Immune Therapy Institute Shanghai Cancer InstituteState Key Laboratory of Oncogenes and Related GenesRenji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China Wondercel Biotechnology Shenzhen 518052China

Ligand-induced receptor dimerization or oligomerization is a widespread mechanism for ensuring communication specificity,safeguarding receptor activation,and facilitating amplification of signal transduction across the cellular ***,cell-surface antigeninduced multimerization(dubbed AIM herein)has not yet been consciously leveraged in chimeric antigen receptor(CAR)engineering for enriching T cell-based *** co-developed ciltacabtagene autoleucel(cilta-cel),whose CAR incorporates two B-cell maturation antigen(BCMA)-targeted nanobodies in tandem,for treating multiple *** we elucidated a structural and functional model in which BCMA-induced cilta-cel CAR multimerization amplifies myeloma-targeted T cell-mediated *** analysis of BCMA–nanobody complexes revealed atomic details of antigen–antibody hetero-multimerization whilst analytical ultracentrifugation and small-angle X-ray scattering characterized interdependent BCMA apposition and CAR juxtaposition in ***-induced nanobody CAR multimerization enhanced cytotoxicity,alongside elevated immune synapse formation and cytotoxicity-mediating cytokine release,towards myeloma-derived *** results provide a framework for contemplating the AIM approach in designing next-generation CARs.

关键词： cytotoxicity Antigen elevated

SRY-Box transcription factor 9 triggers YAP nuclear entry via direct interaction in tumors

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2285-2297页

作者： Hui Qian chen-Hong Ding Fang Liu Shi-jie chen chen-Kai Huang Meng-Chao Xiao Xia-Lu Hong Ming-chen Wang Fang-Zhi yan Kai Ding Ya-Lu Cui Bai-Nan Zheng Jin Ding cheng Luo Xin zhang Wei-Fen Xie Department of Gastroenterology Changzheng HospitalNaval Medical UniversityShanghaiChina Department of Gastroenterology Shanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina Drug Discovery and Design Center CAS Key Laboratory of Receptor ResearchState Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina Department of Gastroenterology First Affiliated Hospital of Nanchang UniversityNanchangChina Clinical Cancer Institute Center for Translational MedicineNaval Medical UniversityShanghaiChina

The translocation of YAP from the cytoplasm to the nucleus is critical for its activation and plays a key role in tumor ***,the precise molecular mechanisms governing the nuclear import of YAP are not fully *** this study,we have uncovered a crucial role of SOX9 in the activation of ***9 promotes the nuclear translocation of YAP by direct ***,we have identified that the binding between Asp-125 of SOX9 and Arg-124 of YAP is essential for SOX9-YAP interaction and subsequent nuclear entry of ***,we have discovered a novel asymmetrical dimethylation of YAP at Arg-124(YAP-R124me2a)catalyzed by ***-R124me2a enhances the interaction between YAP and SOX9 and is associated with poor prognosis in multiple ***,we disrupted the interaction between SOX9 and YAP using a competitive peptide,S-A1,which mimics anα-helix of SOX9 containing Asp-125.S-A1 significantly inhibits YAP nuclear translocation and effectively suppresses tumor *** study provides the first evidence of SOX9 as a pivotal regulator driving YAP nuclear translocation and presents a potential therapeutic strategy for YAP-driven human cancers by targeting SOX9-YAP interaction.

关键词： interaction interaction precise

Two different autorefractors for vision screening in children and adolescents

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International Journal of Ophthalmology(English edition) 2024年第2期17卷 331-338页

作者： Xiao-Jun chen Lin-jie Liu Bing Sun dan-dan Jiang Shu-Shu Zuo yan-Hui Wang Chun-Hua zhang yan-yan chen School of Optometry and Ophthalmology Wenzhou Medical UniversityWenzhou 325027Zhejiang ProvinceChina National Clinical Research Center for Ocular Diseases Eye HospitalWenzhou Medical UniversityWenzhou 325027Zhejiang ProvinceChina

AIM:To compare the consistency of two autorefractors(Tianle RM-9000 and Topcon KR-800)for school-age myopia children,and to provide a basis for largescale data analysis and ***:The refractive error in 909 subjects(age 4–18y)were measured using both autorefractors without *** data were analyzed using Fourier decomposition and the correlation coefficients,intraclass correlation coefficients(ICC),and Bland-Altman limits of agreement(LoA)for each parameter were ***:There was a strong correlation between the spherical equivalent(SE),sphere diopter(DS),and cylinder diopter(DC)readings of the Tianle RM-9000 and those of the Topcon KR-800,with correlation coefficient values of 0.98,0.98 and 0.83 and ICC values of 0.99,0.99 and 0.93,***,the correlation coefficients and ICC values of J0 and J45 were unreliable(R=-0.004,-0.034;both ICC<0.10).Bland-Altman analysis revealed that SE,DS,and DC measured by the Tianle RM-9000 were significantly biased toward myopia compared with the Topcon KR-800,and the mean differences were-0.072,-0.026,-0.091 D,respectively(all P<0.01).The minimum absolute value of the difference within the 95%LoA for SE,DS,and DC was 0.63 D,0.50 D,0.62 D,respectively;all these values were in the clinically acceptable *** J0 and J45,the mean differences were close to zero(P=0.43,0.84);however,the 95%LoA were relatively wide(J0 SD:0.53;95%CI:-1.00,1.10;J45 SD:0.52;95%CI:-1.00,1.00).CONCLUSION:The two autorefractors are consistent with each other,as the differences in SE,DS,and DC were within the clinically acceptable *** can compare the data measured by either device in different studies and use the two devices in the same study to generate a dataset that can be analyzed ***,the J0 and J45 vectors are unreliable and should not be used to assess astigmatism.

关键词： refractive error autorefractors school-age myopia children