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Combined gemcitabine and CHK1 inhibitor treatment induces apoptosis resistance in cancer stem cell-like cells enriched with tumor spheroids from a non-small cell lung cancer cell line

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Frontiers of Medicine 2013年第4期7卷 462-476页

作者： douglas d.fang Joan Cao Jitesh P.Jani Konstantinos Tsaparikos Alessandra Blasina Jill Kornmann Maruja E.Lira Jianying Wang Zuzana Jirout Justin Bingham Zhou Zhu Yin Gu Gerrit Los Zdenek Hostomsky Todd VanArsdale Oncology Research Unit PfizerInc.10777 Science Center DriveSan DiegoCA 92121USA WuXi AppTec(Shanghai)Co. Ltd.288 Fute Zhong RdWaigaoqiao Free Trade ZoneShanghai 200131China

Evaluating the effects of novel drugs on appropriate tumor models has become crucial for developing more effective therapies that target highly tumorigenic and drug-resistant cancer stem cell(CSC)*** this study,we demonstrate that a subset of cancer cells with CSC properties may be enriched into tumor spheroids under stem cell conditions from a non-small cell lung cancer cell *** these CSC-like cells with gemcitabine alone and a combination of gemcitabine and the novel CHK1 inhibitor PF-00477736 revealed that PF-00477736 enhances the anti-proliferative effect of gemcitabine against both the parental and the CSC-like cell ***,the CSC-like cells exhibited resistance to gemcitabine-induced ***,the spheroid-forming CSC-like cells may serve as a model system for understanding the mechanism underlying the drug resistance of CSCs and for guiding the development of better therapies that can inhibit tumor growth and eradicate CSCs.

关键词： drug resistance cancer stem cell checkpoint kinase 1(CHK1) PF-00477736 lung cancer tumorigenicity

Reconstruction characteristics of gut microbiota from patients with type 1 diabetes affect the phenotypic reproducibility of glucose metabolism in mice

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Science China Life Sciences 2025年第1期68卷 176-188页

作者： Zhiyi Wang Mengxue Gong Yuanyuan fang Huijuan Yuan Chenhong Zhang State Key Laboratory of Microbial Metabolism School of Life Sciences and BiotechnologyShanghai Jiao Tong University department of Endocrinology Henan Provincial People's HospitalPeople's Hospital of Zhengzhou University

The human microbiota-associated(HMA) mice model, especially the germ-free(GF)-humanized mice, has been widely used to probe the causal relationships between gut microbiota and human diseases such as type 1 diabetes(T1d). However, most studies have not clarified the extent to which the reconstruction of the human donor microbiota in recipient mice correlates with corresponding phenotypic reproducibility. In this study, we transplanted fecal microbiota from five patients with T1d and four healthy people into GF mice, and microbiota from each donor were transplanted into 10 mice. Mice with similar microbiota structure to the donor exhibited better phenotypic reproducibility. The characteristics of the microbial community assembly of donors also influenced the phenotypic reproducibility in mice, and individuals with a higher proportion of stochastic processes showed more severe disorders. Microbes enriched in patients with T1d had a stronger colonization potential in mice with impaired glucose metabolism, and microbiota functional features related to T1d were better reproduced in these mice. This indicates that assembly traits and colonization efficacy of microbiota influence phenotypic reproducibility in GF-humanized mice. Our findings provide important insights for using HMA mice models to explore links between gut microbiota and human diseases.

关键词： gut microbiome human microbiota-associated animal model type 1 diabetes

Inexact proximal gradient algorithm with random reshuffling for nonsmooth optimization

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Science China(Information Sciences) 2025年第1期68卷 219-237页

作者： Xia JIANG Yanyan fang Xianlin ZENG Jian SUN Jie CHEN National Key Lab of Autonomous Intelligent Unmanned Systems School of AutomationBeijing Institute of Technology Beijing Institute of Technology Chongqing Innovation Center School of Electronic and Information Engineering Tongji University

Proximal gradient algorithms are popularly implemented to achieve convex optimization with nonsmooth regularization. Obtaining the exact solution of the proximal operator for nonsmooth regularization is challenging because errors exist in the computation of the gradient; consequently, the design and application of inexact proximal gradient algorithms have attracted considerable attention from researchers. This paper proposes computationally efficient basic and inexact proximal gradient descent algorithms with random reshuffling. The proposed stochastic algorithms take randomly reshuffled data to perform successive gradient descents and implement only one proximal operator after all data pass through. We prove the convergence results of the proposed proximal gradient algorithms under the sampling-without-replacement reshuffling *** computational errors exist in gradients and proximal operations, the proposed inexact proximal gradient algorithms can converge to an optimal solution neighborhood. Finally, we apply the proposed algorithms to compressed sensing and compare their efficiency with some popular algorithms.

关键词： proximal operator random reshuffling inexact computation compressed sensing nonsmooth optimization

Preparation and applications of calcium ferrite as a functional material:A review

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International Journal of Minerals,Metallurgy and Materials 2025年第2期32卷 292-310页

作者： Xiuli Han Bowen duan Lei Liu Shilong fang Weiwei Wang College of Mining Engineering North China University of Science and TechnologyTangshan 063210China Collaborative Innovation Center of Green development and Ecological Restoration of Mineral Resources of Hebei Province Tangshan 063210China Key Laboratory of Mining development and Security Technology of Hebei Province Tangshan 063210China

Calcium ferrite(CF)is recognized as a potential green and efficient functional material because of its advantages of magnetism,electrochemistry,catalysis,and biocompatibility in the fields of materials chemistry,environmental engineering,and ***-fore,the obtained research results need to be systematically summarized,and new perspectives on CF and its composite materials need to be *** on the presented studies of CF and its composite materials,the types and structures of the crystal are *** addition,the current application technologies and theoretical mechanisms with various properties in different fields are ***,the various preparation methods of CF and its composite materials are elaborated in *** importantly,the advantages and disadvantages of the synthesis methods of CF and its composite materials are discussed,and the existing problems and emerging challenges in practical production are ***,the key future research directions of CF and its composite materials have been prospected from the potential application technologies to provide references for its synthesis and efficient utilization.

关键词： calcium ferrite mineral functional materials preparation application perspectives

Inhibitory gamma-aminobutyric acidergic neurons in the anterior cingulate cortex participate in the comorbidity of pain and emotion

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Neural Regeneration Research 2025年第10期20卷 2838-2854页

作者： Lu Guan Mengting Qiu Na Li Zhengxiang Zhou Ru Ye Liyan Zhong Yashuang Xu Junhui Ren Yi Liang Xiaomei Shao Jianqiao fang Junfan fang Junying du department of Neurobiology and Acupuncture Research Third School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina Key Laboratory for Research of Acupuncture Treatment and Transformation of Emotional diseases Third School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina Fuchun Community Health Service Center of Fuyang district HangzhouZhejiang ProvinceChina

Pain is often comorbid with emotional disorders such as anxiety and *** of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid *** review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain *** understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these ***,the mechanisms that regulate gamma-aminobutyric acidergic systems remain *** is also unclear as to whether the mechanisms are presynaptic or *** exploration of the complexities of this system may reveal new pathways for research and drug development.

关键词： anterior cingulate cortex anxiety chronic pain circuit communication comorbidity depression gamma-aminobutyric acidergic neurons parvalbumin neurons synaptic transmission

dietary carbohydrate intake and risk of type 2 diabetes:a 16-year prospective cohort study

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Science China Life Sciences 2025年

作者： Lu Gan Yi Yang Bin Zhao Kai Yu Kehua Guo fang fang Zhiguang Zhou demetrius Albanes Jiaqi Huang Key Laboratory of diabetes Immunology Ministry of Education and Department of Metabolism and Endocrinology The Second Xiangya Hospital of Central South University CSU-Sinocare Research Center for Nutrition and Metabolic Health Xiangya School of Public Health Central South UniversityFurong Laboratory division of Cancer Epidemiology and Genetics National Cancer Institute NIH Department of Health and Human Services School of Computer Science and Engineering Central South University Institute of Environmental Medicine Karolinska Institute National Clinical Research Center for Metabolic diseases Key Laboratory of Diabetes Immunology Ministry of Education and Department of Metabolism and Endocrinology The Second Xiangya Hospital of Central South University

despite considerable research underscoring the importance of carbohydrate intake in relation to the risk of type 2 diabetes(T2d), a comprehensive assessment of this relationship is currently lacking. We aimed to examine the associations of various types and food sources of dietary carbohydrate intake with the risk of T2d, to evaluate potential effect modification by other factors, including genetic susceptibility,and to explore the potential mediators for such associations. The present study included 161,872 participants of the UK Biobank who were free of prevalent cancer, cardiovascular disease, or diabetes, and had at least one validated 24-h dietary recall assessment. Multivariableadjusted age-stratified Cox proportional hazard regression models were applied to estimate hazard ratios(HRs) and 95% confidence intervals(CI) for the associations of various types and food sources of dietary carbohydrate intake with risk of T2d. during a median follow-up of13.6 years, 4,176 incident cases of T2d were identified. In the multivariable-adjusted models, a greater intake of fiber, carbohydrates from whole grains, and carbohydrates from non-starchy vegetables was significantly associated with a lower risk of T2d(highest vs. lowest quantile, HR [95% CI]=0.70 [0.62–0.79], 0.74 [0.67–0.82], and 0.83 [0.75–0.92], respectively, all P for trend d carbohydrate from starchy vegetables was associated with an increased risk of T2d(highest vs. lowest quantile, HR [95%CI]=1.31 [1.16–1.48] and 1.19 [1.09–1.31], respectively, both P for trend d grains or starchy vegetables with an equal amount of whole grains or non-starchy vegetables was associated with 4% to 10% lower risk of T2d(all P values d associations were generally similar across population subgroups, including individuals with different genetic susceptibility to T2d. Mediation analyses of the inverse association between T

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Two Second-Order Ecient Numerical Schemes for the Boussinesq Equations

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应用数学 2025年第1期38卷 114-129页

作者： LIU fang WANG danxia ZHANG Jianwen School of Mathematics Taiyuan University of TechnologyJinzhong 030600China Shanxi Key Laboratory for Intelligent Optimization Computing and Blockchain Technology Jinzhong 030600China

In this paper,we construct two fully decoupled,second-order semi-discrete numerical schemes for the Boussinesq equations based on the scalar auxiliary variable(SAV)*** introducing a scalar auxiliary variable,the original Boussinesq system is transformed into an equivalent *** we discretize it using the second-order backward di erentiation formula(BdF2)and Crank-Nicolson(CN)to obtain two second-order time-advanced *** both numerical schemes,a pressure-correction method is employed to decouple the velocity and *** two schemes possess the desired property that they can be fully decoupled with satisfying unconditional *** rigorously prove both the unconditional stability and unique solvability of the discrete ***,we provide detailed implementations of the decoupling ***,various 2d numerical simulations are performed to verify the accuracy and energy stability of the proposed schemes.

关键词： Scalar auxiliary variable approach Pressure-correction method Fully decoupled Unconditional stability Boussinesq equations

Stability and transferability assessment of the cotton fiber strength QTL qFS-c7-1 on chromosome A07

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The Crop Journal 2021年第2期9卷 380-386页

作者： david d.fang Linghe Zeng Gregory N.Thyssen Christopher d.delhom Efrem Bechere don C.Jones Ping Li Cotton Fiber Bioscience Research Unit USDA-ARS-SRRCNew OrleansLA 70124USA Crop Genetics Research Unit USDA-ARSStonevilleMS 38776USA Cotton Chemistry&Utilization Unit USDA-ARS-SRRCNew OrleansLA 70124USA Cotton Structure and Quality Research Unit USDA-ARS-SRRCNew OrleansLA 70124USA Cotton Incorporated CaryNC 27513USA

Previously we identified a major cotton fiber strength QTL(qFS-c7-1)on chromosome A07 using a multiparent advanced generation intercross(MAGIC)*** assess the stability and transferability of this QTL and its utility in cotton breeding,we made ten new *** populations were developed from crosses between MAGIC recombinant inbred lines,or between cotton cultivars that are different from the MAGIC parents.A total of 2801 F_(2) plants were grown and their fiber quality traits were *** also selected a subset of F_(3) seeds from two populations,and grew F_(3) progeny plots to further evaluate the stability of this *** results showed that the peak of qFS-c7-1 is at 70–72 Mb *** QTL had a major effect on fiber strength explaining 21.9%phenotypic *** effect on other fiber quality attributes such as micronaire,short fiber content,length and uniformity varied between populations,and no effect on fiber elongation was *** QTL effects were stable in the populations analyzed,and in different generations of the same *** SSR and SNP markers near and within the QTL peak reported herein will assist selecting superior fiber quality traits in breeding,with a recommendation that the parental cotton lines should be analyzed using the seven dNA markers within the QTL peak before fully implementing marker assisted selection in a cotton breeding program.

关键词： Cotton Fiber quality Fiber strength MAGIC population qFS-c7-1

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