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VX-509 attenuates the stemness characteristics of colorectal cancer stem-like cells by regulating the epithelial-mesenchymal transition through Nodal/Smad2/3 signaling

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World Journal of Stem Cells 2024年第2期16卷 207-227页

作者： Yun Yuan Xu-Fan Zhang Yu-chen Li Hong-Qing chen Tian Wen Jia-Lian Zheng Zi-Yi Zhao qiong-Ying Hu Department of Laboratory Medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072Sichuan ProvinceChina Department of Nuclear Medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072Sichuan ProvinceChina College of Medical Technology Chengdu University of Traditional Chinese MedicineChengdu 611137Sichuan ProvinceChina Department of Hepatology Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang 110032Liaoning ProvinceChina Hospital of chengdu University of Traditional Chinese Medicine Chengdu 610072Sichuan ProvinceChina Traditional Chinese Medicine Regulating Metabolic Diseases Key Laboratory of Sichuan Province Chengdu 610072Sichuan ProvinceChina

BACKGROUND Colorectal cancer stem cells(CCSCs)are heterogeneous cells that can self-renew and undergo multidirectional differentiation in colorectal cancer(CRC)patients.CCSCs are generally accepted to be important sources of CRC and are responsible for the progression,metastasis,and therapeutic resistance of CRC.Therefore,targeting this specific subpopulation has been recognized as a promising strategy for overcoming CRC.AIM To investigate the effect of VX-509 on CCSCs and elucidate the underlying mechanism.METHODS CCSCs were enriched from CRC cell lines by in conditioned serum-free medium.Western blot,Aldefluor,transwell and tumorigenesis assays were performed to verify the phenotypic characteristics of the CCSCs.The anticancer efficacy of VX-509 was assessed in HCT116 CCSCs and HT29 CCSCs by performing cell viability analysis,colony formation,sphere formation,flow cytometry,and western blotting assessments in vitro and tumor growth,immunohistochemistry and immunofluorescence assessments in vivo.RESULTS Compared with parental cells,sphere cells derived from HCT116 and HT29 cells presented increased expression of stem cell transcription factors and stem cell markers and were more potent at promoting migration and tumori-genesis,demonstrating that the CRC sphere cells displayed CSC features.VX-509 inhibited the tumor malignant biological behavior of CRC-stem-like cells,as indicated by their proliferation,migration and clonality in vitro,and suppressed the tumor of CCSC-derived xenograft tumors in vivo.Besides,VX-509 suppressed the CSC character-istics of CRC-stem-like cells and inhibited the progression of epithelial-mesenchymal transition(EMT)signaling in vitro.Nodal was identified as the regulatory factor of VX-509 on CRC stem-like cells through analyses of differen-tially expressed genes and CSC-related database information.VX-509 markedly downregulated the expression of Nodal and its downstream phosphorylated Smad2/3 to inhibit EMT progression.Moreover,VX-509 reversed the dedifferentiation of CCSCs and inhibit

关键词： Colorectal cancer stem cells Stemness VX-509 Epithelial-mesenchymal transition Nodal

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A Clinical Observation Report on Prenatal Management and Postnatal Treatment of Congenital Granular Cell Epulis

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Maternal-Fetal Medicine 2024年第2期6卷 102-105页

作者： Feng Qin Xiaochuan Xu Yong Yang qiong Li Ting Huang Xiaoyan chen Xiaolan chen Yamin Liu Gongli chen Department of Gynecology and Obstetrics Chongqing Health Center for Women and ChildrenWomen and Children's Hospital of Chongqing Medical UniversityChongqing 401147China Department of Pathology Chongqing Health Center for Women and ChildrenWomen and Children's Hospital of Chongqing Medical UniversityChongqing 401147China.

Introduction Congenital granular cell epulis(CGCE)is a rare,benign tumor that manifests on the mucosal surface of the alveolar ridge in newborns.It was initially described by Neumann in 1871 and has been referred to by various names such as congenital epulis,congenital epulis of the newborn,and congenital granular cell tumor.1 Documentation on larger tumors is limited and reported diameters vary.2 Diagnosis necessitates histological examination and immunohistochemical staining,typically revealing negative immunoreactivity for S-100 and cluster of differentiation 68(CD68).3,4 This article presents a case of CGCE with weakly positive S-100 and CD68 staining,alongside a relatively large size.Additionally,it conducts a literature review on diverse aspects,encompassing multidisciplinary prenatal diagnosis,antenatal management,choice of delivery mode during childbirth,and postnatal treatment,with the objective of augmenting clinicians’comprehension of the ailment.The study adhered to the guidelines of the Declaration of Helsinki and obtained informed consent from the patient and approval from the medical ethics committee of Chongqing Health Center for Women and Children.

关键词： Congenital epulis Fetal Immunohistochemical Prenatal management Postnatal treatment

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The impact of the Rural Minimum Living Standard Guarantee(Rural Dibao)Program on child nutrition outcomes

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Journal of Integrative Agriculture 2024年第2期23卷 444-456页

作者： Dian chen Xiangming fang Yu chen Xiaodong Zheng Zhuo chen Rodney B.W.Smith Academy of Global Food Economics and Policy China Agricultural UniversityBeijing 100083China School of Public Health Georgia State UniversityAtlanta 30303USA School of Economics Zhejiang Gongshang UniversityHangzhou 310018China College of Public Health University of GeorgiaAthens 30602USA Department of Applied Economics University of MinnesotaSaint Paul 55108USA

The Rural Minimum Living Standard Guarantee(Rural Dibao)is an important unconditional cash transfer program to alleviate poverty in rural China.Despite the importance of children’s nutrition in breaking poverty cycles,little is known about the impact of Rural Dibao on child nutrition outcomes.Using China Family Panel Studies(CFPS),this paper examines the effects of Rural Dibao on child nutrition outcomes and investigates potential pathways and heterogeneous effects.We exploit propensity score matching and difference-in-differences techniques to evaluate the effects of the Rural Dibao program on child nutrition outcomes.Our results suggest that Rural Dibao significantly impacts the nutrition outcomes of children up to 15 years of age.Specifically,our results suggest that Rural Dibao improves child height-to-age z-scores by 1.05 standard deviations and lowers the probability of stunting by 11.9 percentage points.Additional analyses suggest that increased protein intake is the main pathway through which Rural Dibao participation contributes to better nutrition outcomes.We also find that the effect of the program is more pronounced among girls,children who are non-left-behind or live with highly educated mothers,and those from low-income families and poor areas.Our findings suggest that Rural Dibao participation helps improve child nutrition outcomes through improving diet quality.

关键词： Rural Minimum Living Standard Guarantee nutrition height-to-age z-scores stunting rural China

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Recent progress and prospects of electrolytes for electrocatalytic nitrogen reduction toward ammonia

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Chinese Chemical Letters 2024年第4期35卷 3-16页

作者： Sajid Mahmood Haiyan Wang fang chen Yijun Zhong Yong Hu Key Laboratory of the Ministry of Education for Advanced Catalysis Materials Department of ChemistryZhejiang Normal UniversityJinhua 321004China The Center for Applied Mathematics and Bioinformatics(CAMB) Gulf University for Science and TechnologyMishref 32093Kuwait Hangzhou Institute of Advanced Studies Zhejiang Normal UniversityHangzhou 311231China

Electrochemical nitrogen reduction reaction(ENRR) provides a promising strategy to achieve sustainable synthesis of ammonia. However, despite great efforts devoted to this research field, the problems such as low energy efficiency and weak selectivity still impede its practical implementation. Most of the research to date has been concentrated on creating sophisticated electrocatalysts, and adequate knowledge of electrolytes is still lacking. Herein, the recent progress in electrolytes for ENRR, including alkaline, neutral,acidic, water-in-salt, organic, ionic liquid, and mixed water-organic electrolytes, is thoroughly reviewed to obtain an in-depth understanding of their effects on electrocatalytic performance. Recently developed representative electrocatalysts in various types of electrolytes are also introduced, and future research priorities of different electrolytes are proposed to develop new and efficient ENRR systems.

关键词： Electrocatalytic nitrogen reduction Ammonia Electrolytes Production rate Faradaic efficiency

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Kelp Fucoidans Facilitate Vascular Recanalization via Inhibiting Excessive Activation of Platelet in Deep Venous Thrombosis Model of Mouse

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Journal of Ocean University of China 2024年第2期23卷 550-556页

作者： SUN Taohua LIU Jie YAN Taishan chen Anjin ZHANG fang Department of Clinical Drug Trials Qingdao Municipal HospitalQingdao 266100China Department of Pharmacy Qingdao Municipal HospitalQingdao 266100China

This study was carried out explore the mechanism underlying the inhibition of platelet activation by kelp fucoidans in deep venous thrombosis(DVT)mouse.In the control and sham mice,the walls of deep vein were regular and smooth with intact intima,myometrium and adventitia.The blood vessel was wrapped with the tissue and there was no thrombosis in the lumen.In the DVT model,the wall was uneven with thicken intima,myometrium and adventitia.After treated with fucoidans LF1 and LF2,the thrombus was dissolved and the blood vessel was recanalized.Compared with the control group,the ROS content,ET-1 and VWF content and the expression of PKC-βand NF-κB in the model were significantly higher(P<0.05);these levels were significantly reduced following treatments with LF2 and LF1.Compared with H_(2)O_(2)treated-HUVECs,combined LF1 and LF2 treatment resulted in significant decrease in the expression of PKC-β,NF-κB,VWF and TM protein(P<0.05).It is clear that LF1 and LF2 reduces DVT-induced ET-1,VWF and TM expressions and production of ROS,thus inhibiting the activation of PKC-β/NF-κB signal pathway and the activation of coagulation system and ultimately reducing the formation of venous thrombus.

关键词： kelp fucoidans LF1 LF2 deep vein thrombosis platelet

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Revealing Al-O/Al-F reaction dynamic effects on the combustion of aluminum nanoparticles in oxygen/fluorine containing environments:A reactive molecular dynamics study meshing together experimental validation

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Defence Technology（防务技术） 2024年第4期34卷 313-327页

作者： Gang Li Chuande Zhao Qian Yu fang Yang Jie chen Institute of Chemical Materials China Academy of Engineering Physics(CAEP)P.O.Box 919-311Mianyang 621900SichuanChina

Improving the energy conversion efficiency in metallic fuel(e.g.,Al)combustion is always desirable but challenging,which often involves redox reactions of aluminum(Al)with various mixed oxidizing environments.For instance,Al-O reaction is the most common pathway to release limited energy while Al-F reaction has received much attentions to enhance Al combustion efficiency.However,microscopic understanding of the Al-O/Al-F reaction dynamics remains unsolved,which is fundamentally necessary to further improve Al combustion efficiency.In this work,for the first time,Al-O/Al-F reaction dynamic effects on the combustion of aluminum nanoparticles(n-Al)in oxygen/fluorine containing environments have been revealed via reactive molecular dynamics(RMD)simulations meshing together combustion experiments.Three RMD simulation systems of Al core/O_(2)/HF,n-Al/O_(2)/HF,and n-Al/O_(2)/CF4 with oxygen percentage ranging from 0%to 100%have been performed.The n-Al combustion in mixed O_(2)/CF_4 environments have been conducted by constant volume combustion experiments.RMD results show that Al-O reaction exhibits kinetic benefits while Al-F reaction owns thermodynamic benefits for n-Al combustion.In n-Al/O_(2)/HF,Al-O reaction gives faster energy release rate than Al-F reaction(1.1 times).The optimal energy release efficiency can be achieved with suitable oxygen percentage of 10%and 50%for n-Al/O_(2)/HF and n-Al/O_(2)/CF_4,respectively.In combustion experiments,90%of oxygen percentage can optimally enhance the peak pressure,pressurization rate and combustion heat.Importantly,Al-O reaction prefers to occur on the surface regions while Al-F reaction prefers to proceed in the interior regions of n-Al,confirming the kinetic/thermodynamic benefits of Al-O/Al-F reactions.The synergistic effect of Al-O/Al-F reaction for greatly enhancing n-Al combustion efficiency is demonstrated at atomicscale,which is beneficial for optimizing the combustion performance of metallic fuel.

关键词： Al-O/Al—F reaction Kinetic benefits Thermodynamic benefits Molecular dynamics Combustion

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Cobalt-nitrogen co-doped porous carbon sphere as highly efficient catalyst for liquid-phase cyclohexane oxidation with molecular oxygen and the active sites investigation

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Frontiers of Chemical Science and Engineering 2024年第3期18卷 101-112页

作者： Lei chen Yuan Sun Jinshan Chi Wei Xiong Pingle Liu fang Hao College of Chemical Engineering National&Local United Engineering Research Centre for Chemical Process Simulation and IntensificationXiangtan UniversityXiangtan411105China

The selective oxidation of cyclohexane to cyclohexanone and cyclohexanol(KA oil)is a challenging issue in the chemical industry.At present the industrial conversion of cyclohexane to cyclohexanone and cyclohexanol is normally controlled at less than 5%selectivity.Thus,the development of highly active and stable catalysts for the aerobic oxidation of cyclohexane is necessary to overcome this low-efficiency process.Therefore,we have developed a cobalt-nitrogen co-doped porous sphere catalyst,Co-NC-x(x is the Zn/Co molar ratio,where x=0,0.5,1,2,and 4)by pyrolyzing resorcinol-formaldehyde resin microspheres.It achieved 88.28%cyclohexanone and cyclohexanol selectivity and a cyclohexane conversion of 8.88%under Co-NC-2.The results showed that the introduction of zinc effectively alleviated the aggregation of Co nanoparticles and optimized the structural properties of the material.In addition,Co0 and pyridinic-N are proposed to be the possible active species,and their proportion efficiently increased in the presence of Zn^(2+)species.In this study,we developed a novel strategy to design highly active catalysts for cyclohexane oxidation.

关键词： KA oil production cyclohexane selective oxidation cobalt-nitrogen co-doped porous carbon spheres metal-organic framework

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Atomically dispersed Ni electrocatalyst for superior urea-assisted water splitting

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Journal of Energy Chemistry 2024年第3期90卷 1-6,I0002页

作者： fang Luo Shuyuan Pan Yuhua Xie chen Li Yingjie Yu Zehui Yang College of Materials Science and Engineering State Key Laboratory of New Textile Materials&Advanced Processing TechnologyWuhan Textile UniversityWuhan 430200China Hubei Hydrogen Energy Technology Innovation Center Faculty of Materials Science and ChemistryChina University of GeosciencesWuhan 430074HubeiChina

Urea oxidation reaction(UOR) has been selected as substitution for oxygen evolution reaction ascribing to its low thermodynamic voltage as well as utilization of nickel as electrocatalyst.Herein,we report the formation of nickel single atoms(Ni-SAs) as exceptional bifunctional electrocatalyst toward UOR and hydrogen evolution reaction(HER) in urea-assisted water splitting.In UOR catalysis,Ni-SAs perform a superior catalytic performance than Ni-NP/NC and Pt/C ascribing to the formation of HOO-Ni-N_(4) structure evidenced by in-situ Raman spectroscopy,corresponding to a boosted mass activity by 175-fold at 1.4 V vs.RHE than Ni-NP/NC.Furthermore,Ni-SAs requires only 450 mV overpotential to obtain HER current density of 500 mA cm^(-2).136 mA cm^(-2) is achieved in urea-assisted water splitting at1.7 V for Ni-SAs,boosted by 5.7 times than Pt/C-IrO_(2) driven water splitting.

关键词： Urea oxidation reaction Hydrogen evolution reaction Nickel single atoms Water splitting

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Safety and efficacy of omalizumab for antihistamine-resistant chronic urticaria in children:a case series and literature review

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World Journal of Pediatrics 2024年第3期20卷 294-298页

作者： Wei-fang Zhu chen Wang Jian-Jun Qiao Lan-Juan Li Department of Dermatology First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Chronic urticaria(CU)is a common skin disease characterized by the occurrence of wheals,with or without angioedema,lasting more than 6 weeks.The prevalence of CU is about 0.7%[1],but higher in children,with an incidence of 1.38%[1].The occurrence of severe pruritus and unpredictable wheals may severely impact patients'quality of life,cause psychological problems,including sleep disorders and depression,and lead to economic burden due to limitation on daily life and work[2,3].

关键词： edema prevalence children

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Super-resolution imaging for in situ monitoring sub-cellular micro-dynamics of small molecule drug

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1864-1877页

作者： Huimin chen Guiqian fang Youxiao Ren Weiwei Zou Kang Ying Zhiwei Yang Qixin chen School of Pharmaceutical Sciences&Institute of Materia Medica Medical Science and Technology Innovation CenterShandong First Medical University&Shandong Academy of Medical SciencesJinan 250062China MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter School of PhysicsXi'an Jiaotong UniversityXi'an 710049China Reproductive Medicine Center Department of Obstetrics and Gynecologythe First Affiliated Hospital of Anhui Medical UniversityHefei 230022China

Small molecule drugs play a pivotal role in the arsenal of anticancer pharmacological agents. Nonetheless, their small size poses a challenge when directly visualizing their localization, distribution, mechanism of action (MOA), and target engagement at the subcellular level in real time. We propose a strategy for developing triple-functioning drug beacons that seamlessly integrate therapeutically relevant bioactivity, precise subcellular localization, and direct visualization capabilities within a single molecular entity. As a proof of concept, we have meticulously designed and constructed a boronic acid fluorescence drug beacon using coumarin–hemicyanine (CHB). Our CHB design includes three pivotal features: a boronic acid moiety that binds both adenosine triphosphate (ATP) and adenosine diphosphate (ADP), thus depleting their levels and disrupting the energy supply within mitochondria;a positively charged component that targets the drug beacon to mitochondria;and a sizeable conjugated luminophore that emits fluorescence, facilitating the application of structured illumination microscopy (SIM). Our study indicates the exceptional responsiveness of our proof-of-concept drug beacon to ADP and ATP, its efficacy in inhibiting tumor growth, and its ability to facilitate the tracking of ADP and ATP distribution around the mitochondrial cristae. Furthermore, our investigation reveals that the micro-dynamics of CHB induce mitochondrial dysfunction by causing damage to the mitochondrial cristae and mitochondrial DNA. Altogether, our findings highlight the potential of SIM in conjunction with visual drug design as a potent tool for monitoring the in situ MOA of small molecule anticancer compounds. This approach represents a crucial advancement in addressing a current challenge within the field of small molecule drug discovery and validation.

关键词： Mitochondrial Drug beacon Sub-cellular Small molecule Energy supply Anti-tumor

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