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SBL-JP-0004:A promising dual inhibitor of JAK2 and PI3KCD against gastric cancer

Oncology Research 2025年第1期33卷 235-243页

作者： HASSAN m.OTIFI Department of Pathology College of MedicineKing Khalid UniversityAbha62521Saudi Arabia

Background:Gastric cancer(GC)remains a global health burden and is often characterized by heterogeneous molecular profiles and resistance to conventional *** phosphoinositide 3-kinase and PI3K and Janus kinase(JAK)signal transducer and activator of transcription(JAK-STAT)pathways play pivotal roles in GC progression,making them attractive targets for therapeutic ***:This study applied a computational and molecular dynamics simulation approach to identify and characterize SBL-JP-0004 as a potential dual inhibitor of JAK2 and PI3KCD *** and SNU-5 GC cells were used for in vitro ***:SBL-JP-0004 exhibited a robust binding affinity for JAK2 and PI3KCD kinases,as evidenced by molecular docking scores and molecular dynamics *** interactions and Gibbs binding free energy estimates confirmed stable and favorable interactions with target ***-JP-0004 displayed an half-maximal inhibitory concentration(ic_(50))value of 118.9 nm against JAK2 kinase and 200.9 nm against PI3KCD ***-JP-0004 exhibited potent inhibition of cell proliferation in KATOIII and SNU-5 cells,with half-maximal growth inhibitory concentration(GI50)values of 250.8 and 516.3 nm,respectively.A significant elevation in the early phase apoptosis(28.53%in KATOIII cells and 26.85%in SNU-5 cells)and late phase apoptosis(17.37%in KATOIII cells and 10.05%in SNU-5 cells)were observed with SBL-JP-0004 treatment compared to 2.1%and 2.83%in their respective ***:The results highlight SBL-JP-0004 as a promising dual inhibitor targeting JAK2 and PI3KCD kinases for treating GC and warrant further preclinical and clinical investigations to validate its utility in clinical settings.

关键词： Gastric cancer(GC) Dual inhibition JAK2 PI3KCD SBL-JP-0004 molecular docking molecular dynamics simulation

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消旋棉酚及其旋光异构体对小鼠乳酸脱氢酶(LDH)抑制作用的比较研究

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生殖与避孕 1991年第1期11卷 20-25页

作者：梁志国 Kim ic Waller DP goldberg e 国家计划生育委员会科学技术研究所美国芝加哥伊利诺伊大学药物所美国西北大学生物系

本文用消旋棉酚及其旋光异构体比较研究了对纯化小鼠肝脏LDH-A_4,心脏LDH-B_4和睾丸LDH-C_4的抑制作用。其抑制程度与实验温度和棉酚剂量有关。37℃时的抑制作用比25℃时强得多。棉酚低浓度(1～4μm)时三种酶对同一种棉酚的反应有明显... 详细信息

本文用消旋棉酚及其旋光异构体比较研究了对纯化小鼠肝脏LDH-A_4,心脏LDH-B_4和睾丸LDH-C_4的抑制作用。其抑制程度与实验温度和棉酚剂量有关。37℃时的抑制作用比25℃时强得多。棉酚低浓度(1～4μm)时三种酶对同一种棉酚的反应有明显的不同,而在较高棉酚浓度(20～100μm)时棉酚对三种酶的抑制作用大体相同。对同一种酶来说,消旋棉酚,右旋棉酚和左旋棉酚对LDH的抑制作用并无差异。结论是,棉酚及其旋光异构体并不特异地抑制LDH-C_4,而在离体试验中,不能反映棉酚在体内试验中所表现的光学立体结构特异性。

关键词：棉酚旋光异构体 NADH LDH同功酶

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Label-free detection of single nanoparticles and biological molecules using microtoroid optical resonators

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Light(Science & Applications) 2016年第1期5卷 863-868页

作者： Judith Su Alexander FG goldberg Brian m Stoltz Division of Biology and Biological engineering California Institute of TechnologyPasadenaCAUSA Divison of Chemistry and Che.ical engineering California Institute of TechnologyPasadenaCAUSA

Single-molecule detection is one of the fundamental challenges of modern *** experiments often use labels that can be expensive,difficult to produce,and for small analytes,might perturb the molecular events being *** size plays an important role in determining *** we use laser-frequency locking in the context of sensing to improve the signal-to-noise ratio of microtoroid optical resonators to the extent that single nanoparticles 2.5 nm in radius,and 15.5 kDa molecules are detected in aqueous solution,thereby bringing these detectors to the size limits needed for detecting the key macromolecules of the *** results,covering several orders of magnitude of particle radius(100 nm to 2 nm),agree with the‘reactive’model pre.iction for the frequency shift of the resonator upon particle *** confirms that the main contribution of the frequency shift for the resonator upon particle binding is an increase in the effective path length due to part of the evanescent field coupling into the adsorbed *** anticipate that our results will enable many applications,including more sensitive me.ical diagnostics and fundamental studies of single receptor–ligand and protein–protein interactions in real time.

关键词： biosensing frequency locking label-free microtoroid single molecule

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The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3317-3329页

作者： Jennifer m.Colón-mercado Aranza I.Torrado-Tapias Iris K.Salgado Jose m.Santiago Samuel e.Ocasio Rivera Dina P.Bracho-Rincon Luis H.Pagan Rivera Jorge D.miranda Department of Physiology University of Puerto RicoMedical Sciences CampusSan JuanPRUSA National Institutes of Health National Human Genome Research InstituteBethesdaMDUSA Universidad Central del Caribe School of MedicineBayamónPRUSA University of Puerto Rico Carolina CampusCarolinaPRUSA Institute of Neurobiology San JuanPRUSA

In addition to the loss of motor function,~60% of patients develop pain after spinal cord *** cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,e.icenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic *** can lead to the formation of new connections triggering abnormal sensory *** excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and *** previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator *** this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord *** hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant *** and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical *** treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent *** expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,e.icenter,and caudal areas of the spinal cord with a pattern of expression primarily on *** rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased

关键词： allodynia central neuropathic pain eAAT-1/GLAST eAAT-2/GLT-1 glutamate transporters selective estrogen receptor modulator sexual dimorphism spinal cord injury trauma

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Impact of Zika virus non-structural protein mutations on hippocampal damage

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Neural Regeneration Research 2025年第8期20卷 2307-2308页

作者： Larissa m.G.Cassiano Roney S.Coimbra Neurogenômica/Imunopatologia Instituto RenéRachouFiocruzBelo HorizonteBrazil Departamento de Bioquímica e Imunologia Instituto de Ciências BiológicasUniversidade Federal de Minas GeraisBelo HorizonteBrazil

The Zika virus(ZIKV),a member of the Flaviviridae family,attracted worldwide attention for its connection to severe neurological effects,notably microcephaly in newborns,first reported during the 2015 epide.ic in ***,its impact goes beyond fetal and neonatal abnormalities,also affecting the central nervous system(CNS)in both children and adults,leading to enduring cognitive and behavioral impairments.

关键词： damage fetal neonatal

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A Le.ically Based Proposal of Argument Structure meaningi

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外国语 2005年第1期28卷 3-13页

作者： Adele e.goldberg Devin Casenhiser Nitya Sethuraman Princeton University Princeton UniversityIndiana UniversityUSA

Children conservatively produce syntactic patterns on a verb-by-verb basis (Akhtar and Tomasello, 1997;Baker, 1979; Bates and macWhinney, 1987; Bowerman, 1982; Braine, 1976; Brooks and Tomasello, 1999;Gropen et al., 1989; Ingram and Thompson, 1996; Lieven et al., 1997; macWhinney, 1982; Olguin and Tomasello, 1993; Schlesinger, 1982; Tomasello, 1992). Ultimately, however,

关键词：构词法副词词汇语法

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environmental variation shifts the relationship between trees and scatterhoarders along the continuum from mutualism to antagonism

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Integrative Zoology 2018年第3期13卷 319-330页

作者： Gina m.SAWAYA Adam S.goldberg michael A.STeeLe Harmony J.DALGLeISH Department of Biology College of William and MaryWilliamsburgVirginiaUSA Department of Biology Wilkes UniversityWilkes-BarrePennsylvaniaUSA

The conditional mutualism between scatterhoarders and trees varies on a continuum from mutualism to antagonism and can change across time and space,and among *** examined 4 tree species(red oak[Quercus rubra],white oak[Quercus alba],Ame.ican chestnut[Castanea dentata]and hybrid chestnut[***×Castanea] mollissima)across 5 sites and 3 years to quantify the variability in this conditional *** used a published model to compare the rates of seed emergence with and without burial to the probability that seeds will be cached and left uneaten by scatterhoarders to quantify variation in the conditional mutualism that can be explained by environmental variation among sites,years,species,and seed provenance within *** species tested had increased emergence when ***,comparing benefits of burial to the probability of caching by scatterhoarders indicated a mutualism in red oak,while white oak was nearly always *** was variable around the boundary between mutualism and antagonism,indicating a high degree of context dependence in the relationship with *** found that different seed provenances did not vary in their potential for *** did not explain microsite differences in seed emergence in any of the species *** hybrid chestnut only,emergence on the surface declined with soil moisture in the *** quantifying the variation in the conditional mutualism that was not caused by changes in scatterhoarder behavior,we show that environmental conditions and seed traits are an important and underappreciated component of the variation in the relationship between trees and scatterhoarders.

关键词： Castanea dentata conditional mutualism Quercus alba Quercus rubra temperate forest

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Gender Differences in Acute Cadmium-Induced Syste.ic Inflammation in Rats

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Biome.ical and environmental Sciences 2009年第1期22卷 1-7页

作者： mILeNA KATARANOVSKI SRDJA JANKOVic DRAGAN KATARANOVSKI JeLeNA STOic DeSA BOGOJe.ic Department of ecology Institute for Biological Research"Sinia Stankovi"Bulevar Despota Stefana 14211060 BelgradeSerbia Department of molecular Biology Institutefor Biological Research"Sinia Stankovi"Bulevar Despota Stefana 14211060 BelgradeSerbia

Objective To examine the presence of gender differences in pro-inflammatory potential of cadmium in rats by comparing syste.ic inflammatory response to acute cadmium intoxication in animals of the two sexes. methods Basic aspects of this response were evaluated, including plasma levels of inflammatory cytokines tumor necrosis factor （TNF） and interleukin-6 （IL-6） and of major rat acute phase protein alpha 2-macroglobulin （alpba2-m）, as soluble indicators of inflammation, and the number and activity of peripheral blood leukocytes, as cellular indicators of inflammation. Results Differential increases of IL-6 and alpha 2-m （higher in males than in females） in peripheral blood cell counts and types （leukocytosis and shift in the ratio of granulocytes to lymphocytes more pronounced in males vs females） and in levels of neutrophil priming （higher in males vs females） were noted. Conclusion The data document a more intense inflammatory response to cadmium administration in males. The sex differences in inflammatory effects of cadmium might be taken into consideration in studying the toxicity of this heavy metal.

关键词： Cadmium Sex Rats Inflammation

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Performance characteristics of retrograde single-balloon endoscopy: A single center experience

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World Journal of Gastrointestinal endoscopy 2016年第15期8卷 501-507页

作者： Kaci e Christian Karan Kapoor e.ic m goldberg Department of me.icine Division of Gastroenterology University of Maryland Medical Center

AIm: To evaluate the technical success, diagnostic yield(DY) and therapeutic potential of retrograde single balloon enteroscopy(rS Be). meTHODS: A retrospective review of 136 rS Be procedures performed at a tertiary acade.ic referral center from January 2006 and September 2013 was completed. Patient characteristics including age, gender and inpatient status were collected. The indication for the procedure was categorized into one of three groups: Obscure gastrointestinal bleeding(GIB), evaluation for Crohn's disease and abnormal imaging. Procedural characteristics including insertion depth(ID), procedure time, concordance with pre-procedural imaging and complications were also recorded. Lastly, DY, defined as the percentage of cases producing either a definitive diagnosis or findings that could explain clinical symptoms and therapeutic yield(TY), defined as the percentage of cases in which a definitive intervention was performed, were determined. mucosal tattooing and biopsy alone were not included in the TY. ReSULTS: A total of 136 rS Be procedures were identified. mean patient age was 57.5(± 16.2) years, 67(49.2%) were male, and 110(80.9%) procedures were performed on an outpatient basis. Indications for rS Be included GIB in 55(40.4%), evaluation of inflammatory bowel disease(IBD) in 29(21.3%), and imaging suggestive of pathology other than GIB or IBD in 43(31.6%). Nine(6.6%) rS Bes were performed for other indications. mean ID was 68.3(± 39.3) cm proximal to the ileocecal valve and mean time to completion was 41.7(± 15.5) min. Overall, 73(53.7%) cases were diagnostic and 25(18.4%) cases were therapeutic in which interventions(argon plasma coagulation, stricture dilatation, polypectomy, etc.) were performed. Pre-procedural imaging was performed in 88(64.7%) patients. endoscopic concordance of positive imaging findings was seen in 31(35.2%) cases. Follow up data was available in 93(68.4%) patients; 2(2.2%) reported post-procedural abdominal pain within 30 d follow

关键词： Retrograde Single-balloon enteroscopy endoscopy

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Constructions: A new theore.ical approach to language

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外国语 2003年第3期26卷 1-11页

作者： Adele e. goldberg (Linguistics Department, University of Illinois, Urbana, IL 61801-0168, USA) LinguisticsDepartmant UniversityofIllinoisUrbanaIL61801-0168USA

A new theore.ical approach to language has emerged in the past 10-15 years that allows linguistic observations about form-meaning pairings constructions — to be stated directly. Constructionist approaches aim to account for the full range of facts about language, without assuming that a particular subset of the data is part of a privileged 揷ore? Researchers argue that unusual constructions shed light on more general issues, and serve to illuminate what is required for a complete account of language.

关键词：语言语言学理论语法综述建构理论搭配

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