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Estrogen augmented visceral pain and colonic neuron modulation in a double-hit model of prenatal and adult stress

World Journal of Gastroenterology 2021年第30期27卷 5060-5075页

作者： Jing-hong Chen Ying Sun Pei-Jun Ju Jin-Bao Wei Qing-Jie Li john h winston Shanghai Key Laboratory of Psychotic Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200030China Department of Internal Medicine University of Texas Medical BranchGalvestonTX 77555United States

BACKGROUND Chronic stress during pregnancy may increase visceral hyperalgesia of offspring in a sex-dependent *** adult stress in offspring will increase this *** on the evidence implicating estrogen in exacerbating visceral hypersensitivity in female rodents in preclinical models,we predicted that chronic prenatal stress(CPS)+chronic adult stress(CAS)will maximize visceral hyperalgesia;and that estrogen plays an important role in colonic *** The aim was to illuminate the role of estrogen in colonic hyperalgesia and its underlying *** We established a CPS plus CAS rodent model in which the balloon was used to distend the *** single-fiber recording in vivo and patch clamp experiments in vitro were used to monitor the colonic neuron’s *** reverse transcription-polymerase chain reaction,western blot,and immunofluorescence were used to study the effects of CPS and CAS on colon primary afferent *** used ovariectomy and letrozole to reduce estrogen levels of female rats respectively in order to assess the role of estrogen in female-specific enhanced primary afferent *** Spontaneous activity and single fiber activity were significantly greater in females than in *** enhanced sensitization in female rats mainly came from lowthreshold *** significantly increased single-unit afferent fiber activity in L6-S2 dorsal roots in *** was further enhanced by *** addition,the excitability of colon-projecting dorsal root ganglion(DRG)neurons increased in CPS+CAS rats and was associated with a decrease in transient Atype K+*** with ovariectomy,treatment with the aromatase inhibitor letrozole significantly reduced estrogen levels in female rats,confirming the gender ***,mice treated with letrozole had decreased colonic DRG neuron *** intrathecal infusion of estrogen increased brain-derived neurotrophic factor(BDNF)p

关键词： Chronic prenatal stress Estrogen Visceral pain Neuronal sensitization Excitability Letrozole

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Upregulation of transient receptor potential vanilloid 1 contributes to hyperalgesia in rats with painful chronic pancreatitis

Upregulation of transient receptor potential vanilloid 1 con...

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： john h winston Mohan ShENOY Pankaj Jay PASRIChA Division of Gastroenterology and hepatology Department of Internal MedicineUniversity of Texas Medical BranchGalvestonTexas 77555USA

＜正＞The neurobiological basis of pancreatic hyperalgesia in chronic pancreatitis（CP） is poorly understood and treatment of pain in this condition remains empirical and often *** have previously developed a rat model of trinitrobenzene sulphonic acid（TNBS）-induced chronic pancreatitis that results in nociceptive sensitization in rats manifested by pancreatic hyperalgesia and referred somatic *** aim of this study was to investigate the molecular substrate of these changes,specifically focusing on the role of the transient receptor potential vanilloid subfamily 1 （TRPV1）.CP was induced in adult rats by a single intraductal injection of *** root ganglion（DRG） neurons innervating the pancreas were identified by DiI or cholera B toxin fluorescence ***1 currents in pancreasspecific DRG neurons were measured using perforated patch-clamp ***-PCR was used to measure mRNA expression of TRPV1 in pancreas-specific DRG neurons after laser capture microdissection（LCM）.Immunofluorescence and western blot analysis,using TRPV1-specific antibodies,were also *** hyperalgesia was assessed by observing nocifensive behaviors after electrical stimulation of the pancreas and belly withdrawal responses were also recorded after von Fray Filament *** weeks after injection of TNBS,Capsaicin-induced current density of pancreas specific DRG neurons was increased about four-folds（P ＜ 0.02）,along with an increase in proportion of pancreas -specific DRG neurons that responded to capsaicin（52.9%in controls versus 79.0%in TNBS,P ＜ 0.05）.CP was also associated with a significant enhancement of TRPV1 expression both at the mRNA and protein level,including western blots in whole thoracic DRG and immunoreactivity in pancreas specific sensory *** administration of the TRPV1 antagonist（SB-366791） markedly reduced the pain behavioral response to noxious electrical stimulation of pancreas and von Frey Filament stimulation

关键词： Chronic pancreatitis transient receptor potential vanilloid subfamily 1 rat

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Desialylated Platelet Clearance in the Liver is a Novel Mechanism of Systemic Immunosuppression

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Research 2024年第3期2023卷 35-50页

作者： June Li Danielle Karakas Feng Xue Yingyu Chen Guangheng Zhu Yeni h.Yucel Sonya A.MacParland haibo Zhang john W.Semple john Freedman Qizhen Shi heyu Ni Department of Laboratory Medicine and Pathobiology University of TorontoTorontoONCanada Toronto Platelet Immunobiology Group TorontoONCanada Keenan Research Centre for Biomedical Science of St.Michael's hospital TorontoONCanada Canadian Blood Services Centre for Innovation TorontoONCanada Departments of Pediatrics Medical College of WisconsinMilwaukeeWIUSA Blood Research Institute Versiti WisconsinMilwaukeeWIUSA Departments of Ophthalmology and Vision Sciences Medicine University of TorontoTorontoONCanada Faculty of Engineering and Architectural Science Ryerson UniversityTorontoONCanada Multi-Organ Transplant Program Toronto General Hospital Research InstituteTorontoONCanada Department of Immunology University of TorontoTorontoONCanada Critical Care Medicine Department ofAnesthesiology and PainUniversity of TorontoTorontoONCanada Department of Physiology University of TorontoTorontoONCanada Department of Pharmacology University of TorontoTorontoONCanada. Division of hematology and Transfusion Medicine Lund UniversityLundSweden clinical Immunology and Transfusion Medicine Ofice of Medical ServicesRegion SkaneLundSweden Department of Medicine University of TorontoTorontoONCanada Children's Research Institute Children's WisconsinWauwatosaWIUSA Midwest Athletes Against Childhood Cancer Fund Research Center MilwaukeeWIUSA.

Platelets are small, versatile blood cells that are critical for hemostasis/thrombosis. Local platelet accumulation is a known contributor to proinflammation in various disease states. however, the anti-inflammatory/immunosuppressive potential of platelets has been poorly explored. here, we uncovered, unexpectedly, desialylated platelets (dPLTs) down-regulated immune responses against both platelet-associated and -independent antigen challenges. Utilizing multispectral photoacoustic tomography, we tracked dPLT trafficking to gut vasculature and an exclusive Kupffer cell-mediated dPLT clearance in the liver, a process that we identified to be synergistically dependent on platelet glycoprotein Ibα and hepatic Ashwell–Morell receptor. Mechanistically, Kupffer cell clearance of dPLT potentiated a systemic immunosuppressive state with increased anti-inflammatory cytokines and circulating CD4+ regulatory T cells, abolishable by Kupffer cell depletion. Last, in a clinically relevant model of hemophilia A, presensitization with dPLT attenuated anti-factor VIII antibody production after factor VIII ( infusion. As platelet desialylation commonly occurs in daily-aged and activated platelets, these findings open new avenues toward understanding immune homeostasis and potentiate the therapeutic potential of dPLT and engineered dPLT transfusions in controlling autoimmune and alloimmune diseases.

关键词： Platelet transfusion homeostasis

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Optimizing oncolytic virus design:a“Swiss army knife”approach to create a systemically delivered therapeutic

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1791-1792页

作者： Carolina S.Ilkow john Cameron Bell Ottawa hospital Research Institute 501 Smyth RoadOttawaONK1H 8L6Canada

In a recent paper published in Nature Biotechnology,Chen et al.1 describe a multiplex oncolytic virus platform that coupled with adoptive T cell therapy could solve the problem of repeat,systemic delivery of virus based *** is widely accepted that multi-targeted therapeutic approaches attacking several facets of cancer biology are necessary to effectively deal with the tumor heterogeneity that exists within and between patients.

关键词： therapeutic al. targeted

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Stable hydrogen isoscape in precipitation generated using data fusion for East China

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Science China Earth Sciences 2024年第9期67卷 2972-2988页

作者： Jiacheng ChEN Jie ChEN Xunchang john ZhANG Peiyi PENG State Key Laboratory of Water Resources Engineering and Management Wuhan UniversityWuhan 430072China hubei Key Laboratory of Water System Science for Sponge City Construction Wuhan UniversityWuhan 430072China USDA-ARS Oklahoma and Central Plains Agricultural Research Center El Reno OK 73036USA Southwest Research Institute for hydraulic and Water Transport Engineering Chongqing Jiaotong UniversityChongqing 400016China

The stable hydrogen isotope in precipitation is an effective environmental tracer for climatic and hydrologic ***,accurate and high-precision precipitation hydrogen isoscapes are currently unavailable in *** this study,a data fusion method based on Convolutional Neural Networks(CNN)is used to fuse the hydrogen isotopic composition(δ^(2)h_(p))of observations and isotope-equipped general circulation model(iGCM)simulations.A precipitation hydrogen isoscape with a temporal resolution of monthly and a spatial resolution of 50-60 km is established for East China for the 1969-2017 *** to building the isoscape,the performance of three data fusion methods(DFMs)and two bias correction methods(BCMs)is *** results indicate that the CNN fusion method performs the best with a correlation coefficient larger than 0.90 and root mean square error smaller than 10.5‰ when using observation as a *** fusion methods based on back propagation and long short-term memory neural network perform similarly,while slightly outperforming the bias correction ***,the CNN method is used to generate the hydrogen isoscape,and the temporal and spatial distribution characteristics of the hydrogen isotope in precipitation are analyzed based on this *** generated isoscape shows similar spatial and temporal distribution characteristics to *** general,the distribution pattern of δ^(2)h_(p) is consistent with the temperature effect in northern China,and consistent with the precipitation amount effect in southern *** trend of the δ^(2)h_(p) time series is consistent with that of observed precipitation and ***,the generated isoscape effectively reproduces the observations,and has the characteristics of time continuity and relative spatial regularity,which can provide valuable data support for tracking atmospheric and hydrological processes.

关键词： Precipitation Precipitation isotope General circulation model Data fusion Dataset

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从h1N1血凝素序列提取的沙门氏菌传递的COBRA-hA1抗原对甲型流感亚型产生广谱保护作用

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Engineering 2024年第1期32卷 41-56页

作者： Ram Prasad Aganja Amal Senevirathne Chandran Sivasankar john hwa Lee Department of Veterinary Public health College of Veterinary MedicineJeonbuk National UniversityIksan 54596Republic of Korea Department of Preventive Medicine College of Veterinary MedicineChungnam National UniversityDaejeon 34134Republic of Korea

A universal vaccine is in high demand to address the uncertainties of antigenic drift and the reduced effectiveness of current influenza *** this study,a strategy called computationally optimized broadly reactive antigen(COBRA)was used to generate a consensus sequence of the hemagglutinin globular head portion(hA1)of influenza virus samples collected from 1918 to 2021 to trace evolutionary changes and incorporate them into the designed *** carrying different hA1regions were delivered into eukaryotic cells by Salmonella-mediated bactofection using a Semliki Forest virus RNA-dependent RNApolymerase(RdRp)-based eukaryotic expression system,*** protein expression was confirmed by Western blot and immunofluorescence *** immunized with the designed constructs produced a humoral response,with a significant increase in immunoglobulin G(IgG)levels,and a cell-mediated immune response,including a 1.5-fold increase in CD4^(+) and CD8^(+)T ***,constructs #1 and #5 increased the production of interferon-γ(IFN-γ)producing CD4^(+)and CD8^(+)T cells,skewing the response toward the T helper type 1 cell(Th1)***,interleukin-4(IL-4)-producing T cells were upregulated *** efficacy was demonstrated,with up to 4-fold higher production of neutralizing antibodies and a hemagglutination inhibition titer>40 against the selected viral *** designed constructs conferred a broadly protective immune response,resulting in a notable reduction in viral titer and minimal inflammation in the lungs of mice challenged with the influenza A/PR8/34,A/Brisbane/59/2007,A/California/07/2009,KBPV VR-92,and NCCP 43021 *** discovery revolutionizes influenza vaccine design and delivery;Salmonella-mediated COBRA-hA1 is a highly effective in vivo antigen presentation *** approach can effectively combat seasonal h1N1 influenza strains and potential pandemic outbreaks.

关键词： COBRA Influenza A Salmonella Vaccine Broad spectral protection

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Free vibration and buckling analysis of polymeric composite beams reinforced by functionally graded bamboo fbers

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Applied Mathematics and Mechanics(English Edition) 2024年第3期45卷 543-562页

作者： h.M.FEIZABAD M.h.YAS Department of Mechanical Engineering Razi UniversityKermanshah ***Iran

Natural fibers have been extensively researched as reinforcement materials in polymers on account of their environmental and economic advantages in comparison with synthetic fibers in the recent *** fibers are renowned for their good mechanical properties,abundance,and short cycle *** beams are one of the fundamental structural components and are susceptible to mechanical loads in engineering applications,this paper performs a study on the free vibration and buckling responses of bamboo fiber reinforced composite(BFRC)beams on the elastic *** different functionally graded(FG)layouts and a uniform one are the considered distributions for unidirectional long bamboo fibers across the *** elastic properties of the composite are determined with the law of *** hamilton’s principle,the governing equations of motion are *** generalized differential quadrature method(GDQM)is then applied to the equations to obtain the *** achieved outcomes exhibit that the natural frequency and buckling load values vary as the fiber volume fractions and distributions,elastic foundation stiffness values,and boundary conditions(BCs)and slenderness ratio of the beam ***,a comparative study is conducted between the derived analysis outcomes for BFRC and homogenous polymer beams to examine the effectiveness of bamboo fibers as reinforcement materials,demonstrating the significant enhancements in both vibration and buckling responses,with the exception of natural frequencies for cantilever beams on the Pasternak foundation with the FG-◇fiber ***,the obtained analysis results of BFRC beams are also compared with those for carbon nanotube reinforced composite(CNTRC)beams found in the literature,indicating that the buckling loads and natural frequencies of BFRC beams are lower than those of CNTRC beams.

关键词： bamboo fiber free vibration buckling analysis functionally graded(FG)beam elastic foundation generalized differential quadrature method(GDQM)

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Nonuniform Dependence on the Initial Data for Solutions of Conservation Laws

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Communications on Applied Mathematics and Computation 2024年第1期6卷 489-500页

作者： john M.holmes Barbara Lee Keyfitz Department of Mathematics The Ohio State UniversityColumbusOH43210USA

In this paper,we study systems of conservation laws in one space *** prove that for classical solutions in Sobolev spaces h^(s),with s>3/2,the data-to-solution map is not uniformly *** results apply to all nonlinear s... 详细信息

关键词： Conservation laws Data-to-solution map Nonuniform dependence

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holographic dark energy in non-conserved gravity theory

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Communications in Theoretical Physics 2024年第4期76卷 126-133页

作者： h R Fazlollahi Institute of Gravitation and Cosmology Peoples Friendship University of Russia(RUDN University)6 Miklukho-Maklaya StMoscow117198Russia

Recently, reconsidering the Rastall idea T_(μ;νν)^(v)=α_(,μ) through relativistic thermodynamics gives a new form for the scalar field α which led us to construct modern modified theory of gravity debugged ‘non-conserved gravity theory’ Fazlollahi 2023 Euro. Phys. J. C 83 923. This theory unlike other modified theories of gravity cannot directly explain the current acceleration expansion in the absence of the cosmological constant and or existence of other forms of dark energy. hence, in this study we have reinvestigated holographic dark energy Ρ_(X)~h^(2) in the non-conserved theory of gravity. In this context, the density and pressure of dark energy depend on the non-conserved term and density of the dust matter field. As shown, due to non-conservation effects on large-scale structures, unlike the original holographic model, our model onsets an acceleration epoch for the current Universe satisfies observations. Moreover, the interaction and viscous scenarios are studied for this model.

关键词： non-conserved gravity covariant form of thermodynamics holographic dark energy

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Novel synthesis of stabilized Bi1-x-yGdxDyyO1.5 solid electrolytes with enhanced conductivity for intermediate temperature solid oxide fuel cells（SOFCs）

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Journal of Rare Earths 2024年第10期42卷 1903-1911页

作者： Ahmed h.Ibrahim Yehia M.Abbas h.A.Ayoub Marwa h.Ali Mustafa Aldoori Materials Science Laboratory Physics DepartmentFaculty of ScienceSuez Canal University Ministry of higher Education and Scientific Research Aliraqia University

herein,we report the synthesis of a Dy-Gd co-doped cubic phase-stabilized Bi2O3solid electrolyte system via solid-state processing under atmospheric *** with Dy3+and Gd3+has been observed to significantly enhance the densification process during sintering for stabilization purposes,thereby improving the electrical properties of δ-Bi2O3-type *** synthesized ceramics were characterized using X-ray diffraction（XRD）,field emission scanning electron microscopy-energy dispersive X-ray spectroscopy（FESEM-EDX）,thermal gravimetry/differential thermal analysis（TG/DTA）,and the four-point probe technique（4PPT）.XRD analysis reveals that the samples Bi1-x-yGdxDyyO1.5（y=0.05/x=0.05,0.10,0,15,and 0.20,and x=0.05/y=0.10,0.15,and 0.20） exhibit a stable face-centered cubic δ-phase and a mixed-phase crystallographic *** XRD analysis of the stabilized δ-phase suggests that the prepared oxides show a face-centered cubic（FCC） structure with a space group of *** micrographs reveal that the composition Bi0.90Gd0.05Dy0.05O1.5has no significant ***,an evident increase in the pore formation is observed as the amount of Gd2O3increases until it reaches 20%.This finding suggests that dense pellets are formed during the sintering process at 900-1000℃.The DTA analyses were performed to verify the phase stability,which agrees with the XRD *** electrochemical performance of the synthesized Dy-Gd co-doped Bi2O3solid electrolyte system was evaluated and analyzed in detail by using the electrochemical impedance spectroscopy（EIS） technique,Based on EIS and conductivity measurements,Bi0.75Gd0.20Dy0.05O1.5exhibits the lowest activation energy of 0.519 eV and the highest conductivity value of 0.398 S/cm at 627℃compared to the other samples;this composition can be used as a solid electrolyte for intermediatetemperature solid oxide fuel cells（SOFCs）.

关键词： Electrochemical impedance spectroscopy (EIS) Fast Fourier transform (FFT) Rare earths Rietveld Solid oxide fuel cells (SOFCs) Solid-state processing

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