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Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk

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Genes & Diseases 2024年第1期11卷 103-134页

作者： Kevin Qin Michael Yu Jiaming Fan hongwei Wang Piao Zhao Guozhi Zhaoo Wei Zeng Connie Chen Yonghui Wang Annie Wang Zander Schwartz Jeffrey hong Lily Song William Wagstaff Rex C.haydon hue h.Luu Sherwin h.ho Jason Strelzow Russell R.Reid tong-Chuan he Lewis L.Shi Chicago Medical School Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA Laboratory of Craniofacial Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Wnt signaling plays a major role in regulating cell proliferation and *** Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical *** of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling *** crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ ***-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic *** complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic ***,both stimulatory and inhibitory treatments come with potential risks that need to be *** review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt *** thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+*** description involved each of its components and their involvement in other cellular ***,this review explained the various other pathways and processes that crosstalk with Wnt signaling.

关键词： β-catenin Canonical Wnt Noncanonical Wnt Signal transduction Signaling crosstalk

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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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Investigation of hCAR2 antagonists as a potential strategy to modulate bovine leukocytes

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Journal of Animal Science and Biotechnology 2024年第4期15卷 1567-1577页

作者： Laman K.Mamedova Kirby C.Krogstad Paiton O.McDonald Laxman Pokhrel Duy h.hua Evan C.titgemeyer Barry J.Bradford Department of Animal Science Michigan State UniversityEast LansingMichigan 48824USA Department of Animal Sciences and Industry Kansas State UniversityManhattanKS 66506USA Comparative Medicine and Integrative Biology East LansingMI 48824USA Department of Chemistry Kansas State UniversityManhattanKS 66506USA

Background Dairy cows experiencing ketosis after calving suffer greater disease incidence and are at greater risk of leaving the herd. In vitro administration of beta-hydroxybutyric acid(BhBA;the primary blood ketone) has inhibitory effects on the function of bovine leukocytes. BhBA is a ligand of hCAR2 and the activation of these receptors promotes an anti-inflammatory response which may be related with immunosuppression observed in transition dairy cattle. the objective of this study was to identify and test antagonists for hCAR2 in bovine immune cells cultured with *** We observed expression of hCAR2 at the protein level within lymphocytes, monocytes, and granulocytes. the proportion of cells expressing hCAR2 tended to be greater in mid-lactation compared to early lactation cows;the increase was a result of increased proportion of t and B cells expressing hCAR2. Stimulation of hCAR2 with niacin or BhBA promoted Ca^(2+) mobilization in neutrophils and mononuclear cells. Mononuclear cells treated with BhBA had diminished intracellular Ca^(2+) responses when hCAR2 was knocked down by si RNA silencing, indicating Ca^(2+) mobilization was mediated by hCAR2 signaling. two candidate antagonists for hCAR2, synthesized from niacin(NA-1 and NA-5), were tested;monocytes and neutrophils pre-treated with NA-1 and NA-5 had reduced Ca^(2+) mobilization after incubation with BhBA. Furthermore, NA-5 but not NA-1 prevented BhBA-associated reductions in cyclic *** We demonstrated that hCAR2 is present on bovine leukocytes and has greater expression later in lactation. We confirmed that BhBA and niacin derived hCAR2 antagonists alter bovine leukocyte activity. Our results demonstrate that both BhBA and niacin affect bovine leukocyte Ca^(2+) mobilization in a hCAR2-dependent manner.

关键词： Flow cytometry GPR109A hM74A Ketosis

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肾脏恶性肿瘤冷冻消融术后早期对比增强：影像表现与良性相关

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国际医学放射学杂志 2024年第1期 130-131页

作者： t.Grand C.Delavaud C.Dariane t.Ramtohul S.Guinebert O.hélénon 李江

摘要目的肾脏恶性肿瘤冷冻消融术后早期MRI对比增强可能提示肿瘤残留（Rt）。但冷冻消融术后48 h内MRI上出现强化的病人在6周后没有对比度增强，研究旨在分析

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Obstructive sleep apnea:Overlooked comorbidity in patients with diabetes

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World Journal of Diabetes 2024年第7期15卷 1448-1460页

作者： Eric D tenda Joshua henrina Jin h Cha Muhammad R triono Ersananda A Putri Dahliana J Aristy Dicky L tahapary Division of Respirology and Critical Care Department of Internal MedicineFaculty of Medicine Universitas Indonesia-Cipto Mangunkusumo HospitalDKI JakartaJakarta Pusat 10430Indonesia head of Research Group Artificial Intelligence and Digital health Indonesian Medical Education and Research InstituteFaculty of Medicine University of IndonesiaDKI JakartaJakarta Pusat 10430Indonesia Division of Endocrinology Metabolism and DiabetesDepartment of Internal MedicineFaculty of Medicine Universitas Indonesia-Cipto Mangunkusumo HospitalDKI JakartaJakarta Pusat 10430Indonesia

In this review article,we explore the interplay between obstructive sleep apnea(OSA)and type 2 diabetes mellitus(t2DM),highlighting a significant yet often overlooked *** delve into the pathophysiological links between OSA and diabetes,specifically how OSA exacerbates insulin resistance and disrupts glucose *** research examines the prevalence of OSA in diabetic patients and its role in worsening diabetes-related *** the importance of comprehensive management,including weight control and positive airway pressure therapy,the study advocates integrated approaches to improve outcomes for patients with t2DM and *** review underscores the necessity of recognizing and addressing OSA in diabetes care to ensure more effective treatment and better patient outcomes.

关键词： Obstructive sleep apnea type 2 diabetes mellitus Macrovascular Microvascular Weight loss Positive airway pressure

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Application of novel constrained friction processing method to produce fine grained biomedical Mg-Zn-Ca alloy

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Journal of Magnesium and Alloys 2024年第2期12卷 516-529页

作者： ting Chen Banglong Fu Junjun Shen Uceu F.h.R.Suhuddin Björn Wiese Yuanding huang Min Wang Jorge F.dos Santos Jean Pierre Bergmann Benjamin Klusemann Solid State Materials Processing Institute of Material MechanicsHelmholtz-Zentrum HereonMax-Planck-Str.1Geesthacht 21502Germany Functional Magnesium Materials Institute of Metallic BiomaterialsHelmholtz-Zentrum HereonMax-Planck-Str.1Geesthacht 21502Germany Shanghai Key Laboratory of Materials Laser Processing and Modification Shanghai Jiao Tong UniversityDongchuan Road 800Shanghai 200240China Applied Materials and Manufacturing Energy and Environment DivisionPacific Northwest National LaboratoryPO Box 999RichlandWA 99352USA Production technology Group Technisiche Universität IlmenauGustav-Kirchhoff-Platz 2Ilmenau 98693Germany Institute for Production technology and Systems Leuphana University of LüneburgUniversitätsallee 1Lüneburg 21335Germany

In order to obtain Mg alloys with fine microstructures and high mechanical performances,a novel friction-based processing method,name as“constrained friction processing(CFP)”,was *** CFP,defect-free Mg-Zn-Ca rods with greatly refined grains and high mechanical properties were *** to the previous as-cast microstructure,the grain size was reduced from more than 1 mm to around 4μm within 3 s by a single process *** compressive yield strength was increased by 350%while the ultimate compressive strength by 53%.According to the established material flow behaviors by“tracer material”,the plastic material was transported by shear *** the base material to the rod,the material experienced three stages,*** by the tool,upward flow with additional tilt,followed by upward *** microstructural evolution was revealed by“stop-action”*** microstructural development at regions adjacent to the rod is mainly controlled by twinning,dynamic recrystallization(DRX)as well as particle stimulated nucleation,while that within the rod is related to DRX combined with grain growth.

关键词： Constrained friction processing Magnesium alloys Microstructure Mechanical properties Grain refinement Plastic deformation

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Simple and high-Yield Synthesis of a thinner Layer of Graphenic Carbon from Coconut Shells

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Journal of Renewable Materials 2024年第5期12卷 969-979页

作者： Retno Asih haniffudin Nurdiansah Mochamad Zainuri Deni S.Khaerudini Angelinus t.Setiawan A.Y.Dias Pudji Untoro Ahmad Sholihand Darminto Department of Physics Institut Teknologi Sepuluh NopemberSurabaya60111Indonesia Department of Material and Metallurgical Engineering Institut Teknologi Sepuluh NopemberSurabaya60111Indonesia Research Centre for Advanced Materials National Research and Innovation Agency(BRIN)Tangerang Selatan15314Indonesia Pt.Graphene Nanomaterial Consulting Malang65141Indonesia Department of Physical Engineering Surya UniversityBanten15143Indonesia

Biomass has become of recent interest as a raw material for‘green’graphenic carbon(GC)since it promotes an environmentally friendly ***,we investigate a single pyrolysis route to synthesize GC from coconut shells which provides a simple method and can produce a high yield,thus being convenient for large-scale *** pyrolysis involves a stepped holding process at 350℃ for 1 h and at 650℃ or 900℃ for 3 *** GC sample resulted at the 900℃ pyrolysis has a thinner sheet,a less porous structure,a higher C/O ratio,and an enhanced electrical conductivity than those pyrolyzed at 650℃.the addition of Na3PO4 catalyst has no signiﬁ-cant effects on the GC structures obtained by this *** single pyrolysis route generates thinner GC sheets compared to the two-step heat treatment followed by the liquid phase exfoliation(LPE)***,the latter method offers a formation of clean samples with a porous or holey feature which has potential for advanced energy-storage applications.

关键词： Graphenic carbon biomass coconut shells pyrolysis synthesis route

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Large signal of h → μτ within the constraints of e_(i) → e_(j)γ decays in the 3-3-1 model with neutral leptons

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Chinese Physics C 2022年第12期46卷 106-125页

作者： h.t.hung D.t.Binh h.V.Quyet Department of Physics Hanoi Pedagogical University 2Phuc YenVinh Phuc 15000Vietnam Institute of theoretical and Applied Research Duy Tan UniversityHanoi 10000Vietnam Faculty of Natural Science Duy Tan UniversityDa Nang 50000Vietnam

In the framework of the 3-3-1 model with neutral leptons,we investigate lepton-flavor-violating sources based on the higgs mass spectrum,which has two neutral higgs identified with the corresponding ones of the two-higgs-doublet *** note that at the 13teV scale of the LhC,the parameter space regions satisfy the experimental limits of e_(i)→e_(j)γ*** regions depend heavily on the mixing of exotic leptons but are predicted to have large h_(1)^(0)→μτ*** also show that Br(h_(1)^(0)→μτ)can reach a value of 10^(-4).

关键词： higgs boson electroweak interaction beyond the SM LFV decays

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由超拍电子伏特加速器产生的超高能伽马射线气泡

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Science Bulletin 2024年第4期69卷 449-457页

作者： LhAASO Collaboration Zhen Cao Chuandong Gao Cong Li Ruo-Yu Liu Ruizhi Yang 不详 Key Laboratory of Particle Astrophyics&Experimental Physics Division&Computing Center Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China University of Chinese Academy of Sciences Beijing 100049China tIANFU Cosmic Ray Research Center ChengduChina Institute of Frontier and Interdisciplinary Science Shandong UniversityQingdao 266237China School of Astronomy and Space Science Nanjing UniversityNanjing 210023China University of Science and technology of China Hefei 230026China

We report the detection of aγ-ray bubble spanning at least 100deg2 in ultra-high energy(UhE)up to a few PeV in the direction of the star-forming region Cygnus X,implying the presence super PeVatron(s)accelerating protons to at least 10 PeV.A log-parabola form with the photon indexΓ(E)=(2.71±0.02)+(0.11±0.02)×log10(E/10 teV)is found fitting the gamma-ray energy spectrum of the bubble *** sources,“hot spots”correlated with very massive molecular clouds,and a quasi-spherical amorphousγ-ray emitter with a sharp central brightening are observed in the *** the core of~0.5°,spatially associating with a region containing massive OB association(Cygnus OB2)and a microquasar(Cygnus X-3),as well as previously reported multi-teV sources,an enhanced concentration of UhEγ-rays is observed with 2 photons at energies above 1 *** general feature of the bubble,the morphology,and the energy spectrum,are reasonably reproduced by the assumption of a particle accelerator in the core,continuously injecting protons into the ambient medium.

关键词： Cosmic rays γ-rays Interstellar medium Star cluster

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Leptin Modulates the Differentiation of Keratinocytes via Autophagy in Psoriasis Patients with Metabolic Syndrome

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International Journal of Dermatology and Venereology 2024年第3期7卷 121-130页

作者： Song C.-h. Wang R. Zhao Z.-K. Zhang Y. Sun J. Zhang X. Ding X.-Y. Bai J. Liang X.-Q. Wei X.-J. Liu X.-L. Yang t. Liang X.-L. Li C.-X. Lin B.-W. Department of Dermatology PLA General Hospital Beijing 100853 China Department of Clinical Laboratory PLA General Hospital Beijing 100853 China Department of Dermatology Southern Medical University Guangdong Guangzhou 510515 China

Objective: Psoriasis is associated with a high prevalence of metabolic syndrome (MS), and patients with concomitant psoriasis and MS are more severely affected and less responsive to treatment. however, the molecular mechanisms behind these effects are unknown. Recent studies have shown that leptin may serve as a molecular link between psoriasis and MS, suggesting that high leptin concentrations may exacerbate psoriasis. however, the molecular mechanism of this effect is still unclear. We aimed to investigate the effect of leptin on autophagy in patients with psoriasis. Methods: From January 2021 to June 2022 in PLA General hospital, we enrolled 51 patients with psoriasis, including 21 patients with MS and 30 without MS, and 30 healthy controls who had undergone nevus surgery. We measured the epidermal leptin, P62, and LC3B concentrations of patients by immunohistochemistry, and measured the serum leptin concentration by enzyme-linked immunosorbent assay. We then performed correlation analyses to compare these proteins' concentrations between patients with concomitant psoriasis and MS, patients with psoriasis alone, and healthy control groups. Additionally, we performed western blotting after in vitro culture of haCat cells with different concentrations of leptin and measured the expression levels of the autophagy markers Beclin1, LC3B, and P62; the differentiation markers K10, K16, and K17; and PI3K/AKt/mtOR signaling pathway-related proteins of haCat cells. Next, we transfected AtG5 into haCat cells to revert autophagy and used the specific PI3K inhibitor LY294002 to block PI3K/AKt/mtOR signaling. the expression levels of K10, K16, and K17 of haCat cells were again measured. One-way analysis of variance was used for the comparison of means of multiple samples, and LSD-t post hoc test was used for comparison between the 2 groups. the counting data were analyzed by the chi-square test. Correlations were evaluated by Pearson correlation analysis. Results: the serum l

关键词： autophagy keratinocyte differentiation leptin metabolic syndrome PI3K/AKt/mtOR psoriasis signal pathway

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