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neuroprotective effects of InT-777 against Aβ1-42-induced cognitive impairment, neuroinflammation, apoptosis, and synaptic dysfunction in mice

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中国药理学与毒理学杂志 2018年第9期32卷 688-689页

作者： WU Xian LYU Yang-ge DU Yi-feng CHEn Fang miranda n reed HU Mei Vishnu SUPPIRAMAnIAM TAnG Su-su HOnG Hao Department of Pharmacology Key Laboratory of Neuropsychiatric Diseases China Pharmaceutical University Nanjing 210009 China Department of Drug Discovery and Development School of Pharmacy Auburn University Auburn Alabama USA

OBJECTIVE To investigate the neuroprotective effects of TGR5 agonist InT-777 in the Aβ_(1-42)-treated mouse model of acute *** Cognitive impairment was induced by single intracerebroventricular injection of aggregated Aβ_(1-42)(410 pmol per mouse;5 μL)into the mouse brain in normal ICR ***3 d,InT-777(0.75,1.5 or 3.0 μg per mouse) was infused into the same *** 3 d later,the cognition function was evaluated by Morris water maze(MWM),novel objective recognition(nOR),and Y maze ***,the levels of TGR5,TnF-α,IL-1β,IL-6,nF-κB p65,Iba1,caspase 3,Bcl-2,Bax,PSD95,and synaptophysin in the hippocampus and frontal cortex were detected using Western *** activation in the hippocampal CA1,CA3 and DG regions and frontal cortex were detected by *** staining was used to detect the apoptotic *** number of spines in the hippocampal CA1,CA3 and DG regions and frontal cortex was detected by GolgiCox *** InT-777(1.5 or 3.0 μg per mouse) significantly ameliorated memory impairment in the Aβ_(1-42)-treated mice,evidenced by increased the time spent in the target quadrant(Pnd the number of target crossings(Pn the MWM test,increased the discrimination index in the nOR test(Pnd increased the number of correct choices(Pnd decreased the latency(Pnter the shock-free compartment in the Y-maze ***,this treatment reversed Aβ_(1-42)-induced TGR5 down-regulation(Pncrease of nuclear nF-κB p65(Pnd mitigated neuroinflammation,evidenced by lower proinflammatory cytokines such as TnF-α(Pnd less Iba1-positive cells in the hippocampal CA1,CA3 and DG regions and frontal cortex(Pn level of ***-777(1.5 or3.0 μg per mouse) also pronouncedly suppressed apoptosis through the reduction of TUnEL-positive cells(P<0.05,P<0.01),de

关键词： Alzheimer disease InT-777 TGR5 Aβ1-42 neurotoxicity

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Association of Congenital Heart Defects (CHD) with Factors Related to Maternal Health and Pregnancy in newborns in Puerto Rico

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Congenital Heart Disease 2024年第1期19卷 19-31页

作者： Yamixa Delgado Caliani Gaytan naydi Perez Eric miranda Bryan Colón Morales Mónica Santos Biochemistry&Pharmacology Department San Juan Bautista School of MedicineCaguas00726Puerto Rico Hispanic Alliance for Clinical and Translational Research University of Puerto Rico Medical Sciences CampusSan Juan00936Puerto Rico Department of Internal Medicine University of Puerto Rico Medical Sciences CampusSan Juan00936Puerto Rico

Background:Given the pervasive issues of obesity and diabetes both in Puerto Rico and the broader United States,there is a compelling need to investigate the intricate interplay among body mass index(BMI),pregesta-tional,and gestational maternal diabetes,and their potential impact on the occurrence of congenital heart defects(CHD)during neonatal ***:Using the comprehensive System of Vigilance and Surveillance of Congenital Defects in Puerto Rico,we conducted a focused analysis on neonates diagnosed with CHD between 2016 and *** assessment encompassed a range of variables,including maternal age,gestational age,BMI,pregestational diabetes,gestational diabetes,hypertension,history of abortion,and presence of ***:A cohort of 673 patients was included in our *** average maternal age was 26 years,within a range of 22 to 32 *** mean gestational age measured 39 weeks,with a median span of 38 to 39 *** the 673 patients,274(41%)mothers gave birth to neonates diagnosed with *** this group,22 cases were linked to pre-gestational diabetes,while 202 were not;20 instances were associated with gestational diabetes,compared to 200 without;and 148 cases exhibited an overweight or obese BMI,whereas 126 displayed a normal ***:We identiﬁed a statistically signiﬁcant correlation between pre-gestational diabetes mellitus and the occurrence of ***,our analysis did not show a statistically signiﬁcant association between maternal BMI and the likelihood of *** results may aid in developing effective strategies to prevent and manage CHD in neonates.

关键词： Congenital heart defects(CHD) obesisty maternal health diabetes body mass index(BMI)

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Assessment of CO_(2)storage prospect based on physical properties of Rio Bonito Formation rock units

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Energy Geoscience 2024年第1期5卷 321-330页

作者： Richardson M.Abraham-A Stephanie San Martín Cañas Isabella F.S.miranda Colombo C.G.Tassinari Institute of Energy and Environment(IEE) University of São Paulo(USP)Brazil Research Centre for Greenhouse Gas Innovation(RCGI) University of Sãao Paulo(USP)Brazil

The physical properties of the rock units associated with the Rio Bonito Formation are presented in this study with the focus on modelling reservoir quality based on petrophysics-derived parameters to evaluate CO_(2)storage *** involves the modelling of the reservoir depths,thicknesses,flow zone indicators(FZI),and effective permeability(Keff)and presenting the CO_(2)storage efficiency factors peculiar to the rock units of the study *** results presented by this study for the stated objectives are not quite common in the *** values range from 200 mD to higher than 2000 mD,and FZI values are generally above 1.0 mm and up to 13.0 mm within the portions covered by the drilled *** sandstone units recorded are up to 20 m thick in some *** Keff and FZI models indicate the sandstone reservoirs as permeable units to support the injection and circulation of CO_(2)within the potential reservoir units of the Rio Bonio Formation across São Paulo *** from some points in the southeastern part of the study location,where the Rio Bonito are delineated at depths less than 800 m(minimum CO_(2)storage depth based on best practices),other portions are deeper,ranging from 950 m to 3500 ***-bedded layers will affect the integrity of the rocks as CO_(2)storage tanks or reservoir seals/traps/overburden within the *** bed thicknesses are up to 20 m in some ***,hybrid CO_(2)reservoir units are feasible,especially in portions where thin siltstone layers are sandwiched between sandstone units to provide considerable thicknesses based on CO_(2)storage *** current study shows that useable areas considering reservoir thickness,depth,and other physical qualities will significantly control the CO_(2)storage efficiency of the study *** studies featuring a detailed geophysical exploration of the site to confirm the availability and saturations of preexisting fluid(hydrocarbon and water)are encouraged

关键词： Rio Bonito Effective permeability Fluid transmissibility CO_(2)storage prospect Reservoir quality Overburden integrity Flow zones

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Immunoregulatory and Anti-cancer Activities of Combination Treatment of novel Four-Herb Formula and Doxorubicin in 4T1-Breast Cancer Bearing Mice

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Chinese Journal of Integrative Medicine 2024年第4期30卷 311-321页

作者： Lea Ling-Yu Kan Ben Chung-Lap Chan Grace Gar-Lee Yue LI Pei-ting Sharon Sze-Man Hon HUAnG Dan-qi miranda Sin-Man Tsang Clara Bik-San Lau Ping-Chung Leung Chun-Kwok Wong Institute of Chinese Medicine The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Department of Chemical Pathology The Chinese University of Hong KongHong Kong SARChina China-Australia International Research Centre for Chinese Medicine School of Health and Biomedical SciencesSTEM CollegeRMIT UniversityBundooraVictoriaAustralia Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine The Chinese University of Hong Kong SARHong KongChina

Objective To investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula(4HF)and doxorubicin in triple-negative breast cancer(TnBC).Methods Murine-derived triple-negative mammary carcinoma cell line,4T1 cells,was cultured and inoculated into mouse mammary ***-six mice were randomly assigned into 6 groups(n=11 in ench):naive,control,LD 4HF(low dose 4HF),HD 4HF(high dose 4HF),LD 4HF+D(low dose and doxorubicin),and D(doxorubicin).Apart from the naive group,each mouse received subcutaneous inoculation with 5×10^(5)4T1 cells resuspended in 100µL of normal saline in the mammary fat *** from the day of tumor cell inoculation,tumors were grown for 6 *** LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF,*** LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin(5 mg/kg).The D group received weekly intraperitoneal injections of doxorubicin(5 mg/kg).The treatment naive mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a *** control group received daily oral gavage of 0.2 mL double-distilled *** treatment period was 30 *** the end of treatment,mice organs were harvested to analyze immunological activities via immunophenotyping,gene and multiplex analysis,histological staining,and gut microbiota *** Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens(Pnd overall immune lymphocyte landscape,and manipulated gut microbiota to favor the anti-tumor immunological ***,immunosuppressive genes,cytokines,and chemokines such as C-C motif chemokine 2 and interleukin-10 of tumors were significantly downregulated(Pn combination treatment demonstrated synergetic activities and was most effective

关键词： adjunctivetherapy breast cancer cytokines Chinese medicine tumor microenvironment

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Does the use of double hormone replacement therapy for trauma patient organ donors improve organ recovery for transplant

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World Journal of Transplantation 2024年第2期14卷 119-125页

作者： Eden M Gallegos Tanner reed Paige Deville Blake Platt Claudia Leonardi Lillian Bellfi Jessica Dufrene Saad Chaudhary John Hunt Lance Stuke Patrick Greiffenstein Jonathan Schoen Alan Marr Anil Paramesh Alison A Smith Department of Physiology Louisiana State University Health Sciences Center New OrleansNew OrleansLA 70124United States Department of Medicine Louisiana State University Health Sciences Center New OrleansNew OrleansLA 70112United States Department of Surgery Louisiana State University Health Sciences Center New OrleansNew OrleansLA 70112United States Department of Trauma Surgery Tacoma General HospitalTacoma 98405United States Department of Public Health Louisiana State University Health Sciences Center New OrleansNew OrleansLA 70112United States Department of Donation Services Louisiana Organ Procurement AgencyCovingtonLA 70433United States Department of Surgery Tulane Transplant InstituteTulane University School of MedicineNew OrleansLA 70112United States

BACKGROUnD With an ongoing demand for transplantable organs,optimization of donor management protocols,specifically in trauma populations,is important for obta-ining a high yield of viable organs per *** management of brain-dead potential organ donors(BPODs)is controversial,leading to heterogeneous clinical management *** studies have shown that when levo-thyroxine was combined with other treatments,including steroids,vasopressin,and insulin,BPODs had better organ recovery and survival outcomes were increased for transplant *** To determine if levothyroxine use in combination with steroids in BPODs increased the number of organs donated in trauma *** A retrospective review of adult BPODs from a single level 1 trauma center over ten years was *** criteria included patients who were not solid organ donors,patients who were not declared brain dead(donation after circulatory death),and patients who did not receive steroids in their hospital *** and steroid administration,the number of organs donated,the types of organs donated,and demographic information were *** analyses were performed with Pnsidered to be statistically *** A total of 88 patients met inclusion criteria,69(78%)of whom received levothyroxine and steroids(ST/LT group)vs 19(22%)receiving steroids without levothyroxine(ST group).no differences were observed between the groups for gender,race,pertinent injury factors,age,or other hormone therapies used(P>0.05).In the ST/LT group,68.1%(n=47)donated a high yield(3-5)of organ types per donor compared to 42.1%(n=8)in the ST group(P=0.038).There was no difference in the total number of organ types donated between the groups(P=0.068).COnCLUSIOn This study suggests that combining levothyroxine and steroid administration increases high-yield organ donation per donor in BPODs in the trauma patient *** to this study include

关键词： Organ donation Trauma Brain death Levothyroxine Hormone replacement therapy Steroids Organ donor Retrospective

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Universal silicon ring resonator for error-free transmission links

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Photonics Research 2024年第4期12卷 701-711页

作者： JUnBO ZHU WEIWEI ZHAnG KE LI BHARAT PAnT MARTIn EBERT XInGZHAO YAn MEHDI BAnAKAR DEHn T.TRAn CALLUM G.LITTLEJOHnS FUWAn GAn GRAHAM reed DAVID J.THOMSOn Optoelectronics Research Centre University of SouthamptonSouthampton SO171BJUK national Key Laboratory of Materials for Integrated Circuits Shanghai Institute of Microsystem and Information TechnologyChinese Academy of SciencesShanghai 200050China University of Chinese Academy of Sciences Beijing 100049China Peng Cheng Laboratory ShenzhenChina

We report the design, fabrication, and characterization of a universal silicon Pn junction ring resonator for C band error-free communication links operated up to 50 Gb/s with co-designed optical modulation and detection performance. The universal p-n junction ring device shows co-designed detection responsivity up to 0.84 A/W, in conjunction with a modulation efficiency of -4 V·mm and>8 d B optical modulation extinction ratio, enabling C band 50 Gb/s nRZ communication link with a bit error rate≤3×10^(-12).

关键词： Gb/s resonator communication

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Associations between health-related fitness and patient-reported symptoms in newly diagnosed breast cancer patients

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Journal of Sport and Health Science 2024年第6期13卷 851-862页

作者： Ki-Yong An Fernanda Z.Arthuso Myriam Filion Spencer J.Allen Stephanie M.ntoukas Gordon J.Bell Jessica Mcneil Qinggang Wang Margaret L.Mcneely Jeff K.Vallance Lin Yang S.nicole Culos-reed Leanne Dickau John R.Mackey Christine M.Friedenreich Kerry S.Courneya Faculty of Kinesiology Sportand RecreationCollege of Health SciencesUniversity of AlbertaEdmonton T6G 2H9Canada Department of Kinesiology School of Health and Human SciencesUniversity of North Carolina at GreensboroGreensboroNC 27412USA Department of Cancer Epidemiology and Prevention Research Cancer Care AlbertaAlberta Health ServicesCalgary T2S 3C3Canada Faculty of Rehabilitation Medicine University of AlbertaEdmonton T6G 2H9Canada Faculty of Health Disciplines Athabasca UniversityAthabasca T9S 3A3Canada Department of Oncology Cumming School of MedicineUniversity of CalgaryCalgary T2N 4N1Canada Faculty of Kinesiology University of CalgaryCalgary T2N 1N4Canada Faculty of Medicine and Dentistry University of AlbertaEdmonton T6G 2H9Canada

Background:newly diagnosed breast cancer patients experience symptoms that may affect their quality of life,treatment outcomes,and *** and managing breast cancer-related symptoms soon after diagnosis is *** purpose of this study was to investigate the associations between health-related fitness(HRF)and patient-reported symptoms in newly diagnosed breast cancer ***:This study utilized baseline data from the Alberta Moving Beyond Breast Cancer Cohort Study that were collected within 90 days of *** measures included peak cardiopulmonary fitness(peak volume of oxygen consumption(VO_(2peak))),maximal muscular strength and endurance,flexibility,and body *** measures included depression,sleep quality,and *** multivariable logistic regression was performed for ***:Of 1458 participants,51.5%reported poor sleep quality,26.5%reported significant fatigue,and 10.4%reported moderate *** multivariable-adjusted models,lower relative VO_(2peak)was independently associated with a greater likelihood of all symptom measures,including moderate depression(pnificant fatigue(p=0.008),any symptom(pnd multiple symptoms(pnstrated threshold associations with all symptom measures such that all 3 lower quartiles exhibited similar elevated risk compared to the highest *** strength of the threshold associations varied by the symptom measure with odds ratios ranging from-1.5 for poor sleep quality to-3.0 for moderate depression and multiple ***,lower relative upper body muscular endurance was also independently associated with fatigue in a dose-response manner(p=0.001),and higher body weight was independently associated with poor sleep quality in an inverted U pattern(p=0.021).Conclusion:Relative VO_(2peak)appears to be a critical HRF component associated with multiple patient-reported symptoms in newly diag

关键词： Breast cancer Fatigue Depression Sleep quality Cardiorespiratory fitness

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High-speed silicon photonic electro-optic Kerr modulation

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Photonics Research 2024年第1期12卷 51-60页

作者： JOnATHAn PELTIER WEIWEI ZHAnG LEOPOLD VIROT CHRISTIAn LAFFORGUE LUCAS DEnIEL DELPHInE MARRIS-MORInI GUY AUBIn FARAH AMAR DEnH TRAn XInGZHAO YAn CALLUM G.LITTLEJOHnS CARLOS ALOnSO-RAMOS KE LI DAVID J.THOMSOn GRAHAM reed LAUREnT VIVIEn University Paris-Saclay CNRSCentre for Nanoscience and Nanotechnology(C2N)Palaiseau 91120France University Grenoble Alpes CEALETIGrenoble 38000France Optoelectronics Research Centre Zepler Institute for Photonics and NanoelectronicsFaculty of Engineering and Physical SciencesUniversity of SouthamptonSouthampton SO171BJUK

Silicon-based electro-optic modulators contribute to easing the integration of high-speed and low-power consumption circuits for classical optical communications and data *** the plasma dispersion modulation,an alternative solution in silicon is to exploit the DC Kerr effect,which generates an equivalent linear electro-optical effect enabled by applying a large DC electric *** some theoretical and experimental studies have shown its existence in silicon,limited contributions relative to plasma dispersion have been achieved in high-speed modulation so *** paper presents high-speed optical modulation based on the DC Kerr effect in silicon PIn *** contributions of both plasma dispersion and Kerr effects have been analyzed in different waveguide configurations,and we demonstrated that the Kerr induced modulation is dominant when a high external DC electric field is applied in PIn ***-speed optical modulation response is analyzed,and eye diagrams up to 80 Gbit/s in nRZ format are obtained under a *** of 30 *** work paves the way to exploit the Kerr effect to generate high-speed Pockels-like optical modulation.

关键词： waveguide dispersion effect

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Therapies for Tau-associated neurodegenerative disorders:targeting molecules,synapses,and cells

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neural Regeneration Research 2023年第12期18卷 2633-2637页

作者： miranda Robbins MRC Laboratory of Molecular Biology Cambridge Biomedical CampusFrancis Crick AveTrumpingtonCambridgeUKUniversity of CambridgeDepartment of ZoologyCambridgeUK

Advances in experimental and computational technologies continue to grow rapidly to provide novel avenues for the treatment of neurodegenerative disorders. Despite this, there remain only a handful of drugs that have shown success in late-stage clinical trials for Tau-associated neurodegenerative disorders. The most commonly prescribed treatments are symptomatic treatments such as cholinesterase inhibitors and n-methyl-D-aspartate receptor blockers that were approved for use in Alzheimer's disease. As diagnostic screening can detect disorders at earlier time points, the field needs pre-symptomatic treatments that can prevent, or significantly delay the progression of these disorders(Koychev et al., 2019). These approaches may be different from late-stage treatments that may help to ameliorate symptoms and slow progression once symptoms have become more advanced should early diagnostic screening fail. This mini-review will highlight five key avenues of academic and industrial research for identifying therapeutic strategies to treat Tau-associated neurodegenerative disorders. These avenues include investigating(1) the broad class of chemicals termed “small molecules”;(2) adaptive immunity through both passive and active antibody treatments;(3) innate immunity with an emphasis on microglial modulation;(4) synaptic compartments with the view that Tau-associated neurodegenerative disorders are synaptopathies. Although this mini-review will focus on Alzheimer's disease due to its prevalence, it will also argue the need to target other tauopathies, as through understanding Alzheimer's disease as a Tau-associated neurodegenerative disorder, we may be able to generalize treatment options. For this reason, added detail linking back specifically to Tau protein as a direct therapeutic target will be added to each topic.

关键词： Alzheimer's disease antibody frontotemporal dementia immunotherapy small molecules synapses tau therapeutics

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Comparison between Care Strategies for Patients with Osteoarthritis of the Hands Based on the Use of Joint Protection, Assistive Technology and Exercises

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Open Journal of Orthopedics 2024年第7期14卷 295-311页

作者： Daniele dos Santos Scarcella Talita Dias da Silva Victoria Yanara Hernandes da Silva Maria Cândida de miranda Luzo Selma Lancman Marcia Uchoa de Rezende Carlos Bandeira de Mello Monteiro Instituto de Ortopedia e Traumatologia Hospital das Clnicas HCFMUSP Faculdade de Medicina Universidade de So Paulo So Paulo Brazil Programa de Ps-Graduao em Cincias da Reabilitao Faculdade de Medicina Universidade de So Paulo So Paulo Brazil Escola de Artes Cincias e Humanidades Universidade de So Paulo So Paulo Brazil

Background: Osteoarthritis (OA) is a disabling disease that can affect 6% to 12% of the adult population and more than a third of people over 65 years of age. Purpose: To assess whether a group of people with hand osteoarthritis (hOA) who received different types of treatment improved their function after two years of follow-up. Method: The entire sample (n = 97) underwent three follow-up assessments regarding anthropometric parameters of the upper limbs and ability to perform functional activities. Subsequently, the sample was divided into two groups for the intervention periods, called the First Period (n = 73) and the Second Period (n = 24);the First Period kept the same protocol with orientations, and the Second Period went to an intervention with orientation strength exercises and use of orthosis. Findings: In the separate analysis of the three questions of the DASH pain module, no differences were found between the assessment moments for groups of guidelines, treatment, or symptoms. Significant effects were observed for F(2, 162) = 3.5, p = 0.033, η2 = 0.04, and interaction for moments and intervention F(2, 162) = 4.3, p = 0.016, η2 = 0.05. Implications: It can be concluded that only guidance treatment does not benefit patients with hand osteoarthritis. In contrast, guidance, exercise, and orthosis treatment can significantly improve the disease.

关键词： Hand Osteoarthritis Hand Deformities Occupational Therapy

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