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Journal of Pharmaceutical Analysis 2020年第2期10卷 157-163页

作者： Obed A.Gyamfi Nesta Bortey-sam Abigail B.Donkor Carl W.White Brian A.Logue Department of Chemistry and Biochemistry South Dakota State UniversityBox 2202BrookingsSD57007USA Pediatrics-Pulmonary medicine University of Colorado-DenverDenverCO80045USA

The noxious effects from exposure to toxic inhalation hazards(TIHs,such as isocyanates,chlorine,etc.)are known to be triggered by the activation of transient receptor potential ankyrin 1(TRPA1)ion *** of TRPA1 have shown near complete attenuation of the noxious effects from TIH *** of the TRPA1 antagonists,(1E,3E)-1-(4-fluorophenyl)-2-methyl-1-pentene-3-one oxime(A-967079),has shown impressive efficacy,high selectivity,high potency,and oral *** a vali-dated method to quantify A-967079 in biological matrices is vital for the further development of A-967079 as a therapeutic agent,no method for its analysis from any matrix is currently ***,a rapid and simple HPLC-mS/mS method was developed and validated to quantify A-967079 in rabbit *** method presented here features an excellent LOD of 25 nm and a wide linear range(0.05-200μm),with good accuracy and precision(100±10.5%andma was excellent for most of the storage conditions *** method was successfully applied to determine A-967079 from treated animals and it may facilitate the development of this TRPA1 antagonist as a therapeutic agent against the noxious effects of TIH exposure.

关键词： Transient receptor potential(TRP)ion channel HPLC-mS/mS Toxic inhalation hazard(TIH) method development Pharmacokinetics

Liver-specific deletion of mechanistic target of rapamycin does not protect against acetaminophen-induced liver injury in mice

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Liver Research 2021年第2期5卷 79-87页

作者： Hua Sun Hong-min Ni Jennifer m.mcCracken Jephte Y Akakpo sam Fulte Tara mcKeen Hartmut Jaeschke Hua Wang Wen-Xing Ding Department of Pharmacology Toxicology and TherapeuticsThe University of Kansas Medical CenterKansas CityKSUSA Department of Oncology The First Affiliated Hospital of Anhui Medical UniversityHefeiChina

Background:Acetaminophen(APAP)overdose can cause liver injury and liver failure,which is one of the most common causes of drug-induced liver injury in the United *** activation of autophagy by inhibiting mechanistic target of rapamycin(mTOR)protects against APAP-induced liver injury likely via autophagic removal of APAP-adducts and damaged *** the present study,we aimed to investigate the role of genetic ablation of mTOR pathways in mouse liver in APAP-induced liver injury and liver repair/***:Albumin-Cre(Alb-Cre)mice,mTOR^(f/f) and Raptor^(f/f) mice(C57BL/6J background)were crossbred to produce liver-specific mTOR knockout(L-mTOR KO,Alb Cret/-,mTOR^(f/f))and liver-specific Raptor KO(L-Raptor,Alb Cret/-,Raptor^(f/f))***-Cre littermates were used as wild-type(WT)*** mice were treated with APAP for various time points for up to 48 *** injury,cell proliferation,autophagy and mTOR activation were ***:We found that genetic deletion of neither Raptor,an important adaptor protein in mTOR complex 1,nor mTOR,in the mouse liver significantly protected against APAP-induced liver injury despite increased hepatic autophagic *** deletion of Raptor or mTOR in mouse livers did not affect APAP metabolism and APAP-induced c-Jun N-terminal kinase(JNK)activation,but slightly improved mouse survival likely due to increased hepatocyte ***:Our results indicate that genetic ablation of mTOR in mouse livers does not protect against APAP-induced liver injury but may slightly improve liver regeneration and mouse survival after APAP overdose.

关键词： Acetaminophen(APAP) Autophagy Hepatotoxicity Liver injury Liver regeneration mechanistic target of rapamycin(mTOR) Regulatory associated protein of mTOR complex(Raptor)

POLY(N-ISOPROPYL ACRYLAmIDE) mICROGEL DOPED WITH LUmINESCENT PBS QUANTUm DOTS

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Chinese Journal of Reactive Polymers 2007年第Z1期 55-60页

作者： CHUCHI sam Department of Electrical & Computer Engineering University of Toronto 10 King’s College Rd Toronto ON m5S 3G4 Canada

Thiol-stabilized PbS quantum dots (QDs) with dimensions 3-5 nm capped with a mixture of 1-thioglycerol/dithioglycerol (TGL/DTG) were colloidally prepared at room temperature. Room temperature photoluminescence quantum efficiency of freshly prepared PbS QDs (7%-11%) remained higher than 5% upon aging for three weeks when the nanocrystals (NCs) were stored in an ice-bath in the dark, and higher than 5% for at least five weeks when extra DTG ligands were introduced into the nanocrystal solution followed by stirring every two weeks. Poly(N-isopropyl acrylamide) (PNIPAm) microgels were produced via precipitation polymerization with dimensions of ca. 230 nm and polydispersity of 3-5%. Incorporation of PbS QDs into PNIPAm microgels indicated that PbS can be incorporated into the interior of microgel particles and not at the microgel interface. The combination of reasonable room temperature quantum efficiency and strong, efficient luminescence covering the 1.3-1.55 μm telecommunication window makes these nanoparticles promising materials in optical devices and telecommunications.

关键词： Poly(N-isopropyl acrylamide) microgel PbS quantum dots Photoluminescence Photoluminescence quantum efficiency Incorporation/infiltration.

Whole-genome amplification/preimplantation genetic testing for propionic acidemia of successful pregnancy in an obligate carrier mexican couple:A case report

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World Journal of Clinical Cases 2021年第29期9卷 8797-8803页

作者： Adina Neumann miguel Angel Alcantara-Ortigoza Ariadna González-del Angel Nestor Alejandro Zarate Díaz Javier sam Santana Leonardo m Porchia Esther López-Bayghen Laboratorio de Investigación y Diagnóstico molecular IngenesMexico City 05320Mexico Laboratorio de Biología molecular Subdirección de Investigación MédicaInstituto Nacional de PediatríaMexico City 04530Mexico DNA-GEN S.C.Centro de Alta Especialidad en Genética Humana Mexico City 14070Mexico Investigación Clínica IngenesPuebla 72820Mexico Departamento de Toxicología Centro de Investigación y de Estudios Avanzados del Instituto Politécnico NacionalMexico City 07360Mexico

BACKGROUND Identifying a potential single monogenetic disorder in healthy couples is costly due to the Assisted Reproduction facilities'current methodology for screening,which focuses on the detecting multiple genetic disorders at ***,we report the successful application of a low-cost and fast preimplantation genetic testing for monogenic/single gene defects(PGT-m)approach for detecting propionic acidemia(PA)in embryos obtained from a confirmed heterozygous propionyl-CoA carboxylase alpha subunit(PCCA)*** SUmmARY A fertile 32-years old mexican couple with denied consanguinity sought antenatal genetic *** were suspected obligate PA carriers due to a previous deceased PA male newborn with an unknown PCCA/propionyl-CoA carboxylase beta subunit(PCCB)***-Generation Sequencing revealed a heterozygous genotype for a pathogenic PCCA variant(c.2041-1G>T,ClinVar:RCV-000802701.1;dbSNP:rs1367867218)in both *** couple requested in vitro fertilization(IVF)and PGT-m for *** IVF,12 oocytes were collected and fertilized,of which two resulted in high-quality *** biopsies and Whole Genome Amplification by a fragmentation/amplification-based method were performed and revealed that the two embryos were *** polymerase chain reaction and further Sanger sequencing of the exon-intron borders revealed a wild-type PCCA male embryo and a heterozygous c.2041-1G>T female *** embryos were transferred,resulting in a clinical pregnancy and the delivery of a healthy male newborn(38 wk,weight:4080 g,length:49 cm,APGAR 9/9).The absence of PA was confirmed by expanded newborn *** We show that using PGT-m with Whole Genome Amplification templates,coupled with IVF,can reduce the transmission of a pathogenic variant of the PCCA gene.

关键词： Propionic acidemia Autosomal recessive Propionyl-CoA carboxylase alpha subunit(PCCA)gene Preimplantation genetic testing Next-generation sequencing Embryo transfer

Cost/Charges Appraisal and Clinical Evidence Considerations in Orthopaedic Literature

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Open Journal of Orthopedics 2012年第2期2卷 40-46页

作者： Joe sam Robinson III m. sami Walid Waldo E. Floyd Joe sam Robinson Jr. School of medicine Mercer University Macon USA Kingsbrook Jewish medical Center Brooklyn USA OrthoGeorgia Macon USA Georgia Neurosurgical Institute Macon USA.

Introduction: Health care expenditures in the United States have rapidly risen in the last decade, including orthopaedic induced expenses. This paper addresses the methodology by which clinical evidence is obtained to better direct orthopaedic practice and encourage cost-efficiency. Questions: We conducted this inquiry to answer these questions: 1) Have orthopaedic expenses increased in the United States? 2) Does high grade clinical evidence prevail in orthopaedic literature? 3) Does clinical orthopaedic research include cost in outcome analysis? 4) Does the increase in orthopaedic expenses correlate with cost awareness in orthopaedic literature? methods: The aggregate hospital charges (national bill) associated with three major orthopaedic procedures were extracted from the Nationwide Inpatient sample (NIS) website (data available from 1997 to 2008). Using the biomedical search engine Pubmed (launched 1996), different types of literature pertaining to general orthopaedic and three major orthopaedic procedures—hip replacement, knee replacement, and spine fusion, were probed regarding level of evidence and cost inclusion. Results: From 1997 to 2008, the national hospital charges for spine fusion increased by 10.4 times while for total knee replacement it increased by 4.9 times and for total/partial hip replacement by 3.4 times. From 1996 to 2010, Pubmed indexed 1113 randomized controlled trials (RCTs) related to hip replacement, 942 related to knee replacement and 357 related to spine fusion. During the same period, RCTs related to total/partial hip replacement, total knee replacement and spine fusion procedures have increased by 3 times, 6 times, and 3.4 times, respectively. The percentage of blinded RCTS with cost analysis among all RCTs related to each procedure were 0%, 0.001% and 0.003% for total/partial hip replacement, total knee replacement and spine fusion procedures respectively. The correlation in the national hospital charges of all three procedures indiv

关键词： Clinical Evidence Randomized Clinical Trial Blinded Cost

Perioperative liver and spleen elastography in patients without chronic liver disease

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World Journal of Gastrointestinal Surgery 2018年第2期10卷 21-27页

作者： sam Eriksson Hanna Borsiin Carl-Fredrik Oerg Hannes Brange Zoran mijovic Christian Sturesson Department of Surgery Lund UniversitySkae University HospitalLund S-221 85Sweden Department of Radiology Lund UniversitySkae University HospitalLund S-221 85Sweden

AIm To investigate changes in hepatic and splenic stiffness in patients without chronic liver disease during liver resection for hepatic *** Patients scheduled for liver resection for hepatic tumors were considered for enrollment. Tissue stiffness measurements on liver and spleen were conducted before and two days after liver resection using point shear-wave elastography. Histological analysis of the resected liver specimen was conducted in all patients and patients with marked liver fibrosis were excluded from further study analysis. Patients were divided into groups depending on size of resection and whether they had received preoperative chemotherapy or not. The relation between tissue stiffness and postoperative biochemistry was investigated. RESULTS Results are presented as median(interquartile range). 35 patients were included. The liver stiffness increased in patients undergoing a major resection from 1.41(1.24-1.63) m/s to 2.20(1.72-2.44) m/s(P = 0.001). No change in liver stiffness in patients undergoing a minor resection was found [1.31(1.15-1.52) m/s vs 1.37(1.12-1.77) m/s, P = 0.438]. A major resection resulted in a 16%(7%-33%) increase in spleen stiffness, more(P = 0.047) than after a minor resection [2(-1-13) %]. Patients who underwent preoperative chemotherapy(n = 20) did not differ from others in preoperative right liver lobe [1.31(1.16-1.50) vs 1.38(1.12-1.56) m/s, P = 0.569] or spleen [2.79(2.33-3.11) vs 2.71(2.37-2.86) m/s, P = 0.515] stiffness. Remnant liver stiffness on the second postoperative day did not show strong correlations with maximum postoperative increase in bilirubin(R^2 = 0.154, Pearson's r = 0.392, P = 0.032) and international normalized ratio(R^2 = 0.285, Pearson's r = 0.534, P = 0.003). CONCLUSION Liver and spleen stiffness increase after a major liver resection for hepatic tumors in patients without chronic liver disease.

关键词： Chemotherapy Adjuvant Colorectal neoplasms Elasticity imaging techniques Hepatectomy Liver neoplasms

Reusable and durable electrostatic air filter based on hybrid metallized microfibers decorated with metal–organic–framework nanocrystals

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Journal of materials Science & Technology 2021年第26期85卷 44-55页

作者： min-Woo Kim Yong-Il Kinv Chanwoo Park Ali Aldalbahi Hamdah SAlanazi Seongpil An Alexander L.Yarin sam S.Yoon School of mechanical Engineering Korea UniversitySeoul 02841Republic of Korea SKKU Advanced Institute of Nanotechnology(SAINT) Sungkyunkwan University(SKKU)Suwon 16419Republic of Korea Department of Chemistry College of ScienceKing Saud UniversityRiyadh 11451Saudi Arabia Department of Nano Engineering Sungkyunkhwan University(SKKU)Suwon 16419Republic of Korea Department of mechanical and Industrial Engineering University of Illinois at Chicago842 W.Taylor St.ChicagoIL 60607-7022USA

As global air pollution becomes increasingly severe,various types of fibrous filters have been developed to improve air filter ***,fibrous filters have limitations such as high packing density that generally causes high-pressure drop and ultimately deterioration in the filtration ***-pressure particulate matter precipitators are limited in terms of scope for commercialization because they require high voltage supplies and ozone *** this study,we develop fibrous filters with enhanced durability and improved performance using metallized microfibers decorated with metal-organic-framework(mOF)*** only does the efficiency of the developed filters remain at or above 97%for 0.50-1.5μm Pms but the durability also significantly *** addition,using the water purification ability of the mOF,we explore the dye degradation effect of the hybrid microfibers by immersing them into Rhodamine B aqueous *** such an experiment the Rhodamine B aqueous solution is completely purified by the presence of the hybrid microfibers under the UV irradiation.

关键词： Electrospinning metallized microfibers metal organic framework(mOF)nanocrystals Corona discharge Reusable fibrous filter for air purification

The Effects of Zinc Sulfate on the in Vitro Digestibility of Feeds in Cervids

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Open Journal of Animal Sciences 2024年第3期14卷 157-167页

作者： Reese J. Thibodeaux Philip m. Urso Stanley F. Kelley marcy m. Beverly Chris R. Stewart Ian C. Dunn Gentech Diagnostics Dallas Texas USA Department of Animal Science South Dakota State University Brookings South Dakota USA School of Agricultural Sciences Sam Houston State University Huntsville Texas USA 3-S Texas Outdoors/3-S Whitetails Bedias Texas USA

The captive white-tailed deer industry has an estimated impact of 1.6 billion USD in the state of Texas alone. However, nutritional requirements for cervids are determined through research based on sheep and goats. The objective of this study was to determine the effects of zinc on differences in dry matter digestibility in vitro for white-tailed does (Odocoileus virginianus). Deer (n = 2) were ethically harvested, rumens were collected, and placed into a cooler containing warm water. Rumen contents were agitated, and fluid was filtered using cheese cloth while applying CO2. Fluid was placed into four separate incubator jars with filter bags containing a 1:1 alfalfa to coastal hay blend. Zinc doses of 0.073 mg/kg/d equivalents were added to two of the jars ( Zn), and the additional two jars received 0.00 mg/kg/d (CON). Following 48 h of incubation, in vitro true digestibility (IVTD) showed no significant differences between the control and the treatment groups. Average dry matter digested in vitro was 91.87% and 95.13%, respectively. There were no differences detected in ADF, NDF, IVTD, or Om between the treatment groups. While no detectable differences were observed in this study, this methodology did prove to be viable and functional for microbial digestion in vitro. This study can be replicated with multiple experimental units to confirm the observations of increased digestibility. Formal nutritional guidelines can be created to allow for more efficient feeding of cervids thereby reducing feed costs and continuing the growth of the captive deer industry.

关键词： Zinc IVDmD In Vitro Cervids

用多感官型分心装置缓解患儿伤口处理时疼痛的研究

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中华烧伤杂志 2009年第5期25卷 352-356页

作者： Kate miller Sylvia Rodger sam Bucolo Xue-Qing Wang Roy m Kimble 4029 Stuart Pegg Paediatric Burns Centre Royal Children's Hospital Brisbane Australia Bums Research Group Department of Paediatrics & Child Health The School of Medicine The University of Queensland Brisbane Australia Department of Occupational Therapy The School of Health and Rehabilitation Sciences The University of Queensland Brisbane Australia Department of Design Queensland University of Technology Brisbane Australia

目的设计多感官型分心装置（mmD），观察其在烧伤换药和其他医疗过程中减轻患儿焦虑和疼痛的效果。方法设计3项前瞻性、随机对照临床试验。选择澳大利亚布里斯班皇家儿童医院烧伤中心和骨折整形外科患儿182例，共计354个医疗过程，分别... 详细信息

目的设计多感官型分心装置（mmD），观察其在烧伤换药和其他医疗过程中减轻患儿焦虑和疼痛的效果。方法设计3项前瞻性、随机对照临床试验。选择澳大利亚布里斯班皇家儿童医院烧伤中心和骨折整形外科患儿182例，共计354个医疗过程，分别应用标准分心法、手握电子游戏机和mmD（前mmD—D型、mmD-D型及mmD-PP型）。采用改良面部表情评分法、面部疼痛评分法、视觉模拟评分法及Wong，Baker面部表情疼痛评分法，记录患儿报告的疼痛分数、父母和护理人员报告的患儿焦虑和疼痛分数以及换药时间。结果与标准分心法组和电子游戏机组[（3．60±O．25）、（3．83±1．49）分]比较，mmD—D组与mmD—PP组患儿首次换药时的疼痛分数[（2．13±0．23）、（2．15±0．17）分]显著降低（P〈0．01），换药时间明显缩短（P〈0．01），且mmD在连续3次换药过程中均能发挥缓解疼痛的作用。此外，mmD-PP组患儿在换药前由焦虑引起的疼痛分数也较其他组显著降低（P〈0．01）。结论mmD较标准分心法和手握电子游戏机更能有效减轻患儿伤口处理过程中的焦虑和疼痛。该装置仍在临床试验中，且继续显示其有效性。

关键词：镇痛儿童分心法虚拟现实

Chemistry-led investigations into the mode of action of NAmPT activators,resulting in the discovery of non-pyridyl class NAmPT activators

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Acta Pharmaceutica Sinica B 2023年第2期13卷 709-721页

作者： Siyuan Tang miguel Garzon Sanz Oliver Smith Andreas Krämer Daniel Egbase Paul W.Caton Stefan Knapp sam Butterworth Division of Pharmacy and Optometry School of Health SciencesManchester Academic Health Sciences CentreUniversity of ManchesterManchester M139PLUK Structural Genomics Consortium(SGC) 60438 Frankfurt Am MainGermany Buchmann Institute for Life Sciences(BmLS) 60438 Frankfurt Am MainGermany Institut für Pharmazeutische Chemie Goethe University60438 Frankfurt Am MainGermany Frankfurt Cancer Institute(FCI) 60596 Frankfurt Am MainGermany Department of Diabetes School of Cardiovascular and Metabolic Medicine&SciencesFaculty of Life Sciences&MedicineKing's College LondonLondon SE11ULUK

The cofactor nicotinamide adenine dinucleotide(NAD+)plays a key role in a wide range of physiological processes and maintaining or enhancing NAD+levels is an established approach to enhancing healthy ***,several classes of nicotinamide phosphoribosyl transferase(NAmPT)activators have been shown to increase NAD+levels in vitro and in vivo and to demonstrate beneficial effects in animal *** best validated of these compounds are structurally related to known urea-type NAmPT inhibitors,however the basis for the switch from inhibitory activity to activation is not well *** we report an evaluation of the structure activity relationships of NAmPT activators by designing,synthesising and testing compounds from other NAmPT ligand chemotypes and mimetics of putative phosphoribosylated adducts of known *** results of these studies led us to hypothesise that these activators act via a through-water interaction in the NAmPT active site,resulting in the design of the first known urea-class NAmPT activator that does not utilise a pyridine-like warhead,which shows similar or greater activity as a NAmPT activator in biochemical and cellular assays relative to known analogues.

关键词： Nicotinamide phosphoribosyl transferase activator Healthy aging Drug discovery Bioisosteres medicinal chemistry