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Elucidating the Degradation Pathways of Human Insulin in the Solid State

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Journal of Analysis and Testing 2024年第3期8卷 288-299页

作者： Andrew Fagan Lorraine M.Bateman Joseph P.O'Shea Abina M.Crean SSPC the SFI Centre for Pharmaceutical Research School of Pharmacy University College Cork School of pharmacy University College Cork Analytical and Biological Chemistry Research Facility (ABCRF) University College Cork School of Chemistry University College Cork

While there have been significant advances in the development of peptide oral dosage forms in recent years, highlighted by the clinical and commercial success of approved peptides such as Rybelsus?, there remain several barriers in the way of broad range applicability of this approach to peptide delivery. One such barrier includes the poor physical and chemical stability inherent to their structures, which persists in the solid state although degradation typically occurs at different rates and via different pathways in comparison to the solution state. Using insulin as a model peptide, this work sought to contribute to the development of analytical techniques for investigating common insulin degradation pathways. Chemically denatured,deamidated and aggregated samples were prepared and used to benchmark circular dichroism spectroscopy, reverse phase HPLC and size exclusion chromatography methods for the investigation of unfolding, chemical modifications and covalent aggregation of the insulin molecule respectively. Solid state degraded samples were prepared by heating insulin powder at 60 °C and 75% relative humidity for 1, 3, 5 and 7 d, and the degradation profiles of the samples were evaluated and compared with those observed in solution. While no unfolding was observed to occur, significant deamidation and covalent aggregation were detected. Reductive disulfide bond cleavage using dithiothreitol allowed for separation of the insulin A-and B-chains,offering a facile yet novel means of assessing the mechanisms of deamidation and covalent aggregation occurring in the solid state.

关键词： Biopharmaceutical analysis Covalent aggregation Deamidation Disulfide cleavage Insulin Solid state Stability

Olfactory dysfunction and its related molecular mechanisms in Parkinson’s disease

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Neural Regeneration Research 2024年第3期19卷 583-590页

作者： Yingying Gu Jiaying Zhang Xinru Zhao Wenyuan Nie Xiaole Xu Mingxuan Liu Xiaoling Zhang college of pharmacy Nantong UniversityNantongJiangsu ProvinceChina

Changes in olfactory function are considered to be early biomarkers of Parkinson’s *** dysfunction is one of the earliest non-motor features of Parkinson’s disease,appearing in about 90%of patients with early-stage Parkinson’s disease,and can often predate the diagnosis by ***,olfactory dysfunction should be considered a reliable marker of the ***,the mechanisms responsible for olfactory dysfunction are currently *** this article,we clearly explain the pathology and medical definition of olfactory function as a biomarker for early-stage Parkinson’s *** the basis of the findings of clinical olfactory function tests and animal model experiments as well as neurotransmitter expression levels,we further characterize the relationship between olfactory dysfunction and neurodegenerative diseases as well as the molecular mechanisms underlying olfactory dysfunction in the pathology of early-stage Parkinson’s *** findings highlighted in this review suggest that olfactory dysfunction is an important biomarker for preclinical-stage Parkinson’s ***,therapeutic drugs targeting non-motor symptoms such as olfactory dysfunction in the early stage of Parkinson’s disease may prevent or delay dopaminergic neurodegeneration and reduce motor symptoms,highlighting the potential of identifying effective targets for treating Parkinson’s disease by inhibiting the deterioration of olfactory dysfunction.

关键词： biomarker early-stage olfactory disorders olfactory dysfunction Parkinson’s disease

Spark plasma sintering of tungsten-based WTaVCr refractory high entropy alloys for nuclear fusion applications

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International Journal of Minerals,Metallurgy and Materials 2024年第1期31卷 146-154页

作者： Yongchul Yoo Xiang Zhang Fei Wang Xin Chen Xing-Zhong Li Michael Nastasi Bai Cui Department of Mechanical&Materials Engineering University of Nebraska-LincolnLincolnNE 68588USA nebraska Center for Materials and Nanoscience University of Nebraska-LincolnLincolnNE 68588USA Department of Nuclear Engineering Texas A&M UniversityCollege StationTX 77843USA

W-based WTaVCr refractory high entropy alloys (RHEA) may be novel and promising candidate materials for plasma facing components in the first wall and diverter in fusion reactors. This alloy has been developed by a powder metallurgy process combining mechanical alloying and spark plasma sintering (SPS). The SPSed samples contained two phases, in which the matrix is RHEA with a body-centered cubic structure, while the oxide phase was most likely Ta2VO6through a combined analysis of X-ray diffraction (XRD),energy-dispersive spectroscopy (EDS), and selected area electron diffraction (SAED). The higher oxygen affinity of Ta and V may explain the preferential formation of their oxide phases based on thermodynamic calculations. Electron backscatter diffraction (EBSD) revealed an average grain size of 6.2μm. WTaVCr RHEA showed a peak compressive strength of 2997 MPa at room temperature and much higher micro-and nano-hardness than W and other W-based RHEAs in the literature. Their high Rockwell hardness can be retained to at least 1000°C.

关键词： refractory high entropy alloy plasma-facing material fusion reactor spark plasma sintering

Tetramic acid-motif natural products from a marine fungus Tolypocladium cylindrosporum FB06 and their anti-Parkinson activities

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Marine Life Science & Technology 2024年第1期6卷 84-92页

作者： Yuna Jung Chaesun Kwon Taeyeon Kim Jin Woo Lee Min-Kyoo Shin Sang Hee Shim Natural Products Research Institute College of PharmacySeoul National UniversitySeoul 08826Republic of Korea college of pharmacy and Research Institute of Pharmaceutical Sciences Seoul National UniversitySeoul 08826Republic of Korea college of pharmacy Duksung Women’s UniversitySeoul 01369Republic of Korea

Tetramic acid-containing natural products are attracting significantly increasing attention from biologists and chemists due to their intriguing structures and biological *** the present study,two new tetramic acid alkaloids tolypyridone I(1)and tolypyridone J(2),together with five known ones(3–7),were isolated from cultures of a marine fungus Tolypocladium cylindrosporum FB06 isolate obtained from a marine sediment in Beaufort sea of North *** structures were elucidated using 1D,2D NMR,and *** configurations were established on the basis of 1H coupling constants,ROESY correlations and DP4 *** 2 was isolated as mixtures of rotational isomers with C-3 to C-7 axis between 4-hydroxy-2-pyridone and 1-ethyl-3,5-dimethylcyclohexane,hindering *** our unbiased screening to discover neuroprotective compounds in an in vitro Parkinson’s disease(PD)model,SH-SY5Y dopaminergic cells were treated with isolated compounds followed by treatment with 1-methyl-4-phenylpyridinium(MPP^(+)),a parkinsonian *** tested compounds,F-14329(7)significantly protected cells from MPP^(+)-induced ***^(+)-mediated cell death is known to be related to the regulation of Bcl-2 family proteins,specifically the down-regulation of anti-apoptotic Bcl-2 and the up-regulation of pro-apoptotic Bax *** with 2 mmol/L of MPP^(+)for 24 h significantly reduced Bcl-2 levels compared to control treated with ***,treatment with F-14329(7)attenuated such *** study demonstrates that tetramic acid-motif compounds could be potential lead compounds for treating PD.

关键词： Tolypocladium cylindrosporum Tetramic acid Tolypyridone Parkinson’s disease

CuInS_(2)quantum-dot-modified g-C_(3)N_(4)S-scheme heterojunction photocatalyst for hydrogen production and tetracycline degradation

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Journal of Materials Science & Technology 2024年第5期172卷 145-155页

作者： Jingjing Zhang Yue Zhao Kezhen Qi Shu-yuan Liu college of pharmacy Dali UniversityDali 671000China Department of Pharmacology Shenyang Medical CollegeShenyang 110034China

CuInS_(2)quantum-dot(CIS QD)-modified g-C_(3)N_(4)(CN)catalysts(CIS/CN)were prepared with the aid of an in-situ growth *** as-obtained photocatalysts were explored by measuring their crystallinity,surface morphology,binding energy and light absorption *** photocatalytic efficiency of the pho-tocatalysts was evaluated through photocatalytic water splitting for hydrogen production and tetracycline(TC)antibiotic degradation under the simulated solar light and visible light *** optimized sample(10CIS/CN)showed the best photocatalytic activity:producing 102.4μmol g^(-1)h^(-1)of hydrogen in 1 h,or degrading 52.16%of TC in 120 min,which were respectively 48 or 3.4 times higher than the photocatalytic activity of CN *** enhancement in the efficiency of the composite system was prin-cipally accredited to the enlargement of light absorption,the more effective in charge transfer and the dropping of the charge carrier pair recombination through a formed S-scheme heterojunctional *** work is an effort to adjust CN-based polysulfide QD for speedy *** enriched photo-catalytic activity grants a new sense for adjusting the optical properties of CN.

关键词： CuInS_(2)QDs g-C_(3)N_(4) Photocatalysis Hydrogen production S-scheme heterojunction

Phase-dependent lithium-alloying reactions for lithium-metal batteries

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Chinese Chemical Letters 2024年第4期35卷 1-2页

作者： Shu Lin Kezhen Qi college of pharmacy Dali UniversityDali 671000China

With the increasing demand for higher energy lithium-ion batteries (LIBs), it is imperative to develop high-capacity electrode materials [1–4]. Due to the unique electrochemical Li-alloying reactions, Li-alloys offer high theoretical capacity, especially lithiumrich phase alloys, which exceeds the theoretical capacity of graphite anodes [5–7]. Phase-transition, which significantly influences lithium alloy reactions, determines high voltage hysteresis,low Coulombic efficiency (CE), and short cycling life [8,9].

关键词： alloying alloys cycling

Considerations for the use of porcine organ donation models in preclinical organ donor intervention research

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Animal Models and Experimental Medicine 2024年第3期7卷 283-296页

作者： Frazer I.Heinis Shaheed Merani Nicholas W.Markin Kim F.Duncan Michael J.Moulton Lance Fristoe William E.Thorell Raechel A.Sherrick Tami R.Wells Matthew T.Andrews Marian Urban School of Natural Resources Institute of Agriculture and Natural ResourcesUniversity of Nebraska-LincolnLincolnNebraskaUSA Division of Transplantation and Vascular Surgery Department of SurgeryUniversity of Nebraska Medical CenterOmahaNebraskaUSA Department of Anesthesiology University of Nebraska Medical CenterOmahaNebraskaUSA Division of Cardiothoracic Surgery Department of SurgeryUniversity of Nebraska Medical CenterOmahaNebraskaUSA Clinical Perfusion Nebraska Medicine-Nebraska Medical CenterOmahaNebraskaUSA Department of Neurosurgery University of Nebraska Medical CenterOmahaNebraskaUSA Nutrition and Health Sciences College of Education and Human SciencesUniversity of Nebraska-LincolnLincolnNebraskaUSA Department of Comparative Medicine University of Nebraska Medical CenterOmahaNebraskaUSA

Use of animal models in preclinical transplant research is essential to the optimization of human allografts for clinical *** models of organ donation and preservation help to advance and improve technical elements of solid organ recovery and facilitate research of ischemia-reperfusion injury,organ preservation strategies,and future donor-based *** considerations include cost,public opinion regarding the conduct of animal research,translational value,and relevance of the animal model for clinical *** present an overview of two porcine models of organ donation:donation following brain death(DBD)and donation following circulatory death(DCD).The cardiovascular anatomy and physiology of pigs closely resembles those of humans,making this species the most appropriate for pre-clinical *** are also considered a potential source of organs for human heart and kidney *** is imperative to minimize animal loss during procedures that are surgically *** present our experience with these models and describe in detail the use cases,procedural approach,challenges,alternatives,and limitations of each model.

关键词： animal model brain death circulatory death organ transplantation

Probing the Bardeen-Kiselev black hole with the cosmological constant caused by Einstein equations coupled with nonlinear electrodynamics using quasinormal modes and greybody bounds

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Communications in Theoretical Physics 2024年第6期76卷 102-119页

作者： S R Wu B Q Wang Z W Long college of Physics Guizhou UniversityGuiyang 550025China college pharmacy Guizhou University of Traditional Chinese MedicineGuiyang 550025China

In this work,we investigate a static and spherically symmetric Bardeen-Kiselev black hole(BH)with the cosmological constant,which is a solution of the Einstein-non-linear Maxwell field *** compute the quasinormal frequencies for the Bardeen-Kiselev BH with the cosmological constant due to electromagnetic and gravitational *** varying the BH parameters,we discuss the behavior of both real and imaginary parts of the BH quasinormal frequencies and compare these frequencies with the Reissner-Nordström-de Sitter BH surrounded by quintessence(RN-dSQ).Interestingly,it is shown that the responses of the Bardeen-Kiselev BH with the cosmological constant and the RN-dSQ under electromagnetic perturbations are different when the charge parameter q,the state parameter w and the normalization factor c are varied;however,for the gravitational perturbations,the responses of the Bardeen-Kiselev BH with the cosmological constant and the RN-dSQ are different only when the charge parameter q is ***,compared with the gravitational perturbations,the electromagnetic perturbations can be used to understand nonlinear and linear electromagnetic fields in curved spacetime *** interesting observation is that,due to the presence of Kiselev quintessence,the electromagnetic perturbations around the Bardeen-Kiselev BH with the cosmological constant damps faster and oscillates slowly;for the gravitational perturbations,the quasinormal mode decays slowly and oscillates *** also study the reflection and transmission coefficients along with the absorption cross section in the Bardeen-Kiselev BH with the cosmological constant;it is shown that the transmission coefficients will increase due to the presence of Kiselev quintessence.

关键词： quasinormal modes greybody factors Bardeen-Kiselev black hole with cosmological constant

Current perspective on amyloid aggregation accelerating properties of the artificial butter flavoring,diacetyl

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Neural Regeneration Research 2024年第10期19卷 2113-2114页

作者： Ashish P.Vartak Swati S.More Center for Drug Design College of PharmacyUniversity of MinnesotaMinneapolisMNUSA

The amyloid—what peptide can resist its entropic bliss?Without kinetic barricades and chaperones,most peptides would simply tumble down that *** amyloid-β(Aβ) peptides are understood to underlie the hallmark pathology of Alzheimer's disease(AD) and are considered one of the causative factors for neurodegeneration and cognitive *** affects critical connected structures within the brain that are responsible for memory,language,and social behavior.

关键词： amyloid Alzheimer Aβ