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Location matters: The role of TRPV4/calmodulin mediated AQP4 translocation in human astrocyte in response to hypoxia and mild therapeutic hypothermia

Location matters: The role of TRPV4/calmodulin mediated AQP4...

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中国神经科学学会第十二届全国学术会议

作者： mootaz Salman Philip Kitchen Roslyn m.bill Alex C.Conner m.Nicola Woodroofe matthew T.Conner Biomolecular Sciences Research Centre (BmRC) Sheffield Hallam University molecular Assembly and Organisation in Cells Doctoral Training Centre University of Warwick School of Life & Health Sciences and Aston Research Centre for Healthy Ageing Aston University School of Clinical and Experimental medicine University of Birmingham School of Biology Chemistry and Forensic Science University of Wolverhampton

Therapeutic hypothermia is the one of the most effective measures against brain injury. Astrocytes are the brain’s most abundant cell type so it is essential to understand their stress response. One of the main mechanism by which hypothermia attenuates oedema formation, is preserving the brain’s water homeostasis. This water homeostasis is tightly regulated by a group of membrane proteins called aquaporins（AQPs）. In this study, we investigated the alterations in the expressional profile of all the cerebral AQPs with a particular interest of AQP4 membrane expression and calmodulin level in astrocytes cultured under hypoxic conditions for 6 h at mild hypothermia of 32 ℃. Human aquaporin 4（AQP4） is the primary water channel protein in brain astrocytes. Hypothermia is known to cause astrocyte swelling in culture, but the precise role of AQP4 in this swelling is unknown. Primary human cortical astrocytes were cultured under hypothermic（32 ℃） or normothermic（37 ℃） conditions. AQP4 transcript, total protein and surface localized protein were quantified using RT-q PCR, sandwich ELISA with whole cell lysates, or cell-surface biotinylation followed by ELISA analysis of the surface-localized protein, respectively. 4 h mild hypothermic incubation increased the surface localization of AQP4 in human astrocytes to 256 ± 2% of normothermic controls, despite no change in total protein expression. Hypothermia-mediated increase in the AQP4 surface abundance in human astrocytes was blocked using a calmodulin antagonist（trifluoperazine;TFP） or the TRPV4 inhibitor HC-067047. Hypothermia leads to an increase in surface localization of AQP4 in human astrocytes through a mechanism likely dependent on the TRPV4 calcium channel and calmodulin activation. Hypothermia has a complex effect and there is no single factor that could explain its neuroprotection effect. Understanding the effects of hypothermia on astrocytic AQP4 cell-surface expression may help develop new treatments for brain swelli

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Ems-Griltech:新型特种纤维

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国际纺织导报 2006年第11期34卷 8-8,10,11页

作者： m．bill 桑榆（译）申熠（校） Ems—Grihech公司（瑞士）不详

Ems公司销售各种各样的短纤维和复丝,主要是聚酰胺纤维,以Grilon为商品名称,已经50多年了。最近该公司专心于生产独特的特种纤维,这些纤维具有异乎寻常的性质,与标准纤维相比,能实现更加广泛的不同功能。

关键词：特种纤维性能用途

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逃离导向基团:非活化烯烃的不对称碳-碳键构筑

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Science Bulletin 2024年第3期69卷 290-292页

作者： Hongyu Zhong bill morandi Laboratorium für Organische Chemie ETH ZürichZürich 8093Switzerland

Unfunctionalized olefins are produced on an enormous scale in the petroleum *** example,propene and butenes are produced annually on over 100-and 40-million-ton *** metal catalysis is an attractive approach for the valorization of such chemical feedstocks,which provides value-added building blocks that can be further transformed into pharmaceuticals and functional ***,unfunctionalized olefins are relatively inert molecules due to their weak interaction with the metal ***,the functionalization of unactivated olefins has been a long-standing challenge in transition metal *** use of directing groups has become a universal strategy to overcome the reactivity and selectivity issues[1].Directing groups are strongly binding functionalities that serve to coordinate to the metal center and bring the unactivated moiety closer to the metal.

关键词： moiety overcome closer

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Speed and surface steepness affect internal tibial loading during running

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Journal of Sport and Health Science 2024年第1期13卷 118-124页

作者： Hannah Rice markus Kurz Patrick mai Leon Robertz Kevin bill Timothy R.Derrick Steffen Willwacher Department of Physical Performance Norwegian School of Sport SciencesOslo 0806Norway Sports Tech Research Centre Mid Sweden UniversityÖstersund SE-83125Sweden Department of mechanical and Process Engineering Offenburg University of Applied SciencesOffenburg 77652Germany Institute of Biomechanics and Orthopaedics German Sport University CologneCologne 50933Germany Department of Kinesiology Iowa State UniversityAmesIA 50011USA

Background:Internal tibial loading is influenced by modifiable factors with implications for the risk of stress *** encounter varied surface steepness(gradients)when running outdoors and may adapt their speed according to the *** study aimed to quantify tibial bending moments and stress at the anterior and posterior peripheries when running at different speeds on surfaces of different ***:Twenty recreational runners ran on a treadmill at 3 different speeds(2.5 m/s,3.0 m/s,and 3.5 m/s)and gradients(level:0%;uphill:+5%,+10%,and+15%;downhill:-5%,-10%,and-15%).Force and marker data were collected synchronously *** moments were estimated at the distal third centroid of the tibia about the medial-lateral axis by ensuring static equilibrium at each 1%of *** was derived from bending moments at the anterior and posterior peripheries by modeling the tibia as a hollow ***-way repeated-measures analysis of variance were conducted using both functional and discrete statistical ***:There were significant main effects for running speed and gradient on peak bending moments and peak anterior and posterior *** running speeds resulted in greater tibial *** uphill at+10%and+15%resulted in greater tibial loading than level *** downhill at-10%and-15%resulted in reduced tibial loading compared to level *** was no difference between+5%or-5%and level ***:Running at faster speeds and uphill on gradients≥+10%increased internal tibial loading,whereas slower running and downhill running on gradients≥-10%reduced internal *** running speed according to the gradient could be a protective mechanism,providing runners with a strategy to minimize the risk of tibial stress injuries.

关键词： Bending moments Gradient musculoskeletal modeling Overuse injury Tibial stress Training factors

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Gold Standard for Skin Cancer Treatment: Surgery (mohs) or microscopic molecular-Cellular Therapy (Curaderm)?

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Journal of Cancer Therapy 2024年第2期15卷 33-47页

作者： bill Elliot Cham Australasian medical Research Port Vila Republic of Vanuatu

Non-melanoma skin cancers or keratinocyte cancers such as basal cell carcinoma and squamous cell carcinoma make up approximately 80% and 20% respectively, of skin cancers with the 6 million people that are treated annually in the United States. 1 in 5 Americans and 2 in 3 Australians develop skin cancer by the age of 70 years and in Australia it is the most expensive, amassing $1.5 billion, to treat cancers. Non-melanoma skin cancers are often self-detected and are usually removed by various means in doctors’ surgeries. mohs micrographic surgery is acclaimed to be the gold standard for the treatment of skin cancer. However, a novel microscopic molecular-cellular non-invasive topical therapy described in this article, challenges the status of mohs procedure for being the acclaimed gold standard.

关键词： Skin Cancer Basal Cell Carcinoma Squamous Cell Carcinoma mohs Surgery microscopic molecular-Cellular Curaderm Actinic Keratosis Cosmesis

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Unique Clinical Features of Curaderm when Treating Skin Cancers

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Journal of Cancer Therapy 2024年第1期15卷 13-27页

作者： Tania Robyn Chase Kai Elliot Cham.bill Elliot Cham Australasian medical Research Port Vila Republic of Vanuatu

Basal cell carcinoma is the most common form of skin cancer and the most frequently occurring form of all cancers. Conventional treatments to remove or destroy basal cell carcinoma are indiscriminate and also remove or destroy normal skin cells resulting in compromised cosmetic outcomes. Consequences of these treatments include body-image issues, anxiety, post-traumatic stress disorder, depression, and poorer quality of social and family life. A progressive topical cream formulation, Curaderm, containing the natural BEC glycoalkaloids, have shown to have advantages over conventional treatments. However, comprehensive clinical features of the skin cancer lesions during treatment with Curaderm have to date not been reported. This report shows that using unpublished data from a large number of patients with varying sizes, types and locations of basal cell carcinomas when treated with Curaderm in a phase 3 trial, an initial increase in size of the lesions occur, followed by a reverse course, leading to complete removal of the skin cancer. The specificity and mode of action of Curaderm explains the superior cosmetic outcomes when compared with conventional therapies.

关键词： Curaderm Skin Cancer Basal Cell Carcinoma BEC Glycoalkaloids Conventional Treatments

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The Value of Excipients and the Required Understanding of the Biological System in Product Development: An Impactful Example of Curaderm, a Topical Skin Cancer Treatment

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International Journal of Clinical medicine 2024年第2期15卷 68-87页

作者： Tania Robyn Chase Kai Elliot Cham.bill Elliot Cham Australasian medical Research Port Vila Republic of Vanuatu

The incidences of nonmelanoma skin cancer are increasing worldwide, and the ongoing war on its treatment necessitates the development of effective and non-invasive methods. Through basic and clinical research, non-invasive treatments like Curaderm have been developed, leading to improved quality of life for patients. Excipients, previously considered inactive ingredients, play a crucial role in enhancing the performance of topical formulations. The development of Curaderm emphasizes the importance of understanding the interactions between active ingredients, excipients, and the biological system to create effective and affordable pharmaceutical formulations. The systematic approach taken in the development of Curaderm, starting from the observation of the anticancer activity of natural solasodine glycosides and progressing through toxicological and efficacy studies in cell culture, animals, and humans, has provided insights into the pharmacokinetics and pharmacodynamics of solasodine glycosides. It is crucial to determine these pharmacological parameters within the skin’s biological system for maximal effectiveness and cost-effectiveness of a skin cancer treatment. Curaderm, as a topical treatment for nonmelanoma skin cancer, offers benefits beyond those obtained from other topical treatments, providing hope for improved quality of life for patients.

关键词： Curaderm BEC Solasodine Glycosides Solamargine Apoptosis Skin Cancer Actinic Keratosis Keratoacanthoma Basal Cell Carcinoma Squamous Cell Carcinoma

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Frequency-dependent viscoelasticity effects on the wave attenuation performance of multi-layered periodic foundations

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Applied mathematics and mechanics(English Edition) 2024年第3期45卷 407-424页

作者： m.SAFI m.VAKILIFARD m.J.mAHmOODI Faculty of Civil Water&Environmental EngineeringShahid Beheshti UniversityTehran ***Iran Faculty of mechanical and Energy Engineering Shahid Beheshti UniversityTehran ***Iran

In this paper,layered periodic foundations(LPFs)are numerically examined for their responses to longitudinal and transverse modes in the time and frequency *** different unit-cells,i.e.,2-layer,4-layer,and 6-layer unit-cells,comprising concrete/rubber,concrete/rubber/steel/rubber,and concrete/rubber/steel/rubber/lead/rubber materials,respectively,are taken into ***,the viscoelasticity behavior of the rubber is modeled with two factors,i.e.,a frequency-independent(FI)loss factor and a linear frequency-dependent(FD)loss *** the extraction of the complex dispersion curves and the identification of the band gaps(BGs),the simulations of wave transmission in the time and frequency domains are performed using the COmSOL *** parametric studies evaluate the effects of the rubber viscoelasticity models on the dispersion curves and the wave transmission for the longitudinal and transverse *** results show that considering the rubber viscoelasticity enhances the wave attenuation ***,the transverse-mode damping is more sensitive to the viscoelasticity model than its longitudinal *** 6-layer unit-cell LPF exhibits the lowest BG,ranging from 4.8 Hz to 6.5 Hz.

关键词： layered metamaterial periodic foundation complex dispersion curve wave transmission diagram

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Engineering of efficient visible light photocatalysts:Ti_(1-x+y)Cu_(x)La_(y)O_(2)(x=0.03;y=0,0.005,0.01) compositions

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Journal of Rare Earths 2024年第3期42卷 497-505,I0003页

作者： S.m.Yakout A.m.Youssef Inorganic Chemistry Department National Research Centre(NRC)El Buhouth StDokkiCairo12622Egypt

In dye-photocatalysis, widening the wavelengths absorption range of catalysts as well as aborting the recombination of the photoexcited charge carriers(electrons-holes pairs) are of paramount *** the current study, we report the photocatalytic characteristics of four compositions composed of TiO_(2),Ti_(0.97)Cu_(0.03)O_(2), Ti_(0.965)Cu_(0.03)La_(0.005)O_(2)and Ti_(0.96)Cu_(0.03)La_(0.01)O_(2)powders for two harmful dyes(Congo red and methylene blue). The X-ray diffraction technique verified the configuration of mixed anatase and rutile phases in pure TiO_(2)and Ti_(0.97)Cu_(0.03)O_(2)powders while Ti_(0.965)Cu_(0.03)La_(0.005)O_(2)and Ti_(0.96)Cu_(0.03)La_(0.01)O_(2)powders possess anatase phase only. The changes of the band gap structure and dimensions of the unit cell volume of TiO_(2)confirm the substitution of Ti^(4+)sites by Cu^(2+)and La^(3+)ions. Remarkable widening of wavelengths absorption with formation of long absorption tails were found in TiO_(2)(3.13 e V) through insertion of La^(3+)plus Cu^(2+)ions. Ti_(0.965)Cu_(0.03)La_(0.005)O_(2)and Ti_(0.96)Cu_(0.03)La_(0.01)O_(2)samples exhibit a visible light band gap of 2.3 and 2.7 e V, respectively. Based on SEm images, incorporation of Cu^(2+)and La^(3+)ions influences the surface morphology of TiO_(2). The resulting Ti_(0.97)Cu_(0.03)O_(2), Ti_(0.965)Cu_(0.03)La_(0.005)O_(2)and Ti_(0.96)Cu_(0.03)La_(0.01)O_(2)powders present enhanced photocatalytic activity towards Congo red dye degradation compared to pure one under natural solar spectrum. The best Ti_(0.96)Cu_(0.03)La_(0.01)O_(2)catalyst exhibits superior photocatalytic activity of 96% for 10 ppm CR dye in 20 min as well as above average photocatalytic efficiency of 63% for 30 ppm CR dye in 120 min. As well, it showed acceptable photodegradation activity of 52% for 30 ppm mB solution in 140 min of sunlight irradiation. The heightened photodegradation efficiency of Ti_(0.96)Cu_(0.03)La_(0.01)O_(2)catalyst can be clarified in terms of higher ch

关键词： Semiconductor TiO_(2) Rare earths Congo red methylene blue Solar spectrum Photodegradation

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Nonlinear dynamic modeling of planar moving Timoshenko beam considering non-rigid non-elastic axial effects

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Applied mathematics and mechanics(English Edition) 2024年第3期45卷 479-496页

作者： m.ABBASI GAVARI m.R.HOmAEINEZHAD Faculty of mechanical Engineering K.N.Toosi University of TechnologyTehran 19991-43344Iran

Due to the importance of vibration effects on the functional accuracy of mechanical systems,this research aims to develop a precise model of a nonlinearly vibrating single-link mobile flexible *** manipulator consists of an elastic arm,a rotary motor,and a rigid carrier,and undergoes general in-plane rigid body motion along with elastic transverse *** accurately model the elastic behavior,Timoshenko’s beam theory is used to describe the flexible arm,which accounts for rotary inertia and shear deformation *** applying Newton’s second law,the nonlinear governing equations of motion for the manipulator are derived as a coupled system of ordinary differential equations(ODEs)and partial differential equations(PDEs).Then,the assumed mode method(Amm)is used to solve this nonlinear system of governing equations with appropriate shape *** assumed modes can be obtained after solving the characteristic equation of a Timoshenko beam with clamped boundary conditions at one end and an attached mass/inertia at the *** addition,the effect of the transverse vibration of the inextensible arm on its axial behavior is *** the axial rigidity,the effect makes the rigid body dynamics invalid for the axial behavior of the ***,numerical simulations are conducted to evaluate the performance of the developed model,and the results are compared with those obtained by the finite element *** comparison confirms the validity of the proposed dynamic model for the *** to the mentioned features,this model can be reliable for investigating the system’s vibrational behavior and implementing vibration control algorithms.

关键词： planar moving Timoshenko beam non-rigid non-elastic axial effect as-sumed mode method(Amm) nonlinear motion analysis

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