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Targeting LIF/LIFR signaling in cancer

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Genes & Diseases 2022年第4期9卷 973-980页

作者： Suryavathi Viswanadhapalli kalarickal V.Dileep kam Y.j.Zhang Hareesh B.nair Ratna k.Vadlamudi Department of Obstetrics and Gynecology University of Texas Health San AntonioSan AntonioTX 78229USA Laboratory for Structural Bioinformatics Center for Biosystems Dynamics ResearchRIKENYokohamaKanagawa 230-0045Japan Evestra Inc.San AntonioTX 78245USA Mays Cancer Center University of Texas Health San AntonioSan AntonioTX 78229USA

Leukemia inhibitory factor (LIF), and its receptor (LIFR), are commonly over-expressed in many solid cancers and recent studies have implicated LIF/LIFR axis as a promising clinical target for cancer therapy. LIF/LIFR activate oncogenic signaling pathways including jAk/STAT3 as immediate effectors and MApk, AkT, mTOR further downstream. LIF/LIFR signaling plays a key role in tumor growth, progression, metastasis, stemness and therapy resistance. Many solid cancers show overexpression of LIF and autocrine stimulation of the LIF/LIFR axis;these are associated with a poorer relapse-free survival. LIF/LIFR signaling also plays a role in modulating multiple immune cell types present in tumor micro environment (TME). Recently, two targeted agents that target LIF (humanized anti-LIF antibody, MSC-1) and LIFR inhibitor (EC359) were under development. Both agents showed effectivity in preclinical models and clinical trials using MSC-1 antibody are in progress. This article reviews the significance of LIF/LIFR pathways and inhibitors that disrupt this process for the treatment of cancer.

关键词： LIF LIFR LIFR inhibitor STAT3 Targeted therapy

Mechanistically Novel Frontal-Inspired In Situ photopolymerization:An Efficient Electrode|Electrolyte Interface Engineering Method for High Energy Lithium Metal polymer Batteries

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Energy & Environmental Materials 2023年第6期6卷 273-282页

作者： Ishamol Shaji Diddo Diddens Martin Winter jijeesh Ravi nair Helmholtz-Institute Münster(HI MS) IEK-12Forschungszentrum Jülich GmbHCorrensstr.4648149Münster Germany MEET Battery Research Center Institute of Physical ChemistryUniversity of MünsterCorrensstr.46Münster 48149Germany

The solvent-free in situ polymerization technique has the potential to tailor-make conformal interfaces that are essential for developing durable and safe lithium metal polymer batteries(LMpBs).Hence,much attention has been given to the eco-friendly and rapid ultraviolet(UV)-induced in situ photopolymerization process to prepare solid-state polymer *** this respect,an innovative method is proposed here to overcome the challenges of UV-induced photopolymerization(UV-curing)in the zones where UV-light cannot penetrate,especially in LMpBs where thick electrodes are *** proposed frontal-inspired photopolymerization(FIpp)process is a diverged frontal-based technique that uses two classes(dual)of initiators to improve the slow reaction kinetics of allyl-based monomers/oligomers by at least 50%compared with the conventional UV-curing *** possible reaction mechanism occurring in FIpp is demonstrated using density functional theory calculations and spectroscopic ***,the initiation mechanism identified for the FIpp relies on a photochemical pathway rather than an exothermic propagating front forms during the UV-irradiation step as the case with the classical frontal photopolymerization ***,the FIpp-based in situ cell fabrication using dual initiators is advantageous over both the sandwich cell assembly and conventional in situ photopolymerization in overcoming the limitations of mass transport and active material utilization in high energy and high power LMpBs that use thick ***,the LMpB cells fabricated using the in situ-FIpp process with high mass loading LiFepO_(4)electrodes(5.2 mg cm^(-2))demonstrate higher rate capability,and a 50%increase in specific capacity against a sandwich cell encouraging the use of this innovative process in large-scale solid-state battery production.

关键词： cathodelelectrolyte interface frontal-inspired photopolymerization in situ polymerization lithium metal polymer battery solid polymer electrolyte

Models and form factors for stand volume estimation in natural forest ecosystems: a case study of katarniaghat Wildlife Sanctuary (kGWS), Bahraich District, India

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journal of Forestry Research 2013年第2期24卷 217-226页

作者： V. A. j Adekunle k. N. nair A. k. Srivastava N. k. Singh Federal University of Technology Dept of Forestry & Wood Technology National Botanical Research Institute (Council for Scientific & Industrial Research) plant Diversity Systematics & Herbarium Division Rana Pratap Marg Department of Forests Sidhauli Forest Division

In view of the difficulties in stand volume estimation in natural forests, we derived real form factors and models for volume estimation in these types of forest ecosystems, using katarniaghat Wildlife Sanctuary as a case study. Tree growth data were obtained for all trees （dbh 〉10 cm） in 4 plots （25 × 25 m） randomly located in each of three strata selected in the forest. The form factor calculated for the stand was 0.42 and a range of 0.42 0.57 was estimated for selected species （density 〉10）. The parameters of model variables were consistent with general growth trends of trees and each was statistically significant. There was no significant difference （p〉0.05） between the observed and predicted volumes for all models and there was very high correlation between observed and predicted volumes. The output of the performance statistics and the logical signs of the regression coefficients of the models demonstrated that they are useful for volume estimation with minimal error. plotting the biases with respect to considerable regressor variables showed no meaningful and evident trend of bias values along with the independent variables. This showed that the models did not violate regression assumptions and there were no heteroscedacity or multiculnarity problems. We recommend use of the form factors and models in this ecosystem and in similar ones for stand and tree volume estimation.

关键词： natural forest tree volume Estimation biodiversity tree height forest inventory

Vitamin E ameliorates aflatoxin-induced biochemical changes in the testis of mice

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Asian journal of Andrology 2001年第4期3卷 305-309页

作者： R.j.Verma Anita nair Department of Zoology University School of Sciences Gujarat University Ahmedabad-380 009 IndiaDepartment of Zoology University School of Sciences Gujarat University Ahmedabad-380 009 India

Aim: To assess the effect of aflatoxin on biochemical changes in the testis of mice and the possibility of ameliorationby vitamin E treatment. Methods: Adult male albino mice were orally administered with 25 or 50μg of aflatoxin/animal/day (750 or 1500 μg/kg body weight) for 45 days. The testis was isolated and processed for biochemical anal-ysis. Results; There was a significant, dose-dependent reduction in DNA, RNA, protein, sialic acid contents andthe activities of succinic dehydrogenase, adenosine triphosphatase and alkaline phosphatase in the testis of aflatoxin-treated mice as compared to the vehicle control. However, the acid phosphatase activity was significantly increased inthe aflatoxin-treated mice. Vitamin E (2 mg/animal/day) treatment significantly ameliorated the aflatoxin-inducedchanges, except the acid and alkaline phosphatase activities in the high dose group. Conclusion; Vitamin E treat-ment ameliorates the aflatoxin-induced changes in the testis of mice. (Asian j Androl 2001 Dec; 3: 305 - 309)

关键词： aflatoxin vitamin E testis biochemical changes

Ameliorative effect of vitamin E on aflatoxin-induced lipid peroxidation in the testis of mice

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Asian journal of Andrology 2001年第3期3卷 217-221页

作者： R.j.Verma Anita nair Department of Zoology University School of Sciences Guarat University Ahmedabad 380009 IndiaDepartment of Zoology University School of Sciences Guarat University Ahmedabad 380009 India

Aim: To evaluate the ameliorative effect of vitamin E on aflatoxin-induced lipid peroxidation in the testis. Meth-ods: Adult male albino mice were orally administered 25 or 50 μg of aflatoxin in 0.2 mL olive oil per d for 45 *** testis was isolated, blotted free of blood and processed for biochemical analysis. Results: There was a dose-de-pendent significantly higher lipid peroxidation in the testis of aflatoxin treated mice than in the controls. The levels ofnon-enzymatic antioxidants such as glutathione, total and reduced ascorbic acid, as well as the activities of enzymaticantioxidants, such as superoxide dismutase, glutathione peroxidase and catalase were significantly lower in the testis ofaflatoxin treated mice. Vitamin E (2 mg/d per animal; orally) pretreatment significantly ameliorates the aflatoxin-in-duced lipid peroxidation which could be due to higher enzymatic and non-enzymatic antioxidants in the testis of mice ascompared with those given aflatoxin alone. Conclusion: Vitamin E pretreatment significantly ameliorates aflatoxin-induced lipid peroxidation in the testis of mice. (Asian j Androl 2001 Sep; 3: 217 - 221)

关键词： aflatoxins vitamin E testis lipid peroxidation

Use of direct-acting antiviral agents in hepatitis C virusinfected liver transplant candidates

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World journal of Gastroenterology 2018年第3期24卷 315-322页

作者： Chiranjeevi Gadiparthi George Cholankeril Brandon j perumpail Eric R Yoo Sanjaya k Satapathy Satheesh nair Aijaz Ahmed Division of Gastroenterology and Hepatology University of Tennessee Health Sciences CenterMemphisTN 38104United States Division of Gastroenterology and Hepatology Stanford University School of MedicineStanfordCA 94304United States Drexel University College of Medicine PhiladelphiaPA 19129United States Department of Medicine Santa Clara Valley Medical CenterSan JoseCA 95128United States

Since the advent of direct acting antiviral(DAA) agents, chronic hepatitis C virus(HCV) treatment has evolved at a rapid pace. In contrast to prior regimen involving ribavirin and pegylated interferon, these newer agents are highly effective, well-tolerated, have shorter course of therapy and safer essentially in all HCV patients including those with advanced liver disease and following liver transplantation. Clinicians caring for HCV-infected patients on the liver transplant(LT) waitlist are often faced with a dilemma whether to treat HCV infection before or after liver transplantation. Sustained virological response(SVR) rates following HCV treatment may improve hepatic function sufficiently enough to negate the need for LT in certain patients. On the other hand, the decrease in MELD without improvement in quality of life in certain patients may lead to delay or dropout from potentially curative LT surgery list. In this context, our review focuses on the approach to and optimal timing of DAA-based treatment of HCV infection in LT candidates in the peri-transplant period.

关键词： Hepatitis C virus Direct-acting antiviral therapy Liver transplantation purgatory Model for End-stage liver disease Sustained virological response

Emerging role of caldesmon in cancer:A potential biomarker for colorectal cancer and other cancers

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World journal of Gastrointestinal Oncology 2022年第9期14卷 1637-1653页

作者： Alya R Alnuaimi Vidhya A nair Lara j Bou Malhab Eman Abu-Gharbieh Anu Vinod Ranade Gianfranco pintus Mohamad Hamad Hauke Busch jutta kirfel Rifat Hamoudi Wael M Abdel-Rahman Sharjah Institute for Medical Research University of SharjahSharjah 27272United Arab Emirates College of Medicine University of SharjahSharjah 27272United Arab Emirates Department of Clinical Sciences University of SharjahSharjah 27272United Arab Emirates Department of Basic Medical Sciences University of SharjahSharjah 27272United Arab Emirates Department of Medical Laboratory Sciences University of SharjahSharjah 27272United Arab Emirates Department of Biomedical Sciences University of SassariSassari 07100Italy University Cancer Center Schleswig-Holstein and Luebeck Institute for Experimental Dermatology University of LuebeckLuebeck 23560Germany Institute of pathology University Hospital Schleswig-HolsteinLuebeck 23560Germany Division of Surgery and Interventional Science University College LondonLondon WC1E 6BTUnited Kingdom

Colorectal cancer(CRC) is a devastating disease, mainly because of metastasis. As a result, there is a need to better understand the molecular basis of invasion and metastasis and to identify new biomarkers and therapeutic targets to aid in managing these tumors. The actin cytoskeleton and actin-binding proteins are known to play an important role in the process of cancer metastasis because they control and execute essential steps in cell motility and contractility as well as cell division. Caldesmon(CaD) is an actin-binding protein encoded by the CALD1 gene as multiple transcripts that mainly encode two protein isoforms: High-molecular-weight CaD, expressed in smooth muscle, and low-molecular weight CaD(l-CaD), expressed in nonsmooth muscle cells. According to our comprehensive review of the literature, CaD, particularly l-CaD, plays a key role in the development, metastasis, and resistance to chemoradiotherapy in colorectal, breast, and urinary bladder cancers and gliomas, among other malignancies. CaD is involved in many aspects of the carcinogenic hallmarks, including epithelial mesenchymal transition via transforming growth factor-beta signaling, angiogenesis, resistance to hormonal therapy, and immune evasion. Recent data show that CaD is expressed in tumor cells as well as in stromal cells, such as cancerassociated fibroblasts, where it modulates the tumor microenvironment to favor the tumor. Interestingly, CaD undergoes selective tumor-specific splicing, and the resulting isoforms are generally not expressed in normal tissues, making these transcripts ideal targets for drug design. In this review, we will analyze these features of CaD with a focus on CRC and show how the currently available data qualify CaD as a potential candidate for targeted therapy in addition to its role in the diagnosis and prognosis of cancer.

关键词： Bladder cancer CALD1 Caldesmon Chemoresistance Colorectal cancer Gastric cancer Glioma Epithelial to mesenchymal transition Invasion Metastasis

Transcanal endoscopic excision of tympanic paraganglioma: A three-case series

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Laparoscopic, Endoscopic and Robotic Surgery 2020年第4期3卷 126-130页

作者： Satish nair k.V.R.Brijith j.G.Aishwarya V.pavithra Department of ENT-HNS Apollo HospitalsBannerghatta RoadBangaloreKarnataka560076India

paragangliomas are rare neuroendocrine tumors that arise in sympathetic and parasympathetic paraganglion system,derived from neural crest *** paraganglioma is a type of head and neck paraganglioma involving the middle ear *** transcanal approach is currently in vogue for the excision of tympanic paragangliomas that is limited to middle ear *** present a series of 3 cases who underwent endoscopic excision of tympanic paraganglioma.

关键词： Tympanic paraganglioma Glomus tympanicum Endoscopic excision

An experimental study of elastic properties of dragonfly-like flapping wings for use in biomimetic micro air vehicles(BMAVs)

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Chinese journal of Aeronautics 2017年第2期30卷 726-737页

作者： praveena nair Sivasankaran Thomas Arthur Ward Erfan Salami Rubentheren Viyapuri Christopher j.Fearday Mohd Rafie johan Department of Mechanical Engineering University of Malaya KuaIa Lumpur 50603 Malaysia School of Engineering and physical Sciences Heriot-Watt University Malaysia Putrajaya 62200 Malaysia Department of Electrical Engineering University of Malaya Kuala Lumpur 50603 Malaysia

This article studies the elastic properties of several biomimetic micro air vehicle（BMAV）wings that are based on a dragonfly *** are a new class of unmanned micro-sized air vehicles that mimic the flapping wing motion of flying biological organisms（e.g.,insects,birds,and bats）.Three structurally identical wings were fabricated using different materials：acrylonitrile butadiene styrene（ABS）,polylactic acid（pLA）,and *** wing frame structures were fabricated from these materials and then a nanocomposite film was adhered to them which mimics the membrane of an actual *** wings were then attached to an electromagnetic actuator and passively flapped at frequencies of 10-250 Hz.A three-dimensional high frame rate imaging system was used to capture the flapping motions of these wings at a resolution of 320 pixels x 240 pixels and 35000 frames per *** maximum bending angle,maximum wing tip deflection,maximum wing tip twist angle,and wing tip twist speed of each wing were measured and compared to each other and the actual dragonfly *** results show that the ABS wing has considerable flexibility in the chordwise direction,whereas the pLA and acrylic wings show better conformity to an actual dragonfly wing in the spanwise *** studies have shown that the aerodynamic performance of a BMAV flapping wing is enhanced if its chordwise flexibility is increased and its spanwise flexibility is ***,the ABS wing（fabricated using a 3D printer） shows the most promising results for future applications.

关键词： ABS Acrylic Biomimetic micro air vehicle Flapping mechanism pLA Wing structure