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S1P/S1PR1 signaling differentially regulates the allogeneic response of CD4 and CD8 T cells by modulating mitochondrial fission

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Cellular & Molecular Immunology 2022年第11期19卷 1235-1250页

作者： Linlu Tian Yongxia Wu Hee-Jin Choi Xiaohui Sui Xinlei Li M.Hanief Sofi Mohamed Faisal Kassir Xiao Chen shikhar mehrotra Besim Ogretmen Xue-zhong Yu Department of Microbiology&Immunology Medical University of South CarolinaCharlestonSCUSA Department of Microbiology&Immunology Medical College of WisconsinMilwaukeeWIUSA Department of Medicine Medical College of WisconsinMilwaukeeWIUSA Department of Biochemistry&Molecular Biology Medical University of South CarolinaCharlestonSCUSA Department of Surgery Medical University of South CarolinaCharlestonSCUSA Hollings Cancer Center Medical University of South CarolinaCharlestonSCUSA The Cancer Center Medical College of WisconsinMilwaukeeWIUSA

Graft-versus-host disease (GVHD) significantly contributes to patient morbidity and mortality after allogeneic hematopoietic cell transplantation (allo-HSCT). Sphingosine-1-phosphate (S1P) signaling is involved in the biogenetic processes of different immune cells. In the current study, we demonstrated that recipient sphingosine kinase 1 (Sphk1), but not Sphk2, was required for optimal S1PR1-dependent donor T-cell allogeneic responses by secreting S1P. Using genetic and pharmacologic approaches, we demonstrated that inhibition of Sphk1 or S1PR1 substantially attenuated acute GVHD (aGVHD) while retaining the graft-versus-leukemia (GVL) effect. At the cellular level, the Sphk1/S1P/S1PR1 pathway differentially modulated the alloreactivity of CD4+ and CD8+ T cells;it facilitated T-cell differentiation into Th1/Th17 cells but not Tregs and promoted CD4+ T-cell infiltration into GVHD target organs but was dispensable for the CTL activity of allogeneic CD8+ T cells. At the molecular level, the Sphk1/S1P/S1PR1 pathway augmented mitochondrial fission and increased mitochondrial mass in allogeneic CD4+ but not CD8+ T cells by activating the AMPK/AKT/mTOR/Drp1 pathway, providing a mechanistic basis for GVL maintenance when S1P signaling was inhibited. For translational purposes, we detected the regulatory efficacy of pharmacologic inhibitors of Sphk1 and S1PR1 in GVHD induced by human T cells in a xenograft model. Our study provides novel mechanistic insight into how the Sphk1/S1P/S1PR1 pathway modulates T-cell alloreactivity and validates Sphk1 or S1PR1 as a therapeutic target for the prevention of GVHD and leukemia relapse. This novel strategy may be readily translated into the clinic to benefit patients with hematologic malignancies and disorders.

关键词： Sphk1 S1P S1PR GVHD GVL mitochondrial fission

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Data-driven failure diagnosis in transmission protection system with multiple events and data anomalies

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Journal of Modern Power Systems and Clean Energy 2019年第4期7卷 767-778页

作者： Amir GHOLAMI Anurag K.SRIVASTAVA shikhar PANDEY Washington State University PullmanUSA

To guarantee a reliable power supply,the expected operation of all the components in the power system is *** protection system is primarily responsible of isolating the faulty section from the healthy part for the *** in protection devices can result in multiple conflicting alarms at the power grid operation center and complex event analysis to manually find the root cause of the observed system *** not handled in time,it may lead to the propagation of the faults/failures to the adjacent transmission lines and *** availability of the synchronized measurements from phasor measurement units(PMUs),real-time system monitoring and automated failure diagnosis are *** multiple adverse events and possible data anomalies,the complexity of the problem will be *** this paper,a PMUbased algorithm is presented and discussed to detect the root cause of the failure in transmission protection system based on the observed state,*** line tripping andbreaker *** failure diagnosis algorithm is further enhanced to come up with the fully functional version of the failure diagnosis tool,which is tailored for the cases in which the PMU anomalies are *** the developed algorithm,the validity of the PMU data is ***,such causes as communication errors or cyber-attacks might lead to the PMU data *** issue is welladdressed in this paper and some major types of anomaly detection methods suitable for PMU data are *** show that the ensemble approach has some distinct advantages in data anomaly detection compared to the previously used standalone ***,the enhanced failure diagnosis method is developed to clean the inaccurate data in case of the anomaly in measured voltage ***,both original and enhanced versions of the tool are tested on 96-bus test system using the real-time OPAL-RT *** results show the accuracy of the enhanced tool and

关键词： Failure diagnosis Transmission protection system Protection mis-operation Phasor measurement unit(PMU) Data anomaly and cleaning Ensemble method

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Performance evaluation of deep neural networks for forecasting time-series with multiple structural breaks and high volatility

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CAAI Transactions on Intelligence Technology 2021年第3期6卷 265-280页

作者： Rohit Kaushik shikhar Jain Siddhant Jain Tirtharaj Dash Department of Computer Science and Information Systems Birla Institute of Technology and Science PilaniK.K.Birla Goa CampusZuarinagarGoaIndia

The problem of automatic and accurate forecasting of time-series data has always been an interesting challenge for the machine learning and forecasting community.A majority of the real-world time-series problems have non-stationary characteristics that make the understanding of trend and seasonality *** applicability of the popular deep neural networks(DNNs)as function approximators for non-stationary TSF is *** following DNN models are evaluated:Multi-layer Perceptron(MLP),Convolutional Neural Network(CNN),and RNN with Long Short-Term Memory(LSTM-RNN)and RNN with Gated-Recurrent Unit(GRU-RNN).These DNN methods have been evaluated over 10 popular Indian financial stocks ***,the performance evaluation of these DNNs has been carried out in multiple independent runs for two settings of forecasting:(1)single-step forecasting,and(2)multi-step *** DNN methods show convincing performance for single-step forecasting(one-day ahead forecast).For the multi-step forecasting(multiple days ahead forecast),the methods for different forecast periods are *** performance of these methods demonstrates that long forecast periods have an adverse effect on performance.

关键词： networks neural forecasting

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Novel vertically aligned nanocomposite of Bi_(2)WO_(6)-Co_(3)O_(4) with room-temperature multiferroic and anisotropic optical response

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Nano Research 2021年第12期14卷 4789-4794页

作者： Leigang Li shikhar Misra Xingyao Gao Juncheng Liu Han Wang Jijie Huang Bruce Zhang Ping Lu Haiyan Wang School of Materials Engineering Purdue UniversityWest LafayetteIndiana47907USA School of Electrical and Computer Engineering Purdue UniversityWest LafayetteIndiana47907USA Sandia National Laboratory AlbuquerqueNew Mexico87185USA

A new vertically aligned nanocomposite(VAN)structure based on two-dimensional(2D)layered oxides has been designed and self-assembled on both LaAlO_(3)(001)and SrTiO3(001)*** new VAN structure consists of epitaxially grown Co_(3)O_(4) nanopillars embedded in the Bi_(2)WO_(6) matrix with a unique 2D layered structure,as evidenced by the microstructural *** property measurements show that the new Bi_(2)WO_(6)-Co_(3)O_(4) VAN structure exhibits strong ferromagnetic and piezoelectric response at room temperature as well as anisotropic permittivity *** work demonstrates a new approach in processing multifunctional VANs structure based on the layered oxide systems towards future nonlinear optics,ferromagnets,and multiferroics.

关键词： vertically aligned nanocomposite(VAN) multiferroics Aurivillius oxides layered oxides Co_(3)O_(4) Bi_(2)WO_(6)

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硒对甲状腺疾病的影响

硒对甲状腺疾病的影响

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作者： Prajaya shikhar Shrestha 新乡医学院

学位级别：硕士

背景硒是人体必不可少的微量元素,是瑞典化学家Berzelius于1817年发现的。当时硒被认为是有毒矿物,直到1957年大约过了140多年,人类才认识到它的重要性。甲状腺在人类有机体的新陈代谢中有巨大的影响,它被认为可能调节人体内的各种不平... 详细信息

背景硒是人体必不可少的微量元素,是瑞典化学家Berzelius于1817年发现的。当时硒被认为是有毒矿物,直到1957年大约过了140多年,人类才认识到它的重要性。甲状腺在人类有机体的新陈代谢中有巨大的影响,它被认为可能调节人体内的各种不平衡。随着各方面的最新研究发现和文献的发表,人们认为硒缺乏是导致甲状腺疾病的因素之一。硒参与碘的代谢,目前许多研究认为硒可通过抗氧化及调节免疫等机制保护甲状腺组织,降低炎症活动性,故与自身免疫性甲状腺疾病的治疗密切相关。我们假设为甲状腺功能紊乱的患者短期持续提供硒有治疗作用。目的对甲状腺疾病患者补充硒元素,观察硒对自身免疫性甲状腺炎中甲状腺功能减退和甲状腺功能亢进组自身抗体滴度的影响并进行探讨。方法观察研究临床诊断为自身免疫性甲状腺炎患者2组：A组(28例)为诊断为甲状腺功能减退者;B组(18例)为被诊断为甲状腺功能亢进者。A组患者在被随机分为两个小组,其中HA组(14例)中的患者应用左旋甲状腺素和硒;CA组(14例)为HA组的对照组,仅应用甲状腺素。B组(18例)同样也被随机分为两组,其中的HB组(7例)患者应用硒和甲巯咪唑;CB组(11例)患者仅应用甲巯咪唑。分别测定患者基础的FT3、FT4、TSH、TGAb和TPOAb水平,并观察3月补硒治疗后的上述指标的变化。结果在A组的HA亚组中,补硒3月后TPOAb从394.33(170.636,726.27)降至134.32(22.87,529.00),P值0.05;FT4从14.23(10.44,15.49)改变为11.99(10.64,13.73)P值>0.05,TSH从3.81(1.86,9.38)改变为2.15(1.42,9.77)P值>0.05.差异无统计学意义。CA亚组,治疗前后FT3、FT4、TSH、TGAb和TPOAb水平,差异无统计学意义。在B组的HB亚组中,补硒3月后TPOAb从332.17(117.19,447.85)降至234.86(57.69,303.29),P值0.05;FT4从13.05(12.27,14.97)改变为11.29(9.74,13.81)P值>0.05;TSH从1.85(0.87,2.67)改变为1.85(0.68,3.21)P值>0.05,差异无统计学意义。尽管差异无统计学意义,但数值水平明显降低,我们考虑是因为小样本所至。CA亚组,治疗前后FT3、FT4、TS、TGAb和TPOAb水平,差异无统计学意义。结论补硒治疗可显著降低自身免疫性甲状腺炎患者的甲状腺抗体TGAb和TPOAb。

关键词：硒甲状腺功能减退甲状腺功能亢进甲状腺功能检测甲状腺过氧化物酶抗体甲状腺球蛋白抗体

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Pharmacognostic Evaluation and Antioxidant Activity of <i>Urtica dioica</i>L.

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Chinese Medicine 2012年第3期3卷 128-135页

作者： Vertika Khare Pradeep Kushwaha shikhar Verma Abhishek Gupta Sharad Srivastava AKS Rawat Pharmacognosy & Ethnopharmacology Division CSIR-National Botanical Research Institute Lucknow India

Background: Urtica dioica L. is a common Himalayan species which produces allergenic substances causing oedema and inflammation in humans. It has become a source of folk medicine for the treatment of many diseases. The leaves and roots both are used internally as a blood purifier and diuretic and an infusion of the plant is used for nasal and menstrual haemorrhage, diabetes, rheumatism, eczema, anaemia, hair loss, as an expectorant and antidiarrhoeal. Present study includes pharmacognostic evaluation, antioxidant activity and HPTLC analysis of Urtica dioica L. Methods: Pharmacognostic evaluation of aerial part of U. dioica has been performed as per Indian pharmacopoeia. In-vitro antioxidant evaluation of U. dioica has been performed using DPPH free radical scavenging activity. Ferulic acid, a potential phenolic antioxidant present in this species, has been studied through HPTLC. Results: U. dioica hydro-alcoholic extract shows positive results for antioxidant activity with IC50 value of 88.33 ± 2.88 μg/ml. Standard ascorbic acid showed IC50 value of 2.8 ± 0.62 μg/ml. Ferulic acid was identified at Rf 0.61 ± 0.01 and quantified to 0.73% in this species through CAMAG HPTLC analysis. Conclusion: The pharmacognostical parameters reported can be considered as quality standards of U. dioica in herbal industry. Hydro-alcoholic extract of U. dioica showed positive in vitro antioxidant activity. Presence of phenolic compound suggests that antioxidant activity may be due to ferulic acid content.

关键词： Antioxidant Activity DPPH Ferulic Acid HPTLC U. Dioica

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Evaluation of quantitative variation of secondary metabolites in Bergenia ciliata(Haw.)using high performance thin layer chromatography

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The Journal of Biomedical Research 2014年第4期28卷 328-331页

作者： Nishi Srivastava Sharad Srivastava shikhar Verma Ajay Kumar Singh Rawat Abdul Rahman Khan Pharmacognosy and Ethnopharmacology Division CSIR-National Botanical Research Institute Chemistry Division Integral University Pharmacognosy and Ethnopharmacology Division CSIR-National Botanical Research Institute

Dear Editor： Therapeutically active metabolite contents in a med- icinal plant vary in nature, which may impact on its therapeutic efficacy. Bergenia （Saxifragaceae） is an evergreen perennial herb widely distributed in Central and East Asia with about 30 species reported worldwide. It grows at a range of altitudes from the Khasia hills at 400 feet to the temperate Himalayas from Kashmir to Bhutan at 7,000-10,000 feet. Its distribution over a wide range of altitudinal zones makes it a good candidate for studying variations in its metabolic profiles under different climatic conditions. Bergenin （C-glycoside of 4-O-methyl gallic acid） has been identified as a potent active secondary metabolite in Bergenia and other therapeutically active constituents including, among others, gallic acid （3,4,5 trihydroxybenzoic acid）, （＋） catechin, and gallicin （Fig. 1）.

关键词： HPTLC using high performance thin layer chromatography Evaluation of quantitative variation of secondary metabolites in Bergenia ciliata Haw high

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Hematological, antioxidant and protective performance of Usnea longissima on chemical induced hepatotoxicity in experimental animals

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Journal of Coastal Life Medicine 2017年第5期5卷 224-232页

作者： Pritt Verma Shravan Kumar Paswan Abhisek Raj Virendra Nath Ramesh Kumar Gupta shikhar Verma Sajal Srivastava ChandanaVenketshwara Rao Pharmacognosy and Ethnopharmacology Division CSIR-National Botanical Research InstituteLucknowIndia Amity Institute of Pharmacy Amity UniversityLucknowIndia Department of Pharmaceutical Sciences Central University of RajasthanRajasthanIndia Sherwood College of Pharmacy Barabanki-225001India

Objective: To investigated the hematological, antioxidant and protective performance of Usnea longissima (U. longissima) on CCl4 induced hepatotoxicity in experimental animals. Methods: Hepatotoxicity was induced by CCl4 (1 mL/kg body weigt 1:1 CCl4 i.p.), ethanolic U. longissima extracts at a doses (200 and 400 mg/kg body weigt) were administered to and compared with Silymarin (25 mg/kg body weigt) and hematological, antioxidant and enzymatic, non-enzymatic parameters were assessed through the liver functions test. All the observation was also supplemented with histopathological examination of liver sections. Results: Phytochemical investigation showed that ethanolic extract contains poly phenolic compounds tannins, flavonoids, alkaloids and saponins and acute toxicity study shows that ethanolic extract was safe up to 2000 mg/kg body weight. The toxicant induced a rise in the plasma enzyme levels of ALT, AST, ALP and total bilirubin level. This increased level was significantly decreased by the extract at 400 mg/kg body weight than 200 mg/kg body weight. The animals were prevented (partly or fully) which was showed in the histopathological changes using ethonolic U. longissima extract. Conclusions: The outcome of this study reveals that, there is a powerful antioxidant and hepatoprotective activity of U. longissima. It is believed that the present constituents are responsible for courting the hepatic disease and alternative components have the power to act as free radical scavenging properties.

关键词： Usnea longissima Carbon tetra chloride (CCl4) Hematological Antioxidant Histopathological

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Nepal,China and India-A Potential trilateral economic Union

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科技致富向导 2011年第11期 52-52页

作者： shikhar Acharya 上海大学

A dramatic increase in trade between China and India in recent years has made significant changes in Asia. Sino-Indian trade was only a few million dollars till the mid 1990’s. It had reached $7.5 billion in

关键词： Asia than link

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