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Journal of Integrative Medicine 2023年第1期21卷 62-76页

作者： sumera Malik Mubashir J.Mintoo Chilakala Nagarjuna Reddy Rajesh Kumar Pankul Kotwal Sandip BBharate Utpal Nandi Dilip M.Mondhe Sanket K.Shukla Pharmacology Division Council of Scientific and Industrial Research(CSIR)-Indian Institute of Integrative MedicineJammu 180001Jammu&KashmirIndia Academy of Scientific&Innovative Research(AcSIR) Ghaziabad 201002Uttar PradeshIndia Medicinal Chemistry Division CSIR-Indian Institute of Integrative MedicineJammu 180001Jammu&KashmirIndia Pharmacokinetics-Pharmacodynamics(PK-PD) Toxicology DivisionCSIR-Indian Institute of Integrative MedicineJammu 180001Jammu&KashmirIndia

Objective: The current study evaluated various new colchicine analogs for their anticancer activity and to study the primary mechanism of apoptosis and in vivo antitumor activity of the analogs with selective anticancer properties and minimal toxicity to normal cells.Methods: Sulforhodamine B(SRB) assay was used to screen various colchicine analogs for their in vitro cytotoxicity. The effect of N-[(7S)-1,2,3-trimethoxy-9-oxo-10-(pyrrolidine-1-yl)5,6,7,9-tetrahydrobenzo[a] heptalene-7-yl] acetamide(ⅢM-067) on clonogenicity, apoptotic induction, and invasiveness of A549 cells was determined using a clonogenic assay, scratch assay, and staining with 4’,6-diamidino-2-phenylindole(DAPI) and annexin v/propidium iodide. Mitochondrial membrane potential(MMP) and reactive oxygen species(ROS) levels were observed using fluorescence microscopy. Western blot analysis was used to quantify expression of proteins involved in apoptosis, cell cycle, and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR) signaling. Pharmacokinetic and in vivo efficacy studies against Ehrlich ascites carcinoma(EAC) and Ehrlich solid tumor models were conducted using Swiss albino mice.Results: ⅢM-067 showed potent cytotoxicity and better selectivity than all other colchicine analogs screened in this study. The selective activity of ⅢM-067 toward A549 cells was higher among other cancer cell lines,with a selectivity index(SI) value of 2.28. ⅢM-067 demonstrated concentration-and time-dependent cytotoxicity against A549 cells with half-maximal inhibitory concentration values of 0.207, 0.150 and0.106 μmol/L at 24, 48 and 72 h, respectively. It also had reduced toxicity to normal cells(SI > 1) than the parent compound colchicine(SI = 1). ⅢM-067 reduced the clonogenic ability of A549 cells in a dose-dependent manner. ⅢM-067 enhanced ROS production from 24.6% at 0.05 μmol/L to 82.1% at 0.4 μmol/L and substantially decreased the MMP(100% in control to 5.6% at 0.4 μmol/L). The annexin v-FITC assay demonstrated78% ap

关键词： Colchicine 1IIM-067 Apoptosis Antineoplastic agents Carcinoma Ehrlich tumor A549 cells

Anterior glenohumeral instability:Current review with technical pearls and pitfalls of arthroscopic soft-tissue stabilization

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World Journal of Orthopedics 2021年第1期12卷 1-13页

作者： John M Apostolakos Joshua Wright-Chisem lawrence v Gulotta Samuel A Taylor Joshua S Dines Department of Sports Medicine and Shoulder Surgery Hospital for Special SurgeryNew YorkNY 10021United States

The glenohumeral joint(GHJ)allows for a wide range of motion,but is also particularly vulnerable to episodes of instability.Anterior GHJ instability is especially frequent among young,athletic populations during contact sporting events.Many first time dislocators can be managed non-operatively with a period of immobilization and rehabilitation,however certain patient populations are at higher risk for recurrent instability and may require surgical intervention for adequate stabilization.Determination of the optimal treatment strategy should be made on a case-by-case basis while weighing both patient specific factors and injury patterns(i.e.,bone loss).The purpose of this review is to describe the relevant anatomical stabilizers of the GHJ,risk factors for recurrent instability including bony lesions,indications for arthroscopic vs open surgical management,clinical history and physical examination techniques,imaging modalities,and pearls/pitfalls of arthroscopic soft-tissue stabilization for anterior glenohumeral instability.

关键词： Arthroscopic Soft-tissue Anterior instability Glenohumeral Functional anatomy Recurrent instability

Calcium at the Cell Wall-Cytoplast Interface

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Journal of Integrative Plant Biology 2010年第2期52卷 147-160页

作者： Peter K.Hepler lawrence J.Winship Department of Biology University of MassachusettsAmherstMA 01003USA School of Natural Science Hampshire CollegeAmherstMA 01002USA

Attention is given to the role of Ca^2＋ at the interface between the cell wall and the cytoplast, especially as seen in pollen tubes. While the cytoplasm directs the synthesis and deposition of the wall, it is less well appreciated that the wall exerts considerable self control and influences activities of the cytoplasm. Ca^2＋ participates as a crucial factor in this two way communication. In the cytoplasm, a [Ca^2＋] above 0.1 μM, regulates myriad processes, including secretion of cell wall components. In the cell wall Ca^2＋ , at 10μM to 10 mM, binds negative charges on pectins and imparts structural rigidity to the wall. The plasma membrane occupies a pivotal position between these two compartments, where selective channels regulate influx of Ca^2＋ , and specific carriers pump the ion back into the wall. In addition we draw attention to different factors, which either respond to the wall or are present in the wall, and usually generate elevated[Ca^2＋ ] in the cytoplasm. These factors include：（i） stretch activated channels; （ii） calmodulin; （iii） annexins; （iv） wall associated kinases; （v） oligogalacturonides; and （vi） extracellular adenosine 5＇-triphosphate. Together they provide evidence for a rich and multifaceted system of communication between the cytoplast and cell wall, with Ca^2＋ as a carrier of information.

关键词： Calcium at the Cell Wall-Cytoplast Interface CNGC

Antimicrobial and plant growth-promoting activities of bacterial endophytes isolated from Calotropis procera(Ait.)W.T.Aiton

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BIOCELL 2021年第2期45卷 363-369页

作者： MUHAMMAD HAMAYUN NASIR KHAN MUHAMMAD NAUMAN KHAN MUHAMMAD QADIR ANWAR HUSSAIN AMJAD IQBAL sumera AFZAL KHAN KHUSHNOOD UR REHMAN IN-JUNG LEE Plant-Microbe Interactions Lab Department of BotanyAbdul Wali Khan University MardanKPPakistan Department of Botany Bacha Khan University CharsaddaCharsadda24420Pakistan Department of Food Science and Technology Abdul Wali Khan University MardanMardan23200Pakistan Centre of Biotechnology and Microbiology University of PeshawarPeshawar25000Pakistan Department of Botany Islamia College UniversityPeshawar25000Pakistan Department of Applied Biosciences Kyungpook National UniversityDaegu41566Korea

Bacterial endophytes are beneficial to their hosts as they can fix nitrogen in the soil and make it available to the host.Endophytic bacteria also secrete plant growth-promoting hormones to support their host plants under normal as well as stress conditions.The current study aimed to isolate endophytic bacteria from different parts of Calotropis procera,i.e.,roots,stem and leaves of Calotropis procera(Ait.)W.T.Aiton.Plants were collected from the Lundkhwar,district Mardan.A total of 12 bacterial strains,i.e.,six from roots,three from the stem and three from the leaves were isolated.The strains were screened for their growth-promoting activity in rice plants because rice shows a quick and easy response to the bioactive compounds present in the culture filtrate(CF)of the potent endophytic strains.The rice plants were cultivated in pots containing 30 mL of 0.8%w/v water-agar medium.The pots were placed in a growth chamber,operated at 28±0.3℃ for 14 h(day);and 25±0.3℃ for 10 h(night),at 70%relative-humidity.Among the isolated strains,R1,S1,S3,L1,R5 and R6 showed visible growth promotion in rice plants.The biochemical analysis revealed that the strains were able to produce indole acetic acid(IAA)and flavonoids in higher quantities.Moreover,the strains also produced bioactive compounds that inhibited the growth of Escherichia coli and Aspergillus flavus using the well diffusion method.From the results,it was concluded that these strains can secrete potent compounds that can promote the host plant growth and inhibit the growth of pathogenic microorganisms and,therefore,can be used as bio-fertilizer and bio-control agents.

关键词： Endophytic bacteria Growth promotion Antimicrobial activity Plant-microbe interaction

Activity origin and design principles for atomic vanadium anchoring on phosphorene monolayer for nitrogen reduction reaction

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Nano Research 2020年第11期13卷 2925-2932页

作者： Xiongyi Liang Xiangxuan Deng Chen Guo Chi-Man lawrence Wu Department of Materials Science and Engineering City University of Hong KongHong KongChina

Conversion of inert N2 molecules into NH3 via electrochemical methods is an environmentally friendly alternative to replace the traditional Haber-Bosch process.However,the development of highly efficient catalyst is still challenging.Herein,we report a density functional theory(DFT)based high-throughput screening to investigate the potential of 23 atomic transition metals(Sc,Ti,v,Cr,Mn,Fe,Co,Ni,Cu,Zn,Y,Zr,Nb,Mo,Tc,Ru,Rh,Pd,Ag,Cd,W,Pt and Au)supported on phosphorene monolayer as electrocatalyst for nitrogen reduction reaction(NRR).Our theoretical results demonstrate that v single atom anchoring on phosphorene monolayer exhibits good thermal stability,selectivity and excellent catalytic activity with a low overpotential of 0.18 v.Importantly,rational design principles and electronic descriptor between the intrinsic electronic properties and activation barrier have been developed.Our work offers a new promising noble metal-free catalyst for NRR and reveals profound insights into the activity origin to guide further design.

关键词： high-throughput screening density functional theory phosphorene electronic descriptor single atomic catalyst transition metal

Sodium-Coordinated Polymeric Phthalocyanines as Stable High-Capacity Organic Anodes for Sodium-Ion Batteries

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Energy & Environmental Materials 2023年第4期6卷 22-30页

作者： Jeongyeon Lee Yoonbin Kim Soyong Park Kang Ho Shin Gun Jang Min Jun Hwang Daekyu Kim Kyung-Ah Min Ho Seok Park Byungchan Han Dennis K.P.Ng lawrence Yoon Suk Lee Department of Applied Biology and Chemical Technology and Research Institute for Smart Energy The Hong Kong Polytechnic UniversityHung HomKowloon Hong Kong SAR China Department of Chemistry The Chinese University of Hong KongShatinNew Territories Hong Kong SAR China Convergence Research Center for Energy and Environmental Sciences Sungkyunkwan UniversitySuwon Korea Department of Chemical and Biomolecular Engineering Yonsei UniversitySeoul Korea School of Chemical Engineering Sungkyunkwan UniversitySuwon Korea

Sodium-ion batteries(SIBs)have attracted considerable interest as an alternative to lithium-ion batteries owing to their similar electrochemical performance and superior long-term cycle stability.Organic materials are regarded as promising anode materials for constructing SIBs with high capacity and good retention.However,utilization of organic materials is rather limited by their low energy density and poor stability at high current densities.To overcome these limitations,we utilized a novel polymeric disodium phthalocyanines(pNaPc)as SIB anodes to provide stable coordination sites for Na ions as well as to enhance the stability at high current density.By varying the linker type during a one-pot cyclization and polymerization process,two pNaPc anodes with O-(O-pNaPc)and S-linkers(S-pNaPc)were prepared,and their structural and electrochemical properties were investigated.The O-pNaPc binds Na ions with a lower binding energy compared with S-pNaPc,which leads to more facile Na-ion coordination/dissociation when engaged as SIB anode.The use of O-pNaPc significantly improves the redox kinetics and cycle stability and allows the fabrication of a full cell against Na_(3)v_(2)(PO_(4))_(2)F_(3)/C cathode,which demonstrates its practical application with high energy density(288 Wh kg^(-1))and high power density(149 W kg^(-1)).

关键词： coordination chemistry organic anode phthalocyanine polymerization sodium ion battery

vascularization in interconnected 3D printed Ti-6Al-4v foams with hydrogel matrix for biomedical bone replacement implants

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Science China Materials 2018年第4期61卷 565-578页

作者： victor L.Correa Kristine M.Garza lawrence E.Murr Department of Metallurgical Materials and Biomedical Engineering University of Texas at El Paso Department of Biological Sciences University of Texas at El Paso

vascularization on newly implanted metal orthopedic implants has remained a challenge in the field of tissue engineering. To address this challenge, in this research,an interconnected foam structure of Ti-6 Al-4 v was microfabricated by electron beam melting(EBM) technique. The foam in question has a density of 1.77 g cm-3 with 60% porosity and a tensile strength of 18 GPa. An extracellular matrix based hydrogel was added as an aqueous matrix to the foam.Hypoxia mimetic stress has been closely related to many wound healing biomedical applications as it increases survival and proliferation molecular signals. To that end, increased expression of hypoxia-inducible factor-1α(Hif-1α) and vascular endothelial growth factor(vEGF) in the aqueous hydrogel matrix was achieved by the addition of a hypoxia mimetic deferoxamine mesylate(DFM). In this study, the formation of an endothelial network was achieved in a hydrogel matrix in the presence of the before mentioned 3 D printed metal foam. Cellular viability, fluorescent microscopy and scanning electron microscopy imaging analysis demonstrate that pre-osteoblasts undergo proliferation and also attach efficiently to the foam when exposed to DFM. Human umbilical vascular endothelial cells(HUvECs) were grown in an extracellular matrix-like 3 D hydrogel and a hypoxia-like stress was achieved. This research demonstrates that pre-osteoblast cells undergo cell differentiation and increase the production of hydroxyapatite on exposure to the hypoxia mimetic molecule. This proposed approach encompasses an ideal prototype for a completely living implanted structure for future orthopedic implants.

关键词： Ti-6Al-4v electron beam melting angiogenesis deferoxamine mesylate hydrogel vascularization

Learning to Predict in Complex Biological Domains

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系统仿真学报 2002年第11期14卷 1464-1471页

作者： Steven Eschrich Nitesh v.Chawla lawrence O.Hall DepartmentofComputerScienceandEngineering DepartmentofComputerScienceandEngineering DepartmentofComputerScienceandEngineering ENB118UniversityofSouthFlorida4202E.FowlerAveTampaFL.33620ENB118UniversityofSouthFlorida4202E.FowlerAveTampaFL.33620

Protein secondary structure prediction and high-throughput drug screen data mining are two important applications in bioinformatics. The data is represented in sparse feature spaces and can be unrepresentative of future data. There is certainly some noise in the data and there may be significant noise. Supervised learners in this context will display their inherent bias toward certain solutions, generally solutions that fit the training set well. In this paper, we first describe an ensemble approach using subsampling that scales well with dataset size. A sufficient number of ensemble members using subsamples of the data can yield a more accurate classifier than a single classifier using the entire dataset. Experiments on several datasets demonstrate the effectiveness of the approach. We report results from the KDD Cup 2001 drug discovery dataset in which our approach yields a higher weighted accuracy than the winning entry. We then ex-tend our ensemble approach to create an over-generalized classifier for prediction by reducing the individual subsample size. The ensemble strategy using small subsamples has the effect of averaging over a wider range of hypotheses. We show that both protein secondary structure prediction and drug discovery prediction can be improved by the use of over-generalization, specifically through the use of ensembles of small subsamples.

关键词：生物信息学蛋白质再生结构 DNA 系统方法

Microstructure and mechanical properties of Ti-6Al-4v-5% hydroxyapatite composite fabricated using electron beam powder bed fusion

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Journal of Materials Science & Technology 2019年第2期35卷 309-321页

作者： César A.Terrazas lawrence E.Murr Diego Bermudez Edel Arrieta David A.Roberson Ryan B.Wicker W.M.Keck Center for 3D Innovation The University of Texas at El PasoEl PasoTX 79968USA Department of Mechanical Engineering The University of Texas at El PasoTX 79968USA Department of Metallurgical Materials and Biomedical EngineeringThe University of Texas at El PasoTX 79968USA

A novel, Ti-6 Al-4 v(Ti64)/Hydroxyapatite(HA at 5% by weight concentration) metal/ceramic composite has been fabricated using electron beam powder bed fusion(EPBF) additive manufacturing(AM): specifically, the commercial electron beam melting(EBM?) process. In addition to solid Ti64 and Ti64/5% HA samples, four different unit cell(model) open-cellular mesh structures for the Ti64/5% HA composite were fabricated having densities ranging from 0.68 to 1.12 g/cm^3, and corresponding Young's moduli ranging from 2.9 to 8.0 GPa, and compressive strengths ranging from ~3 to 11 MPa. The solid Ti64/5%HA composite exhibited an optimal tensile strength of 123 MPa, and elongation of 5.5% in contrast to a maximum compressive strength of 875 MPa. Both the solid composite and mesh samples deformed primarily by brittle deformation, with the mesh samples exhibiting erratic, brittle crushing. Solid, EPBF-fabricated Ti64 samples had a vickers microindentation hardness of 4.1 GPa while the Ti64/5%HA solid composite exhibited a vickers microindentation hardness of 6.8 GPa. The lowest density Ti64/5%HA composite mesh strut sections had a vickers microindentation hardness of 7.1 GPa. Optical metallography(OM) and scanning electron microscopy(SEM) analysis showed the HA dispersoids to be highly segregated along domain or grain boundaries, but homogeneously distributed along alpha(hcp) platelet boundaries within these domains in the Ti64 matrix for both the solid and mesh composites. The alpha platelet width varied from ~5 μm in the EPBF-fabricated Ti64 to ~1.1 m for the Ti64/5%HA mesh strut. The precursor HA powder diameter averaged 5 μm, in contrast to the dispersed HA particle diameters in the Ti64/5%HA composite which averaged 0.5 m. This work highlights the use of EPBF AM as a novel process for fabrication of a true composite structure, consisting of a Ti64 matrix and interspersed and exposed HA domains, which to the authors' knowledge has not been reported before. The results also illustrate the prospects not only for fabricating sp

关键词： Hydroxyapatite (HA) Metal-matrix ceramic composites Open-cellular (mesh) structures Electron-beam powder bed fusion (EPBF) Additive manufacturing (AM) Mechanical properties Microstructure characterization