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Acellular scaffold‑based approach for in situ genetic engineering of host T‑cells in solid tumor immunotherapy

Military Medical Research 2025年第1期12卷 16-35页

作者： Hiren Y.dandia Mamatha M.Pillai deepak Sharma Meghna Suvarna Neha dalal Ayush Madhok Arvind Ingle Shubhada v.Chiplunkar Sanjeev Galande Prakriti Tayalia department of biosciences and bioengineering Indian Institute of Technology BombayPowaiMumbai 400076India Radiation biology and Health Sciences division Bhabha Atomic Research CentreMumbai 400085India Centre of Excellence in Epigenetics Department of BiologyIndian Institute of Science Education and ResearchPune 411008India Advanced Centre for Treatment Research and Education in Cancer(ACTREC)Tata Memorial CentreKhargharMumbai 410210India

background:Targeted T-cell therapy has emerged as a promising strategy for the treatment of hematological ***,its application to solid tumors presents significant challenges due to the limited accessibility and *** delivery of tumor-specific T-cells using biomaterials has shown promise,however,procedures required for genetic modification and generation of a sufficient number of tumor-specific T-cells ex vivo remain major obstacles due to cost and time ***:Polyethylene glycol(PEG)-based three-dimensional(3d)scaffolds were developed and conjugated with positively charged poly-L-lysine(PLL)using carbamide chemistry for efficient loading of lentiviruses(Lvs)carrying tumor antigen-specific T-cell receptors(TCRs).The physical and biological properties of the scaffold were extensively ***,the scaffold loaded with OvA-TCR Lvs was implanted in b16F10 cells expressing ovalbumin(b16-OvA)tumor model to evaluate the anti-tumor response and the presence of transduced ***:Our findings demonstrate that the scaffolds do not induce any systemic inflammation upon subcutaneous implantation and effectively recruit T-cells to the *** b16-OvA melanoma tumor-bearing mice,the scaffolds efficiently transduce host T-cells with OvA-specific *** genetically modified T-cells exhibit homing capability towards the tumor and secondary lymphoid organs,resulting in a significant reduction of tumor size and systemic increase in anti-tumor *** cell profiling revealed a significantly high percentage of transduced T-cells and a notable reduction in suppressor immune cells within the tumors of mice implanted with these ***:Our scaffold-based T-cell therapy presents an innovative in situ localized approach for programming T-cells to target solid *** approach offers a viable alternative to in vitro manipulation of T-cells,circumventing the need for large-scale in vitro generat

关键词： Polyethylene glycol diacrylate Poly-L-lysine Lentiviruses T-cell therapy b16F10-OvA melanoma

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LHAASO detection of very-high-energy γ-ray emission surrounding PSR J0248+6021

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Science China(Physics,Mechanics & Astronomy) 2025年

作者： Zhen Cao F.Aharonian Axikegu Y.X.bai Y.W.bao d.bastieri X.J.bi Y.J.bi W.bian A.v.bukevich Q.Cao W.Y.Cao Zhe Cao J.Chang J.F.Chang A.M.Chen E.S.Chen H.X.Chen Liang Chen Lin Chen Long Chen M.J.Chen M.L.Chen Q.H.Chen S.Chen S.H.Chen S.Z.Chen T.L.Chen Y.Chen N.Cheng Y.d.Cheng M.C.Chu M.Y.Cui S.W.Cui X.H.Cui Y.d.Cui b.Z.dai H.L.dai Z.G.dai danzengluobu X.Q.dong K.K.duan J.H.Fan Y.Z.Fan J.Fang J.H.Fang K.Fang C.F.Feng H.Feng L.Feng S.H.Feng X.T.Feng Y.Feng Y.L.Feng S.Gabici b.Gao C.d.Gao Q.Gao W.Gao W.K.Gao M.M.Ge T.T.Ge L.S.Geng G.Giacinti G.H.Gong Q.b.Gou M.H.Gu F.L.Guo J.Guo X.L.Guo Y.Q.Guo Y.Y.Guo Y.A.Han O.A.Hannuksela M.Hasan H.H.He H.N.He J.Y.He Y.He Y.K.Hor b.W.Hou C.Hou X.Hou H.b.Hu Q.Hu S.C.Hu C.Huang d.H.Huang T.Q.Huang W.J.Huang X.T.Huang X.Y.Huang Y.Huang Y.Y.Huang X.L.Ji H.Y.Jia K.Jia H.b.Jiang K.Jiang X.W.Jiang Z.J.Jiang M.Jin M.M.Kang I.Karpikov d.Khangulyan d.Kuleshov K.Kurinov b.b.Li C.M.Li Cheng Li Cong Li d.Li F.Li H.b.Li H.C.Li Jian Li Jie Li K.Li S.d.Li W.L.Li W.L.Li X.R.Li Xin Li Y.Z.Li Zhe Li Zhuo Li E.W.Liang Y.F.Liang S.J.Lin b.Liu C.Liu d.Liu d.b.Liu H.Liu H.d.Liu J.Liu J.L.Liu M.Y.Liu R.Y.Liu S.M.Liu W.Liu Y.Liu Y.N.Liu Q.Luo Y.Luo H.K.Lv b.Q.Ma L.L.Ma X.H.Ma J.R.Mao Z.Min W.Mitthumsiri H.J.Mu Y.C.Nan A.Neronov K.C.Y.Ng L.J.Ou P.Pattarakijwanich Z.Y.Pei J.C.Qi M.Y.Qi b.Q.Qiao J.J.Qin A.Raza d.Ruffolo A.Sáiz M.Saeed d.Semikoz L.Shao O.Shchegolev X.d.Sheng F.W.Shu H.C.Song Yu.v.Stenkin v.Stepanov Y.Su d.X.Sun Q.N.Sun X.N.Sun Z.b.Sun J.Takata P.H.T.Tam Q.W.Tang R.Tang Z.b.Tang W.W.Tian L.H.Wan C.Wang C.b.Wang G.W.Wang H.G.Wang H.H.Wang J.C.Wang Kai Wang Kai Wang L.P.Wang L.Y.Wang P.H.Wang R.Wang W.Wang X.G.Wang X.Y.Wang Y.Wang Y.d.Wang Y.J.Wang Z.H.Wang Z.X.Wang Zhen Wang Zheng Wang d.M.Wei J.J.Wei Y.J.Wei T.Wen C.Y.Wu H.R.Wu Q.W.Wu S.Wu X.F.Wu Y.S.Wu S.Q.Xi J.Xia G.M.Xiang d.X.Xiao G.Xiao Y.L.Xin Y.Xing d.R.Xiong Z.Xiong d.L.Xu R.F.Xu R.X.Xu W.L.Xu L.Xue d.H.Yan J.Z.Yan T.Yan C.W.Yang C.Y.Yang F.Yang F.F.Yang L.L.Yang M.J.Yang R.Z.Yang W.X.Yang Y.H.Yao Z.G.Yao L.Q.Yin N.Yin X.H.You Z.Y.You Y.H Southwest Jiaotong University School of Astronomy and Space Science Nanjing University Center for Astrophysics Guangzhou University Tsung-dao Lee Institute & School of Physics and Astronomy Shanghai Jiao Tong University Institute for Nuclear Research of Russian Academy of Sciences Hebei Normal University University of Science and Technology of China LHAASO Collaboration State Key Laboratory of Particle detection and Electronics Key Laboratory of dark Matter and Space Astronomy & Key Laboratory of Radio Astronomy Purple Mountain Observatory Chinese Academy of Sciences Research Center for Astronomical Computing Zhejiang Laboratory Key Laboratory for Research in Galaxies and Cosmology Shanghai Astronomical Observatory Chinese Academy of Sciences School of Physics and Astronomy Key Laboratory of Particle Astrophysics & Experimental Physics division & Computing Center Yunnan University Key Laboratory of Cosmic Rays (Tibet University) Ministry of Education department of Physics The Chinese University of Hong Kong Key Laboratory of Radio Astronomy and Technology National Astronomical Observatories Chinese Academy of Sciences School of Physics and Astronomy (Zhuhai) & School of Physics (Guangzhou) & Sino-French Institute of Nuclear Engineering and Technology (Zhuhai) Sun Yat-sen University Institute of High Energy Physics Institute of Frontier and Interdisciplinary Science Shandong University APC Université Paris Cité CNRS/IN2P3 CEA/IRFU Observatoire de Paris department of Engineering Physics & department of Astronomy Tsinghua University School of Physics and Microelectronics Chinese Academy of Sciences Zhengzhou University Yunnan Observatories Chinese Academy of Sciences China Center of Advanced Science and Technology College of Physics Sichuan University School of Physics Peking University Guangxi Key Laboratory for Relativistic Astrophysics School of Physical Science and Technology University of Chinese Academy of Sciences Guangxi University department of Physics Faculty of Science Mahidol University Moscow Institute

We report the detection of an extended very-high-energy(vHE) γ-ray source coincident with the location of middle-aged(62.4 kyr) pulsar PSR J0248+6021, by using the LHAASO-WCdA data of live 796 d and LHAASO-KM2A data of live 1216d. A significant excess of γ-ray induced showers is observed both by WCdA in energy bands of 1-25 Te v and KM2A in energy bands of >25 Tev with 7.3σ and 13.5σ, respectively. The best-fit position derived through WCdA data is R.A. = 42.06°± 0.12°and dec. = 60.24°± 0.13°with an extension of 0.69°±0.15°and that of the KM2A data is R.A.= 42.29°± 0.13°and dec. =60.38°± 0.07°with an extension of 0.37°±0.07°. No clear extended multiwavelength counterpart of this LHAASO source has been found from the radio band to the Gev band. The most plausible explanation of the vHE γ-ray emission is the inverse Compton process of highly relativistic electrons and positrons injected by the pulsar. These electrons/positrons are hypothesized to be either confined within the pulsar wind nebula or to have already escaped into the interstellar medium, forming a pulsar halo.

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Observation of the γ-ray emission from W43 with LHAASO

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Science China(Physics,Mechanics & Astronomy) 2025年

In this paper, we report the detection of the very-high-energy (vHE, 100 Ge v100 Tev) γ-ray emissions from the direction of the young star-forming region W43, observed by the Large High Altitude Air Shower Observation (LHAASO). The extended γ-ray source was detected with a significance of～16σby KM2A and～17σby WCdA, respectively. The angular extension of this γ-ray source is about 0.5 degrees, corresponding to a physical size of about 50pc. We discuss the origin of the γ-ray emission and possible cosmic ray acceleration in the W43 region using multi-wavelength data. Our findings suggest that W43 is likely another young star cluster capable of accelerating cosmic rays (CRs) to at least several hundred Tev.

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Petrogenesis of the crater-facies Tokapal kimberlite pipe,Indrvati basin,Central India

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Geoscience Frontiers 2014年第6期5卷 781-790页

作者： N.v.Chalapathi Rao b.Lehmann b.K.Panwar Alok Kumar d.Mainkar department of Geology Centre of Advanced StudyBanaras Hindu UniversityVaranasi 221005India Mineral Resources Technical University of Clausthal38678 Clausthal-ZellerfeldGermany directorate of Geology and Mining RaipurChhattisgarh 492007India

New geochemical data of the crater-facies Tokapal kimberlite system sandwiched between the lower and upper stratigraphic horizons of the Mesoproterozoic lndravati basin a：：e presented. The kimberlite has been subjected to extensive and pervasive low-temperature alteration. Spinel is the only primary phase identifiable, while olivine macrocrysts and juvenile lapilli are largely pseudomorphed （talc-serpentine- carbonate alteration）. However, with the exception of the alkalies, major element oxides display systematic fractionation trends; likewise, HFSE patterns are well correlated and allow petrogenetic interpretation. various crustal contamination indices such as （SiO2 ＋ AI：：O3 ~ Na20）]（MgO ~ K20） and Si] Mg are close to those of uncontaminated kimberlites. Similar La]Yb （＇79-109） of the Tokapal samples with those from the kimberlites of Wajrakarur （73-145） and Narayanpet （72-156）, Eastern dharwar craton, southern India implies a similarity in their genesis. In the discriminant plots involving HFSE the Tokapal samples display strong affinities to Group 1I kimberlites from southern Africa and central India as well as to ＇transitional kimberlites＇ from the Eastern dharwar craton, southern India, and those from the Prieska and Kuruman provinces of southern Africa. There is a striking ~;imilarity in the depleted-mantle （TOM） Nd model ages of the Tokapal kimberlite system, bastar craton, th~ kimberlites from NKF and WKE Eastern dharwar craton, and the Majhgawan diatreme, bundelkhand craton, with the emplacement age of some of the lamproites from within and around the Palaeo^Mesoproterozoic Cuddapah basin, southern India. These similar ages imply a major tectonomagmatic event, possibly related to the break- up of the supercontinent of Columbia, at 1.3-1.5 Ga across the l：hree cratons. The ＇transitional＇ geochemical features displayed by many of the Mesoproterozoic po~：assic-ultrapotassic rocks, across these Indian cratons are inferred to be memories of the metasomatising f

关键词： Kimberlite Tokapal Columbia bastar craton India

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Effect of alpha-lipoic acid and Silybum marianum supplementation with a Mediterranean diet on metabolic dysfunction-associated steatosis

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World Journal of Hepatology 2025年第1期17卷 86-95页

作者： Ana d Cano Contreras María del Rocío Francisco Jose L vargas basurto Kevin d Gonzalez-Gomez Mercedes Amieva-balmori Federico Roesch dietlen JoséM Remes-Troche Instituto de Investigaciones Médico-biológicas Universidad VeracruzanaVeracruz 91700Mexico

bACKGROUNd The treatment of metabolic dysfunction-associated steatotic liver disease(MA-SLd)has focused on the control of *** marianum(SM)and alpha-lipoic acid(ALA)have shown antioxidant and adjuvant effects on the control of metabolic *** To evaluate whether the SM-ALA formulation(LUdLEv®),in combination with the Mediterranean diet(Md),could improve MASLd-related liver *** A randomized,double-blind clinical trial was conducted on patients with *** of SM-ALA plus Md(group A)vs placebo plus Md(group b)was compared for 24 *** baseline and weeks 12 and 24,anthropometric measurements,metabolic parameters,and liver function were *** effectiveness was evaluated through transient *** Fifty patients aged 54±10 years were included,and the majority(74%)were *** visceral fat and umbilical circumference were reported in both groups,with significance in group A(P=0.045 and 0.003,respectively).The de-crease in controlled attenuation parameter was gradual and maintained at 12 and 24 weeks in group A(P=0.026),whereas in group b the decrease was greater at week 12 and remained unchanged at week 24(∆controlled attenuation parameter:-27 db/m).Mild adverse effects were reported in 4 patients in group A(16%)and 4 patients in group b(16%),with no significant differences between groups(P=0.641).CONCLUSION SM-ALA(LUdLEv®)combined with the Md can promote the improvement of metabolic parameters,reducing visceral fat and hepatic steatosis in Mexican patients with MASLd.

关键词： Steatotic liver disease Silybum marianum Alpha-lipoic acid Mediterranean diet Fatty liver

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Numerical analysis of Shiobara hydropower cavern using practical equivalent approach

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Journal of Rock Mechanics and Geotechnical Engineering 2018年第2期10卷 402-410页

作者： v.b.Maji department of Civil Engineering Indian Institute of Technology Madras

Three-dimensional(3 d) numerical simulation of Shiobara hydropower cavern was attempted with the developed practical equivalent approach. This simple equivalent approach integrates the effect of joints and corresponding nonlinearity in the rock and predicts its deformation behaviour. The model requires minimum inputs from field or laboratory tests and is efficient to capture the nonlinear stress-strain responses associated with the jointed rock mass. In this study, the applicability of the model was demonstrated with the 3 d analysis of Shiobara hydropower cavern. The numerical results were also compared with those of six other computational models to analyse the same cavern. The 3 d modelling of powerhouse cavern shows that the present approach, though simple, can be applied to large-scale field problems. The model can precisely predict the deformation values well, and this study confirmed the effectiveness of the approach for simulation of underground structures in jointed rocks.

关键词： Jointed rocks Equivalent model Shiobara hydropower cavern dimensions(FLAC3d)

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buckling analysis of functionally graded material(FGM) sandwich truncated conical shells reinforced by FGM stiffeners filled inside by elastic foundations

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Applied Mathematics and Mechanics(English Edition) 2016年第7期37卷 879-902页

作者： d.v.dUNG L.K.HOA b.T.THUYET N.T.NGA Faculty of Mathematics Mechanics and Informatics Vietnam National University Faculty of basic Science Military Logistic AcademyHanoi Faculty of Mining Hanoi University of Mining and Geology

An analytical solution for buckling of an eccentrically stiffened sandwich truncated conical shell is investigated. The shell consists of two functionally graded material （FGM） coating layers and a core layer which are metal or ceramic subjected to an axial compressive load and an external uniform pressure. Shells are reinforced by stringers and rings, in which the material properties of shells and stiffeners are graded in the thickness direction following a general sigmoid law distribution. Two models of coated shell-stiffener arrangements are investigated. The change of the spacing between stringers in the meridional direction is taken into account. A couple set of three-variable- coefficient partial differential equations in terms of displacement components are solved by the Galerkin method. A closed-form expression for determining the buckling load is obtained. The numerical examples are presented and compared with previous works.

关键词： functionally graded material (FGM) sandwich truncated conical shell,stiffener elastic foundation buckling analysis

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Influence of the safety factor profile on the particle and heat transport in the Globus-M spherical tokamak

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Plasma Science and Technology 2019年第11期21卷 1-6页

作者： A YU TELNOvA G S KURSKIEv E O KISELEv N N bAKHAREv v K GUSEv N A KHROMOv S YU MEdvEdEv v b MIINAEv I v MIROSHNIKOv M I PATROv Yu v PETROv N v SAKHAROv A d SLAdKOMEdOvA P b SHCHEGOLEv v v SOLOKHA v A TOKAREv S YU TOLSTYAKOv E A TUKHMENEvA Ioffe Institute Saint-Petersburg 194021Russia Keldysh Institute Russian Academy of SciencesMoscow 125047Russia NRC'Kurchatov Institute’ Moscow 123098Russia

The advanced tokamak scenario is a promising operation scenario for ITER and fusion neutron *** this scenario the minimum value of the safety factor in the center of the plasma exceeds *** the compact spherical tokamak Globus-M,the formation of such conditions is possible with neutral beam injection at the current ramp-up *** to the slower diffusion of current inside the plasma,a zone is formed with reduced heat and particle transport across the magnetic field,which affects the temperature and density profiles of the *** leads to the peaked density profile formation and improvement of the energy confinement *** achieve a high fraction of the bootstrap current,it is necessary to increase the plasma *** the same time,the maximum allowable pressure is limited to the normalized beta limit.

关键词： advanced tokamak mode transport analysis internal transport barriers

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Effect of wall temperature modulation on the heat transfer characteristics of droplet-train flow inside a rectangular microchannel

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Chinese Journal of Chemical Engineering 2020年第3期28卷 685-697页

作者： vivekanand S.v.b.,Raju v.R.K. department of Mechanical Engineering National Institute of TechnologyWarangalTelangana 506004India

The numerical studies of water–oil two-phase slug flow inside a two-dimensional vertical microchannel subjected to modulated wall temperature boundary conditions have been discussed in the present *** researchers have contributed their efforts in exploring the characteristics of Taylor flows inside microchannel under constant wall heat flux or isothermal wall ***,there is no study available in the literature which discusses the impact of modulated thermal wall boundary conditions on the heat transfer behavior of slug flows inside ***,to bridge this gap,an effort has been made to understand the heat transfer characteristics of the flow under sinusoidal wall temperature ***,a single phase flow and heat transfer study was performed in microchannels,and the results of the fully developed velocity profile and heat transfer rate were validated with benchmark analytical *** an optimal selection of the combination of sinusoidal thermal wall boundary conditions has been made for the two-phase slug flow ***,the effects of amplitude(0 bεb 0.03)and frequency(0 bωb 750πrad·s-1)of the sinusoidal wall temperature profile on the heat transfer have been studied using the optimal combination of the wall boundary *** results of the numerical study using modulated temperature conditions on channel walls showed a significant improvement in the heat transfer over liquid-only flow by approximately 50%as well as over two-phase flow without wall temperature *** non-dimensional temperature contours obtained for different cases of temperature modulation clearly explain the root cause of such improvement in the heat ***,the results based on the hydrodynamics of the flow have also been reported in terms of variation of droplet shapes and film *** influence of Capillary number on the film thickness as well as heat transfer rates has also been *** addition,the measured fil

关键词： Heat transfer Microchannel Modulation Surface tension Taylor flow

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Study the Hydration and the Microstructure of Cement blended with Rice Husk Ash in Comparison with Silica Fume

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武汉理工大学学报 2010年第17期32卷 252-255,260页

作者： NGUYEN v T YE G vAN b K bUI d d Faculty of Civil Engineering and Geosciences Delft University of TechnologyP.O. Box 50482600 GADelftThe Netherlands department of building Materials Hanoi University of Civil EngineeringHanoi 700803Vietnam

Rice husk ask (RHA) is not a ultra-fine material as silica fume (SF),but possesses a very high specific surface area because of its porous structure. With the similar chemical composition of RHA and SF,the activity of RHA,therefore,is different from that of SF. The objective of this work is to study the hydration and the microstructure of Portland cement blended with RHA in comparison with SF. The test results show that SF refined the pore structure of cement paste better than RHA. However,the effect of RHA on cement hydration is more pronouned than that of SF for the mixture with low water to binder ratio.

关键词： hydration isothermal calorimetry mercury intrusion porosimetry (MIP) microstructure rice husk ash silica fume

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