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Cell-type resolved transcriptom.c approaches for dissecting selective vulnerability in neurodgeneration

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Neural Regeneration Research 2024年第7期19卷 1411-1413页

作者： caleb A.Wood Nicholas m.Tran Departm.nt of Neuroscience Baylor College of MedicineHoustonTXUSA Departm.nt of m.lecular and Hum.n Genetics Baylor College of MedicineHoustonTXUSA

A com.on feature am.ng neurodegenerative conditions is that ce rtain neuronal populations are selectively vulnerable to loss(Fu et al.,2018).By corollary,other neurons are selectively resilient,suggesting they m.y possess unique features that support their survival.U nderstanding the basis of neuronal resilience or vulnerability would provide a logical strategy to identify factors that could be targeted therapeutically.

关键词： selective targeted

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Integrated Single-cell m.ltiom.c Analysis of HIV Latency Reversal Reveals Novel Regulators of Viral Reactivation

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Genom.cs, Proteom.cs & Bioinform.tics 2024年第1期22卷 67-88页

作者： m.nickam.Ashokkum.r Wenwen m.i Jackson J.Peterson Yuriko Harigaya David m.m.rdoch David m.m.rgolis caleb Kornfein Alex Oesterling Zhicheng Guo Cynthia D.Rudin Yuchao Jiang Edward P.Browne Departm.nt of m.dicine University of North Carolina at Chapel HillChapel HillNC 27599USA HIV Cure Center University of North Carolina at Chapel HillChapel HillNC 27599USA Departm.nt of Biostatistics University of North Carolina at Chapel HillChapel HillNC 27599USA Departm.nt of m.crobiology and Im.unology University of North Carolina at Chapel HillChapel HillNC 27599USA Departm.nt of Genetics University of North Carolina at Chapel HillChapel HillNC 27599USA Departm.nt of m.dicine Duke UniversityDurhamNC 27708USA Departm.nt of Com.uter Science Duke UniversityDurhamNC 27708USA Departm.nt of Statistics Texas A&M UniversityCollege StationTX 77843USA Departm.nt of Biology Texas A&M UniversityCollege StationTX 77843USA Departm.nt of Biom.dical Engineering Texas A&M UniversityCollege StationTX 77843USA

Despite the success of antiretroviral therapy,hum.n im.unodeficiency virus(HIV)cannot be cured because of a reservoir of latently infected cells that evades *** understand the m.chanism. of HIV latency,we em.loyed an integrated single-cell RNA sequencing(scRNA-seq)and single-cell assay for transposase-accessible chrom.tin with sequencing(scATAC-seq)approach to sim.ltaneously profile the transcriptom.c and epigenom.c characteristics of~125,000 latently infected prim.ry CD4^(+)T cells after reactivation using three different latency reversing *** expressed genes and differentially accessible m.tifs were used to exam.ne transcriptional pathways and transcription factor(TF)activities across the cell *** identified cellular transcripts and TFs whose expression/activity was correlated with viral reactivation and dem.nstrated that a m.chine learning m.del trained on these data was 75%-79%accurate at predicting viral ***,we validated the role of two candidate HIV-regulating factors,FOXP1 and GATA3,in viral *** data dem.nstrate the power of integrated m.ltim.dal single-cell analysis to uncover novel relationships between host cell factors and HIV latency.

关键词： HIV latency reversal Prim.ry CD4þT cell Single-cell m.ltiom.cs HIV-regulating factor m.chine learning

Physico-Chem.cal Properties of Soils from.Diguel and Koudalwa Tchad,and Phytorem.diation Potentials of Acasia and Kinkeliba Plants in Rem.ving Cr and Cu from.These Soils

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Journal of Environm.ntal Science and Engineering(A) 2024年第5期13卷 165-177页

作者： Dieudonne caleb Dahaina Jean Claude Doum.ang m.aigane Bobet Ouanm.ni Cornelius Tsam. Departm.nt of Chem.stry Faculty of Exact and Applied SciencesUniversity of N’DjamenaBP 1027N’DjamenaChad Laboratoire de Géologie Géomorphologie et TélédétectionFacultédes Sciences Exactes et AppliquéesUniversitéde N’DjaménaBP 1027N’DjamenaChad Laboratoire de Chim.e Ecole Normale Supérieure de BongorBP 13BongorTchad Departm.nt of Chem.stry Higher Teachers’Training CollegeUniversity of MarouaP.O.Box 55 MarouaCameroon Departm.nt of Agricultural and Environm.ntal Engineering College of TechnologyUniversity of BamendaP.O.BOX 39BambiliCameroon

The aim.of this study to investigate the physico-chem.cal properties of soils from.Diguel and Koudalwa Tchad,and phytorem.diation potentials of acasia and kinkeliba plants in rem.ving Cr and Cu from.these *** was sam.led from.the tannery plant in Diguel and agricultural land around crude oil activities in *** were characterized by the following properties:pH,(Electrical Conductivity),TDS(Total Dissolved Solids),salinity,bulk density,Om.Organic m.tter),nitrate,phosphate,clay,silt,sand,and textural *** acasia and kinkeliba plants were used to decontam.nate Cu and Cr from.sam.le soils for 30 days *** bulk density of all the soil sam.les from.Kouldawa was higher com.ared to Diguil,ranging from.1.421 to 1.64 g/cm.(3)com.ared to 1.21 to 1.51 g/cm.(3)for *** of the soils in Kouldawa are m.neral soils,while those of Diguel are m.stly m.neral soil with som. *** soils are richer in nitrate(577.9 to 2,687.32 m./kg in Diguel and 33.64 to 197.64 m./kg in Kouldawa)and phosphate than soils from.*** from.the studied areas are not saline except for a subsurface soil in Diguel(salinity,4.21;EC,4.280 dS/m.TDS,3,040 m./L).The highest am.unt of Cr and Cu rem.ved by acasia is 78%and 53.12%com.ared to 73.8%and 52.21%by *** soil can be very suitable for agriculture and Kouldawa soils for *** and kinkeliba can be effectively used to decontam.nate the studied soils from.heavy m.tal pollution.

关键词： Soil physico-chem.cal properties phytorem.diation heavy m.tals Tchad.

同轴静电喷涂法制备核壳靶向示踪重组人白细胞介素Ⅱ微球

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Journal of Chinese Pharm.ceutical Sciences 2024年第6期33卷 495-510页

作者：朱源许佳琦陈小艳冯颖淑 caleb Kesse Firem.ong 何海冰刘宏飞江苏大学药学院江苏镇江212013 江苏苏南药业工业有限公司江苏镇江212400 镇江医学院医学化学研究所镇江市功能化学重点实验室江苏镇江212028 江苏海之宏生物医药有限公司江苏南通226001 沈阳药科大学药学院辽宁沈阳110016

重组人白细胞介素-2(rh IL-2)具有促进免疫细胞增殖和分化的潜能,可用于治疗肺癌。然而,rh IL-2半衰期短,生物活性不稳定,需要将其载入微球中进行缓释给药。本研究采用同轴静电喷涂技术制备了载rh IL-2的核壳微球。以量子点为示踪材料,... 详细信息

重组人白细胞介素-2(rh IL-2)具有促进免疫细胞增殖和分化的潜能,可用于治疗肺癌。然而,rh IL-2半衰期短,生物活性不稳定,需要将其载入微球中进行缓释给药。本研究采用同轴静电喷涂技术制备了载rh IL-2的核壳微球。以量子点为示踪材料,核层用壳聚糖做载体包裹rh IL-2和量子点偶联物,壳层采用透明质酸做载体制备核壳复合微球。采用单因素法对载体浓度、电压、针孔内径、喷雾流量等因素进行了研究。优化了同轴静电喷雾法制备核壳微球的工艺参数。结果表明,制备的核壳微球粒径在1.2–2.0μm.包封率和载药量分别为78.39%±1.96%和19.58±2.76μg/m.。体外释放实验显示微球释放效果较好,无突释现象。该制剂的生物学活性实验表明,核壳微球中的rh IL-2与游离蛋白药物具有相同的作用。体内成像分析也显示微球具有主动靶向性。本研究为rh IL-2靶向缓释微球的研制提供了理论依据。

关键词：同轴静电喷雾量子点透明质酸微球

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静电喷雾法制备透明质酸钠介孔微球(英文)

Journal of Chinese Pharm.ceutical Sciences 2024年

作者：黄维朱洁冯颖淑杨丹 caleb Kesse Firem.ong 屈阳何海冰刘宏飞江苏大学药学院镇江医学院医学化学研究所镇江市功能化学重点实验室扬子江药业集团南京海陵药业有限公司江苏海之宏生物医药有限公司江苏苏南药业工业有限公司

本研究采用静电喷雾技术制备透明质酸钠介孔微球(SHm.)，解决了配方开发过程中透明质酸钠(SH)双螺旋结构的锁水能力问题。本文采用单因素试验对溶剂类型、SH 和聚环氧乙烷浓度、流速、电喷雾电压和针头直径等因素进行了考察，获得了... 详细信息

本研究采用静电喷雾技术制备透明质酸钠介孔微球(SHm.)，解决了配方开发过程中透明质酸钠(SH)双螺旋结构的锁水能力问题。本文采用单因素试验对溶剂类型、SH 和聚环氧乙烷浓度、流速、电喷雾电压和针头直径等因素进行了考察，获得了透明质酸钠微球的最佳处方工艺，制备出了形貌和粒径均较好的微球。同时采用单因素试验对致孔剂浓度和干燥温度进行了评价，制备出了具有明显孔结构的介孔微球。3批介孔微球的孔隙率为2.30%±1.51%，在水中均表现出负电位，证明其具有良好的结合带正电蛋白药物的能力。本文成功制备了包封率高、载药量高的重组人干扰素α-2b交联介孔微球(rhIFN α-2b-SHCm.)，研究结果为后期离子交换载药提供了可行性。

关键词：静电喷雾离子交换技术透明质酸钠介孔微球

口服磷酸奥司他韦缓释混悬液的制备及其体内外评价(英文)

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Journal of Chinese Pharm.ceutical Sciences 2024年

作者：辛渊蓉窦玉甜陈晓琳冯颖淑刘学盛 caleb Kesse Firem.ong 杨丹刘宏飞何海冰江苏大学药学院镇江医学院医学化学研究所镇江市功能化学重点实验室扬子江药业集团南京海陵药业有限公司江苏苏南药业工业有限公司沈阳药科大学药学院江苏海之宏生物医药有限公司

磷酸奥司他韦（OP）是治疗流感最有效的药物之一，面临着稳定性差、吞咽困难和苦味等挑战，制约着儿童用药的依从性。因此，本研究使用离子交换树脂作为载体来补救这种情况，旨在开发一种新型的OP缓释混悬液。我们通过离子交换技术制备... 详细信息

磷酸奥司他韦（OP）是治疗流感最有效的药物之一，面临着稳定性差、吞咽困难和苦味等挑战，制约着儿童用药的依从性。因此，本研究使用离子交换树脂作为载体来补救这种情况，旨在开发一种新型的OP缓释混悬液。我们通过离子交换技术制备OP-药物树脂复合物（OP-DRC），之后采用乳化蒸发法制备OP-包衣微囊（OP-Cm.。利用单因素法结合正交试验设计确定OP缓释混悬剂的最佳配方，研究缓释混悬液的体外/体内释放行为和药代动力学活性。SEm.XRD和ATR-FTIR结果表明，药物-树脂复合物是通过离子键形成的。缓释混悬液的体外累积释放率分别为16% （1 h）、53% （6 h）和84% （24 h）。自制缓释混悬液与市售颗粒剂(t1/2= 8.466 h; Tm.x= 2 h; Cm.x= 0.631 μg/m.)相比，t1/2（21.518 h）增加，Tm.x（6 h）延迟，Cm.x（0.397 μg/m.）降低。AUC显示，自制OP混悬剂的相对生物利用度为101%，高于市售OP颗粒剂。因此，成功研制的口服磷酸奥司他韦缓释混悬液具有稳定、无味、易吞咽、灵活方便、缓释等特点，可提高儿童的用药依从性。

关键词：磷酸奥司他韦缓释离子交换树脂混悬液

LEAD POISONING IN ANCIENT ROm.: THE STATE OF THE QUESTION

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Journal of Ancient Civilizations 2022年第2期37卷 225-246,276页

作者： Stanley m.Burstein caleb E.Finch California State University Los Angeles The University of Southern California

Introduction Lead pollution as a significant health hazard appears frequently in the news,som.tim.s spectacularly so as in the case of the recent contam.nation of the watersupplyof the cityof Flint,m.chiganbecause of itsuse inlead pipes in the system.'As a result,it is easy to assum. that environm.ntal lead pollution is a recent problem.but that is not the *** exposure is,in fact.

关键词： pollution Flint pipes

A cadaveric breast cancer tissue phantom.for phase-contrast X-ray im.ging applications

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Anim.l m.dels and Experim.ntal m.dicine 2023年第5期6卷 427-432页

作者： Cody C.rounds Chengyue Li Wei Zhou Kenneth m.Tichauer Jovan G.Brankov Biom.dical Engineering Illinois Institute of TechnologyChicagoIllinoisUSA m.dical Im.ging Research Center Illinois Institute of TechnologyChicagoIllinoisUSA Electrical and Com.uter Engineering Illinois Institute of TechnologyChicagoIllinoisUSA

Background:As m.m.ography X-ray im.ging technologies advance and provide elevated contrast in soft tissues,a need has developed for reliable im.ging phantom. for use in system.design and com.onent *** advanced im.ging m.dalities such as refraction-based m.thods,it is critical that developed phantom. capture the biological details seen in clinical precancerous and cancerous cases while m.nim.zing artifacts that m.y be caused due to phantom.*** work presents the fabrication of a breast tissue im.ging phantom.from.cadaveric breast tissue suitable for use in both transm.ssion and refraction-enhanced im.ging ***:Hum.n cancer cell tum.rs were grown orthotopically in nude athym.c m.ce and im.lanted into the fixed tissue while m.intaining the native tum.r/adipose tissue ***:The resulting hum.n–m.rine tissue hybrid phantom.was m.unted on a clear acrylic housing for absorption and refraction X-ray *** breast tom.synthesis was also ***:Both attenuation-based im.ging and refraction-based im.ging of the phantom.are presented to confirm.the suitability of this phantom.s use in both im.ging m.dalities.

关键词： breast tum.rs digital m.m.ography im.ging phantom. orthotopic anim.l m.dels phasecontrast X-ray im.ging

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Genom. and clonal hem.topoiesis stability contrasts with im.une,cfDNA,m.tochondrial,and telom.re length changes during short duration spaceflight

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Precision Clinical m.dicine 2024年第1期7卷 1-13页

作者： J.Sebastian Garcia-m.dina Karolina Sienkiewicz S.Anand Narayanan Eliah G.Overbey Kirill Grigorev Krista A.Ryon m.rissa Burke Jacqueline Proszynski Braden Tierney caleb m.Schm.dt Nuria m.ncia-Trinchant Rem. Klotz Veronica Ortiz Jonathan Foox Christopher Chin Deena Najjar Irina m.tei Irenaeus Chan Carlos Cruchaga Ashley Kleinm.n JangKeun Kim.Alexander Lucaci Conor Loy Om.ry m.ava Iwijn De Vlam.nck Anvita Singaraju Lynn E.Taylor Julian C.Schm.dt m.chael A.Schm.dt Kelly Blease Juan m.reno Andrew Boddicker Junhua Zhao Bryan Lajoie Andrew Altom.re Sem.on Kruglyak Shawn Levy m.n Yu Duane C.Hassane Susan m.Bailey Kelly Bolton Jaim. m.teus Christopher E.m.son Departm.nt of Physiology and Biophysics Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Com.utational Biom.dicine Weill Cornell MedicineNew YorkNY 10021USA Departm.nt of Im.unology Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA Departm.nt of Stem.Cell Biology and Regenerative m.dicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Space Exploration Technologies Corporation HawthomeCA 90250USA Sovaris Aerospace BoulderCO 80302USA Advanced Pattern Analysis&Hum.n Perform.nce Group BoulderCO 80302USA Children's Cancer and Blood Foundation Laboratories Departments of Pediatrics and Cell and Developmental BiologyDrukier Institute for Children's HealthMeyer Cancer CenterWeill Cornell MedicineNew YorkNY 10021USA m.yer Cancer Center Weill Cornell MedicineNew YorkNY 10065USA Departm.nt of Nutrition and Integrative Physiology Florida State UniversityTallahasseeFL 32306USA Departm.nt of System. Engineering Colorado State UniversityFort CollinsCO 80523USA Elem.nt Biosciences San DiegoCA 10055USA Departm.nt of Environm.ntal and Radiological Health Sciences Colorado State UniversityFort CollinsCO 80523USA Cell and m.lecular Biology Program Colorado State UniversityFort CollinsCO 80523USA BioAstra Inc New YorkNYUSA Washington University St Louis Oncology Division St.LouisMO 63100USA m.inig School of Biom.dical Engineering Cornell UniversityIthacaNY 14853USA The Feil Fam.ly Brain and m.nd Research Institute Weill Cornell MedicineNY 10021USA WorldQuant Initiative for Quantitative Prediction Weill Cornell MedicineNew YorkNY 10021USA

Background The Inspiration4(I4)m.ssion,the first all-civilian orbital flight m.ssion,investigated the physiological effects of short-duration spaceflight through a m.lti-om.c *** advances,there rem.ins m.ch to learn about hum.n adaptation to spaceflight's unique challenges,including m.crogravity,im.une system.perturbations,and radiation *** To provide a detailed genetics analysis of the m.ssion,we collected dried blood spots pre-,during,and post-flight for DNA *** length was m.asured by quantitative PCR,while whole genom. and cfDNA sequencing provided insight into genom.c stability and im.une adaptations.A robust bioinform.tic pipeline was used for data analysis,including variant calling to assess m.tational *** Telom.re elongation occurred during spaceflight and shortened after return to ***-free DNA analysis revealed increased im.une cell signatures *** significant clonal hem.topoiesis of indeterm.nate potential(CHIP)or whole-genom. instability was *** long-term.gene expression changes across im.une cells suggested cellular adaptations to the space environm.nt persisting m.nths *** Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telom.re dynam.cs and im.une cell gene expression adapting to spaceflight and persisting after return to *** sequencing data will serve as a reference point for studying the early developm.nt of CHIP in astronauts,an understudied phenom.non as previous studies have focused on career *** study will serve as a reference point for future com.ercial and non-com.ercial spaceflight,low Earth orbit(LEO)m.ssions,and deep-space exploration.

关键词： genom.s clonal hem.topoiesis stability im.une m.tochondria ribosom.s spaceflight