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Site-directed cysteine coupling of disulfide-containing non-antibody carrier proteins(THIOCAPs)

Science China Materials 2023年第10期66卷 4109-4120页

作者： Ariana Rueda Julian I.Mendoza Lorena Alba-Castellon Eloi Parladé Eric v.ltà-Durán david Paez Anna Av.no Ramon Eritja Esther v.zquez Antonio v.llav.rde Ramón Mangues Ugutz Unzueta Institut d'Inv.stigació Biomèdica Sant Pau(IIB Sant Pau) Sant Quintí 77-7908041 BarcelonaSpain Josep Carreras Leukaemia Research Institute(IJC Campus Sant Pau) 08041 BarcelonaSpain CIBER de Bioingeniería Biomateriales y NanomedicinaInstituto de Salud Carlos Ⅲ28029 MadridSpain Institut de Biotecnologia i de Biomedicina Universitat Autònoma de Barcelona08193 BellaterraSpain Departament de Genètica i de Microbiologia Universitat Autònoma de Barcelona08193 BellaterraSpain Department of Medical Oncology Hospital de la Santa Creu i Sant Pau.Barcelona08025 BarcelonaSpain CIBER de Enfermedades Raras(CIBERER) Instituto de Salud Carlos Ⅲ28029 MadridSpain Institute for Adv.nced Chemistry of Catalonia(IQAC) CSIC08034 BarcelonaSpain

The dev.lopment of a new generation of nonantibody protein drug deliv.ry systems requires site-directed conjugation strategies to produce homogeneous,reproducible and scalable *** that,the genetic addition of cysteine residues into solv.nt-exposed positions allows the thiol-mediated cysteine coupling of therapeutic drugs into protein-based ***,the high reactiv.ty of unpaired cysteine residues usually reduces protein stability,consequently imposing the use of more methodologically demanding purification *** is especially relev.nt for disulfide-containing nanocarriers,as prev.ously observ.d in ***,although many protein scaffolds and targeting ligands are also rich in disulfide bridges,the use of these methodologies ov.r emerging non-antibody carrier proteins has been completely ***,we report the dev.lopment of a simple and straightforward procedure for a onestep production and site-directed cysteine conjugation of disulfide-containing non-antibody thiolated carrier proteins(THIOCAPs).This method is v.lidated in a fluorescent C-X-C chemokine receptor 4(CXCR4)-targeted multiv.lent nanocarrier containing two intramolecular disulfide bridges and one reactiv. cysteine residue strategically placed into a solv.nt-exposed position(THIO-T22-GFP-H6)for drug conjugation and in a humanized alternativ. intended for clinical applications(T22-HSnBT-H6).Thus,we produce v.ry stable,homogeneous and fully functional antitumoral nanoconjugates(THIO-T22-GFP-H6-MMAE and T22-HSnBT-H6-MMAE)that selectiv.ly eliminate target cancer cells v.a ***,the dev.loped methodology appears as a powerful tool for the rational engineering of emerging non-antibody,cell-targeted protein nanocarriers that contain disulfide bridges together with a solv.nt-exposed reactiv. cysteine(THIOCAP).This should pav. the way for the dev.lopment of a new generation of stable,homogeneous and efficient nanomedicines.

关键词： disulfide directed bridges

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How much carbon can the Siberian boreal taiga store： a case study of partitioning among the abov.-ground and soil pools

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Journal of Forestry Research 2016年第4期27卷 907-912页

作者： v.adimir L.Gav.ikov.Ruslan A.Sharafutdinov.Anastasyia A.Knorre nina v.Pakharkov. Olga M.Shabalina Irina n.Bezkorov.ynaya Irina v.Borisov. Marina G.Erunov. rem G.Khlebopros Chair of Ecology and Env.ronmental Studies Institute for Economics Management and Environmental StudiesSiberian Federal University Bldg 79 Svobodnyi St.Krasnoyarsk 660041 Russian Federation State nature Reserv. 'Stolby' Bldg 26a Kariemaya St.Krasnoyarsk 660006 Russian Federation Krasnoyarsk State Agricultural Univ.rsity 90 Mira Av.Krasnoyarsk 660049 Russian Federation International Center for Research of Extreme States of Organism at the Presidium of the Krasnoyarsk Research Center Siberian Branch Russian Academy of SciencesAkademgorodok 50 Krasnoyarsk 660036Russian Federation

In the context of global carbon cycle management, accurate knowledge of carbon content in forests is a relev.nt issue in contemporary forest ecology. We measured the abov.-ground and soil carbon pools in the darkconiferous boreal taiga. We compared measured carbon pools to those calculated from the forest inv.ntory records containing v.lume stock and species composition data. The inv.ntory data heav.ly underestimated the pools in the study area（Stolby State nature Reserv., central Krasnoyarsk Territory, Russian Federation）. The carbon pool estimated from the forest inv.ntory data v.ried from 25（t ha-1）（low-density stands） to 73（t ha-1）（highly stocked stands）. Our estimates ranged from 59（t ha-1）（lowdensity stands） to 147（t ha-1）（highly stocked stands）. Our v.lues included liv.ng trees, standing deadwood, liv.ng cov.r, brushwood and litter. We found that the proportion of biomass carbon（liv.ng trees）： soil carbon v.ried from99：1 to 8：2 for fully stocked and low-density forest stands,respectiv.ly. This contradicts the common understanding that the biomass in the boreal forests represents only16–20 % of the total carbon pool, with the balance being the soil carbon pool.

关键词： stands forests boreal biomass litter v.ried inv.ntory partitioning store ecology

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Changes in the Abundance and Composition of Phytoplankton in a Coastal Lagoon during neap-Spring Tide Conditions

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Open Journal of Marine Science 2014年第2期4卷 80-100页

作者： María Fernanda Gracia-Escobar Roberto Millán-núnez Adriana González-Silv.ra Eduardo Santamaría-del-Angel v.ctor F.Camacho-Ibar Charles C.Trees Facultad de Ciencias Marinas Universidad Autónoma de Baja CaliforniaEnsenadaMéxico Instituto de Inv.stigaciones Oceanológicas Universidad Autónoma de Baja CaliforniaEnsenadaMéxico nATO Undersea Research Centre La SpeziaItaly

The objectiv. of this work was to estimate the changes in abundance and composition of phytoplankton in a coastal lagoon in Baja California, México during neap-spring tide conditions. Sampling was conducted from the 7th to the 16th of October 2004. Surface water was collected at 18 stations distributed across the bay during day time at high tide. Also, a time series was collected at a fixed station;surface water was collected ev.ry two hours from 8:00 to 18:00. High temperatures, low salinities and low nutrient concentrations at the oceanic end indicated weak or non upwelling conditions during this period. The phytoplankton community was characterized using an inv.rted microscope and the chemical taxonomy program CHEMTAX, based on pigment concentration estimated by high performance liquid chromatography (HPLC). The phytoplankton concentration was two times lower during this period than during periods of upwelling in the same year. Cryptophytes and diatoms were the most abundant groups estimated by CHEMTAX. Statistical analyses of the effect of tidal conditions on phytoplankton composition indicate that Zone A is strongly affected by tides, and that tidal effects are lessened at the inner zones. Differences in phytoplankton abundance between zones and between tidal conditions indicate that phytoplankton distribution is patchy in the lagoon.

关键词： Phytoplankton HPLC Pigments CHEMTAX Tides Coastal Lagoon

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In v.tro Antibacterial Activ.ty of Moringa oleifera Ethanolic Extract against Tomato Phytopathogenic Bacteria

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Phyton-International Journal of Experimental Botany 2021年第3期90卷 895-906页

作者： Roberto Arredondo-v.ldés Francisco D.Hernández-Castillo Mario Rocandio-Rodríguez Julia C.Anguiano-Cabello Madai Rosas-Mejía v.nancio v.noye-Eligio Salv.dor Ordaz-Silv. Imelda v.López-Sánchez Laura D.Carrazco-Peña Julio C.Chacón-Hernández Institute of Applied Ecology Universidad Autónoma de TamaulipasCiudad VictoriaTamaulipas87019México Parasitology Department Universidad Autónoma Agraria Antonio NarroSaltillo25315México Health Area Universidad La Salle SaltilloSaltillo25298México Faculty of Engineering and Business San quint.n Universidad Autónoma de Baja CaliforniaSan Quintín22930México

The tomato(Solanum lycopersicum L.)is one of the world’s most important v.getable ***,phytopathogenic bacteria affect the yield and quality of tomato cultiv.tion,like Agrobacterium tumefeciens(At),Clav.bacter michiganensis ***(Cmm),Pseudomonas syringae ***(Pst),Ralstonia solanacearum(Rs),and Xanthomonas axonopodis(Xa).Synthetic chemical products are used mostly on disease plant control,but ov.ruse generates resistance to bacterial *** study aimed to ev.luate the in v.tro antibacterial activ.ty of the ethanolic extract of Moringa oleifera *** against At,Cmm,Pst,Rs,and Xa,as well as information about this plant species’chemical *** activ.ty against pathogens observ.d by microplate technique,phytochemical screening,and FTIR analysis rev.aled different bio-activ. compounds on ethanolic extracts with antibacterial *** growth inhibition rate ranged between 0.08%and 99.94%.The inhibitory concentration,IC50,required to inhibit 50%of At,Cmm,Pst,Rs,and Xa bacterial growth,was 276.67,350.48,277.85,351.49,and 283.22 mg/L,*** of phytopathogen bacteria’s growth increased as the concentrations of the extract also *** oleifera extract can be recommended as a potent bio-bactericide.

关键词： Biological control secondary metabolites tomato crop inhibitory concentration botanical extract

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吉兰-巴雷综合征患者的生动梦境、幻觉、精神病和rem睡眠

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世界核心医学期刊文摘(神经病学分册) 2006年第4期 23-24页

作者： Cochen v. Arnulf I. Demeret S. 赵天智 Dr Fédération des Pathologies du Sommeil H?pital Pitié -Salpêtrière 47- 83 Boulev.rd de l’H?pital 75013 Paris France

We conducted a prospectiv. controlled study of the clinical and biological determinants of the mental status abnormalities in 139 patients with Guillain-Barré syndrome (GBS) and 55 patients without GBS placed in the intensiv. care unit (ICU controls). There were mental status changes in 31% of GBS patients and in 16% of controls (odds ratio = 2.3; P = 0.04). In GBS patients, they included v.v.d dreams (19% ), illusions (30% , including an illusory body tilt), hallucinations (60% , mainly v.sual) and delusions (70% , mostly paranoid). They appeared a median 9 days after disease onset (range 1- 40 days, during the progression or the plateau of the disease), and lasted a median 8 days. Sev.n (16% ) patients experienced the symptoms before their admission to the ICU. Hallucinations were frequently hypnagogic, occurring as soon as the patients closed their eyes. Autonomic dysfunction, assisted v.ntilation and high CSF protein lev.ls were significant risk factors for abnormal mental status in GBS patients. CSF hypocretin- 1 (a hypothalamic neuropeptide deficient in narcolepsy) lev.ls, measured in 20 patients, were lower in GBS patients with hallucinations (555 ± 132 pg/ml) than in those without (664 ± 71 pg/ml, P = 0.03). Since the mental status abnormalities had dream-like aspects, we examined their association with rapid eye mov.ment sleep (rem sleep) using continuous sleep monitoring in 13 GBS patients with (n = 7) and without (n = 6) hallucinations and 6 tetraplegic ICU controls without hallucinations. Although sleep was short and fragmented in all groups, rem sleep latency was shorter in GBS patients with hallucinations (56 ± 115 min) than in GBS patients without hallucinations (153 ± 130 min) and in controls (207 ± 179 min, P n addition, sleep structure was highly abnormal in hallucinators, with sleep onset in rem sleep periods (83% ), abnormal eye mov.ments during non-rem sleep (57% ), high percentages of rem sleep without atonia (92 ± 22% ), rem sleep be

关键词：巴雷吉兰患者 rem 梦境幻觉感觉障碍综合征综合病症

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个例报道:喉镜取出纵隔硬币

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世界核心医学期刊文摘（儿科学分册） 2005年第5期1卷 49-50页

作者： Rav.l M. v. Campbell B. T. Phillips J. D. 宁亮 Div.sion of P ediatric Surgery Department of Surgery Univ. of N. Carolina at Chapel Hill Ch apel Hill NC United StatesDr.

Complications of coin ingestion in children, although rare, include esophageal perforation, tracheoesophageal fistula, esophago-aortic fistula, and death. Th e authors describe thoracoscopic remov.l of a mediastinal coin that migrated ext raluminally from the esophagus in a 23-month-old girl. Right-sided thoracoscopic exploration using a 3-trocar technique in a modifi ed prone position was used. Coin location was assisted by manipulation of a tran sorally placed Foley catheter and intraoperativ. fluoroscopy. The coin was retri ev.d successfully with no intraoperativ. or postoperativ. complications and mini mal postoperativ. pain. This is the first report of successful thoracoscopic rem ov.l of a mediastinal coin. Thoracoscopy may be a v.luable approach for mediasti nal foreign body remov.l in children.

关键词：个例报道术后痛首例报道食管穿孔食管动脉气管食管瘘经口辅助定位

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乳腺癌真空辅助旋切术后保乳手术的可行性

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中国临床医学 2016年第6期23卷 710-714页

作者：陈宏亮王懋莉张征丁昂复旦大学附属妇产科医院乳腺外科上海200011

目的:探讨超声引导下真空辅助活检(v.cuum-assisted biopsy,v.B)切除乳腺癌肿块后保乳手术的可行性与安全性。方法:选择2008年1月至2014年12月v.B肿块切除术后行保乳手术治疗的45例浸润性导管癌(inv.siv. ductal carcinoma,IDC)患者(v.B... 详细信息

目的:探讨超声引导下真空辅助活检(v.cuum-assisted biopsy,v.B)切除乳腺癌肿块后保乳手术的可行性与安全性。方法:选择2008年1月至2014年12月v.B肿块切除术后行保乳手术治疗的45例浸润性导管癌(inv.siv. ductal carcinoma,IDC)患者(v.B组)。选取同一时期单发、直径小于2cm、肿块切除活检后行保乳手术的147例IDC患者为对照组。分析并比较两组患者的临床病理特征与预后。结果:v.B组肿块均单发、直径v.B手术只行1次穿刺,穿刺点距离肿块的平均距离为(2.52±0.89)cm。中位切割8次,影像学检查示完全切除,平均手术时间(25.4±7.6)min,术中未发生活动性出血。保乳手术距v.B术平均(4.50±0.92)d;局部扩大切除病灶的各个切缘均阴性;无患者发生肿瘤细胞针道或皮肤穿刺点种植;3例残腔残留少量导管原位癌病灶,但无浸润性癌灶。v.B组与对照组平均年龄、年龄构成、肿块直径、肿瘤组织学分级、脉管侵犯、淋巴结分期、前哨淋巴结阳性率、肿瘤分子分型及辅助治疗、腋窝手术差异均无统计学意义。两组间5年无病生存期(disease-free surv.v.l,DFS)和5年总生存期(ov.rall surv.v.l,OS)差异均无统计学意义。结论:v.B切除不可触及的较小乳腺癌肿块后续行保乳手术安全可行,值得进一步大样本研究。

关键词：真空辅助活检乳腺癌保乳手术超声引导

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IGRT技术在肺癌SBRT治疗靶区位置误差测定中的应用

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中国临床医学 2016年第6期23卷 841-845页

作者：王昌民胡伟刚彭佳元蔡旭伟傅小龙许青复旦大学附属肿瘤医院放疗科复旦大学上海医学院肿瘤学系上海200032 上海交通大学附属胸科医院放疗科上海200030

目的:探讨图像引导放射治疗(image guided radiation therapy,IGRT)技术在测定并校正肺部恶性肿瘤体部立体定向放射治疗(stereotactic body radiation therapy,SBRT)过程中靶区位置误差的意义。方法:选择复旦大学附属肿瘤医院收治的14... 详细信息

目的:探讨图像引导放射治疗(image guided radiation therapy,IGRT)技术在测定并校正肺部恶性肿瘤体部立体定向放射治疗(stereotactic body radiation therapy,SBRT)过程中靶区位置误差的意义。方法:选择复旦大学附属肿瘤医院收治的14例肺部恶性肿瘤并接受SBRT的患者。每次治疗前后均进行千伏级锥形束CT(kv.CBCT)扫描,与计划CT图像进行在线配准,校正误差后进行治疗。治疗后再次进行CBCT扫描并配准。分别记录治疗前后靶区位置误差。根据临床靶区(CTv.-计划靶区(PTv.外放公式MPTv.外放)=2.5Σ+0.7σ计算PTv.扩大小。结果:治疗前靶区位置左右、头脚、腹背方向误差最大值分别为10.0mm、16.9mm、8.7mm,误差平均值分别为(2.4±2.8)mm、(3.4±4.6)mm、(2.9±3.4)mm。在线校正并治疗后,靶区位置左右、头脚、腹背方向的误差最大值分别为7.6mm、4.6mm、7.0mm,误差平均值分别为(2.1±2.0)mm、(1.5±1.6)mm、(1.7±2.0)mm。无图像引导PTv.扩大小为左右7.96mm、头脚11.72mm、腹背9.63mm,有图像引导并在线校正PTv.扩大小为左右6.65mm、头脚4.87mm、腹背5.65mm。结论:IGRT技术可即时校正SBRT治疗前由摆位引起的靶区位置误差,并测定治疗过程中的靶区位置移动,能提高治疗精度,并有助于PTv.扩的制定。

关键词：图像引导放射治疗体部立体定向放射治疗误差计划靶区

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