HIV感染真的被“治愈”了吗?

人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染靶细胞需要识别细胞表面CD4分子及其辅助受体,C-C趋化因子受体5 (C-C chemokine receptor type 5,CCR5)和C-X-C趋化因子受体4 (C-X-C-motif receptor 4,CXCR4)是HIV识别靶细胞的两种重要辅助受体。CCR5Δ32基因突变使得HIV无法识别CCR5受体,从而阻止嗜CCR5的HIV病毒株入侵靶细胞。"柏林病人"和"伦敦病人"正是利用这一原理,通过移植携带纯合子CCR5Δ32突变基因的异基因骨髓,实现了停用抗病毒药物后病毒无反弹的目标,故而被誉为HIV感染"治愈"案例。然而,这一成功是否存在偶然性?事实上,人群中携带CCR5Δ32纯合子基因突变概率极低、异基因骨髓配型十分困难、骨髓移植医疗费用昂贵、移植后HIV病毒株嗜性迁移等客观因素的存在,使得通过携带纯合子CCR5Δ32基因突变异基因骨髓移植法实现HIV感染者停用抗病毒药物且保持病毒不反弹的目标困难重重。因此,"柏林病人"和"伦敦病人"的成功经验为治疗HIV感染提供了新的方向和希望,但如认为HIV感染已被"治愈"为时尚早,需进一步研究证实。     

连续重整缠绕管式换热器的研制及工业应用

过去连续重整装置的混合进料换热器都是采用全焊接板壳式或直管立式换热器,由于结构原因,一直存在传热效率低或易损坏的问题,使得装置操作费用高、影响长周期运行。介绍了一种兼具板壳式换热器和管壳式换热器优点的,在连续重整装置中首次采用的缠绕管式换热器,作为新型的混合进料换热器的设计、研制和应用情况。该设备具有优良的传热工艺性能,又具有耐高温高压、抗操作波动的特点,是连续重整装置中较为理想的高效、高可靠性的设备。     

斜入射条件下角锥棱镜光学特性分析

角锥棱镜具有严格的后向反射特性。激光斜入射条件下,会造成角锥棱镜有效反射面积的减小及附加光程差,对激光主动探测及激光精确测距产生影响。利用几何光学原理,建立了斜入射条件下角锥棱镜有效反射面积数学模型,针对激光精确测距要求,推导了附加光程差与入射角的关系。理论分析及数值仿真结果表明,激光主动探测系统回波功率随入射角的增大而减小,不同的入射方位角对应不同的最大可探测入射角。对于给定的角锥棱镜,测距精度随入射角的增大而减小,在角锥棱镜最大允许入射范围内,测距精度误差可达2.85 mm。这对角锥棱镜的设计和实际应     

连续重整催化剂密度分级技术的应用

海南炼油化工有限公司1.2 Mt/a连续重整装置首次大检修卸剂期间,约10.17 t铂重整催化剂被装置运行中产生的滞底高碳催化剂污染,采用颗粒状催化剂振动流态化密度分级技术对其进行分级处理,回收低碳催化剂4.71 t.开工过程中未发生再生器床层超温现象,避免了催化剂高温失活、再生器约翰逊网高温烧穿等现象发生,催化剂性能...     

重整预加氢反应器压力降过大原因分析及对策

2009年中国石油化工股份有限公司塔河分公司催化重整装置预加氢反应器压力降增大,装置生产能力受到限制,被迫停工。从原料油性质、反应器顶部结垢、催化剂床层积炭积盐、催化剂粉化等方面分析了预加氢反应器压力降过大的原因,提出并实施了在催化剂撇头表面装填HPT系列加氢脱铁保护剂,严格控制原料油性质,检修时及时对炉管清焦,加强平稳操作等手段,使催化剂床层压力降稳定在46 kPa以下,达到了理想的操作效果,并提出了装置长期运转建议。     

噬菌体随机肽库技术筛选抗CCR5单克隆抗体的识别表位

目的利用噬菌体随机肽库技术筛选趋化因子受体5(CCchemokine receptor 5,CCR5)单克隆抗体的识别表位。方法用抗CCR5单克隆抗体筛选噬菌体随机12肽库,采用双抗体夹心ELISA法鉴定噬菌体阳性克隆,挑取阳性克隆测定DNA序列,推导其氨基酸序列并进行同源性分析。结果从噬菌体随机12肽库中筛选出30株可与抗CCR5单抗特异结合的噬菌体克隆,其中多数克隆呈现核心序列HY-TC-SS-XX-P/FYS-X,该序列与CCR5的一级序列ECL2具有一定的同源性。结论 HY-TC-SS-XX-P/FYS-X序列是抗CCR5单抗的识别表位。     

Potent CCR3 Receptor Antagonist,SB328437, Suppresses Colonic Eosinophil Chemotaxis and Inflammation in the Winnie Murine Model of Spontaneous Chronic Colitis

Eosinophils and their regulatory molecules have been associated with chronic intestinal inflammation and gastrointestinal dysfunctions; eosinophil accumulation in the gut is prominent in inflammatory bowel disease (IBD). The chemokine receptor CCR3 plays a pivotal role in local and systemic recruitment and activation of eosinophils. In this study, we targeted CCR3-ligand interactions with a potent CCR3 receptor antagonist, SB328437, to alleviate eosinophil-associated immunological responses in the Winnie model of spontaneous chronic colitis. Winnie and C57BL/6 mice were treated with SB328437 or vehicle. Clinical and histopathological parameters of chronic colitis were assessed. Flow cytometry was performed to discern changes in colonic, splenic, circulatory, and bone marrow-derived leukocytes. Changes to the serum levels of eosinophil-associated chemokines and cytokines were measured using BioPlex. Inhibition of CCR3 receptors with SB328437 attenuated disease activity and gross morphological damage to the inflamed intestines and reduced eosinophils and their regulatory molecules in the inflamed colon and circulation. SB328437 had no effect on eosinophils and their progenitor cells in the spleen and bone marrow. This study demonstrates that targeting eosinophils via the CCR3 axis has anti-inflammatory effects in the inflamed intestine, and also contributes to understanding the role of eosinophils as potential end-point targets for IBD treatment.     

Biological Profiling of Anti‐HIV Agents and Insight into CCR5 Antagonist Binding Using in silico Techniques

Molecular requirements and determinants for efficient binding to CCR5 were interpreted by computational techniques based on comparative receptor structure modeling, advanced 3D‐QSAR, docking, and shape‐based virtual screening of commercially available entry blockers. Results of this study may be valuable for predicting new HIV entry‐blocking leads.

     

Increased L-Selectin on Monocytes Is Linked to the Autoantibody Profile in Systemic Sclerosis

Monocytes are known to be implicated in the pathogenesis of systemic sclerosis (SSc), as they exert prominent migratory, adhesive, and chemotactic properties. The aim of our study was to characterize the surface expression of adhesion/chemotactic molecules (CD62L, CD11b, CCR2, CCR5) on the SSc monocytes and determine correlations with the clinical presentation of SSc. We included 38 SSc patients and 36 healthy age-and sex-matched controls. Isolated monocytes, as well as in vitro serum-treated monocytes, were analyzed by flow cytometry; additionally, soluble CD62L was measured in serum. We found increased soluble CD62L in the SSc serum samples and increased CD62L on the surface of the SSc monocytes in the in the same set of patients. Among samples with determined SSc-specific autoantibodies, the surface CD62L was the lowest in patients positive for anti-PM/Scl autoantibodies and the highest in patients with anti-topoisomerase I autoantibodies (ATA). The treatment of isolated healthy monocytes with ATA-positive SSc serum resulted in increased surface CD62L expression. Moreover, surface CCR5 was reduced on the monocytes from SSc patients with interstitial lung disease but also, along with CCR2, negatively correlated with the use of analgesics/anti-inflammatory drugs and immunosuppressants. In conclusion, increased CD62L on SSc monocytes, particularly in ATA-positive patients, provides new insights into the pathogenesis of SSc and suggests CD62L as a potential therapeutic target.     

连续重整反应器的制造和检验

以某连续重整反应器制造为例，介绍了连续重整反应器的制造技术要点、无损检测技术要求以及制造过程中应注意的问题。为制造连续重整反应器以及制造类似压力容器产品的制造工艺和产品制造质量控制方面提供参考，为连续重整反应器国产化提供制造经验。