细胞核凋亡过程中核基质的变化

在非细胞体系中以细胞色素C作为诱导剂，诱导小鼠有细胞核发生凋亡，在透射电子显微镜及扫描电子显微镜下观察到凋亡的一现典型的凋亡形态学特征，整装电镜的结果显示，在凋亡过程中核基质结构被破坏，但核基质结构仍然存在，并最终形成凋亡小体的结构基础。     

双氢青蒿素诱导前列腺癌PC-3细胞凋亡的形态学研究

目的：研究双氢青蒿素（DHA）诱导前列腺癌PC-3细胞凋亡作用,并观察其形态学变化。方法：以前列腺癌PC-3细胞为研究对象,在体外经不同浓度的DHA处理48小时后,扫描电镜（SEM）观察细胞凋亡;并建立PC-3细胞裸鼠种植瘤模型,20只模型鼠随机分为对照组、溶剂组、DHA大剂量组及DHA小剂量组,经13天干预后,透射电镜（TEM）观察肿瘤组织形态学变化,体视学分析肿瘤微血管密度（MVD）。结果：PC-3细胞经DHA处理后,SEM观察到典型的凋亡细胞;裸鼠种植瘤经治疗后,TEM观察肿瘤组织中散在凋亡细胞及凋亡小体,且DHA大小剂量组MVD均低于对照组（P〈0．05）。结论：DHA具有较强的抗肿瘤作用,其作用机制可能与诱导肿瘤细胞凋亡有关。     

小鼠肝细胞核凋亡的超微结构观察

用胡萝卜细胞胞浆制备的非细胞体系中 ,加入纯化的小鼠肝细胞核并以细胞色素 C诱导细胞核发生凋亡。在透射电子显微镜和扫描电子显微镜下都观察到凋亡的细胞核呈现典型的凋亡形态学特征 ,例如染色质的凝集及趋边化 ,细胞核表面形成空泡化结构并有大量的凋亡小体结构出现。在此基础上对凋亡小体结构在形成及排出核外的过程进行了详细的观察和分析。     

全反式维甲酸对卵巢上皮性癌荷瘤鼠干预后肿瘤细胞的超微结构变化

探讨全反式维甲酸(all-trans retinoic acid,ATRA)对裸鼠卵巢上皮性癌细胞(CAOV3)荷瘤动物模型干预后肿瘤细胞超微结构的变化及意义。每只荷瘤裸鼠经胃管针给药ATRA剂量为2mg/kg 2d×4周,取新鲜肿瘤组织进行电镜制样观察。结果显示CAOV3荷瘤裸鼠经ATRA干预后,肿瘤细胞出现细胞表面微绒毛明显增多,细胞间常见桥粒和紧密连接,胞浆内粗面内质网、线粒体和糖原颗粒增加,还有发育良好的高尔基体,细胞核异染色质增加,常染色质减少,偶见被吞噬的凋亡细胞。上述超微结构变化提示ATRA可诱导和促进CAOV3细胞分化,抑制肿瘤生长。     

小鼠肝细胞核调亡的超微结构观察

用胡萝卜细胞胞浆制备的非细胞体系中,加入纯化的小鼠肝细胞核并以细胞色素C诱导细胞核发生调亡。在透射电子显微镜和扫描电子显微镜下都观察到凋亡的细胞核呈现典型的调亡形态学特征,例如染色质的凝集及趋边化,细胞核表面形成空泡化结构并有大量的凋亡小体结构出现。在此基础上对调亡小体结构在形成及排出核外的过程进行了详细的观察和分析。     

shRNA靶向干扰COX-2促进人肝癌裸鼠皮下移植瘤肿瘤细胞凋亡

目的：探讨重组干扰质粒pshRNA-COX-2对人肝癌细胞Hep3B裸鼠皮下移植瘤肿瘤细胞凋亡的促进作用。方法：重组干扰质粒pshRNA-COX-2转染Hep3B细胞并筛选后,将被成功转染的Hep3B细胞种植于裸鼠皮下,测量肿瘤大小,成瘤4周后处死裸鼠,绘制肿瘤生长曲线,RT-PCR和Western blot检测肿瘤组...     

巴西菇多糖对肝癌细胞株凋亡的影响及其机制

目的 :研究巴西菇多糖诱导人肝癌细胞株 (SMMC-772 1)凋亡的作用及机制。方法 :采用电镜、DNA电泳、免疫组化法 ,对SMMC-772 1株细胞凋亡以及凋亡抑制基因 bcl-2的表达进行检测。结果 :SMMC-772 1株细胞经巴西菇多糖处理后出现核固缩、膜起泡、凋亡小体形成 ,琼脂糖凝胶电泳呈现出典型凋亡 DNA梯状带 ,细胞内 bcl-2表达较对照组低。结论 :巴西菇多糖能诱导 SMMC-772 1株细胞发生典型凋亡 ,其抑制细胞内 bcl-2的表达 ,是诱发肿瘤细胞凋亡的机制之一。     

骨髓瘤瘤细胞的超微形态研究

本文报道了8例骨髓瘤(包括5例多发性骨髓瘤,3例轻链病)瘤细胞的超微形态改变。所见各例瘤细胞的分化程度不同,电镜下瘤细胞的形态变化较大,分化较好的瘤细胞,形态接近正常浆细胞,分化越差,异常形态特征明显。8例标本中,一例有大量核内包涵体(图1),3例有Russell小体(图2),其中一例的Russell小体特别丰富。另一例中,见到结晶体(图3)具有周期性排列的线条结构。此外,在4例骨髓瘤细胞中见到微丝,其中二例尤为显著。本文对骨髓瘤细胞在电镜下主要超微形态改变,以及核内包涵体,胞浆包涵体、胞浆微丝的     

所谓"肺硬化性血管瘤"的超微结构及组织发生

为探讨所谓“肺硬化性血管瘤”的组织发生，本文对6例标本进行病理形态学观察，着重观察其中2例的超微结构，发现实质区瘤细胞之分化较好者富于粗面内质网，可出现板层小体。此外瘤细胞间形成镶嵌连接及中间连接，细胞间隙含有分布不规则的基膜样物。这种细胞和基膜的特殊排列及密切联系，提示细胞的分化方向是Ⅱ型肺泡上皮细胞，故为本肿瘤的上皮性起源提供新的依据。     

自然杀伤细胞抗肿瘤治疗研究进展

自然杀伤(NK)细胞是最重要的抗肿瘤免疫细胞。提高NK细胞抗瘤活性的最新研究包括:同种异体NK细胞过继性免疫治疗;通过基因工程的方法使肿瘤细胞表达肿瘤抗原特异性嵌合受体;选择具有高亲和力Fc受体NK细胞,联合单克隆抗体通过ADCC效应杀伤肿瘤细胞;提高靶细胞对NK细胞介导的凋亡的敏感性;解除抑制因素对NK细胞的影响;促进NK细胞浸润肿瘤组织及淋巴结;NK细胞不同亚群间的功能差异研究。     

Targeted Delivery of Apoptotic Cell-Derived Nanovesicles prevents Cardiac Remodeling and Attenuates Cardiac Function Exacerbation

The modulation of inflammatory responses plays an important role in the pathobiology of cardiac failure. In a natural healing process, the ingestion of apoptotic cells and their apoptotic bodies by macrophages in a focal lesion result in resolution of inflammation and regeneration. However, therapeutic strategies to enhance this natural healing process using apoptotic cell-derived biomaterials have not yet been established. In this study, apoptotic bodies-mimetic nanovesicles derived from apoptotic fibroblasts (ApoNVs) conjugated with dextran and ischemic cardiac homing peptide (CHP) (ApoNV-DCs) for ischemia-reperfusion (IR)-injured heart treatment are developed. Intravenously injected ApoNV-DCs actively targeted the ischemic myocardium via conjugation with CHP, and are selectively phagocytosed by macrophages in an infarcted myocardium via conjugation with dextran. ApoNV-DCs polarized macrophages from the M1 to M2 phenotype, resulting in the attenuation of inflammation. Four weeks after injection, ApoNV-DCs attenuated cardiac remodeling, preserved blood vessels, and prevented cardiac function exacerbation in IR-injured hearts. Taken together, the findings may open a new avenue for immunomodulation using targeted delivery of anti-inflammatory nanovesicles that can be universally applied for various inflammatory diseases.     

Measurement of wall charge and capacitance variation for a single cell in the AC plasma display panel

Real-time dynamic measurements are performed on a single cell in a standard commercially available large plasma panel. The measurements determine cell response to variations in address pulses, sustain waveforms, or priming from neighboring cells. The wall-charge measurement indicates the internal dielectric surface charge and the capacitance measurement indicates the existence of a plasma in the gas volume. These measurements have shown that neighboring on cells can cause a large wall-charge transfer in off cells that results in reduced write and sustain voltage margins. Direct wall-charge measurements allows use of a simple technique for determination of the voltage transfer curve of the plasma cell which greatly aids device characterization. The capacitance measurement has shown that a plasma exists in commercial MgO panels for 10-15 µs after the discharge-current peak. The capacitance and wall-charge measurements can be combined to give simultaneous real-time results.     

Appearance of the reticular cells which trap antigens in the rat lymph node in postnatal development.

The cells binding and retaining immune complexes on their cell surface existed in rat lymph nodes with no germinal centers. This study attempted to clarify the relationship between the two types of cells, reticular cells and follicular dendritic cells (FDCs), in the rat lymph node at early stages of postnatal development by immuno-electron microscopy on anti-horseradish peroxidase (HRP) and HRP injected rat. On the 19th and 23rd day after birth, germinal centers were not yet constructed nor were typical FDCs visible. However, immune complex binding cells were observed on the 23rd day, and not on the 19th. HRP reactive materials (immune complexes) were localized between lymphocytes and large lucent cells, making meshworks. They were revealed by electron microscopy on the cell surface which invaginated into the cytoplasm. The HRP reactive cells extended their cytoplasmic processes and formed a connection by their processes. They were reticular cells which enclosed reticular fibers by their cytoplasmic processes or contacted with reticular fibers closely. The reticular cells may be precursors of the FDCs.     

高可靠性Cu BCE a-IGZO TFTs的制作

背沟道刻蚀型（BCE）非晶氧化铟镓锌薄膜晶体管（a-IGZO TFT）具有工艺简单、寄生电容小以及开口率高等优点,但BCE IGZO器件背沟道易受酸液和等离子体损伤,进而引起TFT均匀性和稳定性等方面问题,随着GOA技术的导入,对TFT器件电学性能的均匀性和稳定性提升的要求也日益迫切,因此开发高信赖性BCE IGZO TFT是技术和市场的迫切要求。本文主要分析了基于IGZO的背沟道刻蚀型薄膜晶体管电学性质,通过优化钝化层材料,色阻材料以及GOA TFT结构等削弱因背沟道水汽吸附引起的器件劣化,偏压温度应力测试结果显示优化后的TFT展现了良好的稳定性——在80℃,栅极30 V负向偏压条件下,2 000 s的ΔV_th小于1 V。最终,利用优化的IGZO TFT制作了215.9 mm（85 in）8K4K 120 Hz液晶显示器。     

Macrophage-Mediated Tumor Cell Phagocytosis: Opportunity for Nanomedicine Intervention

Macrophages are one of the most abundant non-malignant cells in the tumor microenvironment, playing critical roles in mediating tumor immunity. As important innate immune cells, macrophages possess the potential to engulf tumor cells and present tumor-specific antigens for adaptive antitumor immunity induction, leading to growing interest in targeting macrophage phagocytosis for cancer immunotherapy. Nevertheless, live tumor cells have evolved to evade phagocytosis by macrophages via the extensive expression of anti-phagocytic molecules, such as CD47. In addition, macrophages also rapidly recognize and engulf apoptotic cells (efferocytosis) in the tumor microenvironment, which inhibits inflammatory responses and facilitates immune escape of tumor cells. Thus, intervention of macrophage phagocytosis by blocking anti-phagocytic signals on live tumor cells or inhibiting tumor efferocytosis presents a promising strategy for the development of cancer immunotherapies. Here, the regulation of macrophage-mediated tumor cell phagocytosis is first summarized, followed by an overview of strategies targeting macrophage phagocytosis for the development of antitumor therapies. Given the potential off-target effects associated with the administration of traditional therapeutics (for example, monoclonal antibodies and small molecule inhibitors), the opportunity for nanomedicine in macrophage phagocytosis intervention is highlighted.     

Co‐delivery of Cell‐permeable Chimeric Apoptosis AVPIR8 Peptide/p53 DNA for Cocktail Therapy

The tetra‐peptide AVPI, derived from the Smac/DIABLO N‐terminal epitope, is able to trigger caspase activation and apoptotic process. However, its clinical value is greatly hampered by the nature of membrane‐impermeability. Herein, the cell‐penetrating chimeric apoptotic peptide of AVPIR₈ is synthesized, of which the apoptosis‐induced AVPI is strategically blended with the cell‐penetrating sequence of octaarginine (R₈). The dual‐functionalized AVPIR₈ is not only potent in inducing apoptosis in tumor cells due to the cell penetration ability, but also is able to work as gene carrier for transfering the tumor suppressor p53 DNA into cells, thus constructing a co‐delivery drug system (AVPIR₈/p53). Such system efficiently promotes apoptosis in cancer cells while sparing normal cells, and its antitumor activity is further significantly enhanced in combination with doxorubicin as cocktail therapy. More importantly, the anticancer efficacy of the cocktail is demonstrated to be able to arrest tumor growth in two animal tumor models (melanoma and cervical cancers), respectively. The chemotherapeutic dose in the AVPIR₈/p53‐based cocktail is significantly reduced by 80%, compared to the monotherapy of doxorubicin. The present results show the promise of the co‐delivered AVPIR₈/p53 as adjuvant therapy for boosting the conventional chemotherapeutics, with a unique benefit of enhanced productive treatment outcomes yet greatly reduced adverse toxicity.     

Emancipating Target‐Functionalized Carbon Dots from Autophagy Vesicles for a Novel Visualized Tumor Therapy

Killing the tumor cells by a visualized targeting system is a promising strategy with which to achieve high efficiency, low side effects, and a high survival rate for tumor therapy. Here, an autophagy regulation strategy is reported by emancipating target‐functionalized carbon dots from autophagy vesicles for the efficient visualized tumor therapy. The folic acid modified N‐doped carbon dots (FN‐CDs) are selectively endocytosed (specific cellular uptake rate >93.40%) and stably existed in autophagic vacuoles in tumor cells. Next, the autophagic vacuoles are “opened” by the autophagy inhibitors. Released FN‐CDs activate both the intrinsic and extrinsic apoptotic signaling pathway and kill tumor cells efficiently. This method achieves therapeutic effects with high performance in 26 types of tumor cell lines. Animal experiments show that the 30 d survival rate of this therapeutic strategy is much higher than that with traditional drug treatment. Real‐time imaging/monitoring and its effects on the intelligent tumor therapy are also demonstrated based on the stable, strong, green emission from FN‐CDs.     

An Apoptotic Body-based Vehicle with Navigation for Photothermal-Immunotherapy by Precise Delivery and Tumor Microenvironment Regulation

Tumor precision therapy and preventing tumor recurrence and metastasis are the main challenges to tumor eradication. Herein, an apoptotic body-based vehicle with imaging navigation is developed for precise tumor delivery and photothermal-immunotherapy by IR820-conjugated apoptotic body loaded with R848 nanoparticles. The apoptotic body serves as ammunition stores as well as vehicle drive engines, while IR820 acts as a fluorescence imaging navigation and photothermal controlling system. The apoptotic body vehicle can deliver the ammunition to tumor and achieve deep penetration by macrophage-hitchhiking. Fluorescence imaging navigation opens a control window for photothermal treatment, followed by photothermal triggering of in situ vaccine formation. Further, CD47 antibody loaded hydrogel strengthens innate and adaptive immunity, simultaneously the polarization of macrophages regulates the immunosuppressive microenvironment to further promote the combined antitumor immunotherapy. With breast tumor (4T1)-bearing mice model, the apoptotic body vehicle performs excellent therapeutic efficacy for primary tumor, distant tumor, tumor metastasis, and recurrence prevention.     

Intracellular Bottom-up Synthesis of Ultrasmall CuS Nanodots in Cancer Cells for Simultaneous Photothermal Therapy and COX-2 Inactivation

The clinical application of photothermal therapy (PTT) is limited by the accuracy of thermal damage and the risk of tumor metastasis and relapse induced by hyperthermia-related inflammation. Intracellular bottom-up synthesis (iBuS) of CuS nanoparticles from small-molecule precursors inside tumor cells triggered by tumor specific stimuli is a promising strategy to enhance the precision of PTT treatment and reduce the risk of nondegradable metal nanoparticles. Herein, monolocking nanoparticles (MLNPs) with Cu-meloxicam complexes encapsulated by human serum albumin (HSA) are reported, which efficiently form CuS nanodots via the elevated concentration of endogenous H₂S inside tumor cells and meanwhile release meloxicam for anti-inflammatory effects. The intracellular bottom-up fabrication of CuS nanodots is directly visualized by TEM. An enhanced PTT effect is observed with 4T1 cells caused by additional meloxicam-induced inactivation of the COX-2 enzyme. After systemic administration, MLNPs completely ablate tumors under laser exposure, simultaneously inhibiting the inflammation induced by photothermal damage, and can be cleared via the kidney into urine. This strategy provides a new route for activated multimodal therapy, which could be applicable to precisely combat cancer.