Developing nanozymes for cancer therapy has attracted great attention from researchers. However, enzymes-loaded magnetic particles triggered by both a low-frequency vibrating magnetic field (VMF) and laser for inhibiting tumor growth have never been reported. Herein, we developed a magnetic nanozyme with 3D flower-like nanostructures for cancer therapy. Specifically, the flower-like nanozymes exposed to a VMF could efficiently damage the mitochondrial membrane and cell structure, and inhibit tumor growth through magneto-mechanical force. In parallel, magnetic nanozymes in a weak acid environment containing glucose could generate abundant hydrogen peroxide through glucose oxidase-catalyzed oxidation of glucose, and further significantly promote the Fenton reaction. Interestingly, both glucose oxidase- and Fenton-based catalytic reactions were significantly promoted by the VMF exposure. Flower-like magnetic nanospheres upon a near-infrared laser irradiation could also damage cancer cells and tumor tissues through photothermal effect. The cell-killing efficiency of magnetic nanozymes triggered by the VMF or laser significantly increased in comparison with that of nanozymes without exposures. Mouse tumors grown after injection with magnetic nanozymes was inhibited in a significant way or the tumors disappeared after exposure to a VMF and laser due to the synergistic effect of four major stimuli, viz., magneto-mechanical force, photothermal conversion, improved Fenton reaction, and intratumoral glucose consumption-based starvation effect. This is a great platform that may be suitable for treating many solid tumors.

MicroRNAs have been studied extensively in neurodegenerative diseases. In a previous study, miR-153 promoted neural differentiation and projection formation in mouse hippocampal HT-22 cells. However, the pathways and molecular mechanism underlying miR-153-induced neural differentiation remain unclear. To explore the molecular mechanism of miR-153 on neural differentiation, we performed RNA sequencing on miR-153-overexpressed HT-22 cells. Based on RNA sequencing, differentially expressed genes (DEGs) and pathways in miR-153-overexpressed cells were identified. The Database for Annotation, Visualization and Integrated Discovery and Gene Set Enrichment Analysis were used to perform functional annotation and enrichment analysis of DEGs. Targetscan predicted the targets of miR-153. The Search Tool for the Retrieval of Interacting Genes and Cytoscape, were used to construct protein-protein interaction networks and identify hub genes. Q-PCR was used to detect mRNA expression of the identified genes. The expression profiles of the identified genes were compared between embryonic days 9.5 (E9.5) and E11.5 in the embryotic mouse brain of the GDS3442 dataset. Cell Counting Kit-8 assay was used to determine cell proliferation and cellular susceptibility to amyloid β-protein (Aβ) toxicity in miR-153-overexpressed cells. The results indicated that miR-153 increased cell adhesion/Ca2+ (Cdh5, Nrcam, and P2rx4) and Bdnf/Ntrk2 neurotrophic signaling pathway, and decreased ion channel activity (Kcnc3, Kcna4, Clcn5, and Scn5a). The changes in the expression of the identified genes in miR-153-overexpressed cells were consistent with the expression profile of GDS3442 during neural differentiation. In addition, miR-153 overexpression decreased cellular susceptibility to Aβ toxicity in HT-22 cells. In conclusion, miR-153 overexpression may promote neural differentiation by inducing cell adhesion and the Bdnf/Ntrk2 pathway, and regulating electrophysiological maturity by targeting ion channels. MiR-153 may play an important role in neural differentiation; the findings provide a useful therapeutic direction for neurodegenerative diseases.

The use of magneto-mechanical force to kill cancer cells has attracted significant attention in recent years. However, many reports have focused on in vitro experiments with a single treatment. Herein, CaO2-coated Fe3O4 core—shell magnetic nanoenzymes (Fe3O4/CaO2) are developed for low frequency vibrating magnetic field (VMF)-induced multimodal cancer therapy. Fe3O4/CaO2 are shown to efficiently generate O2, H2O2, and ·OH through hydrolysis of CaO2 and a CaO2-strengthened Fenton reaction, killing laryngeal carcinoma cells and inhibiting mouse tumor growth (chemodynamic therapy (CDT)). Both Fe3O4 and Fe3O4/CaO2 triggered by a VMF are shown to damage the cytoskeleton of cancer cells through magneto-mechanical force (maxima: 223 piconewtons or larger by Fe3O4/CaO2 aggregations) and induce the generation of intracellular reactive oxygen species (ROS), and the VMF-triggered Fe3O4/CaO2 is shown to generate additional intracellular ROS. Upon exposure to a VMF, the cell killing efficiency and tumor growth inhibition were further significantly improved by Fe3O4/CaO2 through CDT, magnetomechanical force, force-induced ROS, and the cytotoxicity of Ca2+ ions. In addition, the Fe3O4/CaO2 nanoenzymes and VMF-induced treatment are shown to be safe for mice. The results of this study open the door for treating solid tumors without inducing multidrug resistance through the combination of CDT and force.

Bacteria-mediated cancer therapy has attracted much attention in recent years. However, using magnetotactic bacteria as both a drug carrier and a drug for cancer therapy has never been reported. Herein, we incorporated a photosensitizer chlorin e6 (Ce6) into the M. magneticum strain AMB-1 through a chemical bond or physical blending. A chemical reaction was finally selected for fabricating AMB-1/Ce6 micromotors, as such micromotors exhibited high drug payload and normal bacterial activities. An interesting finding is that AMB-1 is not only an excellent drug carrier but also a unique drug that could inhibit mouse tumor growth. We also, for the first time, demonstrated that AMB-1 is a photosensitizer. Under laser irradiation, micromotors killed cancer cells with high efficiency due to the high-level reactive oxygen species generated by the micromotors. Micromotors could target the hypoxic and normoxic regions in vitro via both the active swimming of AMB-1 and external magnetic field guidance. Micromotors showed high tumor-homing ability owing to the above double targeting mechanisms. After injection with the micromotors followed by magnetic field guidance and laser irradiation, the growth of mouse tumors was significantly inhibited owing to the AMB-1-based biotherapy and phototoxicity of AMB-1 and Ce6. This micromotor-mediated tumor-targeted therapy strategy may be a great platform for treating many types of solid tumors.

According to the characteristics of interdisciplinary and applied knowledge teaching and skill training of Resource Botany course, experiments related to the quality evaluation and application of fiber plant resources were designed and developed. The results of implementation show that through the excavation of fiber plant resources and the design of a series of experiments, the purpose that students can carry out self-selectable exploratory series of experiments was achieved, and the feedbacks from students were well. As a new measure to explore the cultivation of high-quality and applied talents in life science in China, it is worthwhile to apply such teaching method in this subject.

"植物愈伤组织培养研究型实验项目"的教学采用微信平台和开放课堂混合教学模式.微信平台主要用于开展相关理论内容和实验仪器操作的学习、研究型实验方案的设计、瓶颈问题及实验结果讨论等.开放课堂主要用于研究型实验方案的实施、结果观察记录及教师对实验数据分析的点评等.该实验项目建立以"教师引导+学生为主体"的教学模式,促使参课学生在团队协作能力、问题分析能力、思维创新能力等方面均得到较大的提升.

经过不断的实验教学改革与实践,逐渐形成一套与专业培养目标相适应的实验教学体系.在课程的设置上,采用面授实验与线上实验相结合的实验教学模式,形成"验证性实验—综合性实验—设计性实验—研究性实验—虚拟仿真实验"逐步进阶的创新型实验教学体系,将学生的能力培养贯穿于实验教学的全过程.学生在学习实验课程过程中,专业技能、实践应用能力、研究思辨能力、科研创新能力、信息化素养和实践拓展能力等方面都得到了显著提升.

为优化分子生物学精品实验项目,以"通过报告基因检测细胞内cAMP水平变化"实验为例进行研究.结果显示通过开放实验室,扩展实验过程,完善实验操作,尤其是让学生充分了解整个实验流程,亲自参与各个实验步骤,掌握实验操作每个细节,大大增强了学生的操作技能,加深了学生对实验内容的认识与理解.同时从实验过程优化入手,更新仪器,提高实验准确性;优化实验设计,拓展实验深度和广度.培养学生实验数据处理和分析总结能力,为本科实验教学建立"大数据"提供依据.总之该研究使学生逐步形成以自主式、合作式、研究式相结合的学习方式,激发学生兴趣,锻炼科研思维,培养运用科研思维和系统组合各种实验技术来实现科研目标的能力.

本文以提升学生操作使用生物电镜的实践能力为教学目标,基于虚拟仿真技术,建成了"细胞超微结构分析虚拟仿真实验教学系统".通过虚拟仿真实验再现了生物样品制备、超薄切片、染色及透射电镜观察超微结构的全过程.通过教学实践表明:生物电镜技术虚拟仿真实验打破了传统线下生物电镜实验在设备、时间、空间等方面的限制,能够有效地促进学生自主学习,提高生物电镜实验线下实践教学效率,为创新型人才培养创造了条件.

Alzheimer’s disease (AD) is a growing health concern worldwide. MicroRNAs (miRNAs) have been extensively studied in many diseases, including AD. To identify differentially expressed miRNAs (DEmiRNAs) and genes specific to AD, we used bioinformatic analyses to investigate candidate miRNA-mRNA pairs involved in the pathogenesis of AD. We focused on differentially expressed genes (DEGs) that are targets of DEmiRNAs. The GEO2R tool and the HISAT2-DESeq2 software were used to identify DEmiRNAs and DEGs. Bioinformatic tools available online, such as TAM and the Database for Annotation, Visualization and Integrated Discovery (DAVID), were used to perform functional annotation and enrichment analysis. Targets of miRNAs were predicted using the miRTarBase. The Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape, which are available online, were utilized to construct protein–protein interaction (PPI) networks and identify hub genes. Furthermore, transcription factors (TFs) encoded by the DEGs were predicted using the TransmiR database and TF-miRNA-mRNA networks were constructed. Finally, the expression profile of a hub gene in peripheral blood mononuclear cells was compared between healthy individuals and AD patients. We identified 26 correlated miRNA-mRNA pairs. In the parietal lobe, miRNA-mRNA pairs involved in protein folding were enriched, and in the frontal lobe, miRNA-mRNA pairs involved in synaptic transmission, abnormal protein degradation, and apoptosis were enriched. In addition, HSP90AB1 in peripheral blood mononuclear cells was found to be significantly downregulated in AD patients, and this was consistent with its expression profile in the parietal lobe of AD patients. Our results provide brain region-specific changes in miRNA-mRNA associations in AD patients, further our understanding of potential underlying molecular mechanisms of AD, and reveal promising diagnostic and therapeutic targets for AD.

miR-155 is associated with the promotion of tumorigenesis. Herein, we indicate that abnormal miR-155 was negatively correlated with the expression of P21WAF1/Cip1. Our results suggest that miR-155 alters the transcriptome and inhibits the expression of H3F3A in liver cancer cells. Therefore, miR-155 inhibits the methylation modification of histone H3 on the 27th lysine. Notably, on the one hand, miR-155-dependent CTCF loops cause the CDK2 interacting with cyclin E in liver cancer cells; on the other hand, miR-155 promotes the phosphorylation modification of CDK2 by inhibiting H3F3A. Subsequently, miR-155 competitively blocks the binding of RNA polymerase II (RNA Pol II) to the P21WAF1/CIP1 promoter by increasing the phosphorylation of CDK2, inhibiting the transcription and translation of P21WAF1/CIP1. Strikingly, excessive P21WAF1/CIP1 abolishes the cancerous function of miR-155. In conclusion, miR-155 can play a positive role in the development of liver cancer and influence a series of gene expression through epigenetic regulation.

Hollow mesoporous particles for drug delivery and cancer therapy have attracted significant attention over recent decades. Here, we develop a simple and highly efficient strategy for preparing fluorescent hollow mesoporous carbon spheres (HMCSs). Compared with typical carbon materials such as fullerene C60, carbon nanotubes, reduced graphene oxide, and carbon nanohorns; HMCSs showed fewer effects on cell cycle distribution and lower toxicity to cells. Ten different drugs were incorporated into the HMCSs, and the maximum loading efficiency reached 42.79 ± 2.7%. Importantly, microwaves were found to improve the photothermal effect generated by HMCSs when combined with 980-nm laser irradiation. The cell killing and tumor growth inhibition efficiencies of HMCSs and drug-loaded HMCSs under co-irradiation with laser and microwaves were significantly improved compared with those under laser irradiation alone. After local administration HMCSs were only distributed in tissue at the injection site. HMCSs showed almost no toxicity in mice after local injection and could be completely removed from the injection site.

该文通过研究认为,生命科学实验教学中心经过多年的实践探索,初步建立了实验教学中心的规范化安全管理体系,包括实验室安全基础设施建设、教室规范化使用、课程规范化管理、仪器设备规范化操作、生化试剂规范化管理、耗材规范化储存以及安全巡查制度.安全规范化管理体系的建立保障了实验教学中心的稳定发展,促进了教育教学质量的全面提升.

MicroRNA24-2 (miR24-2) is associated with human tumorigenesis; however, its molecular mechanisms are poorly understood. Herein, our findings demonstrate that miR24-2 promotes the proliferation ability in vitro and the tumorigenic ability in vivo in human liver cancer stem cells (hLCSCs). Mechanically, the miR24-2 targets for 3' UTR (2,627-2,648) of protein arginine methyltransferase 7 (PRMT7) inhibit the translational ability of prmt7 gene. Moreover, miR24-2 inhibits the di-/tri-methylation of histone H4 arginine 3 by reducing PRMT7 and then promotes the expression of Nanog via long noncoding RNA HULC. Notably, miR24-2 inhibits histone deacetylase HDAC3 through miR675, which promotes the acetylation of histone H4 at lysine 16. Subsequently, miR24-2 enhances the interaction between LC3 and ATG4 dependent on PI3K and triggers cellular autophagy. Strikingly, miR24-2 inhibits the degradation of pyruvate kinase M1 via autophagosome-P62 in hLCSCs. Furthermore, miR24-2 enhances the activity of Src by promoting the binding of PKM1 to the Src promoter regions in hLCSCs. In particular, our results also indicate that src gene determines the oncogenic functions of miR24-2. These results provided a valuable theoretical basis for the discovery of liver cancer therapeutic targets and diagnosis markers based on miR24-2.

"对分课堂"教学模式是一种新型教学模式,它强调内化和吸收过程,突出课堂讨论过程,使学生在听课的基础上开展个性化学习和思考,从而让学生在充分准备的前提下开展课堂讨论.在细胞工程实验教学中应用的"对分课堂"教学模式,从实验教学理念、实验教学方法、实验考核方式等方面开展教学改革.研究了"对分课堂"在生物技术专业实验课教学中的应用,收集了典型教学案例,取得良好的实验教学效果.

Circular RNA (CircRNA) is a newly identified special class of non-coding RNA (ncRNA) that plays an important regulatory role in the progression of certain diseases. Herein, our results indicate that CircMEG3 is downregulated expression and negatively correlated with the expression of telomerase-related gene Cbf5 in human liver cancer. Moreover, CircMEG3 inhibits the growth of human liver cancer stem cells in vivo and in vitro. CircMEG3 inhibits the expression of m6A methyltransferase METTL3 dependent on HULC. Moreover, CircMEG3 inhibits the expression of Cbf5, a component of telomere synthetase H/ACA ribonucleoprotein (RNP; catalyst RNA pseudouracil modification) through METTL3 dependent on HULC. Thereby, CircMEG3 inhibits telomerase activity and shortens telomere lifespan dependent on HULC and Cbf5 in human liver cancer stem cell. Strikingly, increased Cbf5 abrogates the ability of CircMEG3 to inhibit malignant differentiation of human liver cancer stem cells. In summary, these observations provide important basic information for finding effective liver cancer therapeutic targets.

BACKGROUND:The functions of HULC have been demonstrated in several cancers. However, its mechanism has not been elucidated in human liver cancer stem cells.METHODS:Liver cancer stem cells were isolated from Huh7 cells; gene infection and tumorigenesis test in vitro and in vivo were performed.RESULTS:We demonstrate that HULC promotes growth of liver cancer stem cells in vitro and in vivo. Mechanistically, HULC enhances the expression of Sirt1 dependent on miR675 and then induces the cellular autophagy through Sirt1. HULC enhances CyclinD1 and thereby increases pRB and inhibited P21 WAF1/CIP 1 via autophagy-miR675-PKM2 pathway in human liver cancer stem cells. Ultimately, our results demonstrate that CyclinD1 is required for the oncogenic functions of HULC in liver cancer stem cells.CONCLUSIONS:It reveals the key molecular signaling pathways for HULC and provides important basic information for finding effective tumor therapeutic targets based on HULC.

Several microRNAs are associated with carcinogenesis and tumour progression. Herein, our observations suggest both miR24-2 and Pim1 are up-regulated in human liver cancers, and miR24-2 accelerates growth of liver cancer cells in vitro and in vivo. Mechanistically, miR24-2 increases the expression of N6-adenosine-methyltransferase METTL3 and thereafter promotes the expression of miR6079 via RNA methylation modification. Furthermore, miR6079 targets JMJD2A and then increased the tri-methylation of histone H3 on the ninth lysine (H3K9me3). Therefore, miR24-2 inhibits JMJD2A by increasing miR6079 and then increases H3K9me3. Strikingly, miR24-2 increases the expression of Pim1 dependent on H3K9me3 and METTL3. Notably, our findings suggest that miR24-2 alters several related genes (pHistone H3, SUZ12, SUV39H1, Nanog, MEKK4, pTyr) and accelerates progression of liver cancer cells through Pim1 activation. In particular, Pim1 is required for the oncogenic action of miR24-2 in liver cancer. This study elucidates a novel mechanism for miR24-2 in liver cancer and suggests that miR24-2 may be used as novel therapeutic targets of liver cancer.