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研究生导师是决定研究生培养质量的关键因素。一名合格的导师应当具备较高的综合素质，其中最重要的素质是师德。不仅要从严规范自己的言行，而且要刻苦钻研,不断提高自己的专业能力，从而给研究生的成长树立学习的榜样，并在研究生培养的各个环节给研究生提供有效的指导和帮助。

间斑寇蛛 Latrodectus tredecimguttatus 的一个显著特点是其毒腺外组织甚至卵粒中也存在毒性成分。研究毒腺外的毒素不但可以加深对蜘蛛毒素的了解，而且可以发现具有重要应用前景的新型毒素分子。为了探究间斑寇蛛卵粒中低丰度表达的蛋白质类毒素，利用生物信息学方法从间斑寇蛛卵粒转录组中挖掘出一条编码多肽毒素的基因序列，利用基于 3′-RACE 和巢式 PCR 的策略成功克隆并异源表达了该基因。表达的多肽毒素命名为间斑寇蛛卵粒毒素-Ⅵ (Latroeggtoxin-Ⅵ，LETX-Ⅵ)。生物学活性鉴定结果表明，LETX-Ⅵ能抑制 ND7/23 细胞膜上的钠离子通道电流和促进 PC12 细胞多巴胺的释放，但对美洲蜚蠊 Periplaneta americana 和金黄色葡萄球菌及白色念珠菌等细菌和真菌不显示明显的毒性，说明 LETX-Ⅵ是一种哺乳动物特异的神经毒素，在神经生物学研究工具试剂和相关疾病治疗药物的研发等方面具有潜在的应用前景。

Latroeggtoxin-VI (LETX-VI) is a peptide neurotoxin newly found from the eggs of spider L. tredecimguttatus. To explore the mechanism of action of the LETX-VI on nerve cells, the effects of LETX-VI on PC12 cells, a commonly used neuron model, were analyzed using a pull-down assay-guided strategy. LETX-VI was shown to interact with 164 PC12 cell proteins that have diverse molecular functions such as binding, catalysis, regulation, structural activity, etc., thereby extensively affecting the biological processes in the PC12 cells, particularly protein metabolism, response to stimulus, substance transport, and nucleic acid metabolism, with 56.71%, 42.07%, 29.88% and 28.66% of the identified proteins being involved in these biological processes, respectively. By interacting with the relevant proteins, LETX-VI enhanced the synthesis of dopamine; positively regulated cell division and proliferation; and negatively regulated cell cycle arrest, cell death, and apoptotic processes, and therefore has limited cytotoxicity against the PC12 cells, which were further experimentally confirmed. In general, the effects of LETX-VI on PC12 cells are more regulatory than cytotoxic. These findings have deepened our understanding of the action mechanism of LETX-VI on nerve cells and provided valuable clues for further related researches including those on Parkinson’s disease.

Latroeggtoxin‐VI (LETX‐VI) is a peptide neurotoxin discovered from Latrodectus tredecimguttatus eggs. In the current study, the action features of the neurotoxin on PC12 cells were systematically investigated. LETX‐VI could promote dopamine release from PC12 cells in the absence and presence of Ca2+, involving an even more complex action mechanism in the presence of Ca2+ and when the treatment time was longer. Although LETX‐VI enchanced the autophagy and secretion activity in PC 12 cells, it showed no remarkable influence on the proliferation, cell cycle, apoptosis and ultrastructure of the cells. Pulldown combined with CapLC‐MS/MS analysis suggested that LETX‐VI affected PC12 cells by interacting with multiple proteins involved in the metabolism, transport, and release of neurotransmitters, particularly dopamine. The low cytotoxicity and effective regulatory action of LETX‐VI on PC12 cells suggest the potential of the active peptide in the development of drugs for the treatment of some dopamine‐related psychotic diseases and cancers.

body of the L. tredecimguttatus newborn and adult spiders. For revealing the differences in the protein expression profiles and toxicity bases of the spiders at different developmental stages, the spiderling and adult spider proteins were comparatively analyzed using a proteomic strategy. Totals of 429 and 958 proteins were identified from the spiderlings and adult spiders, respectively, with 239 proteins being identified from both of them. Although some similarities between the spiderling and adult spider proteomes exist, there are obvious differences between the two proteomes in size, complexity, molecular weight (MW) distribution, acid-base property, and hydropathicity, etc. Gene ontology (GO) analysis demonstrates that, comparing based on the percentages of proteins, the spiderling and adult spider proteins have generally similar distribution profiles with respect to the subcellular localization, molecular function and biological process. However, there are still some differences between these two sets of proteins in some classifications of the three GO categories. For the adult spiders, latrotoxins together with other toxins and toxin-like proteins, etc. constitute their toxicity basis, whereas the toxicity of the spiderlings depends mainly on the synergistic action of atypical latrotoxins and toxin-like proteins, most of which are different from those of the adult spiders, demonstrating that the spiders at different developmental stages have largely different toxicity mechanisms.

It has been reported that Heteropodatoxin3 (HpTx3), a peptidic neurotoxin purified from the venom of the spider species Heteropoda venatoria, could inhibit Kv4.2 channels. Our present studynewly found that HpTx3 also has potent and selective inhibitory action on Nav1.7, with an IC50 of 135.61 ± 12.98 nM.Without effect on the current–voltage (I-V) relationship of Nav1.7, HpTx3 made minor alternation in the voltage-dependence of activation and steady-state inactivation of Nav1.7(4.15 mV and 7.29 mV, respectively) by interacting with the extracellular S3–S4 loop (S3b–S4 sequence) in domain II and the domain IV of the Nav channel subtype, showing the characteristics of both pore blocker and gate modifier toxin. During the interaction of HpTx3 with the S3b–S4 sequence of Nav1.7,the amino acid residue D in the sequence played a key role. When administered intraperitoneally or intramuscularly, HpTx3 displayed potent analgesic activity in a dose-dependent manner in different mouse pain models induced by formalin, acetic acid, complete Freund’s adjuvant, hot plate, or spared nerve injury, demonstrating that acute, inflammatory, and neuropathic pains were all effectively inhibited by the toxin. In most cases HpTx3 at doses of ≥ 1mg/kg could produce the analgesic effectcomparable to that of 1 mg/kg morphine. These results suggest that HpTx3 not only can be used as a molecular probe to investigate ion channel function and pain mechanism., but also has potential in the development of the drugs that treat the Nav1.7 channel-related pain.