The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities tha...The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC cells.We found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro.RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy.Further,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC cells.Mechanistically,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of ATF4.In summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth.Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.展开更多
By double beam and double wave interferomatric (DDI) method, the optical constants of thin films, i.e. refractive index, extinction coefficient and thickness may be determined in infrared (3.39 μm) and in visible (...By double beam and double wave interferomatric (DDI) method, the optical constants of thin films, i.e. refractive index, extinction coefficient and thickness may be determined in infrared (3.39 μm) and in visible (0.633 μm) wavelengths in the same optical path with a tunable double wave He Ne laser designed by ourselves. The measuring principle and the device are describod.展开更多
采用傅里叶变换红外(FT-IR)光谱法研究了二聚脂肪酸二异氰酸酯(DDI)/端羟基聚丁二烯(HTPB)体系的固化反应动力学,并与异佛尔酮二异氰酸酯(IPDI)/HTPB体系进行了比较。初步探索了DDI在HTPB推进剂中的应用。结果表明,DDI/HTPB体系的固化...采用傅里叶变换红外(FT-IR)光谱法研究了二聚脂肪酸二异氰酸酯(DDI)/端羟基聚丁二烯(HTPB)体系的固化反应动力学,并与异佛尔酮二异氰酸酯(IPDI)/HTPB体系进行了比较。初步探索了DDI在HTPB推进剂中的应用。结果表明,DDI/HTPB体系的固化反应为二级反应,表观活化能为37.02 k J·mol-1,相比IPDI/HTPB体系降低了3.5 k J·mol-1,说明DDI的反应活性稍高于IPDI,反应活性适中,可作为低毒固化剂应用于HTPB推进剂中。DDI/HTPB体系推进剂具有较好的常温力学性能,抗拉强度为0.85 MPa时,最大伸长率为44.1%,可基本满足推进剂的常温力学性能要求。展开更多
基金supported by the National Natural Science Foundations of China(82273554,82073470)the Shandong Provincial Key R&D Program(ZR2019ZD36).
文摘The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC cells.We found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro.RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy.Further,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC cells.Mechanistically,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of ATF4.In summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth.Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.
文摘By double beam and double wave interferomatric (DDI) method, the optical constants of thin films, i.e. refractive index, extinction coefficient and thickness may be determined in infrared (3.39 μm) and in visible (0.633 μm) wavelengths in the same optical path with a tunable double wave He Ne laser designed by ourselves. The measuring principle and the device are describod.
文摘供者来源性感染（donor derived infection,DDI）是指在器官捐献后,捐献者体内存在的病原体通过器官移植过程使受者罹患相同的感染。产生DDI的客观原因是绝大部分捐献者在原发疾病救治过程中可能经历重大手术、持续气管插管或切开行机械通气,留置深静脉导管、导尿管等各种导管,时常需要血液透析、人工肝、体外膜肺氧合等治疗,都曾入住重症监护病房（intensive care unit,ICU）,
文摘采用傅里叶变换红外(FT-IR)光谱法研究了二聚脂肪酸二异氰酸酯(DDI)/端羟基聚丁二烯(HTPB)体系的固化反应动力学,并与异佛尔酮二异氰酸酯(IPDI)/HTPB体系进行了比较。初步探索了DDI在HTPB推进剂中的应用。结果表明,DDI/HTPB体系的固化反应为二级反应,表观活化能为37.02 k J·mol-1,相比IPDI/HTPB体系降低了3.5 k J·mol-1,说明DDI的反应活性稍高于IPDI,反应活性适中,可作为低毒固化剂应用于HTPB推进剂中。DDI/HTPB体系推进剂具有较好的常温力学性能,抗拉强度为0.85 MPa时,最大伸长率为44.1%,可基本满足推进剂的常温力学性能要求。
