Background::Cancer immunotherapy has emerged as a promising strategy against triple-negative breast cancer (TNBC). One of the immunosuppressive pathways involves programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), but many patients derived little benefit from PD-1/PD-L1 checkpoint blockades treatment. Prior research has shown that MYC, a master transcription amplifier highly expressed in TNBC cells, can regulate the tumor immune microenvironment and constrain the efficacy of immunotherapy. This study aims to investigate the regulatory relationship between MYC and PD-L1, and whether a cyclin-dependent kinase (CDK) inhibitor that inhibits MYC expression in combination with anti-PD-L1 antibodies can enhance the response to immunotherapy. Methods::Public databases and TNBC tissue microarrays were used to study the correlation between MYC and PD-L1. The expression of MYC and PD-L1 in TNBCs was examined by quantitative real-time polymerase chain reaction and Western blotting. A patient-derived tumor xenograft (PDTX) model was used to evaluate the influence of a CDK7 inhibitor THZ1 on PD-L1 expression. Cell proliferation and migration were detected by 5-ethynyl-2′-deoxyuridine (EdU) cell proliferation and cell migration assays. Tumor xenograft models were established for in vivo verification. Results::A high MYC expression level was associated with a poor prognosis and could alter the proportion of tumor-infiltrating immune cells (TIICs). The positive correlation between MYC and PD-L1 was confirmed by immunostaining samples from 165 TNBC patients. Suppression of MYC in TNBC caused a reduction in the levels of both PD-L1 messenger RNA and protein. In addition, antitumor immune response was enhanced in the TNBC cancer xenograft mouse model with suppression of MYC by CDK7 inhibitor THZ1. Conclusions::The combined therapy of CDK7 inhibitor THZ1 and anti-PD-L1 antibody appeared to have a synergistic effect, which might offer new insight for enhancing immunotherapy in TNBC.

Terahertz (THz) waves,also known as T-rays,encompass frequencies ranging from 0.1 to 10 THz and possess unique properties that render them applicable in various biomedical domains,particularly in neurobiology[1]. Synaptic transmission,the process through which signals propagate between neurons at synapses,is pivotal for brain function and information processing.

目的:基于肝癌细胞系与类器官的药物基因组学数据探讨骨髓细胞瘤癌基因(c-Myc)的潜在治疗效果.方法:收集肝癌细胞系的药敏、功能基因组和基因表达数据,评估c-Myc的表达与药敏的关联.统计c-Myc表达在肝癌测序队列中的差异和预后相关性.免疫组织化学染色验证c-Myc在肝癌患者的表达,检测其与类器官生物库类器官的药敏关联.选取三种不同的c-Myc抑制剂在肝癌细胞系和类器官上进行药物筛选,检测干预c-Myc对二维、三维水平的肿瘤杀伤作用.生物信息学分析探究c-Myc与靶向耐药的相关性.结果:生物信息学分析联合免疫组织化学鉴定c-Myc在肝癌中调控药敏的潜在作用.c-Myc在癌组织中的表达明显高于癌旁组织,而且c-Myc的表达在靶向药耐药患者中高于靶向药敏感患者(P<0.05).药敏实验揭示了c-Myc抑制剂THZ1、ABBV-744、JQ1可杀伤肿瘤细胞及类器官,并且与仑伐替尼在细胞系SNU-739中显示出显著的协同致死作用(协同系数均>1).进一步的类器官生物库数据分析显示,c-Myc与干性介导的靶向耐药显著正相关(R=0.87).结论:c-Myc在在靶向治疗耐药患者中高表达,并且抑制c-Myc可在二维、三维体外模型中起到很好的肿瘤杀伤效果,肝癌中可作为一个新的靶点.

目的:探讨细胞周期蛋白依赖性激酶7 (cyclin-dependent kinase 7,CDK7)对卵巢癌细胞增殖的作用.方法:应用特异性siRNA转染法沉默卵巢癌OVCA433、TOV-112D和IGROV1细胞中CDK7基因表达后,采用CCK-8法检测细胞增殖能力.应用成簇的规律间隔短回文重复序列(clustered regularly interspaced short palindromic repeat,CRISPR)及其相关核酸内切酶9(CRISPR-associated endonuclease 9,Cas9)基因编辑系统敲除卵巢癌HEY、OVCA420、OVCA433和IGROV1细胞中的CDK7基因后,采用克隆形成实验检测细胞克隆形成能力.用CDK7抑制剂THZ1处理卵巢癌TOV-112D、IGROV1、OVCA433、OVCAR8、OV90、SKOV3和COV413B细胞后,采用CCK-8法和克隆形成实验检测TOV-112D、IGROV1、OVCA433、OVCAR8和OV90细胞增殖和克隆形成能力,蛋白质印迹法检测IGROV1、OVCA433、SKOV3和COV413B细胞中CDK7蛋白表达水平和RNA聚合酶Ⅱ磷酸化水平.结果:沉默或敲除CDK7基因后,卵巢癌细胞的增殖和克隆形成能力均明显减弱(P值均＜ 0.05).THZ1处理可抑制卵巢癌细胞的增殖和克隆形成,并下调CDK7蛋白表达和RNA聚合酶Ⅱ磷酸化(P值均＜0.05).结论:CDK7可能通过调控RNA聚合酶Ⅱ磷酸化,促进卵巢癌细胞的增殖.

太赫兹(terahertz,THz,1THz=1012Hz)光谱技术作为一种新兴的、无标记、非侵入性的检测方法,已广泛应用于多个领域的研究中.在生物医学领域,THz光谱的独特优势显示了其在实时检测活细胞及组织中有着诱人的发展前景.在细胞检测中,其应用在以下几个方面有了较大发展:细菌细胞的鉴别、肿瘤细胞的鉴定和血细胞的检测.在组织检测中,THz光谱技术显示了其在活组织实时监测和疾病快速诊断中的潜力.并且,将THz光谱及THz成像结合于同一系统能够为组织检测增加敏感性并提供更加综合性的信息.然而,一些技术瓶颈的存在是实现THz波谱技术应用于临床亟需解决的问题.本文着重介绍了太赫兹波谱技术在细胞及组织检测中的应用现状,进一步讨论了面临的挑战及机遇,以期加速其在临床的实际应用.

目的:建立天麻素的太赫兹波段图谱特征.方法:采用太赫兹时域光谱技术检测两种不同产地的天麻素及两种全天麻胶囊在太赫兹波段的光谱,对得到的实验数据进行分析,同时采用模拟软件对天麻素晶体在太赫兹波段的光谱进行模拟,并指认其在太赫兹波段的振动模式.结果:两个产地的天麻所提取的天麻素的太赫兹光谱基本一致.其在0.51、0.77、1.01、1.18和1.59 THz处存在较明显的吸收峰.对于全天麻胶囊样品1和样品2,有4个较明显的吸收峰,但是与天麻素对比,仅有3个吸收峰的位置较为对应.结论:太赫兹时域光谱技术可用于在物性鉴别领域.

目的:研究人体劳宫穴、少府穴与手掌部非穴位区的太赫兹光谱特征.方法:运用太赫兹光谱技术,对50名在校大学生的右手劳宫、少府穴与非穴位部位(掌心大鱼际部位正中距离劳宫穴1cm)分别进行太赫兹波检测.结果:发现手掌所检测部位的太赫兹波辐射光谱在0.90～3.60THz,最高峰值在3.05THz;劳宫穴太赫兹辐射量显著大于非穴位区太赫兹辐射量(P＜0.01);少府穴太赫兹辐射量显著大于非穴位区太赫兹辐射量(P＜0.01).结论:人体太赫兹辐射量的个体差异以及穴位与非穴位区的太赫兹辐射量的差别都较大,但频谱特性的差异较小,表明人体手掌部太赫兹辐射具有相同的生物物理学基础,穴位具有太赫兹波的特异性.

[背景]辣椒疫霉是一种毁灭性的土传病害,当前主要使用化学合成杀菌剂防治,但容易导致环境污染和食品安全等问题.[目的]筛选可拮抗辣椒疫霉的候选菌株,探究分离菌株拮抗辣椒疫霉的生理生化作用机制.[方法]综合应用形态学、核糖体RNA (rRNA)基因非转录区ITS序列相似性方法鉴定分离菌株,通过对峙实验筛选抑菌效果较高的拮抗菌株,基于比色法测定分离菌株发酵液粗提物对辣椒疫霉菌丝脂质过氧化、纤维素酶、β-葡萄糖苷酶(β-GC)和多聚半乳糖醛酸酶(PG)活性的影响.[结果]从腐木和土壤样品中分离得到11株木霉,分属于绿色木霉(Trichoderma virens)、哈茨木霉(Trichoderma harzianum)、钩状木霉(Trichoderma hamatum)和棘孢木霉(Trichoderma asperellum) 4个种.11株木霉对辣椒疫霉均有一定的抑制作用,抑制率达到90％以上的菌株包括:绿色木霉Tv-1(92.68％)、Tv-2 (95.12％),哈茨木霉Thz-2 (92.68％),钩状木霉Tha-1 (90.24％).以4株高效木霉的发酵液粗提物处理辣椒疫霉菌丝5 d后,因脂质过氧化产生的丙二醛含量显著增加,分别达到1.20、1.48、2.69和3.16 nmol/g,显著高于对照处理的0.77 nmol/g;与对照组相比,β-GC、PG酶活性显著下降,分别降低了12.28％?64.91％、7.2％?15.5％;同时纤维素酶活性呈上升趋势,最显著组为2.647 U/mL,相对于对照组增加了0.831 U/mL.[结论]分离得到4株明显抑制辣椒疫霉菌生长的高效木霉菌,主要通过破坏细胞壁结构、降低致病因子酶活力和增强脂质过氧化等方式起拮抗作用,可为辣椒疫病的生物防治提供理论依据和技术支持.

Cancer cells always require more nutrients,energy,and biosynthetic activity to sustain their rapid proliferation than normal cells.Previous studies have shown the impact of THZ1,a covalent inhibitor of cyclin-dependent kinase 7 (CDK7),on transcription regulation and cell-cycle arrest in numerous cancers,but its effects on cellular metabolism in cancer cells remain unknown.In this study we elucidated the anticancer mechanism of THZ1 in human non-small-cell lung cancer (NSCLC) cells.We showed that treatment with THZ1 (10-1000 nM) dose-dependently suppressed the proliferation of human NSCLC cell lines H1299,A549,H292,and H23,and markedly inhibited the migration of these NSCLC cells.Furthermore,treatment with THZ1 (50 nM) arrested cell cycle at G2/M phase and induced apoptosis in these NSCLC cell lines.More importantly,we revealed that treatment with THZ1 (50 nM) blocked the glycolysis pathway but had no effect on glutamine metabolism.We further demonstrated that THZ1 treatment altered the expression pattern of glutaminase 1 (GLS1) isoforms through promoting the ubiquitination and degradation of NUDT21.Combined treatment of THZ1 with a glutaminase inhibitor CB-839 (500 nM) exerted a more potent anti-proliferative effect in these NSCLC cell lines than treatment with THZ1 or CB-839 alone.Our results demonstrate that the inhibitory effect of THZ1 on the growth of human NSCLC cells is partially attributed to interfering with cancer metabolism.Thus,we provide a new potential therapeutic strategy for NSCLC treatment by combining THZ1 with the inhibitors of glutamine metabolism.

目的:研究中渚穴、合谷穴与非经穴外劳宫的太赫兹波特征.方法:运用太赫兹光谱技术,对50名在校大学生的右手背中渚穴、合谷穴、非经穴外劳宫、手掌劳宫穴和非穴位部位(掌心大鱼际部位正中距离劳宫穴1cm)分别进行太赫兹波检测.结果:穴位太赫兹波辐射光谱在0.90～3.60THz,最高峰值在3.05THz;合谷穴太赫兹辐射量大于外劳宫太赫兹辐射量(P＜0.01),中渚穴太赫兹辐射量小于外劳宫太赫兹辐射量(P＜0.01);手掌部劳宫穴太赫兹辐射量大于非穴位(P＜0.01).结论:经穴与非经穴具有太赫兹波信息联系;穴位相对于非穴位的太赫兹波辐射具有显著差异.