Theranostic nanoagents have attracted considerable research interest due to their fascinating capability to simultaneously offer therapeutic and diagnostic functions. Here, novel iodine-doped carbon dots (I-CDs) were fabricated from arginine and iohexol via a facile hydrothermal strategy. I-CDs exhibited excellent stability and biocompatibility. Owing to a high quantum yield of 18.67%, the prepared I-CDs were suitable for the fluorescence imaging of tumor cells. Subcellular localization analysis showed that I-CDs were mostly distributed in lysosomes and mitochondria. Notably, the I-CD-treated A549 and HeLa cells simultaneously exhibited outstanding intracellular nitric oxide (NO) and reactive oxygen species (ROS) release capacities under an LED lamp illumination. The NO generation ability of I-CDs originated from the arginine moieties on their outer surface. The outcomes of in vitro investigations indicated that I-CDs were an effective nanophotosensitizer for the photodynamic therapy (PDT) of A549 and HeLa cells. Computed tomography (CT) scan data revealed that the Hounsfield unit (HU) value of I-CDs surpassed that of iohexol. Thereafter, the obtained I-CDs were successfully applied for performing the fast CT contrast imaging of mouse kidneys and bladders (within 1 minute); notably, I-CDs displayed negligible histopathological and hemolytic toxicity. I-CDs showed potential in the fields of fluorescence/CT bimodal imaging and PDT.

Aluminum is widely used in diverse fields of our daily life including maquillage, vaccine adjuvants, food packing, etc. Long-term aluminum exposure will lead to osteoporosis, Alzheimer's disease, and chronic renal failure. There still remains a need to develop low-cost, suitable, and rapid methods for the detection of Al3+. Herein, trypan blue-carbon dots (TB-CDs) were fabricated via a facile hydrothermal approach. The obtained TB-CDs were thoroughly analyzed by TEM, X-ray diffraction, FT-IR, XPS, UV-vis spectrophotometry, and fluorescence spectrophotometry. TB-CDs were spherical with a mean particle size of 2.9 nm and exhibited a high aqueous solubility with a fluorescence quantum yield of 6.37%. The obtained TB-CDs showed excellent photostability and relatively low cytotoxicity. The extent of fluorescence enhancement of TB-CDs was linearly related to the logarithmic concentration of Al3+. Thus, a fluorescence-on method was developed for fast and highly specific detection of Al3+ within the range of 0.5 to 4 μmol L-1. The limit of detection was 0.2 μmol L-1. Furthermore, the established sensing platform was successfully utilized for Al3+ determination in real samples and the intracellular imaging of Al3+. Owing to their convenience, low cost, and fast response, TB-CDs displayed promising potential in biochemical analysis and bioimaging fields.

目的 探讨不同模式的血流切应力对人脐静脉内皮细胞(HUVECs)Pim1表达的影响,以及对内皮型一氧化氮合酶(eNOS)Ser1177和Ser633位点磷酸化的调控作用.方法 体外原代培养的HUVECs,采用平行平板流动腔系统给HUVECs分别施加15 dyn/cm2层流切应力(LSS)和(0.5±4)dyn/cm2振荡切应力(OSS),Western blotting法检测Pim1、Akt和Akt Ser473磷酸化、eNOS、eNOS Ser1 177和Ser633位点磷酸化蛋白表达.用特异性小干扰RNA(siRNA)技术分别敲低HUVECs中Pim1和Akt进行干预.结果 与OSS刺激相比较,LSS显著上调HUVECs中Pim1蛋白表达水平(P＜0.01),同时,Akt Ser473磷酸化、eNOS Ser633和Seri 177位点磷酸化蛋白表达增加(P＜0.05或P＜0.01);siPim1和Pim1特异性抑制剂SMI-4a干预后,LSS诱导的Pim1蛋白表达显著被抑制(P＜0.05),同时Akt Ser473磷酸化、eNOS Ser633和Seri 177位点磷酸化蛋白表达均降低(P＜0.05或P＜0.01).敲低Akt,LSS诱导的Akt Ser473磷酸化蛋白表达显著被抑制(P＜0.05),同时也显著抑制LSS上调的eNOS Ser633和Ser1177磷酸化蛋白表达(P＜0.05),而对LSS上调的Pim1表达无影响(P＞0.05).结论 切应力可以通过Pim1/Akt信号通路调节HUVECs eNOS Ser633和Ser1 177位点磷酸化.

目的 探讨Pim-1在结核性胸膜炎及在肺癌患者胸膜组织中的表达及临床意义.方法 收集我院2021年1月-2021年11月内科胸腔镜手术切除的结核性胸膜炎及肺癌的胸膜活检标本共41例,其中结核性胸膜炎21例,肺癌20例.利用免疫组织化学法和Western-Blot法分别测定胸膜组织中Pim-1蛋白的表达情况,同时探寻与Pim-1表达有关的临床因素.结果 Pim-1在结核性胸膜炎组中的阳性率为95.24％(20/21),在肺癌组中的阳性率为70％(12/20),结核性胸膜炎胸膜组织Pim-1表达水平更高(P<0.001);Western-Blot结果显示Pim-1在结核性胸膜炎中表达水平也高于肺癌组(P<0.01);结核组Pim-1蛋白表达与性别、吸烟史、BMI指数均无明显相关性(P>0.05),肺癌组中Pim-1蛋白表达与性别、吸烟史、BMI指数均无明显相关性(P>0.05),可能与淋巴结转移有关(P<0.01).结论 结核性胸膜炎胸膜组织中的Pim-1表达较高,检测胸膜组织中Pim-1对结核性胸膜炎和肺癌有鉴别诊断价值.

目的 采用贝叶斯网状Meta分析方法比较含多黏菌素B的抗菌方案与其他抗菌方案治疗多重耐药革兰阴性菌医院获得性肺炎/呼吸机相关性肺炎(HAP/VAP)的临床疗效.方法 计算机检索 PubMed、EMbase、The Cochrane Library、Web of Science、CNKI、SinoMed、ChiCTR、WanFang Data 和 VIP 数据库,搜集含多黏菌素 B的抗菌方案治疗多重耐药革兰阴性菌HAP/VAP的临床对照研究,检索时限均从建库到2022年10月15日.由2位研究员独立筛选文献、提取资料并评估纳入研究的偏倚风险后,采用Stata 17.0和R 4.1.2软件进行贝叶斯网状Meta分析.结果 共纳入1个随机对照试验(RCT)和10项观察性研究,共1 385例患者,涉及8种治疗方案.贝叶斯网状Meta分析结果表明,在临床有效率方面,8种用药方案组间差异无统计学意义(P＞0.05),累积排序概率曲线下面积(SUCRA)显示多黏菌素B静脉滴注联合多黏菌素B雾化吸入方案的临床有效率高于多黏菌素B静脉滴注单用或其联合替加环素等方案;在病死率方面,文中涉及的4种用药方案中,SUCRA显示多黏菌素B静脉滴注联合多黏菌素B雾化方案的病死率较低,低于多黏菌素B静脉滴注、替加环素单用或两者联用等方案,其中多黏菌素B静脉滴注联合多黏菌素雾化吸入方案的病死率低于多黏菌素B静脉滴注联合替加环素方案,且差异有统计学意义[OR=0.21,95％CrI(0.05,0.94),P＜0.05],其余涉及的治疗方案组间差异无统计学意义(P＞0.05);在细菌清除率方面,涉及的4种用药方案组间差异无统计学意义(P＞0.05).结论 现有证据表明,就生存获益而言,推荐使用多黏菌素B静脉滴注联合多黏菌素B雾化吸入方案治疗多重耐药革兰阴性菌HAP/VAP.受纳入研究数量和质量限制,上述结论尚待更多大样本、高质量、多中心的RCT予以验证.

Herein, a one-step hydrothermal synthesis method was adopted to fabricate carbon dots (CDs) from amido black 10b in a sodium hydroxide solution. The morphology and composition of the CDs were investigated by XRD, FTIR TEM, XPS, UV-vis, and fluorescence spectroscopy. The obtained CDs (AB-CDs) with an average diameter of 19.4 nm displayed a well-dispersed characteristic in aqueous solutions. The as-prepared CDs showed bright blue fluorescence and good photostability, with a high quantum yield of 24.1%. AB-CDs displayed a selective and noticeable turn-off response to Fe3+. Accordingly, the quantitative detection of Fe3+ was achieved in the range of 5-200 μmol L-1 with a detection limit of 1.84 μmol L-1. The fluorescence response mechanism of Fe3+ to AB-CDs was ascribed to static quenching due to the emergence of the ground-state complex. Moreover, ascorbic acid could restore the fluorescence of AB-CDs quenched by Fe3+ by reducing Fe3+ to Fe2+. The developed nanoprobe was used to detect ascorbic acid with a limit of detection of 7.26 μmol L-1 in the range of 20-300 μmol L-1. Furthermore, the developed sensing system was successfully applied for an Fe3+ assay in a lake water sample and ascorbic acid detection in a human urine sample. The AB-CD-based analytical system showed its latent practical value in the chemical analysis and bioanalytical fields.

目的:探讨流体切应力作用下水通道蛋白1(AQP1)的表达对血管内皮细胞迁移和血管生成的影响及可能的机制.方法:取雄性C57BL/6小鼠主动脉弓和胸主动脉血管壁组织,用qPCR和Western blot检测体内不同切应力作用部位血管壁AQP1表达的差异.原代培养人脐静脉内皮细胞(HUVECs),体外采用平行平板流动腔系统给HUVECs分别加载层流(LF,15 dyn/cm2单向层切应力)和扰流[DF,(0.5±4)dyn/cm2振荡切应力],用特异性小干扰RNA(siRNA)转染技术沉默AQP1基因,采用Transwell实验和Matrigel小管形成实验检测HUVECs迁移和血管生成能力;用Western blot检测内皮型一氧化氮合酶(eNOS)Ser1177和Ser633磷酸化水平.结果:在体胸主动脉中AQP1的mRNA和蛋白表达显著高于主动脉弓(P<0.05).HUVECs静态下敲减AQP1可以显著抑制细胞迁移和血管生成(P<0.01).与DF组相比,LF显著上调HUVECs中AQP1的mRNA和蛋白表达(P<0.05),促进HUVECs迁移(P<0.01)和血管生成能力(P<0.05),同时显著增加eNOS Ser1177(P<0.01)和Ser633(P<0.05)磷酸化水平.转染siAQP1后,LF诱导的AQP1表达增强被抑制(P<0.01),HUVECs的迁移和血管生成能力也随之降低(P<0.01),同时eNOS Ser1177和Ser633的磷酸化水平降低(P<0.05或P<0.01).eNOS抑制剂NG-硝基-L-精氨酸甲酯(L-NAME)预处理HUVECs后,LF诱导的细胞迁移和血管生成能力被抑制(P<0.01).结论:AQP1在流体切应力调节血管内皮细胞迁移和血管生成中发挥作用,其机制可能和eNOS信号有关.

目的:探讨Pim1在巨噬细胞M1型极化中的作用及M1型巨噬细胞对内皮细胞黏附分子表达的影响,并观察其在ApoE-/-小鼠动脉粥样硬化(AS)形成中的作用.方法:采用脂多糖(LPS)刺激小鼠Raw264.7细胞建立M1型巨噬细胞模型,用Pim1特异性抑制剂SMI-4a和转染Pim1小干扰RNA(siPim1)进行干预,分为对照组、LPS组、LPS+SMI-4a组、LPS+siNC组和LPS+siPim1组.收集以上各组Raw264.7细胞上清作为条件培养液(CM)孵育原代培养的人脐静脉内皮细胞(HUVECs),分为CMM0、CMM1、CMSMI-4a、CMsiNC和CMsiPim1组.动物采用颈动脉部分结扎术建立颈动脉AS模型,用6周龄ApoE-/-雄性小鼠18只建模后,随机分为模型组及SMI-4a干预组,每组各9只.采用油红O染色法观察颈动脉脂质蓄积变化.免疫荧光法和Western blot法检测M1型巨噬细胞标志物诱导型一氧化氮合酶(iNOS)、Pim1、血管内皮标志物血管内皮钙黏蛋白(VE-cadherin)、细胞间黏附分子1(ICAM1)和血管细胞黏附分子1(VCAM1)在血管壁和细胞中的表达变化.结果:与对照组相比,LPS显著上调了Raw264.7细胞M1型极化标志物iNOS蛋白表达(P<0.01),同时Pim1蛋白表达也显著增高(P<0.05);SMI-4a干预和siPim1转染Raw264.7细胞,显著抑制LPS诱导的Pim1和iNOS表达(P<0.05或P<0.01).与CMM0相比,CMM1显著上调HUVEC中ICAM1和VCAM1蛋白表达(P<0.05或P<0.01);CMSMI-4a和CMsiPim1均显著抑制了HUVECs中ICAM1和VCAM1表达(P<0.01).动物实验水平,建模后结扎侧左颈动脉可见脂质沉积,有AS斑块形成,血管壁iNOS表达显著增多(P<0.01),Pim1、ICAM1和VCAM1蛋白表达上调(P<0.05).SMI-4a干预后,与模型组相比,左颈动脉脂质沉积被抑制,Pim1和iNOS表达显著降低(P<0.05或P<0.01),血管内皮标志物VE-cadherin蛋白水平升高(P<0.05),同时ICAM1和VCAM1蛋白表达显著下降(P<0.01).结论:抑制Pim1可以抑制ApoE-/-小鼠AS斑块形成,其机制可能与减少巨噬细胞M1型极化,降低内皮细胞炎症反应有关.

Objective: The aim of the research was to study the effect of azithromycin (AZM) in the treatment of MDR P. aeruginosa VAP combined with other antimicrobial therapies. Methods: The clinical outcomes were retrospectively collected and analyzed to elucidate the efficacy of different combinations involving azithromycin in the treatment of MDR-PA VAP. The minimal inhibitory concentration (MIC) of five drugs was measured by the agar dilution method against 27 isolates of MDR-PA, alone or in combination. Results: The incidence of VAP has increased approximately to 10.4% (961/9245) in 5 years and 18.4% (177/961) caused by P. aeruginosa ranking fourth. A total of 151 cases of MDR P. aeruginosa were included in the clinical retrospective study. Clinical efficacy results are as follows: meropenem + azithromycin (MEM + AZM) was 69.2% (9/13), cefoperazone/sulbactam + azithromycin (SCF + AZM) was 60% (6/10), and the combination of three drugs containing AZM was 69.2% (9/13). The curative effect of meropenem + amikacin (MEM + AMK) was better than that of the meropenem + levofloxacin (MEM + LEV) group, p = 0.029 (p < 0.05). The curative effect of cefoperazone/sulbactam + amikacin (SCF + AMK) was better than that of the cefoperazone/sulbactam + levofloxacin (SCF + LEV) group, p = 0.025 (p < 0.05). There was no significant difference between combinations of two or three drugs containing AZM, p > 0.05 (p = 0.806). From the MIC results, the AMK single drug was already very sensitive to the selected strains. When MEM or SCF was combined with AZM, the sensitivity of them to strains can be significantly increased. When combined with MEM and AZM, the MIC50 and MIC90 of MEM decreased to 1 and 2 ug/mL from 8 to 32 ug/mL. When combined with SCF + AZM, the MIC50 of SCF decreased to 16 ug/mL, and the curve shifted obviously. However, for the combination of SCF + LEV + AZM, MIC50 and MIC90 could not achieve substantive changes. From the FIC index results, the main actions of MEM + AZM were additive effects, accounting for 72%; for the combination of SCF + AZM, the additive effect was 40%. The combination of AMK or LEV with AZM mainly showed unrelated effects, and the combination of three drugs could not improve the positive correlation between LEV and AZM. Conclusion: AZM may increase the effect of MEM or SCF against MDR P. aeruginosa VAP. Based on MEM or SCF combined with AMK or AZM, we can achieve a good effect in the treatment of MDR P. aeruginosa VAP.

For wide applications of the lacZ gene in cellular/molecular biology, small animal investigations, and clinical assessments, the improvement of noninvasive imaging approaches to precisely assay gene expression has garnered much attention. In this study, we investigate a novel molecular platform in which alizarin 2-O-β-d-galactopyranoside AZ-1 acts as a lacZ gene/β-gal responsive 1H-MRI probe to induce significant 1H-MRI contrast changes in relaxation times T1 and T2in situ as a concerted effect for the discovery of β-gal activity with the exposure of Fe3+. We also demonstrate the capability of this strategy for detecting β-gal activity with lacZ-transfected human MCF7 breast and PC3 prostate cancer cells by reaction-enhanced 1H-MRI T1 and T2 relaxation mapping.

目的 探究钙调蛋白在骨骼肌损伤内质网应激相关性自噬中的作用及机制.方法 制备小鼠肌损伤内质网应激(ERS)模型,采用钙调蛋白激动剂/拮抗剂干扰该信号;同时体外以衣霉素化学诱导C2C12细胞分化的肌管发生ERS,继而添加钙调蛋白干扰剂刺激.检测未折叠蛋白反应(UPR)标志物mRNA和UPR通路关键分子蛋白表达水平,以及ERS诱导自噬相关蛋白的表达.结果 肌损伤后,肌内UPR标志物(BiP、XBP1-S和ATF6)mRNA显著上调(P<0.05),ERS激活的UPR关键通路分子eIF2α、IRE1α和ATF6蛋白活性显著上调(均P<0.05),自噬标志物LC3Ⅱ/Ⅰ增加,采用钙调蛋白激动剂CALP1可增强此反应.结论 钙调蛋白参与了未折叠蛋白反应,并可能通过调节ERS相关性自噬促进骨骼肌损伤修复过程.

An emerging body of evidence indicates that transient receptor potential TRP channels act as important mediators for a wide variety of physiological functions and are potential targets for drug discovery. Our previous study has identified transient receptor potential channel 3 (TRPC3) and TRPC6 as cation channels through which most of the damaging calcium enters, aggravates pathological changes in vivo and increases ischemia/reperfusion (I/R) injury in mice. This study aimed to verify the effects of TRPC3 inhibitor Pyr3 on myocardial I/R injury in mice. C57BL/6J wild-type male mice (8 to 12 weeks old) were anesthetized with 3.3% chloral hydrate. A murine I (30 min)/R (24 h) injury model was established by temporary occlusion of the left anterior descending (LAD) coronary artery. Pyr3 was administered at concentrations of 0, 2.5, 5, or 10 mg/kg via the right jugular vein 5 min before reperfusion. We observed that the selective TRPC3 inhibitor, 10 mg/kg Pyr3, significantly decreased the infarct size of left ventricle, and reduced the myocardial cell apoptosis rate and inflammatory response in mice. In a conclusion, TRPC3 can function as a candidate target for I/R injury prevention, and Pyr3 may directly bind to TRPC3 channel protein, inhibit TRPC3 channel activity, and improve TRPC3-related myocardial I/R injury. Pyr3 may be used for clarification of TRPC3 functions and for treatments of TRPC3-mediated diseases.

目的:探讨层流切应力是否可通过Pim1调节内皮型一氧化氮合酶(eNOS)活性,从而调节血管内皮细胞一氧化氮(NO)分泌.方法:体外原代培养人脐静脉内皮细胞(HUVECs),运用平行平板流动腔系统给HUVECs加载层流切应力(15 dyn/cm2).采用Western blot法检测Pim1蛋白表达及eNOS-Ser1177磷酸化水平;硝酸还原酶法检测NO分泌量;利用特异性小干扰RNA(siRNA)转染技术沉默Pim1基因后再检测上述指标的变化.结果:切应力作用HUVECs 15 min,可以显著上调Pim1蛋白表达(P＜0.05),同时显著增强eNOS-Ser1 177磷酸化水平(P＜0.05),伴随HUVECs NO分泌显著增多(P＜0.05).转染siPim1可以抑制切应力诱导的Pim1表达(P＜0.05),同时抑制eNOS-Ser1177磷酸化(P＜0.05),NO分泌随之显著降低(P＜0.05).结论:流体切应力可能通过Pim1/eNOS途径调节血管内皮细胞NO分泌.

Doxorubicin (DOX) has dose-dependent toxicity on ovarian follicles (OFs), and the inhibition of different signaling molecules along with the DOX application for enhancing its efficacy can also upsurge this toxicity. Therefore, it is strongly required to explore the mechanism of DOX-induced toxicity in 3D culture systems for protecting the OFs. A microfluidic chip was used to culture a single OF to identify the potential signaling molecules and their combined effects on OFs dynamically. The chip offers better 3D biomimetic microenvironment to the growing OF than 2D culture systems. The OFs cultured on the chip were treated with DOX and the inhibitors of Src, Ca2+, and PIM. Their mutual effects were studied on OFs growth and 17β-estradiol secretion. Besides, the RNA levels of B4GALT2 and UNC5C genes of DOX-exposed OFs were detected by RT-qPCR, and TUNEL staining experiments were conducted to check the OF apoptosis. The results showed that DOX application reduced the OFs growth and hormone secretion and induced apoptosis in the OFs. Moreover, the DOX-induced toxic effects were enriched by Src and PIM inhibition, while reduced by the ER-Ca2+ channel inhibitor. This study specifically demonstrates the synergistic effects of some signaling molecules on DOX-mediated cellular functions of OFs and demands some meditative measures to decipher this toxicity for supporting the female endocrine and reproductive functions.

目的 探讨低切应力刺激对血管内皮细胞Bmi1表达的影响及其在迁移中的作用.方法 体外原代培养人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs),运用平行平板流动腔系统给HUVECs加载正常切应力(1.5 Pa)和低切应力(0.5 Pa)12 h,用实时定量PCR法和免疫印迹法检测Bmi1 mRNA和蛋白表达水平,用细胞划痕实验检测细胞迁移能力,利用特异性小干扰RNA (siRNA)转染技术沉默Bmi1基因.结果 HUVECs受力12 h后,与1.5 Pa切应力组相比,0.5 Pa低切应力能显著上调Bmi1表达,同时抑制细胞迁移.siRNA敲低Bmi1表达后,减弱了低切应力对HUVECs迁移的抑制作用.结论 低切应力对HUVECs迁移的抑制作用可能是通过上调Bmi1蛋白的表达实现.Bmi1表达沉默后可逆转低切应力对HUVECs迁移的抑制.

Objective: To evaluate therapeutic efficacy of different combined antimicrobial treatments against Acinetobacter baumannii ventilator-associated pneumonia (VAP). Methods: Clinical outcomes were retrospectively analyzed to elucidate the efficacy of four combined antimicrobial regimens. The chessboard and micro broth dilution methods determined the minimum inhibitory concentrations (MICs) of four antiseptic drugs singly used and combined two drugs against 36 isolates of multidrug-resistant (MDR) A. baumannii. Results: The incidence of VAP was approximately 6.9% (237/3424) between January 1, 2015 and December 31, and 35.9% (85/237) of the cases were caused by A. baumannii. Among these cases, 60 belonged to AB-VAP, for whom antimicrobial treatment plan was centralized and clinical data was complete. Moreover, all 60 strains of A. baumannii were MDR bacteria from reports microbiological laboratory. Resistance rate was lowest for amikacin (68.3%) and ampicillin sulbactam (71.7%). Resistance rate for imipenem increased from 63.2 to 90.9% during the 3 years. However, in these 60 cases of AB-VAP, the combination between 4 antibiotics was effective in most cases: the effective rate was 75% (18/24) for sulbactam combined with etilmicin, 71.4% (10/14) for sulbactam combined with levofloxacin, 72.7% (8/11) for meropenem combined with etilmicin, and 63.6% (7/11) for meropenem combined with levofloxacin. There was no statistical difference between four regimens (P > 0.05). Sulbactam combined with etilmicin decreased 1/2 of MIC50 and MIC90 of sulbactam while the decreases in etilmicin were more obviously than single drug. When adopting meropenem combined with levofloxacin or etilmicin, the MIC of meropenem reduced to 1/2 of that in applying single drug. As for sulbactam or meropenem combined with levofloxacin, it also lessened the MIC50 of levofloxacin to 1/2 of that for single drug. FIC results suggested that the effects of four combined antimicrobial regimens were additive or unrelated. When sulbactam was combined with etimicin, the additive effect was 63.89%. Conclusion: Drug combination sensitivity test in vitro may be helpful for choosing antimicrobial treatment plans. Sulbactam or meropenem as the basis of treatment regimens can function as the alternatives against AB-VAP. Sulbactam combined with etimicin has been regarded as a recommended regimen in Suizhou, Hubei, China.

A facile one-step hydrothermal synthesis approach was proposed to prepare nitrogen and chlorine co-doped carbon dots (CDs) using l-ornithine hydrochloride as the sole precursor. The configuration and component of CDs were characterized by transmission electron microscopy and X-ray photoelectron and Fourier transform infrared spectroscopies. The obtained CDs (Orn-CDs) with a mean diameter of 2.1 nm were well monodispersed in aqueous solutions. The as-prepared CDs exhibited a bright blue fluorescence with a high yield of 60%, good photostability and low cytotoxicity. The emission of Orn-CDs could be selectively and effectively suppressed by Fe3+. Thus, a quantitative assay of Fe3+ was realized by this nanoprobe with a detection limit of 95.6 nmol l-1 in the range of 0.3-50 µmol l-1. Furthermore, ascorbic acid could recover the fluorescence of Orn-CDs suppressed by Fe3+, owing to the transformation of Fe3+ to Fe2+ by ascorbic acid. The limit of detection for ascorbic acid was 137 nmol l-1 in the range of 0.5-10 µmol l-1. In addition, the established method was successfully applied for Fe3+ and ascorbic acid sensing in human serum and urine specimens and for imaging of Fe3+ in living cells. Orn-CD-based sensing platform showed its potential to be used for biomedicine-related study because it is cost-effective, easily scalable and can be used without additional functionalization and sample pre-treatment.

Aim To investigate the effect of low shear stress (LSS) on the expression of Bmi-1 in human umbilical vein endothelial cells (HUVEC) and its possible mechanism.Methods Human umbilical vein endothelial cells were cultured in vitro.Immunofluorescence was used to detect the localization of Bmi-1 in the cells.0.5 h,1 h,2 h and 4 h were loaded into human umbilical vein endothelial cells by parallel plate flow chamber system.The expression of Bmi1 mRNA was detected by real-time quantitative RT-PCR.The expression of Bmi-1 protein was detected by Western blot.Specific signal inhibitor SB2219 was used to investigate the signal transduction pathway.Results Immunofluorescence observation showed that Bmi-1 was mainly distributed in the nucleus of human umbilical vein endothelial cells.The expression of Bmi-1 was significantly increased after 0.5 h of LSS,the expression of Bmi-1 mRNA and protein decreased gradually with the prolongation of the time (1 h,2 h and 4 h);the shear stress could significantly activate phosphorylated p38 expression;SB2219 could significantly inhibit the expression of Bmi-1.Conclusion LSS can induce the expression of Bmi-1 in human umbilical vein endothelial cells,the expression of Bmi-1 is closely related to the length of stimulation,this effect may be regulated by p38 signal.

Although doxorubicin has been widely used as an anticancer drug, it has dose-dependent toxic effects on ovarian follicle development and apoptosis, oocyte maturation, and hormone secretion. Ca2+ signaling also has vital roles in the same cellular functions of ovarian follicles, indicating a strong link with doxorubicin-induced ovarian toxicity. In the current project, doxorubicin-induced Ca2+ alternations in cultured rat ovarian follicles have been explored with the fluorescence resonance energy transfer technology. The results reveal that doxorubicin enhances the cytosolic Ca2+ level smoothly. Further experiments confirm that the endoplasmic reticulum (ER) calcium, but not the extracellular calcium influx, is the main source of intracellular calcium increase. Moreover, Src kinase activation could be the upstream of doxorubicin-induced ER calcium release. Therefore, this project demonstrates that doxorubicin increases the cytosolic Ca2+ mainly by releasing calcium from ER via Src kinase activation in ovarian follicles, which provides deeper understanding of doxorubicin-induced ovarian toxicity.

Insulin resistance is caused by various environmental and genetic factors leading to a number of serious health issues. Due to its multifactorial origin, molecular characterization may provide better tools for its effective treatment. On molecular level, dysregulation of signaling pathway by insulin receptor substrates (IRSs) is one of the most common reasons of this disease. IRSs are regulated by >50 serine/threonine kinases, which may have positive or negative effects on insulin sensitivity. Among these serine/threonine kinases, PIM kinases have garnered much attention as they not only affect insulin sensitivity by phosphorylating IRSs directly and/or indirectly but also alter the activities of their downstream molecules like PI3K, AKT, and mTOR. In this review, interactions of PIM kinases with IRSs and their downstream proteins and their action mechanism in the regulation of insulin resistance are elaborated. Furthermore, this review offers fundamental understandings of the role of PIM kinases in this signaling pathway.