A Critical Analysis of Quadratic Boost Based High-Gain Converters for Electric Vehicle Applications: A Review.

Conventional DC-DC boost converters have played a vital role in electric vehicle (EVs) powertrains by enabling the necessary voltage to increase to meet the needs of electric motors. However, recent developments in high-gain converters have introduced new possibilities with enhanced voltage amplification capabilities and efficiency. This study discusses and evaluates the state-of-the-art high-gain DC-DC converters for EV applications based on the Quadratic Boost Converter (QBC). Research into innovative topologies has increased in response to the increasing demand for efficient and high-performance power electronic converters in the rapidly expanding EV industry. Due to its ability to provide more significant voltage gains than conventional boost converters, the QBC has become a viable option for meeting the unique requirements of EV power systems. This survey focuses on the efficiency, power density, and overall performance parameters of QBC-based high-gain converters. The literature review provides a foundation for comprehending power electronics converters' trends, challenges, and opportunities. The acquired knowledge can enhance the design and optimization of high-gain converters based on the QBC, thereby fostering more sustainable and efficient power systems for the expanding electric mobility industry. In the future, the report suggests that investigating new high-gain converter design methodologies will reduce component stress and enhance the intact system efficiency.

Fracture Performance of Cementitious Composites Based on Quaternary Blended Cements.

This study presents test results and in-depth discussion regarding the measurement of the fracture mechanics parameters of new concrete composites based on quaternary blended cements (QBC). A composition of the two most commonly used mineral additives, i.e., fly ash (FA) and silica fume (SF), in combination with nanosilica (nS), has been proposed as a partial replacement for ordinary Portland cement (OPC) binder. Four series of concrete were made, one of which was the reference concrete (REF) and the remaining three were QBC. During the research, the main mechanical parameters of compressive strength (fcm) and splitting tensile strength (fctm), as well as fracture mechanics parameters and the critical stress intensity factor KIcS, along with critical crack-tip opening displacements (CTODc) were investigated. Based on the tests, it was found that the total addition of siliceous materials, i.e., SF + nS without FA, increases the strength and fracture parameters of concrete by approximately 40%. On the other hand, supplementing the composition of the binder with SF and nS with 5% of FA additive causes an increase in all mechanical parameters by approximately 10%, whereas an increase by another 10% in the FA content in the concrete mix causes a significant decrease in all the analyzed factors by 10%, compared to the composite with the addition of silica modifiers only.

Effect of circAGFG1 targeting miR-4429 on the proliferation, migration and invasion of cholangiocarcinoma QBC939 cells and its possible mechanism / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the effect of circAGFG1 on the proliferation, migration and invasion of cholangiocarcinoma QBC939 cells and its possible mechanism. Methods: The tumor tissues and corresponding para-cancerous tissues of 33 patients with cholangiocarcinoma who underwent surgical resection in the 988th Hospital of the Joint Logistics Support Force from April 2017 to October 2019 were collected. qPCR was used to detect the expression level of circAGFG1 and miR-4429 in the tissues. Cholangiocarcinoma QBC939 cells were cultured in vitro and transfected with si-circAGFG1 or miR-4429 mimics, or co-transfected with si-circAGFG1 and anti-miR-4429. Then, cell proliferation was detected by CCK-8 method and clone formation test, cell migration and invasion were detected by scratch test and Transwell assay, and the protein expression of E-cadherin and N-cadherin in cells was determined by Western blotting. Dual-luciferase reporter gene experiment was adopted to verify the regulatory relationship between circAGFG1 and miR-4429. Results: The expression of circAGFG1 was higher (3.89±0.26 vs 1.00±0.08, P<0.05) while the expression of miR-4429 (0.28±0.03 vs 1.00±0.05, P<0.05) was lower in cholangiocarcinoma tissues than those in para-cancerous tissues. After the interference with circAGFG1 or over-expression of miR-4429, the cell proliferation level, number of clone formation, scratch healing rate, number of invaded cells, and the protein expression of N-cadherin in QBC939 cells were reduced (all P<0.05), but the protein expression of E-cadherin was elevated (P<0.05). circAGFG1 could targetedly bind with miR-4429, and interfering circAGFG1 promoted the expression of miR-4429 in QBC939 cells (all P<0.05). Down-regulation of miR-4429 reversed the effect of interfering circAGFG1 on the proliferation, migration and invasion of QBC939 cells (all P<0.05). Conclusion: The expression of circAGFG1 is up-regulated in cholangiocarcinoma tissues, which may promote the proliferation, migration and invasion of cholangiocarcinoma QBC939 cells by targetedly inhibiting the expression of miR-4429.

circ_0000615 regulates proliferation, migration and invasion of cholangiocarcinoma cells by targeting miR-432-5p / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨circ_0000615在胆管癌细胞中的表达及其对胆管癌细胞增殖、迁移和侵袭能力的影响和可能的调控机制。方法：通过qPCR检测circ_0000615在正常胆管上皮HIBEC细胞和胆管癌CCLP-1、QBC939、TFK-1和RBE细胞中的表达水平。双荧光素酶报告基因实验验证circ_0000615与miR-432-5p的靶向关系。将si-NC、si-circ_0000615（si-circ-1、si-circ-2）、inhibitor-NC和inhibitor-miR-432-5p转染至CCLP-1和QBC939细胞，转染细胞分为si-NC组、si-circ-1组、si-circ-2组、si-NC+inh-NC组、si-NC+inh-miR-432-5p组和si-circ-1+inh-miR-432-5p组，通过CCK-8、EdU和Transwell实验检测各转染组胆管癌细胞的增殖、迁移和侵袭能力。结果：在胆管癌细胞中circ_0000615呈高表达而miR-432-5p呈低表达（P<0.05或P<0.01）；双荧光素酶报告基因实验证实circ_0000615与miR-432-5p之间存在靶向关系（P<0.01）；敲减circ_0000615可明显抑制CCLP-1、QBC939细胞的增殖、侵袭和迁移能力（P<0.05或P<0.01）；下调miR-432-5p可部分逆转敲减circ_0000615对胆管癌CCLP-1和QBC939细胞增殖、迁移和侵袭的抑制作用（P<0.05或P<0.01）。结论：circ_0000615通过靶向miR-432-5p调控胆管癌细胞的增殖、侵袭和迁移。

Complete Blood Count as point of care testing QBC STAR™: Preliminary evaluation.

INTRODUCTION: Point of care testing (POCT) represents a valuable option when laboratory data shall be urgently available for timely clinical management, with a turnaround time (TAT) that is unfeasible using conventional laboratory instrumentation. This study was aimed to compare the performance of QBC STAR™ compared to Sysmex XN-module and the reference optical microscopy (OM) assessment. MATERIAL AND METHODS: One hundred peripheral blood samples, collected in K3 EDTA tubes, and 50 capillary blood samples obtained by finger stick were analyzed with QBC STAR™, Sysmex XN-module, and OM. Data were compared with Passing-Bablok regression and Bland-Altman plots. RESULTS: The Passing-Bablok regression analysis (QBC STAR™ capillary sample vs XN-module) yielded slopes comprised between 0.30 and 1.37, while the intercepts ranged between -17.57 and 232.6. Bland-Altman plots yielded relative bias comprised between -4.87% (for MN QBC STAR™ capillary sample vs XN-module) and 27% (PLT QBC STAR™ capillary sample vs XN-module). A significant bias was found for all parameters except MN and WBC, RBC in all and pediatric samples, and HB in adults samples. CONCLUSION: The results of this analytical evaluation suggest that QBC STAR™ may not be the ideal tool for performing complete blood count analysis for diagnostic purposes, while it could be more useful in urgent/emergent conditions, such as for rapid monitoring of some hematological parameters (eg, WBC and HB).

Evaluation of a Combined MHE-NMPC Approach to Handle Plant-Model Mismatch in a Rotary Tablet Press.

The transition from batch to continuous processes in the pharmaceutical industry has been driven by the potential improvement in process controllability, product quality homogeneity, and reduction of material inventory. A quality-by-control (QbC) approach has been implemented in a variety of pharmaceutical product manufacturing modalities to increase product quality through a three-level hierarchical control structure. In the implementation of the QbC approach it is common practice to simplify control algorithms by utilizing linearized models with constant model parameters. Nonlinear model predictive control (NMPC) can effectively deliver control functionality for highly sensitive variations and nonlinear multiple-input-multiple-output (MIMO) systems, which is essential for the highly regulated pharmaceutical manufacturing industry. This work focuses on developing and implementing NMPC in continuous manufacturing of solid dosage forms. To mitigate control degradation caused by plant-model mismatch, careful monitoring and continuous improvement strategies are studied. When moving horizon estimation (MHE) is integrated with NMPC, historical data in the past time window together with real-time data from the sensor network enable state estimation and accurate tracking of the highly sensitive model parameters. The adaptive model used in the NMPC strategy can compensate for process uncertainties, further reducing plant-model mismatch effects. The nonlinear mechanistic model used in both MHE and NMPC can predict the essential but complex powder properties and provide physical interpretation of abnormal events. The adaptive NMPC implementation and its real-time control performance analysis and practical applicability are demonstrated through a series of illustrative examples that highlight the effectiveness of the proposed approach for different scenarios of plant-model mismatch, while also incorporating glidant effects.

Functions of the Plant Qbc SNARE SNAP25 in Cytokinesis and Biotic and Abiotic Stress Responses.

Eukaryotes transport biomolecules between intracellular organelles and between cells and the environment via vesicle trafficking. Soluble N -ethylmaleimide-sensitive factor attachment protein receptors (SNARE proteins) play pivotal roles in vesicle and membrane trafficking. These proteins are categorized as Qa, Qb, Qc, and R SNAREs and form a complex that induces vesicle fusion for targeting of vesicle cargos. As the core components of the SNARE complex, the SNAP25 Qbc SNAREs perform various functions related to cellular homeostasis. The Arabidopsis thaliana SNAP25 homolog AtSNAP33 interacts with Qa and R SNAREs and plays a key role in cytokinesis and in triggering innate immune responses. However, other Arabidopsis SNAP25 homologs, such as AtSNAP29 and AtSNAP30, are not well studied; this includes their localization, interactions, structures, and functions. Here, we discuss three biological functions of plant SNAP25 orthologs in the context of AtSNAP33 and highlight recent findings on SNAP25 orthologs in various plants. We propose future directions for determining the roles of the less well-characterized AtSNAP29 and AtSNAP30 proteins.

Performance evaluation of different strategies based on microscopy techniques, rapid diagnostic test and molecular loop-mediated isothermal amplification assay for the diagnosis of imported malaria.

OBJECTIVES: Malaria is one of most common tropical diseases encountered in travellers and migrants. It requires an urgent and reliable diagnosis considering its potential severity. In this study, performance of five diagnostic assays were evaluated in a nonendemic region and compared prospectively to quantitative PCR (qPCR). METHODS: A prospective study was conducted at Toulouse Hospital from August 2017 to January 2018 and included all patients with initial Plasmodium screening. Thin and thick blood smears (TnS, TkS), quantitative buffy coat (QBC), rapid diagnostic tests (RDTs) and commercial loop-mediated isothermal amplification (LAMP) were independently performed on each blood sample and compared to our qPCR reference standard. RESULTS: The study encompassed 331 patients, mainly returning from Africa. qPCR detected 73 Plasmodium-positive samples (including 58 falciparum). Individually, LAMP had a 97.3% (71/73) sensitivity, far ahead of TnS (84.9%, 62/73), TkS (86.3%, 63/73), QBC (86.3%, 63/73) and RDT (86.3%, 63/73). RDT demonstrated a high sensitivity for falciparum (98.3%, 57/58) but missed all ovale, malariae and knowlesi infections. Specificity was excellent for all techniques (99.6-100%). The most sensitive diagnosis strategies were TnS + RDT (95.9%, 70/73), TnS + LAMP (97.3%, 71/73) and TnS + RDT + LAMP (100%, 73/73), about 10% higher than strategies using exclusively microscopy, TkS + TnS (87.7%, 64/73) or QBC + TnS (87.7%, 64/73). TnS remains necessary for Plasmodium species identification and quantification. Adding sequentially TnS only on LAMP-positive samples did not decrease TnS + LAMP strategy sensitivity. CONCLUSIONS: In nonendemic countries, the currently recommended microscopy-based strategies seem unsatisfactory for malaria diagnosis considering RDT and LAMP performance, two rapid and sensitive assays that require limited training.

Effects of propofol on human cholangiocarcinoma and the associated mechanisms.

Cholangiocarcinoma (CCA) is the most common type of biliary duct malignancy. Propofol is a fast-acting intravenous anesthetic, which also exerts an anti-cancer effect. The aim of the current study was to explore the effects of propofol on human CCA and the associated mechanisms in vitro. The results indicated that as concentration (0, 1, 5 and 10 µg/ml) of propofol and treatment time (24, 48 and 72 h) increased, the cell inhibition rate of human CCA QBC939 cells increased. Furthermore, treatment with various concentrations of propofol for 48 h resulted in a decrease in migration and invasion capacity in QBC939 cells. Propofol also induced the apoptosis of QBC939 cells and cell cycle arrest in G1 phase. Propofol treatment increased the expression level of Bax and decreased that of Bcl-2. In addition, the effects of propofol on gene expression were evaluated, including Wnt3α, ß-catenin, Snail1 and c-myc in the Wnt/ß-catenin signaling pathway. It was identified that as the concentration of propofol increased, the expression of these genes decreased. In conclusion, the current results indicate that propofol is a promising therapeutic agent for the treatment of CCA.

Multiplex real-time PCR for diagnosing malaria in a non-endemic setting: a prospective comparison to conventional methods.

Almost a decade ago our diagnostic laboratory implemented an in-house real-time PCR for the detection of Plasmodium DNA to diagnose malaria in parallel with conventional diagnostics, i.e., microscopy (thick and thin smears), quantitative buffy coat microscopy (QBC), and a rapid diagnostic test (RDT). Here we report our experiences and make a comparison between the different diagnostic procedures used in this non-endemic setting. All patients during the period February 2009-December 2017 suspected of malaria were prospectively tested at the moment of sample collection. Both PCR and conventional malaria diagnostics were carried out on a total of 839 specimens from 825 patients. In addition, three Plasmodium falciparum (Pf) patients were closely followed by real-time PCR and microscopy after treatment. Overall, 56 samples (55 patients) tested positive by real-time PCR, of which six were missed by microscopy and seven by QBC. RDT showed fairly good results in detecting Pf, whereas specificity was not optimal. RDT failed to detect 10 of 17 non-Pf PCR positive specimens. One Plasmodium malariae patient would have been missed if only conventional diagnostic tests had been used. The high sensitivity of the PCR was confirmed by the number of PCR positive, microscopy negative post-treatment samples. In conclusion, within our routine diagnostic setting, malaria real-time PCR not only showed a high level of agreement with the conventional methods used, but also showed higher sensitivity and better specificity. Still, for complete replacement of the conventional procedures in a non-endemic setting, the time-to-results of the real-time PCR is currently too long.

Comparing the tested results of QBC Star and Sysmex XP-100 hematology analyzers and analyzing their operational performance / 国际检验医学杂志

Objective Both QBC Star and Sysmex XP-100 hematology analyzers are convenient to carry,which can be used nor-mally under the condition of the field(emergency).This study would compare their test results and operating performance,so to provide guidance for rational use of the instruments.Methods 100 fresh blood samples of 100 health soldiers anti-coagulated by EDTA-K2 were detected by QBC Star and Sysmex XP-100 haematology analyzers respectively,the results of two analyzers were comparatively analyzed and their test time and operating convenience were analyzed.Results There was no significant difference in the results of hemoglobin concentration (HGB),hematocrit (HCT)tested by the two methods (P >0.05).There were significant difference of the mean corpuscular hemoglobin concentration (MCHC),the sum of lymphocyte percent and middle type cells (LYM%+MID%),neutrophil percentage(NEUT%),white blood cell count(WBC),platelet count(PLT)tested by the two meth-ods(P <0.05).The values of MCHC and LYM%+MID% tested by the QBC Star were significantly lower than that detected by Sysmex XP-100(P <0.05),while the rest indicators tested by the former were higher than that of the latter.It took about 5 minutes to complete a blood sample analysis with QBC Star,while about 1 min was needed for Sysmex XP-100.Conclusion The test results of QBC Star and Sysmex XP-100 hematology analyzers couldn′t exchanged except for that of HCT and HGB.Under the condition of field(emergency),QBC Star hematology analyzer is suitable for individual medical examination,and Sysmex XP-100 hematology an-alyzer can be used for the batch medical examination.

Killing effect of CIK cells combined with Gemcitabine on QBC939 cells / 中国现代普通外科进展

Objective:To investigate the anti-tumor effects of cytokine-induced kill cells(CIK)methods combined with chemotherapeuticdrug Gemcitabine against Cholangiocarcinoma cancer cell lines QBC-939.Methods:Peripheral blood mononuclear cells(PBMC) of healthy people were stimulated by different cytokines,and were induced into CIK cells.CIK cells were cultured for 14 days as effector cells.The phenotype of CIK cells were analyzed by flow cytometer.QBC939 cells were cultured with the CIK cells at different effector-target ratio or various concentrations of Gemcitabine for 24 and 48 hours.The antitumor effects were measured by CCK8 methods.The expression of Bax was detected by using Western blot.Results:The CD3+CD4+,CD3+CD8+,CD3+HLA-DR+,CD3+CD56+,CD4+CD25+ double positive cel1 was up to 10.89％,60.27％,71.82％,9.03％ and 4.01％ after 14 days' cultivation.The killing effect of CIK and Gemcitabine increased with the increase of effector-target ratio and drug concentration or the extension of time.The killing effect of combination of CIK and Gemcitabine was obviously higher than that of each single factor.The protein levels detected hints of CIK cells and gemcitabine can up-regulated the expression of Bax,and the joint action of both is more significant.Conclusions:CIK cells have strong anti-tumor effect against QBC939 cells by inducing apoptosis of QBC939 cells,and it can enhance the anti-tumor effects of Gemcitabine against QBC939 cells when CIK and Gemcitabine are combined together.

Hemozoin Pigment: An Important Tool for Low Parasitemic Malarial Diagnosis.

Low parasitemic condition in malaria remains a diagnostic challenge; as the available diagnostic methods failed to detect. Currently, hemozoin (Hz) pigment is gaining attention in the diagnosis of malaria. The major drawback is ease of detection of Hz in routine practice. A pilot study was conducted to evaluate the role of Hz pigment and to compare the performance of quantitative buffy coat assay (QBC) and PCR in such conditions. Clinically suspected cases of malaria were examined by both Giemsa stain and immunochromatographic test (ICT). Samples positive by ICT and negative by Giemsa stain were further examined by nested PCR targeting 18S rRNA and QBC for the presence of malaria parasites and pigments. Thirty blood samples fulfilled the inclusion criteria out of which 23 were Plasmodium vivax (Pv), 4 Plasmodium falciparum (Pf), and 3 mixed (Pv and Pf) by immunochromatographic test. Twenty-one out of 30 (70%) were positive by nested PCR in comparison to 25/30 (83%) by QBC. Samples containing both malaria parasites and Hz pigment by QBC completely showed concordance with the PCR result. However, 61% of total samples containing only Hz pigment were observed positive by PCR. Hz pigment remains an important tool for malaria diagnosis. Identification of leukocytes containing pigments by QBC not only indicates recent malarial infections but also puts light on severity of the disease. QBC assay is a rapid, highly sensitive, and cost-effective method to detect malaria parasites and Hz pigment especially in low parasitemic conditions.

Hemozoin Pigment: An Important Tool for Low Parasitemic Malarial Diagnosis

Low parasitemic condition in malaria remains a diagnostic challenge; as the available diagnostic methods failed to detect. Currently, hemozoin (Hz) pigment is gaining attention in the diagnosis of malaria. The major drawback is ease of detection of Hz in routine practice. A pilot study was conducted to evaluate the role of Hz pigment and to compare the performance of quantitative buffy coat assay (QBC) and PCR in such conditions. Clinically suspected cases of malaria were examined by both Giemsa stain and immunochromatographic test (ICT). Samples positive by ICT and negative by Giemsa stain were further examined by nested PCR targeting 18S rRNA and QBC for the presence of malaria parasites and pigments. Thirty blood samples fulfilled the inclusion criteria out of which 23 were Plasmodium vivax (Pv), 4 Plasmodium falciparum (Pf), and 3 mixed (Pv and Pf) by immunochromatographic test. Twenty-one out of 30 (70%) were positive by nested PCR in comparison to 25/30 (83%) by QBC. Samples containing both malaria parasites and Hz pigment by QBC completely showed concordance with the PCR result. However, 61% of total samples containing only Hz pigment were observed positive by PCR. Hz pigment remains an important tool for malaria diagnosis. Identification of leukocytes containing pigments by QBC not only indicates recent malarial infections but also puts light on severity of the disease. QBC assay is a rapid, highly sensitive, and cost-effective method to detect malaria parasites and Hz pigment especially in low parasitemic conditions.

On spacecraft maneuvers control subject to propellant engine modes.

The paper attempts to address a new control approach to spacecraft maneuvers based upon the modes of propellant engine. A realization of control strategy is now presented in engine on mode (high thrusts as well as further low thrusts), which is related to small angle maneuvers and engine off mode (specified low thrusts), which is also related to large angle maneuvers. There is currently a coarse-fine tuning in engine on mode. It is shown that the process of handling the angular velocities are finalized via rate feedback system in engine modes, where the angular rotations are controlled through quaternion based control (QBCL)strategy in engine off mode and these ones are also controlled through an optimum PID (OPIDH) strategy in engine on mode.

Reducing error in feline platelet enumeration by addition of Iloprost to blood specimens: comparison to prostaglandin E1 and EDTA.

BACKGROUND: Prostaglandin E1 (PGE1) and Iloprost inhibit platelet aggregation and should prevent or minimize preanalytic error with feline platelet enumeration. OBJECTIVES: The objective was to compare the relative effectiveness in reducing errors in platelet enumeration by adding Iloprost to feline EDTA blood specimens in comparison to adding PGE1 or EDTA alone. In addition, a grading system for platelet aggregation in blood smears was evaluated for effectiveness in predicting prominent errors and compared to ADVIA's PLT-CLM flag. Finally, the use of plateletcrit in feline blood with platelet aggregation was evaluated. METHODS: Blood specimens from 35 cats were included. Blood was collected into EDTA tubes with or without Iloprost or PGE1, and was rapidly mixed. Platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV), and platelet flags were determined with an ADVIA 2120. Manual PLT was performed with a Leucoplate stain. PLT was determined by an IDEXX VetAutoread hematology analyzer (QBC). RESULTS: Neither addition of Iloprost nor PGE1 to EDTA blood specimens completely prevented platelet aggregation. Iloprost-treated specimens had the least severe aggregation. PGE1 was better than EDTA alone. Significant errors in PLT results were consistently identified by the grading system. ADVIA's PLT-CL flag usually predicted significant errors in PLT. QBC PLT results showed high imprecision. Manual PLT error was smaller than ADVIA PLT in EDTA specimens with aggregation. CONCLUSIONS: Adding Iloprost to feline blood specimens improved platelet enumeration accuracy. A grading system for severity of platelet aggregation and usually the ADVIA's PLT-CL alarm predicted specimens with significant errors in platelet enumeration.

Upregulation of the MCL-1S protein variant following dihydroartemisinin treatment induces apoptosis in cholangiocarcinoma cells.

The aim of the present study was to determine whether dihydroartemisinin (DHA) induces apoptosis in the human cholangiocarcinoma QBC939 cell line through the regulation of myeloid cell leukemia-1 (MCL-1) expression. The inhibitory rates of DHA on QBC939 cell proliferation and the effects of DHA on the cell death rates at various DHA concentrations and following various treatment times were examined. The rate of apoptosis and cell cycle changes following DHA treatment were examined and the changes in the expression of MCL-1 mRNAs and MCL-1 proteins following DHA treatment were also examined. The MTT assay and trypan blue staining demonstrated that DHA significantly inhibited the proliferation (P<0.05) and promoted the death of QBC939 cells (P<0.05). The DNA ladder assay and flow cytometry (FCM) analysis demonstrated that the rate of apoptosis in the experimental group was significantly increased following DHA treatment (P<0.01). FCM analysis also demonstrated that DHA treatment led to a reduction in the percentage of QBC939 cells in the G0/G1 and G2/M phases, and the majority of the DNA-treated cells were arrested in the S phase of the cell cycle (P<0.01). Western blot analysis demonstrated that DHA treatment significantly upregulated the expression of the pro-apoptotic MCL-1S protein. In contrast, no significant difference in the expression of the anti-apoptotic MCL-1L protein was observed following DHA treatment. DHA affected the expression of the apoptosis-associated protein MCL-1 through multiple mechanisms. DHA treatment increased the ratio of MCL-1S/MCL-1L protein, thus inducing apoptosis in cholangiocarcinoma cells.

Effects of Staurosporine on the Proliferation and Apoptosis of Human Cholangiocarcinoma QBC-939 Cells / 医药导报

Objective To study the effects of protein kinase C (PKC) inhibitor staurosporine (STS) on the proliferation and apoptosis of human cholangiocarcinoma QBC-939 cells and to explore its possible mechanism. Methods CCK-8 was used to detect the effects of PKC inhibitor STS on the proliferation of human cholangiocarcinoma QBC-939 cells. The effects of STS on the ultrastructural characteristics of QBC-939 cells were observed by routine transmission electron microscopy (TEM). The apoptosis rate and the cell cycle distribution of QBC-939 cells were detected by flow cytometry. The expression of cyclin B1,Cdk1 and p-Cdk1 in QBC-939 cells was detected by Western blotting. Results STS could significantly inhibit the proliferation of QBC-939 cells in a dose-dependent manner (P <0. 05) and the half inhibitory concentration ( IC50 ) of QBC-939 cells at 24th and 48th h was 334 nmol·L-1 and 118 nmol · L-1 , respectively. TEM observed that STS could induce typical apoptotic bodies and super-microstructural changes of QBC-939 cells. By Annexin V-FITC/ PI double labeling flow cytometry,we found that the apoptotic rate of QBC-939 cells after treatment with STS for 0,12,24 and 48 h was (10. 16±4. 52)% ,(22. 35±2. 19)% ,(34. 27±2. 30)% and (59. 70±5. 97)% ,respectively. By flow cytometry,compared with the control group,STS could significantly increase apoptosis rate of QBC-939 cells,decrease the percentage of cells in G0 / G1 phase and increase the percentage of cells in G2 / M phase (P<0. 05). Western blotting proved that the expression levels of cyclin B1 and Cdk1 proteins in the STS-treated QBC-939 cells were significantly decreased (P<0. 05),while the expression level of p-Cdk1 protein in the STS-treated QBC-939 cells was significantly increased ( P < 0. 05 ). Conclusion STS can significantly inhibit cell proliferation and induce apoptosis of human cholangiocarcinoma QBC-939 cells and the mechanism may be related to cell cycle arrest at G2 / M phase.

Photosan-II loaded hollow silica nanoparticles: preparation and its effect in killing for QBC939 cells.

BACKGROUND: Nanoparticles have been explored recently as an efficient means to deliver photosensitizers for photodynamic therapy. However, it is largely unknown if polyhematoporphyrin (C34H38N4NaO5, Photosan-II, PS) or other photosensitizers can be efficiently delivered by hollow silica nanoparticles (HSNP). METHODS: Polyhematoporphyrin (C34H38N4NaO5, Photosan-II, PS) was loaded into hollow silica nanoparticles (HSNP) by one-step wet chemical-based synthetic route. Dynamic light scattering (DLS) and polydispersive index (PDI) were used for measurement of the particles size and size distribution. Transmission electron microscope and scanning electron microscopy were used for the microstructure, morphological and chemical composition analysis. Fourier transform infrared spectrometry spectra and fluorescence emission spectrum were obtained. The photobiological activity of the PS-loaded HSNP was evaluated on human cholangiocarcinoma QBC939 cells. The cellular viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Apoptotic and necrotic cells were measured by flow cytometry. RESULTS: DLS measurements showed that the size of the particles is in the range of 25-90 nm. PDI of the PS-loaded HSNP is 0.121 ± 0.01, indicating that samples have excellent quality with narrow size distribution to monomodal systems. In MTT assay, PS-loaded HSNP and free PS of the same concentration killed about 95.3% ± 2.0% and 55.7% ± 1.9% of QBC939 cells, respectively. The flow cytometry demonstrated that the laser induced cell death with PS-loaded HSNP was much more severe than that of free PS (P<0.05). CONCLUSIONS: Photosan-II-loaded hollow silica nanoparticles not only can quickly deliver Photosan-II into cells but also can reach a more high concentration than free Photosan-II. HSNP is a desirable vehicle and the release system that shows promises for photodynamic therapy use, which not only improve the aqueous solubility, stability and transport efficiency of PS, but also increase its photodynamic efficacy compared to free PS.