Biogenesis of circular RNAs in vitro and in vivo from the Drosophila Nk2.1 / scarecrow gene.

scarecrow ( scro ) encodes a fly homolog of mammalian Nkx2.1 that is vital for early fly development as well as for optic lobe development. Interestingly, scro was reported to produce a circular RNA (circRNA). In this study, we identified 12 different scro circRNAs, which are either mono- or multi-exonic forms. The most abundant forms are circE2 carrying the second exon only and bi-exonic circE3-E4. Levels of circE2 show an age-dependent increase in adult heads, supporting a general trend of high accumulation of circRNAs in aged fly brains. Aligning sequences of introns flanking exons uncovered two pairs of intronic complementary sequences (ICSs); one pair residing in introns 1 and 2 and the other in introns 2 and 4. The first pair was demonstrated to be essential for the circE2 production in cell-based assays; furthermore, deletion of the region including potential ICS components in the intron-2 reduced in vivo production of circE2 and circE3-E4 by 80%, indicating them to be essential for the biogenesis of these isoforms. Besides the ICS, the intron regions immediately abutting exons seemed to be responsible for a basal level of circRNA formation. Moreover, the replacement of scro -ICS with those derived from laccase2 was comparably effective in scro -circRNA production, buttressing the importance of the hairpin-loop structure formed by ICS for the biogenesis of circRNA. Lastly, overexpressed scro affected outcomes of both linear and circular RNAs from the endogenous scro locus, suggesting that Scro plays a direct or indirect role in regulating expression levels of either or both forms.

Development of an Emulsion Gel Containing Peanut Sprout Oil as a Fat Replacer in Muffins: Physicochemical, Tomographic, and Texture Properties.

Peanut sprouts are known to increase their resveratrol content during germination, leading to cultivation in smart farms. Recently, peanut sprout oil extraction and sales have gained traction; however, processed foods utilizing peanut sprout oil have yet to be developed. In this study, water-in-oil (W/O) emulsion gels were structured with water, peanut sprout oil (PSO), sorbitan monostearate (SMS), and candelilla wax (CW) in different ratios, and their potential as shortening substitutes in muffins was evaluated on physicochemical and sensory properties. PSO comprised 67% unsaturated fatty acids and had higher phospholipid (17.97%) and resveratrol (15.95 µg/L) contents and antioxidant activity (71.52%) compared to peanut oil. The PSO emulsion gels were physically structured without changing their chemical compositions. The SMS and CW ratios were found to have a significant influence on the textural properties, solid fat content, rheology, and crystallization of the emulsion gels. The viscoelastic properties of the emulsion gels showed a higher storage modulus than loss modulus and increased with increasing gelator content. Muffins prepared with emulsion gels were characterized by a harder texture and larger pore size, while in the case of muffins mixed with a ratio of 25% SMS and 75% CW, there was no significant difference in overall preference of sensory evaluation compared to shortening muffins. Thus, these findings reveal the potential utility of PSO as a fat substitute and indicate that W/O emulsion gels are suitable for producing muffins without a loss of quality.

Optimization of differential filtration-based mitochondrial isolation for mitochondrial transplant to cerebral organoids.

BACKGROUND: Mitochondrial dysfunction is involved in several diseases ranging from genetic mitochondrial disorders to chronic metabolic diseases. An emerging approach to potentially treat mitochondrial dysfunction is the transplantation of autologous live mitochondria to promote cell regeneration. We tested the differential filtration-based mitochondrial isolation protocol established by the McCully laboratory for use in cellular models but found whole cell contaminants in the mitochondrial isolate. METHODS: Therefore, we explored alternative types of 5-µm filters (filters A and B) for isolation of mitochondria from multiple cell lines including HEK293 cells and induced pluripotent stem cells (iPSCs). MitoTracker™ staining combined with flow cytometry was used to quantify the concentration of viable mitochondria. A proof-of-principle mitochondrial transplant was performed using mitoDsRed2-tagged mitochondria into a H9-derived cerebral organoid. RESULTS: We found that filter B provided the highest quality mitochondria as compared to the 5-µm filter used in the original protocol. Using this method, mitochondria were also successfully isolated from induced pluripotent stem cells. To test for viability, mitoDsRed2-tagged mitochondria were isolated and transplanted into H9-derived cerebral organoids and observed that mitochondria were engulfed as indicated by immunofluorescent co-localization of TOMM20 and MAP2. CONCLUSIONS: Thus, use of filter B in a differential filtration approach is ideal for isolating pure and viable mitochondria from cells, allowing us to begin evaluating long-term integration and safety of mitochondrial transplant using cellular sources.

ERdj5 protects goblet cells from endoplasmic reticulum stress-mediated apoptosis under inflammatory conditions.

Endoplasmic reticulum stress is closely associated with the onset and progression of inflammatory bowel disease. ERdj5 is an endoplasmic reticulum-resident protein disulfide reductase that mediates the cleavage and degradation of misfolded proteins. Although ERdj5 expression is significantly higher in the colonic tissues of patients with inflammatory bowel disease than in healthy controls, its role in inflammatory bowel disease has not yet been reported. In the current study, we used ERdj5-knockout mice to investigate the potential roles of ERdj5 in inflammatory bowel disease. ERdj5 deficiency causes severe inflammation in mouse colitis models and weakens gut barrier function by increasing NF-κB-mediated inflammation. ERdj5 may not be indispensable for goblet cell function under steady-state conditions, but its deficiency induces goblet cell apoptosis under inflammatory conditions. Treatment of ERdj5-knockout mice with the chemical chaperone ursodeoxycholic acid ameliorated severe colitis by reducing endoplasmic reticulum stress. These findings highlight the important role of ERdj5 in preserving goblet cell viability and function by resolving endoplasmic reticulum stress.

Chemical constituents from the stem bark of Albizia julibrissin and their SREBP-1c inhibitory activity.

One new lignan, julibrissinoside II, along with thirteen known compounds, was isolated from the stem bark of Albizia julibrissin. The structure of julibrissinoside II was determined on the basis of extensive spectroscopic methods, including NMR and CD spectroscopic data. The isolated compounds were tested for their SREBP-1c inhibitory activity at different concentrations using mouse hepatocyte AML12 cell lines. Among them, linoleic acid (2) and 3-O-methylfisetin (4) showed significant SREBP-1c inhibitory activity at the concentration of 100 µM.

Systemic Inflammatory Biomarkers in DSM-5-Defined Disorders and COVID-19: Evidence From Published Meta-analyses.

On March 11, 2020, the World Health Organization declared the outbreak of the novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) as a global pandemic. At the center of SARS-CoV-2 is the activation of inflammatory markers; remarkably, interleukin 6 and C-reactive protein seem to be consistently elevated in patients with SARS-CoV-2. Here, we showed that increased systemic C-reactive protein and interleukin 6 are common biomarkers of both severe COVID-19 and DSM-5-defined disorders. However, it is not known whether patients with psychiatric disorders with preexisting increased interleukin 6 and C-reactive protein are more vulnerable to severe complications of COVID-19 because of the additive inflammatory processes.

Amelioration of DSS-Induced Acute Colitis in Mice by Recombinant Monomeric Human Interleukin-22.

IL-22, a pleiotropic cytokine, is known to have a profound effect on the regeneration of damaged intestinal barriers. The tissue-protective properties of IL-22 are expected to be potentially exploited in the attenuation and treatment of colitis. However, because of the disease-promoting role of IL-22 in chronic inflammation, a comprehensive evaluation is required to translate IL-22 into the clinical domain. Here, we present the effective production of soluble human IL-22 in bacteria to prove whether recombinant IL-22 has the ability to ameliorate colitis and inflammation. IL-22 was expressed in the form of a biologically active monomer and non-functional oligomers. Monomeric IL-22 (mIL-22) was highly purified through a series of 3 separate chromatographic methods and an enzymatic reaction. We reveal that the resulting mIL-22 is correctly folded and is able to phosphorylate STAT3 in HT-29 cells. Subsequently, we demonstrate that mIL-22 enables the attenuation of dextran sodium sulfate-induced acute colitis in mice, as well as the suppression of pro-inflammatory cytokine production. Collectively, our results suggest that the recombinant mIL-22 is suitable to study the biological roles of endogenous IL-22 in immune responses and can be developed as a biological agent associated with inflammatory disorders.

Circulating cell-free mitochondrial DNA in brain health and disease: A systematic review and meta-analysis.

OBJECTIVES: Circulating cell-free mitochondrial DNA (ccf-mtDNA) are detectable fragments of mtDNA released from the cell as a result of mitochondrial dysfunction or apoptosis. The brain is one of the most energy demanding organs in the human body, and many neuropsychiatric and non-psychiatric neurological diseases have mitochondrial dysfunction associated with disease pathophysiology. Thus, we aimed to assess ccf-mtDNA as a potential biomarker for brain diseases. METHODS: We conducted a systematic review and meta-analyses of studies that examined peripheral and/or cerebrospinal fluid (CSF) ccf-mtDNA relevant to neuropsychiatric conditions, which we define as disorders of affect, behaviour and mood, and non-psychiatric neurological diseases, which consist of neurological diseases not related to psychiatry including neurodegenerative diseases. RESULTS: The results of the sensitivity analysis investigating the levels of peripheral ccf-mtDNA in neuropsychiatric studies showed no significant difference between cases and controls (Z = 1.57; p = 0.12), whereas the results of the sensitivity analysis investigating the levels of CSF ccf-mtDNA in non-psychiatric neurological diseases showed a decreasing trend in cases compared with controls (Z = 2.32; p = 0.02). Interestingly, the results indicate an overall mitochondrial stress associated mainly with non-psychiatric neurological diseases. CONCLUSIONS: Our study supports the involvement of mitochondrial stress, here defined as ccf-mtDNA, in brain diseases and encourage further investigation of ccf-mtDNA among patients with brain diseases.

Inflammatory markers, brain-derived neurotrophic factor, and the symptomatic course of adolescent bipolar disorder: A prospective repeated-measures study.

BACKGROUND: Numerous studies have found elevated pro-inflammatory markers and reduced brain-derived neurotrophic factor (BDNF) during symptomatic episodes of bipolar disorder (BD) in adults. There is a paucity of research examining these markers in youth with BD, or longitudinally in any BD age group. METHODS: 79 adolescents, ages 13-19 years, were enrolled, including 43 symptomatic adolescents with BD and 36 age-matched healthy controls (HC). Blood samples were collected from all participants at intake, and repeatedly from BD participants at pre-specified intervals over the course of two years. Serum was assayed for levels of pro-inflammatory markers (c-reactive protein [CRP], interleukin [IL]-6, tumor necrosis factor alpha [TNF-α]), BDNF and the anti-inflammatory marker, IL-10. Week-by-week severity of mood symptoms was assessed using semi-structured interviews. RESULTS: Adolescents with BD provided an average of 4.6 blood samples, on average every 5.0 months. During the most severe symptomatic interval (i.e., highest sum of mood symptom scores) among BD adolescents, levels of CRP (p = 0.01) and pro- to anti-inflammatory ratios (CRP/IL-10; p < 0.001 and IL-6/IL-10; p = 0.046) were significantly greater, and IL-10 levels (p = 0.004) were significantly lower, vs. HC. There were no differences between BD and HC in IL-6, TNF-α or BDNF. Within BD participants, higher BDNF (p = 0.01) and IL-10 levels (p = 0.001) significantly predicted greater burden of mood symptoms over the subsequent epoch. Moreover, higher CRP levels (p = 0.009) at intake predicted greater time to recovery from the index symptomatic episode. CONCLUSIONS: In the first repeated-measures study on this topic in adolescents with BD, we found evidence that CRP, an inexpensive and ubiquitous blood test, may be useful in predicting the prospective course of BD symptoms. Future larger studies are warranted.

A Novel Anti-PD-L1 Antibody Exhibits Antitumor Effects on Multiple Myeloma in Murine Models via Antibody-Dependent Cellular Cytotoxicity.

Multiple myeloma is a malignant cancer of plasma cells. Despite recent progress with immunomodulatory drugs and proteasome inhibitors, it remains an incurable disease that requires other strategies to overcome its recurrence and non-response. Based on the high expression levels of programmed death-ligand 1 (PD-L1) in human multiple myeloma isolated from bone marrow and the murine myeloma cell lines, NS-1 and MOPC-315, we propose PD-L1 molecule as a target of anti-multiple myeloma therapy. We developed a novel anti-PD-L1 antibody containing a murine immunoglobulin G subclass 2a (IgG2a) fragment crystallizable (Fc) domain that can induce antibody-dependent cellular cytotoxicity. The newly developed anti-PD-L1 antibody showed significant antitumor effects against multiple myeloma in mice subcutaneously, intraperitoneally, or intravenously inoculated with NS-1 and MOPC-315 cells. The anti-PD-L1 effects on multiple myeloma may be related to a decrease in the immunosuppressive myeloid-derived suppressor cells (MDSCs), but there were no changes in the splenic MDSCs after combined treatment with lenalidomide and the anti-PD-L1 antibody. Interestingly, the newly developed anti-PD-L1 antibody can induce antibody-dependent cellular cytotoxicity in the myeloma cells, which differs from the existing anti-PD-L1 antibodies. Collectively, we have developed a new anti-PD-L1 antibody that binds to mouse and human PD-L1 and demonstrated the antitumor effects of the antibody in several syngeneic murine myeloma models. Thus, PD-L1 is a promising target to treat multiple myeloma, and the novel anti-PD-L1 antibody may be an effective anti-myeloma drug via antibody-dependent cellular cytotoxicity effects.

Morin Hydrate Inhibits Influenza Virus entry into Host Cells and Has Anti-inflammatory Effect in Influenza-infected Mice.

Influenza virus is the major cause of seasonal and pandemic flu. Currently, oseltamivir, a potent and selective inhibitor of neuraminidase of influenza A and B viruses, is the drug of choice for treating patients with influenza virus infection. However, recent emergence of oseltamivir-resistant influenza viruses has limited its efficacy. Morin hydrate (3,5,7,2',4'-pentahydroxyflavone) is a flavonoid isolated from Morus alba L. It has antioxidant, anti-inflammatory, neuroprotective, and anticancer effects partly by the inhibition of the NF-кB signaling pathway. However, its effects on influenza virus have not been studied. We evaluated the antiviral activity of morin hydrate against influenza A/Puerto Rico/8/1934 (A/PR/8; H1N1) and oseltamivir-resistant A/PR/8 influenza viruses in vitro. To determine its mode of action, we carried out time course experiments, and time of addition, hemolysis inhibition, and hemagglutination assays. The effects of the co-administration of morin hydrate and oseltamivir were assessed using the murine model of A/PR/8 infection. We found that morin hydrate reduced hemagglutination by A/PR/8 in vitro. It alleviated the symptoms of A/PR/8-infection, and reduced the levels of pro-inflammatory cytokines and chemokines, such as TNF-α and CCL2, in infected mice. Co-administration of morin hydrate and oseltamivir phosphate reduced the virus titers and attenuated pulmonary inflammation. Our results suggest that morin hydrate exhibits antiviral activity by inhibiting the entry of the virus.

Investigation of symptoms of hand skin changes with aging in Korean women and development of a new standard grading scale for hand aging.

BACKGROUND: Skin aging, particularly facial skin, has been actively studied. However, hand skin research is limited. METHODS: Aging symptoms of 100 hands of Korean women aged from 20s to 60s were measured by noninvasive and bioengineering methods. Standard grade images were produced. RESULTS: As people got older, skin wrinkles were getting worse and skin tone was uneven with the occurrence of structural flexion. For each symptom, a suitable standard photograph of the skin of the hand was chosen and a new grading scale was made. CONCLUSIONS: The new grading scale developed in the present study could be employed in studies to explore aging of hand skin as one of objective indicators.

Peripheral biomarkers of mitochondrial dysfunction in adolescents with bipolar disorder.

BACKGROUND: Mitochondrial dysfunction has been implicated in the pathophysiology of bipolar disorder (BD). Impediment of mitochondrial oxidative phosphorylation results in a shift toward anaerobic respiration and lactate production. Elevated CNS lactate levels in adults with BD inform the need to evaluate lactate in peripheral samples and early in the course of BD. Furthermore, there exists a recent surge of investigations looking at circulating cell-free mitochondrial DNA (ccf-mtDNA) as a potential biomarker as they are released from cells under physiological stress, apoptosis, or bioenergetic compromise. OBJECTIVES: To compare lactate and ccf-mtDNA, two different ways in assessing the mitochondrial health and function, in adolescents with BD versus healthy control adolescents (HC). METHODS: One-hundred and five adolescents (n = 64 BD, n = 41 HC) were included. Serum lactate level was measured using a commercially available colorimetric kit. Serum ccf-mtDNA concentration was measured using quantitative polymerase chain reaction from ccfDNA purified by commercially available spin columns. Diagnosis and mood symptoms were evaluated using semi-structured interviews. RESULTS: There is an increase in serum lactate level of adolescents with BD (1.319 ± 0.444 nmol/uL) versus HC (1.168 ± 0.353 nmol/uL; p = 0.043), but not ccf-mtDNA. Among BD adolescents, depression symptoms were negatively correlated with ccf-mtDNA levels (ρ = -0.289; p = 0.038) but loses significance when corrected for multiple comparison. Lactate was positively correlated with ccf-mtDNA in the overall sample (ρ = 0.201; p = 0.043). When examined by diagnosis, this association remained in BD (ρ = 0.273; p = 0.032), but not HC. CONCLUSION: These preliminary results indicate that elevated lactate is observed even among adolescents early in their course of BD, that the association between lactate and ccf-mtDNA appears to be specific to BD, and that ccf-mtDNA is potentially associated with depression symptoms in adolescent BD. In addition, the effect of psychotropic medications used in the treatment of BD on peripheral lactate and ccf-mtDNA requires further investigation.

B Cell-Based Vaccine Transduced With ESAT6-Expressing Vaccinia Virus and Presenting α-Galactosylceramide Is a Novel Vaccine Candidate Against ESAT6-Expressing Mycobacterial Diseases.

Early secretory antigenic target-6 (ESAT6) is a potent immunogenic antigen expressed in Mycobacterium tuberculosis as well as in some non-tuberculous mycobacteria (NTM), such as M. kansasii. M. kansasii is one of the most clinically relevant species of NTM that causes mycobacterial lung disease, which is clinically indistinguishable from tuberculosis. In the current study, we designed a novel cell-based vaccine using B cells that were transduced with vaccinia virus expressing ESAT6 (vacESAT6), and presenting α-galactosylceramide (αGC), a ligand of invariant NKT cells. We found that B cells loaded with αGC had increased levels of CD80 and CD86 after in vitro stimulation with NKT cells. Immunization of mice with B/αGC/vacESAT6 induced CD4+ T cells producing TNF-α and IFN-γ in response to heat-killed M. tuberculosis. Immunization of mice with B/αGC/vacESAT6 ameliorated severe lung inflammation caused by M. kansasii infection. We also confirmed that immunization with B/αGC/vacESAT6 reduced M. kansasii bacterial burden in the lungs. In addition, therapeutic administration of B/αGC/vacESAT6 increased IFN-γ+ CD4+ T cells and inhibited the progression of lung pathology caused by M. kansasii infection. Thus, B/αGC/vacESAT6 could be a potent vaccine candidate for the prevention and treatment of ESAT6-expressing mycobacterial infection caused by M. kansasii.

Anticancer effects of a novel chroman analog in HeLa cells are associated with G2­phase arrest and mitochondrial­mediated apoptosis.

In the present study, the anticancer activity of 1­[(3S,4R)­2,2­dimethyl­3­oxo­4­(2­piperidonyl)chroman­6­yl]­3­phenylurea (S32) was investigated by testing its effect in vitro on the growth of HeLa cells. First, we showed that the IC50 value of S32 was ~70 µM by using WST­8 assay, and that it significantly inhibited the proliferation and viability of HeLa cells in a dose­dependent manner after 48 h. Morphological changes in apoptotic cells included cellular shrinkage and nuclear condensation. The results of [3H]­thymidine incorporation and flow cytometric analysis indicated that S32 induced inhibition of DNA replication and G2­phase cell cycle arrest. Moreover, S32 induced the levels of reactive oxygen species (ROS) and decreased the mitochondrial membrane potential (MMP) in a time­dependent manner. Using Annexin V­FITC/propidium iodide (PI) dual staining assay, we found that S32 noticeably increased early apoptosis in HeLa cells in a time­dependent manner. The result of western blot analysis showed that the apoptotic induction was associated with an increase in Bax levels and a decrease in Bcl­2 levels, which led to activation of caspase­8, ­9 and ­3. Taken together, our findings demonstrated that S32 induces mitochondrial­mediated apoptosis in HeLa cells and suggest that S32 has potential as an anticancer drug.

Lactate in bipolar disorder: A systematic review and meta-analysis.

Bipolar disorder (BD) is a debilitating mood disorder with no specific biological marker. No novel treatment has been developed specifically for BD in the last several decades. Although the pathophysiology of BD remains unclear, there is strong evidence in the literature supporting the role of mitochondrial dysfunction in BD. In this systematic review, we identified and investigated 12 studies that measure lactate, which is a direct marker for mitochondrial dysfunction, in BD patients and healthy controls. Six studies measured lactate levels in the brain through proton echo-planar spectroscopy or magnetic resonance spectroscopy and five of these studies reported significantly elevated lactate levels in patients with BD. Two studies reporting cerebrospinal fluid lactate levels also found significantly elevated lactate in BD compared to healthy controls. Two other studies that reported peripheral lactate levels did not demonstrate significant findings. The meta-analysis, using standardized means and a random-effect model for five studies that measured brain lactate levels, corroborated the findings of the systematic review. Although the meta-analysis had a nearly significant overall effect (Z = 1.97, P = 0.05), high statistical heterogeneity (I2 = 86%) and possible publication bias suggest that the results should be interpreted with caution. To validate lactate abnormalities in BD, further studies should be carried out, including larger sample sizes, not excluding female patients, and using standardized methodologies. Peripheral lactate levels and other bioenergetic markers should be thoroughly studied to better understand the role of mitochondrial dysfunction in BD and to help develop more objective diagnostic tools.

Circulating tumor cells detected by lab-on-a-disc: Role in early diagnosis of gastric cancer.

BACKGROUND: The use of circulating tumor cells (CTCs) as an early diagnostic biomarker and prognostic indicator after surgery or chemotherapy has been suggested for various cancers. This study aimed to evaluate CTCs in patients who underwent gastrectomy for gastric cancer and to explore their clinical usefulness in the early diagnosis of gastric cancer. METHODS: A total of 116 patients with gastric cancer who underwent gastrectomy and 31 healthy volunteers were prospectively included between 2014 and 2015. Peripheral blood samples were collected before gastrectomy, and CTCs were examined using a centrifugal microfluidic system with a new fluid-assisted separation technique. RESULTS: After creating a receiver operating characteristic curve to identify the discriminative CTC value needed differentiate patients with gastric cancer from healthy volunteers, sensitivity and specificity were nearly optimized at a CTC threshold of 2 per 7.5 mL of blood. Of the 102 persons with a CTC level ≥2 per 7.5 mL of blood, 99 (97.1%) had gastric cancer, and of the 45 persons with a CTC level <2 per 7.5 mL of blood, 28 (62.2%) were healthy controls. Accordingly, the sensitivity and specificity for the differentiation of patients with gastric cancer from healthy controls were 85.3% and 90.3%, respectively. However, the presence of CTCs was not associated with any clinicopathologic features such as staging, histologic type, or mucin phenotype. CONCLUSION: Although we could not prove the clinical feasibility of CTCs for gastric cancer staging, our results suggest a potential role of CTCs as an early diagnostic biomarker of gastric cancer.

FAST: Size-Selective, Clog-Free Isolation of Rare Cancer Cells from Whole Blood at a Liquid-Liquid Interface.

Circulating tumor cells (CTCs) have great potential to provide minimally invasive ways for the early detection of cancer metastasis and for the response monitoring of various cancer treatments. Despite the clinical importance and progress of CTC-based cancer diagnostics, most of the current methods of enriching CTCs are difficult to implement in general hospital settings due to complex and time-consuming protocols. Among existing technologies, size-based isolation methods provide antibody-independent, relatively simple, and high throughput protocols. However, the clogging issues and lower than desired recovery rates and purity are the key challenges. In this work, inspired by antifouling membranes with liquid-filled pores in nature, clog-free, highly sensitive (95.9 ± 3.1% recovery rate), selective (>2.5 log depletion of white blood cells), rapid (>3 mL/min), and label-free isolation of viable CTCs from whole blood without prior sample treatment is achieved using a stand-alone lab-on-a-disc system equipped with fluid-assisted separation technology (FAST). Numerical simulation and experiments show that this method provides uniform, clog-free, ultrafast cell enrichment with pressure drops much less than in conventional size-based filtration, at 1 kPa. We demonstrate the clinical utility of the point-of-care detection of CTCs with samples taken from 142 patients suffering from breast, stomach, or lung cancer.

A novel bispidinone analog induces S­phase cell cycle arrest and apoptosis in HeLa human cervical carcinoma cells.

2,4,6,8-(3)-Tetranitrophenyl-3,7-diazabicyclo[3.3.1]nonan-9-one (B16), a bispidinone analog, was synthesized to investigate its effects on cell viability, the cell cycle, and apoptotic pathways in HeLa human cervical cancer cells. B16 decreased the percentage of viable cells in WST-8 assays, and morphological changes associated with apoptotic cell death were observed, including cell shrinkage and disruption. Annexin V-FITC/PI dual staining assays showed that B16 significantly increased the early apoptosis of HeLa cells after 24 h of treatment. Moreover, DNA content analysis and [3H]-thymidine incorporation assays showed that B16 induced S-phase cell cycle arrest and inhibited DNA replication after 24 h of treatment. Following treatment with 25 µM of B16, an increase in reactive oxygen species and a decrease in mitochondrial membrane potential were observed by flow cytometry. In addition, the expression levels of caspase cascade and Bcl-2 family proteins determined by western blotting suggested that the induction of apoptosis by B16 was associated with a caspase- and mitochondrial-dependent pathway in HeLa cells. In conclusion, B16 induced early apoptosis and S-phase cell cycle arrest in HeLa cells via a caspase- and mitochondrial­dependent pathway.

Synthesis and Electroluminescent Property of New Orange Iridium Compounds for Flexible White Organic Light Emitting Diodes.

Recently, white organic light-emitting diodes (OLEDs) have aroused considerable attention because they have the potential of next-generation flexible displays and white illuminated applications. White OLED applications are particularly heading to the industry but they have still many problems both materials and manufacturing. Therefore, we proposed that the new iridium compounds of orange emitters could be demonstrated and also applied to flexible white OLEDs for verification of potential. First, we demonstrated the chemical properties of new orange iridium compounds. Secondly, conventional two kinds of white phosphorescent OLEDs were fabricated by following devices; indium-tin oxide coated glass substrate/4,4'-bis[N-(napthyl)-N-phenylamino]biphenyl/N,N'-dicarbazolyl-3,5-benzene doped with blue and new iridium compounds for orange emitting 8 wt%/1,3,5-tris[N-phenylbenzimidazole-2-yl]benzene/lithium quinolate/aluminum. In addition, we fabricated white OLEDs using these emitters to verify the potential on flexible substrate. Therefore, this work could be proposed that white light applications can be applied and could be extended to additional research on flexible applications.