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Chestnut inner shell was fermented in solid state with Aspergillus sojae, and then extracted using ethanol (95%) to analyze its cosmeceutical activity and phenolic composition. The fermentation significantly increased the antioxidant activity, and in vitro cosmeceutical activities. The ethanol extract showed the higher activities than ethyl acetate and water extracts. DPPH radical scavenging activity of the alcoholic extract was 80.53%, and tyrosinase and elastase inhibition activities were 101.01%, and 76.73%, respectively, after 10 days of fermentation. Kojic acid, a secondary metabolite of A. sojae was produced by the fermentation as a major bioactive component. Gallic acid, ellagic acid, and coumaric acid appeared the major phenolic acids in the alcoholic extract from fermented chestnut inner shell. The alcoholic extract from chestnut inner shell fermented by A. sojae may be used as an effective and bioactive cosmeceutical. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-022-01044-9.

Objective The data showing the association between gout and dementia are inconsistent. The objective of this study was to examine whether gout is associated with the risk of dementia in the elderly. Methods This retrospective cohort study used population-based representative claims data from the National Health Insurance Service in Korea. We used the Elderly Cohort database which represents 10% of the elderly Koreans over the age of 60, from 2002 to 2013. We assessed the association of gout with a new diagnosis of dementia with Cox proportional hazard models and adjusted the data for potential covariates such as demographics (age, sex) and comorbidities. Results We included 22,178 patients with gout and 113,590 without. In each group, 2,557 (11.53%) and 18,264 (16.08%) patients, respectively, had dementia. In multivariable analyses, gout was independently associated with a significantly lower hazard ratio of incident dementia, with an adjusted hazard ratio of 0.63 (95% CI, 0.60–0.66). A sub-group analysis conducted to find out the effects of gout medication showed that febuxostat use significantly decreased incident dementia. Conclusion Gout was independently associated with a 37% lower risk of dementia in the elderly.

Background Rotaviruses are a major cause of pediatric gastroenteritis. The rotavirus P[6] genotype is the most prevalent genotype isolated from Korean neonates but has rarely been reported in other countries. Histo-blood group antigen (HBGA) is known to play an important role in rotavirus infection. We investigated the relationship between rotavirus genotype and HBGA-Lewis blood type in Korean children and explored the reasons for the predominance of rotavirus P[6] strain in Korean neonates. Methods Blood and stool samples were collected from 16 rotavirus-infected patients. Rotavirus G (VP7) and P (VP4) genotyping was performed using reverse transcription-PCR and sequencing. Lewis antigen phenotypes (Lea/Leb) were tested, and HBGA-Lewis genotype was determined by sequencing the secretor (FUT2) and Lewis (FUT3) genes. Deduced amino acid sequences and three-dimensional structures of the VP8* portion of the rotavirus VP4 protein were analyzed. Results All P[6] rotaviruses were isolated from neonates under one month of age, who were negative or weakly positive for the Leb antigen. However, 10 of the 11 non-P[6] rotaviruses were isolated from older children who were Leb antigen-positive. The VP8* amino acid sequences differed among P[6], P[4], and P[8] genotypes. Korean P[6] strains showed a unique VP8* sequence with amino acid substitutions, including Y169>L169, which differed from the sequences of P[6] strains from other countries. Conclusions The predominance of the rotavirus P[6] genotype in Korean neonates may be related to the interaction between HBGA-Lewis antigen and the VP8* portion of the VP4 protein, and this information will be helpful in future neonatal vaccine development.

Mid-aortic syndrome (MAS) is a rare condition characterized by stenosis of the distal thoracic and/or abdominal aorta. Williams-Beuren syndrome (WBS) is a relatively rare cause of MAS. We report a case of incidentally diagnosed MAS caused by WBS without typical manifestations caused by an atypical small-sized deletion in chromosome 7q11.23, which was initially misdiagnosed as Takayasu arteritis.

허혈 재관류 손상은 기관 이식, 외과적 혈관 재개통 및 출혈 시에 발생하며 조직 및 기관 기능 장애를 유발한다. 최근 허혈 재관류 손상의 기전적 연구를 위해 간장 허혈 모델을 많이 이용하고 있다. 본 연구는 허혈 재관류 랫드 모델을 이용하여 항산화와 항염증 효과를 가진 것으로 알려진 Vanillin에 의한 간장 및 신장 손상에 대한 보호 효과를 알아보고 관련된 기전을 조사하기 위하여 실시하였다. 시험물질은 각각 100 mg/kg의 농도로 3일간 투여한 후, 60분동안 간을 결찰하여 허혈 재관류를 유도하여 관찰하였으며, 음성대조군, sham대조군 및 허혈재관류만 실시한 허혈 재관류대조군을 따로 두어, 약물투여군과 비교하였다. Vanillin 처치군에서는 AST, ALT 활성이 허혈 재관류대조군에 비해 유의하게 억제되었고, 조직병리학적 관찰에서도 염증 부분과 괴사부분이 현저하게 감소하였다. MDA와 SOD는 허혈 재관류군에 비해 유의적인 변화를 보였다. 이상의 결과를 종합하면 Vanillin은 간장 허혈 재관류에 의한 세포염증 및 세포괴사를 완화시켜 간세포 보호작용을 나타내었고, 신장의 사구체 및 원 위세뇨관에 염증 변화를 완화 시키고 있어 세포 손상을 방어하는 것으로 생각되며, 이러한 방어효과는 항산화 기능에 의한 영향으로 사료된다.

Mutations in Fms-like tyrosine kinase 3 (FLT3) have been implicated in the pathogenesis of acute myeloid leukemia (AML) by affecting the proliferation and differentiation of hematopoietic stem and progenitor cells. Although several FLT3 inhibitors have been developed, the occurrence of secondary TKD mutations of FLT3 such FLT3/D835Y and FLT3/F691L lead to drug resistance and has become a key area of unmet medical needs. To overcome the obstacle of secondary TKD mutations, a new series of indirubin-3'-aminooxy-acetamide derivatives was discovered as potent and selective FLT3 and FLT3/D835Y inhibitors that were predicted to bind at the DFG-in active conformation of FLT3 in molecular docking studies. Through structure-activity relationship studies, the most optimized compound 13a was developed as a potent inhibitor at FLT3 and FLT3/D835Y with IC

Studies that investigate the association between toll-like receptor (TLR)-4 or TLR9 gene polymorphisms and remission from the disease in RA patients taking tumor necrosis factor alpha (TNF-α) inhibitors have yet to be conducted. In this context, this study was designed to investigate the effects of polymorphisms in TLR4 and TLR9 on response to TNF-α inhibitor and develop various machine learning approaches to predict remission. A total of six single nucleotide polymorphisms (SNPs) were investigated. Logistic regression analysis was used to investigate the association between genetic polymorphisms and response to treatment. Various machine learning methods were utilized for prediction of remission. After adjusting for covariates, the rate of remission of T-allele carriers of TLR9 rs352139 was about 5 times that of the CC-genotype carriers (95% confidence interval (CI) 1.325–19.231, p = 0.018). Among machine learning algorithms, multivariate logistic regression and elastic net showed the best prediction with the AUROC value of 0.71 (95% CI 0.597 - 0.823 for both models). This study showed an association between a TLR9 polymorphism (rs352139) and treatment response in RA patients receiving TNF-α inhibitors. Moreover, this study developed various machine learning methods for prediction, among which the elastic net provided the best model for remission prediction.

e15103 Background: Mutations of the FMS-like tyrosine kinase 3 (FLT3) gene occur in approximately 30% of all acute myeloid leukemia (AML) cases, with the internal tandem duplication (ITD) representing the most common type of FLT3 mutation (FLT3-ITD; approximately 25% of all AML cases). Although several FLT3 inhibitors have been developed, occurrence of secondary TKD mutations of FLT3 such as FLT3/D835Y and FLT3/F691L causes the acquired resistance to the current FLT3 inhibitors and eventually become a key area of unmet medical needs. Here, we have revealed that PLM-102, a novel, orally active FLT3 and RET dual inhibitor, has a potential to overcome the acquired resistance to current FLT3 inhibitors. Methods: 1. Kinase assay- Biochemical assays for FLT3 (WT and D835Y) and RET (WT and Mutants) were performed according to ADP-Glo kinase assay protocol(Promega). 2. Cell proliferation and Apoptosis- Human leukemia cell line MV4-11 and MOLM-14 were purchased from ATCC and DSMZ. Cells were seeded at a density of 2 X 103 cells per well and treated with the indicated concentrations of inhibitors for 72 hours at 37°C. Cell viability was determined by an Alamar Blue assay (Bio-Rad). Caspase-3/7 activity was measured by using the Caspase-Glo 3/7 assay (Promega). 3. Western blot analysis- Immunoblotting using MOLM-14 cells was performed using anti-phospho-FLT3 (Cell Signaling Technology #3461) and anti-FLT3 antibody (Cell Signaling Technology #3462). 4. In vivo mouse models- The MV4-11 and MOLM-14 cells are implanted into the subcutaneous space of the left flank of the mice. Resulting tumors are monitored by calipering twice weekly. Treatment started after randomization when tumor volumes had reached a size of approximately 100-150 mm3. For statistical analysis, analysis of variance (ANOVA) was performed using Prism 9.0 to examine statistical differences. Results: In compared to FDA-approved Gilteritinib, PLM-102 showed stronger sub-nanomolar IC50 values in FLT3 kinases regardless of wild-type, ITD, TKD and ITD/TKD mutants in both kinase- and cell-based assays. PLM-102 inhibited phosphorylation of FLT3 and its downstream signaling pathways, and induced apoptosis as evidenced by PARP-cleavage and caspase-3 activation. Moreover, PLM-102 showed an excellent anti-tumor activity in mouse xenograft models implanted with MV4-11 and MOLM-14 AML cells. Conclusions: Taken together, PLM-102 showing potent anti-cancer activity against various in vitro and in vivo AML models could be developed as a valuable agent overcoming the acquired resistance to the current FLT3 inhibitor.

Moringa oleifera leaf (ML) is rich in vitamins and minerals, specially abundant calcium, therefore it is widely used as a calcium supplement for food. This study aimed to investigate the antioxidant activity and calcium bioaccessibility of M. oleifera leaf hydrolysate (MLH) as a calcium supplement for kimchi. MLH was prepared under three different proteases, two different protease contents, and three different incubation times. Total phenol content (TPC), total flavonoid content (TFC), and antioxidant activities were investigated. Cellular activity and calcium bioaccessibility were also investigated. The highest calcium level of MLH was observed in 3% Protamex treatment for 4 h. TPC, TFC, and antioxidant activities of MLH in Protamex and Alcalase treatments were higher than those in Flavourzyme treatment (p

More than 50% of human cancers harbor TP53 mutations and increased expression of Mouse double minute 2 homolog (MDM2), which contribute to cancer progression and drug resistance. Renal cell carcinoma (RCC) has an unusually high incidence of wild-type p53, with a mutation rate of less than 4%. MDM2 is master regulator of apoptosis in cancer cells, which is triggered through proteasomal degradation of wild-type p53. Recently, we found that p53 protein levels in RCC are regulated by autophagic degradation. Transglutaminase 2 (TGase 2) was responsible for p53 degradation through this pathway. Knocking down TGase 2 increased p53-mediated apoptosis in RCC. Therefore, we asked whether depleting p53 from RCC cells occurs via MDM2-mediated proteasomal degradation or via TGase 2-mediated autophagic degradation. In vitro gene knockdown experiments revealed that stability of p53 in RCC was inversely related to levels of both MDM2 and TGase 2 protein. Therefore, we examined the therapeutic efficacy of inhibitors of TGase 2 and MDM2 in an in vivo model of RCC. The results showed that inhibiting TGase 2 but not MDM2 had efficient anticancer effects.

To investigate the effects of Gastrodia elata Blume (GEB) and 4-hydroxybenzyl alcohol (HBA) on brain damage, GEB or HBA was administered orally for 14 days before middle cerebral artery occlusion (MCAO). After 24 h reperfusion, the proportion of circling was significantly reduced in the GEB (79%) or HBA (69%) group compared to the MCAO group (100%) in the corner test, and the removal time in the adhesive removal test was significantly decreased in the GEB (117 ± 21.0 s) and HBA (101 ± 20.9 s) groups compared to the MCAO group (161 ± 12.6 s). GEB treatment significantly reduced infarct volume compared to the MCAO group. In the GEB and HBA group, necrosis of nerve cells in hippocampus and cortex, expressions of TNF-α and TUNEL positive cells were significantly reduced compared to the MCAO group. These results suggest that GEB and HBA prevents brain damage by anti-inflammatory and anti-apoptotic effects.

Cu-catalyzed azide–alkyne cycloaddition reaction in aqueous medium was dramatically accelerated by a simple zwitterionic additive, betaine, at ambient temperature. In the presence of betaine, 1,4-disubstituted-1,2,3-triazoles were obtained from azides and terminal alkynes in excellent yields under 2.5–200 ppm levels of Cu(I) in water. This method resulted in the remarkable reduction of the Cu(I) concentration down to ppm levels. The advantages of this protocol include the use of a conventional Cu catalytic system with commercially available betaine, which is generally non-toxic for biological application. Therefore, this efficient catalytic system should have broad applications in life science research and materials science.

We report first case of pulmonary siderosis appearing as a consolidation upon radiological examination and being misdiagnosed as pneumonia. A 59-year-old man visited our hospital with a cough and sputum that had persisted for more than a month. He had undergone chest computed tomography (CT) after abnormal findings on chest X-ray at other hospitals. Based on the chest CT results, he was diagnosed with pneumonia. He was then administered antibiotics for 3 weeks, but there was no improvement. We identified the patient's occupational history first, and then performed bronchoalveolar lavage and chest CT-guided transthoracic lung biopsy. The obtained specimen showed alveolar, macrophage-containing, Prussian blue-positive iron particles. Based on the results, we diagnose/d the patient with pulmonary siderosis. We advised him to discontinue his job. He is currently undergoing observation, and has not shown any special symptoms. Keywords: Pulmonary siderosis, Bronchoalveolar lavage, Transthoracic lung biopsy

This paper proposes a Low Inrush Current Low Dropout Regulator circuit using the method of pre-charging the load. The Low Dropout Regulator is a circuit to provide an efficient and stable supply voltage. One of the most important things of Low Dropout Regulator design is controlling the inrush current. The output voltage of the Low Dropout Regulator may be unstable when the inrush current is Large. The method proposed in this paper reduced inrush current from 438 mA to 5 mA. The designed Low Dropout Regulator has been implemented 55nm CMOS fabrication.

Octopus ocellatus meat (OM) is well known as a plentiful protein source. In this study, we evaluated the hepatoprotective effect of an aqueous extract of OM (OMA) against H

In this paper, we describe Ultra-Low Power (ULP) Low-Dropout Regulator (LDO) circuits for SPI module management in DSRC system. So LDO is Always-On domain. Circuit uses a CMOS 18 nm process. Proposed ULP LDO's output voltage and input voltage is 3.3 V and 1.2 V and total current consumption is 66 nA. By using 2-Transistor voltage reference circuit, Error Amplifier.

Octopus ocellatus meat (OM) is well known as a plentiful protein source. In this study, we evaluated the hepatoprotective effect of an aqueous extract of OM (OMA) against H2O2-triggered oxidative stress in human hepatocytes. First of all, taurine rich OMA showed a good ORAC value and reducing power and it was similar with that of ascorbic acid, which is known as a strong antioxidant. Also, OMA significantly improved H2O2-decreased cell viability by reducing the generation of intracellular reactive oxygen species (ROS) in hepatocytes. Interestingly, the stimulation of H2O2-induced the formations of apoptotic bodies and sub-G1 DNA content, whereas they were inhibited by the treatment with OMA. Furthermore, OMA regulated the protein expression levels of apoptotic molecules, such as Bax and Bcl-2. Taken together, this study suggests that OMA, which contains an abundant amount of taurine, protects hepatocytes from H2O2-triggered oxidative stress and might be a functional food material with hepatoprotective effects.

Rice bran was subjected to solid-state fermentation for 8 and 14 days using different Aspergillus strains: A. brasiliensis, A. awamori, and A. sojae. Alcoholic extracts (95% ethanol) from the fermented rice bran were analyzed for DPPH• scavenging activity and cosmeceutical activity (tyrosinase and elastase inhibitory activities). The levels of bioactive components including total phenolics, total flavonoids, kojic acid, and phenolic acids were also determined. The fungal fermentation increased the cosmeceutical activities and overall content of the bioactive components. Aspergillus sojae sample exhibited the highest radical scavenging activity and tyrosinase inhibitory activity (IC50 1.55 mg/mL) after 6 days of fermentation, whereas A. brasiliensis sample showed the highest elastase inhibitory activity. Kojic acid appeared to be one of the key substances responsible for the tyrosinase inhibition activity of the alcoholic extracts. Extensive fermentation over a week, however, induced the loss of phenolic acids and cosmeceutical activity, indicating that proper control of the fermentation period was critical.

This study analyzed the phonetic realizations of devoiced vowels in Mandarin Chinese. First, the target vowels were acoustically examined and classified in three categories: completely devoiced,...

File similarity is a numerical indicator that how many duplicated data exist in target files. With this information, we can reduce storage capacity with data deduplication scheme, further it can be exploited in the digital forensic field for finding malicious software. However, measuring file similarity between files can cause a high overhead in terms of processing time and the capacity of disk storage. For this reason, in this paper, we propose a novel file similarity evaluation algorithm called PHISA (Partial Hash Information String Algorithm). To evaluate the performance of the proposed system, we compare PHISA to well-known file similarity tools. The evaluation result shows that PHISA reduces the processing time and increases the similarity evaluation accuracy.

BACKGROUND/AIMS Brain and bone metastases are common in patients with lung cancer. The development of metastasis is associated with poor survival in lung cancer patients. Although tumor morphologic features on radiographs are routinely assessed for differentiation between benign and malignant lung nodules, they are not used to predict metastasis. We assessed morphologic features of pulmonary adenocarcinomas with brain/bone metastasis on computed tomography (CT) to identify related factors for metastasis. METHODS We performed a retrospective analysis of initial chest CT findings (size, type of contour, percentage of necrosis, enhancement, presence or absence of calcification, and air cavity) from 2009 to 2010 of patients with brain or bone metastasis and compared the findings with those of patients without metastases. RESULTS In total, 128 patients were included (78 men, 52 women; mean age 69 years; range, 36 to 87). Nineteen patients had brain metastases and 32 had bone metastases. Morphologic features associated with brain metastasis included size ≥ 50 mm (odds ratio [OR], 3.37; 95% confidence interval [CI], 1.24 to 9.17; p = 0.013), necrosis ≥ 30% (OR, 4.51; 95% CI, 1.62 to 12.55; p =0.002), and presence of calcification (OR, 3.97; 95% CI, 1.16 to 13.55; p = 0.035). Morphologic features associated with bone metastasis included necrosis ≥ 30% (OR, 4.639; 95% CI, 1.98 to 10.82; p < 0.001) and T 3 to 4 stage (OR, 2.53; 95% CI, 1.07 to 6.00; p = 0.031). CONCLUSIONS We found that necrosis ≥ 30% was associated with pulmonary adenocarcinoma with brain and bone metastasis at initial chest CT morphologic feature. To validate these results, further research should be conducted.

Simple Summary We found a conserved pathway for the energy supply in cancer. The present study revealed that glucose is not a major source of ATP production, whereas fatty acid is a major source of electrons for ATP production through fatty acid oxidation (FAO) and oxidative phosphorylation (OxPhos) in cancer cells. NADH is mainly recruited from FAO, which is used for ATP synthesis via OxPhos with electron transfer complexes in cancer cells while ATP is synthesized from NADH produced in the TCA cycle in the normal cells. Therefore, a calorie-balanced low-fat diet showed 3-fold reduction of tumor formation, whereas a high-fat diet caused a 2-fold increase of tumor to compare to the control in a human pancreatic ductal adenocarcinoma xenograft and a homograft KC models. Abstract Glycolysis is known as the main pathway for ATP production in cancer cells. However, in cancer cells, glucose deprivation for 24 h does not reduce ATP levels, whereas it does suppress lactate production. In this study, metabolic pathways were blocked to identify the main pathway of ATP production in pancreatic ductal adenocarcinoma (PDAC). Blocking fatty acid oxidation (FAO) decreased ATP production by 40% in cancer cells with no effect on normal cells. The effects of calorie balanced high- or low-fat diets were tested to determine whether cancer growth is modulated by fatty acids instead of calories. A low-fat diet caused a 70% decrease in pancreatic preneoplastic lesions compared with the control, whereas a high-fat diet caused a two-fold increase in preneoplastic lesions accompanied with increase of ATP production in the Kras (G12D)/Pdx1-cre PDAC model. The present results suggest that ATP production in cancer cells is dependent on FAO rather than on glycolysis, which can be a therapeutic approach by targeting cancer energy metabolism.

Angiogenesis and the expression of vascular endothelial growth factor (VEGF) are increased in renal cell carcinoma (RCC). Transglutaminase 2 (TGase 2), which promotes angiogenesis in endothelial cells during wound healing, is upregulated in RCC. Tumor angiogenesis involves three domains: cancer cells, the extracellular matrix, and endothelial cells. TGase 2 stabilizes VEGF in the extracellular matrix and promotes VEGFR-2 nuclear translocation in endothelial cells. However, the role of TGase 2 in angiogenesis in the cancer cell domain remains unclear. Hypoxia-inducible factor (HIF)-1α-mediated VEGF production underlies the induction of angiogenesis in cancer cells. In this study, we show that p53 downregulated HIF-1α in RCC, and p53 overexpression decreased VEGF production. Increased TGase 2 promoted angiogenesis by inducing p53 degradation, leading to the activation of HIF-1α. The interaction of HIF-1α and p53 with the cofactor p300 is required for stable transcriptional activation. We found that TGase 2-mediated p53 depletion increased the availability of p300 for HIF-1α-p300 binding. A preclinical xenograft model suggested that TGase 2 inhibition can reverse angiogenesis in RCC.

The aim of this study was to increase the sulfur content by developing natural sulfur additives and applying Kimchi. Broccoli sprout was selected as a natural sulfur additives, and sulfur content was improved using a methionine (Met) loaded polyvinyl alcohol (PVA)-sodium alginate (AG) hydrogel (Met-PVA-AG). The optimized Met-PVA-AG exhibited a small particle size (220.63 ± 18.87 nm), a high zeta potential (−37.49 ± 1.29 mV), encapsulation efficiency of methionine (91.91 ± 0.22%), and water content (97.35 ± 1.55%). Additionally, the retention rates of Met (up to 65%) and water (up to 57.18%) were high in Met-PVA-AG stored for 7 days under acidic, neutral and alkaline conditions. The sulfur compound content (sulfur 1607 mg/100 g, sulforaphane 53.12 mg/100 g and glusocinolates 206.79 mg/100 g) of broccoli sprout grown with Met-PVA-AG was higher than broccoli sprouts grown with water and 1% Met solution. The highest antioxidant activity was observed in broccoli sprout grown with Met-PVA-AG in all treatments. To apply sulfur-enriched broccoli sprout in Kimchi, sulfur-enriched broccoli sprouts were coated using a maltodextrin and spray-drying. The coated broccoli sprouts can improve the retention rate of sulfur in Kimchi at 10 °C for 7 day.

The tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial heat shock protein that has been related to drug resistance in some tumors. Epithelial-mesenchymal transition (EMT) is known to play an important role in cancer progression, metastasis and drug resistance. The aim of the present study was to determine the role of TRAP1 on EMT in lung cancer cell lines and to evaluate the prognostic role of TRAP1 in NSCLC patients. We developed an in vitro model of acquired resistance to gefitinib by continuously treating HCC827 with escalating doses. The effects of TRAP1 on EMT and lung cancer migration and invasion in gefitinib resistance (GR) cells were examined by western blotting and confocal microscopy. Downregulation of TRAP1 through siRNA or G-TPP inhibited GR-induced EMT, as indicated by upregulation of E-cadherin, and downregulation of mesenchymal markers and transcriptional factors. TRAP1 expression was analysed by immunohistochemistry in a series of 97 NSCLC patients. TRAP1 expression correlates with poor outcome in NSCLC patients. We next showed that TRAP1 downregulation enhanced the reversal of TGF-β1-induced EMT and hypoxia-induced EMT. Furthermore, TRAP1 downregulation attenuated migration and invasion of HCC827GR cells. In conclusions, these results suggested that TRAP1 downregulation could overcome gefitinib resistance in NSCLC via EMT reversal in tumor microenvironment.

TNF receptor-associated protein 1 (TRAP1) has been reported to be upregulated in some tumors, and protected against apoptosis and oxidative stress. This study was designed to investigate overcoming gefitinib resistance in NSCLC through a mechanism-based approach using gamitrinib variant containing triphenylphosphonium (G-TPP), TRAP1 inhibitor. We developed an in vitro model of acquired resistance to gefitinib. The effects of G-TPP on apoptosis and ROS-dependent mitochondrial dysfunction in HCC827GR cells were examined by annexin V binding assay, MitoSoX, and immunoblot analysis. and we tested the effects of pretreated with NAC or DPI, free radical scavenger. In addition, TRAP1 and antioxidant MnSOD were respectively knocked down or overexpressed to determine its role in modulating ROS-mediated apotosis signals by G-TPP. Downregulation of TRAP1 through siRNA or G-TPP enhanced ROS-mediated apoptosis whereas TRAP1 overexpression attenuated ROS-mediated apoptosis induced by gefitinib. On the other hand, pretreatment with NAC or DPI prevents apoptosis induced by gefitinib and G-TPP. We next showed that the combination of gefitinib and G-TPP resulted in decreased expression of MnSOD in HCC827GR cells, not HCC827 cells. MnSOD siRNA and combined with gefitinib and G-TPP resulted in a greater apoptosis. In contrast, overexpression of MnSOD could confer protection against the apoptosis reduced by gefitinib and G-TPP. TRAP1 downregulation could overcome gefitinib resistance in NSCLC via ROS-mediated apoptotic pathway. Moreover, enhanced apoptosis by gefitinib and G-TPP in HCC827GR cells was due, at least in part, to the down-regulation of MnSOD.

An anaerobic incubation for the enzymatic production of gamma-aminobutyric acid (GABA) in rice bran with the addition of glutamate, hydrolyzed wheat protein (HWP), yeast extract (YE) and pyridoxal-5-phosphate (PLP) was investigated. Rice bran was moistened (30% moisture content) with an electrolyzed oxidizing water and anaerobically incubated under nitrogen at 40 °C for 8 h. The incubation activated the glutamate decarboxylase (GAD) in rice bran and increased the GABA content from 10.7 to 171.5 mg/100 g. The addition of glutamate and protein hydrolysates further amplified the GABA content in the treated rice bran: 974.9, 487.4, and 372.8 mg/100 g, with 2.25% glutamate, 6% HWP, and 8% YE, respectively. Furthermore, addition of PLP (1.48 mg/100 g) as a coenzyme for GAD, together with 2.25% glutamate addition, could raise the GABA accumulation in rice bran to 2242 mg/100 g. Other amino acids in rice bran were changed in their composition by the anaerobic treatment.

Based on the central dogma of protein synthesis, traditional methods for protein engineering require that altering protein structure and function must be accompanied by changing the nucleotide sequence of the genes encoding the protein. However, the preparation of a template gene for each individual protein requires a great deal of time and effort, thereby limiting the throughput and scope of studying engineered proteins. In this study, we describe translation-level engineering of proteins using cell-free protein synthesis. Taking advantage of the promiscuity of aminoacyl tRNA synthetases in accepting structurally similar amino acid analogues, unnatural amino acids were introduced into elastin-like polypeptides in place of the corresponding cognate amino acids. Through the incorporation of various analogues and starting from the same gene, the phase transition temperatures of elastin-like polypeptides became tunable. Our results demonstrate the usefulness of cell-free protein synthesis for protein engineering using unnatural amino acids without the need for cloning.

These days, Windows Operating System is widely used and it is dominant than other commercial operating systems. Besides, most of the commercial software vendors provide a number of software mainly for Windows OS. Therefore, software similarity analysis systems for Windows OS are highly useful for software plagiarism detection and copyright protection. However, mostly the software similarity analysis systems and techniques work on source codes, not executables, even though the majority of commercial software barely makes public its source codes. In this paper, we propose a novel scheme for software plagiarism detection for Windows executables. Our technique exploits both extended basic blocks' opcode sequences and imported API functions information in executable files. We implemented our scheme and measured its performance through several kinds of experiments using code samples and different versions of commercial software.