High-efficiency Electroreduction of O2 into H2 O2 over ZnCo Bimetallic Triazole Frameworks Promoted by Ligand Activation.

Co-based metal-organic frameworks (MOFs) as electrocatalysts for two-electron oxygen reduction reaction (2e- ORR) are highly promising for H2 O2 production, but suffer from the intrinsic activity-selectivity trade-off. Herein, we report a ZnCo bimetal-triazole framework (ZnCo-MTF) as high-efficiency 2e- ORR electrocatalysts. The experimental and theoretical results demonstrate that the coordination between 1,2,3-triazole and Co increases the antibonding-orbital occupancy on the Co-N bond, promoting the activation of Co center. Besides, the adjacent Zn-Co sites on 1,2,3-triazole enable an asymmetric "side-on" adsorption mode of O2 , favoring the reduction of O2 molecules and desorption of OOH* intermediate. By virtue of the unique ligand effect, the ZnCo-MTF exhibits a 2e- ORR selectivity of ≈100 %, onset potential of 0.614 V and H2 O2 production rate of 5.55 mol gcat -1 h-1 , superior to the state-of-the-art zeolite imidazole frameworks. Our work paves the way for the design of 2e- ORR electrocatalysts with desirable coordination and electronic structure.

Application of low dose pancreas perfusion CT combined with enhancement scanning in diagnosis of pancreatic neuroendocrine tumors.

PURPOSE: To explore the diagnostic value of pancreatic perfusion CT combined with contrast-enhanced CT in one-time scanning (PCECT) in pancreatic neuroendocrine tumors (PNETs) and to evaluate the difference of perfusion parameters between different grades of PNETs. MATERIALS AND METHODS: From October 2016 to December 2018, forty consecutive patients with histopathological-proven PNETs were identified retrospectively that received PCECT for the preoperative PNETs evaluation. Two board certified radiologists who were blinded to the clinical data evaluated the images independently. The image characters of PNETs vs. tumor-free pancreatic parenchymal and different grades of PNETs were analyzed. RESULTS: One-time PCECT scanning had a detection rate of 89.1% for PNETs, which was higher than the detection accuracy of the perfusion CT only (83.6%). The perfusion parameters of PNETs including blood volume (BV), blood flow (BF), mean slope of increase (MSI), and capillary surface permeability (PS) were significantly increased than those of tumor-free pancreatic parenchyma (p < 0.05, respectively). For differential comparison between grade I (G1) and grade II (G2) tumors, the parameters of BF and impulse residue function (IRF) of tumor tissue were significantly higher in the G2 tumors (p < 0.05, for both). In this study, the total radiation dose of the whole PCECT scan was 16.241 ± 2.289 mSv. CONCLUSION: The one-time PCECT scan may improve the detection of PNETs according to morphological features and perfusion parameters with a relative small radiation dose. The perfusion parameters of BF and IRF may be used to help distinguish G1 and G2 tumors in the preoperative evaluation.

[Effect of total saponins from Panax japonicus on non-alcoholic steatohepatitis by regulating autophagy].

Non-alcoholic steatohepatitis(NASH) was induced by high-sugar and high-fat diet in mice to investigate the intervention effect of total saponins from Panax japonicus(TSPJ) and explore its possible mechanism. Mice were fed with high-sugar and high-fat diet to establish NASH model, and intervened with different doses of TSPJ(15, 45 mg·kg~(-1)). The animals were fed for 26 weeks. The histomorphology and pathological changes of liver tissues were observed by HE staining. The transcriptional expression levels of miR-199 a-5 p, autophagy related gene 5(ATG5) and inflammatory cytokines interleukin-6(IL-6), interleukin-1ß(IL-1ß) and tumor necrosis factor α(TNF-α) in mouse liver were measured by quantitative Real-time polymerase chain reaction(qRT-PCR). Western blot was used to detect the expression of autophagy-related proteins ATG5, P62/SQSTM1(P62), and microtubule-associated protein light chain 3(LC3)-I/Ⅱ proteins in mouse liver. The expression of P62 protein was detected by immunofluorescence staining. In order to verify the targeting regulation relationship between miR-199 a-5 p and ATG5, miR mimic/inhibitor NC and miR-199 a-5 p mimic/inhibitor were transfected into Hepa 1-6 cells, and the expression of ATG5 mRNA and protein was detected. pMIR-reportor ATG5-3'UTR luciferase reporter gene plasmid was constructed and co-transfected with miR mimic/inhibitor NC and miR-199 a-5 p mimic/inhibitor into Hepa 1-6 cells to detect luciferase activity. In vivo, HE staining in the model group showed typical fatty degeneration and inflammatory infiltration, with increased expression of miR-199 a-5 p and decreased expression of ATG5 mRNA and protein. The expression of autophagy-associated protein P62 increased significantly, the ratio of LC3Ⅱ/Ⅰ decreased, and the transcriptional expression of inflammatory factors increased significantly. After the intervention by TSPJ, the pathological performance of liver tissue was significantly improved, the expression of miR-199 a-5 p decreased and the expression of ATG5 mRNA and protein increased, the expression of autophagy-associated protein P62 decreased significantly, the ratio of LC3Ⅱ/Ⅰ increased, and the transcriptional expression of inflammatory cytokines IL-6, IL-1ß and TNF-α decreased significantly. In vitro, it was found that the expression of ATG5 mRNA and protein and luciferase activity decreased significantly in miR-199 a-5 p overexpression cells, while after inhibition of miR-199 a-5 p expression, the expression level of ATG5 mRNA and protein and luciferase activity increased. The results showed that TSPJ can improve NASH in mice fed with high-sugar and high-fat diet, and its mechanism may be related to the regulation of miR-199 a-5 p/ATG5 signal pathway, the regulation of autophagy activity and the improvement of inflammatory response of NASH.

[Chikusetsu saponin â £a ameliorates myocardial hypertrophy of rats through regulating expression of miR199a-5p/Atg5].

The present study investigated the effects of chikusetsu saponin Ⅳa(CHS Ⅳa) on isoproterenol(ISO)-induced myocardial hypertrophy in rats and explored the underlying molecular mechanism. ISO was applied to establish a rat model of myocardial hypertrophy, and CHS Ⅳa(5 and 15 mg·kg~(-1)·d~(-1)) was used for intervention. The tail artery blood pressure was measured. Cardiac ultrasound examination was performed. The ratio of heart weight to body weight(HW/BW) was calculated. Morphological changes in the myocardial tissue were observed by HE staining. Collagen deposition in the myocardial tissue was observed by Masson staining. The mRNA expression of myocardial hypertrophy indicators(ANP and BNP), autophagy-related genes(Atg5, P62 and beclin1), and miR199 a-5 p was detected by qRT-PCR. Atg5 protein expression was detected by Western blot. The results showed that the model group exhibited increased tail artery blood pressure and HW/BW ratio, thickened left ventricular myocardium, enlarged myocardial cells, disordered myocardial fibers with widened interstitium, and a large amount of collagen aggregating around the extracellular matrix and blood vessels. ANP and BNP were largely expressed. Moreover, P62 expression was up-regulated, while beclin1 expression was down-regulated. After intervention by CHS Ⅳa at different doses, myocardial hypertrophy was ameliorated and autophagy activity in the myocardial tissue was enhanced. Meanwhile, miR199 a-5 p expression declined and Atg5 expression increased. As predicted by bioinformatics, Atg5 was a target gene of miR199 a-5 p. CHS Ⅳa was capable of preventing myocardial hypertrophy by regulating autophagy of myocardial cells through the miR-199 a-5 p/Atg5 signaling pathway.

[Effect of Panax japonicus saponin â £a on alleviating nonalcoholic steatohepatitis by regulating miR-17-5p/MFN2 signaling pathway].

To study the effect of Panax japonicas saponin Ⅳa(SPJ-Ⅳa) on nonalcoholic steatohepatitis(NASH) through miR-17-5 p/MFN2 signaling pathway. The nonalcoholic steatohepatitis model was induced by a high-fat diet combined with CCl_4 in Balb/c male mice. The mouse serum and liver were collected, the body weight and liver weight were measured, the liver index was calculated, and the serum biochemical indicators alanine amino transferase(ALT), triglyceride(TG), and glucose(Glu) were measured. The morphological changes in the liver were detected by HE and Masson staining, Real-time PCR was used to detect lipid metabolism-related genes, inflammation-related genes interleukin-6(IL-6) and interleukin-1ß(IL-1ß), miR-17-5 p and MFN2 expressions, and Western blot was used to detect MFN2 protein expression level. Compared with the normal control group, the liver index in the HFD+CCl_4 group was significantly increased, and the contents of ALT, TG, and Glu were significantly increased; the morphology showed obvious steatosis and collagen fiber deposition; mRNA expression levels of lipid metabolism-related genes, inflammation-related genes and miR-17-5 p increased significantly, the mRNA expression level of MFN2 decreased significantly, and the protein level of MFN2 decreased. After intervention with SPJ-Ⅳa, the levels of ALT, TG and Glu decreased, morphological steatosis decreased, collagen fiber deposition decreased, and mRNA expression levels of lipid metabolism-related genes, inflammation-related genes and miR-17-5 p decreased. The mRNA expression level of MFN2 increased, and the protein level of MFN2 also increased. The results of this study indicated that miR-17-5 p/MFN2 signaling pathway may be involved in the occurrence and development of NASH, and SPJ-Ⅳa had a protective effect on NASH, its mechanism may be related to the regulation of miR-17-5 p/MFN2 signaling pathway.

Prevalence of hepatitis B virus, hepatitis C virus, human immunodeficiency virus and Treponema pallidum infections in hospitalized patients before transfusion in Xiangya hospital Central South University, China from 2011 to 2016.

BACKGROUND: Human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and Treponema pallidum (TP) infections are considered classic transfusion-transmissible infections (TTIs). Few data are available about the prevalence of TTIs in patients before blood transfusion in China. This study aimed to investigate the seroprevalence of four TTIs among patients before blood transfusion in Xiangya Hospital Central South University, China. METHODS: From 2011 to 2016, 442,121 hospitalized patients before possible blood transfusion were tested for hepatitis B surface antigen (HBsAg), anti-HCV, syphilis antibody (anti-TP) and anti-HIV. RESULTS: Of the 442,121 patients, the overall positivity of the four TTI serum markers was 15.35%. The positive rates of HBsAg, anti-HCV, anti-HIV and anti-TP were 10.98, 1.43, 0.16 and 2.78%, respectively. TTI serum markers showed a significant difference by gender, with positive rates of 17.98% for males and 12.79% for females. The prevalence of TTI serum markers varied significantly by age. The overall co-infection rate was 0.63%, and the top three multiple infections were HBV-TP, HBV-HCV, and HCV-TP. The co-infection rates of HBV-TP and HBV-HCV showed a significant decrease from 2011 to 2016, while the rates of other co-infections remained stable. CONCLUSIONS: The prevalence of TTIs in patients before blood transfusion is much higher compared to that in blood donors in the region. The infection rates of HIV and TP increased, and the infection rate of HBsAg decreased in recent years.

[Protective effects of total saponins of Panax japonicas on non-alcoholic fatty liver disease through regulating expression of miR-199-5p].

To research the effection and probable mechanism for the total saponins of Panax japonicas(TPSJ) in mice on non-alcoholic fatty liver disease. Forty SPF male Kunming mice were randomily divided into four group:control group,NAFLD group, low-dose TPSJ treated group,high-dose TPSJ treated group. High-fatty and high-frutose-diet was applied to eatablish NAFLD model，and TPSJ (100 and 200 mg·kg⁻¹) in feeding were given for the TPSJ groups for 4 weeks. To collect the serum with liver and the ALT and TC of serum were monitored after 4 weeks. The hepatic histopathologic structure was observed by haematoxylin-eosin (HE) staining, RT-PCR and RT-qPCR was applied for the detection of miR-199-5p，VEGFa，HGF，c-Met and protein expression level was detected bv laser confocal microscope.Compared with control group, the level of serum ALT and TC in the model group was higher,the liver of the model group showed that hepatocytes display obvious lipid deposition. Then TPSJ treated showed that markedly improved histopathologic changes, decreased fatty deposition. In the meantime,the expression level of miR-199-5p was significantly decreased, thus the expression of HGF and c-Met were significantly increased. TPSJ play a role of prevention on fatty liver, the machanism maybe by blocking miR-199-5p targeted to c-Met signaling pathways in NAFLD.

Chikusetsusaponin V attenuates lipopolysaccharide-induced liver injury in mice.

Chikusetsusaponin V (CsV), a saponin from Panax japonicus, has been reported to inhibit inflammatory responses in lipopolysaccharide (LPS)-induced macrophage cells. However, whether CsV could alleviate LPS-induced liver injury in vivo and the potential mechanisms involved remain unclear. In the present study, we investigated the anti-inflammatory effects of CsV on LPS-induced acute liver injury in mice and further explored the potential mechanisms involved. Our results showed that CsV significantly attenuated elevation of alanine transaminase (ALT) and aspartate aminotransferase (AST) levels and improved liver histopathological changes in LPS-induced mice. In addition, CsV decreased serum tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels and inhibited mRNA expressions of inducible nitric oxide synthase (iNOS), TNF-α and IL-1ß in LPS challenged mice. Furthermore, CsV inhibited nuclear factor kappa B (NF-κB) activation by downregulating phosphorylated NF-κB, IκB-α, ERK, c-Jun N-terminal kinase (JNK) and p38 levels in the liver tissue, which ultimately decreased nucleus NF-κB protein level. In conclusion, our data suggested that CsV could be a promising drug for preventing LPS challenged liver injury since it attenuated LPS-induced inflammatory responses, partly via inhibiting NF-κB and MAPK signaling pathways.

Discovery of 3,5-substituted 6-azaindazoles as potent pan-Pim inhibitors.

Pim kinase inhibitors are promising cancer therapeutics. Pim-2, among the three Pim isoforms, plays a critical role in multiple myeloma yet inhibition of Pim-2 is challenging due to its high affinity for ATP. A co-crystal structure of a screening hit 1 bound to Pim-1 kinase revealed the key binding interactions of its indazole core within the ATP binding site. Screening of analogous core fragments afforded 1H-pyrazolo[3,4-c]pyridine (6-azaindazole) as a core for the development of pan-Pim inhibitors. Fragment and structure based drug design led to identification of the series with picomolar biochemical potency against all three Pim isoforms. Desirable cellular potency was also achieved.

Chikusetsu saponin V attenuates MPP+-induced neurotoxicity in SH-SY5Y cells via regulation of Sirt1/Mn-SOD and GRP78/caspase-12 pathways.

Studies have shown that saponins from Panax japonicus (SPJ) possess neuroprotective effects. However, whether Chikusetsu saponin V (CsV), the most abundant member of SPJ, can exert neuroprotective effects against 1-methyl-4-phenylpyridinium ion (MPP+)-induced cytotoxicity is not known. In this study, we aimed to investigate the neuroprotective effects of CsV on MPP+-induced cytotoxicity in human neuroblastoma SH-SY5Y cells and explore its possible mechanisms. Our results show that CsV attenuates MPP+-induced cytotoxicity, inhibits ROS accumulation, and increases mitochondrial membrane potential dose-dependently. We also found that levels of Sirt1 protein and Mn-SOD mRNA significantly decreased in MPP+-treated group but were restored with CsV treatment in a dose-dependent manner. Furthermore, GRP78 protein and Caspase-12 mRNA levels were elevated by MPP+ exposure but reversed by CsV treatment. CsV inhibited the MPP+-induced downregulation of Bcl-2 and up-regulation of Bax in a dose-dependent manner and, thus, increased the ratio of Bcl-2/Bax. Overall, these results suggest that Sirt1/Mn-SOD and GRP78/Caspase-12 pathways might be involved in the CsV-mediated neuroprotective effects.

[Study on protective effect of total saponins of Panax japonicus on LPS-induced RAW264. 7 cell inflammation through NF-kappaB pathway].

OBJECTIVE: To observe the anti-inflammatory effect of total saponins of Panax japonicus on LPS-induced RAW264. 7 macrophages. METHOD: The effect of total saponins of P. japonicus of different concentrations on RAW264. 7 cell viability was determined with the MTT method. The NO kit assay was adopted to detect the NO release of total saponins of P. japonicus to LPS-induced RAW264. 7 cells. The enzyme linked immunosorbent assay (ELISA) was used to detect the secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin 1-beta (IL-1beta). The reverse transeriptase-polymerase chain reaction (RT-PCR) was used to determine the expression of inducible nitric oxide synthase (iNOS) ,TNF-alpha,IL-1beta. The protein expression of nuclear transcription factor-kappaB p65 (NF-kappaB p65) was tested by Western blot. RESULT: The safe medication range of total saponins of P. japonicus was less than 80 mg x L(-1). Compared with the LPS model group, total saponins of P. japonicus high, middle and low dose groups (0.1, 1, 10, 40 mg x L(-1)) could significantly reduce the secretion of NO, TNF-alpha, IL-1beta of LPS-induced RAW264. 7 cells, and inhibit the expressions of iNOS, TNF-alpha and IL-1beta mRNA and the protein expression of NF-kappaB p65. CONCLUSION: This study preliminarily proves the protective effect of total saponins of P. japonicus on LPS-induced RAW264.7 macrophages. Its action mechanism may be related to NF-kappaB signal pathway.

Case report: A case of widespread soft tissue infection and multiple abscesses secondary to hidradenitis suppurativa inducing septic shock caused by Lawsonella clevelandensis in China.

Lawsonella clevelandensis is rare to associated with human infection, which may cause abscesses in abdominal cavity, liver, breast, and spine. Lawsonella clevelandensis is very difficult to be cultivated in regular manner; detection of 16S rRNA sequence is the main evidence for L. clevelandensis infection. The clinical manifestations of L. clevelandensis infection resemble other agents of Nocardia, Tuberculosis and non-tuberculous Mycobacterium (NTM) due to their morphologic similarities. Hidradenitis suppurativa (HS) is a chronic inflammatory disorder, which affects the intertriginous skin and is associated with numerous systemic comorbidities. HS eventually leads to severe pain, multiple abscesses, pus discharge, and irreversible tissue destruction. Lawsonella clevelandensis has not been reported to cause HS and systemic comorbidities. We presented the case of a 33-year-old male with widespread soft tissue infection and multiple abscesses secondary to HS (Hurley stage III) inducing septic shock caused by L. clevelandensis in China. He was diagnosed as HS and treated with intravenous antibiotic empirically. He developed multiple abscesses including lung and scrota. Bacterial and fungal cultures on blood and secretions from multiple skin lesions were all negative. Due to the misdiagnosis and progression of disease, the patient was transferred to intensive care unit, and he underwent drainage of the chest and right hemothorax removal under thoracoscopic. During the hospitalization, the patient developed septic shock and received mechanical ventilation. Computerized tomography (CT) scans revealed mediastinal emphysema, multiple subcutaneous emphysema, and severe pneumonia. Gene analysis of samples of incision and drainage of pus at the skin showed the rare infection of L. clevelandensis. Finally, the patients with recurrent soft tissue infections and multiple abscesses with negative microbiological culture results recovered after effective abscess drainage and antibiotic therapy. We suggested that NGS is a crucial supplementary diagnostic tool in individuals with recurrent skin infections and multiple abscesses, especially when conventional diagnostic methods are inconclusive.

The Influence of Post-Treatment on Micropore Evolution and Mechanical Performance in AlSi10Mg Alloy Manufactured by Laser Powder Bed Fusion.

Gas-induced porosity is almost inevitable in additively manufactured aluminum alloys due to the evaporation of low-melting point elements (e.g., Al, Mg, and Zn) and the encapsulation of gases (e.g., hydrogen) during the multiple-phase reaction in the melt pool. These micropores are highly unstable during post-heat treatment at elevated temperatures and greatly affect mechanical properties and service reliability. In this study, the AlSi10Mg samples prepared by LPBF were subjected to solution heat treatment at 560 °C for 0.5 and 2 h, followed by artificial aging at 160 °C, 180 °C and 200 °C, respectively. The defect tolerance of gas porosity and associated damage mechanisms in the as-built and heat treated AlSi10Mg alloy were elucidated using optical, scanning electron microscopic analysis, X-ray micro computed tomography (XCT) and room temperature tensile testing. The results showed the defect tolerance of AlSi10Mg alloy prepared by LPBF was significantly reduced by the artificial aging treatment due to the precipitation of Mg-Si phases. Fracture analysis showed that the cooperation of fine precipitates and coarsened micropores assists nucleation and propagation of microcracks sites due to stress concentration upon tensile deformation and reduces the tensile elongation at break.

Sleep promoting and omics exploration on probiotics fermented Gastrodia elata Blume.

Fermenting Chinese medicinal herbs could enhance their bioactivities. We hypothesized probiotic-fermented gastrodia elata Blume (GE) with better potential to alleviate insomnia than that of unfermented, thus the changes in chemical composition and the insomnia-alleviating effects and mechanisms of fermented GE on pentylenetetrazole (PTZ)-induced insomnia zebrafish were explored via high-performance liquid chromatography (HPLC) and mass spectroscopy-coupled HPLC (HPLC-MS), phenotypic, transcriptomic, and metabolomics analysis. The results demonstrated that probiotic fermented GE performed better than unfermented GE in increasing the content of chemical composition, reducing the displacement, average speed, and number of apoptotic cells in zebrafish with insomnia. Metabolomic investigation showed that the anti-insomnia effect was related to regulating the pathways of actin cytoskeleton and neuroactive ligand-receptor interactions. Transcriptomic and reverse transcription qPCR (RT-qPCR) analysis revealed that secondary fermentation liquid (SFL) significantly modulated the expression levels of neurod1, msh2, msh3, recql4, ercc5, rad5lc, and rev3l, which are mainly involved in neuron differentiation and DNA repair. Collectively, as a functional food, fermented GE possessed potential for insomnia alleviation.

MiR-21 down-regulation suppresses cell growth, invasion and induces cell apoptosis by targeting FASL, TIMP3, and RECK genes in esophageal carcinoma.

BACKGROUND: miR-21 is overexpressed in esophageal squamous cell carcinoma (ESCC) and is thought to be correlated with the development of the cancer. The target gene of miR-21 including FASL, TIMP3 and RECK is revealed by researchers. miR-21 may be involved in the tumorgenesis of ESCC by targeting FASL, TIMP3 and RECK. AIMS: The purpose of this study was to explore the mechanism of miR-21 in the development of ESCC. METHODS: miR-21 expression in ESCC and the matched non-malignant adjacent tissues (NMATs) was examined by qRT-PCR. Cell growth, cell apoptosis and cell invasion ability of EC9706 and EC-1 cells was examined after the cells were transfected with miR-21 inhibitor. The potential target genes of miR-21 including FASL, TIMP3 and RECK were examined by western blot and Luciferase reporter assay. RESULTS: miR-21 expression was increased significantly in ESCC tissues compared with NMAT. miR-21 down-regulation inhibits cell growth, cell invasion and induces cells to apoptosis. FASL, TIMP3 and RECK are direct targets of miR-21. CONCLUSIONS: miR-21 down-regulation inhibits cell growth, invasion and induces cells to apoptosis by targeting FASL, TIMP3 and RECK genes.

Advances and Prospects of Ultrasound Targeted Drug Delivery Systems Using Biomaterial-modified Micro/Nanobubbles for Tumor Therapy.

The incidence of malignant tumors is rising rapidly and tends to be in the younger, which has been one of the most important factors endangering the safety of human life. Ultrasound micro/nanobubbles, as a noninvasive and highly specific antitumor strategy, can reach and destroy tumor tissue through their effects of cavitation and acoustic perforation under the guidance of ultrasound. Meanwhile, micro/nanobubbles are now used as a novel drug carrier, releasing drugs at a target region, especially on the prospects of biomaterial-modified micro/nanobubbles as a dual modality for drug delivery and therapeutic monitoring. Successful evaluation of the sonoporation mechanism(s), ultrasound parameters, drug type, and dose will need to be addressed before translating this technology for clinical use. Therefore, this paper collects the literature on the experimental and clinical studies of ultrasound biomaterial-modified micro/nanobubbles therapy in vitro and in vivo in recent years.

Granulomatous Inflammation of Greater Omentum Caused by a Migrating Fishbone.

Fishbone is the most common ingested gastrointestinal foreign matter and is less than 1% perforate. However, a fishbone penetrating the gastrointestinal tract and causing granulomatous inflammation of the greater omentum with local suppuration is not common. Because of the nonspecific clinical symptoms, gastrointestinal perforation may be manifested only as dull abdominal pain, which is often ignored and timely clinical treatment may be delayed. We report a case of a 61-year male who experienced intermittent right median ventral abdominal pain for half a year. These symptoms were the result of granulomatous inflammation of the greater omentum with local suppuration caused by a migrating fishbone (3.5 cm in length). Finally, the fishbone was removed by exploratory laparotomy. Key Words: Fishbone, Gastrointestinal perforation, Greater omentum, Granulomatous inflammation, Laparotomy.

AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML).

Activating mutations in the receptor tyrosine kinase FLT3 are present in up to approximately 30% of acute myeloid leukemia (AML) patients, implicating FLT3 as a driver of the disease and therefore as a target for therapy. We report the characterization of AC220, a second-generation FLT3 inhibitor, and a comparison of AC220 with the first-generation FLT3 inhibitors CEP-701, MLN-518, PKC-412, sorafenib, and sunitinib. AC220 exhibits low nanomolar potency in biochemical and cellular assays and exceptional kinase selectivity, and in animal models is efficacious at doses as low as 1 mg/kg given orally once daily. The data reveal that the combination of excellent potency, selectivity, and pharmacokinetic properties is unique to AC220, which therefore is the first drug candidate with a profile that matches the characteristics desirable for a clinical FLT3 inhibitor.

4-Quinazolinyloxy-diaryl ureas as novel BRAFV600E inhibitors.

Aryl phenyl ureas with a 4-quinazolinoxy substituent at the meta-position of the phenyl ring are potent inhibitors of mutant and wild type BRAF kinase. Compound 7 (1-(5-tert-butylisoxazol-3-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)urea hydrochloride) exhibits good pharmacokinetic properties in rat and mouse and is efficacious in a mouse tumor xenograft model following oral dosing.

Weight and volume estimation of poultry and products based on computer vision systems: a review.

The appearance, size, and weight of poultry meat and eggs are essential for production economics and vital in the poultry sector. These external characteristics influence their market price and consumers' preference and choice. With technological developments, there is an increase in the application and importance of vision systems in the agricultural sector. Computer vision has become a promising tool in the real-time automation of poultry weighing and processing systems. Owing to its noninvasive and nonintrusive nature and its capacity to present a wide range of information, computer vision systems can be applied in the size, mass, volume determination, and sorting and grading of poultry products. This review article gives a detailed summary of the current advances in measuring poultry products' external characteristics based on computer vision systems. An overview of computer vision systems is discussed and summarized. A comprehensive presentation of the application of computer vision-based systems for assessing poultry meat and eggs was provided, that is, weight and volume estimation, sorting, and classification. Finally, the challenges and potential future trends in size, weight, and volume estimation of poultry products are reported.