Catalytic conversion of glucose to 5-hydroxymethylfurfural using zirconium-containing metal-organic frameworks

5-hydroxymethylfurfural (5-HMF) can be obtained by the catalytic dehydration of glucose or fructose using different homogeneous or heterogeneous catalysts. In my research project, four closely related zirconium-containing Metal-Organic Frameworks (MOFs) were chosen as catalysts for the conversion of glucose to 5-HMF due to their chemical and thermal stability as well as the Lewis acidity of zirconium. The initial research focused on the use of UiO-66-X (X= H, NH2 and SO₃H), optimization of reaction conditions and investigation of the relationship between their catalytic activity and properties. The highest yield of 5-HMF (28%) was obtained using UiO-66 under the optimal reaction conditions. In catalyst recycling experiments, UiO-66 could be re-used after five runs with a small reduction in the yield of-5-HMF. We assumed that this is due to the formation of humin after reaction. Thus, used UiO-66 catalyst, named UiO-66-humin, was characterized by several techniques such as PXRD, FTIR, ¹³C Solid State NMR spectroscopy, and N2 adsorption measurements. MOF 808 was another potential candidate for the conversion of glucose since it possesses lower connectivity (6-connected) with larger surface area compared with UiO-66. MOF 808 was synthesized via a solvothermal method and characterized by PXRD and N2 adsorption measurements. Notably, MOF 808 afforded higher yields of 5-HMF when compared with UiO-66-X

Bryostatin I inhibits growth and proliferation of pancreatic cancer cells via suppression of NF-κB activation

Purpose: To evaluate the effect of bryostatin I on proliferation of pancreatic cancer cells as well as tumor growth in mice tumor xenograft model.Methods: Activation of NF-κB was evaluated by preparing nuclear material extract using nuclear extract kit (Carlsbad, CA, USA) followed by enzyme-linked immunosorbent assay (ELISA). Mice were injected with 3 x 105 MIApaCa 2 cells in 100 μL volume of PBS. The animals in the treatment group were injected with 50 μg/kg of bryostatin 1 daily for 1 month in the morning whereas those in the untreated group received an equal volume of normal saline.Results: Treatment of the MIApaCa 2 cells with bryostatin I caused a significant reduction in the activity of NF-κB in nucleoplasm (p = 0.0002). The increase in the concentration of bryostatin I from 10 to 50 μM reduced MIApaCa 2 cell proliferation from 87 to 26 %. Bryostatin I treatment also led to increase in the proportion of cells in M1 phase with subsequent reduction in sub-G1 phase of cell cycle. Examination of the cell lysates revealed a higher expression level of cleaved caspase-8 in bryostatin Itreated MIApaCa 2 cells. Mean tumor diameter in the treatment and untreated groups was 5.34 ± 2.16 and 19.45 ± 5.71 mm, respectively, after 2 months of treatment (p < 0.0002). The mean weight of the tumors in the treatment and untreated groups was 123.67 ± 22.56 and 939.14 ± 213.51 mg, respectively, after 2 months of treatment.Conclusion: Bryostatin I inhibits growth and proliferation of pancreatic cancer through inhibition of NF- κB expression, and therefore, needs to be further investigated for therapeutic application in pancreatic cancer.Keywords: Bryostatin I, NF-κB expression, Proliferation, Apoptosis, Pancreatic cancer, Tumor volum

Catalytic conversion of glucose to 5-hydroxymethylfurfural using zirconium-containing metal–organic frameworks using microwave heating

5-Hydroxymethylfurfural (5-HMF) can be prepared by the catalytic dehydration of glucose or fructose using a range of homogeneous or heterogeneous catalysts. For our research, a selection of closely related Metal–Organic Frameworks (MOFs) were used as catalysts in the conversion of glucose to 5-HMF due to their chemical and thermal stability as well as the Lewis acidity of zirconium. Our initial study focused on the use of UiO-66–X (X = H, NH2 and SO3H), optimization of the dehydration reaction conditions, and correlation of the catalytic activity with the MOF's properties, in particular, their surface area. The highest yield of 5-HMF (28%) could be obtained using UiO-66 under optimal reaction conditions in dimethylsulfoxide and this could be increased to 37% in the presence of water. In catalyst recycling tests, we found the efficiency of UiO-66 was maintained across five runs (23%, 19%, 21%, 20%, 22.5%). The post-catalysis MOF, UiO-66–humin, was characterized using a range of techniques including PXRD, FT-IR, 13C Solid State NMR and N2 gas adsorption. We continued to optimize the reaction using MOF 808 as the catalyst. Notably, MOF 808 afforded higher yields of 5-HMF under the same conditions compared with the three UiO-66–X compounds. We propose that this might be attributed to the larger pores of MOF 808 or the more accessible zirconium centres

Genome-wide interrogation of structural variation reveals novel African-specific prostate cancer oncogenic drivers

ADDITIONAL FILE 1: FIGURE S1. Concordant SV call generation from Manta and GRIDSS. FIGURE S2. Summary of SVs in each type, compared to other studies. FIGURE S3. CIRCOS plot of hyper-SV mutated tumours. FIGURE S4. The spread of SV breakpoints and samples in each 1 Mbp genomic bin. FIGURE S5. TMPRSS2-ERG fusion with interstitial region retention. TABLE S1. Clinical and pathological characteristics of 180 prostate cancer patients included in this study. TABLE S2. Biallelic assessment of CDK12 in hyper-duplicated samples. TABLE S3. Biallelic assessment of BRCA2 in hyper-deleted samples.ADDITIONAL FILE 2: TABLE S4. Summary of gene fusions identified from SVs. ADDITIONAL FILE 3: TABLE S5. SV calls resulting in gene fusions.DATA AND MATERIALS AVAILABILITY : The datasets analysed in this study were obtained and accessible through Jaratlerdsiri et al [6], with sequence data deposited in the European GenomePhenome Archive (EGA; https://ega-archive.org) under overarching accession EGAS00001006425 and including the Southern African Prostate Cancer Study (SAPCS) Dataset (EGAD00001009067) and Garvan/St Vincent’s Prostate Cancer Database (EGAD00001009066). The computational code used to analyse SV subtypes, SV hotspots and gene fusions is available on GitHub [68].BACKGROUND : African ancestry is a significant risk factor for advanced prostate cancer (PCa). Mortality rates in sub- Saharan Africa are 2.5-fold greater than global averages. However, the region has largely been excluded from the benefits of whole genome interrogation studies. Additionally, while structural variation (SV) is highly prevalent, PCa genomic studies are still biased towards small variant interrogation. METHODS : Using whole genome sequencing and best practice workflows, we performed a comprehensive analysis of SVs for 180 (predominantly Gleason score ≥ 8) prostate tumours derived from 115 African, 61 European and four ancestrally admixed patients. We investigated the landscape and relationship of somatic SVs in driving ethnic disparity (African versus European), with a focus on African men from southern Africa. RESULTS : Duplication events showed the greatest ethnic disparity, with a 1.6- (relative frequency) to 2.5-fold (count) increase in African-derived tumours. Furthermore, we found duplication events to be associated with CDK12 inactivation and MYC copy number gain, and deletion events associated with SPOP mutation. Overall, African-derived tumours were 2-fold more likely to present with a hyper-SV subtype. In addition to hyper-duplication and deletion subtypes, we describe a new hyper-translocation subtype. While we confirm a lower TMPRSS2-ERG fusion-positive rate in tumours from African cases (10% versus 33%), novel African-specific PCa ETS family member and TMPRSS2 fusion partners were identified, including LINC01525, FBXO7, GTF3C2, NTNG1 and YPEL5. Notably, we found 74 somatic SV hotspots impacting 18 new candidate driver genes, with CADM2, LSAMP, PTPRD, PDE4D and PACRG having therapeutic implications for African patients. CONCLUSIONS : In this first African-inclusive SV study for high-risk PCa, we demonstrate the power of SV interrogation for the identification of novel subtypes, oncogenic drivers and therapeutic targets. Identifying a novel spectrum of SVs in tumours derived from African patients provides a mechanism that may contribute, at least in part, to the observed ethnic disparity in advanced PCa presentation in men of African ancestry.The Medical Health and Medical Research Council (NHMRC) of Australia, University of Sydney Bridging Grant, the USA. Department of Defense (DoD) Prostate Cancer Research Program (PCRP) Idea Development.https://genomemedicine.biomedcentral.comam2023School of Health Systems and Public Health (SHSPH

Can locally-recruited R&D personnel significantly contribute to multinational subsidiary innovation in an emerging economy?

This paper assesses the role of locally-recruited R&D personnel relative to their expatriate counterparts as regards innovation in multinational subsidiaries in an emerging economy. Two hypotheses are developed based on a network approach to multinational enterprises in an emerging economy setting, and tested on a sample of 317 multinational subsidiaries in China. Our results indicate that locally-recruited R&D personnel have played a limited role in innovation within multinational subsidiaries. While making a marginally significant contribution to R&D output due to their direct supply of technological knowledge, locally-recruited R&D personnel are unable to translate subsidiary R&D expenditure into successful patent applications probably because of their lack of technology management skills. In comparison, R&D expatriates significantly contribute to multinational subsidiary R&R output in both dimensions

Heterodimerization of Glycosylated Insulin-Like Growth Factor-1 Receptors and Insulin Receptors in Cancer Cells Sensitive to Anti-IGF1R Antibody

Identification of predictive biomarkers is essential for the successful development of targeted therapy. Insulin-like growth factor 1 receptor (IGF1R) has been examined as a potential therapeutic target for various cancers. However, recent clinical trials showed that anti-IGF1R antibody and chemotherapy are not effective for treating lung cancer.In order to define biomarkers for predicting successful IGF1R targeted therapy, we evaluated the anti-proliferation effect of figitumumab (CP-751,871), a humanized anti-IGF1R antibody, against nine gastric and eight hepatocellular cancer cell lines. Out of 17 cancer cell lines, figitumumab effectively inhibited the growth of three cell lines (SNU719, HepG2, and SNU368), decreased p-AKT and p-STAT3 levels, and induced G 1 arrest in a dose-dependent manner. Interestingly, these cells showed co-overexpression and altered mobility of the IGF1R and insulin receptor (IR). Immunoprecipitaion (IP) assays and ELISA confirmed the presence of IGF1R/IR heterodimeric receptors in figitumumab-sensitive cells. Treatment with figitumumab led to the dissociation of IGF1-dependent heterodimeric receptors and inhibited tumor growth with decreased levels of heterodimeric receptors in a mouse xenograft model. We next found that both IGF1R and IR were N-linked glyosylated in figitumumab-sensitive cells. In particular, mass spectrometry showed that IGF1R had N-linked glycans at N913 in three figitumumab-sensitive cell lines. We observed that an absence of N-linked glycosylation at N913 led to a lack of membranous localization of IGF1R and figitumumab insensitivity.The data suggest that the level of N-linked glycosylated IGF1R/IR heterodimeric receptor is highly associated with sensitivity to anti-IGF1R antibody in cancer cells