De Novo Asymmetric Syntheses of Bioactive Natural Products and Carbohydrate Motifs

De novo asymmetric syntheses of daumone I-1 and the fluorescent analog have been described. This route took advantage of the Noyori asymmetric hydrogenation of acetyl furan and alkynyl ketone, the Pd-catalyzed glycosylation and various post-glycosylation transformations to finish the total synthesis of Daumone I-1, which provided materials for mechanism of action studies.;In an effort to mimics natures use of rare sugars in the synthesis of biologically important natural products (e.g., the carbohydrate portion of Daumone I-1), the O\u27Doherty group has been interested in developing new methods for practical and stereoselective synthesis. As part of these efforts, a concise synthesis of benzyl alpha-6-deoxy-altro-pyranoside and benzyl-ascarylo-pyranoside has been developed. The synthesis relied upon a Pd-catalyzed glycosylation reaction, a highly diastereoselecitve epoxidation and ring opening.;An enantioselective synthesis of cladospolide B, C and (ent)-cladospolide D has been achieved. This synthesis not only provided access to these antimicrobial natural products but also corrected the structural assignment of cladospolide D by means of a de novo synthesis and kinetic/thermodynamic alkene isomerization. The synthesis coupled the Noyori reduction of alkynyl ketone and the alkyl zipper reaction with the conversion to and asymmetric oxidation of dienoates to enable the successful synthesis of cladospolides B-D.;A de novo asymmetric total synthesis of aspergilliges has been investigated. The challenge of our route is using a novel palladium-catalyzed addition of a vinyl group to install the key trans-pyran ring system. To date, an intermediate which is five steps away from a formal synthesis of aspergillide C has been prepared by Pd-catalyzed C-glycosylation and Julia olefination. Noyori reductions of furyl and propargyl ketone, alkyne zipper reaction and Au-catalyzed alkyne hydration have been utilized

Loss-of-Function Screen Reveals Novel Regulators Required for Drosophila Germline Stem Cell Self-Renewal

The germline stem cells (GSCs) of Drosophila melanogaster ovary provide an excellent model system to study the molecular mechanisms of stem cell self-renewal. To reveal novel factors required for Drosophila female GSC maintenance and/or division, we performed a loss-of-function screen in GSCs by using a collection of P-element–induced alleles of essential genes. Mutations in genes of various functional groups were identified to cause defects in GSC self-renewal. Here we report that a group of mutations affecting various ubiquitin-conjugating enzymes cause significant GSCs loss, including Plenty of SH3s (POSH), Ubiquitin-conjugating enzyme 10 (UbcD10), and pineapple eye (pie). Ubiquitin-mediated protein degradation plays a variety of roles in the regulation of many developmental processes, including mediating stem cell division through degradation of cell cycle regulators. We demonstrated that pie, sharing highly conserved RING domains with human E3 ubiquitin ligase G2E3 that are critical for early embryonic development, is specifically required for GSC maintenance, possibly through regulation of bone morphogenetic protein signaling pathway. Despite the previously reported role in imaginal disc cell survival, pie loss-of-function induced GSC loss is not to the result of caspase-involved cell death. Further efforts are needed to elucidate the functions of ubiquitin ligases in GSC maintenance, which will ultimately contribute to a better understanding of how the ubiquitin-conjugating enzymes regulate stem cell biology in mammalian systems

Unraveling the Prognostic Significance of Rgs Gene Family in Gastric Cancer and the Potential Implication of Rgs4 in Regulating Tumor-infiltrating Fibroblast

Regulator of G-protein signaling (RGS) proteins are regulators of signal transduction mediated by G protein-coupled receptors (GPCRs). Current studies have shown that some molecules in the RGS gene family are related to the occurrence, development and poor prognosis of malignant tumors. However, the RGS gene family has been rarely studied in gastric cancer. In this study, we explored the mutation and expression profile of RGS gene family in gastric cancer, and evaluated the prognostic value of RGS expression. Then we established a prognostic model based on RGS gene family and performed functional analysis. Further studies showed that RGS4, as an independent prognostic predictor, may play an important role in regulating fibroblasts in the immune microenvironment. In conclusion, this study explores the value of RGS gene family in gastric cancer, which is of great significance for predicting the prognosis and guiding the treatment of gastric cancer

Influence of Metal Fiber Content and Arrangement on Shielding Effectiveness for Blended Electromagnetic Shielding Fabric

More metal fiber content of blended electromagnetic shielding (EMS) fabric results in higher shielding effectiveness (SE) of the fabric. However, there is little information about the influence of the metal fiber content on the SE considering the fabric structure. This study constructs an index of metal fiber content per unit area (MFCPUA), and discusses the influence of the metal fiber content on the SE of the EMS fabric when fabric parameters are changed. Computations for the MFCPUA and the thickness and porosity of the metal fiber arrangement are given, and then experiments are designed to test the SE of different EMS fabric samples. According to the experimental results, the influence of the MFCPUA on the SE is analyzed and influence mechanism is discussed when the fabric weaves, emission frequencies and weft and warp densities are changed. Results show that the MFCPUA and the SE are positive increase relation; the frequency and the SE are the negative increase relation when the metal fiber content is unchanged; the influence of the fabric weave type on the SE depends on the length of the yarn floats; the SE values of fabric with same weave are same when the MFCPUA is same regardless of the fabric density.DOI: http://dx.doi.org/10.5755/j01.ms.21.2.6529</p

Zinc regeneration in rechargeable zinc-air fuel cells:a review

Zinc-air fuel cells (ZAFCs) present a promising energy source with a competing potential with the lithium-ion battery and even with proton-exchange membrane fuel cells (PEMFCs) for applications in next generation electrified transport and energy storage. The regeneration of zinc is essential for developing the next-generation, i.e., electrochemically rechargeable ZAFCs. This review aims to provide a comprehensive view on both theoretical and industrial platforms already built hitherto, with focus on electrode materials, electrode and electrolyte additives, solution chemistry, zinc deposition reaction mechanisms and kinetics, and electrochemical zinc regeneration systems. The related technological challenges and their possible solutions are described and discussed. A summary of important R&D patents published within the recent 10 years is also presented

Evidence for Transgenerational Transmission of Epigenetic Tumor Susceptibility in Drosophila

Transgenerational epigenetic inheritance results from incomplete erasure of parental epigenetic marks during epigenetic reprogramming at fertilization. The significance of this phenomenon, and the mechanism by which it occurs, remains obscure. Here, we show that genetic mutations in Drosophila may cause epigenetic alterations that, when inherited, influence tumor susceptibility of the offspring. We found that many of the mutations that affected tumorigenesis induced by a hyperactive JAK kinase, HopTum-l, also modified the tumor phenotype epigenetically, such that the modification persisted even in the offspring that did not inherit the modifier mutation. We analyzed mutations of the transcription repressor Krüppel (Kr), which is one of the hopTum-l enhancers known to affect ftz transcription. We demonstrate that the Kr mutation causes increased DNA methylation in the ftz promoter region, and that the aberrant ftz transcription and promoter methylation are both transgenerationally heritable if HopTum-l is present in the oocyte. These results suggest that genetic mutations may alter epigenetic markings in the form of DNA methylation, which are normally erased early in the next generation, and that JAK overactivation disrupts epigenetic reprogramming and allows inheritance of epimutations that influence tumorigenesis in future generations

Unraveling the prognostic significance of RGS gene family in gastric cancer and the potential implication of RGS4 in regulating tumor-infiltrating fibroblast

Regulator of G-protein signaling (RGS) proteins are regulators of signal transduction mediated by G protein-coupled receptors (GPCRs). Current studies have shown that some molecules in the RGS gene family are related to the occurrence, development and poor prognosis of malignant tumors. However, the RGS gene family has been rarely studied in gastric cancer. In this study, we explored the mutation and expression profile of RGS gene family in gastric cancer, and evaluated the prognostic value of RGS expression. Then we established a prognostic model based on RGS gene family and performed functional analysis. Further studies showed that RGS4, as an independent prognostic predictor, may play an important role in regulating fibroblasts in the immune microenvironment. In conclusion, this study explores the value of RGS gene family in gastric cancer, which is of great significance for predicting the prognosis and guiding the treatment of gastric cancer

Evaluation of Epigallocatechin-3-Gallate as a Radioprotective Agent During Radiotherapy of Lung Cancer Patients: A 5-Year Survival Analysis of a Phase 2 Study

BackgroundPrevious analysis of the study (NCT02577393) had demonstrated the application of epigallocatechin-3-gallate (EGCG) could be safe and effective in the prevention and treatment of acute radiation esophagitis in patients with advanced lung cancer. EGCG seemed to improve the response rate of small cell lung cancer (SCLC) to radiotherapy in a subgroup analysis. This research continued to analyze the impact of EGCG application on cancer-radiation efficacy and patient survival.MethodsAll patients with SCLC in the NCT02577393 study were included. Patients were randomized into EGCG group or conventional therapy group as protocol. The primary endpoints of the study were radiation response rate and progression-free survival (PFS). Overall survival (OS) and the efficacy of EGCG in the treatment of esophagitis were assessed as secondary endpoints.ResultsA total of 83 patients with lung cancer in the NCT02577393 study were screened, and all 38 patients with SCLC were eligible for analysis. No significant differences with regard to baseline demographic and clinical characteristics were observed between the two groups. The objective response rate (ORR) was higher than that of conventionally treated patients (84.6 vs 50%, P = 0.045), while the median PFS and OS were not significantly prolonged. At data cut-off (1 January 2021), 5-year PFS was 33% with EGCG versus 9.3% with conventional treatment, and 5-year OS was 30.3% versus 33.3%, respectively. The mean adjusted esophagitis index and pain index of patients with EGCG application were lower than conventional treatment (5.15 ± 2.75 vs 7.17 ± 1.99, P = 0.030; 8.62 ± 5.04 vs 15.42 ± 5.04, P &lt; 0.001).ConclusionThe study indicates EGCG may alleviate some esophagitis-related indexes in SCLC patients exposed to ionizing radiation without reducing survival. However, this conclusion should be confirmed by further studies with large sample size

Simple, Rapid Mycobacterium ulcerans Disease Diagnosis from Clinical Samples by Fluorescence of Mycolactone on Thin Layer Chromatography

Introduction: Mycobacterium ulcerans infection, known as Buruli ulcer, is a disease of the skin and subcutaneous tissues which is an important but neglected tropical disease with its major impact in rural parts of West and Central Africa where facilities for diagnosis and management are poorly developed. We evaluated fluorescent thin layer chromatography (f-TLC) for detection of mycolactone in the laboratory using samples from patients with Buruli ulcer and patients with similar lesions that gave a negative result on PCR for the IS2404 repeat sequence of M. ulcerans Methodology/Principal findings Mycolactone and DNA extracts from fine needle aspiration (FNA), swabs and biopsy specimen were used to determine the sensitivity and specificity of f-TLC when compared with PCR for the IS2404. For 71 IS2404 PCR positive and 28 PCR negative samples the sensitivity was 73.2% and specificity of 85.7% for f-TLC. The sensitivity was similar for swabs (73%), FNAs (75%) and biopsies (70%). Conclusions: We have shown that mycolactone can be detected from M. ulcerans infected skin tissue by f-TLC technique. The technique is simple, easy to perform and read with minimal costs. In this study it was undertaken by a member of the group from each endemic country. It is a potentially implementable tool at the district level after evaluation in larger field studies

Efficient rate-power allocation for OFDM in a realistic fading environment

The implementation of practical adaptive resource allocation scheme remains a key criterion to be satisfied for realising spectrally efficient multitone wireless communications. The ever-increasing demand for spectrally efficient broadband wireless transmission technologies has spurred intensive research leading towards the implementation of adaptive OFDM and adaptive MIMO systems. Efforts in this direction have been frustrated however by the lack of a clear and accurate description of the fading behaviour typically encountered in the broadband wireless transmission environment. This has been partially been overcome by the use of mathematical modelling which captures certain large-scale characteristics of the channel and facilitates theoretical research. The “average” channel parameters gleaned from these processes is typically then used to inform the design and configuration of wireless networking equipment after the broad application of generous safety margins. The resulting solu�tion is therefore quite robust to certain transient channel quality degradation yet the generous safety tolerances render it unable to exploit other transient transmission quality improvements We seek to overcome the problems associated with this ap�proach by applying a theoretically sound novel adaptive resource allocation framework to actual broadband wireless channel development data. The allocation framework is derived from the optimal OFDM allocation scheme for a known channel [1]: the channel development data is obtained from actual measurement of a broadband wireless mobile environment [2]. Prediction tech�niques are employed to overcome the time lag between channel assessment and symbol transmission. We present the details of the predictive resource allocation scheme used and include a broad characterisation of the transmission environment in terms of the time-varying fading processes observed. We provide some results of the application of this scheme as typical performance levels that may be achieved in an actual transmission environment