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A dearomative electrophilic fluorination of 2-methylindoles is reported, delivering 3,3-difluoroindolines bearing an exomethylidene. The model substrate was synthesized on up to a 20 mmol scale and was purified by a practical recrystallization as a crystalline bench-stable, yet reactive solid. The olefin is amphoteric and can react both as a nucleophile and as an electrophile. A wide range of metal-free, palladium, rhodium, and copper reactions was explored, forming new C-H, C-B, C-C (alkyl and aryl), C-N, C-O, C-P, and C-S bonds.Up to 10% of patients with atrial fibrillation (AF) undergo percutaneous coronary intervention (PCI). A systematic review and network meta-analysis were conducted by searching PubMed, Embase, and the Cochrane database of systematic reviews for randomized control trials that studied the safety and efficacy of different antithrombotic strategies in these patients. Six studies, including 12,158 patients were included. Compared to that in the triple antithrombotic therapy group (vitamin K antagonist (VKA) plus P2Y12 inhibitor and aspirin), thrombolysis in myocardial infarction (TIMI) major bleeding was significantly reduced in the dual antithrombotic therapy (non-vitamin K oral anticoagulants (NOACs) plus P2Y12 inhibitor) group by 47% (Odds ratio (OR), 0.53; 95% credible interval [CrI], 0.35-0.78; I2 = 0%). Besides, NOAC plus a P2Y12 inhibitor was associated with less intracranial hemorrhage compared to VKA plus single antiplatelet therapy (OR 0.20, 95% CrI 0.05-0.77). There was no significant difference in the trial-defined major adverse cardiac events or the individual outcomes of all-cause mortality, cardiovascular death, myocardial infarction, stroke or stent thrombosis among all antithrombotic strategies. In conclusion, antithrombotic strategy of NOACs plus P2Y12 inhibitor is safer than, and as effective as, the strategies including aspirin when used in AF patients undergoing PCI.Triple negative breast cancer (TNBC) constitutes the most aggressive molecular subtype among breast tumors. iJMJD6 Despite progress on the underlying tumor biology, clinical outcomes for TNBC unfortunately remain poor. The median overall survival for patients with metastatic TNBC is approximately eighteen months. Chemotherapy is the mainstay of treatment while there is a growing body of evidence that targeted therapies may be on the horizon with poly-ADP-ribose polymerase (PARP) and immune check-point inhibitors already established in the treatment paradigm of TNBC. A large number of novel therapeutic agents are being evaluated for their efficacy in TNBC. As novel therapeutics are now incorporated into clinical practice, it is clear that tumor heterogeneity and clonal evolution can result to de novo or acquired treatment resistance. As precision medicine and next generation sequencing is part of cancer diagnostics, tailored treatment approaches based on the expression of molecular markers are currently being implemented in clinical practice and clinical trial design. The scope of this review is to highlight the most relevant current knowledge regarding underlying molecular profile of TNBC and its potential application in clinical practice.Saltpans are a class of ephemeral wetland characterized by alternating periods of inundation, rising salinity, and desiccation. We obtained soil cores from a saltpan on the Mississippi Gulf coast in both the inundated and desiccated state. The microbiomes of surface and 30 cm deep sediment were determined using Illumina sequencing of the V4 region of the 16S rRNA gene. Bacterial and archaeal community composition differed significantly between sediment depths but did not differ between inundated and desiccated states. Well-represented taxa included marine microorganisms as well as multiple halophiles, both observed in greater proportions in surface sediment. Functional inference of metagenomic data showed that saltpan sediments in the inundated state had greater potential for microbial activity and that several energetic and degradation pathways were more prevalent in saltpan sediment than in nearby tidal marsh sediment. Microbial communities within saltpan sediments differed in composition from those in adjacent freshwater and brackish marshes. These findings indicate that the bacterial and archaeal microbiomes of saltpans are highly stratified by sediment depth and are only minimally influenced by changes in hydration. The surface sediment community is likely isolated from the shallow subsurface community by compaction, with the microbial community dominated by marine and terrestrial halophiles.Powder metallurgy is a group of advanced processes for the synthesis, processing, and shaping of various kinds of materials. Initially inspired by ceramics processing, the methodology comprising of the production of a powder and its transformation to a compact solid product has attracted great attention since the end of World War II. At present, there are many technologies for powder production (e.g., gas atomization of the melt, chemical reduction, milling, and mechanical alloying) and its consolidation (e.g., pressing and sintering, hot isostatic pressing, and spark plasma sintering). The most promising ones can achieve an ultra-fine or nano-grained structure of the powder, and preserve it during consolidation. Among these methods, mechanical alloying and spark plasma sintering play a key role. This Special Issue gives special focus to the advancement of mechanical alloying, spark plasma sintering and self-propagating high-temperature synthesis methods, as well as to the role of these processes in the development of new materials.Seaweeds have been exploited as both food products and therapeutics to manage human ailments for centuries. This study investigated the metabolite profile of five seaweeds (Halimeda spp., Spyridia hypnoides (Bory de Saint-Vincent) Papenfuss, Valoniopsis pachynema (G. Martens) Børgesen, Gracilaria fergusonii J. Agardh and Amphiroa anceps (Lamarck) Decaisne using ultra-high-performance liquid chromatography coupled with electrospray ionization mass spectrometry (UHPLC-ESI-MS/MS). Furthermore, these seaweeds were assessed for antioxidant and inhibitory effects against α-amylase, α-glucosidase, acetyl-cholinesterase (AChE), butyryl-cholinesterase (BChE) and tyrosinase. Valoniopsis pachynema and A. anceps yielded the highest flavonoid (4.30 ± 0.29 mg RE/g) and phenolic content (7.83 ± 0.08 mg RE/g), respectively. Additionally, A. anceps exhibited significant antioxidant properties with all assays and significantly depressed BChE (IC50 = 6.68 ± 0.83 mg/mL) and α-amylase activities (IC50 = 5.34 ± 0.14 mg/mL). Interestingly, the five seaweeds revealed potent inhibitory effects against tyrosinase activity. In conclusion, A. anceps might be considered as a key source of phytoantioxidants and a potential candidate to develop nutritional supplements. Besides, the five tested seaweeds warrant further study and may be exploited as promising natural sources for managing hyperpigmentation.The initial exposure to influenza virus usually occurs during childhood. This imprinting has long-lasting effects on the immune responses to subsequent infections and vaccinations. Animal models that are used to investigate influenza pathogenesis and vaccination do recapitulate the pre-immune history in the human population. The establishment of influenza pre-immune ferret models is necessary for understanding infection and transmission and for designing efficacious vaccines.Food waste (FW) is a critical challenge in the Gulf Cooperation Council (GCC). This paper analyzes research dealing with food waste in the GCC countries (viz. Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, United Arab Emirates). It draws upon a systematic review performed on Scopus in January 2020. The paper covers both bibliometrics (e.g., authors, affiliations, journals) and research topics (e.g., causes, food supply chain stages, extent and quantity, food security, economic impacts, environmental implications, management strategies). A main finding of the review is the scarcity of data on FW in the GCC in general and in Kuwait, Oman, and Bahrain in particular. Most of the selected articles address FW reuse and recycling (e.g., waste-to-energy conversion, compost production). Indeed, other FW management strategies, such as reduction/prevention and redistribution, are overlooked. The systematic review highlights that further research on FW in the GCC is highly needed with a focus on the identified research gaps such as causes and drivers, trends, magnitude and extent, environmental and economic impacts, along with implications of food wastage in terms of food security. Since food wastage is a common issue for all GCC countries, these research gaps should be addressed in a shared regional research agenda.BACKGROUND Prostate cancer (PCa) is the most prevalent malignancy diagnosed in men in Western countries. There is currently no effective therapy for advanced PCa aggressiveness, including castration-resistant progression. The aim of this study is to evaluate the potential efficacy and determine the molecular basis of Davallia formosana (DF) in PCa. Methods LNCaP (androgen-sensitive) and C4-2 (androgen-insensitive/castration-resistant) PCa cells were utilized in this study. An MTT-based method, a wound healing assay, and the transwell method were performed to evaluate cell proliferation, migration, and invasion. Intracellular fatty acid levels and lipid droplet accumulation were analyzed to determine lipogenesis. Moreover, apoptotic assays and in vivo experiments were conducted. RESULTS DF ethanol extract (DFE) suppressed proliferation, migration, and invasion in PCa cells. DFE attenuated lipogenesis through inhibition of the expression of sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FASN). Moreover, DFE decreased androgen receptor (AR) and prostate-specific antigen (PSA) expression in PCa cells. We further showed the potent therapeutic activity of DFE by repressing the growth and leading to apoptosis of subcutaneous C4-2 tumors in a xenograft mouse model. CONCLUSIONS These data provide a new molecular basis of DFE in PCa cells, and co-targeting SREBP-1/FASN/lipogenesis and the AR axis by DFE could be employed as a novel and promising strategy for the treatment of PCa.Heterologous expression of the NAD+-dependent phosphite dehydrogenase (PTXD) bacterial enzyme from Pseudomonas stutzerii enables selective growth of transgenic organisms by using phosphite as sole phosphorous source. Combining phosphite fertilization with nuclear expression of the ptxD transgene was shown to be an alternative to herbicides in controlling weeds and contamination of algal cultures. Chloroplast expression of ptxD in Chlamydomonas reinhardtii was proposed as an environmentally friendly alternative to antibiotic resistance genes for plastid transformation. However, PTXD activity in the chloroplast is low, possibly due to the low NAD+/NADP+ ratio, limiting the efficiency of phosphite assimilation. We addressed the intrinsic constraints of the PTXD activity in the chloroplast and improved its catalytic efficiency in vivo via rational mutagenesis of key residues involved in cofactor binding. Transplastomic lines carrying a mutagenized PTXD version promiscuously used NADP+ and NAD+ for converting phosphite into phosphate and grew faster compared to those expressing the wild type protein.
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