Synthesis and Morphological Transformation of Conjugated Amphiphilic Diblock Copolymers in Mixed Solvents

The synthesis, morphological transformation, and photophysical properties of a rod-coil block copolymer, poly[2,7-(9,9-dihexylfluorene)]-block-poly(2-vinylpyridine) (PF-b-P2VP), with P2VP coils of various lengths in a mixed methanol/tetrahydrofuran (MeOH/THF) solvent are reported. Various morphological structures of PF-b-P2VP aggregates, including spheres, short worm-like structures, long cylinders, and large compound micelles (LCMs), were observed after varying the coil length of PF-b-P2VP and the selectivity of mixed solvents. These aggregated structures demonstrated considerable variation with regard to optical absorption, fluorescence, and the PL quantum yield of rod-coil copolymers. The degree of hypsochromic spectral shift was enhanced as the length of P2VP coils and the content of poor solvent increased. This study reveals the influence of coil length and selectivity of solvents on the morphology and the optical characteristics of rod-coil amphiphilic copolymers

Pterostilbene, a Methoxylated Resveratrol Derivative, Efficiently Eradicates Planktonic, Biofilm, and Intracellular MRSA by Topical Application

Pterostilbene is a methoxylated derivative of resveratrol originated from natural sources. We investigated the antibacterial activity of pterostilbene against drug-resistant Staphylococcus aureus and the feasibility of using it to treat cutaneous bacteria. The antimicrobial effect was evaluated using an in vitro culture model and an in vivo mouse model of cutaneous infection. The minimum inhibitory concentration (MIC) assay demonstrated a superior biocidal activity of pterostilbene compared to resveratrol (8~16-fold) against methicillin-resistant S. aureus (MRSA) and clinically isolated vancomycin-intermediate S. aureus (VISA). Pterostilbene was found to reduce MRSA biofilm thickness from 18 to 10 μm as detected by confocal microscopy. Pterostilbene showed minimal toxicity to THP-1 cells and was readily engulfed by the macrophages, facilitating the eradication of intracellular MRSA. Pterostilbene exhibited increased skin absorption over resveratrol by 6-fold. Topical pterostilbene application improved the abscess formation produced by MRSA by reducing the bacterial burden and ameliorating the skin architecture. The potent anti-MRSA capability of pterostilbene was related to bacterial membrane leakage, chaperone protein downregulation, and ribosomal protein upregulation. This mechanism of action was different from that of resveratrol according to proteomic analysis and molecular docking. Pterostilbene has the potential to serve as a novel class of topically applied agents for treating MRSA infection in the skin while demonstrating less toxicity to mammalian cells

Drug-eluting bead transarterial chemoembolization for hepatocellular carcinoma: does size really matter?

PURPOSEWe aimed to compare the safety and effectiveness of 100–300 μm versus 300–500 μm drug-eluting bead transarterial chemoembolization (DEB-TACE) and to investigate the impact of tumor and feeding artery size on treatment outcome of different particle sizes in the treatment of hepatocellular carcinoma (HCC).METHODSThis retrospective cohort study enrolled 234 consecutive patients who underwent TACE using 100–300 μm DEB (Group A, n=75) and 300–500 μm DEB (Group B, n=159) in a tertiary center between August 2012 and March 2017. Initial treatment response and adverse events were assessed using modified Response Evaluation Criteria in Solid Tumors (mRECIST) and National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, respectively.RESULTSA total of 704 HCCs in 234 patients were evaluated. The average index tumor size was 3.8 cm. Multivariate analysis showed that tumor size, lobe involvement, particle size, and tumor location were significant predictive factors of complete response. The overall rate of complete response in groups A and B were 56.0% and 33.3% (P = 0.001), respectively. Group A had higher complete response rate than group B in the subgroup of BCLC B with tumor <3 cm (57.9% vs. 21.1%; P = 0.020) and subgroup of feeding artery ≥0.9 mm (55.2% vs. 30.9%; P = 0.014). There were fewer major complications in group A compared with group B (0% vs. 6.9%, P = 0.018).CONCLUSIONTACE with 100–300 μm DEB is associated with better initial treatment response and fewer major complications compared with 300–500 μm. Our study also highlights the impact of tumor characteristics on treatment outcome of different DEB size, which might help to select the optimal sphere size for TACE in the treatment of HCC

Frequent occurrence of unreduced gametes in Triticum turgidum-Aegilops tauschii hybrids.

Abstract Spontaneous chromosome doubling via union of unreduced (2n) gametes has been thought to be the way that common wheat (Triticum aestivum L.) was originated from the hybridization of T. turgidum L. with Ae. tauschii Cosson. Previous works have observed unreduced gametes in F 1 hybrids of Ae. tauschii with six of the eight T. turgidum subspecies. It is not clear, however, whether the formation of these unreduced gametes is a norm in the F 1 hybrids. In the present study, we tried to answer this question by assessing the occurrence frequency of unreduced gametes in 115 T. turgidum-Ae. tauschii hybrid combinations, involving 76 genotypes of seven T. turgdium subspecies and 24 Ae. tauschii accessions. Our data show that these hybrid combinations differed significantly (P B 0.01, F = 11.40) in selfed seedset, an indicator for production of unreduced gametes. This study clearly showed that meiotic restitution genes are widely distributed within T. turgidum. However, significant differences were found between as well as within T. turgidum subspecies and in the interaction of the T. turgidum genotypes with those of Ae. taushii. The possible application of the meiotic restitution genes from T. turgidum in production of double haploids is also discussed

4β-Hydroxywithanolide E from Physalis peruviana (golden berry) inhibits growth of human lung cancer cells through DNA damage, apoptosis and G2/M arrest

<p>Abstract</p> <p>Background</p> <p>The crude extract of the fruit bearing plant, <it>Physalis peruviana </it>(golden berry), demonstrated anti-hepatoma and anti-inflammatory activities. However, the cellular mechanism involved in this process is still unknown.</p> <p>Methods</p> <p>Herein, we isolated the main pure compound, 4β-Hydroxywithanolide (4βHWE) derived from golden berries, and investigated its antiproliferative effect on a human lung cancer cell line (H1299) using survival, cell cycle, and apoptosis analyses. An alkaline comet-nuclear extract (NE) assay was used to evaluate the DNA damage due to the drug.</p> <p>Results</p> <p>It was shown that DNA damage was significantly induced by 1, 5, and 10 μg/mL 4βHWE for 2 h in a dose-dependent manner (<it>p </it>< 0.005). A trypan blue exclusion assay showed that the proliferation of cells was inhibited by 4βHWE in both dose- and time-dependent manners (<it>p </it>< 0.05 and 0.001 for 24 and 48 h, respectively). The half maximal inhibitory concentrations (IC₅₀) of 4βHWE in H1299 cells for 24 and 48 h were 0.6 and 0.71 μg/mL, respectively, suggesting it could be a potential therapeutic agent against lung cancer. In a flow cytometric analysis, 4βHWE produced cell cycle perturbation in the form of sub-G₁accumulation and slight arrest at the G₂/M phase with 1 μg/mL for 12 and 24 h, respectively. Using flow cytometric and annexin V/propidium iodide immunofluorescence double-staining techniques, these phenomena were proven to be apoptosis and complete G₂/M arrest for H1299 cells treated with 5 μg/mL for 24 h.</p> <p>Conclusions</p> <p>In this study, we demonstrated that golden berry-derived 4βHWE is a potential DNA-damaging and chemotherapeutic agent against lung cancer.</p

Oct-4 Expression Maintained Cancer Stem-Like Properties in Lung Cancer-Derived CD133-Positive Cells

CD133 (prominin-1), a 5-transmembrane glycoprotein, has recently been considered to be an important marker that represents the subset population of cancer stem-like cells. Herein we report the isolation of CD133-positive cells (LC-CD133+) and CD133-negative cells (LC-CD133−) from tissue samples of ten patients with non-small cell lung cancer (LC) and five LC cell lines. LC-CD133+ displayed higher Oct-4 expressions with the ability to self-renew and may represent a reservoir with proliferative potential for generating lung cancer cells. Furthermore, LC-CD133+, unlike LC-CD133−, highly co-expressed the multiple drug-resistant marker ABCG2 and showed significant resistance to chemotherapy agents (i.e., cisplatin, etoposide, doxorubicin, and paclitaxel) and radiotherapy. The treatment of Oct-4 siRNA with lentiviral vector can specifically block the capability of LC-CD133+ to form spheres and can further facilitate LC-CD133+ to differentiate into LC-CD133−. In addition, knock-down of Oct-4 expression in LC-CD133+ can significantly inhibit the abilities of tumor invasion and colony formation, and increase apoptotic activities of caspase 3 and poly (ADP-ribose) polymerase (PARP). Finally, in vitro and in vivo studies further confirm that the treatment effect of chemoradiotherapy for LC-CD133+ can be improved by the treatment of Oct-4 siRNA. In conclusion, we demonstrated that Oct-4 expression plays a crucial role in maintaining the self-renewing, cancer stem-like, and chemoradioresistant properties of LC-CD133+. Future research is warranted regarding the up-regulated expression of Oct-4 in LC-CD133+ and malignant lung cancer

Neutrino Physics with JUNO

The Jiangmen Underground Neutrino Observatory (JUNO), a 20 kton multi-purposeunderground liquid scintillator detector, was proposed with the determinationof the neutrino mass hierarchy as a primary physics goal. It is also capable ofobserving neutrinos from terrestrial and extra-terrestrial sources, includingsupernova burst neutrinos, diffuse supernova neutrino background, geoneutrinos,atmospheric neutrinos, solar neutrinos, as well as exotic searches such asnucleon decays, dark matter, sterile neutrinos, etc. We present the physicsmotivations and the anticipated performance of the JUNO detector for variousproposed measurements. By detecting reactor antineutrinos from two power plantsat 53-km distance, JUNO will determine the neutrino mass hierarchy at a 3-4sigma significance with six years of running. The measurement of antineutrinospectrum will also lead to the precise determination of three out of the sixoscillation parameters to an accuracy of better than 1\%. Neutrino burst from atypical core-collapse supernova at 10 kpc would lead to ~5000inverse-beta-decay events and ~2000 all-flavor neutrino-proton elasticscattering events in JUNO. Detection of DSNB would provide valuable informationon the cosmic star-formation rate and the average core-collapsed neutrinoenergy spectrum. Geo-neutrinos can be detected in JUNO with a rate of ~400events per year, significantly improving the statistics of existing geoneutrinosamples. The JUNO detector is sensitive to several exotic searches, e.g. protondecay via the $p\to K^++\bar\nu$ decay channel. The JUNO detector will providea unique facility to address many outstanding crucial questions in particle andastrophysics. It holds the great potential for further advancing our quest tounderstanding the fundamental properties of neutrinos, one of the buildingblocks of our Universe

Potential causal association between gut microbiome and posttraumatic stress disorder

Background: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome. Results: In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability. Conclusion: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

The use of plants in the traditional management of diabetes in Nigeria: Pharmacological and toxicological considerations

Ethnopharmacological relevance: The prevalence of diabetes is on a steady increase worldwide and it is now identified as one of the main threats to human health in the 21st century. In Nigeria, the use of herbal medicine alone or alongside prescription drugs for its management is quite common. We hereby carry out a review of medicinal plants traditionally used for diabetes management in Nigeria. Based on the available evidence on the species׳ pharmacology and safety, we highlight ways in which their therapeutic potential can be properly harnessed for possible integration into the country׳s healthcare system. Materials and methods: Ethnobotanical information was obtained from a literature search of electronic databases such as Google Scholar, Pubmed and Scopus up to 2013 for publications on medicinal plants used in diabetes management, in which the place of use and/or sample collection was identified as Nigeria. ‘Diabetes’ and ‘Nigeria’ were used as keywords for the primary searches; and then ‘Plant name – accepted or synonyms’, ‘Constituents’, ‘Drug interaction’ and/or ‘Toxicity’ for the secondary searches. Results: The hypoglycemic effect of over a hundred out of the 115 plants reviewed in this paper is backed by preclinical experimental evidence, either in vivo or in vitro. One-third of the plants have been studied for their mechanism of action, while isolation of the bioactive constituent(s) has been accomplished for twenty three plants. Some plants showed specific organ toxicity, mostly nephrotoxic or hepatotoxic, with direct effects on the levels of some liver function enzymes. Twenty eight plants have been identified as in vitro modulators of P-glycoprotein and/or one or more of the cytochrome P450 enzymes, while eleven plants altered the levels of phase 2 metabolic enzymes, chiefly glutathione, with the potential to alter the pharmacokinetics of co-administered drugs. Conclusion: This review, therefore, provides a useful resource to enable a thorough assessment of the profile of plants used in diabetes management so as to ensure a more rational use. By anticipating potential toxicities or possible herb–drug interactions, significant risks which would otherwise represent a burden on the country׳s healthcare system can be avoided