Identification of gene mutations in six Chinese patients with maple syrup urine disease

Background: Maple syrup urine disease (MSUD) is a rare autosomal recessive amino acid metabolic disease. This study is to identify the pathogenic genetic factors of six cases of MUSD and evaluates the application value of high-throughput sequencing technology in the early diagnosis of MUSD.Methods: Clinical examination was carried out for patients and used blood tandem mass spectrometry (MS/MS), urine gas chromatography-mass spectrometry (GC/MS), and the application of high-throughput sequencing technology for detection. Validate candidate mutations by polymerase chain reaction (PCR)—Sanger sequencing technology. Bioinformatics software analyzed the variants’ pathogenicity. Using Swiss PDB Viewer software to predict the effect of mutation on the structure of BCKDHA and BCKDHB proteins.Result: A total of six MSUD patients were diagnosed, including four males and two females. Nine variants were found in three genes of six MSUD families by high-throughput sequencing, including four missense mutations: c.659C>T(p.A220V), c.818C>T(p.T273I), c.1134C>G(p.D378E), and c.1006G>A(p.G336S); two non-sense mutations: c.1291C>T(p.R431*) and c.331C>T(p.R111*); three deletion mutations: c.550delT (p.S184Pfs*46), c.718delC (p.P240Lfs*14), and c.795delG (p.N266Tfs*64). Sanger sequencing’s results were consistent with the high-throughput sequencing. The bioinformatics software revealed that the mutations were harmful, and the prediction results of Swiss PDB Viewer suggest that variation affects protein conformation.Conclusion: This study identified nine pathogenic variants in the BCKDHA, BCKDHB, and DBT genes in six MSUD families, including two novel pathogenic variants in the BCKDHB gene, which enriched the genetic mutational spectrum of the disease. High-throughput sequencing is essential for the MSUD’s differential diagnosis, early treatment, and prenatal diagnosis

Interactions of metal-based nanoparticles (MBNPs) and metal-oxide nanoparticles (MONPs) with crop plants: a critical review of research progress and prospects

Over the past decade, the production and applications of metal-based and metal-oxide nanoparticles (MBNPs and MONPs, respectively) have increased significantly due to their enhanced physicochemical properties and biological activities when compared with their bulk parent materials. Once MBNPs and MONPs enter agricultural soil via direct or indirect pathways, they can interact with crop plants and thus pose a threat to both animal and human health through food chain pathways. Although many review articles on engineered nanoparticles have been published, few have focused on the interactions of MBNPs and MONPs with crop plants and their current applications. Therefore, we reviewed the sources and behaviors of MBNPs and MONPs in agricultural soil, physiological and biochemical effects of MBNPs and MONPs on plants, uptake, translocation of MBNPs and MONPs in crop plants, factors affecting the interaction between MBNPs and MONPs and plants, and the applications of MBNPs and MONPs. Lastly, we propose where the future research priorities should be focused to provide a better understanding of MBNPs and MONPs. This review will help to promote scientific research regarding MBNPs and MONPs and to understand the risks and benefits of their association with plants and will contribute to the advancement of nanotechnology.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

The Novel Triazolonaphthalimide Derivative LSS-11 Synergizes the Anti-Proliferative Effect of Paclitaxel via STAT3-Dependent MDR1 and MRP1 Downregulation in Chemoresistant Lung Cancer Cells

Multidrug resistance (MDR) is a major cause of the inefficacy and poor response to paclitaxel-based chemotherapy. The combination of conventional cytotoxic drugs has been a plausible strategy for overcoming paclitaxel resistance. Herein, we investigated the cytotoxic effects and underlying mechanism of LSS-11, a novel naphthalimide derivative-based topoisomerase inhibitor, in paclitaxel-resistant A549 (A549/T) lung cancer cells. LSS-11 enhanced cell death in A549/T cells by inducing apoptosis through increasing the DR5 protein level and PARP1 cleavage. Importantly, LSS-11 dose-dependently reduced STAT3 phosphorylation and downregulated its target genes MDR1 and MRP1, without affecting P-gp transport function. Chromatin coimmunoprecipitation (ChIP) assay further revealed that LSS-11 hindered the binding of STAT3 to the MDR1 and MRP1 promoters. Additionally, pharmacological inhibition of p-STAT3 by sulforaphane downregulated MDR1 and MRP1, resulting in A549/T cell death by triggering apoptosis. Collectively, our data show that LSS-11 is a potent naphthalimide-based chemosensitizer that could enhance cell death in paclitaxel-resistant lung cancer cells through the DR5/PARP1 pathway and STAT3/MDR1/MRP1 STAT3 inhibition

Glycybridins A–K, Bioactive Phenolic Compounds from <i>Glycyrrhiza glabra</i>

In an attempt to discover bioactive agents from the herbal medicine <i>Glycyrrhiza glabra</i> (widely known as licorice), 11 new phenolic compounds, glycybridins A–K (<b>1</b>–<b>11</b>), along with 47 known phenolics (<b>12</b>–<b>58</b>) were isolated. Their structures were elucidated on the basis of extensive NMR and MS analyses as well as experimental and computed ECD data. According to the clinical therapeutic effects of licorice, enzyme or cell-based bioactivity screenings of <b>1</b>–<b>58</b> were conducted. A number of compounds significantly activate Nrf2, inhibit tyrosinase or PTP1B, inhibit LPS-induced NO production and NF-κB transcription, and inhibit the proliferation of human cancer cells (HepG2, SW480, A549, MCF7). Glycybridin D (<b>4</b>) showed moderate cytotoxic activities against the four cancer cell lines, with IC₅₀ values ranging from 4.6 to 6.6 μM. Further studies indicated that <b>4</b> (10 mg/kg, ip) decreased tumor mass by 39.7% on an A549 human lung carcinoma xenograft mice model, but showed little toxicity

Bioactive Constituents of <i>Glycyrrhiza uralensis</i> (Licorice): Discovery of the Effective Components of a Traditional Herbal Medicine

Traditional herbal medicines have been reported to possess significant bioactivities. In this investigation, a combined strategy using both phytochemical and biological approaches was conducted to discern the effective components of licorice, a widely used herbal medicine. Altogether, 122 compounds (<b>1</b>–<b>122</b>), including six new structures (<b>1</b>–<b>6</b>), were isolated and identified from the roots and rhizomes of <i>Glycyrrhiza uralensis</i> (licorice). These compounds were then screened using 11 cell- and enzyme-based bioassay methods, including Nrf2 activation, NO inhibition, NF-κB inhibition, H1N1 virus inhibition, cytotoxicity for cancer cells (HepG2, SW480, A549, MCF7), PTP1B inhibition, tyrosinase inhibition, and AChE inhibition. A number of bioactive compounds, particularly isoprenylated phenolics, were found for the first time. Echinatin (<b>7</b>), a potent Nrf2 activator, was selected as an example for further biological work. It attenuated CCl₄-induced liver damage in mice (5 or 10 mg/kg, ip) and thus is responsible, at least in part, for the hepatoprotective activity of licorice

Observation of Several Sources of CPCP Violation in B+→π+π+π−B^+ \to \pi^+ \pi^+ \pi^- Decays

International audienceObservations are reported of different sources of CP violation from an amplitude analysis of B+→π+π+π- decays, based on a data sample corresponding to an integrated luminosity of 3  fb-1 of pp collisions recorded with the LHCb detector. A large CP asymmetry is observed in the decay amplitude involving the tensor f2(1270) resonance, and in addition significant CP violation is found in the π+π-S wave at low invariant mass. The presence of CP violation related to interference between the π+π-S wave and the P wave B+→ρ(770)0π+ amplitude is also established; this causes large local asymmetries but cancels when integrated over the phase space of the decay. The results provide both qualitative and quantitative new insights into CP -violation effects in hadronic B decays

Measurement of CPCP-violating and mixing-induced observables in Bs0→ϕγB_s^0 \to \phi\gamma decays

International audienceA time-dependent analysis of the Bs0→ϕγ decay rate is performed to determine the CP -violating observables Sϕγ and Cϕγ and the mixing-induced observable AϕγΔ. The measurement is based on a sample of pp collision data recorded with the LHCb detector, corresponding to an integrated luminosity of 3  fb-1 at center-of-mass energies of 7 and 8 TeV. The measured values are Sϕγ=0.43±0.30±0.11, Cϕγ=0.11±0.29±0.11, and AϕγΔ=-0.67-0.41+0.37±0.17, where the first uncertainty is statistical and the second systematic. This is the first measurement of the observables S and C in radiative Bs0 decays. The results are consistent with the standard model predictions