Application of next-generation sequencing in clinical oncology to advance personalized treatment of cancer

With the development and improvement of new sequencing technology,next-generation sequencing(NGS) has been applied increasingly in cancer genomics research over the past decade.More recently,NGS has been adopted in clinical oncology to advance personalized treatment of cancer.NGS is used to identify novel and rare cancer mutations,detect familial cancer mutation carriers,and provide molecular rationale for appropriate targeted therapy.Compared to traditional sequencing,NGS holds many advantages,such as the ability to fully sequence all types of mutations for a large number of genes(hundreds to thousands) in a single test at a relatively low cost.However,significant challenges,particularly with respect to the requirement for simpler assays,more flexible throughput,shorter turnaround time,and most importantly,easier data analysis and interpretation,will have to be overcome to translate NGS to the bedside of cancer patients.Overall,continuous dedication to apply NGS in clinical oncology practice will enable us to be one step closer to personalized medicine.

Synthesis of Pyrrole-Imidazole Polyamide

One simple and versatile method is established far the synthesis of DNA recognition molecules-polyamides containing alternating N-methylpyrrole and N-methylimidazole without necessitating NH2- group protection.

Crystal Structure of 2,6-Dihistidine Dimethyl Ester Pyridine Acylamine Monohydrate

The crystal structure of the title compound,C21H25N7O7,has been determined in the orthorhombic space group C222（1） with a=8.993（10）,b=12.149（14）,c=22.20（2）A and Z=4.There exist intramolecular C-H…O and N-H…N hydrogen bonds in the title crystal structure.The intermolecular N-H…N and C-H…O hydrogen bonds together with π-π stacking interactions（face-to-face） link the molecules into an infinite three-dimensional supramolecular network.

Molecular modeling on Zn(Ⅱ) binding modes of Alzheimer's amyloid β-peptide in insoluble aggregates and soluble complexes

Aggregation of the amyloid b-peptide (A b) into insoluble fibrils is a key pathologi-cal event in Alzheimers disease. Zn(II) ion induces significant Ab aggregation at nearly physio-logical concentrations in vitro. In order to explore the induce mechanism, the possible binding modes of Zn(II) in Ab peptide are studied by molecular modeling method. First, the Ab species containing 1,2,4 and 12 peptides are established respectively. And next a Zn(II) ion is manually hold the different sits of the Ab species based on the experimental data and subsequently the coordinate atom and number are assigned. Finally, the optimum binding site is found by the system energy minimization. Modeling results show that in soluble Zn(II) complex, Nt of imidazole ring of His14, O of carbonyl of main-chain, and two O of water occupy the four ligand positions of the tetrahedral complex; in the aggregation of Ab, the His13(Nt)-Zn(II)-His14(Nt) bridges are formed by Zn(II) cross-linking action. Therefore, the possible Zn(II) binding mode obtained by the studies will be helpful to reveal the form mechanism of pathogenic aggregates in brain.

Cost-effective hybrid long-short read assembly delineates alternative GC-rich Streptomyces hosts for natural product discovery

With the advent of rapid automated in silico identification of biosynthetic gene clusters(BGCs),genomics pre-sents vast opportunities to accelerate natural product(NP)discovery.However,prolific NP producers,Strepto-myces,are exceptionally GC-rich(>80%)and highly repetitive within BGCs.These pose challenges in sequencing and high-quality genome assembly which are currently circumvented via intensive sequencing.Here,we outline a more cost-effective workflow using multiplex Illumina and Oxford Nanopore sequencing with hybrid long-short read assembly algorithms to generate high quality genomes.Our protocol involves subjecting long read-derived assemblies to up to 4 rounds of polishing with short reads to yield accurate BGC predictions.We successfully sequenced and assembled 8 GC-rich Streptomyces genomes whose lengths range from 7.1 to 12.1 Mb with a median N50 of 8.2 Mb.Taxonomic analysis revealed previous misrepresentation among these strains and allowed us to propose a potentially new species,Streptomyces sydneybrenneri.Further comprehensive characterization of their biosynthetic,pan-genomic and antibiotic resistance features especially for molecules derived from type I polyketide synthase(PKS)BGCs reflected their potential as alternative NP hosts.Thus,the genome assemblies and insights presented here are envisioned to serve as gateway for the scientific community to expand their avenues in NP discovery.

Fluorescence study on the interaction between apoCopC and cupric

The interaction between apoCopC and cupric was investigated by fluorescence spectra, in phosphate (20 mmol/L) buffer at pH 6.0. Results suggest that the environ- ment is measured to be hydrophobic completely around tryptophan (83). At the same time, apoCopC fluorescence at 320 nm was significantly quenched with the addition of cu- pric and the 1:1 stoichiometric ratio of apoCopC to cupric was confirmed by fluorescence. In addition, the conditional binding constants were calculated to be KCu-Copc = (1.8±0.58)× 1013 mol?1 L on the basis of the results of fluorescence titra- tion curves. The apoCopC has the ability to bind specifically cupric ion.

Effects of La^3+ on inward K^+ channels at plasma membrane in guard cells

The effects of La3+ on inward K+ channels at plasma membrane in vicia guard cells are investigated using the whole-cell patch-clamp recording mode. It is shown that La3+ on both sides of plasma membrane blocks inward K+ currents in a concentration- dependent manner, indicating that La3+ binding sites may exist on both sides of plasma membrane in guard cells in vicia. The dose response is fitted by the Michaelis-Menten relation characterized by an inhibitor constant Ki of 2.56±0.25 μmol·L?1 (outside membrane) and (1.18±0.11)×10?15 mol·L?1 (inside membrane). Intracellular La3+ has much stronger inhibitory effect on inward K+ currents than ex- tracellular La3+ does, suggesting there may exist stronger binding sites inside membrane than outside membrane. Since ion channel activities of guard cells directly affect plant stomatal movement and water status, our results imply that rare earth elements might have potential practical values in regulating plant water status and strengthening plant drought endurance.

Nitric oxide suppresses stomatal opening by inhibiting inward-rectifying K_(in)^+ channels in Arabidopsis guard cells

We explore nitric oxide (NO) effect on K+in channels in Arabidopsis guard cells. We observed NO inhib- ited K+in currents when Ca2+ chelator EGTA (Ethylene glycol-bis(2-aminoethylether)-N,N,N′,N′-tetraacetic acid) was not added in the pipette solution; K+in currents were not sensitive to NO when cytosolic Ca2+ was chelated by EGTA. NO inhibited the Arabidopsis stomatal opening, but when EGTA was added in the bath solution, inhibition effect of NO on stomatal opening vanished. Thus, it implies that NO ele- vates cytosolic Ca2+ by activating plasma membrane Ca2+ channels firstly, then inactivates K+in chan- nels, resulting in stomatal opening suppressed subsequently.

Recent Progress in Metal-Organic Frameworks@Cellulose Hybrids and Their Applications

In recent years,metal-organic frameworks(MOFs)are attracting increasing attention due to their charming properties.However,the intrinsic fragility,powdered crystalline state,and poor processibility of MOFs hinder their further application.By this,the designs of MOF-based aerogels,hydrogels,membranes are effective ways to solve this problem.Graphene,silica,synthetic polymer and cellulose are the commonly used raw materials for fabricating MOF-based aerogels,hydrogels,and membranes.Among them,cellulose and its derivatives are the best candidates to support the powdered MOFs from the perspectives of economy,environmental protection and property.This review focuses on discussing the advantages of MOF@cellulose hybrids in applications such as water treatment,antibacterial,gas separation and adsorption,energy storage,drug delivery,catalysis,and other smart composites.MOF@cellulose-based aerogels,hydrogels and membranes can provide valuable guidance for investigating the practical application of MOFs in terms of processability,reusability,stability and easiness in handling.

Study on the interactions between anti-tumor metal complexes and mononucleotides using trans-[en2Os(h^2-H2)(CF3SO3)](CF3SO3) as a 1H NMR probe in a competitive mode

The interaction of several anti-tumor metal complexes with dGMP have been investigated using trans-[en2Os(η2-H2)]2+ as a 1H NMR probe in a competitive mode. Me2SnCl2, Bu2SnCl2, Et2Sn(phen)Cl2 and Et2SnCl2 can bind to dGMP mainly via phosphate; Cp2TiCl2 binds to dGMP mainly via phosphate and N7. The binding constant for (CH3)2SnCl2 binding to phos-phate of dGMP exceeds 2.71×104. The binding constant for Cp2TiCl2 to phosphate is even greater than that of Sn(IV). Cis-platin has high affinity for both N7 and phosphate, but mainly for N7. Binding of the probe to N7 of dGMP reduces the binding affinity for phosphate of the same dGMP molecule by a factor of 5 to 6. Much the same factor is expected to apply to other metals containing agents interacting with dGMP.

Characteristics of mass spectra of dichlorocarbene derivatives of isomeric dodecen-1-ols

The m/z of characteristic ion of the mass spectra of the dichlorocarbene of dodecen-1-ols was used as a parameter to locate the position of double bond in these isomers by a new formula.