bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic mastocytosis in adults: 2019 update on diagnosis, risk stratification and management
Authors: Pardanani Animesh 
Published: December 2018

AbstractOverviewSystemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MCs) in extra‐cutaneous organs.DiagnosisThe major criterion is presence of multifocal clusters of abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC CD25 expression, and presence of KITD816V mutation.Risk stratificationEstablishing SM subtype as per the World Health Organization classification system is an important first step. Broadly, patients either have indolent/smoldering SM (ISM/SSM) or advanced SM, the latter includes aggressive SM (ASM), SM with associated hematological neoplasm (SM‐AHN), and mast cell leukemia (MCL). Identification of poor‐risk mutations (ie, ASXL1, RUNX1, SRSF2, NRAS) further refines the risk stratification. Recently, clinical and hybrid clinical‐molecular risk models have been developed to more accurately assign prognosis in SM patients.ManagementISM patients have a normal life expectancy and treatment is generally limited to anaphylaxis prevention/symptom control/osteoporosis treatment. Patients with advanced SM frequently need MC cytoreductive therapy to ameliorate disease‐related organ dysfunction. High response rates have been seen with small‐molecule inhibitors that target mutant‐KIT, including midostaurin (Food and Drug Administration approved) or avapritinib (investigational). Other options for MC cytoreduction include cladribine or interferon‐α, although head‐to‐head comparisons are lacking. Treatment of SM‐AHN primarily targets the AHN component, if an aggressive disease such as acute myeloid leukemia is present. Allogeneic stem cell transplant can be considered in such patients, or in those with relapsed/refractory advanced SM. Imatinib has a limited therapeutic role in SM; effective cytoreduction is limited to those with imatinib‐sensitive KIT mutations.
Ruxolitinib treatment for steroid refractory acute and chronic graft vs host disease in children: Clinical and immunological results
Authors: González Vicent Marta , Molina Blanca , González de Pablo Jesús , Castillo Ana , Díaz Miguel Ángel 
Published: December 2018

AbstractRuxolitinib is a promising treatment for steroid refractory graft‐vs‐host disease (GvHD). However, data concerning effects on T cells are probably involved in increased risk of opportunistic infections. We analyzed clinical and immunological changes in children with GvHD taking ruxolitinib. Twenty‐two children that underwent transplantation and received ruxolitinib were included. Ruxolitinib indication was acute and chronic GvHD in 13 and 9 patients, respectively. Overall response rate (ORR) in acute GvHD and chronic GvHD was high, of 77% and 89%, respectively. Ruxolitinib was associated with an increase in CD4 effector memory (EM), and decrease of CD4 central memory percentage. CD4 regulatory T cells percentage decreased significantly. Patients who achieved complete response to ruxolitinib had higher natural killer (NK) cells before ruxolitinib that patients who did not respond. Also there was an increase of CD4 lymphocytes percentage, with decrease of CD8 and NK cells percentage in responders against non‐responders. There were 54%, 18% and 13% of infections caused by virus, bacteria and fungi, respectively. Cumulative incidence of relapse and non‐relapse mortality was 19 ± 9%and 28 ± 10%, respectively. Overall survival and disease‐free survival rate at 2 years were 62 ± 11% and 58 ± 11%, respectively. Ruxolitinib is a promising treatment for acute and chronic GvHD with a high ORR of 77% and 89%, respectively. It produces important changes in immune system, such as increase of CD4 EM cells and decrease in NK and regulatory T cells. Now, we need pharmacokinetic studies to determine ruxolitinib dose in children and close surveillance and antimicrobial prophylaxis.
Long‐Life Room‐Temperature Sodium–Sulfur Batteries by Virtue of Transition‐Metal‐Nanocluster–Sulfur Interactions
Authors: Zhang Bin‐Wei , Sheng Tian , Wang Yun‐Xiao , Chou Shulei , Davey Kenneth , Dou Shi‐Xue , Qiao Shi‐Zhang 
Published: December 2018

AbstractRoom‐temperature sodium–sulfur (RT‐Na/S) batteries hold significant promise for large‐scale application because of low cost of both sodium and sulfur. However, the dissolution of polysulfides into the electrolyte limits practical application. Now, the design and testing of a new class of sulfur hosts as transition‐metal (Fe, Cu, and Ni) nanoclusters (ca. 1.2 nm) wreathed on hollow carbon nanospheres (S@M‐HC) for RT‐Na/S batteries is reported. A chemical couple between the metal nanoclusters and sulfur is hypothesized to assist in immobilization of sulfur and to enhance conductivity and activity. S@Fe‐HC exhibited an unprecedented reversible capacity of 394 mAh g−1 despite 1000 cycles at 100 mA g−1, together with a rate capability of 220 mAh g−1 at a high current density of 5 A g−1. DFT calculations underscore that these metal nanoclusters serve as electrocatalysts to rapidly reduce Na2S4 into short‐chain sulfides and thereby obviate the shuttle effect.
Molecular Scaffolds as Double‐Targeting Agents For the Diagnosis and Treatment of Neuroblastoma
Authors: Villaverde Gonzalo , Alfranca Arantzazu , Gonzalez‐Murillo África , Melen Gustavo J. , Castillo Rafael R. , Ramírez Manuel , Baeza Alejandro , Vallet‐Regí María 
Published: December 2018

AbstractThe selective delivery of therapeutic and imaging agents to tumoral cells has been postulated as one of the most important challenges in the nanomedicine field. Meta‐iodobenzilguanidine (MIBG) is widely used for the diagnosis of neuroblastoma (NB) due to its strong affinity for the norepinephrine transporter (NET), usually overexpressed on the membrane of malignant cells. Herein, a family of novel Y‐shaped scaffolds has been synthesized, which have structural analogues of MIBG covalently attached at each end of the Y‐structure. The cellular uptake capacity of these double‐targeting ligands has been evaluated in vitro and in vivo, yielding one specific Y‐shaped structure that is able to be engulfed by the malignant cells, and accumulates in the tumoral tissue, at significantly higher levels than the structure containing only one single targeting agent. This Y‐shaped ligand can provide a powerful tool for the current treatment and diagnosis of this disease.
Palladium‐ and Rhodium‐Catalyzed Dynamic Kinetic Resolution of Racemic Internal Allenes Towards Chiral Pyrazoles
Authors: Hilpert Lukas J. , Sieger Simon V. , Haydl Alexander M. , Breit Bernhard 
Published: December 2018

AbstractA complementing Pd‐ and Rh‐catalyzed dynamic kinetic resolution (DKR) of racemic allenes leading to N‐allylated pyrazoles is described. Such compounds are of enormous interest in medicinal chemistry as certified drugs and potential drug candidates. The new methods feature high chemo‐, regio‐ and enantioselectivities aside from displaying a broad substrate scope and functional group compatibility. A mechanistic rational accounting for allene racemization and trans‐alkene selectivity is discussed.
Azide Passivation of Black Phosphorus Nanosheets: Covalent Functionalization Affords Ambient Stability Enhancement
Authors: Liu Yajuan , Gao Pengfei , Zhang Taiming , Zhu Xianjun , Zhang Mengmeng , Chen Muqing , Du Pingwu , Wang Guan‐Wu , Ji Hengxing , Yang Jinlong , Yang Shangfeng 
Published: December 2018

AbstractTwo‐dimensional (2D) black phosphorus (BP) has a unique band structure, but it suffers from low ambient stability owing to its high reactivity to oxygen. Covalent functionalization has been demonstrated to passivate the reactive BP effectively, however the reported covalent functionalization methods are quite limited to aryl diazonium and nucleophilic additions affording P−C and P−O−C single bonds, for which the retaining of one unpaired electron in the Group 15 phosphorus atom hampers the passivation effect. Now, covalent azide functionalization of BP nanosheets (BPNSs) is reported, leading to significant enhancement of the ambient stability of BP as confirmed by UV/Vis spectroscopic studies. The most stable configuration of the azide functionalized BPNSs (f‐BPNSs) is predicted by theoretical calculations, featuring the grafting of benzoic acid moiety onto BPNSs via the unprecedented P=N double bonds formed through in situ nitrene as a reactive intermediate.
Enhanced Performance of Organic/Inorganic Hybrid Nanomaterials bearing Impregnated [PdL2] Complexes as Counter‐Electrode Catalyst for Dye‐Sensitized Solar Cells
Authors: Dayan Serkan , Özdemir Namık , Özpozan Nilgün Kalaycıoğlu 
Published: December 2018

N‐coordinate Pd2+ complexes [PdL2] (L: N‐N‐quinoline‐8‐yl‐R‐benzenesulfonamides) (6–10) and [PdL2] complexes assembled on multi‐wall carbon nanotubes (MWCNTs) hybrid nanomaterials were fabricated and characterized by various techniques. The [PdL2] impregnated MWCNTs materials (11–15) were applied as a counter electrode (CE) catalyst for triiodide to iodide reduction reaction in the dye‐sensitized solar cells (DSSC) and investigated electro‐catalytic activities.The MWCNTs‐supported [PdL2] CEs (11–15) are exhibits as Pt‐free CE with good power conversion efficiencies (PCEs), and compared to platinum and bare MWCNTs CEs and the PCE of bare MWCNTs was clearly improved by means of [PdL2] complexes (6–10). The DSSCs based on the hybrid counter electrodes (CEs) (11–15) and bare MWCNTs are indicated a relative efficiency (ƞrel) of 64.27%, 54.07%, 53.75%, 51.52% 44.82% and 27.27% concerning a Pt CE control device set at 100%. The report emphasizes that [PdL2] impregnated MWCNTs type counter electrodes (CEs) (11–15) are promising as effectively catalyst in working device design, particularly taking into account the eco‐friendly approach of the hybrids.
Synthetic Methodology for Structurally Defined and Insulated Molecular Wires Bearing Non‐centrosymmetric Conjugated Axle Components via Iterative Intramolecular Slippage
Authors: Chou Sheng‐Ying , Masai Hiroshi , Tsuda Susumu , Terao Jun 
Published: December 2018

AbstractInsulated molecular wires (IMWs) bearing non‐centrosymmetric conjugated axle components were precisely synthesized via iterative cross‐coupling reactions in organic solvents and subsequent intramolecular slippage transformation in aqueous solvents. This programmable synthetic procedure selectively afforded both insulated and uninsulated molecular wires bearing oligo(phenylene ethynylene) and permethylated α‐cyclodextrins with well‐defined conjugation lengths and supramolecular structures. High selectivity of this method was confirmed by NMR and mass spectroscopic analyses. The resultant IMWs exhibited distinct optical properties because of different conjugation lengths and insulated structures. This synthetic strategy for structurally defined IMWs bearing non‐centrosymmetric conjugated axle components could provide a platform for obtaining diverse functionalized materials useful in the fields of non‐centrosymmetric molecular machines and molecular electronics.
microRNA‐96 protects pancreatic β‐cell function by targeting PAK1 in gestational diabetes mellitus
Authors: Li Lei , Wang Shan , Li Hongyan , Wan Jipeng , Zhou Qian , Zhou Yu , Zhang Chunhua 
Published: December 2018

AbstractGestational diabetes mellitus (GDM) is a disease condition in which a woman develops high blood sugar levels during pregnancy, which might be induced by multiple factors. Among those relative factors, microRNA (miRNA) is well‐known to be involved in GDM development. In this study, we investigated the role of miRNA in GDM by analyzing miRNA expression profiling in placenta tissues from healthy or GDM pregnancies. We found that miR‐96 was the most down‐regulated miRNA in GDM samples. Furthermore, miRNA target gene prediction revealed that p21‐activated kinase 1 (PAK1) is a potential target of miR‐96. Functional assays showed that miR‐96 enhanced β‐cell function, whereas PAK1 inhibited β‐cell function and cell viability. Our findings demonstrate that miR‐96 plays a critical role in GDM development by regulating PAK1 expression, insulin secretion, and β‐cell function. © 2018 BioFactors, 44(6):539–547, 2018
Bioinformatic analysis of the prognostic value of the lncRNAs encoding snoRNAs in hepatocellular carcinoma
Authors: Zhu Qingyao , Yang Hongjie , Cheng Peng , Han Qian 
Published: December 2018

AbstractSome lncRNAs can encode small nucleolar RNAs (snoRNAs), called small nucleolar RNA host genes (SNHGs), which exert diverse regulatory effects on cellular processes. In this study, using RNA‐seq and survival data in the Cancer Genome Atlas (TCGA)‐Liver Hepatocellular Carcinoma (LIHC), we examined the expression profile of some SNHG genes and explored their prognostic value in hepatocellular carcinoma (HCC). Level‐3 RNA‐sequencing data, the clinicopathological and survival data of patients with primary HCC were downloaded from the UCSC Xena browser (https://xenabrowser.net/), for a secondary analysis. Results showed that SNHG1, GAS5, SNHG3‐7 and SNHG10‐12 were significantly upregulated in HCC tissues (N = 49) compared with adjacent normal tissues (N = 49). After adjustment for confounding factors, the multivariate analysis confirmed that increased SNHG4 expression was independently associated with shorter OS (HR: 1.319, 95%CI: 1.131–1.537, P < 0.001), while increased GAS5 expression was an independent predictor of shorter RFS (HR: 1.287, 95% CI: 1.027–1.612, P = 0.028). Using the methylation data obtained from the Infinium HumanMethylation450 BeadChip, we found that SNHG4 expression was not likely to be modulated by methylation in HCC. In comparison, the methylation status of 5 CpG sites (cg07177756, cg17025683, cg16290996, cg03044573 and cg06644515) showed a moderately negative correlation (Pearson's r = −0.54, P < 0.001) with GAS5 expression. Based on these findings, we infer that SNHG4 and GAS5 might be valuable prognostic markers in HCC. DNA hypomethylation might play an important role in elevated GAS5 transcription in HCC. © 2018 BioFactors, 45(2):244–252, 2019
Characterization of thin gelatin hydrogel membranes with balloon properties for dynamic tissue engineering
Authors: Jepsen Morten Leth , Nielsen Line Hagner , Boisen Anja , Almdal Kristoffer , Dufva Martin 
Published: December 2018

AbstractCell or tissue stretching and strain are present in any in vivo environment, but is difficult to reproduce in vitro. Here, we describe a simple method for casting a thin (about 500 μm) and soft (about 0.3 kPa) hydrogel of gelatin and a method for characterizing the mechanical properties of the hydrogel simply by changing pressure with a water column. The gelatin is crosslinked with mTransglutaminase and the area of the resulting hydrogel can be increased up 13‐fold by increasing the radial water pressure. This is far beyond physiological stretches observed in vivo. Actuating the hydrogel with a radial force achieves both information about stiffness, stretchability, and contractability, which are relevant properties for tissue engineering purposes. Cells could be stretched and contracted using the gelatin membrane. Gelatin is a commonly used polymer for hydrogels in tissue engineering, and the discovered reversible stretching is particularly interesting for organ modeling applications.
Engineering an EGFR‐binding Gp2 domain for increased hydrophilicity
Authors: Du Feifan , Kruziki Max A. , Zudock Elizabeth J. , Zhang Yi , Lown Patrick S. , Hackel Benjamin J. 
Published: December 2018

AbstractThe Gp2 domain is a 45 amino‐acid scaffold that has been evolved for specific, high‐affinity binding towards multiple targets and was proven useful in molecular imaging and biological antagonism. It was hypothesized that Gp2 may benefit from increased hydrophilicity for improved physiological distribution as well as for physicochemical robustness. We identified seven exposed hydrophobic sites for hydrophilic mutations and experimentally evaluated single mutants, which yielded six mutations that do not substantially hinder expression, binding affinity or specificity (to epidermal growth factor receptor), and thermal stability. Eight combinations of these mutations improved hydrophilicity relative to the parental Gp2 clone as assessed by reverse‐phase high‐performance liquid chromatography (p < 0.05). Secondary structures and refolding abilities of the selected single mutants and all multimutants were unchanged relative to the parental ligand. A variant with five hydrophobic‐to‐hydrophilic mutations was identified with enhanced solubility as well as reasonable binding affinity (
K
d = 53–63 nM), recombinant yield (1.3 ± 0.8 mg/L), and thermal stability (
T
m = 53 ± 3°C). An alternative variant with a cluster of three leucine‐to‐hydrophilic mutations was identified with increased solubility, nominally increased binding affinity (
K
d = 13–28 nM) and reasonable thermal stability (
T
m = 54.0 ± 0.6°C) but reduced yield (0.4 ± 0.3 mg/L). In addition, a ≥7°C increase in the midpoint of thermal denaturation was observed in one of the single mutants (T21N). These mutants highlight the physicochemical tradeoffs associated with hydrophobic‐to‐hydrophilic mutation within a small protein, improve the solubility and hydrophilicity of an existent molecular imaging probe, and provide a more hydrophilic starting point for discovery of new Gp2 ligands towards additional targets.
Increased biomass and lipid production by continuous cultivation of Nannochloropsis salina transformant overexpressing a bHLH transcription factor
Authors: Kang Nam Kyu , Kim Eun Kyung , Sung Min‐Gyu , Kim Young Uk , Jeong Byeong‐ryool , Chang Yong Keun 
Published: December 2018

AbstractMicroalgae are promising feedstocks for sustainable and eco‐friendly production of biomaterials, which can be improved by genetic engineering. It is also necessary to optimize the processes to produce biomaterials from engineered microalgae. We previously reported that genetic improvements of an industrial microalga Nannochloropsis salina by overexpressing a basic helix‐loop‐helix transcription factor (NsbHLH2). These transformants showed an improved growth and lipid production particularly during the early phase of culture under batch culture. However, they had faster uptake of nutrients, resulting in earlier starvation and reduced growth during the later stages. We attempted to optimize the growth and lipid production by growing one of the transformants in continuous culture with variable dilution rate and feed nitrogen concentration. Relative to wild‐type, NsbHLH2 transformant consumed more nitrate at a high dilution rate (0.5 day
−1), and had greater biomass production. Subsequently, nitrogen limitation at continuous cultivation led to an increased fatty acid methyl ester production by 83.6 mg l
−1 day
−1. To elucidate genetic mechanisms, we identified the genes containing E‐boxes, known as binding sites for bHLH transcription factors. Among these, we selected 18 genes involved in the growth and lipid metabolism, and revealed their positive contribution to the phenotypes via quantitative real‐time polymerase chain reaction. These results provide proof‐of‐concept that NsbHLH2 can be used to produce biomass and lipids.
Enhancing cofactor recycling in the bioconversion of racemic alcohols to chiral amines with alcohol dehydrogenase and amine dehydrogenase by coupling cells and cell‐free system
Authors: Liu Ji , Li Zhi 
Published: December 2018

AbstractAlcohol dehydrogenase (ADH) and amine dehydrogenase (AmDH)‐catalyzed one‐pot cascade conversion of an alcohol to an amine provides a simple preparation of chiral amines. To enhance the cofactor recycling in this reaction, we report a new concept of coupling whole‐cells with the cell‐free system to enable separated intracellular and extracellular cofactor regeneration and recycling. This was demonstrated by the respective biotransformation of racemic 4‐phenyl‐2‐butanol 1a and 1‐phenyl‐2‐propanol 1b to (R)‐4‐phenylbutan‐2‐amine 3a and (R)‐1‐phenylpropan‐2‐amine 3b. Escherichia coli cells expressing S‐enantioselective CpsADH, R‐enantioselective PfODH, and NADH oxidase (NOX) was developed to oxidize racemic alcohols 1a–b to ketones 2a–b with full conversion via intracellular NAD+ recycling. AmDH and glucose dehydrogenase (GDH) were used to convert ketones 2a–b to amines (R)‐3a–b with 89–94% conversion and 891–943 times recycling of NADH. Combining the cells and enzymes for the cascade transformation of racemic alcohols 1a–b gave 70% and 48% conversion to the amines (R)‐3a and (R)‐3b in 99% ee, with a total turnover number (TTN) of 350 and 240 for NADH recycling, respectively. Improved results were obtained by using the E. coli cells with immobilized AmDH and GDH: (R)‐3a was produced in 99% ee with 71–84% conversion and a TTN of 1410‐1260 for NADH recycling, the highest value so far for the ADH–AmDH‐catalyzed cascade conversion of alcohols to amines. The concept might be generally applicable to this type of reactions.
Engineering self‐flocculating Halomonas campaniensis for wastewaterless open and continuous fermentation
Authors: Ling Chen , Qiao Guan‐Qing , Shuai Bo‐Wen , Song Kun‐Nan , Yao Wen‐Xi , Jiang Xiao‐Ran , Chen Guo‐Qiang 
Published: December 2018

AbstractHalomonas has been developed as a platform for the next generation industrial biotechnology allowing open and nonsterile growth without microbial contamination under a high‐salt concentration and alkali pH. To reduce downstream cost associated with continuous centrifugation and salt containing wastewater treatment, Halomonas campaniensis strain LS21 was engineered to become self‐flocculating by knocking out an
etf operon encoding two subunits of an electron transferring flavoprotein in the predicted electron transfer chain. Self‐flocculation could be attributed to the decrease of the surface charge and increase of the cellular hydrophobicity resulted from deleted
etf. A wastewaterless fermentation strategy based on the self‐flocculating
H. campaniensis was developed for growth and the production of poly‐3‐hydroxybutyrate (PHB) as an example. Most microbial cells flocculated and precipitated to the bottom of the bioreactor within 1 min after stopping the aeration and agitation. The supernatant can be used again without sterilization or inoculation for the growth of the next batch after collecting the precipitated cell mass. The wastewaterless process was conducted for four runs without generating wastewater. PHB accumulation by the self‐flocculent strain was enhanced via promoter and ribosome binding site optimizations, the productivities of cell dry weight and PHB were increased from 0.45 and 0.18 g·L
−1·hr
−1 for the batch process compared to 0.82 and 0.33 g·L
−1·hr
−1 for the wastewaterless continuous process, respectively. This has clearly demonstrated the advantages of the wastewaterless process in that it not only reduces wastewater but also increases cell growth and product formation efficiency in a given period of time.
A Covalent Inhibitor for Glutathione S‐Transferase Pi (GSTP1‐1) in Human Cells
Authors: Shishido Yuko , Tomoike Fumiaki , Kuwata Keiko , Fujikawa Haruka , Sekido Yoshitaka , Murakami‐Tonami Yuko , Kameda Tomoshi , Abe Naoko , Kimura Yasuaki , Shuto Satoshi , Abe Hiroshi 
Published: December 2018

AbstractGlutathione S‐transferase π (GSTP1‐1) is overexpressed in many types of cancer and is involved in drug resistance. Therefore, GSTP1‐1 is an important target in cancer therapy, and many GST inhibitors have been reported. We had previously developed an irreversible inhibitor, GS‐ESF, as an effective GST inhibitor; however, its cellular permeability was too low for it to be used in inhibiting intracellular GST. We have now developed new irreversible inhibitors by introducing sulfonyl fluoride (SF) into chloronitrobenzene (CNB). The mechanism of action was revealed to be that CNBSF first reacts with glutathione (GSH) through an aromatic substitution in the cell, then the sulfonyl group on the GSH conjugate with CNBSF reacts with Tyr108 of GST to form a sulfonyl ester bond. Our new inhibitor irreversible inhibited GSTP1‐1 both in vitro and in cellulo with a long duration of action.