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Aminoxyl‐mediated electrocatalysis offers a sustainable approach for the oxidation of alcohols to carboxylic acids. However, the high dosage of aminoxyl radicals and the limiting current density hinder the practicality of industrial application. Herein, a nickel‐based electrocatalyst (Ni‐tpdc) was synthesized on a three‐dimensional porous graphite felt substrate. Taking advantage of the synergistic effect of the electrochemically activated Ni‐tpdc/GF electrocatalyst with 4‐acetamido‐TEMPO, the yield of 4‐pyridinecarboxylic acid was up to 99% with only 1 mol% ACT. A series of in situ measurements showed that NiOOH enhanced the activity of the intrinsic electrocatalyst. In addition, the synergistic system was extended to the oxidation of various heterocyclic alcohols. The scale‐up synthesis of chiral acid (LEV‐CO2H) was achieved in an improved electrolyzer with a yield of 95.4%, enantiomeric retention of 99.2%, and space–time yield of 34.12 kg/m3 h. The practicality and effectiveness of this synergistic electrocatalytic strategy in practical electrosynthesis was further demonstrated. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS) are heterogeneous hematopoietic disorders that are incurable with conventional therapy. Their incidence is increasing with global population aging. Although many genetic, epigenetic, splicing, and metabolic aberrations have been identified in patients with MDS, their clinical features are quite similar. Here, we show that hypoxia-independent activation of hypoxia-inducible factor 1α (HIF1A) signaling is both necessary and sufficient to induce dysplastic and cytopenic MDS phenotypes. The HIF1A transcriptional signature is generally activated in MDS patient bone marrow stem/progenitors. Major MDS-associated mutations (Dnmt3a, Tet2, Asxl1, Runx1, and Mll1) activate the HIF1A signature. Although inducible activation of HIF1A signaling in hematopoietic cells is sufficient to induce MDS phenotypes, both genetic and chemical inhibition of HIF1A signaling rescues MDS phenotypes in a mouse model of MDS. These findings reveal HIF1A as a central pathobiologic mediator of MDS and as an effective therapeutic target for a broad spectrum of patients with MDS.Significance: We showed that dysregulation of HIF1A signaling could generate the clinically relevant diversity of MDS phenotypes by functioning as a signaling funnel for MDS driver mutations. This could resolve the disconnection between genotypes and phenotypes and provide a new clue as to how a variety of driver mutations cause common MDS phenotypes. Cancer Discov; 8(11); 1438-57. ©2018 AACR. See related commentary by Chen and Steidl, p. 1355 This article is highlighted in the In This Issue feature, p. 1333.

Nocardiosis is a rare, life-threatening, opportunistic, and suppurative infection. Its clinical manifestation lacks specificity, which makes early diagnosis difficult. A retrospective analysis of the clinical records of 11 patients with nocardiosis admitted to our hospital from January 2013 to November 2018 was conducted. All patients had at least one underlying disorder, such as an autoimmune disease (6/11), a blood malignancy (2/11), avascular necrosis of the femoral head (1/11), bronchiectasis (1/11), or pneumonia (1/11). The first-line treatment was trimethoprim–sulfamethoxazole (TMP–SMX); one or two additional antibiotics were given according to the drug-sensitive test. The median time from onset to treatment was 3 weeks (ranging from 1 to 9 weeks). The median duration of treatment after diagnosis was 20.5 weeks (ranging from 7 to 47 weeks). Eight patients were discharged and survived, and three patients died. This indicates that early use of TMP–SMX combined with sensitive antibiotics could improve the condition of patients and improve the cure rate (8/11). Clinically, it is necessary to consider the possibility of nocardiosis in patients with long-term use of immunosuppressants and poor response to treatment of common bacterial infections. Early diagnosis, timely treatment, and combination drug therapy are keys to improving the outcomes of patients with nocardiosis.

Introduction: In recent years, the development of drug-eluting embolization beads that can be imaged has become a hot research topic in regard to meeting clinical needs. In our previous study, we successfully developed nano-assembled microspheres (NAMs) for multimodal imaging purposes. NAMs can not only be visualized under CT/MR/Raman imaging but can also load clinically required doses of doxorubicin. It is important to systematically compare the pharmacokinetics of NAMs with those of commercially available DC Beads and CalliSpheres to evaluate the clinical application potential of NAMs. Methods: In our study, we compared NAMs with two types of drug-eluting beads (DEBs) in terms of irinotecan, drug-loading capacity, release profiles, microsphere diameter variation, and morphological characteristics. Results: Our results indicate that NAMs had an irinotecan loading capacity similar to those of DC Beads and CalliSpheres but exhibited better sustained release in vitro. Conclusion: NAMs have great potential for application in transcatheter arterial chemoembolization for the treatment of colorectal cancer liver metastases. [ABSTRACT FROM AUTHOR]

α-thalassemia major (α-TM) often causes Hb Bart's (c4) hydrops fetalis and severe obstetric complications in the mother. Step-wise screening for couples at risk of having offspring(s) affected by α-TM is the efficient prevention method but some rare genotypes of thalassemia cannot be detected. A 32-year-old male with low HbA2 (2.4%) and mild anemia was performed real-time PCR-based multicolor melting curve analysis (MMCA) because his wife was –SEA deletion carrier. The result of multiplex ligation-dependent probe amplification (MLPA) suggested the existence of –SEA deletion in the proband. A novel deletion of the α-globin gene cluster was found using self-designed MLPA probes combined with longer PCR, which was further accurately described to be 16.8Kb (hg38, Chr16:1,65,236–1,82,113) deletion by the third-generation sequencing. A fragment ranging from 1,53,226 to 1,54,538(GRch38/hg38) was identified which suggested the existence of the homologous recombination event. The third-generation sequencing is accurate and efficient in obtaining accurate information for complex structural variations. [ABSTRACT FROM AUTHOR]

Simple sequence repeats (SSRs) are found in nonrandom distributions in genomes and are thought to impact gene expression. The distribution patterns of 48 295 SSRs of Paphiopedilum malipoense are mined and characterized based on the first full‐length transcriptome and comprehensive transcriptome dataset from 12 organs. Statistical genomics analyses are used to investigate how SSRs in transcripts affect gene expression. The results demonstrate the correlations between SSR distributions, characteristics, and expression level. Nine expression‐modulating motifs (expMotifs) are identified and a model is proposed to explain the effect of their key features, potency, and gene function on an intra‐transcribed region scale. The expMotif‐transcribed region combination is the most predominant contributor to the expression‐modulating effect of SSRs, and some intra‐transcribed regions are critical for this effect. Genes containing the same type of expMotif‐SSR elements in the same transcribed region are likely linked in function, regulation, or evolution aspects. This study offers novel evidence to understand how SSRs regulate gene expression and provides potential regulatory elements for plant genetic engineering. [ABSTRACT FROM AUTHOR]

Based on the previous work conducted by Fujii et al., NdBaInO4 compounds present modest oxide-ion conductivities. Therefore, it has been an attractive system of significant interest. In this study, we attempted to partially substitute Ca for Nd and the total electrical conductivity was successfully improved due to the generation of oxygen vacancies. The synthesis, crystal structure, density, surface topography, and electrical properties of NdBaInO4 and Ca-doped NdBaInO4 have been studied, respectively. NdBaInO4 and 10% and 20% molar fractions of Ca-doped NdBaInO4 were synthesized through solid-state reactions. The crystal structure of them was obtained from Le Bail refinement of the XRD pattern, giving the result of the monoclinic structure, which belongs to P21/c space group. The highest total electrical conductivity of 4.91 × 10−3 S cm−1 was obtained in the Nd0.9Ca0.1BaInO3.95 sample at a temperature of 760 °C in the dry atmosphere and the activation energy was reduced from 0.68 eV to 0.58 eV when the temperature was above 464 °C (737 K) after doping the NdBaInO4 with a 0.1 molar fraction of Ca2+. Moreover, the total conductivity of Nd0.9Ca0.1BaInO3.95 in the wet atmosphere at moderate temperature was relatively higher than that in the dry atmosphere, which suggests that potential proton conduction may exist in wet atmospheres. In addition, the oxygen diffusion coefficients of Nd0.9Ca0.1BaInO3.95 (D* = 1.82 × 10−8 cm2/s, 850 °C) was about two times higher than that of Nd0.8Ca0.2BaInO3.90 (D* = 7.95 × 10−9 cm2/s, 850 °C) and was increased significantly by two orders of magnitude when compared with the oxygen diffusion coefficient of the undoped NdBaInO4 (D* = 8.25 × 10−11 cm2/s, 850 °C). [ABSTRACT FROM AUTHOR]