Alloying techniques show genuine potential to develop more effective catalysts than Pt for oxygen reduction reaction (ORR), which is the key challenge in many important electrochemical energy ...conversion and storage devices, such as fuel cells and metal‐air batteries. Tremendous efforts have been made to improve ORR activity by designing bimetallic nanocatalysts, which have been limited to only alloys of platinum and transition metals (TMs). The Pt‐TM alloys suffer from critical durability in acid‐media fuel cells. Here a new class of mesostructured Pt–Al catalysts is reported, consisting of atomic‐layer‐thick Pt skin and Pt3Al or Pt5Al intermetallic compound skeletons for the enhanced ORR performance. As a result of strong Pt–Al bonds that inhibit the evolution of Pt skin and produce ligand and compressive strain effects, the Pt3Al and Pt5Al mesoporous catalysts are exceptionally durable and ≈6.3‐ and ≈5.0‐fold more active than the state‐of‐the‐art Pt/C catalyst at 0.90 V, respectively. The high performance makes them promising candidates as cathode nanocatalysts in next‐generation fuel cells.
A mesostructured ordered intermetallic of PtAl is developed by a facilely and cost‐effectively alloying/dealloying approach for the high‐performance ORR. The extremely strong covalent bonds between Pt and Al not only give rise to excellent kinetic stability, but also result in remarkable catalytic activity duo to the downshift of d‐band center.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Aim
We performed a meta‐analysis of randomized controlled trials (RCT) and observational studies to answer the two following questions: (i) whether low maternal circulating 25 hydroxyvitamin D ...(25‐OHD) is associated with an increased risk of preterm birth (PTB) or spontaneous PTB (sPTB); and (ii) whether vitamin D supplementation alone during pregnancy can reduce the risk of PTB.
Methods
Literature search was carried out using Pubmed, Web of Science and Embase databases up to June 2016. Pooled OR or relative risk (RR) with 95%CI were computed using fixed or random effects models depending on the size of heterogeneity. Subgroup analysis was used to explore potential sources of between‐study heterogeneity. Publication bias was evaluated using Egger's test and Begg's test.
Results
Twenty‐four articles (six RCT and 18 observational studies) were identified. Maternal circulating 25‐OHD deficiency (pooled OR, 1.25; 95%CI: 1.13–1.38) rather than insufficiency (pooled OR, 1.09; 95%CI: 0.89–1.35) was associated with an increased risk of PTB, and vitamin D supplementation alone during pregnancy could reduce the risk of PTB (pooled RR, 0.57; 95%CI: 0.36–0.91). This was also the case for the sPTB subgroup (circulating 25‐OHD <50 vs >50 nmol/L; pooled OR, 1.45; 95%CI: 1.20–1.75).
Conclusions
Maternal circulating 25‐OHD deficiency could increase PTB risk and vitamin D supplementation alone during pregnancy could reduce PTB risk. Extrapolation of the results, however, must be done with caution, and there is urgent need for larger, better‐designed RCT to confirm this effect.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
•Phthalate diesters (PE) were measured in multiple urine samples during pregnancy.•Hazard index (HI) for multiple phthalates was calculated for each urine sample.•Components of metabolic syndrome ...were assessed as outcomes.•Inconsistent outcome associations were observed for single PEs and metabolites.•HI was associated with increased risks of GDM, HDOP and excessive GWG.
Few studies have investigated the association of gestational exposure to phthalate with metabolic risk and have reached inconsistent conclusions. Based on the Ma’anshan Birth Cohort, 3273 women were included in the present study. All participants provided up to three urine samples for 7 phthalate metabolite measurements. The hazard index (HI) was used to evaluate the cumulative risk of multiple phthalate coexposures. The outcomes of interest included hypertensive disorders of pregnancy (HDOP), gestational diabetes mellitus (GDM), and gestational weight gain (GWG). The incidences of HDOP, GDM, and excessive GWG were 5.93%, 13.09%, and 28.95%, respectively. Exposure to a single phthalate metabolite or a specific diester during the first trimester of pregnancy elevated blood pressure (BP) and fasting plasma glucose (FPG) in the third trimester and body weight gain throughout pregnancy. However, inverse relationships were revealed for some phthalate metabolites, which were inconsistent with the results of their diesters. The HI value during the first trimester was positively associated with subsequent BP, FPG, and GWG. In addition, HI during the first trimester increased the risks of GDM odds ratio (OR) = 1.34, 95% confidence intervals (CIs) = 1.02–1.75) and excessive GWG (OR = 1.76, 95% CIs = 1.41–2.19) in a linear manner thereafter. Notably, phthalates might directly increase maternal blood glucose and pressure, and these changes were secondary effects of the obesiogenic effects of certain phthalates. In conclusion, exposure to single and multiple phthalates during the first trimester of pregnancy increased the risks of maternal metabolic syndrome components. However, the conflicting findings between phthalates and their metabolites need to be interpreted carefully.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Exosomes are a subset of extracellular vesicles that carry specific combinations of proteins, nucleic acids, metabolites, and lipids. Mounting evidence suggests that exosomes participate in ...intercellular communication and act as important molecular vehicles in the regulation of numerous physiological and pathological processes, including cancer development. Exosomes are released by various cell types under both normal and pathological conditions, and they can be found in multiple bodily fluids. Moreover, exosomes carrying a wide variety of important macromolecules provide a window into altered cellular or tissue states. Their presence in biological fluids renders them an attractive, minimally invasive approach for liquid biopsies with potential biomarkers for cancer diagnosis, prediction, and surveillance. Due to their biocompatibility and low immunogenicity and cytotoxicity, exosomes have potential clinical applications in the development of innovative therapeutic approaches. Here, we summarize recent advances in various technologies for exosome isolation for cancer research. We outline the functions of exosomes in regulating tumor metastasis, drug resistance, and immune modulation in the context of cancer development. Finally, we discuss prospects and challenges for the clinical development of exosome-based liquid biopsies and therapeutics.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We herein report an additive‐free alternative for the generation of cyanoalkyl radicals through photoinduced single electron transfer from dichalcogenides to cyclobutanone oxime esters, resulting in ...chalcogen‐containing nitriles. Experimental and DFT studies supported the occurrence of the process between the two components.
A photoactive charge transfer complex protocol for the generation of cyanoalkyl radicals from cyclobutanone oxime esters with dichalcogenides is established.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Epigallocatechin‐3‐gallate (EGCG) and caffeine in tea exert anti‐obesity effects and induces nonalcoholic fatty liver disease (NAFLD) amelioration. However, previous studies usually performed a ...high‐dose EGCG administration, whereas the insecurity was arisen in recent researches. In this study, we treated obese rats with an elaborate dose—40 mg/kg EGCG, 20 mg/kg caffeine, and the coadministration of them as low dose, which were similar to the daily intake; 160 mg/kg EGCG as high dose, which was the maximum safe dose had touched the contentious edge. The results suggested that the coadministration of EGCG and caffeine exerted more remarkable function on suppressing body weight gain, reducing white adipose tissue weight and decreasing the energy intake than single use. This may be due to the variation in serum lipid profile, oxidative stress, and adipose‐derived and inflammatory cytokines. The pathological micrographs showed long‐term high‐fat diets caused severe NAFLD, but it was ameliorated at different levels by all of the administrations. In summary, low dose of EGCG or caffeine only showed a mild effect of anti‐obesity and NAFLD amelioration. The coadministration of them could exert a superior curative effect as well as high dose EGCG but no anxiety regarding safety.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Eltrombopag was approved as a first‐line treatment for patients older than 2 years old with severe aplastic anemia (SAA). However, data on eltrombopag in children with different types of aplastic ...anemia (AA), especially non‐severe AA (NSAA), are limited. We performed a prospective, single‐arm, and observational study to investigate eltrombopag's efficacy, safety, and pharmacokinetics in children with NSAA, SAA, and very severe AA (VSAA). The efficacy and safety were assessed every 3 months. The population pharmacokinetic (PPK) model was used to depict the pharmacokinetic profile of eltrombopag. Twenty‐three AA children with an average age of 7.9 (range of 3.0‐14.0) years were enrolled. The response (complete and partial response) rate was 12.5%, 50.0%, and 100.0% after 3, 6, and 12 months in patients with NSAA. For patients with SAA and VSAA, these response rates were 46.7%, 61.5%, and 87.5%. Hepatotoxicity occurred in one patient. Fifty‐three blood samples were used to build the PPK model. Body weight was the only covariate for apparent clearance (CL/F) and volume of distribution. The allele‐T carrier of adenosine triphosphate‐binding cassette transporter G2 was found to increase eltrombopag's clearance. However, when normalized by weight, the clearance between the wild‐type and variant showed no statistical difference. In patients with response, children with NSAA exhibited lower area under the curve from time zero to infinity, higher CL/F, and higher weight‐adjusted CL/F than those with SAA or VSAA. However, the differences were not statistically significant. The results may support further individualized treatment of eltrombopag in children with AA.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Proteins UL31 and UL34 encoded by alphaherpesvirus are critical for viral primary envelopment and nuclear egress. We report here that pseudorabies virus (PRV), a useful model for research on ...herpesvirus pathogenesis, uses N‐myc downstream regulated 1 (NDRG1) to assist the nuclear import of UL31 and UL34. PRV promoted NDRG1 expression through DNA damage‐induced P53 activation, which was beneficial to viral proliferation. PRV induced the nuclear translocation of NDRG1, and its deficiency resulted in the cytosolic retention of UL31 and UL34. Therefore, NDRG1 assisted the nuclear import of UL31 and UL34. Furthermore, in the absence of the nuclear localization signal (NLS), UL31 could still translocate to the nucleus, and NDRG1 lacked an NLS, thus suggesting the existence of other mediators for the nuclear import of UL31 and UL34. We demonstrated that heat shock cognate protein 70 (HSC70) was the key factor in this process. UL31 and UL34 interacted with the N‐terminal domain of NDRG1 and the C‐terminal domain of NDRG1 bound to HSC70. Replenishment of HSC70ΔNLS in HSC70‐knockdown cells, or interference in importin α expression, abolished the nuclear translocation of UL31, UL34, and NDRG1. These results indicated that NDRG1 employs HSC70 to facilitate viral proliferation in the nuclear import of PRV UL31 and UL34.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
As a new important gas signaling molecule like nitric oxide (NO) and carbon dioxide (CO), hydrogen sulfide (H
S), which can be produced by endogenous H
S-producing enzymes through l-cysteine ...metabolism in mammalian cells, has attracted wide attention for long. H
S has been proved to play an important regulatory role in numerous physiological and pathophysiological processes. However, the deep mechanisms of those different functions of H
S still remain uncertain. A better understanding of the mechanisms can help us develop novel therapeutic strategies.
H
S can play a regulating role through various mechanisms, such as regulating epigenetic modification, protein expression levels, protein activity, protein localization, redox microenvironment, and interaction with other gas signaling molecules such as NO and CO. In addition to discussing the molecular mechanisms of H
S from the above perspectives, this article will review the regulation of H
S on common signaling pathways in the cells, including the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), mitogen-activated protein kinase (MAPK), Janus kinase (JAK)/signal transducer, and activator of transcription (STAT) signaling pathway.
Although there are many studies on the mechanism of H
S, little is known about its direct target molecules. This article will also review the existing reports about them. Furthermore, the interaction between direct target molecules of H
S and the downstream signaling pathways involved also needs to be clarified.
An in-depth discussion of the mechanism of H
S and the direct target molecules will help us achieving a deeper understanding of the physiological and pathophysiological processes regulated by H
S, and lay a foundation for developing new clinical therapeutic drugs in the future.
This review focuses on the regulation of H
S on signaling pathways and the direct target molecules of H
S. We also provide details on the underlying mechanisms of H
S functions from the following aspects: epigenetic modification, regulation of protein expression levels, protein activity, protein localization, redox microenvironment, and interaction with other gas signaling molecules such as NO and CO. Further study of the mechanisms underlying H
S will help us better understand the physiological and pathophysiological processes it regulates, and help develop new clinical therapeutic drugs in the future.
40, 86-109.
Facial nerve schwannomas are rare, benign, slow-growing tumors that can occur in any segment of the facial nerve, although 71% of cases are intratemporal. Surgical resection can lead to facial nerve ...injury. Facial function recovery after reanimation is usually not better than House-Brackmann (HB) grade III. Thus, for cases of intratemporal facial nerve schwannomas (IFNSs) with favorable facial function (HB grade I or II), observation by periodic magnetic resonance imaging is the mainstay of management. Here, we present a case of a large IFNS with normal facial function in which the mass fully occluded the external auditory canal. The occlusion caused squamous debris to accumulate, potentially leading to cholesteatoma. Faced with this therapeutic dilemma, we chose surgical resection with the patient’s informed consent. Stripping surgery was achieved with normal postoperative facial function. There was no postoperative facial paralysis or recurrence at 2-year follow-up. We describe the experience of diagnosis and treatment process for this case, and discuss the possibility of total resection of the tumor with preserving the integrity of facial nerve.