Low temperature fuel cells are clean, effective alternative fuel conversion technology. Oxygen reduction reaction (ORR) at the fuel cell cathode has required Pt as the electrocatalyst for high ...activity and selectivity of the four-electron reaction pathway. Targeting a less expensive, earth abundant alternative, we have developed the synthesis of cobalt phosphide (Co2P) nanorods for ORR. Characterization techniques that include total X-ray scattering and extended X-ray absorption fine structure revealed a deviation of the nanorods from bulk crystal structure with a contraction along the b orthorhombic lattice parameter. The carbon supported nanorods have comparable activity but are remarkably more stable than conventional Pt catalysts for the oxygen reduction reaction in alkaline environments.
The prevailing view that the evolution of cells in a tumor is driven by Darwinian selection has never been rigorously tested. Because selection greatly affects the level of intratumor genetic ...diversity, it is important to assess whether intratumor evolution follows the Darwinian or the non-Darwinian mode of evolution. To provide the statistical power, many regions in a single tumor need to be sampled and analyzed much more extensively than has been attempted in previous intratumor studies. Here, from a hepatocellular carcinoma (HCC) tumor, we evaluated multiregional samples from the tumor, using either whole-exome sequencing (WES) (n= 23 samples) or genotyping (n= 286) under both the infinite-site and infinite-allele models of population genetics. In addition to the many single-nucleotide variations (SNVs) present in all samples, there were 35 “polymorphic” SNVs among samples. High genetic diversity was evident as the 23 WES samples defined 20 unique cell clones. With all 286 samples genotyped, clonal diversity agreed well with the non-Darwinian model with no evidence of positive Darwinian selection. Under the non-Darwinian model,M
ALL(the number of coding region mutations in the entire tumor) was estimated to be greater than 100 million in this tumor. DNA sequences reveal local diversities in small patches of cells and validate the estimation. In contrast, the genetic diversity under a Darwinian model would generally be orders of magnitude smaller. Because the level of genetic diversity will have implications on therapeutic resistance, non-Darwinian evolution should be heeded in cancer treatments even for microscopic tumors.
Studies on mechanisms underlying the differentiation of dental pulp stem cells are critical for the understanding of the biology of odontogenesis and for dental tissue engineering. Here, we tested ...the hypothesis that stem cells from exfoliated deciduous teeth (SHED) differentiate into functional odontoblasts and endothelial cells. SHED were seeded in tooth slice/scaffolds and implanted subcutaneously into immunodeficient mice. SHED differentiated into functional odontoblasts that generated tubular dentin, as determined by tetracycline staining and confocal microscopy. These cells also differentiated into vascular endothelial cells, as determined by beta-galactosidase staining of LacZ-tagged SHED. In vitro, vascular endothelial growth factor (VEGF) induced SHED to express VEGFR2, CD31, and VE-Cadherin (markers of endothelium) and to organize into capillary-like sprouts. VEGF induced ERK and AKT phosphorylation (indicative of differentiation), while inhibiting phosphorylation of STAT3 (indicative of ‘stemness’). Collectively, this work demonstrates that SHED can differentiate into angiogenic endothelial cells and odontoblasts capable of generating tubular dentin.
We report a size-controllable synthesis of monodisperse core/shell Ni/FePt nanoparticles (NPs) via a seed-mediated growth and their subsequent conversion to Ni/Pt NPs. Preventing surface oxidation of ...the Ni seeds is essential for the growth of uniform FePt shells. These Ni/FePt NPs have a thin (≈1 nm) FePt shell and can be converted to Ni/Pt by acetic acid wash to yield active catalysts for oxygen reduction reaction (ORR). Tuning the core size allows the optimization of their electrocatalytic activity. The specific activity and mass activity of 4.2/0.8 nm core/shell Ni/FePt after acetic acid wash reach 1.95 mA/cm2 and 490 mA/mgPt at 0.9 V (vs reversible hydrogen electrode), which are much higher than those of benchmark commercial Pt catalyst (0.34 mA/cm2 and 92 mA/mgPt at 0.9 V). Our studies provide a robust approach to monodisperse core/shell NPs with nonprecious metal core, making it possible to develop advanced NP catalysts with ultralow Pt content for ORR and many other heterogeneous reactions.
In recent years, foot-and-mouth disease virus (FMDV) serotype O, topotype Middle East-South Asia (ME-SA), lineage Ind-2001d has spread from the Indian subcontinent to the Middle East, North Africa, ...and Southeast Asia. In the current report, we describe the first detection of this lineage in Vietnam in May, 2015 in Đắk Nông province. Three subsequent outbreaks caused by genetically related viruses occurred between May-October, 2015 after which the virus was not detected in clinical outbreaks for at least 15 subsequent months. The observed outbreaks affected (in chronological order): cattle in Đắk Nông province, pigs in Đắk Lắk province and Đắk Nông province, and cattle in Ninh Thuận province. The clinical syndromes associated with these outbreaks were consistent with typical FMD in the affected species. Overall attack rate on affected premises was 0.85 in pigs and 0.93 in cattle over the course of the outbreak. Amongst 378 pigs at risk on affected premises, 85 pigs died during the outbreaks; there were no deaths among cattle. The manner in which FMDV/O/ME-SA/Ind-2001d was introduced into Vietnam remains undetermined; however, movement of live cattle is the suspected route. This incursion has substantial implications for epidemiology and control of FMD in Southeast Asia.
In this work, an acoustic standing wave field (ASWF) is used to simulate the space environment, which shows characteristics such as microgravity and the absence of containment and contact. Zebrafish ...embryos, used as the species under study in this work, were raised within the acoustic field by the authors, allowing the biological effects on such early zebrafish embryos, at each developmental stage and within the ASWF creating the acoustic levitation (AL) technology used, to be studied. In this way, the biological safety of thee specimens, simulating the space environment, could be carefully evaluated. Some important indexes of the process of zebrafish development, such as mortality, malformation rate, hatching rate, voluntary movement and heart rate were detected and analyzed. It has been found that the ASWF exerted considerable influence on the zebrafish embryos at the early development stage, influencing features such as the cleavage, blastula and gastrul stage, over the period 0-8 hour post fertilization (hpf). The zebrafish appear to show some features of teratogenesis, as well as lethal effects and a significant decrease of the hatching rate, after being treated by using the AL that was applied. Furthermore, it was observed that voluntary movements and the embryo heart rates apparently increased under these conditions. However, as the development of the embryo progressed into the bursa pharyngea stage (at 24-32 hpf), the influence of the ASWF creating the AL on zebrafish seemed almost to be insignificant, as there was no obvious difference between the characteristics of the experimental group and the control group. The experiment carried out has provided a scientific reference for the application of AL in this field, allowing the biological safety aspects of such zebrafish embryo development within a space environment to be evaluated.
Influence of acoustic standing wave field creating acoustic levitation, on each development stage of early zebrafish embryos has been studied.
Dengue shock syndrome is characterized by severe vascular leakage and disordered hemostasis and progresses to death in 1 to 5 percent of cases. Although volume replacement is recognized as the ...critical therapeutic intervention, World Health Organization management guidelines remain empirical rather than evidence-based.
We performed a double-blind, randomized comparison of three fluids for initial resuscitation of Vietnamese children with dengue shock syndrome. We randomly assigned 383 children with moderately severe shock to receive Ringer's lactate, 6 percent dextran 70 (a colloid), or 6 percent hydroxyethyl starch (a colloid) and 129 children with severe shock to receive one of the colloids. The primary outcome measure was requirement for rescue colloid at any time after administration of the study fluid.
Only one patient died (<0.2 percent mortality). The primary outcome measure--requirement for rescue colloid--was similar for the different fluids in the two severity groups. The relative risk of requirement for rescue colloid was 1.08 (95 percent confidence interval, 0.78 to 1.47; P=0.65) among children with moderate shock who received Ringer's lactate as compared with either of the colloid solutions, 1.13 (95 percent confidence interval, 0.74 to 1.74; P=0.59) among children who received dextran as compared with starch in the group with severe shock, and 0.88 (95 percent confidence interval, 0.66 to 1.17; P=0.38) among children who received dextran as compared with starch in the combined analysis. Although treatment with Ringer's lactate resulted in less rapid improvement in the hematocrit and a marginally longer time to initial recovery than did treatment with either of the colloid solutions, there were no differences in all other measures of treatment response. Only minor differences in efficacy were detected between the two colloids, but significantly more recipients of dextran than of starch had adverse reactions. Bleeding manifestations, coagulation derangements, and severity of fluid overload were similar for all fluid-treatment groups.
Initial resuscitation with Ringer's lactate is indicated for children with moderately severe dengue shock syndrome. Dextran 70 and 6 percent hydroxyethyl starch perform similarly in children with severe shock, but given the adverse reactions associated with the use of dextran, starch may be preferable for this group.
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•Detailed kinetic mechanism of the OH-initiated oxidation of cyclopentadiene is computationally reported for T = 298 – 2000 K &P = 0.76 – 7600 Torr.•Kinetic discrepancies among ...literature data are resolved.•Reaction mechanism shift is observed with the dominance of OH-addition and H-abstraction channels at low and high temperatures, respectively.•U-shaped T-dependence and weakly positive P-dependence at low temperatures of the rate constants are observed.
This work computationally reports a detailed kinetic mechanism of the OH-initiated reaction of 1,3-cyclopentadiene (CPDN), a key intermediate during the oxidation processes of aromatic and acyclic compounds, in the wide range of T = 298 – 2000 K and P = 0.76 – 7600 Torr. The temperature- and pressure-dependent behaviors of the title reaction were simulated using the RRKM-based Master Equation rate model on the potential energy profile explored at M06-2X/aug-cc-pVTZ level. The model reveals that the OH-addition on Cα of CPDN to form adduct 5-hydroxycyclopent-2-en-1-yl dominates at low temperatures (e.g., T ≤ 1000 K at 760 Torr), while the direct H-abstraction channels from Cα and Cβ of CPDN become predominant at high temperatures (e.g., T > 1000 K at 760 Torr). The observed U-shaped temperature-dependent behaviors and slightly positive pressure dependence at low temperatures (e.g., T ≤ 1000 K &P = 760 Torr) of the total rate constants are described by a double modified Arrhenius expression as ktot(T) = 1.61 × 109 × T−6.67 × exp-1627.6 K/T + 3.87 × 10-17 × T2.08 × exp-2519.9 K/T (cm3/molecule/s) for T = 298 – 2000 K &P = 760 Torr. Discrepancies in ktotal(T, P) between the early calculations and measurements in low- and high-temperature regimes are also resolved. Also, the thermodynamically consistent mechanism is provided to advance modeling and simulation of any CPDN-related applications.
Helicobacter pylori (H. pylori) is a common human pathogenic bacterium. Once infected, it is difficult for the host to clear this organism using the innate immune system. Increased antibiotic ...resistance further makes it challenging for effective eradication. However, the mechanisms of immune evasion still remain obscure, and novel strategies should be developed to efficiently eliminate H. pylori infection in stomachs. Here we uncovered desirable anti-H. pylori effect of vitamin D3 both in vitro and in vivo, even against antibiotic-resistant strains. We showed that H. pylori can invade into the gastric epithelium where they became sequestered and survived in autophagosomes with impaired lysosomal acidification. Vitamin D3 treatment caused a restored lysosomal degradation function by activating the PDIA3 receptor, thereby promoting the nuclear translocation of PDIA3-STAT3 protein complex and the subsequent upregulation of MCOLN3 channels, resulting in an enhanced Ca
2+
release from lysosomes and normalized lysosomal acidification. The recovered lysosomal degradation function drives H. pylori to be eliminated through the autolysosomal pathway. These findings provide a novel pathogenic mechanism on how H. pylori can survive in the gastric epithelium, and a unique pathway for vitamin D3 to reactivate the autolysosomal degradation function, which is critical for the antibacterial action of vitamin D3 both in cells and in animals, and perhaps further in humans.
Abbreviations: 1,25D3: 1α, 25-dihydroxyvitamin D3; ATG5: autophagy related 5; Baf A1: bafilomycin A
1
; BECN1: beclin 1; CagA: cytotoxin-associated gene A; CFU: colony-forming unit; ChIP-PCR: chromatin immunoprecipitation-polymerase chain reaction; Con A: concanamycin A; CQ: chloroquine; CRISPR: clustered regularly interspaced short palindromic repeats; CTSD: cathepsin D; GPN: Gly-Phe-β-naphthylamide; H. pylori: Helicobacter pylori; LAMP1: lysosomal associated membrane protein 1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MCOLN1: mucolipin 1; MCOLN3: mucolipin 3; MCU: mitochondrial calcium uniporter; MOI: multiplicity of infection; NAGLU: N-acetyl-alpha-glucosaminidase; PDIA3: protein disulfide isomerase family A member 3; PMA: phorbol 12-myristate 13-acetate; PRKC: protein kinase C; SQSTM1: sequestosome 1; STAT3: signal transducer and activator of transcription 3; SS1: Sydney Strain 1; TRP: transient receptor potential; VacA: vacuolating cytotoxin; VD3: vitamin D3; VDR: vitamin D receptor
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