The poor electronic conductivity of metal–organic framework (MOF) materials hinders their direct application in the field of electrocatalysis in fuel cells and metal–air batteries. Herein, we present an effective and scalable surface engineering strategy to produce a non-pyrolysis metal–organic framework (MOFs)-based catalyst with high-density Co–Nx active sites and a three-dimensional (3D) conductive network for oxygen reduction reaction (ORR) catalysis. The surface engineering strategy employs a π-conjugated amino-rich hexaaminotriphenylene (HITP) ligand to modify the surface of the zeolite imidazolate skeleton material (ZIF-67) through the coordination of Co in ZIF-67 with N in HITP to construct robust Co coordination sites. The results show that the HITP ligand not only modifies the surface of a single ZIF polyhedron but also connects two or multiple ZIF polyhedrons, constructing a 3D electronic conductive network that is beneficial to facilitate electron transfer during ORR catalysis and thus increase the accessible contact between electrons and Co–Nx sites. The electronic conductivity of the hybrid catalyst was increased by six orders of magnitude than that of pure ZIF-67. The optimized catalyst shows an outstanding electrocatalytic activity for ORR with a half-wave potential of 0.82 V─even comparable to commercial Pt/C─and excellent electrochemical durability. Density functional theory (DFT) calculations indicate that the HITP ligand can not only coordinate with unsaturated Co sites on ZIF-67 using its abundant N atoms but also exchange thermodynamically with the 2-methylimidazole ligand in ZIF-67. The modification of HITP also reduces the free energy barrier of the rate-determining step toward ORR catalysis, leading to an improved ORR activity for the HITP-modified ZIF-67 catalyst. This scalable surface engineering strategy represents a breakthrough in development of nonpyrolysis conductive MOF materials for ORR catalysis.
Retinoblastoma is a childhood cancer of the developing retina that initiates with biallelic inactivation of the RB1 gene. Children with germline mutations in RB1 have a high likelihood of developing retinoblastoma and other malignancies later in life. Genetically engineered mouse models of retinoblastoma share some similarities with human retinoblastoma but there are differences in their cellular differentiation. To develop a laboratory model of human retinoblastoma formation, we make induced pluripotent stem cells (iPSCs) from 15 participants with germline RB1 mutations. Each of the stem cell lines is validated, characterized and then differentiated into retina using a 3-dimensional organoid culture system. After 45 days in culture, the retinal organoids are dissociated and injected into the vitreous of eyes of immunocompromised mice to support retinoblastoma tumor growth. Retinoblastomas formed from retinal organoids made from patient-derived iPSCs have molecular, cellular and genomic features indistinguishable from human retinoblastomas. This model of human cancer based on patient-derived iPSCs with germline cancer predisposing mutations provides valuable insights into the cellular origins of this debilitating childhood disease as well as the mechanism of tumorigenesis following RB1 gene inactivation.
AIM:To evaluate the efficacy of centralized culture and possible influencing factors. METHODS:From January 2010 to July 2012, 66452 patients with suspected Helicobacter pylori (H.pylori ) infection from 26 hospitals in Zhejiang and Jiangsu Provinces in China underwent gastrointestinal endoscopy.Gastric mucosal biopsies were taken from the antrum for culture.These biopsies were transported under natural environmental temperature to the central laboratory in Hangzhou city and divided into three groups based on their transport time: 5, 24 and 48 h.The culture results were reported after 72 h and the positive culture rates were analyzed by a χ 2 test.An additional 5736 biopsies from H. pylori -positive patients (5646 rapid urease test-positive and 9014 C-urease breath test-positive) were also cultured for quality control in the central laboratory setting. RESULTS:The positive culture rate was 31.66%(21036/66452) for the patient samples and 71.72% (4114/5736) for the H. pylori -positive quality control specimens.In the 5 h transport group, the positive culture rate was 30.99% (3865/12471), and 32.84% (14960/45553) in the 24 h transport group.In contrast, the positive culture rate declined significantly in the 48 h transport group (26.25%;P < 0.001).During transportation, the average natural temperature increased from 4.67 to 29.14 ℃, while the positive culture rate declined from 36.67% (1462/3987) to 24.12% (1799/7459).When the temperature exceeded 24 ℃, the positive culture rate decreased significantly, especially in the 48 h transport group (23.17%). CONCLUSION:Transportation of specimens within 24 h and below 24 ℃ is reasonable and acceptable for centralized culture of multicenter H. pylori samples.
A wave glider is a novel unmanned marine vehicle which can convert marine energy into kinetic energy. In practice, it is crucial for the wave glider system to deploy into the ocean environment efficiently and safely. Hence, the present work establishes the wave glider motion equations to analyze the deployment method. Firstly, the wave glider model is simplified in the vertical plane and the cable model is defined as mass nodes connected with a massless spring. Then, two typical deployment methods (Method 1 and Method 2) are proposed based on the multibody dynamic method, and the numerical simulation model is established to investigate the kinematic performance of two deployment methods. Lastly, the dynamic characteristic analysis is conducted to select the determined deployment method. We explain the practical advantages of Method 1, which would provide the reference for the deployment method selection.
Neuronal differentiation with respect to the acquisition of synaptic competence needs to be regulated precisely during neurogenesis to ensure proper formation of circuits at the right place and time in development. This regulation is particularly important for synaptic triads among photoreceptors, horizontal cells (HCs), and bipolar cells in the retina, because HCs are among the first cell types produced during development, and bipolar cells are among the last. HCs undergo a dramatic transition from vertically oriented neurites that form columnar arbors to overlapping laminar dendritic arbors with differentiation. However, how this process is regulated and coordinated with differentiation of photoreceptors and bipolar cells remains unknown. Previous studies have suggested that the retinoblastoma ( Rb ) tumor suppressor gene may play a role in horizontal cell differentiation and synaptogenesis. By combining genetic mosaic analysis of individual synaptic triads with neuroanatomic analyses and multiphoton live imaging of developing HCs, we found that Rb plays a cell-autonomous role in the reorganization of horizontal cell neurites as they differentiate. Aberrant vertical processes in Rb -deficient HCs form ectopic synapses with rods in the outer nuclear layer but lack bipolar dendrites. Although previous reports indicate that photoreceptor abnormalities can trigger formation of ectopic synapses, our studies now demonstrate that defects in a postsynaptic partner contribute to the formation of ectopic photoreceptor synapses in the mammalian retina.
The high durability of proton exchange membrane fuel cells (PEMFCs) is crucial for their large-scale application in hydrogen mobility, while a trace amount of chloride in air significantly affects the durability of PEMFCs. Herein, we demonstrate a type of chloride-tolerant PtCo/C catalyst with a Pt3Co-core@Pt-skin structure showing that the chloride adsorption rate decreased by 34% compared with Pt/C. The introduction of Co weakens chloride adsorption on Pt with a decrease of ≥13% in the adsorption energy due to the downshifted Pt d-band center. The durability of PtCo/C outperforms that of Pt/C, exhibiting a stronger resistance toward the coupling effect of dynamic high-potential/chloride poisoning by mitigating Pt dissolution and hindering the Ostwald ripening of Pt nanoparticles. The presence of chloride aggravates the decay of Pt-based catalysts under the simulated potential cycling operation, and the aggravated effect is less severe for PtCo/C with an ∼40% decrease in the decay percentage in comparison to Pt/C after a 10,000-cycle test. This work provides a valuable guide for the design of robust antipoisoning catalysts by adjusting the Pt d-band center for long-life PEMFC application.
Background Preclinical models of pediatric cancers are essential for testing new chemotherapeutic combinations for clinical trials. The most widely used genetic model for preclinical testing of neuroblastoma is the TH-MYCN mouse. This neuroblastoma-prone mouse recapitulates many of the features of human neuroblastoma. Limitations of this model include the low frequency of bone marrow metastasis, the lack of information on whether the gene expression patterns in this system parallels human neuroblastomas, the relatively slow rate of tumor formation and variability in tumor penetrance on different genetic backgrounds. As an alternative, preclinical studies are frequently performed using human cell lines xenografted into immunocompromised mice, either as flank implant or orthtotopically. Drawbacks of this system include the use of cell lines that have been in culture for years, the inappropriate microenvironment of the flank or difficult, time consuming surgery for orthotopic transplants and the absence of an intact immune system. Principal Findings Here we characterize and optimize both systems to increase their utility for preclinical studies. We show that TH-MYCN mice develop tumors in the paraspinal ganglia, but not in the adrenal, with cellular and gene expression patterns similar to human NB. In addition, we present a new ultrasound guided, minimally invasive orthotopic xenograft method. This injection technique is rapid, provides accurate targeting of the injected cells and leads to efficient engraftment. We also demonstrate that tumors can be detected, monitored and quantified prior to visualization using ultrasound, MRI and bioluminescence. Finally we develop and test a "standard of care" chemotherapy regimen. This protocol, which is based on current treatments for neuroblastoma, provides a baseline for comparison of new therapeutic agents. Significance The studies suggest that use of both the TH-NMYC model of neuroblastoma and the orthotopic xenograft model provide the optimal combination for testing new chemotherapies for this devastating childhood cancer.
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