The human brain is thought to be an extremely complex but efficient computing engine, processing vast amounts of information from a changing world. The decline in the synaptic density of neuronal ...networks is one of the most important characteristics of brain development, which is closely related to synaptic pruning, synaptic growth, synaptic plasticity, and energy metabolism. However, because of technical limitations in observing large-scale neuronal networks dynamically connected through synapses, how neuronal networks are organized and evolve as their synaptic density declines remains unclear. Here, by establishing a biologically reasonable neuronal network model, we show that despite a decline in the synaptic density, the connectivity, and efficiency of neuronal networks can be improved. Importantly, by analyzing the degree distribution, we also find that both the scale-free characteristic of neuronal networks and the emergence of hub neurons rely on the spatial distance between neurons. These findings may promote our understanding of neuronal networks in the brain and have guiding significance for the design of neuronal network models.
Two novel porous aromatic frameworks (PAF-53 and PAF-54) have been obtained by the polymerization of amino compounds (p-phenylenediamine and melamine) and cyanuric chloride. They display high ...selective separation of CO2/CH4 and CO2/N2 and make a promise as ideal candidates to capture CO2.
Novel porous aromatic frameworks (PAF-53 and PAF-54) have been obtained by the polymerization of amino compound (p-phenylenediamine and melamine) and cyanuric chloride. They display a certain amount of CO2 adsorption capacity and highly selective separation of CO2/CH4 and CO2/N2 as 18.1 and 83 by Henry Law respectively. They may be applied as ideal adsorbents to separate and capture CO2.
The epoxidation of ricinoleic acid methyl ester (RAME) has been investigated using an environmentally friendly oxidant (i.e., hydrogen peroxide) and a phase‐transfer catalyst ...(π‐C5H5N(CH2)15CH33PW4O16) in dichloroethane. The response surface methodology (RSM), based on the Box–Behnken design was used to assess individual and interactive effects of the process variables and to optimize the epoxidation reaction condition. The coefficient of determination (R2 = 0.9544) obtained from analysis of the variance confirmed the suitability of the fitted model. The RSM analysis results indicated that the molar ratio of H2O2 to CC bonds and the reaction temperature are the most significant (P < 0.01) factors affecting the conversion of RAME epoxide. In addition, the interaction between the H2O2/CC molar ratio and the catalyst dosage also has significant effect (P < 0.05) on the conversion of RAME epoxide. The optimum reaction conditions for the epoxidation of RAME were H2O2: CC molar ratio of 1.93:1, catalyst dosage of 3.11 wt% (substrate:catalyst molar ratio = 207), reaction temperature of 52°C, and reaction time of 75 min, under which a conversion of 94.52% could be achieved. The epoxidation of RAME by hydrogen peroxide and the (π‐C5H5NCH215CH3)3(PW4O16) phase‐transfer catalyst followed pseudo‐first order kinetics with an activation energy (Ea) of approximately 21.6 kJ/mol. The reaction process is a mass‐transfer control process.
Practical applications: RSM was found to be a useful technique for optimizing epoxidation of RAME. The high conversion of the epoxidation of RAME indicates that (π‐C5H5NCH215CH3)3(PW4O16) is a very efficient phase‐transfer catalyst for the epoxidation of RAME under the mild conditions mentioned above. The epoxidized RAME have the potential to be used as biolubricants, surfactants, biobased polymers, and surface‐active compounds for high‐value cosmetic.
The epoxidized ricinoleic acid methyl ester (RAME) have great potential to be used as biolubricants, biobased polymers, and surface‐active compounds in a variety of industries. RAME is epoxidized using an environmentally friendly oxidant (hydrogen peroxide) and a phase‐transfer catalyst (p‐C5H5N(CH2)15CH33PW4O16) in dichloroethane. The high conversion (94.52%) is achieved by using response surface methodology to optimize the epoxidation reaction variables.
The epoxidized ricinoleic acid methyl ester (RAME) have great potential to be used as biolubricants, biobased polymers, and surface‐active compounds in a variety of industries. RAME is epoxidized using an environmentally friendly oxidant (hydrogen peroxide) and a phase‐transfer catalyst (p‐C5H5N(CH2)15CH33PW4O16) in dichloroethane. The high conversion (94.52%) is achieved by using response surface methodology to optimize the epoxidation reaction variables.
Conotruncal defects (CTDs) account for ~30% of all types of congenital heart disease and contribute to increased morbidity and mortality rates. Increasing evidence suggests that genetic risk factors ...are involved in the pathogenesis of CTDs. Mutations in a number of genes, including the
gene that codes for a T-box transcription factor essential for normal cardiovascular development, may contribute to the development of CTD. CTDs are genetically heterogeneous and the genetic defects responsible for CTDs in the majority of patients remain unknown. The present study sequenced the coding regions and splicing junction boundaries of
in 136 patients with CTDs and 300 matched healthy individuals. The disease-causing potential of the identified
sequence variation was evaluated using MutationTaster, PolyPhen-2, SIFT and PROVEN software. The functional characteristics of the mutant TBX1 gene were defined using a dual-luciferase reporter assay system. A novel heterozygous TBX1 mutation, p.S233Y, was identified in a patient with transposition of the great arteries (TGA) and a ventricular septal defect. This mutation was absent in the 300 controls and altered the amino acid produced, serine, which is evolutionarily conserved across several species, and was predicted to be pathogenic
. Luciferase assays conducted in COS-7 cells demonstrated that the newly identified TBX1 mutation was associated with significantly diminished transcriptional activation of the
promoter compared with the wild-type TBX1. To the best of our knowledge, the present study is the first to associate a TBX1 loss-of-function mutation with enhanced susceptibility to TGA, which adds significant insight to the molecular mechanism of TGA.
Abstract Background Notch and NF-κB signaling pathways both play important roles in the regulation of atherosclerosis (AS). However, the mechanisms of notch and NF-κB signaling pathways on AS are ...still unclear. In this study, we aimed to investigate the effects of notch1,2,3 genes silicing by siRNA on notch and NF-κB signaling pathways of macrophages in patients with atherosclerosis (AS), so as to seek the treatment of AS from genetic perspective. Methods Peripheral blood mononuclears of 31 patients with AS were isolated by density gradient centrifugation and transformed by PMA to macrophages. Then macrophages were transfected with notch1-siRNA (notch1-siRNA group), notch2-siRNA (notch2-siRNA group), notch3-siRNA (notch3-siRNA group), negative control siRNA (NC group) and none (control group). RT-PCR and Western blot analysis were applied to assess the expression level of Delta-like-4 (DLL4), Jagged-1 (JAG1), IκBα and P52. Electrophoretic mobility shift assay (EMSA) was used to observe the NF-κB DNA binding activity. Subcellular distributions of NF-κB/P52 were detected through immunofluorescence. mRNA expression levels of TNF-α, IL-6 and IL-6 in macrophages were also determined with RT- PCR. The expression of 20S proteasome was detected by Western blot. Results After transfected with siRNA, there was no difference in the expression of DLL4, JAG1, IκBα and P52 between NC group and control group (p > 0.05). Compared with NC group and control group, the expression of DLL4, P52 and JAG1 in notch1-siRNA group, notch2-siRNA group and notch3-siRNA group was significantly downregulated (p < 0.05 or p < 0.01, respectively), whereas the expression of IκBα was significantly increased (P < 0.05 or p < 0.01, respectively), especially in notch1-siRNA group. The binding activity of NF-κB DNA was lower in notch1- siRNA group, notch2-siRNA group and notch3-siRNA group compared with NC group and control group (p < 0.05), especially in notch1-siRNA group. The fluorescence intensity of p52 was decreased significantly both in the nucleus and cytoplasm in notch1-siRNA group, notch2-siRNA group and notch3-siRNA group compared with NC group and control group (p < 0.05), which decreased more obviously in the nucleus, especially in notch1-siRNA group. The TNF-α, IL-1 and IL-6 expression of notch1-siRNA group, notch2-siRNA group and notch3-siRNA group was lower compared to NC group and control group (p < 0.05 or p < 0.01, respectively), also especially in notch1-siRNA group. 20S proteasome level was significantly lower in notch1-siRNA group, notch2-siRNA group and notch3-siRNA group than in NC group and control group (p < 0.05 or p < 0.01, respectively), especially in notch1-siRNA group. Conclusions There was a positive regulation between Notch and NF-κB signaling pathway in patients with AS. Notch1 may play a more important role than notch2 and notch 3 in the regulation of NF-κB signaling pathway in AS.
Neuronal networks in the brain are the structural basis of human cognitive function, and the plasticity of neuronal networks is thought to be the principal neural mechanism underlying learning and ...memory. Dominated by the Hebbian theory, researchers have devoted extensive effort to studying the changes in synaptic connections between neurons. However, understanding the network topology of all synaptic connections has been neglected over the past decades. Furthermore, increasing studies indicate that synaptic activities are tightly coupled with metabolic energy, and metabolic energy is a unifying principle governing neuronal activities. Therefore, the network topology of all synaptic connections may also be governed by metabolic energy. Here, by implementing a computational model, we investigate the general synaptic organization rules for neurons and neuronal networks from the perspective of energy metabolism. We find that to maintain the energy balance of individual neurons in the proposed model, the number of synaptic connections is inversely proportional to the average of the synaptic weights. This strategy may be adopted by neurons to ensure that the ability of neurons to transmit signals matches their own energy metabolism. In addition, we find that the density of neuronal networks is also an important factor in the energy balance of neuronal networks. An abnormal increase or decrease in the network density could lead to failure of energy metabolism in the neuronal network. These rules may change our view of neuronal networks in the brain and have guiding significance for the design of neuronal network models.
Abstract Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we ...observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.
Ultrasonic spot welded Cu/Cu joints with and without Cu nanoparticles (Cu NPs) interlayer were successfully achieved. Cu NPs interlayer, possessing the characteristics of high hardness and low melt ...point, could promote to eliminate the un-contacted areas in the weld interface and generate
more effectively net welded areas, leading to the increase of bond density. The peak T-peel force (279.6 N) of the Cu/Cu joint with Cu NPs interlayer was 18.3% higher than that (236.3 N) of the Cu/Cu joint without Cu NPs interlayer. In addition, for the Cu/Cu joint with Cu NPs interlayer,
only welded regions with obvious facture dimples could be observed in the fracture morphology.
The development of gene carriers with high delivery efficiency and enough biosafety to replace the current viral vectors and cationic liposomes has long been a key project to achieve the practical ...application of gene therapy. As an abundant natural polymer, chitosan (CS) possesses incomparably high biocompatibility. However, when it is used as a gene carrier, the gene transfection efficiency is rather disappointing. Herein, we prepared a novel chitosan derivative, poly(tributyl-(4-vinylbenzyl)phosphonium)-grafted CS (CS-P),
via
γ-ray radiation-induced grafting copolymerization of tributyl-(4-vinylbenzyl)phosphonium in an acidic solution of CS. The CS-P could combine with
p
EGFP through a complex coacervation method to form
p
EGFP-loaded CS-P complex particles with a size of about 150 nm and a high positive zeta potential of 41.7 ± 6.1 mV. Agarose gel electrophoresis and an MTT assay show that the
p
EGFP-loaded CS-P particles have excellent biosafety, superior to
p
EGFP-loaded unmodified CS particles.
In vitro
and
in vivo
gene transfection experiments based on HeLa cells confirmed that
p
EGFP loaded into CS-P particles exhibits much higher gene transfection efficiency than that loaded into unmodified CS. This work provides not only a new way to modify CS with quaternary phosphonium, but also a useful and feasible way to obtain new CS-based gene vectors with high gene transfection efficiency and biosafety for potentially practical clinic applications.
The influence of the certain specific vacuum pre-oxidation process on the phase transformation of thermally-grown oxides (TGO) was studied. The CoCrAlY high temperature corrosion resistance coatings ...were produced onto the nickel-based superalloy substrate by high velocity oxygen fuel (HVOF). It suggests that the TGO usually consists of a great number of chromium oxides, cobalt oxides and spinel oxides besides alumina during the initial period of the high temperature oxidation if the specimens are not subjected to the appropriate vacuum pre-oxidation process. Furthermore, the amount of alumina is strongly dependent on the partial pressure of oxygen; while the CoCr2O4 spinel oxides are usually formed under the conditions of higher partial pressure of oxygen during the initial period and the lower partial pressure of oxygen during the subsequent period of the isothermal oxidation. After the appropriate vacuum pre-oxidation process, the TGO is mainly composed of alumina that contains lower Y element, while alumina that contains higher Y element sporadically distributes, and the spinel oxides cannot be found. After a longer period of the isothermal oxidation, a small amount of porous CoCr2O4 and the chrome oxide sporadically distribute near the continuous alumina. Additionally, after the appropriate vacuum pre-oxidation process, the TGO growth rate is relatively slow.
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