Although the synaptic alterations associated with the stress-related mood disorder major depression has been well-documented, the underlying transcriptional mechanisms remain poorly understood. Here, ...we perform complementary bulk nuclei- and single-nucleus transcriptome profiling and map locus-specific chromatin interactions in mouse neocortex to identify the cell type-specific transcriptional changes associated with stress-induced behavioral maladaptation. We find that cortical excitatory neurons, layer 2/3 neurons in particular, are vulnerable to chronic stress and acquire signatures of gene transcription and chromatin structure associated with reduced neuronal activity and expression of Yin Yang 1 (YY1). Selective ablation of YY1 in cortical excitatory neurons enhances stress sensitivity in both male and female mice and alters the expression of stress-associated genes following an abbreviated stress exposure. These findings demonstrate how chronic stress impacts transcription in cortical excitatory neurons and identify YY1 as a regulator of stress-induced maladaptive behavior in mice.
In this study, the room temperature thermal conductivity and microstructure of Mg−Ce, Mg−Sm and Mg−Y binary alloys in as-cast and solution treated conditions were investigated. Quantitative study was ...conducted on the effect of rare earth elements (in solid solution and intermetallic compounds) on the thermal conductivity of Mg−RE alloys. The reduction in thermal conductivity was determined to be about 123.0 W/(m·K) and 6.5–16.4 W/(m·K), respectively, per 1 at.% RE addition in the form of solid solution or intermetallic compounds with Mg. The thermal conductivities of Mg−RE alloys were fitted using modified Maxwell and EMT models based on the distribution, volume fractions and shape of intermetallic compounds. The modified structural models provide a good fit to the experimental thermal conductivity data.
•The reduction in thermal conductivity per at.% of RE in Mg matrix is 123.0 W/(m·K).•Such reduction is only 6.5–16.4 W/(m·K) when intermetallics form.•The modified Maxwell and EMT models fitted well to measured thermal conductivity.•Effective thermal conductivity is determined by RE level and intermetallic volume.
Inverse-electron-demand-hetero-Diels-Alder reactions of alkenes with α,β-unsaturated keto compounds allow rapid access to the tetrahydropyran ring found in numerous natural products and bioactive ...molecules. Despite its synthetic interest, catalytic asymmetric versions of this process remain underdeveloped, especially regarding the use of non-activated alkenes reacting with α,β-unsaturated ketone or aldehyde, for which no report can be found in the literature. Herein, we describe the catalytic inverse-electron-demand-hetero-Diels-Alder reactions between neutral alkenes and an α,β-unsaturated ketones or aldehydes to produce a variety of trans-fused 5,6,8 tricyclic structures containing a central, chiral tetrahydropyran ring. This complex transformation, which is achieved using a chiral phosphoric acid, allows for the formation of four stereogenic centers in a single step with high regio-, diastereo- and enantioselectivity (up to 99% ee). Such level of stereocontrol could be achieved by a key remote double hydrogen atom bonding interaction between the linear substrate and the catalyst.
Fast and effective thrombolysis using tissue plasminogen activator (tPA) is limited by the poor delivery efficiency of thrombolytic drugs, which is induced by an interrupted bloodstream and delayed ...recanalization. Existing magnetic micro/nanodrug‐loaded robots used for targeted thrombotic therapy are limited by the complexity of the clinical verification of nanodrugs and the limited space of magnetic actuation systems. Herein, a general drug delivery strategy based on mass transportation theory for thrombolysis is presented, and an open space C‐shaped magnetic actuation system with laser location and ultrasound imaging navigation for in vivo evaluation is developed. tPA can be guided through an interrupted bloodstream to the thrombi by the locomotion of magnetic nanoparticle swarms (MNSs), thereby improving the thrombolysis efficacy. Notably, this strategy is able to quickly establish a life channel to achieve time‐critical recanalization, which is typically inaccessible using native tPA. Both in vitro and in vivo thrombolysis experiments demonstrate that the thrombus lysis efficacy significantly increases after the application of the MNS under a rotating magnetic field. This study provides an anticipated C‐shaped magnetic actuation system for in vivo validation and also presents a clinically feasible drug delivery strategy for targeted thrombolytic therapy with minimal systemic tPA exposure.
Manipulation of magnetic nanoparticle swarms (MNSs) for thrombolysis is validated in in vivo experiments with an autonomously developed C‐shaped magnetic actuation system. Accompanied by the locomotion of MNSs, a tissue plasminogen activator (tPA) can be transported along with the swarms through the interrupted bloodstream to the clots, thus improving the thrombolysis efficacy and quickly opening a channel for achieving time‐critical recanalization.
Background The mechanism of podocyte apoptosis is not fully understood. In addition, the role of the inositol 1,4,5-triphosphate receptor (IP.sub.3R)/glucose-regulated protein 75 ...(Grp75)/voltage-dependent anion channel 1 (VDAC1)/mitochondrial calcium uniporter (MCU) calcium regulation axis, which is located at sites of endoplasmic reticulum (ER) mitochondria coupling, in the mechanism of podocyte apoptosis is unclear. This study aimed to understand the roles of this axis in podocyte apoptosis and explore potential targets for podocyte protection. Methods The expression of IP.sub.3R, Grp75, VDAC1, and MCU and mitochondrial Ca.sup.2+ were analyzed during Adriamycin- or angiotensin II-induced apoptosis in cultured mouse podocytes. The interaction between IP.sub.3R, Grp75, and VDAC1 was investigated using co-immunoprecipitation experiments. The effects of IP.sub.3R, Grp75, and MCU agonists and antagonists on mitochondrial Ca.sup.2+ and apoptosis were investigated in cultured podocytes. The podocyte-protective effects of an MCU inhibitor were further investigated in rats with Adriamycin-induced nephropathy. Results Increased expression of IP.sub.3R, Grp75, VDAC1 and MCU, enhanced interaction among the IP.sub.3R-Grp75-VDAC1 complex, mitochondrial Ca.sup.2+ overload, and increased active caspase-3 levels were confirmed during Adriamycin- or angiotensin II-induced mouse podocyte apoptosis. Agonists of this axis facilitated mitochondrial Ca.sup.2+ overload and podocyte apoptosis, whereas specific antagonists against IP.sub.3R, Grp75, or MCU prevented mitochondrial Ca.sup.2+ overload and podocyte apoptosis. A specific MCU inhibitor prevented Adriamycin-induced proteinuria and podocyte foot process effacement in rats. Conclusions This study identified a novel pathway in which the IP.sub.3R-Grp75-VDAC1-MCU calcium regulation axis mediated podocyte apoptosis by facilitating mitochondrial Ca.sup.2+ overload. Antagonists that inhibit Ca.sup.2+ transfer from ER to mitochondria protected mouse podocytes from apoptosis. An MCU inhibitor protected podocytes and decreased proteinuria in rats with Adriamycin-induced nephropathy. Therefore, antagonists to this pathway have promise as novel podocyte-protective drugs. Keywords: Podocyte, Apoptosis, Endoplasmic reticulum mitochondria coupling, Mitochondria, Calcium
Nanomaterials can be incorporated in the synthesis of membrane to obtain mixed-matrix membrane with marked improvement in properties and performance. However, stability and dispersion of the ...nanomaterials in the membrane matrix, as well as the need to use high ratio of nanomaterials for obvious improvement of membrane properties, remain a major hurdle for commercialization. Hence, this study aims to investigate the improvement of polyamide 6,6 membrane properties with the incorporation of silver nanoparticles decorated on graphene oxide (Ag-GO) nanoplates and at the same time focus is given to the issues above. Graphene oxide nanoplates were synthesized using the modified Hummers' method and decorated with silver before embedded into the polyamide 6,6 matrix. Physicochemical characterizations were conducted on both nanoplates and the mixed-matrix Ag-GO polyamide 6,6 membrane. The issues of Ag agglomeration and leaching were not observed, which could be attributed to the decoration of Ag on GO that helped to disperse the nanomaterials and provided a better anchor point for the attachment of Ag nanoparticles. The synthesized membrane showed marked improvement regarding flux (135% increment) and antifouling (40% lower irreversible fouling), which could be ascribed to the more negative charge of membrane surface (-14 ± 6 to -31 ± 3.8 mV) and hydrophilicity (46% enhancement) of the membranes. With minimal embedment of Ag nanoparticles, the membrane showed superior antibacterial property where the E. coli bacteria could not form a single colony on the membrane surface. Overall, the decoration of Ag on GO nanoplates could be a promising approach to resolve the agglomeration and leaching issues as well as reduce the amount of precious Ag in the synthesis of Ag-GO polyamide 6,6 membrane.
One of the main challenges for advanced metallic nanoparticles (NPs) supported functional perovskite catalysts is the simultaneous achievement of a high population of NPs with uniform distribution as ...well as long-lasting high performance. These are also the essential requirements for optimal electrode catalysts used in solid oxide fuel cells and electrolysis cells (SOFCs and SOECs). Herein, we report a facile operando manufacture way that the crystal reconstruction of double perovskite under reducing atmosphere can spontaneously lead to the formation of ordered layered oxygen deficiency and yield segregation of massively and finely dispersed NPs. The real-time observation of this emergent process was performed via an environmental transmission electron microscope. Density functional theory calculations prove that the crystal reconstruction induces the loss of coordinated oxygen surrounding B-site cations, serving as the driving force for steering fast NP growth. The prepared material shows promising capability as an active and stable electrode for SOFCs in various fuels and SOECs for CO2 reduction. The conception exemplified here could conceivably be extended to fabricate a series of supported NPs perovskite catalysts with diverse functionalities.
Emerging clinical and experimental evidence demonstrates that neuroinflammation plays an important role in cognitive impairment associated with neuropathic pain. However, how peripheral nerve ...challenge induces remote inflammation in the brain remains largely unknown.
The circulating leukocytes and plasma C-X-C motif chemokine 12 (CXCL12) and brain perivascular macrophages (PVMs) were analyzed by flow cytometry, Western blotting, ELISA, and immunostaining in spared nerve injury (SNI) mice. The memory function was evaluated with a novel object recognition test (NORT) in mice and with Montreal Cognitive Assessment (MoCA) in chronic pain patients.
The classical monocytes and CXCL12 in the blood, PVMs in the perivascular space, and gliosis in the brain, particularly in the hippocampus, were persistently increased following SNI in mice. Using the transgenic CCR2
and CX3CR1
mice, we discovered that at least some of the PVMs were recruited from circulating monocytes. The SNI-induced increase in hippocampal PVMs, gliosis, and memory decline were substantially prevented by either depleting circulating monocytes via intravenous injection of clodronate liposomes or blockade of CXCL12-CXCR4 signaling. On the contrary, intravenous injection of CXCL12 at a pathological concentration in naïve mice mimicked SNI effects. Significantly, we found that circulating monocytes and plasma CXCL12 were elevated in chronic pain patients, and both of them were closely correlated with memory decline.
CXCL12-mediated monocyte recruitment into the perivascular space is critical for neuroinflammation and the resultant cognitive impairment in neuropathic pain.
This study assessed the environmental impacts of a composite polyvinylidene fluoride (PVDF) membrane (incorporating nanomaterials) and compared with neat PVDF membrane on algal membrane photoreactor ...(A-MPR) system's overall sustainability. The life cycle assessment (LCA) was carried out using Simapro 8.4.0 with cradle-to-gate approach, including raw materials, equipment, transportation and electricity consumption using ReCiPe 1.13 (H) and IPCC 2013 GWP 100a methodology. From the LCA analysis, silver/graphene oxide - polyvinylidene fluoride (Ag/GO-PVDF) membrane fabrication showed higher environmental impact than the neat PVDF membrane fabrication due to the addition of Ag/GO nanohybrids into the polymer. However, the A-MPR system using the Ag/GO-PVDF membrane exhibited better environmental footprint due to the improved performance of the modified membrane in producing higher volume of permeate as the output. Therefore, the A-MPR system using Ag/GO-PVDF membrane had outweighed the additional environmental impact of the Ag/GO-PVDF membrane fabrication process. Energy demand was identified as the main environmental hotspot in the LCA analysis. Subsequently, sensitivity analysis was performed to find out the effect of various energy mix for electricity generation towards the environment. The analysis revealed that the energy source for electricity generation had significant influence on the overall sustainability of the A-MPR system. The use of grid with 100% renewable energy (hydropower and geothermal) and solar photovoltaic might be able to mitigate 94.8% and 97.5% of CO2 emission, respectively.
•Fabrication of composite membrane had greater environmental influence.•Composite membrane showed lower environmental footprint in the reactor operation.•Reduction of electricity usage is essential to minimize the environmental impact.•Development of green energy source is crucial to reduce environmental loads.
A small volumetric capacitance resulting from a low packing density is one of the major limitations for novel nanocarbons finding real applications in commercial electrochemical energy storage ...devices. Here we report a carbon with a density of 1.58 g cm(-3), 70% of the density of graphite, constructed of compactly interlinked graphene nanosheets, which is produced by an evaporation-induced drying of a graphene hydrogel. Such a carbon balances two seemingly incompatible characteristics: a porous microstructure and a high density, and therefore has a volumetric capacitance for electrochemical capacitors (ECs) up to 376 F cm(-3), which is the highest value so far reported for carbon materials in an aqueous electrolyte. More promising, the carbon is conductive and moldable, and thus could be used directly as a well-shaped electrode sheet for the assembly of a supercapacitor device free of any additives, resulting in device-level high energy density ECs.
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