Microglial hyperactivation of the NOD‐, LRR‐, and pyrin domain‐containing 3 (NLRP3) inflammasome contributes to the pathogenesis of Parkinson's disease (PD). Recently, neuronally expressed NLRP3 was ...demonstrated to be a Parkin polyubiquitination substrate and a driver of neurodegeneration in PD. However, the role of Parkin in NLRP3 inflammasome activation in microglia remains unclear. Thus, we aimed to investigate whether Parkin regulates NLRP3 in microglia. We investigated the role of Parkin in NLRP3 inflammasome activation through the overexpression of Parkin in BV2 microglial cells and knockout of Parkin in primary microglia after lipopolysaccharide (LPS) treatment. Immunoprecipitation experiments were conducted to quantify the ubiquitination levels of NLRP3 under various conditions and to assess the interaction between Parkin and NLRP3. In vivo experiments were conducted by administering intraperitoneal injections of LPS in wild‐type and Parkin knockout mice. The Rotarod test, pole test, and open field test were performed to evaluate motor functions. Immunofluorescence was performed for pathological detection of key proteins. Overexpression of Parkin mediated NLRP3 degradation via K48‐linked polyubiquitination in microglia. The loss of Parkin activity in LPS‐induced mice resulted in excessive microglial NLRP3 inflammasome assembly, facilitating motor impairment, and dopaminergic neuron loss in the substantia nigra. Accelerating Parkin‐induced NLRP3 degradation by administration of a heat shock protein (HSP90) inhibitor reduced the inflammatory response. Parkin regulates microglial NLRP3 inflammasome activation through polyubiquitination and alleviates neurodegeneration in PD. These results suggest that targeting Parkin‐mediated microglial NLRP3 inflammasome activity could be a potential therapeutic strategy for PD.
Parkin regulates microglial NLRP3 inflammasome activation through polyubiquitination and alleviates neurodegeneration in PD. Combined genetic deletion of Parkin and stimulation by LPS created a PD phenotype that more accurately modeled that of humans. Targeting Parkin‐mediated microglial NLRP3 inflammasome activity using HSP90 inhibitor could be a potential therapeutic strategy for PD.
The difficulty of the cancer classification using multi-class microarray datasets lies in that there are only a few samples in each class. To effectively solve such a problem, we propose a ...hierarchical ensemble strategy, named as Hierarchical Ensemble of Error Correcting Output Codes (HE-ECOC). In this strategy, different feature subsets extracted from a dataset are used as inputs for three data-dependent ECOC algorithms, so as to produce different ECOC coding matrices. The mutual diversity degrees among these coding matrices are then calculated based on two schemes, named as the maximizing local diversity (MLD) and the maximizing global diversity (MGD) schemes. Both schemes can choose diverse coding matrices generated by the same or different ECOC algorithm(s), and the average fusion scheme is used to fuse the outputs of base learners. In the experiments, it is found that both MLD and MGD based HE-ECOC strategies work stably, and outperform individual single ECOC algorithms. In contrast with some ensemble systems, HE-ECOC generates a more robust ensemble system, and achieves better performance in most case. In short, HE-ECOC is a promising solution for the multi-class problem. The matlab code is available upon request.
Electrophilic addition reaction to alkynes is of fundamental importance in organic chemistry, yet the regiocontrol when reacting with unsymmetrical 1,2-dialkyl substituted alkynes is often ...problematic. Herein, it is demonstrated that the rarely recognized β-boron effect can confer a high level of site-selectivity in several alkyne electrophilic addition reactions. A broad range of highly functionalized and complex organoborons are thus formed under simple reaction conditions starting from propargylic MIDA (N-methyliminodiacetic acid) boronates. These products are demonstrated to be valuable building blocks in organic synthesis. In addition to the regiocontrol, this study also observes a drastic rate enhancement upon B(MIDA) substitution. Theoretical calculation reveals that the highest occupied molecular obital (HOMO) energy level of propargylic B(MIDA) is significantly raised by 0.3 eV, and the preferential electrophilic addition to the γ position is due to its higher HOMO orbital coefficient and more negative natural bond orbital (NBO) charge compared to the β position. This study demonstrates the potential of utilizing the β-boron effect in stereoelectronic control of chemical transformations, which can inspire further research in this area.
Wireless power transfer (WPT) plays critical roles in powering deep-tissue implants, which also contributes to several emerging advances for biomedical engineering. To enable a high-power density ...region in implants, this article presents a method, termed the self-phasing technology, to focus electromagnetic fields from various paths at a deep-tissue spot. By performing the phase-conjugated operation on the incident signal and then retransfer back to the source, coherent RF power can be achieved without learning the precise or even dynamic locations of sources and concerning inhomogeneous medium perturbations. An external slot antenna array placed above skin surface 4 mm is considered as a transmitter and an implanted rectenna consisting of a magnetic resonant coil and an RF-to-dc rectifier circuit is treated as a receiver. The conversion efficiency of the rectifier circuit is optimized within the received power range and the measured efficiency of 50% can be achieved at 0 dBm. To visualize the transceiver effects of the integrated system under safety thresholds, a light-emitting diode (LED) is soldered at the terminal of the rectenna and measurements show that smooth drive can be achieved. Certain brightness of LED can demonstrate that the self-phasing technology can support WPT for biomedical applications.
This work provided the first example of selective hydrodeoxygenation of 5‐hydroxymethylfurfural (HMF) to 2,5‐dimethylfuran (DMF) over heterogeneous Fe catalysts. A catalyst prepared by the pyrolysis ...of an Fe‐phenanthroline complex on activated carbon at 800 °C was demonstrated to be the most active heterogeneous Fe catalyst. Under the optimal reaction conditions, complete conversion of HMF was achieved with 86.2 % selectivity to DMF. The reaction pathway was investigated thoroughly, and the hydrogenation of the C=O bond in HMF was demonstrated to be the rate‐determining step during the hydrodeoxygenation, which could be accelerated greatly by using alcohol solvents as additional H‐donors. The excellent stability of the Fe catalyst, which was probably a result of the well‐preserved active species and the pore structure of the Fe catalyst in the presence of H2, was demonstrated in batch and continuous flow fixed‐bed reactors.
Selective and stable Fe: Selective catalytic hydrodeoxygenation of 5‐hydroxymethylfurfural to 2,5‐dimethylfuran over heterogeneous Fe catalysts is demonstrated in batch and continuous flow fixed‐bed reactors. The Fe catalyst exhibited excellent stability, which is probably a result of the well‐preserved active species and the pore structure of the Fe catalyst in the presence of H2.
Seed size and weight are important factors that influence soybean yield. Combining the weighted gene co-expression network analysis (WGCNA) of 45 soybean accessions and gene dynamic changes in seeds ...at seven developmental stages, we identified candidate genes that may control the seed size/weight. Among these, a PLATZ-type regulator overlapping with 10 seed weight QTLs was further investigated. This zinc-finger transcriptional regulator, named as GmPLATZ, is required for the promotion of seed size and weight in soybean. The GmPLATZ may exert its functions through direct binding to the promoters and activation of the expression of cyclin genes and GmGA20OX for cell proliferation. Overexpression of the GmGA20OX enhanced seed size/weight in soybean. We further found that the GmPLATZ binds to a 32-bp sequence containing a core palindromic element AATGCGCATT. Spacing of the flanking sequences beyond the core element facilitated GmPLATZ binding. An elite haplotype Hap3 was also identified to have higher promoter activity and correlated with higher gene expression and higher seed weight. Orthologues of the GmPLATZ from rice and Arabidopsis play similar roles in seeds. Our study reveals a novel module of GmPLATZ-GmGA20OX/cyclins in regulating seed size and weight and provides valuable targets for breeding of crops with desirable agronomic traits.
In this work, Pt nanoparticles were incorporated into SBA-15 to prepare the materials for hydrogen spillover adsorption. We provide a direct modification (DM) strategy to improve the content of Pt ...nanoparticles inside the channels of SBA-15. In this strategy, the Pt precursor was directly incorporated into as synthesized SBA-15 by a solid-state grinding method. The subsequent calcination in air, then H
/Ar gases was conducted to obtain the resultant materials of PtAS. For the samples of PtAS, Pt nanoparticles up to 5.0 wt% have a high dispersion inside the channels of SBA-15. The size of nanoparticles is in control of 3.7 nm. Although much work so far has focused on modification of SBA-15 with Pt nanoparticles. Here, it is the first time the loading amount of Pt nanoparticles raises up to 5.0 wt%, and the location of the Pt nanoparticles is interior channels of SBA-15. We reveal that the high dispersion behaviors of Pt nanoparticles are ascribed to the nanoconfinement effects provided by as synthesized SBA-15. However, the samples derived from template free SBA-15 (PtCS) show sparsely dispersion of Pt nanoparticles with the size of 7.7 nm. We demonstrate that the PtAS samples show better hydrogen adsorption performance than PtCS.
Smoking is a well-established risk factor for atherosclerotic disease, but its role as an independent risk factor for venous thromboembolism (VTE) remains controversial. We conducted a meta-analysis ...to summarize all published prospective studies and case-control studies to update the risk for VTE in smokers and determine whether a dose-response relationship exists.
We performed a literature search using MEDLINE (source PubMed, January 1, 1966 to June 15, 2013) and EMBASE (January 1, 1980 to June 15, 2013) with no restrictions. Pooled effect estimates were obtained by using random-effects meta-analysis. Thirty-two observational studies involving 3,966,184 participants and 35,151 VTE events were identified. Compared with never smokers, the overall combined relative risks (RRs) for developing VTE were 1.17 (95% CI 1.09-1.25) for ever smokers, 1.23 (95% CI 1.14-1.33) for current smokers, and 1.10 (95% CI 1.03-1.17) for former smokers, respectively. The risk increased by 10.2% (95% CI 8.6%-11.8%) for every additional ten cigarettes per day smoked or by 6.1% (95% CI 3.8%-8.5%) for every additional ten pack-years. Analysis of 13 studies adjusted for body mass index (BMI) yielded a relatively higher RR (1.30; 95% CI 1.24-1.37) for current smokers. The population attributable fractions of VTE were 8.7% (95% CI 4.8%-12.3%) for ever smoking, 5.8% (95% CI 3.6%-8.2%) for current smoking, and 2.7% (95% CI 0.8%-4.5%) for former smoking. Smoking was associated with an absolute risk increase of 24.3 (95% CI 15.4-26.7) cases per 100,000 person-years.
Cigarette smoking is associated with a slightly increased risk for VTE. BMI appears to be a confounding factor in the risk estimates. The relationship between VTE and smoking has clinical relevance with respect to individual screening, risk factor modification, and the primary and secondary prevention of VTE. Please see later in the article for the Editors' Summary.
Interfacial host-guest complexation offers a versatile way to functionalize nanomaterials. However, the complicated interfacial environment and trace amounts of components present at the interface ...make the study of interfacial complexation very difficult. Herein, taking the advantages of near-single-molecule level sensitivity and molecular fingerprint of surface-enhanced Raman spectroscopy (SERS), we reveal that a cooperative effect between cucurbit7uril (CB7) and methyl viologen (MV
2I
) in aggregating Au NPs originates from the cooperative adsorption of halide counter anions I
, MV
, and CB7 on Au NPs surface. Moreover, similar SERS peak shifts in the control experiments using CBns but with smaller cavity sizes suggested the occurrence of the same guest complexations among CB5, CB6, and CB7 with MV
. Hence, an unconventional exclusive complexation model is proposed between CB7 and MV
on the surface of Au NPs, distinct from the well-known 1:1 inclusion complexation model in aqueous solutions. In summary, new insights into the fundamental understanding of host-guest interactions at nanostructured interfaces were obtained by SERS, which might be useful for applications related to host-guest chemistry in engineered nanomaterials.
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