A multifunctional biomimetic nanoplatform for image-guideded photothermal-ferroptotic synergistic osteosarcoma therapy.

Much effort has been devoted to improving treatment efficiency for osteosarcoma (OS). However, most current approaches result in poor therapeutic responses, thus indicating the need for the development of other therapeutic options. This study developed a multifunctional nanoparticle, PDA-MOF-E-M, an aggregation of OS targeting, programmed death targeting, and near-infrared (NIR)-aided targeting. At the same time, a multifunctional nanoparticle that utilises Fe-MOFs to create a cellular iron-rich environment and erastin as a ferroptosis inducer while ensuring targeted delivery to OS cells through cell membrane encapsulation is presented. The combination of PDA-MOF-E-M and PTT increased intracellular ROS and LPO levels and induced ferroptosis-related protein expression. A PDA-based PTT combined with erastin showed significant synergistic therapeutic improvement in the anti-tumour efficiency of the nanoparticle in vitro and vivo. The multifunctional nanoparticle efficiently prevents the osteoclasia progression of OS xenograft bone tumors in vivo. Finally, this study provides guidance and a point of reference for clinical approaches to treating OS.

Discrete residual diffusion model for high-resolution prostate MRI synthesis.

Objective.High-resolution magnetic resonance imaging (HR MRI) is an effective tool for diagnosing PCa, but it requires patients to remain immobile for extended periods, increasing chances of image distortion due to motion. One solution is to utilize super-resolution (SR) techniques to process low-resolution (LR) images and create a higher-resolution version. However, existing medical SR models suffer from issues such as excessive smoothness and mode collapse. In this paper, we propose a novel generative model avoiding the problems of existing models, called discrete residual diffusion model (DR-DM).Approach.First, the forward process of DR-DM gradually disrupts the input via a fixed Markov chain, producing a sequence of latent variables with increasing noise. The backward process learns the conditional transit distribution and gradually match the target data distribution. By optimizing a variant of the variational lower bound, training diffusion models effectively address the issue of mode collapse. Second, to focus DR-DM on recovering high-frequency details, we synthesize residual images instead of synthesizing HR MRI directly. The residual image represents the difference between the HR and LR up-sampled MR image, and we convert residual image into discrete image tokens with a shorter sequence length by a vector quantized variational autoencoder (VQ-VAE), which reduced the computational complexity. Third, transformer architecture is integrated to model the relationship between LR MRI and residual image, which can capture the long-range dependencies between LR MRI and the synthesized imaging and improve the fidelity of reconstructed images.Main results.Extensive experimental validations have been performed on two popular yet challenging magnetic resonance image super-resolution tasks and compared to five state-of-the-art methods.Significance.Our experiments on the Prostate-Diagnosis and PROSTATEx datasets demonstrate that the DR-DM model significantly improves the signal-to-noise ratio of MRI for prostate cancer, resulting in greater clarity and improved diagnostic accuracy for patients.

Arbitrary scale super-resolution diffusion model for brain MRI images.

Given the constraints posed by hardware capacity, scan duration, and patient cooperation, the reconstruction of magnetic resonance imaging (MRI) images emerges as a pivotal aspect of medical imaging research. Currently, deep learning-based super-resolution (SR) methods have been widely discussed in medical image processing due to their ability to reconstruct high-quality, high resolution (HR) images from low resolution (LR) inputs. However, most existing MRI SR methods are designed for specific magnifications and cannot generate MRI images at arbitrary scales, which hinders the radiologists from fully visualizing the lesions. Moreover, current arbitrary scale SR methods often suffer from issues like excessive smoothing and artifacts. In this paper, we propose an Arbitrary Scale Super-Resolution Diffusion Model (ASSRDM), which combines implicit neural representation with the denoising diffusion probabilistic model to achieve arbitrary-scale, high-fidelity medical images SR. Moreover, we formulate a continuous resolution regulation mechanism, comprising a multi-scale LR guidance network and a scaling factor. The scaling factor finely adjusts the resolution and dynamically influences the weighting of LR details and synthesized features in the final output. This capability allows the model to seamlessly adapt to the requirements of continuous resolution adjustments. Additionally, the multi-scale LR guidance network provides the denoising block with multi-resolution LR features to enrich texture information and restore high-frequency details. Extensive experiments conducted on the IXI and fastMRI datasets demonstrate that our ASSRDM exhibits superior performance compared to existing techniques and has tremendous potential in clinical practice.

Senktide blocks aberrant RTN3 interactome to retard memory decline and tau pathology in social isolated Alzheimer's disease mice.

Sporadic or late-onset Alzheimer's disease (LOAD) accounts for more than 95% of AD cases without any family history. Although genome-wide association studies (GWAS) have identified associated risk genes and loci for LOAD, numerous studies suggest that many adverse environmental factors, such as social isolation, are associated with an increased risk of dementia. However, the underlying mechanisms of social isolation in AD progression remain elusive. In the current study, we found that 7 days of social isolation could trigger pattern separation impairments and presynaptic abnormalities of the mossy fibre-CA3 circuit in AD mice. We also revealed that social isolation disrupted histone acetylation and resulted in the downregulation of 2 DG-enriched miRNAs, which simultaneously target reticulon 3 (RTN3), an endoplasmic reticulum protein that aggregates in presynaptic regions to disturb the formation of functional mossy fiber boutons (MFBs) by recruiting multiple mitochondrial and vesicle-related proteins. Interestingly, the aggregation of RTN3 also recruits the PP2A B subunits to suppress PP2A activity and induce tau hyperphosphorylation, which in turn further elevates RTN3 and forms a vicious cycle. Finally, using an artificial intelligence (AI)-assisted molecular docking approach, we determined that senktide, a selective agonist of neurokinin3 receptors (NK3R), could reduce the binding of RTN3 with its partners. Moreover, application of senktide in vivo effectively restored DG circuit disorders in socially isolated AD mice. Taken together, our findings not only demonstrate the epigenetic regulatory mechanism underlying mossy fibre synaptic disorders orchestrated by social isolation and tau pathology but also reveal a novel potential therapeutic strategy for AD.

Deubiquitylase YOD1 regulates CDK1 stability and drives triple-negative breast cancer tumorigenesis.

BACKGROUND: Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with the initiation and progression of Triple-negative breast cancer (TNBC). The publicly available TCGA database of breast cancer data was used to analyze the OTUD deubiquitinating family members that were correlated with survival of breast cancer and ovarian tumor domain-containing 2 (OTUD-2), or YOD1 was identified. The aim of present study was to assess YOD1 expression and function in human TNBC and then explored the underlying molecular events. METHODS: We detected the expression of YOD1 in 32 TNBC and 44 NTNBC samples by qRT-PCR, Western blot and immunohistochemistry. Manipulation of YOD1 expression was assessed in vitro and in vivo for TNBC cell proliferation, migration, invasion, cell-cycle and drug resistance, using colony formation assay, transwell assay, CCK8 assay, TUNEL assay, flow cytometric analysis and xenograft tumor assay. Next, proteomic analysis, Western blot, proximity ligation assay, Immunoprecipitation, and Immunofluorescence were conducted to assess downstream targets. RESULTS: It was found that YOD1 was significantly upregulated in TNBC tissues compared with non-triple-negative breast cancer (NTNBC), which was positively correlated with poor survival in TNBC patients. Knockdown of YOD1 effectively inhibited TNBC cell migration, proliferation, cell cycle and resistance to cisplatin and paclitaxel. Mechanistically, YOD1 promoted TNBC progression in a manner dependent on its catalytic activity through binding with CDK1, leading to de-polyubiquitylation of CDK1 and upregulation of CDK1 expression. In addition, YOD1 overexpression was found to be correlated with CDK1 overexpression in human TNBC specimens. Finally, in vivo study demonstrated that YOD1 knockdown or YOD1 inhibitor could inhibit CDK1 expression and suppress the growth and metastasis of TNBC tumors. CONCLUSION: Our study highlights that YOD1 functions as an oncogene in TNBC via binding to CDK1 and mediated its stability and oncogenic activity. Interfering with YOD1 expression or YOD1 inhibitor could suppress TNBC cells in vitro and in vivo, suggesting that YOD1 may prove to be a promising therapeutic target for TNBC.

Remarkable N2 selectivity enhancement of NH3-SCO reactions over V0.5/Pt0.04/TiO2 catalyst through Cu-Er co-modification.

Pt-V bimetallic catalysts maybe promising substitutes to precious metal catalysts for selective catalytic oxidation (SCO) of NH3. But it remains a major challenge for Pt-V bimetallic catalysts to pursue high NH3 conversion rate and N2 selectivity simultaneously. In this work, both Cu and Er were adopted to modify V0.5/Pt0.04/TiO2 catalyst (denoted as V/PT), and the influences of Cu and Er doping amounts on NH3-SCO performance of V/PT catalysts were investigated systematically. The results indicated that the co-modification of Cu and Er imposed little influence on NH3 conversion efficiency, but significantly boosted N2 selectivity. Compared with other Cu-Er-modified V/PT catalysts, CEV/PT-4 catalyst exhibited outstanding NH3-SCO performance, which attained completely 100% NH3 conversion efficiency and > 90% N2 selectivity in the temperature range of 225-450 °C. It was significantly superior to the NH3-SCO performance of most previously reported catalysts. The characterization results indicated that the adequate doping amounts of Cu and Er resulted in an obvious enhancement on redox property and surface acidity of CEV/PT-4 catalyst. It also led to abundant Pt0 and surface chemisorbed oxygen species on catalyst surface, which facilitated the oxidation of NH3 to NOx and enhanced i-SCR reactions. In situ DRIFTS results showed that -NH2 species on the surface of CEV/PT-4 catalyst could actively react with nitrate species to generate N2 and H2O.

Assessment of Instant Loss of Elbow Flexion in Children with Untreated Gartland IIA Humeral Supracondylar Fractures-A Simulation Study with Lateral Elbow Radiographs.

OBJECTIVE: The suitability of in situ cast fixation for treating Gartland IIA humeral supracondylar fractures has remained controversial due to concerns regarding loss of elbow flexion. This study aimed to assess the instant loss of elbow flexion after Gartland IIA humeral supracondylar fractures based on the relationship between the anterior marginal line of the humerus and capitellum in the lateral view. METHODS: This simulation study was conducted with normal radiographs using Adobe Photoshop 14.0, followed by verification using clinical cases. Standard lateral views of normal elbows of children were collected from January 2008 to February 2020. Adobe Photoshop was used to simulate Gartland IIA supracondylar fractures with different degrees of angulation in the sagittal plane. A formula was deduced to assess flexion loss, and this method was verified in three cases. The data were grouped by age, and the relationship between elbow flexion loss and age, as well as the angulation of the fracture, was analyzed using a one-way or multivariate ANOVA. RESULTS: There was a flexion loss of 19° (11-30°) when the anterior margin line of the humerus was tangential to the capitellum. This loss increased with age at injury (r = 0.731, P = 0.000). Moreover, the difference in angulation in the sagittal plane also influenced the extent of elbow flexion loss (r = -0.739, P = 0.000). The more horizontal the fracture line in the lateral view, the greater the loss of elbow flexion. CONCLUSION: Instant elbow flexion loss after Gartland IIA humeral supracondylar fractures increases with age at the time of injury and decreases with angulation in the sagittal plane. When the anterior margin of the humerus is tangential to the capitellum, there will be an average loss of 19° in elbow flexion. These findings provide a quantitative reference for clinical decision-making in the treatment of Gartland IIA supracondylar fractures.

Tau pathology epigenetically remodels the neuron-glial cross-talk in Alzheimer's disease.

The neuron-glia cross-talk is critical to brain homeostasis and is particularly affected by neurodegenerative diseases. How neurons manipulate the neuron-astrocyte interaction under pathological conditions, such as hyperphosphorylated tau, a pathological hallmark in Alzheimer's disease (AD), remains elusive. In this study, we identified excessively elevated neuronal expression of adenosine receptor 1 (Adora1 or A1R) in 3×Tg mice, MAPT P301L (rTg4510) mice, patients with AD, and patient-derived neurons. The up-regulation of A1R was found to be tau pathology dependent and posttranscriptionally regulated by Mef2c via miR-133a-3p. Rebuilding the miR-133a-3p/A1R signal effectively rescued synaptic and memory impairments in AD mice. Furthermore, neuronal A1R promoted the release of lipocalin 2 (Lcn2) and resulted in astrocyte activation. Last, silencing neuronal Lcn2 in AD mice ameliorated astrocyte activation and restored synaptic plasticity and learning/memory. Our findings reveal that the tau pathology remodels neuron-glial cross-talk and promotes neurodegenerative progression. Approaches targeting A1R and modulating this signaling pathway might be a potential therapeutic strategy for AD.

BARX1 promotes osteosarcoma cell proliferation and invasion by regulating HSPA6 expression.

Osteosarcoma (OS) is a bone tumour affecting adolescents. Dysregulation of Barx homeobox 1 (BARX1) expression is involved in various cancers, but its function and mechanism in the process of OS are undefined. This study revealed that BARX1 expression is higher in OS tissue than in adjacent normal tissue. Downregulation of BARX1 in OS cells significantly suppressed their proliferation and migration, whereas enforced expression of exogenous BARX1 exerted the opposite effects on OS cells. Subsequently, heat shock 70-kDa protein 6 (HSPA6) expression was clearly increased after BARX1 overexpression in OS cells, as confirmed by RNA sequencing. The dual-luciferase reporter assay confirmed that HSPA6 expression is directly regulated by BARX1. The in vitro assay indicated that silencing HSPA6 expression attenuated OS proliferation and migration induced by BARX1. A dual immunofluorescence labelling assay provided further evidence that BARX1 was overexpressed and associated with HSPA6 overexpression in OS tumour tissue. In conclusion, BARX1 promotes OS cell proliferation and migration by inducing the expression of HSPA6, which plays an oncogenic role in OS. BARX1 and HSPA6 can potentially act as novel therapeutic targets for OS.

Wen-Shen-Tong-Luo-Zhi-Tong Decoction regulates bone-fat balance in osteoporosis by adipocyte-derived exosomes.

CONTEXT: Wen-Shen-Tong-Luo-Zhi-Tong (WSTLZT) Decoction is a Chinese prescription with antiosteoporosis effects, especially in patients with abnormal lipid metabolism. OBJECTIVE: To explore the effect and mechanism of WSTLZT on osteoporosis (OP) through adipocyte-derived exosomes. MATERIALS AND METHODS: Adipocyte-derived exosomes with or without WSTLZT treated were identified by transmission electron microscopy, nanoparticle tracking analysis (NTA) and western blotting (WB). Co-culture experiments for bone marrow mesenchymal stem cells (BMSCs) and exosomes were performed to examine the uptake and effect of exosome in osteogenesis and adipogenic differentiation of BMSC. MicroRNA profiles, luciferase and IP were used for exploring specific mechanisms of exosome on BMSC. In vivo, 80 Balb/c mice were randomly divided into four groups: Sham, Ovx, Exo (30 µg exosomes), Exo-WSTLZT (30 µg WSTLZT-exosomes), tail vein injection every week. After 12 weeks, the bone microstructure and marrow fat distribution were analysed by micro-CT. RESULTS: ALP, Alizarin red and Oil red staining showed that WSTLZT-induced exosomes from adipocyte can regulate osteoblastic and adipogenic differentiation of BMSC. MicroRNA profiles observed that WSTLZT treatment resulted in 87 differentially expressed miRNAs (p < 0.05). MiR-122-5p with the greatest difference was screened by q-PCR (p < 0.01). The target relationship between miR-122-5p and SPRY2 was tested by luciferase and IP. MiR-122-5p negatively regulated SPRY2 and elevated the activity of MAPK signalling pathway, thereby regulating the osteoblastic and adipogenic differentiation of BMSC. In vivo, exosomes can not only improve bone microarchitecture but also significantly reduce accumulation of bone marrow adipose. CONCLUSIONS: WSTLZT can exert anti-OP effect through SPRY2 via the MAKP signalling by miR-122-5p carried by adipocyte-derived exosomes.

A Novel Method Based on Hydrodynamic Cavitation for Improving Nitric Oxide Removal Performance of NaClO2.

In the removal of nitric oxide (NO) by sodium chlorite (NaClO2), the NaClO2 concentration is usually increased, and an alkaline absorbent is added to improve the NO removal efficiency. However, this increases the cost of denitrification. This study is the first to use hydrodynamic cavitation (HC) combined with NaClO2 for wet denitrification. Under optimal experimental conditions, when 3.0 L of NaClO2 with a concentration of 1.00 mmol/L was used to treat NO (concentration: 1000 ppmv and flow rate: 1.0 L/min), 100% of nitrogen oxides (NOx) could be removed in 8.22 min. Furthermore, the NO removal efficiency remained at 100% over the next 6.92 min. Furthermore, the formation of ClO2 by NaClO2 is affected by pH. The initial NOx removal efficiency was 84.8-54.8% for initial pH = 4.00-7.00. The initial NOx removal efficiency increases as the initial pH decreases. When the initial pH was 3.50, the initial NOx removal efficiency reached 100% under the synergistic effect of HC. Therefore, this method enhances the oxidation capacity of NaClO2 through HC, realizes high-efficiency denitrification with low NaClO2 concentration (1.00 mmol/L), and has better practicability for the treatment of NOx from ships.

Permethrin as a Potential Furin Inhibitor through a Novel Non-Competitive Allosteric Inhibition.

Furin is a potential target protein associated with numerous diseases; especially closely related to tumors and multiple viral infections including SARS-CoV-2. Most of the existing efficient furin inhibitors adopt a substrate analogous structure, and other types of small molecule inhibitors need to be discovered urgently. In this study, a high-throughput screening combining virtual and physical screening of natural product libraries was performed, coupled with experimental validation and preliminary mechanistic assays at the molecular level, cellular level, and molecular simulation. A novel furin inhibitor, permethrin, which is a derivative from pyrethrin I generated by Pyrethrum cinerariifolium Trev. was identified, and this study confirmed that it binds to a novel allosteric pocket of furin through non-competitive inhibition. It exhibits a very favorable protease-selective inhibition and good cellular activity and specificity. In summary, permethrin shows a new parent nucleus with a new mode of inhibition. It could be used as a highly promising lead compound against furin for targeting related tumors and various resistant viral infections, including SARS-CoV-2.

DJ-1 promotes osteosarcoma progression through activating CDK4/RB/E2F1 signaling pathway.

Osteosarcoma (OS) is a primary malignant tumor of the bone characterized by poor prognosis due to chemotherapy resistance and high recurrence rates. DJ-1 (PARK7) is known as an oncogene and its abnormal expression is related to the poor prognosis of various types of malignant tumors. It was found in this study that upregulated expression of DJ-1 was closely correlated with the prognosis of OS patients by promoting the proliferation, migration and chemotherapy resistance of OS cells in vitro through regulating the activity of CDK4 but not through the oxidation mechanism or AKT pathway. The combination of DJ-1 and CDK4 promoted RB phosphorylation, leading to the dissociation of E2F1 into the nucleus to regulate the expression of cell cycle-related genes. The tumor xenograft mouse model demonstrated that DJ-1 knockout suppressed tumor growth in vivo. All these findings indicate that DJ-1 can affect the occurrence and progression of OS by regulating the CDK/RB/E2F1axis, suggesting a novel therapeutic opportunity for OS patients.

Synthesis of W-modified CeO2/ZrO2 catalysts for selective catalytic reduction of NO with NH3.

In this paper, a series of tungsten-zirconium mixed binary oxides (denoted as W m ZrO x ) were synthesized via co-precipitation as supports to prepare Ce0.4/W m ZrO x catalysts through an impregnation method. The promoting effect of W doping in ZrO2 on selective catalytic reduction (SCR) performance of Ce0.4/ZrO2 catalysts was investigated. The results demonstrated that addition of W in ZrO2 could remarkably enhance the catalytic performance of Ce0.4/ZrO2 catalysts in a broad temperature range. Especially when the W/Zr molar ratio was 0.1, the Ce0.4/W0.1ZrO x catalyst exhibited the widest active temperature window of 226-446 °C (NO x conversion rate > 80%) and its N2 selectivity was almost 100% in the temperature of 150-450 °C. Moreover, the Ce0.4/W0.1ZrO x catalyst also exhibited good SO2 tolerance, which could maintain more than 94% of NO x conversion efficiency after being exposed to a 100 ppm SO2 atmosphere for 18 h. Various characterization results manifested that a proper amount of W doping in ZrO2 was not only beneficial to enlarge the specific surface area of the catalyst, but also inhibited the growth of fluorite structure CeO2, which were in favor of CeO2 dispersion on the support. The presence of W was conducive to the growth of a stable tetragonal phase crystal of ZrO2 support, and a part of W and Zr combined to form W-Zr-O x solid super acid. Both of them resulted in abundant Lewis acid sites and Brønsted acid sites, enhancing the total surface acidity, thus significantly improving NH3 species adsorption on the surface of the Ce0.4/W0.1ZrO x catalyst. Furthermore, the promoting effect of adding W on SCR performance was also related to the improved redox capability, higher Ce3+/(Ce3+ + Ce4+) ratio and abundant surface chemisorbed oxygen species. The in situ DRIFTS results indicated that nitrate species adsorbed on the surface of the Ce0.4/W0.1ZrO x catalyst could react with NH3 due to the activation of W. Therefore, the reaction pathway over the Ce0.4/W0.1ZrO x catalyst followed both Eley-Rideal (E-R) and Langmuir-Hinshelwood (L-H) mechanisms at 250 °C.

Cattle Encephalon Glycoside and Ignotin Ameliorate Palmitoylation of PSD-95 and Enhance Expression of Synaptic Proteins in the Frontal Cortex of a APPswe/PS1dE9 Mouse Model of Alzheimer's Disease.

BACKGROUND: Synaptic abnormalities in synaptic proteins are the initial hallmarks of Alzheimer's disease (AD). The higher level of palmitoylation of synaptic proteins was closely associated with amyloid-ß (Aß) in AD. Cattle encephalon glycoside and ignotin (CEGI) have been shown to act as multitarget neurotrophic agents in APPswe/PS1dE9 (APP/PS1) transgenic AD mice. However, it is not clear whether CEGI can influence Aß deposition or whether it does so by the regulation of protein palmitoylation and expression of synaptic proteins in transgenic AD mice. OBJECTIVE: In this study, we investigated the roles of CEGI in modulating postsynaptic density protein 95 (PSD-95) palmitoylation, Aß pathologies, and expression of synaptic-associated proteins in APP/PS1 mice. METHODS: Five-month-old APP/PS1 mice were treated intraperitoneally with 6.6 mL/kg of CEGI for 6 weeks. At the end of the treatment period, APP/PS1 mice were subjected to Morris water maze to test their cognitive functions. Acyl-biotinyl exchange (ABE) for PSD-95 palmitoylation, immunofluorescent staining for expression of PSD-95, N-methyl-D-aspartic acid receptor subunit 2B (NR2B), and synaptotagmin 1 (SYT1) were assessed in mouse brain sections. RESULTS: CEGI treatment in APP/PS1 mice significantly reduced Aß deposition, relieved memory deficits, and decreased PSD-95 palmitoylation while markedly increasing the expression of PSD-95, NR2B, and SYT1 in the frontal cortex. There was a significant correlation between Aß expression and PSD-95 palmitoylation in APP/PS1 mice. CONCLUSION: Our findings demonstrate that CEGI improved AD-like neuropathology, possibly by inhibiting PSD-95 palmitoylation, improving learning memory, and enhancing expression of synaptic-associated proteins, representing a potential therapy for AD treatment.

Analysis of the location and trajectory of the Kirschner wires in the fixation of extension-type supracondylar fracture of the humerus by 3D computational simulation.

BACKGROUND: Closed reduction and percutaneous pinning is still a preference for the treatment of supracondylar humerus fractures in children. However, no reports have shown the pin trajectory and the characteristics of the entry point so far. So we established a computational simulation model of the elbow to observe the trajectory of pinning for supracondylar humerus fractures. METHODS: We reconstructed an adult elbow computationally and simulated pin placement through lateral and medial pinning. Pin trajectories were traced after placement and after the addition of the skin profile; the relative entry points of the pins were determined. We used the center of the dorsal olecranon inflection as an anatomic reference for the entry points of lateral pinning. Four quadrants were established based on the center of the dorsal olecranon inflection: upper medial quadrant, upper lateral quadrant, lower medial quadrant, and lower lateral quadrant (LLQ). RESULTS: The maximum angle of pinning through the lateral column was 64° ± 3°. The minimum angles of pinning through the lateral column and middle column were 37° ± 3° and 20° ± 2°, respectively. The range of safe angle pinning through the medial column was between 18° ± 2° and 57° ± 3° to avoid penetration of the olecranon fossa and the cortex of the medial column. The entry points of lateral pinning were within the lateral half of the LLQ, and the lateral one-third of the LLQ contained all entry points of the pins through the lateral column and minor points of the pins through the middle column. The exit points of the medial pinning were within the lateral fringe of the metaphyseal-diaphyseal junction region; entering from the inferior two-thirds of the medial epicondyle could lead to the exit points in the proximal half of the metaphyseal-diaphyseal junction region laterally. DISCUSSION: For lateral pinning, the entry points would be within the lateral half of the LLQ. For the pins through the lateral column, the entry points should be within the lateral one-third of the LLQ. For medial pinning, entering from the inferior two-thirds of the medial epicondyle would lead to a more proximal exit.

Insight into the promoting effect of support pretreatment with sulfate acid on selective catalytic reduction performance of CeO2/ZrO2 catalysts.

In this paper, sulfated ZrO2 were synthesized via precipitation and impregnation method, and the promoting effects of support sulfation on selective catalytic reduction (SCR) performance of CeO2/ZrO2 catalysts were investigated. The results revealed that sulfated ZrO2 could significantly enhance the SCR activity of CeO2/ZrO2 catalysts in a wide temperature range. Especially when S/Zr molar ratio was 0.1, CeO2/ZrO2-0.1S catalyst exhibited a large operating temperature window of 251 âˆ¼ 500 °C and its N2 selectivity was 100 % in the temperature range of 150 âˆ¼ 500 °C. Moreover, CeO2/ZrO2-0.1S catalyst possessed a superior low-temperature activity over 0.1S-CeO2/ZrO2 catalyst. After exposing to 100 ppm SO2 for 15 h, a high NO conversion efficiency of CeO2/ZrO2-0.1S catalyst (90.7 %) could still be reached. The characterization results indicated that ZrO2 treated with a proper dosage of sulfate acid was beneficial to enlarge the specific surface area greatly. Sulfated ZrO2 was also in favor of promoting the transformation of CeO2 from crystalline state to highly-dispersed amorphous state, and inhibiting the transformation of ZrO2 from tetragonal to monoclinic phase. It could also enhance the total surface acidity greatly with an increase in both Brønsted acid sites and Lewis acid sites, thus significantly improving NH3 adsorption on catalyst surface. Besides, the promoting effect of support sulfation on SCR performance of CeO2/ZrO2 catalysts was also related with the enhanced redox property, higher Ce3+/(Ce3++Ce4+) ratio and abundant surface chemisorbed labile oxygen. The in-situ DRIFTS results implied that nitrate species coordinated on the surface of CeO2/ZrO2-0.1S catalyst could participate in the Selective catalytic reduction with ammonia (NH3-SCR) reactions at either medium or high temperature, suggesting that both Eley-Rideal (E-R) and Langmuir-Hinshelwood (L-H) mechanisms might be followed in SCR reactions.

An investigation on the promoting effect of Pr modification on SO2 resistance over MnOx catalysts for selective reduction of NO with NH3.

Pr-modified MnOx catalyst was synthesized through a facile co-precipitation process, and the results showed that MnPrOx catalyst exhibited much better selective catalytic reduction (SCR) activity and SO2 resistance performance than pristine MnOx catalyst. The addition of Pr in MnOx catalyst led to a complete NO conversion efficiency in 120-220 °C. Moreover, Pr-modified MnOx catalyst exhibited a superior resistance to H2O and SO2 compared with MnOx catalyst. After exposing to SO2 and H2O for 4 h, the NO conversion efficiency of MnPrOx catalyst could remain to 87.6%. The characterization techniques of XRD, BET, hydrogen-temperature programmed reduction (H2-TPR), ammonia-temperature programmed desorption (NH3-TPD), XPS, TG and in situ diffuse reflectance infrared spectroscopy (DRIFTS) were adopted to further explore the promoting effect of Pr doping in MnOx catalyst on SO2 resistance performance. The results showed that MnPrOx catalyst had larger specific surface area, stronger reducibility, and more L acid sites compared with MnOx catalyst. The relative percentage of Mn4+/Mnn+ on the MnPrOx-S catalyst surface was also much higher than those of MnOx catalyst. Importantly, when SO2 exists in feed gas, PrOx species in MnPrOx catalyst would preferentially react with SO2, thus protecting the Mn active sites. In addition, the introduction of Pr might promote the reaction between SO2 and NH3 rather than between SO2 and Mn active sites, which was also conductive to protect the Mn active sites to a great extent. Since the presence of SO2 in feed gas had little effect on NH3 adsorption on the MnPrOx catalyst surface, and the inhibiting effect of SO2 on NO adsorption was alleviated, SCR reactions could still proceed in a near-normal way through the Eley-Rideal (E-R) mechanism on Pr-modified MnOx catalyst, while SCR reactions through the Langmuir-Hinshelwood (L-H) mechanism were suppressed slightly.

miR-135a-5p mediates memory and synaptic impairments via the Rock2/Adducin1 signaling pathway in a mouse model of Alzheimer's disease.

Aberrant regulation of microRNAs (miRNAs) has been implicated in the pathogenesis of Alzheimer's disease (AD), but most abnormally expressed miRNAs found in AD are not regulated by synaptic activity. Here we report that dysfunction of miR-135a-5p/Rock2/Add1 results in memory/synaptic disorder in a mouse model of AD. miR-135a-5p levels are significantly reduced in excitatory hippocampal neurons of AD model mice. This decrease is tau dependent and mediated by Foxd3. Inhibition of miR-135a-5p leads to synaptic disorder and memory impairments. Furthermore, excess Rock2 levels caused by loss of miR-135a-5p plays an important role in the synaptic disorder of AD via phosphorylation of Ser726 on adducin 1 (Add1). Blocking the phosphorylation of Ser726 on Add1 with a membrane-permeable peptide effectively rescues the memory impairments in AD mice. Taken together, these findings demonstrate that synaptic-related miR-135a-5p mediates synaptic/memory deficits in AD via the Rock2/Add1 signaling pathway, illuminating a potential therapeutic strategy for AD.