Search

Background Amphibian-derived peptides exhibit considerable potential in the discovery and development of new therapeutic interventions for clinically challenging chronic skin wounds. MicroRNAs (miRNAs) are also considered promising targets for the development of effective therapies against skin wounds. However, further research in this field is anticipated. This study aims to identify and provide a new peptide drug candidate, as well as to explore the underlying miRNA mechanisms and possible miRNA drug target for skin wound healing. Methods A combination of Edman degradation, mass spectrometry and cDNA cloning were adopted to determine the amino acid sequence of a peptide that was fractionated from the secretion of Odorrana andersonii frog skin using gel-filtration and reversed-phase high-performance liquid chromatography. The toxicity of the peptide was evaluated by Calcein-AM/propidium iodide (PI) double staining against human keratinocytes (HaCaT cells), hemolytic activity against mice blood cells and acute toxicity against mice. The stability of the peptide in plasma was also evaluated. The prohealing potency of the peptide was determined by MTS, scratch healing and a Transwell experiment against HaCaT cells, full-thickness injury wounds and scald wounds in the dorsal skin of mice. miRNA transcriptome sequencing analysis, enzyme-linked immunosorbent assay, real-time polymerase chain reaction and western blotting were performed to explore the molecular mechanisms. Results A novel peptide homodimer (named OA-GL17d) that contains a disulfide bond between the 16th cysteine residue of the peptide monomer and the sequence ‘GLFKWHPRCGEEQSMWT’ was identified. Analysis showed that OA-GL17d exhibited no hemolytic activity or acute toxicity, but effectively promoted keratinocyte proliferation and migration and strongly stimulated the repair of full-thickness injury wounds and scald wounds in the dorsal skin of mice. Mechanistically, OA-GL17d decreased the level of miR-663a to increase the level of transforming growth factor-β1 (TGF-β1) and activate the subsequent TGF-β1/Smad signaling pathway, thereby resulting in accelerated skin wound re-epithelialization and granular tissue formation. Conclusions Our results suggest that OA-GL17d is a new peptide drug candidate for skin wound repair. This study emphasizes the importance of exogenous peptides as molecular probes for exploring competing endogenous RNA mechanisms and indicates that miR-663a may be an effective target for promoting skin repair.

Small extracellular vesicles (sEVs) are considered to play critical roles in intercellular communications during normal and pathological processes since they are enriched with miRNAs and other signal molecules. In bone remodeling, osteoclasts generate large amounts of sEVs. However, there is very few research studying whether and how osteoclast-derived sEVs (OC-sEVs) affect surrounding cells. In our study, microarray analysis identified miR-106a-5p as highly enriched in OC-sEV. Further experiments confirmed that OC-sEVs inhibited Fam134a through miR-106a-5p and significantly promoted bone mesenchymal stem cell (BMSC) osteogenic mineralization in vitro. Next, we prepared an sEV-modified demineralized bone matrix (DBM) as scaffold treating calvarial defect mouse model to evaluate the pro-osteogenic activities of the scaffold. In vivo results indicated that DBM modified with miR-106a-5p-sEVs showed an enhanced capacity for bone regeneration. This important finding further emphasizes that sEV-mediated miR-106a-5p transfer plays a critical role in osteogenesis and indicates a novel communication mode between osteoclasts and BMSCs.

With the increasing demand for high-temperature piezoelectric ceramics, excellent piezoelectricity and high Curie temperature are required simultaneously. Herein, combining the advantages of constructing new-type solid solutions and traditional A-site doping strategy, Aurivillius ferroelectrics (Na0.5Bi0.5)0.5− x/2(Li0.5Ce0.5) x/2Bi2.5Ti0.5Nb1.5O9 (NBTN-LC100 x, x = 0–0.16) were designed to achieve the large piezoelectric response and high Curie temperature simultaneously. The existence of a pseudo-tetragonal phase boundary together with the reduction of domain size produces a large piezoelectric coefficient ( d33 ∼ 24.6 pC/N) with a fairly high TC (∼825 °C). Moreover, pseudo-tetragonal distortion might be responsible for the excellent thermal stability of d33 against thermal depolarization temperature ( Td). For NBTN-LC12, high-temperature electric resistivity is still above 1 × 105 Ω cm at 600 °C. The improved comprehensive properties of NBTN-LC100 x ceramics demonstrate that the construction of a novel Aurivillius ferroelectrics is a promising way to explore high-temperature sensor materials.

Individual survival prediction and risk stratification are of vital importance to optimize the individualized treatment of metastatic leiomyosarcoma (LMS) patients. This study aimed to identify the prognostic factors for metastatic LMS patients and establish prognostic models for overall survival (OS) and cancer-specific survival (CSS). The data of LMS patients with metastasis between 2010 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The entire cohort was randomly divided into a training cohort and a validation cohort. The influences of primary tumor site, localized and distant metastases, and sites and number of metastases on the prognosis of metastatic LMS patients were firstly explored by Kaplan–Meier curves and log-rank tests. Furthermore, the effective therapeutic regimens and prognosticators for metastatic LMS patients were also analyzed by Cox analysis. In addition, two prognostic nomograms for OS and CSS were established, and their predictive performances were evaluated by the methods of receiver operating characteristic (ROC) curves, time-dependent ROC curves, calibration curves, and decision curve analysis (DCA). A total of 498 patients were finally collected from the SEER database and were randomly assigned to the training set (N = 332) and validation set (N = 166). No significant differences in OS were observed in patients with distant organ metastasis and localized metastasis. For patients who have already developed distant organ metastasis, the sites and number of metastases seemed to be not closely associated with survival. Patients who received chemotherapy got significantly longer survival than that of their counterparts. In univariate and multivariate Cox analyses, variables of surgery, chemotherapy, age, and tumor size were identified as independent predictors for OS and CSS, and distant metastasis was also independently associated with CSS. The areas under the curve (AUCs) of ROC curves of the nomogram for predicting 1-, 3-, and 5-year OS were 0.770, 0.800, and 0.843, respectively, and those for CSS were 0.777, 0.758, and 0.761, respectively. The AUCs of time-dependent AUCs were all over 0.750. The calibration curves and DCA curves also showed excellent performance of the prognostic nomograms. Metastasis is associated with reduced survival, while the sites and the number of metastases are not significantly associated with survival. The established nomogram is a useful tool that can help to perform survival stratification and to optimize prognosis-based decision-making in clinical practice.

ObjectivesThe prevalence of childhood hypertension is rising in parallel with the increasing prevalence of overweight and obesity in children. How growth trajectories from childhood to puberty relate to high blood pressure (HBP) is not well defined. We aimed to characterise potential body mass index (BMI) dynamic changing trajectories from childhood to puberty and investigate their association with HBP.DesignA dynamic prospective cohort.SettingChina Health and Nutrition Survey 1991–2015.ParticipantsThere were 1907 participants (1027 men and 880 women) in this study.OutcomesThe primary outcome was HBP defined as systolic blood pressure (SBP)/diastolic blood pressure (DBP) exceeding the standards or diagnosis by medical records or taking antihypertensive medication.ResultsA model of cubic parameters with three groups was chosen, labelled as normal increasing group (85.16%, n=1624), high increasing group (9.81%, n=187) and resolving group (5.03%, n=96). Compared with the normal increasing group, the unadjusted HRs (95% CIs) for the resolving and high increasing groups were 0.91 (0.45 to 1.86) and 1.88 (1.26 to 2.81), respectively. After adjusting for baseline age, region, sex, baseline BMI z-score, baseline SBP and baseline DBP in model 3, the HRs (95% CIs) for the resolving and high increasing groups were 0.66 (0.30 to 1.45) and 1.56 (1.02 to 2.38).ConclusionsThese results indicate that the BMI trajectories from childhood to puberty have significant impact on HBP risk. Puberty is a crucial period for the development of HBP.

Background Alzheimer’s disease (AD) is the most common dementia worldwide, and there is still no satisfactory drug or therapeutic strategy. Polygala tenuifolia is a traditional Chinese medicine with multiple neuroprotective effects. In present study, we investigated the effects of three active constituents [3,6′-disinapoyl sucrose (DISS), onjisaponin B (OB) and tenuifolin (TEN)] of Polygala tenuifolia (PT) on the proliferation and differentiation of neural stem cells (NSCs) to identify the potential active constituent of PT promoting hippocampal neurogenesis. Methods NSCs were isolated from hippocampi of newborn C57BL/6 mice, and transfected with mutant amyloid precursor protein (APP) gene to establish an AD cell model (APP-NSCs). 3-(4,5- Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays were performed, and the proliferation and differentiation of NSCs were assessed by neurosphere formation assay, 5-bromo-2′-deoxyuridine (BrdU) incorporation assay and immunofluorescence (IF) staining analysis. APP/PS1 transgenic mice were administrated with the potential active constituent DISS for 4 weeks. Morris water maze (MWM), Nissl staining assay and IF staining assays were carried out to evaluate the cognitive function, neural damages and hippocampal neurogenesis, respectively. Results DISS exerted the optimal ability to strengthen APP-NSCs proliferation and neuronal differentiation, followed by OB and TEN. Furthermore, DISS treatment for 4 weeks strikingly rescued the cognitive deficits, neuronal injures, and neurogenesis disorder in adult APP/PS1 transgenic mice. Conclusions Our findings demonstrated that DISS is the constituent of PT that triggers the most potent increase of hippocampal neurogenesis in our mouse model of AD.

Small extracellular vesicles (sEVs) are considered to play critical roles in intercellular communications during normal and pathological processes since they are enriched with miRNAs and other signal molecules. In bone remodeling, osteoclasts generate large amounts of sEVs. However, there is very little research about whether and how osteoclast-derived sEVs (OC-sEVs) affect surrounding cells. In our study, microarray analysis identified miR-106a-5p highly enriched in OC-sEV. Further experiments confirmed that OC-sEVs inhibited Fam134a through miR-106a-5p and significantly promoted bone mesenchymal stem cell (BMSC) osteogenic mineralization in vitro. Next, we prepared sEV-modified demineralized bone matrix (DBM) as a repair scaffold, and used a calvarial defect mouse model to evaluate the pro-osteogenic activities of the scaffold. In vivo result indicated DBM modified with miR-106a-5p-sEVs showed an enhanced capacity of bone regeneration. This important finding further emphasizes that sEV-mediated miR-106a-5p transfer play critical roles in osteogenesis and indicate a novel communication mode between osteoclasts and BMSCs.

This paper presents an intelligent permanent magnet synchronous motor-based servo drive system used in automated piano tuning applications. The permanent magnet synchronous motor-based drives are able to improve the accuracy of the piano tuning process in comparison with the traditional direct-current motor-based and step motor-based servo drives. To explain the techniques, firstly, the structure and principles of the automated piano tuning devices with a surface-mounted permanent magnet synchronous motor-based drive system integrated are introduced, illustrating that it is feasible to implement the proposed piano tuning strategy. Secondly, the piano tuning devices have two functions: low-speed rotation and position holding. To ensure that the surface-mounted permanent magnet synchronous motor can rotate stably over the low-speed range with strong anti-interference capacity, a double closed-loop speed-regulation-based control scheme is employed. And to ensure high position control performance, a fuzzy-adaptive triple closed-loop position-regulation-based control scheme is employed. It terms of the control schemes, it deserves to be mentioned that main contributions include, firstly, the parameters of the proportional integral controllers in the double closed-loop speed-regulation structure is tuned relying on both stability and bandwidth analyses. Then, a fuzzy-adaptive proportional integral controller is specially-designed for the triple closed-loop position-regulation to adapt to the piano tuning applications. Simulation is conducted on a 20 rpm three-phase permanent magnet synchronous motor servo drive-based piano tuning system to validate the proposed piano tuning method and to verify the proposed control techniques.

The interface between metal nanoparticles (NPs) and support plays a vital role in catalysis because both electron and atom exchanges occur across the metal-support interface. However, the rational design of interfacial structure facilitating the charge transfer between the neighboring parts remains a challenge. Herein, a guided nucleation strategy based on redox reaction between noble metal precursor and support-surface is introduced to construct epitaxial interfaces between Pt NPs and CeO2 support. The Pt/CeO2 catalyst exhibits near room temperature catalytic activity for CO oxidation that is benefited from the well-defined interface structure facilitating charge transfer from CeO2 support to Pt NPs. Meanwhile, this general approach based on support-surface-induced-nucleation was successfully extended to synthesize Pd and Cu nanocatalysts on CeO2, demonstrating its universal and feasible characteristics. This work is an important step towards developing highly active supported metal catalysts by engineering their interfaces.

Circular RNA (circRNA) has been reported to have great scientific significance and clinical value in multiple cancers including colorectal cancer (CRC). However, the biological function of most circRNAs in CRC is still in its infancy. Herein, we discovered the differential expressed circRNAs (DECs) between CRC tissues and matched adjacent using deep RNA sequencing and further confirmed the DECs expression by combining with another Gene Expression Omnibus dataset. Furthermore, we validated the expression of the top four upregulated circRNAs (hsa_circ_0030632, hsa_circ_0004887, hsa_circ_0001550, and hsa_circ_0001681) in both of paired CRC tissues and CRC cell lines. Then, a circRNA/microRNA/messenger RNA regulatory network was established and the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed these four circRNAs participated in various biological processed including apoptotic process and multiple metabolic processes. Moreover, based on the regulatory network, three bioactive compounds (pergolide, pivampicillin, and methylergometrine) for the treatment of CRC were also found. In conclusion, this study improved our understanding of circRNAs and may also facilitate the finding of promising targets and biomarkers in CRC.

SaaS software that provides services through cloud platform has been more widely used nowadays. However, when SaaS software is running, it will suffer from performance fault due to factors such as the software structural design or complex environments. It is a major challenge that how to diagnose software quickly and accurately when the performance fault occurs. For this challenge, we propose a novel performance fault diagnosis method for SaaS software based on GBDT (Gradient Boosting Decision Tree) algorithm. In particular, we leverage the monitoring mean to obtain the performance log and warning log when the SaaS software system runs, and establish the performance fault type set and determine performance log feature. We also perform performance fault type annotation for the performance log combined with the analysis result of the warning log. Moreover, we deal with the incomplete performance log and the type non-equalization problem by using the mean filling for the same type and combination of SMOTE (Synthetic Minority Oversampling Technique) and undersampling methods. Finally, we conduct an empirical study combined with the disaster reduction system deployed on the cloud platform, and it demonstrates that the proposed method has high efficiency and accuracy for the performance diagnosis when SaaS software system runs.

Zinc-bromine flow batteries are promising for stationary energy storage, and bromine-complexing agents have been used to form phase-separated liquid polybromide products. However, an understanding of the dynamics of polybromide nucleation is limited due to the beam sensitivity and complexity of polybromides. Here we report an in operando platform composed of dark-field light microscopy and a transparent electrochemical cell to reveal the dynamics of polybromide formation in their native environment. Using our platform, we confirm and reveal the liquid nature, chemical composition, pinning effect (strong interaction with Pt), residual effect (residual charge products on the surface), self-discharging, and over-oxidation of the polybromide products. The results provide insights into the role of complexing agents and guide the future design of zinc-bromine flow batteries. Furthermore, our in operando platform can potentially be used to study sensitive species and phases in other electrochemical reactions.

The service stability and safety of nanoscale working cells is an inescapable issue for their larger-scale adoption in industry. Previous works on device design and manufacture in most case would ignore this problem due to the lack of proper accessible techniques. This article presents the initial physical assessment on the Bi2S3 nanowires in virtue of in situ techniques with a microscope. The Bi2S3 compounds prepared via deposition method are potentially applicable for visible-NIR photodetectors with a responsivity of 3.57 A/W. However, the fracture of an individual Bi2S3 nanowire accompanied by a demonstrated change in crystal structure was directly observed, due to Joule Heating under a high bias. In addition, the uniaxial bending will lead to a drop of conductance in nanowires, attributed to a local electric field generated across the radial direction of the nanowire. More importantly, the Young's modulus for the Bi2S3 nanowires, ∼84.7 ± 2 GPa, was firstly reported through in situ experiments, confirming a soft nature of Bi2S3 nanowires as compared to silicon or germanium counterparts, which supports their application in flexible devices. The sum of these findings is of significance for original design and manufacture of more reliable optoelectronic devices and systems in future.

Solid polymer electrolytes (SPEs) have the potential to enhance the safety and energy density of lithium batteries. However, poor interfacial contact between the lithium metal anode and SPE leads to high interfacial resistance and low specific capacity of the battery. In this work, we present a novel strategy to improve this solid-solid interface problem and maintain good interfacial contact during battery cycling by introducing an adaptive buffer layer (ABL) between the Li metal anode and SPE. The ABL consists of low molecular-weight polypropylene carbonate , poly(ethylene oxide) (PEO), and lithium salt. Rheological experiments indicate that ABL is viscoelastic and that it flows with a higher viscosity compared to PEO-only SPE. ABL also has higher ionic conductivity than PEO-only SPE. In the presence of ABL, the interface resistance of the Li/ABL/SPE/LiFePO4 battery only increased 20% after 150 cycles, whereas that of the battery without ABL increased by 117%. In addition, because ABL makes a good solid-solid interface contact between the Li metal anode and SPE, the battery with ABL delivered an initial discharge specific capacity of >110 mA·h/g, which is nearly twice that of the battery without ABL, which is 60 mA·h/g. Moreover, ABL is able to maintain electrode-electrolyte interfacial contact during battery cycling, which stabilizes the battery Coulombic efficiency.

In bone remodeling, after a lifespan of ∼2 weeks, osteoclasts undergo apoptosis in each bone turnover cycle, resulting in generation of a large number of apoptotic bodies (ABs). However, the biological roles of osteoclast-derived ABs (OC-ABs) in bone remodeling have not been investigated and remain unknown. In this study, we stimulated bone marrow macrophages with receptor activator of NF-κB ligand (RANKL) to obtain both preosteoclasts and mature osteoclasts (mOCs). We then used alendronate to induce apoptosis in preosteoclasts and mOCs and generate the respective ABs and used flow cytometry and immunoblotting to characterize the sizes and immunogenic characteristics of the extracted ABs. We show that mOC-ABs are engulfed by preosteoblastic MC3T3-E1 cells and promote the viability of these cells. Among all osteoclast-derived extracellular vesicles, mOC-ABs had the highest osteogenic potency. We further observed that mOC-ABs had the highest vesicular receptor activator of NF-κB (RANK) levels among all types of osteoclast-derived extracellular vesicles. Of note, masking of vesicular RANK by soluble RANKL strongly abolished the osteogenic potency of osteoclast-derived ABs. Mechanistically, we found that mOC-ABs induce osteoblast differentiation by activatingPI3K/AKT/mechanistic target of rapamycin (mTOR)/ribosomal protein S6 kinase signaling. In conclusion, OC-ABs promote osteogenic differentiation by stimulating osteoblast differentiation via activation of RANKL reverse signaling. These findings provide important insights into the reversal phase between the bone resorption and formation stages during bone remodeling and identify an AB-dependent cellular signaling mechanism in osteoclast–osteoblast coupling.

Polyetheretherketone (PEEK) is a potential bone repair material because of its stable chemical and good mechanical properties. However, the biological inertness of PEEK limits its clinical application. Sr

For the landing process of a large-scale airdrop system, flared-maneuver is a common approach to decelerate to prevent huge impacts while touching down. A 6-DOF model of parafoil-load system is used to investigate the effects of different deflection modes on airdrop system’s landing performance. By numerical simulation, three main factors, distance of deflection, rate of deflection and the pattern of rate changing, are discussed according to the results. The conclusion derived is of some significance in assisting control and design of landing procedure of such unpowered heavy airdrop systems.

With the advent of the post-epidemic era, the energy consumption characteristics of hotels have changed, which has an important impact on urban energy conservation. In order to contribute to the goal of carbon neutrality, this study discusses the energy-saving operation strategy of hotels considering the impact of the COVID-19 epidemic. Based on the energy consumption characteristics of large public buildings, this paper analyzes the energy consumption distribution and operation characteristics of hotel buildings in detail. By collecting energy consumption data from five typical large hotel buildings in a tourist city in southern China from 2018 to 2022, the impact of COVID-19 on hotel energy consumption and hotel business characteristics was discussed in detail. Combined with the economic development characteristic in the post-epidemic era, this paper explores the energy-saving strategies that hotels can adopt in the context of normalized epidemic prevention and control and obtains the optimal path of low-carbon economic operation of hotel buildings. This study reveals the energy consumption characteristics and energy-saving potential of hotel buildings, and provides enlightenment for hotel management and low-carbon development in the post-epidemic era.

Silicon possesses a high theoretical specific capacity and is a promising high-performance anode material for lithium-ion batteries (LIBs). However, it shows a poor cycling performance because of volume expansion. A hollow structure can improve Si cycling performance, and the template method is one of the most common methods for hollow micro/nanosphere preparation. A polystyrene (PS) microsphere has the advantages of having a uniform and controllable particle size, easy modification, and high stability, thus being an ideal template for preparing hollow structure material. Herein, PS microspheres are used as templates to obtain hollow silica spheres, and then obtain hollow silicon spheres with an inner pore diameter of ~50 nm by a magnesium thermal reduction method. Lithium-ion battery anode material is obtained using carbon nanotubes supporting hollow silicon spheres (Si-CNTs). Si-CNTs exhibit excellent cycling performance (1188 mAh g−1 after 200 cycles) and excellent rate capability (484 mAh g−1 at 1 A g−1). Hollow porous Si-CNTs show great potential, providing a promising idea for solving the volume expansion problem of Si.

The Li+ diffusion coefficient of Co2VO4 is evaluated by theoretical calculation to be as high as 3.15 × 10–10 cm2 s−1, theoretically proving Co2VO4 a promising anode in fast-charging lithium-ion batteries.A hexagonal porous Co2VO4 nanodisk (PCVO ND) structure is designed, featuring a high specific surface area of 74.57 m2 g−1 and numerous pores with a pore size of 14 nm.The PCVO ND shows excellent fast-charging performance (a high average capacity of 344.3 mAh g−1 at 10 C for 1000 cycles with only 0.024% capacity loss per cycle for 1000 cycles). Supplementary Information The online version contains supplementary material available at 10.1007/s40820-021-00758-5., High-energy–density lithium-ion batteries (LIBs) that can be safely fast-charged are desirable for electric vehicles. However, sub-optimal lithiation potential and low capacity of commonly used LIBs anode cause safety issues and low energy density. Here we hypothesize that a cobalt vanadate oxide, Co2VO4, can be attractive anode material for fast-charging LIBs due to its high capacity (~ 1000 mAh g−1) and safe lithiation potential (~ 0.65 V vs. Li+/Li). The Li+ diffusion coefficient of Co2VO4 is evaluated by theoretical calculation to be as high as 3.15 × 10–10 cm2 s−1, proving Co2VO4 a promising anode in fast-charging LIBs. A hexagonal porous Co2VO4 nanodisk (PCVO ND) structure is designed accordingly, featuring a high specific surface area of 74.57 m2 g−1 and numerous pores with a pore size of 14 nm. This unique structure succeeds in enhancing Li+ and electron transfer, leading to superior fast-charging performance than current commercial anodes. As a result, the PCVO ND shows a high initial reversible capacity of 911.0 mAh g−1 at 0.4 C, excellent fast-charging capacity (344.3 mAh g−1 at 10 C for 1000 cycles), outstanding long-term cycling stability (only 0.024% capacity loss per cycle at 10 C for 1000 cycles), confirming the commercial feasibility of PCVO ND in fast-charging LIBs. Supplementary Information The online version contains supplementary material available at 10.1007/s40820-021-00758-5.

Interrupted sampling pulse repeating jamming is a new type of range deception jamming, which can produce deceptive and suppressive jamming effects on chirp radars. In addition, the jammer has the ability to instantaneously forward such jamming, so that the traditional waveform diversity technology cannot achieve the suppression of such range deception jamming. Therefore, this paper proposes a dictionary learning method based on the quasi-KLT base, which can realize the separation of the target and the jamming signal, and finally achieve the purpose of suppressing the jamming. The results of simulation experiments show that the proposed method can effectively combat the interrupted sampling and repeating range false target jamming.

A low observability electromagnetic protective clothing design method based on artificial magnetic conductor(AMC) structure is proposed. The basic principle of reducing the reflected energy of electromagnetic wave with AMC structure and the typical structure design workflow are introduced. Taking a small vessel model as an example, the maximum radar cross-sectional area corresponding to the typical incident direction before and after the installation is compared and analyzed through simulation calculation, and the effectiveness of the proposed design method in reducing the radar cross-sectional area of the vessel is verified.

This paper established a river flow velocity measurement model in the clutter background of microwave scattering signals generated by Pierson-Moscowitz spectrum. First, the cloud data of the river are generated based on the random wave model and an electromagnetic calculation model is established. Second, the echo signal of the river is obtained based on the fullwave computational electromagnetic algorithm. Finally, the doppler frequency shift of the echo signal is calculated to deduce the river flow speed. Simulation result show that the proposed river velocity microwave measurement model is valid which has high accuracy.

Studying the neurological, genetic and evolutionary basis of human vocal communication mechanisms is an important field of neuroscience. In the absence of high quality data on humans, mouse vocalization experiments in laboratory settings have been proven to be useful in providing valuable insights into mammalian vocal development and evolution, including especially the impact of certain genetic mutations. Data sets from mouse vocalization experiments usually consist of categorical syllable sequences along with continuous inter-syllable interval times for mice of different genotypes vocalizing under various contexts. Few statistical models have considered the inference for both transition probabilities and inter-state intervals. The latter is of particular importance as increased inter-state intervals can be an indication of possible vocal impairment. In this paper, we propose a class of novel Markov renewal mixed models that capture the stochastic dynamics of both state transitions and inter-state interval times. Specifically, we model the transition dynamics and the inter-state intervals using Dirichlet and gamma mixtures, respectively, allowing the mixture probabilities in both cases to vary flexibly with fixed covariate effects as well as random individual-specific effects. We apply our model to analyze the impact of a mutation in the Foxp2 gene on mouse vocal behavior. We find that genotypes and social contexts significantly affect the inter-state interval times but, compared to previous analyses, the influences of genotype and social context on the syllable transition dynamics are weaker., 40 pages, 7 figures

Monoclinic gallium oxide (β-Ga

Introduction Degeneration changes of the basal forebrain (BF) are suggested to play an important role in cognitive impairment and memory loss in patients with Alzheimer's disease and Parkinson's disease. However, little is known about if and how the structure and function of BF are abnormal in Wilson's disease (WD). Methods Here, we employed the structural and resting‐state functional magnetic resonance imaging (fMRI) data from 19 WD individuals and 24 healthy controls (HC). Voxel‐based morphometry (VBM) and functional connectivity analysis were applied to investigate the structural and functional degeneration changes of BF in WD. Moreover, the linear regression analyses were performed in the patient group to depict the correlations between the aberrant gray volume and functional connectivity of the BF and clinical performances, such as the prospective memory (PM) and mini‐mental state examination (MMSE). Results VBM analysis showed that compared with HC, the volume of overlapping cell groups of BF termed CH1–3 and CH4 was significantly reduced in WD. Additionally, the decreased functional connectivity of the CH4 was distributed in the bilateral temporal‐parietal junction (TPJ), right thalamus, orbitofrontal gyrus (ORB), and left middle cingulate cortex (MCC). The performances of the time‐based prospective memory (TBPM) and event‐based prospective memory (EBPM) were related to reduced functional connectivity between CH4 and right ORB. Besides, the functional connectivity of left TPJ was also significantly correlated with EBPM in WD. Conclusion These findings indicated that the degenerative changes of BF may affect PM through the innervation brain function and may help to understand the neural mechanisms underlying cognitive impairment in WD., Voxel‐based morphometry (VBM) and functional connectivity analysis based on RS‐fMRI were applied to investigate the structural and functional degeneration changes of basal forebrain in Wilson's disease. The linear regression analyses were performed to depict the correlations between the aberrant functional connectivity of the basal forebrain and clinical variables, such as the prospective memory (PM) and Mini‐mental State Examination (MMSE) performances. Degeneration changes of basal forebrain affect PM by innervated brain function and may help to understand the neural mechanisms underlying cognitive impairment in WD.

A20 is a potent anti-inflammatory protein that mediates both inflammation and ubiquitination in mammals, but the related mechanisms are not clear. In this study, we performed mass spectrometry (MS) screening, gene ontology (GO) analysis, and coimmunoprecipitation (co-IP) in a lipopolysaccharide (LPS)-induced inflammatory cell model to identify novel A20-interacting proteins. We confirmed that the E3 ubiquitin ligase Nrdp1, also known as ring finger protein 41 (RNF41), interacted with A20 in LPS-stimulated cells. Further co-IP analysis demonstrated that when A20 was knocked out, degradation-inducing K48-linked ubiquitination of inflammatory effector MyD88 was decreased, but protein interaction-mediating K63-linked ubiquitination of another inflammatory effector TBK1 was increased. Moreover, western blot experiments showed that A20 inhibition induced an increase in levels of MyD88 and phosphorylation of downstream effector proteins as well as of TBK1 and a downstream effector, while Nrdp1 inhibition induced an increase in MyD88 but a decrease in TBK1 levels. When A20 and Nrdp1 were coinhibited, no further change in MyD88 was observed, but TBK1 levels were significantly decreased compared with those upon A20 inhibition alone. Gain- and loss-of-function analyses revealed that the ZnF4 domain of A20 is required for Nrdp1 polyubiquitination. Upon LPS stimulation, the inhibition of Nrdp1 alone increased the secretion of IL-6 and TNF-α but decreased IFN-β secretion, as observed in other studies, suggesting that Nrdp1 preferentially promotes the production of IFN-β. Taken together, these results demonstrated that A20/Nrdp1 interaction is important for A20 anti-inflammation, thus revealing a novel mechanism for the anti-inflammatory effects of A20.

Background Our objective is to investigate whether obtaining a higher level of education was causally associated with lower breast cancer risk and to identify the causal mechanism linking them. Methods Firstly, we performed a meta-analysis for educational attainment on breast cancer using 33 MR studies, including 15 case-control studies, 10 cross-sectional studies, and 8 cohort studies. Secondly, the main data analysis used publicly available summary-level data from two large GWAS consortia (Breast Cancer Association Consortium [BCAC] and the Social Science Genetic Association Consortium [SSGAC]). Mendelian randomization (MR) analysis used 65 genetic variants derived from the SSGAC as instrumental variables for years of schooling. The outcomes were the overall breast cancer risk (122,977 cases/105,974 controls in women) and its two subtypes: estrogen receptor (ER)-positive breast cancer (ER+: 69,501 cases) and ER-negative breast cancer (ER-: 21,468 cases). Furthermore, six additional consortia were analyzed to investigate the causal pathways from education to breast cancer. The fixed and random effects inverse variance weighted methods were used to estimate the causal effects, along with other additional MR methods as sensitivity analyses. Results The results showed that each additional standard deviation of 4.2 years of education was causally associated with a 27% lower risk of ER- (OR 0.73, 95% CI [0.64, 0.84]; P-value

Aldehyde dehydrogenase 6 family member A1 (ALDH6A1) is associated with multiple diseases, but its pathogenesis in colon cancer (CC) is ambiguous and needs further study so that this research explores the function of ALDH6A1 in CC.The level of ALDH6A1 in colon adenocarcinoma (COAD), CC tissues, and cells was measured by starBase v2.0, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot. Post transfection with overexpressed (oe)-ALDH6A1, cell biological behaviors, as well as apoptosis-, matrix metalloproteinase (MMP)-, and rat sarcoma virus (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway-related markers were measured by cell function experiments, qRT-PCR, and western blot. Next, the effects of small interfering RNA targeting ALDH6A1 (si-ALDH6A1) and RAS/RAF inhibitor (MCP110) on cell biological behaviors, as well as apoptosis-, MMP-, and RAS/RAF/MEK/ERK pathway-related markers were detected again.ALDH6A1 was low-expressed in COAD, CC tissues, and cells. Oe-ALDH6A1 weakened cell vitality, migration and invasionbut facilitated apoptosis; while it reduced expression levels of Bcl-2, MMP-2, MMP-9 and the RAS/RAF/MEK/ERK pathway-related markers but promoted Bax level. However, the regulation of si-ALDH6A1 on cell biological behaviors and related genes was opposite to that of oe-ALDH6A1. Moreover, MCP110 rescued the regulation of si-ALDH6A1 on cell biological behaviors, expressions of apoptosis- MMP- as well as RAS/RAF/MEK/ERK pathway-related markers. To sum up, ALDH6A1 attenuated CC progression by down-regulating the expressions of RAS/RAF/MEK/ERK pathway-related markers.

As one of the most studied ribonucleic acid (RNA) modifications in eukaryotes, N6‐methyladenosine (m6A) has been shown to play a predominant role in controlling gene expression and influence physiological and pathological processes such as oncogenesis and tumor progression. Writer and eraser proteins, acting opposite to deposit and remove m6A epigenetic marks, respectively, shape the cellular m6A landscape, while reader proteins preferentially recognize m6A modifications and mediate fate decision of the methylated RNAs, including RNA synthesis, splicing, exportation, translation, and stability. Therefore, RNA metabolism in cells is greatly influenced by these three classes of m6A regulators. Aberrant expression of m6A regulators has been widely reported in various types of cancer, leading to cancer initiation, progression, and drug resistance. The close links between m6A and cancer shed light on the potential use of m6A methylation and its regulators as prognostic biomarkers and drug targets for cancer therapy. Given the notable effects of m6A in reversing chemoresistance and enhancing immune therapy, it is a promising target for combined therapy. Herein, we summarize the recent discoveries on m6A and its regulators, emphasizing their influences on RNA metabolism, their dysregulation and impacts in diverse malignancies, and discuss the clinical implications of m6A modification in cancer., As one of the best studied ribonucleic acid (RNA) modifications in eukaryotes, N6‐methyladenosine (m6A) plays a predominant role in controlling gene expression and further influences physiological and pathological processes, including oncogenesis and tumor progression. Here we review the functions of m6A and its regulators in RNA metabolism control, their oncogenic or tumor suppressive roles in diverse malignancies, as well as the application of m6A methylation in cancer diagnosis and therapeutics.