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• Fe-doped Ni-based catalysts have been prepared in a facile method. • Fe doping reduced the hydroxyl and oxygen vacancies in the support. • Strong metal-support interaction suppressed, exposed active sites increased. • Catalytic activity for CO 2 methanation is improved by about an order. CO 2 methanation is an effective way for CO 2 recycling, and nickel-based catalysts have attracted much attention in this field due to their excellent CH 4 selectivity and cost-effectiveness; however, their applications are limited by their suboptimal catalytic activity. In this work, the catalytic activity of Ni-rutile-based catalysts was increased by almost an order of magnitude simply by doping the rutile with Fe. Series characterizations show that three factors that mainly contributed to the improved catalytic performance of the Ni/Fe-Rutile, which are the reduction of the Ni size, the increase of the basic sites, and the inhibition of the encapsulation of the Ni particles by the support. With Fe doping, the OH and oxygen vacancies on the rutile surface were reduced, which made the support difficult to reduce and thus suppressed the encapsulation of Ni by the support. As a result, the number of exposed active sites on the Ni/Fe-Rutile which with a smaller Ni size was further successfully increased, and the catalytic activity was significantly improved. This study provides new ideas for the design of activity-enhanced supported catalysts from the perspective of tuning the metal-support interaction and may be applicable to other reducible oxide-supported metal catalysts. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid carcinoma (PTC) is a common endocrine malignancy. Studies have indicated that estrogen can regulate the expression of miRNAs in numerous malignancies. MiR-570-3p has been shown to have a regulatory function in various cancers. However, studies of the regulatory function of miR-570-3p and a direct link between estrogen (especially estradiol E2) and miR-570-3p in PTC have not been done. Methods: Expression of miR-570-3p and its downstream target DPP4 in PTC tissues and cells was predicted using bioinformatics and validated by qRT-PCR and western blot assays. We then performed a series of gain-and-loss experiments to assess the functional significance of miR-570-3p/DPP4 axis in PTC progression in vitro and in vivo. Additionally, the methylation of the miR-570-3p promoter region was examined via bioinformatics analysis and MSP. Finally, the effects of E2 on PTC progression and the correlation between DNMT1/DNMT3A and EZH2 were predicted by bioinformatic tools and proved by luciferase reporter, ChIP, and co-IP assays. Results: In PTC tumor tissues and cell lines, there was a lower expression level and a higher methylation level of miR-570-3p compared to normal tissues and cell lines. DPP4 was identified as the downstream target of miR-570-3p. Overexpression of miR-570-3p reduced the proliferative, migratory, and invasive capabilities, and promoted apoptosis, while overexpression of DPP4 reversed these effects in PTC cells. It was also discovered that DNMT1 and DNMT3A increased the CpG methylation level of the miR-570-3p promoter in an EZH2-dependent manner, which led to decreased expression of miR-570-3p. Furthermore, we observed that estrogen (E2) enhanced the methylation of miR-570-3p and suppressed its expression levels, resulting in augmented tumor growth in vivo in PTC. Conclusion: Estrogen regulates the EZH2/DNMTs/miR-570-3p/DPP4 signaling pathway to promote PTC progression. [ABSTRACT FROM AUTHOR]

In order to analyze the mechanical properties of a new type of retrievable vena cava filter, the Denali and Aeginsy retrievable filters are selected, and the in vivo and in vitro mechanical properties of the three types of retrievable vena cava filters are compared. The nonlinear deformation process of the filter which is pressed into the transport sheath, flicked and released into the vascular vessel is simulated by using the finite element method, and the mechanical behaviors of the filter and the blood vessel wall are analyzed. During the crimping process, the elastic strain peak value of the filter wall increases with increasing amount of grip. The maximum elastic strain peak value of the three filters is less than 8%, and the safety factor is greater than 2, which meets the strength requirement. Equivalent stress and strain on the vascular wall decreases along the direction of blood flow after the filter is opened. The peak value of equivalent stress and strain on the vascular wall corresponding to Aegisy filter is the largest, and the impact on the vascular wall is the largest. The total displacement of the three filters under the action of thrombus and blood fluids is not more than 80 μ m. The impact of the new filter on the vascular wall is smaller than that of Aegisy filter, and the total displacement after implantation is smaller than that of Denali filter. The results are valuable for the evaluation and clinical application of the new vena cava filter. [ABSTRACT FROM AUTHOR]

Background: Hearing loss has been associated with serious health problems around the globe. Previous studies have found the positive effects of fitting hearing aids on health, but few studies were conducted in developing countries. The aim of this study is to examine the effects of hearing aids on multiple health outcomes among middle-aged and older adults with hearing loss in rural China.Methods: In this randomized controlled trial (RCT), participants aged 45 and above were randomly assigned to the treatment group prescribing with hearing aids or to the control group with no intervention. Trial outcomes for 385 participants were collected during the 20-month follow-up study. Using the difference-in-difference approach, our primary outcomes were hearing-related quality of life (QoL) and generic QoL.Results: The intervention led to improvements in hearing-related QoL, presenting as the reduction in Hearing Handicap Inventory for the Elderly Screening Version (HHIE-S) scores (interaction coefficient = - 2.86, p = 0.005), HHIE-S-Emotional scores (interaction coefficient = - 1.42, p = 0.029), and HHIE-S-Situational scores (interaction coefficient = - 1.43, p = 0.007). The intervention was also effective in alleviating the increase in depressive symptoms (interaction coefficient = - 0.14, p = 0.042). Subgroup analysis revealed that the effects were only shown among people with social activities or active social networks.Conclusions: Our study is the first RCT in China to measure the health effects and heterogeneity of hearing aid interventions. Wearing hearing aids can help improve hearing-related QoL and alleviate the increase in depressive symptoms. The intervention is expected to be applicable to similar settings in other developing countries to combat hearing-related health problems.Trial Registration: Chinese Clinical Trial Registry, ChiCTR1900024739 . Registered on 26 July 2019. [ABSTRACT FROM AUTHOR]

Summary The comprehensive analysis of the proteome and its modulation by post-translational modification (PTM) is increasingly used in biological and biomedical studies. As a result, proteomics data analysis is ever more carried out by scientists with limited expertise in this type of data. While excellent software solutions for comprehensive and rigorous analysis of quantitative proteomic data exist, most are complex and not well suited for non-proteomics scientists. Integrative analysis of multi-level proteomics data on protein and diverse PTMs, like phosphorylation or proteolytic processing, remains particularly challenging and inaccessible to most biologists. To fill this void, we developed SQuAPP, an R-Shiny web-based analysis pipeline for the quantitative analysis of proteomic data. SQuAPP uses a streamlined workflow model to guide expert and novice users through quality control, data pre-processing, statistical analysis and visualization steps. Processing the protein, peptide and PTM datasets in parallel and their quantitative integration enable rapid identification of protein-level-independent modulation of protein modifications and intuitive interpretation of dynamic dependencies between different protein modifications. Availability and implementation SQuAPP is available at http://squapp.langelab.org/. The source code and local setup instructions can be accessed from https://github.com/LangeLab/SQuAPP. [ABSTRACT FROM AUTHOR]

The research on nonintrusive load monitoring (NILM) typically focuses on residential and commercial users. However, high-energy industrial users also require load monitoring analysis to understand their electricity consumption patterns and load operating conditions. Currently used load monitoring methods and parameters are not applicable to industrial environments. In this paper, we propose an innovative multichannel low window sequence-to-point (MLSP) method based on deep neural networks for NILM of high-energy industrial users. First, the data from each channel of the main line terminal are normalized and then aggregated into a time series, which is several times longer than the original data to expand its data volume. Then, the multichannel low window sequence-to-point method is used to select the window data of several times the length, corresponding to the active power of the target device. Finally, the discriminative features of the data are learned using a deep neural network model. The analysis of actual industrial user data shows that the lowest mean absolute error (MAE) of the original sequence-to-point method for related branches is 20.38, and the highest correlation coefficient (CC) is 90.23%. Our proposed method reduces the MAE to 11.02 and increases the CC to 97.42%. The MAE and CC indicators of all branches decreased by 25.8% and increased by 22.4%, respectively. According to Mean Absolute Percentage Error (MAPE), the performance of this model is improved by 39.6% compared with Seq2point. Compared with the original sequence-to-point method, our proposed method achieves better load monitoring results and can more accurately decompose load fluctuations, which are closer to the actual load curve. [ABSTRACT FROM AUTHOR]

Serine metabolism is involved in the fate decisions of immune cells; however, whether and how de novo serine synthesis shapes innate immune cell function remain unknown. Here, we first demonstrated that inflammatory macrophages have high expression of phosphoglycerate dehydrogenase (PHGDH, the rate-limiting enzyme of de novo serine synthesis) via nuclear factor κB signaling. Notably, the pharmacological inhibition or genetic modulation of PHGDH limits macrophage interleukin (IL)-1β production through NAD+ accumulation and subsequent NAD+-dependent SIRT1 and SIRT3 expression and activity. Mechanistically, PHGDH not only sustains IL-1β expression through H3K9/27 acetylation-mediated transcriptional activation of Toll-like receptor 4 but also supports IL-1β maturation via NLRP3-K21/22/24/ASC-K21/22/24 acetylation-mediated activation of the NLRP3 inflammasome. Moreover, mice with myeloid-specific depletion of Phgdh show alleviated inflammatory responses in lipopolysaccharide-induced systemic inflammation. This study reveals a network by which a metabolic enzyme, involved in de novo serine synthesis, mediates post-translational modifications and epigenetic regulation to orchestrate IL-1β production, providing a potential inflammatory disease target. [Display omitted] • Inflammatory macrophage activation promotes PHGDH expression through NF-κB signaling • PHGDH sustains IL-1β production by limiting the activity of NAD+-dependent SIRT1 and SIRT3 • PHGDH promotes Tlr4 transcription through histone acetylation to sustain IL-1β expression • PHGDH supports NLRP3 inflammasome activation via acetylation to maintain IL-1β maturation Wang et al. reveal that de novo serine synthesis mediates inflammatory responses by orchestrating IL-1β production via PHGDH-mediated NAD+ accumulation, which limits SIRT1 and SIRT3 expression and activation. Subsequently, sustained TLR4 transcriptional activation through H3K9/27 acetylation and acetylation-mediated NLRP3 activation supports IL-1β expression and maturation. [ABSTRACT FROM AUTHOR]

Although most studies link job stressors to negative teacher attitudes and behaviours, not all researches support the idea that stressors are solely detrimental. Using the cognitive relational theory of stress, the current study extends the emotional demand stressor (EDs) – conflict teacher–child relationship (TCR) link. Specifically, the study investigates (1) the nonlinear (curvilinear) association between emotional demand stressor and conflict TCR, and (2) the buffering effects of job resources (i.e. job autonomy 'JA' and social support 'SS') on the EDs – conflict TCR curvilinear link. Using data from pre-school teaching staff in China (N = 309), the current cross-sectional study finds evidence for (a) the curvilinear relationship between EDs and conflict TCR, and (b) the buffering role of JA and SS in this link. The study provides recommendations for managing emotional demand stressor through strategic allocation of organizational-level resources. Further implications for theories and educational practices are discussed. [ABSTRACT FROM AUTHOR]

Main observation and conclusion: The reaction of a cyclic osmacarbyne complex with sodium azide led to the formation of a ring expansion‐annulation product, a unique tetrazole annulated polycyclic metallacycle. The reaction proceeds by insertion of a nitrogen atom into the metal carbon triple bond and the second azide participating in the [2+3] cycloaddition. The successful isolation and characterization of metalla‐azirine complex and metallapyridinium derivative strongly validated the mechanism for the formation of the title complex. The work demonstrates a new strategy to enrich the varieties of aza‐metallacyclic species. [ABSTRACT FROM AUTHOR]

The local sequence context is the most fundamental feature determining the post-translational modification (PTM) of proteins. Recent technological improvements allow for the detection of new and less prevalent modifications. We found that established state-of-the-art algorithms for the detection of PTM motifs in complex datasets failed to keep up with this technological development and are no longer robust. To overcome this limitation, we developed RoLiM, a new linear motif deconvolution algorithm and webserver, that enables robust and unbiased identification of local amino acid sequence determinants in complex biological systems demonstrated here by the analysis of 68 modifications found across 30 tissues in the human draft proteome map. Furthermore, RoLiM analysis of a large-scale phosphorylation dataset comprising 30 kinase inhibitors of 10 protein kinases in the EGF signalling pathway identified prospective substrate motifs for PI3K and EGFR. [ABSTRACT FROM AUTHOR]

In order to obtain high yield pomelo peel pectin with better physicochemical properties, four pectin extraction methods, including hot acid extraction (HAE), microwave-assisted extraction (MAE), ultrasound-assisted extraction, and enzymatic assisted extraction (EAE) were compared. MAE led to the highest pectin yield (20.43%), and the lowest pectin recovery was found for EAE (11.94%). The physicochemical properties of pomelo peel pectin obtained by different methods were also significantly different. Pectin samples obtained by MAE had the highest methoxyl content (8.35%), galacturonic acid content (71.36%), and showed a higher apparent viscosity, thermal and emulsion stability. The pectin extracted by EAE showed the highest total phenolic content (12.86%) and lowest particle size (843.69 nm), showing higher DPPH and ABTS scavenging activities than other extract methods. The pectin extracted by HAE had the highest particle size (966.12 nm) and degree of esterification (55.67%). However, Fourier-transform infrared spectroscopy showed that no significant difference occurred among the different methods in the chemical structure of the extracted pectin. This study provides a theoretical basis for the industrial production of pomelo peel pectin. [ABSTRACT FROM AUTHOR]

• The 4000 commercial CORS stations in Russia require unified state regulation. • Russian CORS stations need to switch to domestic GNSS receivers and software. • Requires the creation of a nationwide data center for a network of CORS stations. The GNSS (Global Navigation Satellite Systems) continuous operating reference station network not only provides a reliable technical foundation and data support for achieving high-precision navigation and positioning services, but also can be integrated with other Earth observation systems (such as laser ranging, gravity measurement, etc.) to improve the accuracy and stability of Earth observation data. It is used to establish regional and global coordinate frameworks and provide data to support scientific research such as seismology, geo-tectonics, and oceanography. This article first systematically introduces the construction, development history and current situation of the Russian GNSS continuous operating reference station network, and then carefully analyzes the construction, operation, and application status and existing problems of the Russian reference station network. Finally, after careful consideration, it discusses the problems and challenges faced in the planning of reference station network construction, equipment localization, and national unified reference station network construction, and provides some suggestions and ideas. [ABSTRACT FROM AUTHOR]

The demands for novel and efficient therapies have gradually increased with the rising concerns of osteoporosis (OP). The most popular method in promoting bone regeneration during osteoporotic conditions consists of loading bioactive materials with different drugs to treat osteoporotic bones by either promoting the process of osteogenesis, or by inhibiting the activity of osteoclasts. By analyzing single cell sequencing results, we found that divalent metal transporter 1 (DMT1) played a role in OP. Based on our previous results, we found that melatonin (MT) suppressed expression of DMT1 induced by high glucose during OP, so we determined the efficacy of MT for the treatment of OP. However, the clinical effects of MT on OP were unsatisfactory. To enhance its biological efficacy, we combined MT with porous gelatin chitosan (chitosan) and the conductive material, PLA-b-AP-b-PLA (PAP), then determined how MT incorporation in chitosan@PAP nanoparticles affected the ability to promote MC3T3-E1 osteogenesis and mineralization, both in vitro and in vivo. The results confirmed the effect of MT on DMT1. We then prepared and characterized composites prepared as nanofibers, and determined the efficacy of MT combined with chitosan-PAP modified hydrogels as a slow-release system in a femur model of osteoporosis mice, with associated properties suitable for bone tissue engineering. The results indicated that MT-loaded chitosan@PAP nanospheres showed favorable osteogenic functions, both in vivo and in vitro, providing a practical solution for bone regeneration for OP patients. [ABSTRACT FROM AUTHOR]

Pathological conditions linked to shear stress have been identified in hematological diseases, cardiovascular diseases, and cancer. These conditions often exhibit significantly elevated shear stress levels, surpassing 1000 dyn/cm2 in severely stenotic arteries. Heightened shear stress can induce mechanical harm to endothelial cells, potentially leading to bleeding and fatal consequences. However, current technology still grapples with limitations, including inadequate flexibility in simulating bodily shear stress environments, limited range of shear stress generation, and spatial and temporal adaptability. Consequently, a comprehensive understanding of the mechanisms underlying the impact of shear stress on physiological and pathological conditions, like thrombosis, remains inadequate. To address these limitations, this study presents a microfluidic-based shear stress generation chip as a proposed solution. The chip achieves a substantial 929-fold variation in shear stress solely by adjusting the degree of constriction in branch channels after PDMS fabrication. Experiments demonstrated that a rapid increase in shear stress up to 1000 dyn/cm2 significantly detached 88.2% cells from the substrate. Long-term exposure (24 h) to shear stress levels below 8.3 dyn/cm2 did not significantly impact cell growth. Furthermore, cells exposed to shear stress levels equal to or greater than 8.3 dyn/cm2 exhibited significant alterations in aspect ratio and orientation, following a normal distribution. This microfluidic chip provides a reliable tool for investigating cellular responses to the wide-ranging shear stress existing in both physiological and pathological flow conditions. [ABSTRACT FROM AUTHOR]

Objective: The treatment of eosinophilic chronic rhinosinusitis with nasal polyps (E-CRSwNP) remains a challenge due to its complex pathogenesis. Inositol polyphosphate-4-phosphatase type IA (INPP4A), a lipid phosphatase, has been implicated in allergic asthma. However, the expression and function of INPP4A in E-CRSwNP remain unclear. This study aims to investigate the role of INPP4A in macrophages in E-CRSwNP. Methods: We assessed the expression of INPP4A in human and mouse nasal mucosal tissues via immunofluorescence staining. THP-1 cells were cultured and exposed to various cytokines to investigate the regulation of INPP4A expression and its functional role. Additionally, we established a murine nasal polyp (NP) model and administrated an INPP4A-overexpressing lentivirus evaluate its impact on NP. Results: The percentage of INPP4A + CD68 + macrophages among total macrophages decreased in the E-CRSwNP group compared to the control and the non-eosinophilic CRSwNP (NE-CRSwNP) groups, exhibiting an inverse correlation with an increased percentage of CD206 + CD68 + M2 macrophages among total macrophages. Overexpression of INPP4A led to a reduced percentage of THP-1 cells polarizing towards the M2 phenotype, accompanied by decreased levels of associated chemotactic factors including CCL18, CCL22, CCL24, and CCL26. We also validated the involvement of the PI3K-AKT pathway in the function of INPP4A in vitro. Furthermore, INPP4A overexpression in the murine NP model resulted in the attenuation of eosinophilic inflammation in the nasal mucosa. Conclusions: INPP4A deficiency promotes macrophage polarization towards the M2 phenotype, leading to the secretion of chemokines that recruit eosinophils and Th2 cells, thereby amplifying eosinophilic inflammation in E-CRSwNP. INPP4A may exert a suppressive role in eosinophilic inflammation and could potentially serve as a novel therapeutic strategy. [ABSTRACT FROM AUTHOR]

The mechanisms through which aging increases heart injury remain partially understood. Protein phosphorylation plays a critical regulatory role in cell survival and death. Using an unbiased phosphoproteomics approach, we aimed to identify the proteins whose phosphorylation could be causatively related to aging-related cardiomyocyte apoptosis and elucidate the underlying mechanisms. Comparative phosphoproteomics was conducted on cardiac tissues obtained from young (8 weeks) and aged (24 months) mice. Our findings revealed that the Mammalian Target of Rapamycin phosphorylation at T1262 (mTORT1262) was reduced in the aging heart. Immunohistochemical and Western blot analyses confirmed these findings in aging myocardia and D-galactose-induced senescent AC16 cardiomyocytes. In hypoxia/reoxygenation cardiomyocytes, mTORT1262 phosphorylation deficiency (mTORT1262A, lentivirus-mediated transfection) inhibited AKT1, suppressed NF-κB, activated FOXO1/3a signaling, and ultimately exacerbated apoptosis. Conversely, mTORT1262 pseudophosphorylation (mTORT1262E) exhibited opposite effects. Through bioinformatics and CO-IP, purinergic receptor P2X4 (P2X4R) was found to be the possible receptor responsible for mTORT1262 phosphorylation. Knockdown of P2X4R increased apoptosis, whereas its overexpression decreased it. In senescent cardiomyocytes, P2X4R expression and mTORT1262 and AKT1S473 phosphorylation were reduced, NF-κB signaling was suppressed, and FOXO1/3a signaling was activated. We demonstrated that P2X4R downregulation and the subsequent reduction of mTORT1262 phosphorylation is a novel mechanism contributing to cardiomyocyte apoptosis in aging hearts. The P2X4R-mTOR-AKT1 signaling pathway represents a potential therapeutic target against accelerated cardiac injury in aging. [ABSTRACT FROM AUTHOR]

Propagation effects are one of the main sources of noise in high-precision pulsar timing. For pulsars below an ecliptic latitude of 5°, the ionized plasma in the solar wind can introduce dispersive delays of order |$100\, \mu \mathrm{s}$| around solar conjunction at an observing frequency of 300 MHz. A common approach to mitigate this assumes a spherical solar wind with a time-constant amplitude. However, this has been shown to be insufficient to describe the solar wind. We present a linear, Gaussian-process piecewise Bayesian approach to fit a spherical solar wind of time-variable amplitude, which has been implemented in the pulsar software run_enterprise. Through simulations, we find that the current EPTA+InPTA data combination is not sensitive to such variations; however, solar wind variations will become important in the near future with the addition of new InPTA data and data collected with the low-frequency LOFAR telescope. We also compare our results for different high-precision timing data sets (EPTA+InPTA, PPTA, and LOFAR) of 3 ms pulsars (J0030+0451, J1022+1001, J2145−0450), and find that the solar-wind amplitudes are generally consistent for any individual pulsar, but they can vary from pulsar to pulsar. Finally, we compare our results with those of an independent method on the same LOFAR data of the three millisecond pulsars. We find that differences between the results of the two methods can be mainly attributed to the modelling of dispersion variations in the interstellar medium, rather than the solar wind modelling. [ABSTRACT FROM AUTHOR]

Introduction and Aims: At present, the treatment for moyamoya disease (MMD) primarily consists of combined direct and indirect bypass surgery. Nevertheless, more than half of indirect bypass surgeries fail to develop good collaterals from the dura and temporal muscle. This study aimed to investigate whether microRNAs (miRNAs) in cerebrospinal fluid (CSF) could serve as biomarkers for the prediction of postoperative collateral formation. Methods: Moyamoya disease patients with indirect bypass surgery were divided into angiogenesis and non‐angiogenesis groups, CSF was obtained, and miRNA sequencing was performed using the CSF. Candidate miRNAs were filtered and subsequently verified through qRT‐PCR. The diagnostic utility of these differential miRNAs was investigated by using receiver operating characteristic (ROC) curve analysis. Finally, the potential biological processes and signaling pathways associated with candidate miRNAs were analyzed using R software. Results: The expression levels of four miRNAs (miR‐92a‐3p, miR‐486‐3p, miR‐25‐3p, and miR‐155‐5p) were significantly increased in the angiogenesis group. By combining these four miRNAs (area under the curve [AUC] =0.970), we established an accurate predictive model of collateral circulation after indirect bypass surgery in MMD patients. GO and KEGG analyses demonstrated a high correlation with biological processes and signaling pathways related to angiogenesis. Conclusion: The 4‐miRNA signature is a good model to predict angiogenesis after indirect bypass surgery and help the surgeon to select a appreciate bypass strategy. [ABSTRACT FROM AUTHOR]

Disc degeneration often leads to a highly prevalent symptom known as low back pain. Healthy nucleus pulposus tissue exhibited a hypoxic environment devoid of blood vessels, while degenerated nucleus pulposus experienced hypoxic deterioration and the formation of new blood vessels. In this study, the expression of important genes like HIF-2α was found to vary between normal and degenerated nucleus pulposus cells when compared to the hypoxic surroundings. The aim of this study was to examine how HIF-2α is controlled in nucleus pulposus cells under hypoxic conditions and its role in angiogenic mechanisms. To assess the impact of gradual inhibition of HIF-2α on disc degeneration, we utilized PHBV-based synthetic materials loaded with inhibitors of HIF-2α. Specifically, we employed LPS and PT2399 loaded PHBV-PEG20k (PP20) to intervene with human nucleus pulposus cells. Additionally, we treated APD rat models with PT2399 loaded PP20 to evaluate its effects. The expression levels of target markers in nucleus pulposus cells were detected using PCR, WB, and immunofluorescence. Additionally, the effect of drugs on disc degeneration was identified through HE staining. The findings indicated that HIF-2α, CAIX, PPP1R15A, VEGFA, and EGLN3 could potentially serve as new indicators of disc degeneration. Additionally, HIF-2α might contribute to the progression of disc degeneration through involvement in angiogenesis and the regulation of hypoxia. Furthermore, the utilization of PT2399 loaded PHBV-PEG20k (PP20) could potentially offer a fresh alternative for treating disc degeneration. [ABSTRACT FROM AUTHOR]

Objective: This study was designed to investigate the diagnostic value of plasma SIRT1 levels and whole-brain gray matter (GM) volume in Parkinson's disease (PD) patients with cognitive impairment. Methods: Automated enzymatic analysis was performed to measure plasma SIRT1 levels in 80 healthy controls and 77 PD patients. Motor symptoms and nonmotor symptoms in PD patients were assessed using the corresponding scales. A Siemens MAGNETOM Prisma 3 T MRI scanner was used to acquire images in 35 of 77 PD patients. Results: Plasma SIRT1 levels in PD patients were lower than those in healthy controls. Plasma SIRT1 levels were negatively correlated with the age, Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) scores, anxiety, depression, excessive daytime sleepiness (EDS), quality of life, and especially cognitive impairment. Thus, it showed that plasma SIRT1 levels were relevant to visuospatial/executive function, memory, and language. Receiver-operating characteristic (ROC) analysis confirmed that plasma SIRT1 levels had good diagnostic accuracy for PD with anxiety and EDS. Furthermore, plasma SIRT1 levels had a significant positive correlation with GM volume in the whole brain, and ROC analysis confirmed that plasma SIRT1 levels and the total GM volume had good diagnostic accuracy for PD with cognitive impairment. Conclusions: This study showed that plasma SIRT1 levels were correlated with the nonmotor symptoms of anxiety, depression, EDS, and especially cognitive impairment as well as the total GM volume. Furthermore, the combination of plasma SIRT1 levels and the total GM volume had good diagnostic accuracy for PD with cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Dopamine dysregulation syndrome (DDS) is a complication of Parkinson's disease (PD) that seriously affects the quality of life of PD patients. Currently, the risk factors for DDS are poorly known, and it is critical to identify them in the early stages of PD. Objective: To explore the incidence of and risk factors for DDS in patients with early PD. Methods: A retrospective cohort study was conducted on the general data, clinical features, and imaging data of patients with early PD in the PPMI database. Multivariate Cox regression analysis was performed to analyze the risk factors for the development of DDS in patients with early PD, and Kaplan‒Meier curves examined the frequency and predictors of incident DDS symptoms. Results: At baseline, 2.2% (n = 6) of patients with early PD developed DDS, and the cumulative incidence rates of DDS during the 5-year follow-up period were 2.8%, 6.4%, 10.8%, 15.5%, and 18.7%, respectively. In the multivariate Cox regression model controlling for age, sex, and drug use, hypersexuality (HR = 3.088; 95% CI: 1.416~6.732; P = 0.005), compulsive eating (HR = 3.299; 95% CI: 1.665~6.534; P = 0.001), compulsive shopping (HR = 3.899; 95% CI: 1.769~8.593; P = 0.001), anxiety (HR = 4.018; 95% CI: 2.136~7.599; P < 0.01), and lower Hoehn-Yahr (H-Y) stage (HR = 0.278; 95% CI: 0.152~0.509; P < 0.01) were independent risk factors for DDS in patients with early PD. PD patients with DDS had lower DAT uptake values than those patients without DDS. Conclusion: Early PD patients with hypersexuality, compulsive eating, compulsive shopping, anxiety, and lower H-Y stage were at increased risk for DDS. The occurrence of DDS may be related to the decrease in the average DAT uptake of the caudate and putamen. [ABSTRACT FROM AUTHOR]

Emotional neglect is an under‐recognized but relatively common type of childhood maltreatment. Although it has been reported that adolescents will facilitate positive growth after experiencing childhood maltreatment, such as sexual abuse, it is unknown whether adolescents could also get a promotion after experiencing emotional neglect. Thus, we aimed to examine the association between emotional neglect and posttraumatic growth (PTG) and further explored the potential influence factors underlying such association. Six hundred and thirty‐five adolescents (55.2% female, Mage = 14.12 years old, SD = 1.47) were asked to complete self‐report questionnaires regarding emotional neglect, school engagement, psychological suzhi, and PTG. Results showed that emotional neglect was negatively associated with PTG, and school engagement mediated such association. Further, psychological suzhi moderated the direct pathway from emotional neglect to PTG in which the deleterious effect of emotional neglect on PTG was weaker for adolescents who reported higher psychological suzhi. Meanwhile, psychological suzhi moderated the indirect pathway from emotional neglect to school engagement in the mediated model in which the deleterious effect of emotional neglect on school engagement was weaker for adolescents who reported higher psychological suzhi. Overall, the current study advances our understanding of the relationship between emotional neglect and PTG, and further tests the potential roles of school engagement and psychological suzhi in this relationship. Practitioner points: Emotional neglect may be a factor that impedes the development of adolescents' mental health.It would be necessary to cultivate individuals' psychological suzhi to mitigate the negative effects of external adversities.Fostering students' school engagement could contribute to a promotion in mental health. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is a widespread disease that is frequently comorbid with depression. However, the mechanisms and treatments for depression in AR remain underexplored. Metformin, a widely used antidiabetic drug, has shown antidepressant effects. The aim of this study was to explore the effects and potential mechanisms of metformin on depression-like behaviors in an AR mouse model. In the present study, mice were sensitized and challenged with ovalbumin (OVA) to induce AR. Results showed that mice with AR exhibited significant depression-like behavior which was attenuated by metformin. In addition, the levels of expression of synaptic plasticity markers (anti-microtubule-associated protein 2, synaptophysin, postsynaptic density protein 95), neurogenesis markers (doublecortin and Ki-67), and brain-derived neurotrophic factor were decreased in the olfactory bulb (OB) of mice with AR, while metformin ameliorated all these alterations and reduced apoptosis in the OB of these mice. Furthermore, it enhanced the phosphorylation of AMP-activated kinase (AMPK) and the levels of ten-eleven translocation 2 (TET2) and 5-hydroxymethylcytosine in the OB. In conclusion, our findings suggest that metformin might be a viable strategy for treating AR-related depression, possibly by modulating neuroplasticity, neurogenesis, apoptosis, and BDNF signaling in the OB via the AMPK/TET2 pathway. [ABSTRACT FROM AUTHOR]

This study reports a novel shielding material against high energy electron beam, where bismuth oxide (Bi 2 O 3) and multiwalled carbon nanotube (MWCNT) nanoparticles added in a polymer matrix can solid electron beam radiation several times more efficient than aluminum with the same areal density. The polymer nanocomposites were prepared by dispersing nanoparticles in polydimethylsiloxane (PDMS) with a simple one-step fabrication process, in five areal densities (0.5, 1, 1.5, 3, and 5 g/cm2). All the samples were irradiated by 9, 12, 16, and 20 MeV electron beam. The prepared PDMS/CNT/BiO (CNT and BiO are the shorten name of fillers for coding the samples) showed better electron shielding ability than aluminum (Al) for any areal density. The weight advantageous of nanocomposite over aluminum was calculated up to 36 wt% for same attenuation efficiency. The thermal stability of nanocomposites up to 415 °C, as well as the tensile strength of up to 4.7 MPa, exhibited the high potential of developed samples for high energy electron beam shielding in medical and aerospace applications. PDMS polymer nanocomposites were fabricated for energetic electron radiation protection application. After characterization of samples for thermal and mechanical properties, they were tested for electron shielding performance. Based on the results, the nanocomposites can reach a weight advantage of up to 36 % when comparing to aluminum. [Display omitted] • PDMS polymer nanocomposites can be applied to shield electron radiation. • The nanocomposites can reach up to 36% weight reduction comparing to aluminum (Al). • Nanocomposites show higher attenuation efficiency than Al at all areal densities. [ABSTRACT FROM AUTHOR]

Pulsar timing arrays (PTAs) and the Laser Interferometer Space Antenna (LISA) will open complementary observational windows on massive black hole binaries (MBHBs), i.e. with masses in the range |${\sim} 10^6\!-\!10^{10}\, \rm M_{\odot }$|⁠. While PTAs may detect a stochastic gravitational wave background from a population of MBHBs, during operation LISA will detect individual merging MBHBs. To demonstrate the profound interplay between LISA and PTAs, we estimate the number of MBHB mergers that one can expect to observe with LISA by extrapolating direct observational constraints on the MBHB merger rate inferred from PTA data. For this, we postulate that the common signal observed by PTAs (and consistent with the increased evidence recently reported) is an astrophysical background sourced by a single MBHB population. We then constrain the LISA detection rate, |$\mathcal {R}$|⁠ , in the mass–redshift space by combining our Bayesian-inferred merger rate with LISA 's sensitivity to spin-aligned, inspiral–merger–ringdown waveforms. Using an astrophysically informed formation model, we predict a |$95{{\, \rm per\, cent}}$| upper limit on the detection rate of |$\mathcal {R} \lt 134\, {\rm yr}^{-1}$| for binaries with total masses in the range |$10^7\!-\!10^8\, \rm M_{\odot }$|⁠. For higher masses, i.e. |${\gt} 10^8\, \rm M_{\odot }$|⁠ , we find |$\mathcal {R} \lt 2\, (1)\, \mathrm{yr}^{-1}$| using an astrophysically informed (agnostic) formation model, rising to |$11 \, (6)\, \mathrm{yr}^{-1}$| if the LISA sensitivity bandwidth extends down to 10−5 Hz. Forecasts of LISA science potential with PTA background measurements should improve as PTAs continue their search. [ABSTRACT FROM AUTHOR]

Due to environmental hypoxia on the Tibetan Plateau, local residents often exhibit a compensative increase in hemoglobin concentration to maintain the body's oxygen supply. However, increases in hemoglobin and hematocrit (Hct) pose a serious challenge to the quality of stored suspended red blood cells (SRBCs) prepared from the blood of high-hemoglobin populations, especially populations at high altitude with polycythemia in Tibet. To explore the difference in storage quality of SRBCs prepared from plateau residents with a high hemoglobin concentration, blood donors were recruited from Tibet (> 3600 m) and Chengdu (≈ 500 m) and divided into a high-altitude control (HAC) group, high-altitude polycythemia (HAPC) group and lowland control (LLC) group according to their hemoglobin concentration and altitude of residence. The extracellular acidification rate (ECAR), pyruvate kinase (PK) activity and band 3 tyrosine phosphorylation were analyzed on the day of blood collection. Then, whole-blood samples were processed into SRBCs, and storage quality parameters were analyzed aseptically on days 1, 14, 21 and 35 of storage. Overall, we found that tyrosine 21 phosphorylation activated glycolysis by releasing glycolytic enzymes from the cytosolic domain of band 3, thus increasing glucose consumption and lactate accumulation during storage, in the HAPC group. In addition, band 3 tyrosine phosphorylation impaired erythrocyte deformability, accompanied by the highest hemolysis rate in the HAPC group, during storage. We believe that these results will stimulate new ideas to further optimize current additive solutions for the high-hemoglobin population in Tibet and reveal new therapeutic targets for the treatment of HAPC populations. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a multifaceted, chronic, progressive autoimmune disease. This study aims to explore the potential benefits of an enhanced drug delivery system utilizing optimized Gelatin Methacryloyl (GelMA) vectors in RA management. We evaluated the levels of miR-1124-3p and AGO1 in RA tissues and cell lines using qPCR, WB, and immunofluorescence. The effects of osthole on inflammatory response and joint morphology were determined by qPCR, H&E staining, and micro-CT. The data showed that miR-1224-3p was downregulated in RA tissues and HUM-iCell-s010RA cells, while the overexpression of miR-1224-3p in HUM-iCell-s010RA cells reduced the expression of IL-6 and IL-1β. Luciferase assay demonstrated that AGO1 was a direct target gene of miR-1224-3p. Additionally, osthole treatment increased miR-1224-3p levels and decreased AGO1 expression. The release data showed that osthole loaded on GelMA was released at a slower rate than free osthole. Further studies in a mouse model of CIA confirmed that osthole-loaded GelMA was more effective in attenuating osteopenia in RA as well as alleviating autoimmune arthritis. These findings suggest that osthole can regulate the miR-1224-3p/AGO1 axis in RASFs cells and has the potential to be developed as a clinical anti-RA drug. GelMA could provide a new approach to long-term RA treatment. [ABSTRACT FROM AUTHOR]

Microneedles (MNs) are particularly attractive for transdermal administration because of the improved safety, patient compliance and convenience. Dissolving MNs could provide rapid transdermal delivery, but with relatively low mechanical strength and almost no sustainability. On the other hand, hydrogel MNs are complicated to fabricate and have risk concerns. Herein, we developed a biodegradable MNs array composed of biocompatible silk fibroin and poly(vinyl alcohol) to overcome these limitations. Finite element analysis was employed for parameter optimization. The MNs array fabricated by the optimal parameters and material displayed sufficient mechanical strength to disrupt stratum corneum and formed microchannels for transdermal delivery. Dual-release profile was observed in the MNs array, with rapid release in the beginning, and prolonged release afterward. This release behavior fits Weibull release model and is favorable for topical application. The initial immediate release can quickly deliver active compounds to reach the therapeutic effective concentration and facilitate skin penetration, and the sustained release may supply the skin with active compounds over a prolonged period. This biodegradable MNs array is easy to fabricate, mechanically robust, could eliminate safety concerns, and provide the sustainability and advantage for large-scale production. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: Direct revascularization remains an important tool in the treatment of patients with Moyamoya disease (MMD). The superficial temporal artery (STA) is the most commonly used donor vessel for direct bypass, and an STA graft has traditionally been considered a low‐flow graft for flow augmentation. This study aimed to quantitatively evaluate the blood flow of the STA after direct revascularization. Methods: All direct revascularization procedures performed between 2018 and 2021 by one experienced neurosurgeon were screened. Quantitative ultrasound was used to measure the flow data of the patient's bilateral parietal branch of the STA(STA‐PB), the bilateral frontal branch of the STA(STA‐FB), and the left radial artery. Data on the patients' basic information, Suzuki grade, Matsushima type, anastomosis type, and blood biochemical parameters were collected and analyzed using univariate and multivariate models. An MBC Scale scoring system was proposed to evaluate the recipient artery network of the middle cerebral artery (MCA) tree. The relationship between MBC Scale score and STA graft flow was statistically analyzed. Results: In total, 81 patients (43 males and 38 females) successfully underwent STA‐MCA bypass and were included in this study. The mean flow rates in the STA‐PB graft on 1 day preoperatively, 1 day postoperatively, 7 days postoperatively, and >6 months postoperatively (long‐term) were 10.81, 116.74, 118.44, and 56.20 mL/min respectively. Intraoperative graft patency was confirmed in all patients. Comparing the preoperative and all postoperative time points, the STA‐PB flow rates were statistically significant (p < 0.001). The MCA‐C score was significantly associated with postoperative flow rate on day 1 (p = 0.007). Conclusion: The STA is a useful donor artery for direct revascularization inpatients with MMD and can provide sufficient blood supply to the ischemic cerebral territory. [ABSTRACT FROM AUTHOR]

Dynamic bonds are usually used to endow thermoset materials with excellent reprocessability. Nevertheless, this strategy sacrifices the thermal stability in most instances. In recent years, the dynamic silyl ether (SiOR) has attracted great attention due to its excellent thermal stability. However, the reprocessability of thermoset materials based on it is far from satisfactory because of the inactive dynamic exchange reaction. Herein, a species of activated silyl ether with neighboring groups is identified via small‐molecule model reaction and the corresponding activation energy is calculated by reaction kinetics for the first time. Based on the activated silyl ether linkages, the poly(dimethylsiloxane) elastomers with high mechanical strength, effective reprocessability, and thermal stability are further designed and prepared. In a word, this work fills a research gap about the effect of neighboring groups on the dynamic characteristic of silyl ether and provides a theoretical basis for the construction of activated silyl ether linkages, endowing the materials with thermal stability and efficient reprocessability. [ABSTRACT FROM AUTHOR]

This paper proposes a modified YOLOv4 model, named GYOLO, for coal gangue recognition with the aim of reducing model parameters, improving calculation speed, and reducing equipment requirements. To achieve this, the paper optimizes the feature extraction network structure by using linear operation instead of traditional convolution to obtain redundant feature maps, thus reducing the number of parameters by 29.7%. A feature fusion network structure is also reconstructed to strengthen the model's use of feature information, further explore the dependence of each channel feature, and make better use of feature information. The ablation experiment is designed to verify the effect of each improvement. The image is blurred to improve the difficulty of target detection and test the robustness of the GYOLO model. The generative adversarial network is trained with a small amount of coal gangue data, and then a large amount of virtual data is obtained by using the generative adversarial neural network. The GYOLO model is trained by transfer learning, which reduces the dependence of the model on real data. The GYOLO algorithm is compared with a variety of excellent target detection algorithms to analyze the performance of the algorithm. It is verified that the accuracy of the proposed method is 97.08%, which is 2.3% higher than that of the original model, the amount of parameters is reduced by 19.6%, and the amount of data required is reduced by 57.3%. The balance between data volume, parameter quantity and model performance is further realized. [ABSTRACT FROM AUTHOR]

Then, with the standard of typical buttock's lesions of first PP patient, we screened out 13 PP cases whose lesions were not exclusive to the buttocks (also expatiated the initiated site). Keywords: Porokeratosis ptychotropica; Genitogluteal porokeratosis; Differential diagnosis EN Porokeratosis ptychotropica Genitogluteal porokeratosis Differential diagnosis 2841 2843 3 11/02/23 20231201 NES 231201 Yifan Jin and Fangqi Chen have contributed equally to this work. Porokeratosis ptychotropica (PP) and genitogluteal porokeratosis (PK) are both quite rare subtypes of PK, which are frequently misdiagnosed. [Extracted from the article]

Nuclear factor I B (NFIB) plays an important role in tumors. Our previous study found that NFIB can promote colorectal cancer (CRC) cell proliferation in acidic environments. However, its biological functions and the underlying mechanism in CRC are incompletely understood. Nicotinamide adenine dinucleotide (NAD+) effectively affects cancer cell proliferation. Nevertheless, the regulatory mechanism of NAD+ synthesis in cancer remains to be elucidated. Here we show NFIB promotes CRC proliferation in vitro and growth in vivo, and down-regulation of NFIB can reduce the level of NAD+. In addition, supplementation of NAD+ precursor NMN can recapture cell proliferation in CRC cells with NFIB knockdown. Mechanistically, we identified that NFIB promotes CRC cell proliferation by inhibiting miRNA-182-5p targeting and binding to NAMPT, the NAD+ salvage synthetic rate-limiting enzyme. Our results delineate a combination of high expression of NFIB and NAMPT predicted a clinical poorest prognosis. This work provides potential therapeutic targets for CRC treatment. Nuclear factor I B promotes colorectal cancer cell proliferation in vitro and growth in vivo by increasing intracellular NAD+ levels through downregulation of the NAMPT-targeting micro-RNA, miR-182-5p. [ABSTRACT FROM AUTHOR]

Sensitive skin is defined as skin with low tolerance and high reactivity. Natural products, such as paeoniflorin and madecassoside, have unique skin care functionality. However, because they are hampered by the skin barrier, paeoniflorin and madecassoside have difficulty penetrating the stratum corneum, resulting in weakened skin barrier repair and anti-inflammatory effects. In addition, there is a lack of detailed studies on the efficacy of paeonol and madecassic in human skin, especially in 3D skin models and clinical trials. To overcome the low transdermal delivery issue, we developed nanoemulsions (PM-NEs) loaded with paeonol and madecassoside to improve their delivery efficiency and promote sensitive skin repair and anti-inflammation effects. Furthermore, systematic evaluations of the efficacy in cell line models, 3D skin models, and clinical trials were conducted. The PM-NEs effectively improved the efficacy of paeonol and madecassoside glucoside transdermal penetration and retention and enhanced cellular uptake. Cellular assays and 3D epidermal models showed that the PM-NEs significantly promoted the secretion of filamentous protein, aquaporin 3, Claudin-1, and hyaluronic acid, and considerably inhibited the secretion of interleukin 1α, interleukin 6, tumor necrosis factor-α, and prostaglandin E2 compared to free components. Notably, clinical trial data showed that the PM-NEs significantly reduced transepidermal water loss, a* values, erythropoietin, the amount of non-inflammatory acne, and the amount of inflammatory acne in the facial skin. Three levels of systematic studies suggest that co-delivery of paeoniflorin and madecassoside via nanoemulsions is a promising strategy to improve topical delivery efficiency and anti-inflammatory repair efficacy in sensitive skin. [ABSTRACT FROM AUTHOR]

Carbon fiber (CF) reinforced SiBCN composites were generally considered as key candidates for thermal protection under severe aerodynamic heating in aerospace due to their excellent high-temperature properties, but they were also faced with challenges in stably monitoring the structural integrity of themselves under extreme conditions. Herein, with the introduction of SiC coating, multifunctional CF-SiC/SiBCN composites were fabricated which integrated functions of the thermal protection and the structural health monitoring. Compared to the untreated CF/SiBCN composites, the stability of sensing of CF-SiC/SiBCN composites was greatly improved and the sensitivity of CF-SiC/SiBCN composites maintained at a high level with a gauge factor of 652.65. Furthermore, additional researches revealed that the CF-SiC/SiBCN composites enjoyed a high compressive strength (155.33 MPa), a light weight (1.07–1.61 g/cm3), and a relatively low thermal conductivity (4.02 W/(m·K)), which showed a potentiality of CF-SiC/SiBCN composites to be applied as multifunctional structural components in thermal protection systems. [ABSTRACT FROM AUTHOR]

We propose explicit K-symplectic and explicit symplectic-like methods for the charged particle system in a general strong magnetic field. The K-symplectic methods are also symmetric. The charged particle system can be expressed both in a canonical and a non-canonical Hamiltonian system. If the three components of the magnetic field can be integrated in closed forms, we construct explicit K-symplectic methods for the non-canonical charged particle system; otherwise, explicit symplectic-like methods can be constructed for the canonical charged particle system. The symplectic-like methods are constructed by extending the original phase space and obtaining the augmented separable Hamiltonian, and then by using the splitting method and the midpoint permutation. The numerical experiments have shown that compared with the higher order implicit Runge-Kutta method, the explicit K-symplectic and explicit symplectic-like methods have obvious advantages in long-term energy conservation and higher computational efficiency. It is also shown that the influence of the parameter ε in the general strong magnetic field on the Runge-Kutta method is bigger than the two kinds of symplectic methods. [ABSTRACT FROM AUTHOR]

Objectives: Patients with vascular anomalies (VAs) who receive oral sirolimus may be at high risk of infectious complications. Antibiotic prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) has been advocated. However, there have been few evidence-based analyses on this topic. This study assessed the effect of prophylactic TMP-SMZ on the incidence of infections in VA patients receiving sirolimus monotherapy. Methods: A retrospective, multicenter chart review was performed on all VA patients receiving sirolimus treatment from August, 2013 to January, 2021. Results: Before January 2017, 112 patients were treated with sirolimus without antibiotic prophylaxis. In the subsequent period, 195 patients were treated with TMP-SMZ for at least 12 months during sirolimus therapy. The percentage of patients with at least one serious infection during the initial 12 months of sirolimus treatment did not differ between the groups (difference, 1.1%; 95% CI − 7.0–8.0%). We observed no difference in the incidence of individual infection or total adverse events between the groups. The rate of sirolimus discontinuation due to adverse events did not differ significantly between groups. Conclusions: We demonstrated that prophylactic TMP-SMZ does not decrease the incidence of infection or improve tolerance in VA patients receiving sirolimus monotherapy. [ABSTRACT FROM AUTHOR]

Stream processing systems are widely used to process large amounts of data generated by applications in real time due to their advantages in latency and throughput. In most streaming applications, the system requires a comprehensive analysis of data from multiple data sources, so stream joins are the basis of stream processing systems. Similar to other big data problems, stream joins suffer from load imbalance, where a few nodes responsible for handling most of the load can become bottlenecks, thereby increasing latency and reducing throughput. Therefore, how to obtain a good load-balancing effect with low overhead is a critical issue in designing stream join systems. To solve this problem, we propose an adaptive non-migrating load-balancing method, which is mainly oriented to the stream window join problem. Considering that the completeness of the stream join results during the splitting of state to multiple downstream instances can be guaranteed by replicating the input tuples into multiple replicas and sending them to those downstream instances, our method can control the replication and forwarding of input tuples by setting up routing tables, and then when the system becomes unbalanced, our method can change the load distribution of the system by directly changing the partitioning of the tuples arriving later instead of state migration, and thus achieving load balancing with very low overhead. Based on our method, we develop a distributed stream window join system, NM-Join, which is built on Flink. We theoretically analyze the completeness and effectiveness of our method and provide extensive experimental evaluations of NM-Join in terms of load-balancing effect, latency, and throughput. Experimental results show that our method is able to perform load balancing with very low additional overhead, and thus outperforms existing load-balancing methods in terms of latency and throughput. [ABSTRACT FROM AUTHOR]

Background: Non-involuting congenital hemangiomas (NICHs) are fully formed vascular tumors at birth with distinctive clinical, radiologic, and histopathological profiles. In the literature, there is no effective therapy strategy for patients with NICH except surgery. Currently, no cell line or animal model exists for studying the mechanism of NICH and drug validation. We plan to construct a new strategy by constructing NICH organoids for further study. Result: Here, we report a novel NICH organoid system construction and optimization process. Both HE and immunohistological staining exactly matched NICH tissue. We further performed transcriptome analysis to elucidate the characteristics of NICH organoids. Both NICH tissue and NICH organoids manifested similar trends in download sites. NICH organoids display novel features to new cells derived from organoids and show spectacular multiplication capacity. In the preliminary verification, we found that cells splitting from NICH organoids were human endothelial cells. Drug validation demonstrated that trametinib, sirolimus, and propranolol showed no inhibitory effects on NICH organoids. Conclusion: Our data show that this new NICH-derived organoid faithfully captured the features of this rare vascular tumor. Our study will boost further research on the mechanism of NICH and drug filtering in the future. [ABSTRACT FROM AUTHOR]

Background: Insulin-like growth factor 1 (IGF-1) and epidermal growth factor (EGF) exert neuroprotective effects in Parkinson's disease (PD). To date, studies on the relationships between serum IGF-1 and EGF levels and nonmotor symptoms in PD patients have been rare. Methods: A Siemens automatic chemical analyzer was used to determine serum IGF-1 levels, and enzyme-linked immunosorbent assay was used to detect serum EGF levels in 100 healthy controls and 100 PD patients, including those in the early (n = 49) and middle-late (n = 51) stage of the disease. Evaluation of motor symptoms and nonmotor symptoms in PD patients was assessed by the associated scales. Results: Serum IGF-1 and EGF levels were higher in PD patients than in healthy controls, and serum IGF-1 and EGF levels were higher in early stage PD patients than in middle-late stage PD patients. Serum IGF-1 levels were significantly negatively correlated with anxiety, depression, and cognitive dysfunction; serum EGF levels were significantly negatively correlated with cognitive dysfunction. Combining IGF-1 and EGF in the diagnosis of PD was more valuable than using a single factor in the diagnosis. Conclusions: This study shows that serum IGF-1 levels were correlated with the nonmotor symptoms of anxiety, depression, and cognitive dysfunction and that EGF levels were correlated with cognitive dysfunction. The combination of IGF-1 and EGF increased the value for a PD diagnosis. This is the first report of the simultaneous detection of IGF-1 and EGF levels to explore the correlation with nonmotor symptoms of PD. [ABSTRACT FROM AUTHOR]

In this study, we conducted two surveys in the central and southern parts of the South China Sea, in autumn 2012 and spring 2013. Six juvenile tuna species were caught in each survey. Gradient forest analysis (GFA) and a generalized additive model (GAM) were used to analyze the relationship between the catch per unit effort (CPUE) for the juvenile tuna species and six sea temperature indices for the South China Sea. In the GFA, the temperature difference between the sea surface and 50 m depth (D50) showed the highest importance to CPUE than other indices, which indicates that D50 was the best predictor of the abundance of juvenile tuna species. The GAM analysis showed that lower deep-water temperature, a shallow mixed layer depth, and a higher difference in temperature between the surface and deeper water were associated with increased CPUE. The results indicate that a relatively rapid decrease in vertical water temperature is favorable for the aggregation of juvenile tuna. These results contribute to understanding of the distribution mechanism of juvenile tuna species in the South China Sea and provide a scientific basis for the rational development and utilization of tuna resources. [ABSTRACT FROM AUTHOR]

Leaf chlorophyll content (LCC) is a prominent plant physiological trait and a proxy for leaf photosynthetic capacity. The acquisition of LCC data over large spatial and temporal scales facilitates vegetation growth monitoring and terrestrial carbon cycle modeling. In this study, a global 500 m LCC weekly dataset (GLCC) was produced from ENVISAT MERIS and Sentinel-3 OLCI satellite data using a physical radiative transfer modeling approach that considers the influence of canopy structure and soil background. Firstly, five look-up-tables (LUTs) were generated using PROSPECT-D+4-Scale and PROSAIL-D models for woody and non-woody plants. For the four LUTs applicable to woody plants, each LUT contains three sub-LUTs corresponding to three types of crown height. The one LUT applicable to non-woody vegetation type includes 25 sub-LUTs corresponding to five kinds of canopy structures and five kinds of soil backgrounds. The final retrieval was considered the aggregation of the LCC inversion results of all sub-LUTs for each plant function type (PFT). Then, the GLCC dataset was generated and validated using field measurements, yielding an overall accuracy of R2 = 0.41 and RMSE = 8.94 μg cm−2. Finally, the GLCC dataset presented acceptable consistency with the existing MERIS LCC dataset. OLCI, as the successor to MERIS data, was used for the first time to co-produce LCC data from 2003–2012 to 2018–2020 in conjunction with MERIS data. This new GLCC dataset spanning nearly 20 years will provide a valuable opportunity to analyze variations in vegetation dynamics. [ABSTRACT FROM AUTHOR]

Absent in melanoma 2 (AIM2) is a cytoplasmic sensor that recognises the double-strand DNA. AIM2 inflammasome is a protein platform in the cell that initiates innate immune responses by cleaving pro-caspase-1 and converting IL-1β and IL-18 to their mature forms. Additionally, AIM2 inflammasome promotes pyroptosis by converting Gasdermin-D (GSDMD) to GSDMD-N fragments. An increasing number of studies have indicated the important and decisive roles of the AIM2 inflammasome, IL-1β, and pyroptosis in cardiovascular diseases, such as coronary atherosclerosis, myocardial infarction, ischaemia/reperfusion injury, heart failure, aortic aneurysm and ischaemic stroke. Here, we review the molecular mechanism of the activation and effect of the AIM2 inflammasome in cardiovascular disease, revealing new insights into pathogenic factors that may be targeted to treat cardiovascular disease and related dysfunctions. [Display omitted] [ABSTRACT FROM AUTHOR]

Lithium-oxygen (Li-O 2) batteries are facing challenges in capacity, cycling stability, and kinetics for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). Advanced catalysts should have a high and bifunctional catalytic activity for ORR and OER. Moreover, the trade-off carbon in catalysts should have good oxidation resistance and high electronic conductivity and be used in a tiny amount. Up to now, it is still a challenge. Therefore, this work introduces a low-carbon CeO x /Ru@RuO 2 nanosheet as efficient cathode catalysts for Li-O 2 batteries and studies the preparation and working mechanisms using a variety of characterization and electrochemical techniques. The air oxidation treatment oxidizes Ru into Ru@RuO 2 and simultaneously removes unstable C into CO 2, leaving a tiny amount of stable carbon. CeO x /Ru@RuO 2 has enormous mesopores, well-distributed sub-5 nm CeO x and Ru@RuO 2 nanocrystals, a tiny amount of anti-oxidation carbon (1.2 %), and a high specific surface area of 159.3 m² g−1. These aspects optimize the Li-O reaction and regulate the Li 2 O 2 nucleation to form uniform and ultrathin Li 2 O 2 nanoflakes. As a result, the ORR and OER overpotentials are only 0.17 V and 0.45 V, respectively. This work provides a novel material combination and structure design for developing bifunctional catalyst materials in Li-O 2 batteries. [Display omitted] • Sub-5 nm CeO x and Ru@RuO 2 and 1.2 % carbon form a mesoporous nanosheet. • The nanosheet (~25 nm thick) has massive mesopores and specific surface area. • The average ORR and OER overpotentials are 0.17 V and 0.65 V, respectively. • The nanosheet optimizes the Li-O reaction to form ultrathin Li 2 O 2 nanoflakes. [ABSTRACT FROM AUTHOR]

Background: Excessive extracellular matrix deposition and increased stiffness are typical features of solid tumors such as hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC). These conditions create confined spaces for tumor cell migration and metastasis. The regulatory mechanism of confined migration remains unclear. Methods: LC–MS was applied to determine the differentially expressed proteins between HCC tissues and corresponding adjacent tissue. Collective migration and single cell migration microfluidic devices with 6 μm-high confined channels were designed and fabricated to mimic the in vivo confined space. 3D invasion assay was created by Matrigel and Collagen I mixture treat to adherent cells. 3D spheroid formation under various stiffness environment was developed by different substitution percentage GelMA. Immunoprecipitation was performed to pull down the LH1-binding proteins, which were identified by LC–MS. Immunofluorescent staining, FRET, RT-PCR, Western blotting, FRAP, CCK-8, transwell cell migration, wound healing, orthotopic liver injection mouse model and in vivo imaging were used to evaluate the target expression and cellular phenotype. Results: Lysyl hydroxylase 1 (LH1) promoted the confined migration of cancer cells at both collective and single cell levels. In addition, LH1 enhanced cell invasion in a 3D biomimetic model and spheroid formation in stiffer environments. High LH1 expression correlated with poor prognosis of both HCC and PDAC patients, while it also promoted in vivo metastasis. Mechanistically, LH1 bound and stabilized Septin2 (SEPT2) to enhance actin polymerization, depending on the hydroxylase domain. Finally, the subpopulation with high expression of both LH1 and SEPT2 had the poorest prognosis. Conclusions: LH1 promotes the confined migration and metastasis of cancer cells by stabilizing SEPT2 and thus facilitating actin polymerization. [ABSTRACT FROM AUTHOR]

The search for gravitational waves using Pulsar Timing Arrays (PTAs) is a computationally expensive complex analysis that involves source-specific noise studies. As more pulsars are added to the arrays, this stage of PTA analysis will become increasingly challenging. Therefore, optimizing the number of included pulsars is crucial to reduce the computational burden of data analysis. Here, we present a suite of methods to rank pulsars for use within the scope of PTA analysis. First, we use the maximization of the signal-to-noise ratio as a proxy to select pulsars. With this method, we target the detection of stochastic and continuous gravitational wave signals. Next, we present a ranking that minimizes the coupling between spatial correlation signatures, namely monopolar, dipolar, and Hellings & Downs correlations. Finally, we also explore how to combine these two methods. We test these approaches against mock data using frequentist and Bayesian hypothesis testing. For equal-noise pulsars, we find that an optimal selection leads to an increase in the log-Bayes factor two times steeper than a random selection for the hypothesis test of a gravitational wave background versus a common uncorrelated red noise process. For the same test but for a realistic European PTA (EPTA) data set, a subset of 25 pulsars selected out of 40 can provide a log-likelihood ratio that is 89 % of the total, implying that an optimally selected subset of pulsars can yield results comparable to those obtained from the whole array. We expect these selection methods to play a crucial role in future PTA data combinations. [ABSTRACT FROM AUTHOR]

Insect hemocytes play important biological roles at developmental stages, metamorphosis, and innate immunity. As one of the most abundant cell types, plasmatocytes can participate in various innate immune responses, especially in encapsulation and node formation. Here, 2 molecular markers of plasmatocytes, consisting of integrin β2 and β3, were identified and used to understand the development of plasmatocytes. Plasmatocytes are widely distributed in the hematopoietic system, including circulating hemolymph and hematopoietic organs (HPOs). HPOs constantly release plasmatocytes with high proliferative activity in vitro; removal of HPOs leads to a dramatic reduction in the circulating plasmatocytes, and the remaining plasmatocytes gradually lose their ability to proliferate in vivo. Our results demonstrated that the release of plasmatocytes from HPOs is regulated by insulin‐mediated signals and their downstream pathways, including PI3K/Akt and MAPK/Erk signals. The insulin/PI3K/Akt signaling pathway can significantly irritate the hematopoiesis, and its inhibitor LY294002 could inhibit the hemocytes discharged from HPOs. While the insulin/MAPK/Erk signaling pathway plays a negative regulatory role, inhibiting its activity with U0126 can markedly promote the discharge of plasmatocytes from HPOs. Our results indicate that the circulating plasmatocytes are mainly generated and discharged by HPOs. This process is co‐regulated by the PI3K/Akt and MAPK/Erk signals in an antagonistic manner to adjust the dynamic balance of the hemocytes. These findings can enhance our understanding of insect hematopoiesis. [ABSTRACT FROM AUTHOR]

The structural design and tuning of properties of metallaaromatics are crucial in materials and energy science. Herein, we describe the rapid synthesis of tetracyclic metallaaromatics containing quinoline and pentalene motifs fused by a metal‐bridged fragment. These unique compounds display remarkably broad absorption, enabling for the first time the absorption of metallaaromatics to reach the second near‐infrared (NIR‐II) bio‐window. The formation of osmaquinoline unit involves an unconventional C(sp2)−C(sp3) coupling promoted by AgBF4 to achieve [3+3] cycloaddition. The introduction of cyclic dπ‐pπ conjugation and extension of the aromatic π‐framework can effectively shrink the HOMO–LUMO gap, thus broadening the absorption window. The considerable photothermal conversion efficiency (PCE) in both the NIR‐I and NIR‐II windows, the high photothermal stability and the excellent electrochemical behavior suggest many potential applications of these condensed metallaquinolines. [ABSTRACT FROM AUTHOR]

The structural design and tuning of properties of metallaaromatics are crucial in materials and energy science. Herein, we describe the rapid synthesis of tetracyclic metallaaromatics containing quinoline and pentalene motifs fused by a metal‐bridged fragment. These unique compounds display remarkably broad absorption, enabling for the first time the absorption of metallaaromatics to reach the second near‐infrared (NIR‐II) bio‐window. The formation of osmaquinoline unit involves an unconventional C(sp2)−C(sp3) coupling promoted by AgBF4 to achieve [3+3] cycloaddition. The introduction of cyclic dπ‐pπ conjugation and extension of the aromatic π‐framework can effectively shrink the HOMO–LUMO gap, thus broadening the absorption window. The considerable photothermal conversion efficiency (PCE) in both the NIR‐I and NIR‐II windows, the high photothermal stability and the excellent electrochemical behavior suggest many potential applications of these condensed metallaquinolines. [ABSTRACT FROM AUTHOR]

To explore whether TET2 regulates EMT through PPAR- , we knocked down TET2 and added PPAR- agonist rosiglitazone (20 M) in normal hNECs. Epithelial-to-mesenchymal transition (EMT) is associated with the pathophysiology of NPs.1,2 Ten-eleven translocation 2 (TET2), a member of the TET family, can hydroxylate 5-methylcytosine (5-mC) to produce 5-hydroxymethylcytosine (5-hmC), and thus plays a potential role in epigenetic regulation through modification of DNA methylation. Keywords: CRS; EMT; nasal polyps; PPAR- ; TET2 EN CRS EMT nasal polyps PPAR- TET2 3452 3455 4 11/01/22 20221101 NES 221101 To the Editor, Nasal polyps (NPs) are the product of chronic long-term inflammation of the nasal mucosa and represent the refractory clinical process of chronic sinusitis (CRS). [Extracted from the article]