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Abstract Background Edaravone dexborneol has been reported as an effective neuroprotective agent in the treatment of acute ischemic stroke (AIS). This study aimed at investigating the impact of edaravone dexborneol on functional outcomes and systematic inflammatory response in AIS patient. Methods All participants were recruited from the AISRNA study (registered 21/11/2019, NCT04175691 [ClinicalTrials.gov]) between January 2022 and December 2022. The AIS patients were divided into two groups based on whether they received the treatment of edaravone dexborneol (37.5 mg/12 hours, IV) within 48 h after stroke onset. Inflammatory response was determined by detecting levels of cytokines (interleukin-2 [IL-2], IL-4, IL-5, IL-8, IL-6, IL-10, IL-12p70, IL-17, tumor necrosis factor-α [TNF-α], interferon-γ [IFN-γ], IFN-α, and IL-1β) within 14 days after stroke onset. Results Eighty-five AIS patients were included from the AISRNA study. Patients treated with edaravone dexborneol showed a significantly higher proportion of modified Rankin Scale score 0.05). Conclusions Treatment with edaravone dexborneol resulted in a favorable functional outcome at 90 days post-stroke onset when compared to patients without this intervention; it also suppressed proinflammatory factors expression while increasing anti-inflammatory factors levels. Trial registration ClinicalTrials.gov NCT04175691. Registered November 21, 2019, https://www.clinicaltrials.gov/ct2/show/NCT04175691 .

Abstract Background To elucidate the mechanism of dysfunction of tolerogenic dendritic cells (DCs) is of significance. Telomerase involves the regulation of the cell fate and activities. The objective of this study is to investigate the role of telomerase reverse transcriptase (TERT) in regulating the tolerogenic feature of DCs. Methods The telomerase was assessed in DCs, which were collected from patients with allergic rhinitis (AR), healthy control (HC) subjects, and mice. RNAs were extracted from DCs, and analyzed by RNA sequencing (RNAseq), real-time quantitative RT-PCR, and Western blotting. Results The results showed that expression of TERT was higher in peripheral DCs of AR patients. The expression of IL10 in DCs was negatively correlated with the levels of TERT expression. Importantly, the levels of TERT mRNA in DCs were associated with the AR response in patients with AR. Endoplasmic reticulum (ER) stress promoted the expression of Tert in DCs. Sensitization with the ovalbumin-aluminum hydroxide protocol increased the expression of Tert in DCs by exacerbating ER stress. TERT interacting with c-Maf (the transcription factor of IL-10) inducing protein (CMIP) in DCs resulted in CMIP ubiquitination and degradation, and thus, suppressed the production of IL-10. Inhibition of Tert in DCs mitigated experimental AR. Conclusions Elevated amounts of TERT were detected in DCs of patients with AR. The tolerogenic feature of DCs was impacted by TERT. Inhibited TERT attenuated experimental AR.

Abstract The hippocampus creates a cognitive map of the external environment by encoding spatial and self-motion-related information. However, it is unclear whether hippocampal neurons could also incorporate internal cognitive states reflecting an animal’s exploratory intention, which is not driven by rewards or unexpected sensory stimuli. In this study, a subgroup of CA1 neurons was found to encode both spatial information and animals’ investigatory intentions in male mice. These neurons became active before the initiation of exploration behaviors at specific locations and were nearly silent when the same fields were traversed without exploration. Interestingly, this neuronal activity could not be explained by object features, rewards, or mismatches in environmental cues. Inhibition of the lateral entorhinal cortex decreased the activity of these cells during exploration. Our findings demonstrate that hippocampal neurons may bridge external and internal signals, indicating a potential connection between spatial representation and intentional states in the construction of internal navigation systems.

BackgroundLong-term exposure to ambient fine particulate matter (PM2.5) may increase the risk of diabetes, and a healthy diet can effectively control fasting blood glucose levels. However, it is unclear whether dietary factors have a moderating effect on the risk of diabetes associated with atmospheric PM2.5 exposure. ObjectiveTo investigate the association between long-term exposure to PM2.5 and diabetes in rural areas of Ningxia, and potential interaction of long-term exposure to atmospheric PM2.5 and diet on diabetes.MethodsThe study subjects were selected from the baseline survey data of the China Northwest Cohort-Ningxia (CNC-NX) , a natural population cohort. A total of 13917 subjects were included, excluding participants with missing covariate information. We utilized the annual average ambient PM2.5 concentration from 2014 to 2018 as the long-term exposure level. Logistic regression and multiple linear regression were employed to analyze the associations of long-term atmospheric PM2.5 exposure with diabetes and fasting blood glucose levels. Stratification by frequency of vegetable consumption, frequency of fruit consumption, and salty taste was used to examine moderating effects on the diabetes risk associated with atmospheric PM2.5 exposure.ResultsThe mean age of the 13917 subjects was (56.8±10.0) years, and the prevalence of diabetes was 9.8%. Between 2014 and 2018, the average annual concentration of PM2.5 was (38.10±4.67) μg·m−3. The risk (OR) of diabetes was 1.018 (95%CI: 1.005, 1.032) and the fasting blood glucose was increased by 0.011 (95%CI: 0.004, 0.017) mmol·L−1 for each 1 μg·m−3 increase in PM2.5 concentration. Compared to those who consumed vegetables < 1 time per week, individuals who consume vegetables 1-3 times per week and ≥4 times per week had a reduced risk of developing diabetes by 27.1% (OR=0.729, 95%CI: 0.594, 0.893) and 16.8% (OR=0.832, 95%CI: 0.715, 0.971) respectively. Similarly, when compared to those who consumed fruits

BackgroundThe impact of atmospheric fine particulate matter (PM2.5) and ozone (O3) on the mortality of circulatory system diseases cannot be ignored. However, whether the interaction between PM2.5 and O3 can affect population health is rarely reported and requires study. ObjectiveTo investigate the individual and interactive impacts of atmospheric PM2.5 and O3 on the mortality of circulatory system diseases in the population of Ningxia region. MethodsThe data of 119647 deaths due to circulatory system diseases, daily average concentrations of atmospheric pollutants, and meteorological data in Ningxia from 2013 to 2020 were retrieved. PM2.5 was divided into low, medium, and high concentrations according to the primary and secondary national limits (35 and 75 μg·m−3) of the Ambient air quality standards. Similarly, O3 was divided into low, medium, and high concentrations according to the national limits (100 and 160 μg·m−3). Using a generalized additive mixed model based on quasi Poisson distribution, the impacts of atmospheric PM2.5 and O3 as well as their interaction on the mortality of circulatory system diseases were analyzed using the population data of Ningxia region. ResultsDuring the target period, males and the ≥ 65 year group accounted for larger proportions of deaths due to circulatory system diseases (55.47% and 79.87% respectively). The daily average concentration of PM2.5 (40.25 μg·m−3) exceeded the national primary limit. In the single pollution model, the highest cumulative lag effects for mortality from circulatory system diseases were PM2.5 exposure over previous 1 d (lag01) and O3 exposure for previous 2 d (lag02), and their excess risk (ER) values were 1.03% (95%CI: 0.67%, 1.40%) and 1.02% (95%CI: 0.57%, 1.50%), respectively. The results of concentration stratification analysis showed that the most significant risks of death from circulatory system diseases [ER (95%CI): 1.12% (0.32%, 1.92%) and 0.95% (0.13%, 1.79%) respectively] were found at medium PM2.5 and O3 concentrations. The interaction analysis revealed that under, a synergistic effect on the risk of death from circulatory system diseases was identified (relative excess risk due to interaction=3.08%, attributable proportion of interaction=2.90%, synergy index=1.89) when considering the coexistence of PM2.5 and O3 above the primary limit. As the concentrations of PM2.5 and O3 increased, the synergistic effect increased the risk of death from circulatory system diseases in the general population, men, women, and the ≥ 65 years group. ConclusionBoth atmospheric PM2.5 and O3 can increase the risk of death from circulatory system diseases, and the two pollutants have a synergistic effect on the risk of death from circulatory system diseases.

Since the data samples on client devices are usually non-independent and non-identically distributed (non-IID), this will challenge the convergence of federated learning (FL) and reduce communication efficiency. This paper proposes FedQMIX, a node selection algorithm based on multi-agent reinforcement learning(MARL), to address these challenges. Firstly, we observe a connection between model weights and data distribution, and a clustering algorithm can group clients with similar data distribution into the same cluster. Secondly, we propose a QMIX-based mechanism that learns to select devices from clustering results in each communication round to maximize the reward, penalizing the use of more communication rounds and thereby improving the communication efficiency of FL. Finally, experiments show that FedQMIX can reduce the number of communication rounds by 11% and 30% on the MNIST and CIFAR-10 datasets, respectively, compared to the baseline algorithm (Favor).

In the era of information technology, the exponential growth of data volume has compelled users to entrust their data to database service providers for efficient management. While traditional methods such as user authentication, security auditing, and access control have been implemented to safeguard data security across databases, cloud servers may face security challenges due to excessive internal administrator permissions. The audio technology of the Internet of Things (IoT) offers numerous advantages, including high bandwidth, short data transmission time, long transmission distance, and cost-effectiveness. It has found widespread applications in military, technological, industrial, and everyday life settings. With the advancements in modern information technology and the development and enhancement of wireless radio frequency technology in the IoT sector, IoT-based wireless audio interaction systems utilizing Wi-Fi have gradually become integrated into people's lives. These systems have enriched people's daily experiences and are increasingly popular among consumers. This paper, based on the theory of functional applied linguistics, combs the basic theoretical framework and the practical application prospect of functional Applied Linguistics of systemic language, especially emphasizes the important influence and application enlightenment of systemic functional linguistics on language teaching, and combines the ''Recent Development Zone'' The basic concepts of contemporary language and literature education, such as scaffolding, are summarized and analyzed. The paper establishes a comprehensive theoretical research framework for college spoken English teaching, and through the comprehensive theoretical analysis of communicative teaching methods and practical exploration of some problems that students may appear, it puts forward more effective and targeted specific solutions.

BackgroundThe contribution of long-term ambient PM2.5 exposure to hypertension should not be ignored. However, the conclusions of whether dietary factors play a role in regulating PM2.5-related hypertension are still inconsistent. ObjectiveTo explore the correlation between long-term exposure to ambient PM2.5 and blood pressure indicators (systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure) in adults in Ningxia and a potential moderating effect of dietary factors. MethodsA set of cross-sectional survey data from March, 2013 to May, 2018 was retrieved from the China Northwest Cohort-Ningxia, and the average ambient PM2.5 concentration in the previous three years was also collected to estimate the long-term exposure of the participants. Binary logistic regression model was used to validate the correlation between long-term exposure to ambient PM2.5 and hypertension in Ningxia, and linear model was used to study the correlation between long-term exposure to ambient PM2.5 and blood pressure indicators (systolic blood pressure, diastolic blood pressure, mean arterial pressure and pulse pressure), and to explore the influence of dietary factors on ambient PM2.5-related hypertension. ResultsA total of 11470 participants were included in the study, 42.2% male and 57.8% female. The three-year average ambient PM2.5 concentration before the baseline survey was 37.0 μg·m−3. Each 1 μg·m−3 increase in ambient PM2.5 was associated with an increased risk of hypertension (OR=1.111, 95%CI: 1.097, 1.125), and increased systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure by 0.886 (95%CI: 0.783, 0.990), 0.570 (95%CI: 0.500, 0.641), 0.676 (95%CI: 0.600, 0.751), and 0.316 (95%CI: 0.243, 0.389) mmHg, respectively. The stratified analysis showed that the OR and 95%CI of hypertension were 1.171 (1.097, 1.254), 1.117 (1.064, 1.174), and 1.160 (1.116, 1.207) respectively for each 1 μg·m−3 increased in PM2.5 with low frequency of vegetable and fruit consumption and salty taste respectively. The OR and 95%CI of hypertension were decreased when the moderate and high frequency of vegetable and fruit intake and moderate and light taste applied, the values were 1.091 (1.062, 1.121) and 1.114 (1.097, 1.131), 1.105 (1.082, 1.129) and 1.111 (1.092, 1.13), 1.115 (1.090, 1.140) and 1.102 (1.083, 1.121) respectively. Compared with low frequency of vegetable and fruit intake and salty taste, the increase degree of ambient PM2.5 related systolic blood pressure, diastolic blood pressure, mean arterial pressure and pulse pressure also decreased in middle and high frequency of vegetable and fruit intake and moderate and light taste. ConclusionLong-term exposure to ambient PM2.5 is significantly associated with increased risks of hypertension and blood pressure in Ningxia area. Increasing the frequency of vegetable and fruit intake and decreasing salty taste may reduce the effect of ambient PM2.5 on hypertension and blood pressure.

Modern linguistic theories and network science propose that language and speech processing are organized into hierarchical, segregated large-scale subnetworks, with a core of dorsal (phonological) stream and ventral (semantic) stream. The two streams are asymmetrically recruited in receptive and expressive language or speech tasks, which showed flexible functional segregation and integration. We hypothesized that the functional segregation of the two streams was supported by the underlying network segregation. A dynamic conditional correlation approach was employed to construct framewise time-varying language networks and k-means clustering was employed to investigate the temporal-reoccurring patterns. We found that the framewise language network dynamics in resting state were robustly clustered into four states, which dynamically reconfigured following a domain-separation manner. Spatially, the hub distributions of the first three states highly resembled the neurobiology of speech perception and lexical-phonological processing, speech production, and semantic processing, respectively. The fourth state was characterized by the weakest functional connectivity and was regarded as a baseline state. Temporally, the first three states appeared exclusively in limited time bins (∼15%), and most of the time (> 55%), state 4 was dominant. Machine learning-based dFC-linguistics prediction analyses showed that dFCs of the four states significantly predicted individual linguistic performance. These findings suggest a domain-separation manner of language network dynamics in resting state, which forms a dynamic “meta-network” framework to support flexible functional segregation and integration during language and speech processing.

SAR three-Dimensional (3D) imaging of complex structural facilities is an important and challenging issue in SAR imaging. The existing 3D SAR imaging relies on multiple channels or flights in the elevation direction, exerting high demands on the radar system or data acquisition. This paper proposes a 3D imaging method for complex structural facilities without a prior model, and the full-aspect 3D image of the entire scene in the region with unknown prior information can be obtained solely using a single flight. This method completely utilizes the full-aspect observation as well as the layover and elevation ambiguity resolving capabilities of circular SAR without requiring target pre-modeling and 3D imaging grid construction. Moreover, the method is suitable for fine 3D imaging complex structural facilities in large areas. Significant progress has been made in the practical technology of radar 3D imaging. The full-aspect 3D radar images of the FAST radio telescope are obtained for the first time with the proposed method, thus verifying the correctness and effectiveness of our theory and method.

Abstract With the increasing prevalence and mortality, chronic kidney disease (CKD) has become a world public health problem. As the primary pathological manifestation in CKD, renal fibrosis is often used as a critical target for the treatment of CKD and inhibits the progression of CKD to end-stage renal disease (ESRD). As a potential drug, natural products have been confirmed to have the potential as a routine or supplementary therapy for chronic kidney disease, which may target renal fibrosis and act through various pharmacological activities such as anti-inflammatory and anti-oxidation of natural products. This article briefly introduces the pathological mechanism of renal fibrosis and systematically summarizes the latest research on the treatment of renal fibrosis with natural products of Chinese herbal medicines.

With the expansion of Synthetic Aperture Radar (SAR) applications and the development of SAR data acquisition technology, multiangle SAR datasets of various typical targets need to be constructed. Presently, a comprehensive multiangle SAR image dataset for aircraft targets is still lacking. This study explores a method of dataset construction based on the acquisition of actual data and intelligent simulation. Multiangle SAR images of aircraft targets are collected through flight tests, and the interpolation simulations of SAR images of specific angles are realized based on scattering analysis and self-attention generative adversarial network, which provide a new solution for dataset construction and expansion. Finally, under the assumption that some data are missing, the similarities between the simulated and actual images are evaluated using six evaluation indices, which verify the effectiveness of the proposed method.

Systemic sclerosis (SSc) is a connective tissue disease with high mortality. One of the most common causes of death in potential SSc patients is cardiac arrest. However, the pathogenesis of cardiac death is not very clear. As far as we know, there are few autopsy reports on this subject. Our autopsy report on two fatal cases of heart injury in SSc patients revealed evidence of myocarditis, focal myocardial necrosis, and myocardial fibrosis. Our findings suggest that chronic inflammation of the heart may lead to extensive fibrosis, which could contribute to the high mortality rate observed in SSc patients. Early detection of heart injury in SSc patients using existing technology is necessary to improve patient outcomes. Future research should focus on developing more effective methods for early detection and management of heart involvement in SSc.

Air pollution has become one of the most important public health problems worldwide. Exposure to air pollution during pregnancy is one of the important risk factors for adverse birth outcomes such as preterm birth, low birth weight, and birth defects. Air pollution control has a long way to go. Therefore, it is extremely urgent to analyze and identify relevant protective factors. Some studies have shown that green space may be a protective factor for the adverse birth outcomes related to air pollution. This kind of research mainly utilizes satellite monitoring data, quantifies the green space coverage level in a certain range of buffer zone centered on the pregnant women's home addresses, and analyzes its mediation effect on the adverse pregnancy outcomes related to air pollution. In this paper we reviewed the use of green space data, the estimated effect of green space mediating the relationship between air pollution and adverse birth outcomes, and its possible mechanisms, aiming to clarify the impact of green space on adverse birth outcomes related to air pollution and provide a scientific basis for public health intervention strategies.

The wax deposits of diesel may be formed at low environment temperature during the batch transportation of products pipeline, which will contaminate the subsequent gasoline, resulting in the loss of oil mixing. Therefore, researches on wax deposition of diesel are significant to ensure the economic and efficient operation of products pipelines. Herein, the existing theories on wax deposition were reviewed, and the status of experimental study on wax deposition of diesel was clarified from perspectives of static and dynamic experiments. In addition, the prediction models of wax deposition rate of diesel based on the theories of molecular diffusion and shear dispersion were summarized. Thereby, it is pointed out that strengthening the research on wax deposition mechanism, establishing wax deposition model, and quantitatively characterizing the change rules of quality parameters of the subsequent gasoline with the wax dissolved, are the key direction of research on batch transportation of products pipeline. Besides, by systematically representing the progress of researches on wax deposition of diesel, some reference is provided for the relevant deep researches that may be performed in the future.

The acquisition of movable jaws was a major event during vertebrate evolution. The role of NK3 homeobox 2 (Nkx3.2) transcription factor in patterning the primary jaw joint of gnathostomes (jawed vertebrates) is well known, however knowledge about its regulatory mechanism is lacking. In this study, we report a proximal enhancer element of Nkx3.2 that is deeply conserved in most gnathostomes but undetectable in the jawless hagfish and lamprey. This enhancer is active in the developing jaw joint region of the zebrafish Danio rerio, and was thus designated as jaw joint regulatory sequence 1 (JRS1). We further show that JRS1 enhancer sequences from a range of gnathostome species, including a chondrichthyan and mammals, have the same activity in the jaw joint as the native zebrafish enhancer, indicating a high degree of functional conservation despite the divergence of cartilaginous and bony fish lineages or the transition of the primary jaw joint into the middle ear of mammals. Finally, we show that deletion of JRS1 from the zebrafish genome using CRISPR/Cas9 results in a significant reduction of early gene expression of nkx3.2 and leads to a transient jaw joint deformation and partial fusion. Emergence of this Nkx3.2 enhancer in early gnathostomes may have contributed to the origin and shaping of the articulating surfaces of vertebrate jaws.

Abstract Background Esophagogastroduodenoscopy is very useful in diagnosing and treating upper gastrointestinal mucosal disorders, but too much foam and water in stomach decrease its diagnostic efficiency. Simethicone administration can help remove excessive foam. Aims To determine the optimal simethicone administration strategies in a comparative randomized controlled clinical trial. Methods Adult outpatients with indications for esophagogastroduodenoscopy were enrolled and randomly divided into group 1 (simethicone solution intake 20–30 min before procedure, n = 110), group 2 (simethicone solution intake 31–60 min before procedure, n = 92), and group 3 (simethicone solution intake > 60 min before procedure). Primary and secondary outcomes were procedure time and the patients’ satisfaction after the examination. All symptoms like abdominal pain and distension were recorded. Results No statistically significant differences were found on the patients’ demographic and clinical features and mean examination time (all P values > 0.05). The distribution of patients with different endoscopic and pathological diagnosis was comparable among three groups, respectively (P = 0.607; P = 0.289). However, the proportion of patients with Gastric Cleanness Grade A was most in group 2 (n = 73, 79.3%), and patient proportion with Gastric Cleanness Grade C was most found in group 1 (n = 72, 65.5%), which was greatly different (P < 0.001). There was no statistically significant difference on the satisfaction scores [immediately 6 (3–8) vs. 6 (1–10) vs. 6 (1-9), P = 0.533; 2 h after 10 (8–10) vs. 10 (10–10) vs. 10 (8-10), P = 0.463]. Conclusion Simethicone solution intake 31–60 min before esophagogastroduodenoscopy can help obtain the best gastric cleanness, which is recommended in clinical practice (registered at ClinicalTrials.gov, NCT03776916 on December 13, 2018).

Abstract Ozone treatment is a useful approach to maintain postharvest quality for various fruits and vegetables. In this study, the effects of ozone fumigation on lignification and postharvest quality changes in water bamboo shoots were investigated. Water bamboo shoots were respectively treated with ozone at the concentrations of 0 (control), 3, 6, 9, and 12 µl L−1, packaged in polyethylene packing bag and stored at 2 ± 1°C for 60 days. The results showed that ozone treatment maintained the lightness, whiteness index values and retarded the lignification during storage. Water bamboo shoots treated with 9 µl L−1 ozone showed the best fruit quality and the least lignification. Ozone treatment also slowed the decrease of soluble pectin content and cellulose accumulation by inhibiting the activities of cellulase (Cx) and polygalacturonase. In addition, ozone treatment also protected cell ultrastructure. Ozone treatment could be a potential alternative for inhibiting lignification and delaying quality deterioration of water bamboo shoots during storage.

Circular synthetic aperture radar (CSAR) has the potential to form 3D images with single-pass single-channel radar data, which is very time-efficient. This article proposes a volumetric neural renderer that utilizes CSAR 2D amplitude images to reconstruct the 3D power distribution of the imaged scene. The innovations are two-fold: Firstly, we propose a new SAR amplitude image formation model that establishes a linear mapping relationship between multi-look amplitude-squared SAR images and a real-valued 4D (spatial location (x, y, z) and azimuth angle θ) radar scattered field. Secondly, incorporating the proposed image formation model and SAR imaging geometry, we extend the neural radiance field (NeRF) methods to reconstruct the 4D radar scattered field using a set of 2D multi-aspect SAR images. Using real-world drone SAR data, we demonstrate our method for (1) creating realistic SAR imagery from arbitrary new viewpoints and (2) reconstructing high-precision 3D structures of the imaged scene.

Cell search is the first step to establish downlink synchronization between user equipment (UE) and base station (BS) in the fifth generation (5G) new radio (NR) system. However, frequency offset and noise will cause a massive loss of synchronization performance. To solve this problem, a novel timing synchronization algorithm of primary synchronization signal (PSS) with anti-frequency offset and anti-noise is proposed, which includes the improved coarse synchronization algorithm based on Fourier transform and the fine synchronization algorithm based on the triple auto-correlation algorithm. The improved coarse synchronization algorithm not only has a strong frequency offset resistance, especially for large frequency offset, but also obtains the estimated frequency offset. The fine synchronization algorithm is more resistant to noise than the conventional algorithm. Finally, the algorithm analysis and simulation results show that the improved algorithm can work very well even when the normalized frequency offset increases to greater than 0.8, but the conventional algorithm fails to synchronize properly. Meanwhile, when the SNR is as low as -6dB, the detection accuracy of the timing synchronization based on the proposed fine synchronization algorithm is improved by about 31.7% compared with the conventional algorithm.

Glucagon-like peptide-1 receptor (GLP-1R) is a critical therapeutic target for type 2 diabetes mellitus (T2DM). The GLP-1R cellular signaling mechanism relevant to insulin secretion and blood glucose regulation has been extensively studied. Numerous drugs targeting GLP-1R have entered clinical treatment. However, novel functional molecules with reduced side effects and enhanced therapeutic efficacy are still in high demand. In this review, we summarize the basis of GLP-1R cellular signaling, and how it is involved in the treatment of T2DM. We review the functional molecules of incretin therapy in various stages of clinical trials. We also outline the current strategies and emerging techniques that are furthering the development of novel therapeutic drugs for T2DM and other metabolic diseases.

Chondroitin/dermatan sulfate (CS/DS) proteoglycans are indispensable for animal development and homeostasis but the large number of enzymes involved in their biosynthesis have made CS/DS function a challenging problem to study genetically. In our study, we generated loss-of-function alleles in zebrafish genes encoding CS/DS biosynthetic enzymes and characterized the effect on development in single and double mutants. Homozygous mutants in chsy1, csgalnact1a, csgalnat2, chpfa, ust and chst7, respectively, develop to adults. However, csgalnact1a-/- fish develop distinct craniofacial defects while the chsy1-/- skeletal phenotype is milder and the remaining mutants display no gross morphological abnormalities. These results suggest a high redundancy for the CS/DS biosynthetic enzymes and to further reduce CS/DS biosynthesis we combined mutant alleles. The craniofacial phenotype is further enhanced in csgalnact1a-/-;chsy1-/- adults and csgalnact1a-/-;csgalnact2-/- larvae. While csgalnact1a-/-;csgalnact2-/- was the most affected allele combination in our study, CS/DS is still not completely abolished. Transcriptome analysis of chsy1-/-, csgalnact1a-/- and csgalnact1a-/-;csgalnact2-/- larvae revealed that the expression had changed in a similar way in the three mutant lines but no differential expression was found in any of fifty GAG biosynthesis enzymes identified. Thus, zebrafish larvae do not increase transcription of GAG biosynthesis genes as a consequence of decreased CS/DS biosynthesis. The new zebrafish lines develop phenotypes similar to clinical characteristics of several human congenital disorders making the mutants potentially useful to study disease mechanisms and treatment.

Objective We aimed to develop a nomogram to predict cancer-specific survival (CSS) in patients with hypopharyngeal squamous cell carcinoma (HSCC) treated with primary surgery to provide more accurate risk stratification for patients. Methods We retrospectively collected data of 1144 eligible patients with HSCC from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Patients were randomly divided into training and validation groups (ratio 6:4) and we used univariate and multivariate Cox analysis. We developed and validated a nomogram using calibration plots and time-dependent receiver operating characteristic, Kaplan–Meier, and decision curves. Results Age; marital status; T, N, and M stage; and postoperative adjuvant therapy were independent factors associated with CSS, which were included in the nomogram. The nomogram’s C-index was 0.705 to 0.723 in the training group and 0.681 to 0.736 in the validation group, which were significantly higher than conventional American Joint Committee on Cancer (AJCC) staging. Calibration curves showed good agreement between prediction and observation in both groups. Kaplan–Meier and decision curves suggested the nomogram had better risk stratification and net benefit than conventional AJCC staging. Conclusions We established a nomogram that was superior to conventional AJCC staging in predicting CSS for HSCC.

We investigate the problem of obtaining dense 3D reconstruction from airborne multi-aspect synthetic aperture radar (SAR) image sequences. Dense 3D reconstructions of multi-view SAR images are vulnerable to anisotropic scatters. To address this issue, we propose a probabilistic 3D reconstruction method based on jointly estimating the pixel’s height and degree of anisotropy. Specifically, we propose a mixture distribution model for the stereo-matching results, where the degree of anisotropy is modeled as an underlying error source. Then, a Bayesian filtering method is proposed for dense 3D point cloud generation. For real-time applications, redundancy in multi-aspect observations is further exploited in a probabilistic manner to accelerate the stereo-reconstruction process. To verify the effectiveness and reliability of the proposed method, 3D point cloud generation is tested on Ku-band drone SAR data for a domestic airport area.

Mechanical pigging is a major wax removal technique in crude oil pipeline transportation. To lower the risk of pig stalling accidents in pigging, a superparamagnetic nanoparticle (SPM-NP) pigging system that consists of an electromagnetic pig and nanopaint is designed to soften the wax deposit and reduce the wax resistive force. During pigging, the induction coil on the pig generates an alternating magnetic field, which induces heat production of the nanopaint on the pipe wall. The COMSOL software is used to simulate the temperature distribution of the wax layer. Yield stress measurements reveal that the wax layer yield stress is nearly linearly correlated to temperature. Compared with a regular pig, the SPM-NP pigging system reduces the wax resistive force by up to 20~40%, with an acceptable electrical current intensity of about 20 A in the given cases. Multiple factors affecting the wax layer temperature were analyzed. SPM-NP heating could be a promising technique for wax remediation and hydrate prevention.

As the basic tools for neuroscience research, invasive neural recording devices can obtain high-resolution neuronal activity signals through electrodes connected to the subject’s brain. Existing wireless neural recording devices are large in size or need external large-scale equipment for wireless power supply, which limits their application. Here, we developed an ultra-low-noise, low power and miniaturized dual-channel wireless neural recording microsystem. With the full-differential front-end structure of the dual operational amplifiers (op-amps), the noise level and power consumption are notably reduced. The hierarchical microassembly technology, which integrates wafer-level packaged op-amps and the miniaturized Bluetooth module, dramatically reduces the size of the wireless neural recording microsystem. The microsystem shows a less than 100 nV/Hz ultra-low noise level, about 10 mW low power consumption, and 9 × 7 × 5 mm3 small size. The neural recording ability was then demonstrated in saline and a chronic rat model. Because of its miniaturization, it can be applied to freely behaving small animals, such as rats. Its features of ultra-low noise and high bandwidth are conducive to low-amplitude neural signal recording, which may help advance neuroscientific discovery.

In this paper, a novel adaptive second-order sliding mode (2-SM) control approach, based on online zero-crossing detection, was proposed to solve the problems of the chattering and fixed control gain for buck converters with multi-disturbances. In modeling, the possible parameter perturbations and external disturbances of the converter system were contained. Instead of the traditional first-order sliding mode (1-SM), the twisting algorithm with 2-SM was adopted for the controller design, which could overcome the chattering problem and realize control continuity. Meanwhile, a novel adaptive mechanism was introduced to replace the conventional fixed control gain by time-varying control gain, the idea of which is to calculate the number of the zero-crossing points of the sliding surface online. As a result, the control magnitude of the improved controller could be reduced to a minimal admissible level, and the steady error of the output voltage could converge to the expected value. Furthermore, the robust stability of the converter system with multi-disturbances wads investigated. Comparative simulations and experiments validated the advantages of this paper as offering better robustness and control performance.

According to the recent report, 12 000 new Android malware samples will be generated every day. Efficient identification of evolving malware is an urgent challenge. Traditional methods based on structured features such as permissions and sensitive application programming interface (API) calls lack high-level behavioral semantics to detect evolving malware. The methods based on call graphs (CG) are good at behavioral semantic analysis but face the problem of huge time and space consumption, which leads to low detection efficiency. In this paper, we propose a novel Android malware detection method based on the method-level correlation relationship of application's abstracted API calls. First, we split each Android application's source code into separate function methods and just keep the abstracted API calls of them to form a set of abstracted API calls transactions. And then, we calculate the confidence of association rules between the abstracted API calls, which forms behavioral semantics to describe an application. Finally, we combine machine learning to identify the different behavioral patterns of malicious and benign apps to build the detection system. The results of our empirical evaluation show our system is competitive in terms of classification accuracy and detection efficiency. At dataset Drebin (benign 5.9K and malware 5.6K) and AMD (benign 20.5K and malware 20.8K), our system has achieved 96% and 98% detection results both in accuracy and F-measure. Compared with the state-of-the-art system in detecting evolving malware called MaMaDroid on the dataset of 6.0K benign and 20.5K malicious samples spanning from 2010 to 2017, our system achieves higher accuracy while improving detection efficiency by 15 times (2.9 s versus 45.7 s per sample).

The transcription factor Nkx3.2 (Bapx1) is an important chondrocyte maturation inhibitor. Previous Nkx3.2 knockdown and overexpression studies in non-mammalian gnathostomes have focused on its role in primary jaw joint development, while the function of this gene in broader skeletal development is not fully described. We generated a mutant allele of nkx3.2 in zebrafish with CRISPR/Cas9 and applied a range of techniques to characterize skeletal phenotypes at developmental stages from larva to adult, revealing loss of the jaw joint, fusions in bones of the occiput, morphological changes in the Weberian apparatus, and the loss or deformation of bony elements derived from basiventral cartilages of the vertebrae. Axial phenotypes are reminiscent of Nkx3.2 knockout in mammals, suggesting that the function of this gene in axial skeletal development is ancestral to osteichthyans. Our results highlight the broad role of nkx3.2 in zebrafish skeletal development and its context-specific functions in different skeletal elements.

Summary: Cisplatin-based neoadjuvant chemotherapy has been shown to improve survival in patients with squamous cell carcinoma (SCC), but clinical biomarkers to predict chemosensitivity remain elusive. Here, we show the long noncoding RNA (lncRNA) LINC01011, which we termed cisplatin-sensitivity-associated lncRNA (CISAL), controls mitochondrial fission and cisplatin sensitivity by inhibiting BRCA1 transcription in tongue SCC (TSCC) models. Mechanistically, we found CISAL directly binds the BRCA1 promoter and forms an RNA-DNA triplex structure, sequestering BRCA1 transcription factor-GABPA away from the downstream regulatory binding region. Importantly, the clinical relevance of these findings is suggested by the significant association of CISAL and BRCA1 expression levels in TSCC tumors with neoadjuvant chemosensitivity and overall survival. We propose a new model where lncRNAs are tethered at gene promoter by RNA-DNA triplex formation, spatially sequestering transcription factors away from DNA-binding sites. Our study uncovers the potential of CISAL-BRCA1 signaling as a potential target to predict or improve chemosensitivity. : Biological Sciences; Molecular Biology; Cell Biology; Cancer Subject Areas: Biological Sciences, Molecular Biology, Cell Biology, Cancer

Azimuth non-uniform signal-reconstruction is a critical step for azimuth multi-channel high-resolution wide-swath (HRWS) synthetic aperture radar (SAR) data processing. However, the received non-uniform signal has noise in the actual azimuth multi-channel SAR (MCSAR) operation, which leads to the serious reduction in the signal-to-noise ratio (SNR) of the results processed by a traditional reconstruction algorithm. Aiming to address the problem of reducing the SNR of the traditional reconstruction algorithm in the reconstruction of non-uniform signal with noise, a novel signal-reconstruction algorithm based on two-step projection technology (TSPT) for the MCSAR system is proposed in this paper. The key part of the TSPT algorithm consists of a two-step projection. The first projection is to project the given signal into the selected intermediate subspace, spanned by the integer conversion of the compact support kernel function. This process generates a set of sparse equations, which can be solved efficiently by using the sparse equation solver. The second key projection is to project the first projection result into the subspace of the known sampled signal. The secondary projection can be achieved with a digital linear translation invariant (LSI) filter and generate a uniformly spaced signal. As a result, compared with the traditional azimuth MCSAR signal-reconstruction algorithm, the proposed algorithm can improve SNR and reduce the azimuth ambiguity-signal-ratio (AASR). The processing results of simulated data and real raw data verify the effectiveness of the proposed algorithm.

As the main inorganic component of xenogenic bone graft material, bone-derived biological apatite (BAp) has been widely used in implant dentistry, oral and maxillofacial surgery and orthopedics. However, BAp produced via calcination of animal bones still suffers from some drawbacks, such as insufficient mechanical strength and inadequate degradation rate, which impede its application. Fluoride is known to play important roles in both physiological and pathological processes of human hard tissues for its double effects on bones and teeth. In order to understand the effects of fluoride on the properties of BAp, as well as the mechanism behind them, porcine bone derived hydroxyapatite (PHAp) was prepared via thermal treatment, which was then fluoride incorporated at a series concentrations of sodium fluoride, and noted as 0.25-FPHAp, 0.50-FPHAp, and 0.75-FPHAp respectively. The physicochemical characteristics of the materials, including crystal morphology, crystallinity, functional groups, elemental composition, compressive strength, porosity and solubility, were then determined. The biological properties, such as protein adsorption and cell attachment, were also evaluated. It was found that the spheroid-like crystals of PHAp were changed into rod-like after fluoride substitution, resulting in a fluoride concentration-dependent increase in compressive strength, as well as a decreased porosity and solubility of the apatite. However, even though the addition of fluoride was demonstrated to enhance protein adsorption and cell attachment of the materials, the most favorable results were intriguingly achieved in FPHAp with the least fluoride content. Collectively, low level of fluoride incorporation is proposed promising for the modification of clinically used BAp based bone substitute materials, because of its being able to maintain a good balance between physicochemical and biological properties of the apatite.

Abstract Video analysis of animal behaviour is widely used in fields such as ecology, ecotoxicology, and evolutionary research. However, when tracking multiple animals, occlusion and crossing are problematic, especially when the identity of each individual needs to be preserved. We present a new algorithm, ToxId, which preserves the identity of multiple animals by linking trajectory segments using their intensity histogram and Hu-moments. We verify the performance and accuracy of our algorithm using video sequences with different animals and experimental conditions. The results show that our algorithm achieves state-of-the-art accuracy using an efficient approach without the need of learning processes, complex feature maps or knowledge of the animal shape. ToxId is also computationally efficient, has low memory requirements, and operates without accessing future or past frames.

Long, robust hypocotyls are important for facilitating greenhouse transplant production. The use of far-red light at the end of the day (end-of-day far-red, EOD-FR) is known to prompt hypocotyl elongation, but the mechanism of EOD-FR-mediated hypocotyl elongation in pumpkin remains unclear. Here, we found that hypocotyl length, parenchymal cell size in hypocotyls, and plant IAA levels were significantly greater in pumpkin after EOD-FR treatment. This effect was counteracted by the application of the polar auxin transport inhibitor 1-N-naphthylphthalamic acid. Integrated transcriptomic and metabolomic analysis of pumpkin hypocotyls revealed that the expression of auxin-related genes changed significantly after EOD-FR treatment, and the contents of the auxin biosynthetic precursors tryptophan and indole were also significantly higher. Our results show that auxin plays an essential role in EOD-FR-mediated hypocotyl elongation, shed light on the mechanisms of EOD-FR mediated hypocotyl elongation, and provide a theoretical basis for the use of EOD-FR in facility cultivation.

The capacity of an optical communication system can be greatly increased by using separate orbital angular momentum (OAM) modes as independent channels for signal transmission and encryption. At present, a transmissive OAM mode generator compatible with wavelength division multiplexing is being highly pursued. Here, we introduce a specific double-layer reverse-twist configuration into liquid crystal polymer (LCP) to overcome wavelength dependency. With this design, broadband-applicable OAM array generators are proposed and demonstrated. A Damman vortex grating and a Damman q-plate were encoded via photopatterning two subsequent LCP layers adopted with oppositely handed chiral dopants. Rectangular and hexagonal OAM arrays with mode conversion efficiencies exceeding 40.1% and 51.0% in the ranges of 530 to 930 nm, respectively, are presented. This provides a simple and broadband efficient strategy for beam shaping.

Particle and object tracking is gaining attention in industrial applications and is commonly applied in: colloidal, biophysical, ecological, and micro-fluidic research. Reliable tracking information is heavily dependent on the system under study and algorithms that correctly determine particle position between images. However, in a real environmental context with the presence of noise including particular or dissolved matter in water, and low and fluctuating light conditions, many algorithms fail to obtain reliable information. We propose a new algorithm, the Circular Symmetry algorithm (C-Sym), for detecting the position of a circular particle with high accuracy and precision in noisy conditions. The algorithm takes advantage of the spatial symmetry of the particle allowing for subpixel accuracy. We compare the proposed algorithm with four different methods using both synthetic and experimental datasets. The results show that C-Sym is the most accurate and precise algorithm when tracking micro-particles in all tested conditions and it has the potential for use in applications including tracking biota in their environment.

Biological hydroxyapatite, derived from animal bones, is the most widely used bone substitute in orthopedic and dental treatments. Fluorine is the trace element involved in bone remodeling and has been confirmed to promote osteogenesis when administered at the appropriate dose. To take advantage of this knowledge, fluorinated porcine hydroxyapatite (FPHA) incorporating increasing levels of fluoride was derived from cancellous porcine bone through straightforward chemical and thermal treatments. Physiochemical characteristics, including crystalline phases, functional groups and dissolution behavior, were investigated on this novel FPHA. Human osteoblast-like MG63 cells were cultured on the FPHA to examine cell attachment, cytoskeleton, proliferation and osteoblastic differentiation for in vitro cellular evaluation. Results suggest that fluoride ions released from the FPHA play a significant role in stimulating osteoblastic activity in vitro, and appropriate level of fluoridation (1.5 to 3.1 atomic percents of fluorine) for the FPHA could be selected with high potential for use as a bone substitute.