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Alzheimer's disease (AD) is a disease that affects the cognitive abilities of older adults, and it is one of the biggest global medical challenges of the 21st century. Acetylcholinesterase (AChE) can increase acetylcholine concentrations and improve cognitive function in patients, and is a potential target to develop small molecule inhibitors for the treatment of Alzheimer's disease (AD). In this study, 29 vilazodone-donepezil chimeric derivatives are systematically studied using 3D-QSAR modeling, and a robust and reliable Topomer CoMFA model was obtained with: q2 = 0.720, r2 = 0.991, F = 287.234, N = 6, and SEE = 0.098. Based on the established model and combined with the ZINC20 database, 33 new compounds with ideal inhibitory activity are successfully designed. Molecular docking and ADMET property prediction also show that these newly designed compounds have a good binding ability to the target protein and can meet the medicinal conditions. Subsequently, four new compounds with good comprehensive ability are selected for molecular dynamics simulation, and the simulation results confirm that the newly designed compounds have a certain degree of reliability and stability. This study provides guidance for vilazodone-donepezil chimeric derivatives as a potential AChE inhibitor and has certain theoretical value. [ABSTRACT FROM AUTHOR]

Studying driving factors of the urban heat island phenomenon is vital for enhancing urban ecological environments. Urban functional zones (UFZs), key for planning and management, have a substantial impact on the urban thermal environment through their two-dimensional (2D)/three-dimensional (3D) morphology. Despite prior research on land use and landscape patterns, understanding the effects of 2D/3D urban morphology in different UFZs is lacking. This study employs Landsat-8 remote sensing data to retrieve the land surface temperature (LST). A method combining supervised and unsupervised classification is proposed for UFZ mapping, utilizing multi-source geospatial data. Subsequently, parameters defining the 2D/3D urban morphology of UFZs are established. Finally, the Pearson correlation analysis and GeoDetector are used to analyze the driving factors. The results indicate the following: (1) In the Fifth Ring Road area of Beijing, the residential zones exhibit the highest LST, followed by the industrial zones. (2) In 2D urban morphology, the percentage of built-up landscape (built-PLAND) and Shannon's diversity index (SHDI) are the main factors influencing LST. In 3D urban morphology, building density, the sky view factor (SVF), and the area-weighted mean shape index (shape index) are the main factors influencing LST. Therefore, low-density buildings with simple and dispersed shapes contribute to mitigating LST, while fragmented distributions of trees, grasslands, and water bodies also play important roles in alleviating LST. (3) In the interactive detection results, all UFZs show the highest interaction detection results with the built-PLAND. (4) Spatial variations are observed in the impact of different UFZs on LST. For instance, in the residential zones, industrial zones, green space zones, and public service zones, the SVF is negatively correlated with LST, while in the commercial zones, the SVF exhibits a positive correlation with LST. [ABSTRACT FROM AUTHOR]

The uniform dispersion of hexagonal boron nitride (h‐BN) in a waterborne polymer matrix remains a challenge in preparing waterborne uniform h‐BN/polymer composite coating. Here, cationic Gemini surfactant (GS‐16) is used as a surfactant and intercalator to exfoliate and functionalize bulk h‐BN for preparing GS‐16‐functionalized h‐BN nanosheets (G‐BNNS). For comparison, the conventional hexadecyl trimethyl ammonium bromide (CTAB) surfactant with the same structural unit was utilized to prepare CTAB‐functionalized BNNS (C‐BNNS). Compared with C‐BNNS, G‐BNNS exhibits larger lateral size, lower thickness, and larger specific surface area. G‐BNNS and C‐BNNS are subsequently blended with waterborne polyurethane (WPU) to prepare composite coatings. Their morphologies, surface roughness, water resistance, mechanical properties and anticorrosive performance of composite coatings are comparatively studied. The water resistance, mechanical, and thermal stability of G‐BNNS/WPU‐0.3 wt% composite films are higher than that of C‐BNNS/WPU‐0.3 wt% and WPU films. The impedance modulus of G‐BNNS/WPU‐0.3 wt% is four orders of magnitude higher than that of pristine WPU and at least one order of magnitude higher than C‐BNNS/WPU‐0.3 wt%. GS‐16 is demonstrated to be an effective surfactant and intercalator to exfoliate and functionalize h‐BN. The as‐prepared G‐BNNS is also certified to be a high‐performance anticorrosive filler for waterborne polymer‐based coatings. [ABSTRACT FROM AUTHOR]

Unmanned aerial vehicles (UAV) play a vital role in many fields, such as agricultural planting, security patrol, emergency rescue, and so on. The development and implementation of these devices have become vital in terms of reachability and usability. Unfortunately, as drones become more widely used in various fields, they become more and more vulnerable to attacks and security threats, including, but not limited to, eavesdropping, man-in-the-middle attacks, and known session key attacks. In order to deal with these attacks and security threats and meet the needs of lightweight UAV communication, a secure and efficient authentication scheme is essential. To meet the security and lightweight requirements of an identity authentication scheme in a UAV communication network, this paper proposes an identity authentication scheme sdronelig based on an elliptic curve cryptosystem. The scheme realizes the mutual authentication and session key agreement configuration between the UAV and the ground station, and the authentication and key agreement between the UAVs can be realized with the help of the control station. The sdronelig authentication scheme is based on the ECDH key exchange protocol in the elliptic curve cryptography algorithm and adopts the MAC message authentication code technology and the method of pre-calculating part of the process. Under the premise of ensuring the security of the UAV communication network, the authentication efficiency is improved, the communication overhead and communication times are reduced, and the lightweight requirement of the UAV authentication scheme is met. Additionally, a formal verification tool is used to verify the security of the sdronelig scheme under the Dolev-Yao threat model, which is suitable for UAV networks. Finally, a detailed comparative study was conducted on security features, communication overhead, the number of communications, and computational overhead. The results show that the proposed sdronelig authentication scheme not only provides superior security features but also has better or comparable overhead compared to other existing authentication schemes. [ABSTRACT FROM AUTHOR]

As the most extensive port in Guangxi's inland economic hinterland, waterway transportation is an important driving force for the development of Guigang's cities. On the basis of tracing the development history of Guigang water transport city, this paper summarizes and analyzes the historical characteristics of water transport development and the spatial evolution of Guigang city, and proposes the planning strategy of Guigang's water transport city historical context, in order to improve the competitiveness of Guigang city and promote the development of Guigang city.

The leeches Whitmania pigra and Hirudo nipponia live in similar environments but have different feeding habits. At present, there are few studies of the foraging mechanism of leeches with different feeding habits. In this study, we first used maze tests to show that these two species of leeches could locate and distinguish their prey through chemosensory activity without mechanical stimulation. However, the two leech species have different foraging behaviors: Individuals of W. pigra move slowly and repeatedly adjust direction through probing and crawling to detect the location of prey (snails), whereas individuals of H. nipponia move quickly, and after determining the location of food (porcine blood), they quickly swim or crawl to the vicinity of their prey. Scanning electron microscopy (SEM) revealed that there are two types of sensory cilia and pore structures related to mucus secretion in the heads of both leeches. There are two differently sized types of chemoreceptors on the dorsal lip in W. pigra, which may have different functions during foraging, whereas in H. nipponia there is only one type of chemoreceptor, which is small. We detected the chemical components in the natural food of these two leech species by UHPLC–MS. There were 934 metabolites in the body fluid of snails and 751 metabolites in porcine serum; five metabolites unique to the body fluid of snails and to porcine serum were screened as candidate feeding attractants. Of these metabolites, betaine and arginine effectively attracted individuals of W. pigra and H. nipponia, respectively. In summary, leeches with different feeding habits use chemoreceptors to sense external chemical signals when foraging, and there are significant differences between species in foraging behavior, chemoreceptors, and attractants. [ABSTRACT FROM AUTHOR]

Many studies have reported that the geriatric nutritional risk index (GNRI) and C-reactive protein to albumin ratio (CAR) may be associated with prognosis of esophageal cancer (EC); however, the results are inconsistent. Therefore, we performed a meta-analysis to evaluate the effect of preoperative GNRI and CAR on the prognosis of EC. PubMed, Embase, Cochrane Library, and Web of Science databases were searched. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used to analyze the relationship between GNRI/CAR and prognosis. Publication bias was estimated using Begg's funnel plot asymmetry test and Egger's test. A total of 21 studies comprising 5,018 patients were included in the meta-analysis. A decreased GNRI was significantly associated with poorer overall survival (OS) (HR = 1.808, 95% CI: 1.489-2.196, P < 0.001) and cancer-specific survival (CSS) (HR = 1.769, 95% CI: 1.193-2.624, P = 0.005), and an increased CAR was significantly associated with lower OS (HR = 2.179, 95% CI: 1.587-2.992, P < 0.001), CSS (HR = 1.733, 95% CI: 1.333-2.253, P < 0.001), and recurrence-free survival (HR = 2.178, 95% CI: 1.328-3.573, P = 0.002). Thus, preoperative GNRI and CAR may be noninvasive and powerful tools for predicting survival outcomes in patients with EC. [ABSTRACT FROM AUTHOR]

Optically pumped nonlinear frequency down conversion is a proven approach for monochromatic terahertz (THz)-wave generation that provides superior properties such as continuous and wide tunability as well as laser-like linewidth and beam quality. Phase-matching (PM) is an important connection between the pump sources and nonlinear crystals and determines the direction of energy flow (as well as the output power). In past decades, a variety of peculiar PM configurations in the THz region have been invented and are different from the traditional ones in the optical region. We summarize the configurations that have been applied in nonlinear THz-wave generation, which mainly fall in two categories: scalar (collinear) PM and vector PM (including macroscopic noncollinear PM and microscopic vector PM). The development of this technique could relax the matching conditions in a wide range of nonlinear crystals and pump wavelengths and could finally promote the improvement of coherent THz sources. [ABSTRACT FROM AUTHOR]

Objective. To analyze the distribution of human papilloma virus (HPV) infection in women with cervical lesions of different grades and analyze the relationship of high-risk HPV and cervical lesions in order to facilitate targeted prevention. Methods. The infection status of HPV subtype was statistically analyzed in patients who underwent colposcopy examination from April 2017 to June 2019. Results. The infection rate of HPV was 81.4% in chronic cervicitis, 82.9% in 1ow-grade squamous intraepithelial lesion (LSIL), 63.7% in HSIL (high-grade squamous intraepithelial lesion), and 50% in cervical squamous cell carcinoma (CSCC). Among the 16 high-risk HPV types, the top six HPV types with the comprehensive infection rates were HPV16 > HPV52 > HPV58 > HPV18 > HPV51 > HPV53 in turn, and the infection rates were 23.3%, 14.8%, 13.3%, 9.8%, 9.2%, and 8.8%, respectively. The infection rates of HPV16 in chronic cervicitis group, LSIL group, and HSIL group were significantly different. There was no significant difference in the injection rates of HPV52, HPV58, and HPV18 among the three groups. HPV infection rates were highest in the 31–40 years old group, followed by the 41–50 years old group. Conclusion. The distribution of different types of HPV varies in different tissue types, which can be used to develop relevant vaccines to achieve better prevention and treatment of cervical cancer. [ABSTRACT FROM AUTHOR]

On the basis of studying the basic theory of anisotropic diffusion equation, this paper focuses on the application of anisotropic diffusion equation in image recognition film production. In order to further improve the application performance of P-M (Perona-Malik) anisotropic diffusion model, an improved P-M anisotropic diffusion model is proposed in this paper, and its application in image ultrasonic image noise reduction is discussed. The experimental results show that the model can effectively suppress the speckle noise and preserve the edge features of the image. Based on the image recognition technology, an image frame testing system is designed and implemented. The method of image recognition diffusion equation is used to extract and recognize the multilayer feature points of the test object according to the design of artificial neural network. To a certain extent, it improves the accuracy of image recognition and the audience rating of film and television. Use visual features of the film and television play in similarity calculation for simple movement scene segmentation problem, at the same time, the camera to obtain information, use the lens frame vision measuring the change of motion of the camera, and use weighted diffusion equation and the visual similarity of lens similarity calculation and motion information, by considering the camera motion of image recognition, effectively solve the sports scene of oversegmentation problem such as fighting and chasing. [ABSTRACT FROM AUTHOR]

China is still among the 30 high-burden tuberculosis (TB) countries in the world and TB remains a public health concern. TB can be a cause of mental illness, with prolonged treatment and several anti-TB drugs leading to extreme mental health problems such as depression and anxiety in TB patients. To investigate the prevalence of anxiety and depressive symptoms among TB patients, and to explore whether drug resistance is a covariate for depressive and anxiety symptoms, a total of 167 pulmonary tuberculosis patients were enrolled in this study, which was conducted from January 1 to September 30, 2020. Data were collected, using a structured questionnaire with a demographic component, the Hospital Anxiety and Depression Scale (HADS), General Health Questionnaire 20 (GHQ-20), the Tuberculosis-related Stigma Scale (TSS) and the Social Support Rating Scale (SSRS). Association between demographics, disease/treatment characteristics, stigma, social support, and anxiety/depression symptoms were investigated either based on Pearson's correlation coefficient or group comparisons based on independent t -test (or Mann-Whitney U- test) Multiple linear stepwise regression analysis was used for determining the predictors of anxiety and depression. The results showed that multi-drug resistance pulmonary tuberculosis patients were associated with anxiety challenges. Multiple linear regression analysis indicated that self-esteem accounted for 33.5 and 38% of the variation in anxiety and depression, respectively. This shows that among tuberculosis patients, self-esteem is the factor that could most explains the depression and anxiety symptoms of patients, suggesting that we may could through improving the environment, society, and family respect and tolerance of tuberculosis patients, thereby improving the mental health of tuberculosis patients. [ABSTRACT FROM AUTHOR]

The occurrence and development of Alzheimer's disease (AD) is a continuous clinical and pathophysiological process, molecular biological, and brain functional change often appear before clinical symptoms, but the detailed underlying mechanism is still unclear. The expression profiling of postmortem brain tissue from AD patients and controls provides evidence about AD etiopathogenesis. In the current study, we used published AD expression profiling data to construct spatiotemporal specific coexpression networks in AD and analyzed the network preservation features of each brain region in different disease stages to identify the most dramatically changed coexpression modules and obtained AD-related biological pathways, brain regions and circuits, cell types and key genes based on these modules. As result, we constructed 57 spatiotemporal specific networks (19 brain regions by three disease stages) in AD and observed universal expression changes in all 19 brain regions. The eight most dramatically changed coexpression modules were identified in seven brain regions. Genes in these modules are mostly involved in immune response-related pathways and non-neuron cells, and this supports the immune pathology of AD and suggests the role of blood brain barrier (BBB) injuries. Differentially expressed genes (DEGs) meta-analysis and protein–protein interaction (PPI) network analysis suggested potential key genes involved in AD development that might be therapeutic targets. In conclusion, our systematical network analysis on published AD expression profiling data suggests the immunopathogenesis of AD and identifies key brain regions and genes. [ABSTRACT FROM AUTHOR]

Background: Metachromatic leukodystrophy (MLD) is a rare inherited lysosomal disorder caused by mutations in ARSA. The biological processes of MLD disease caused by candidate pathogenic mutations in the ARSA gene remain unclear. Methods: We used whole‐exome sequencing (WES) and Sanger sequencing to identify the pathogenic mutation in a Chinese family. Literature review and protein three‐dimensional structure prediction were performed to analyze the potential pathogenesis of the identified mutations. Overexpression cell models of wild‐type and mutated ARSA genes were constructed. The accumulated sulfatides and expression profiles in the cell models were detected, and a series of bioinformatics analyses were carried out to compare the biological changes caused by the candidate pathogenic mutations. Results: We identified an ARSA c.925G>A homozygous mutation from a Chinese late‐infantile MLD patient, the first report of this mutation in East Asia. The literature and protein structure analysis indicated that three types of mutations at c.925G (c.925G>A, c.925G>T, c.925G>C) were pathogenic. The overexpression of wild‐type or mutated ARSA genes influenced the accumulation of sulfatides. The co‐expression modules in the mutated cell models were constructed by genes related to calcium signaling and vesicle transport. Conclusion: Our results identified a pathogenic mutation, ARSA homozygosity c.925G>A, from a Chinese MLD family. The pathogenic mechanism of the ARSA mutation in MLD was identified, which may suggest new approaches to diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Retinoic acid- (RA-) triggered neuroblastoma cell lines are widely used cell modules of neuronal differentiation in neurodegenerative disease studies, but the gene regulatory mechanism underlying differentiation is unclear now. In this study, system biological analysis was performed on public microarray data from three neuroblastoma cell lines (SK-N-SH, SH-SY5Y-A, and SH-SY5Y-E) to explore the potential molecular processes of all-trans retinoic acid- (ATRA-) triggered differentiation. RT-qPCR, functional genomics analysis, western blotting, chromatin immunoprecipitation (ChIP), and homologous sequence analysis were further performed to validate the gene regulation processes and identify the RA response element in a specific gene. The potential disturbed biological pathways (111 functional GO terms in 14 interactive functional groups) and gene regulatory network (10 regulators and 71 regulated genes) in neuroblastoma differentiation were obtained. 15 of the 71 regulated genes are neuronal projection-related. Among them, NTRK2 is the only one that was dramatically upregulated in the RT-qPCR test that we performed on ATRA-treated SH-SY5Y-A cells. We further found that the overexpression of the NTRK2 gene can trigger differentiation-like changes in SH-SY5Y-A cells. Functional genomic analysis and western blotting assay suggested that, in neuroblastoma cells, ATRA may directly regulate the NTRK2 gene by activating the RA receptor (RAR) that binds in its promoter region. A novel RA response DNA element in the NTRK2 gene was then identified by bioinformatics analysis and chromatin immunoprecipitation (ChIP) assay. The novel element is sequence conservation and position variation among different species. Our study systematically provided the potential regulatory information of ATRA-triggered neuroblastoma differentiation, and in the NTRK2 gene, we identified a novel RA response DNA element, which may contribute to the differentiation in a human-specific manner. [ABSTRACT FROM AUTHOR]

• Indirect mid-infrared detection with high responsivity based on optical frequency up-conversion in BaGa 4 Se 7 crystal was achieved. • A comprehensive study of the energy conversion characteristics of the MIR-to-NIR nonlinear process was presented. • A theoretical guidance for the calibration and optimal design of this detection system was provided. • Ours work can also be extended to other general MIR up-conversion detection configurations. Currently, non-oxide BaGa 4 Se 7 crystal has been demonstrated as a superior nonlinear medium for both coherent mid-infrared (MIR) generation and up-conversion detection. By bridging the desired MIR region to the well-developed near-infrared devices, the latter addresses the drawbacks of traditional direct detection. Based on our recent report, a comprehensive study is conducted on the nonlinear optical up-conversion process to achieve high responsivity. An analytical model is developed and verified through experiment. Their measurement and calculation cover the relationship between the up-converted signal and the two input lights, the acceptable angle of detection crystal, and the responsivities at a wavelength ranging from 3 to 8 µm. The dependence of responsivity on experimental factors is indicated by the model. The present study provides a theoretical reference for the calibration and optimal design of this detection system, which can also be applied to other general MIR up-conversion configurations. [ABSTRACT FROM AUTHOR]

Primary Sjögren's syndrome (pSS) is a systematic autoimmune disease with evidence of genetic predisposition. The IKZF1 (IKAROS family zinc finger 1 (Ikaros)) gene is located at 7p12.2, encodes a transcription factor related to chromatin remodeling, regulates lymphocyte differentiation, and has been reported to be associated with some autoimmune diseases. However, there have been no reports of an association between IKZF1 and pSS. To investigate the possibility of an association between the IKZF1 locus and pSS, we selected two single nucleotide polymorphisms (SNPs) in the IKZF1 locus, rs4917129 and rs4917014, based on a detailed analysis of genome-wide association study (GWAS) data and performed genotyping in 665 Han Chinese pSS patients and 863 healthy controls. The results of an association test showed significant association signals (rs4917129: P-value = 5.5e-4, OR (odds ratio) = 0.72, 95% CI (confidence interval) = 0.60–0.87; rs4917014: P-value = 1.2e-3, OR = 0.76, 95% CI = 0.64–0.89). A meta-analysis that combined the above results with data from previous GWAS, further confirmed these associations (rs4917129: Pmeta = 4.24e-8, ORmeta = 0.70, 95% CI = 0.61–0.79; rs4917014: Pmeta = 6.0e-8, ORmeta = 0.72, 95% CI = 0.64–0.81). A bioinformatics analysis indicated that both SNPs were located in a putative enhancer area in immune-related cell lines and tissues. A protein-protein interaction analysis found that IKZF1, together with GTF2I (an SS susceptibility gene newly identified through GWAS), could interact with histone deacetylase family proteins. In summary, this is the first study to report an association between IKZF1 and SS in Han Chinese. [ABSTRACT FROM AUTHOR]