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Achieving general artificial intelligence (AGI) has long been a grand challenge in the field of AI, and brain-inspired computing is widely acknowledged as one of the most promising approaches to realize this goal. This paper introduces a novel brain-inspired AI framework, Orangutan . It simulates the structure and computational mechanisms of biological brains on multiple scales, encompassing multi-compartment neuron architectures, diverse synaptic connection modalities, neural microcircuits, cortical columns, and brain regions, as well as biochemical processes including facilitation, feedforward inhibition, short-term potentiation, and short-term depression, all grounded in solid neuroscience. Building upon these highly integrated brain-like mechanisms, I have developed a sensorimotor model that simulates human saccadic eye movements during object observation. The model’s algorithmic efficacy was validated through testing with the observation of handwritten digit images.

This paper explores the characteristics and influencing factors of the spatial distribution of 889 national intangible cultural heritage sites in the Yellow River basin of China based on ArcGIS spatial analysis and Geodetector. The results show that the distribution of national intangible cultural heritage sites in the Yellow River basin is significantly different among provinces, and most of them are distributed in the central and western regions. From east to west, the density of intangible heritage in the Yellow River basin presents a triangular \"one area and three points\" pattern. All kinds of intangible cultural heritage in the Yellow River basin generally show the characteristic of aggregated distribution.Traditional skills, traditional medicine, traditional theatre, traditional music, and folklore have high levels of agglomeration, and traditional dance, Quyi, folk literature, and traditional fine arts have lower levels. The levels of traditional sports, entertainment and acrobatics have the lowest agglomeration. Among social and humanistic factors, highway density is the most influential indicator for the spatial distribution of national intangible cultural heritage in the Yellow River basin. GDP, population density and the urbanization level also have a great impact on the spatial distribution of national intangible cultural heritage in the Yellow River basin. Among geographical environmental factors, the river system and topography have a certain effect on the spatial distribution of national intangible cultural heritage in the Yellow River basin. Based on these facts, this paper finally discusses the specific path to protect and develop intangible cultural heritage in the Yellow River basin in the context of the newerato promote its creative protection and innovative development.

Long noncoding RNAs (lncRNAs) have been confirmed, which are involved in tumorigenesis and metastasis in colorectal cancer (CRC). FOXC2 antisense RNA 1 (FOXC2-AS1) was reported, facilitating the proliferation and progression in several cancers. However, the role of FOXC2-AS1 in CRC cell migration and metastasis is not unclear. In this study, we observed that lncRNA FOXC2-AS1 was upregulated in CRC tissues, and its high expression indicated the poor survival in CRC patients. Meanwhile, FOXC2-AS1 was higher in CRC tissues with metastasis than that of nonmetastatic tumor tissues. We found that FOXC2-AS1 was predominately expressed in the nucleus of tissues and cells. FOXC2-AS1 knockdown suppressed CRC cell growth, invasion, and metastasis in vitro and in vivo. Moreover, FOXC2-AS1 could positively regulate the neighboring gene FOXC2 and stabilized FOXC2 mRNA by forming a RNA duplex. Meanwhile, ectopic expression of FOXC2 could obviously alleviate the suppressed effects caused by silencing FOXC2-AS1. For the mechanism, FOXC2-AS1 knockdown could reduce intracellular Ca 2+ levels, inhibited FA formation and FAK signaling, and these suppressed effects were mitigated by increasing FOXC2 expression. These results demonstrated that FOXC2-AS1 enhances FOXC2 mRNA stability to promote CRC proliferation, migration, and invasion by activation of Ca 2+ -FAK signaling, which implicates that FOXC2-AS1 may represent a latent effective therapeutic target for CRC progression.

A physical unclonable function (PUF) is a foundation of anti-counterfeiting processes due to its inherent uniqueness. However, the self-limitation of conventional graphical/spectral PUFs in materials often makes it difficult to have both high code flexibility and high environmental stability in practice. In this study, we propose a universal, fractal-guided film annealing strategy to realize the random Au network-based PUFs that can be designed on demand in complexity, enabling the tags’ intrinsic uniqueness and stability. A dynamic deep learning-based authentication system with an expandable database is built to identify and trace the PUFs, achieving an efficient and reliable authentication with 0% “false positives”. Based on the roughening-enabled plasmonic network platform, Raman-based chemical encoding is conceptionally demonstrated, showing the potential for improvements in security. The configurable tags in mass production can serve as competitive PUF carriers for high-level anti-counterfeiting and data encryption. In order to be used on a large scale, unclonable tags for anti-counterfeiting should allow mass production at low cost, as well as fast and easy authentication. Here, the authors show how to use one-step annealing of gold films to quickly realize robust tags with high capacity, allowing fast deep-learning based authentication via smartphone readout.

Background Many applications of CRISPR/Cas9-mediated genome editing require Cas9-induced non-homologous end joining (NHEJ), which was thought to be error prone. However, with directly ligatable ends, Cas9-induced DNA double strand breaks may be repaired preferentially by accurate NHEJ. Results In the repair of two adjacent double strand breaks induced by paired Cas9-gRNAs at 71 genome sites, accurate NHEJ accounts for about 50% of NHEJ events. This paired Cas9-gRNA approach underestimates the level of accurate NHEJ due to frequent + 1 templated insertions, which can be avoided by the predefined Watson/Crick orientation of protospacer adjacent motifs (PAMs). The paired Cas9-gRNA strategy also provides a flexible, reporter-less approach for analyzing both accurate and mutagenic NHEJ in cells and in vivo, and it has been validated in cells deficient for XRCC4 and in mouse liver. Due to high frequencies of precise deletions of defined “3n”-, “3n + 1”-, or “3n + 2”-bp length, accurate NHEJ is used to improve the efficiency and homogeneity of gene knockouts and targeted in-frame deletions. Compared to “3n + 1”-bp, “3n + 2”-bp can overcome + 1 templated insertions to increase the frequency of out-of-frame mutations. By applying paired Cas9-gRNAs to edit MDC1 and key 53BP1 domains, we are able to generate predicted, precise deletions for functional analysis. Lastly, a Plk3 inhibitor promotes NHEJ with bias towards accurate NHEJ, providing a chemical approach to improve genome editing requiring precise deletions. Conclusions NHEJ is inherently accurate in repair of Cas9-induced DNA double strand breaks and can be harnessed to improve CRISPR/Cas9 genome editing requiring precise deletion of a defined length.

With the increase of the camera resolution, the number of pixels contained in froth image is increased, which brings many challenges to image segmentation. Froth size and distribution are the important index in froth flotation. The segmentation of froth images is always a problem in building flotation model. In segmenting froth images, Otsu method is usually used to get a binary image for classification of froth images, this method can get a satisfactory segmentation result. However, each gray level is required to calculate each of the between-class variance, it takes a longer time in froth images with a large number of pixels. To solve this problem, an improved method is proposed in this paper. Most froth images have the pixel distribution characteristic that the gray histogram curve is a sawtooth shape. The proposed method uses polynomial to fit the curve of gray histogram and takes the characteristic of gray histogram's valley into consideration in Otsu method. Two performance comparison methods are introduced and used. Experimental comparison between Otsu method and the proposed method shows that the proposed method has a satisfactory image segmentation with a low computing time.

Saponins are natural glycosides of steroid or triterpene which exhibited many different biological and pharmacological activities. Notably, saponins can also activate the mammalian immune system, which have led to significant interest in their potential as vaccine adjuvants. The most widely used saponin-based adjuvants are Quil A and its derivatives QS-21, isolated from the bark of Quillaja saponaria Molina, which have been evaluated in numerous clinical trials. Their unique capacity to stimulate both the Th1 immune response and the production of cytotoxic T-lymphocytes (CTLs) against exogenous antigens makes them ideal for use in subunit vaccines and vaccines directed against intracellular pathogens as well as for therapeutic cancer vaccines. However, Quillaja saponins have serious drawbacks such as high toxicity, undesirable haemolytic effect and instability in aqueous phase, which limits their use as adjuvant in vaccination. It has driven much research for saponin-based adjuvant from other kinds of natural products. This review will summarize the current advances concerning adjuvant effects of different kinds of saponins. The structure–activity relationship of saponin adjuvants will also be discussed in the light of recent findings. It is hoped that the information collated here will provide the reader with information regarding the adjuvant potential applications of saponins and stimulate further research into these compounds.

Conjugated microporous polymers are a new class of porous materials with an extended π-conjugation in an amorphous organic framework. Owing to the wide-ranging flexibility in the choice and design of components and the available control of pore parameters, these polymers can be tailored for use in various applications, such as gas storage, electronics and catalysis. Here we report a class of cobalt/aluminium-coordinated conjugated microporous polymers that exhibit outstanding CO 2 capture and conversion performance at atmospheric pressure and room temperature. These polymers can store CO 2 with adsorption capacities comparable to metal-organic frameworks. The cobalt-coordinated conjugated microporous polymers can also simultaneously function as heterogeneous catalysts for the reaction of CO 2 and propylene oxide at atmospheric pressure and room temperature, wherein the polymers demonstrate better efficiency than a homogeneous salen-cobalt catalyst. By combining the functions of gas storage and catalysts, this strategy provides a direction for cost-effective CO 2 reduction processes. Conjugated microporous polymers are highly flexible materials that may be used for gas storage and catalysis applications. Here, the authors report metal-functionalized conjugated microporous polymers capable of both capturing CO 2 and functioning as a heterogeneous catalyst in its conversion to propylene carbonate.

BackgroundColon adenocarcinoma (COAD) is a common digestive system malignancy with high mortality and poor prognosis. Accumulating evidence indicates that choline metabolism is closely related to tumorigenesis and development. However, the efficacy of choline metabolism-related signature in predicting patient prognosis, immune microenvironment and chemotherapy response has not been fully clarified.MethodsCholine metabolism-related differentially expressed genes (DEGs) between normal and COAD tissues were screened using datasets from The Cancer Genome Atlas (TCGA), Kyoto Encyclopedia of Genes and Genomes (KEGG), AmiGO2 and Reactome Pathway databases. Two choline metabolism-related genes (CHKB and PEMT) were identified by univariate and multivariate Cox regression analyses. TCGA-COAD was the training cohort, and GSE17536 was the validation cohort. Patients in the high- and low-risk groups were distinguished according to the optimal cutoff value of the risk score. A nomogram was used to assess the prognostic accuracy of the choline metabolism-related signature. Calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC) were used to improve the clinical applicability of the prognostic signature. Gene Ontology (GO) and KEGG pathway enrichment analyses of DEGs in the high- and low-risk groups were performed. KEGG cluster analysis was conducted by the KOBAS-i database. The distribution and expression of CHKB and PEMT in various types of immune cells were analyzed based on single-cell RNA sequencing (scRNA-seq). The CIBERSORT and ESTIMATE algorithms evaluated tumor immune cell infiltration in the high- and low-risk groups. Evaluation of the half maximal inhibitory concentration (IC50) of common chemotherapeutic drugs based on the choline metabolism-related signature was performed. Small molecule compounds were predicted using the Connectivity Map (CMap) database. Molecular docking is used to simulate the binding conformation of small molecule compounds and key targets. By immunohistochemistry (IHC), Western blot, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) experiments, the expression levels of CHKB and PEMT in human, mouse, and cell lines were detected.ResultsWe constructed and validated a choline metabolism-related signature containing two genes (CHKB and PEMT). The overall survival (OS) of patients in the high-risk group was significantly worse than that of patients in the low-risk group. The nomogram could effectively and accurately predict the OS of COAD patients at 1, 3, and 5 years. The DCA curve and CIC demonstrate the clinical utility of the nomogram. scRNA-seq showed that CHKB was mainly distributed in endothelial cells, while PEMT was mainly distributed in CD4+ T cells and CD8+ T cells. In addition, multiple types of immune cells expressing CHKB and PEMT differed significantly. There were significant differences in the immune microenvironment, immune checkpoint expression and chemotherapy response between the two risk groups. In addition, we screened five potential small molecule drugs that targeted treatment for COAD. Finally, the results of IHC, Western blot, and qRT-PCR consistently showed that the expression of CHKB in human, mouse, and cell lines was elevated in normal samples, while PMET showed the opposite trend.ConclusionIn conclusion, we constructed a choline metabolism-related signature in COAD and revealed its potential application value in predicting the prognosis, immune microenvironment, and chemotherapy response of patients, which may lay an important theoretical basis for future personalized precision therapy.

A mild, efficient and practical protocol for the preparation of 2-sulfonylquinolines through CS2/Et2NH-induced deoxygenative C2-H sulfonylation of quinoline N-oxides with readily available RSO2Cl was developed. The reaction proceeded well under transition-metal-free conditions and exhibited a wide substrate scope and functional group tolerance. The preliminary studies suggested that the nucleophilic sulfonyl sources were generated in situ via the reaction of CS2, Et2NH and sulfonyl chlorides.