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The future pedagogical systems need anthropocentric inclusive educational programs in which the goal should be adjustable according to the knowledge requirements, intelligence, and learning objective of each student. Prioritizing these needs, innovative AI methods are required to assist and ensure the making of conscious educational decisions, in terms of clear identification and categorization with high accuracy of various forms of skills and knowledge of each student. This paper proposes a neuroevolution emerging technique that combines the searchability of evolutionary computation and the learning capability of a hybrid artificial neural networks method. Specifically, the proposed growing semiorganizing neural gas (GsONG) is a practical AI methodology utilizing advanced clustering techniques to enhance the learning experience by categorizing the true abilities, skills, and needs of learners, in an inclusive differentiated learning framework. It is a neural network architecture that includes competing and cooperating neurons with an unstructured mode whereby a cooperation-competition process delimits the topological neighborhood of neurons in a grid to identify patterns for which their classes are not known. To optimize the above process, a heuristic method was used that investigates the space of an objective function by regulating the optimal topologies of neurons that form pathway segments in a semi-contemplative manner. Based on the extensive experiments and results obtained from the GsONG clustering approach, the proposed algorithm can compensate with high accuracy for difficulties in multicriteria grouping and differentiation of uncertainty structures such as in small or tiny data sets.

For high dimensional gene expression data, one important goal is to identify a small number of genes that are associated with progression of the disease or survival of the patients. In this paper, we consider the problem of variable selection for multivariate survival data. We propose an estimation procedure for high dimensional accelerated failure time (AFT) models with bivariate censored data. The method extends the Buckley-James method by minimizing a penalized [Formula: see text] loss function with a penalty function induced from a bivariate spike-and-slab prior specification. In the proposed algorithm, censored observations are imputed using the Kaplan-Meier estimator, which avoids a parametric assumption on the error terms. Our empirical studies demonstrate that the proposed method provides better performance compared to the alternative procedures designed for univariate survival data regardless of whether the true events are correlated or not, and conceptualizes a formal way of handling bivariate survival data for AFT models. Findings from the analysis of a myeloma clinical trial using the proposed method are also presented.

Echocardiography is essential for evaluating cardiac anatomy and function during early recognition and screening for congenital heart disease (CHD), a widespread and complex congenital malformation. However, fetal CHD recognition still faces many difficulties due to instinctive fetal movements, artifacts in ultrasound images, and distinctive fetal cardiac structures. These factors hinder capturing robust and discriminative representations from ultrasound images, resulting in CHD's low prenatal detection rate. Hence, we propose a multi-scale gated axial-transformer network (MSGATNet) to capture fetal four-chamber semantic information. Then, we propose a SPReCHD: four-chamber semantic parsing network for recognizing fetal CHD in the clinical treatment of the medical metaverse, integrating MSGATNet to segment and locate four-chamber arbitrary contours, further capturing distinguished representations for the fetal heart. Comprehensive experiments indicate that our SPReCHD is sufficient in recognizing fetal CHD, achieving a precision of 95.92%, a recall of 94%, an accuracy of 95%, and a F

We are now in the era of millimeter-scale electron microscopy (EM) volumes collected at nanometer resolution (Shapson-Coe et al., 2021; Consortium et al., 2021). Dense reconstruction of cellular compartments in these EM volumes has been enabled by recent advances in Machine Learning (ML) (Lee et al., 2017; Wu et al., 2021; Lu et al., 2021; Macrina et al., 2021). Automated segmentation methods can now yield exceptionally accurate reconstructions of cells, but despite this accuracy, laborious post-hoc proofreading is still required to generate large connectomes free of merge and split errors. The elaborate 3-D meshes of neurons produced by these segmentations contain detailed morphological information, from the diameter, shape, and branching patterns of axons and dendrites, down to the fine-scale structure of dendritic spines. However, extracting information about these features can require substantial effort to piece together existing tools into custom workflows. Building on existing open-source software for mesh manipulation, here we present “NEURD”, a software package that decomposes each meshed neuron into a compact and extensively-annotated graph representation. With these feature-rich graphs, we implement workflows for state of the art automated post-hoc proofreading of merge errors, cell classification, spine detection, axon-dendritic proximities, and other features that can enable many downstream analyses of neural morphology and connectivity. NEURD can make these new massive and complex datasets more accessible to neuroscience researchers focused on a variety of scientific questions.

Soil salinization has a serious influence on rice yield and quality. How to enhance salt tolerance in rice is a topical issue. In this study, 120 recombinant inbred line populations were generated through nonstop multi-generation selfing using a male indica rice variety Huazhan (Oryza sativa L. subsp. indica cv. ‘HZ’) and a female variety of Nekken2 (Oryza sativa L. subsp. japonica cv. ‘Nekken2’) as the parents. Germination under 80 mM NaCl conditions was measured and analyzed, and quantitative trait locus (QTL) mapping was completed using a genetic map. A total of 16 salt-tolerance QTL ranges were detected at bud stage in rice, which were situated on chromosomes 3, 4, 6, 8, 9, 10, 11, and 12. The maximum limit of detection was 4.69. Moreover, the qST12.3 was narrowed to a 192 kb region on chromosome 12 using map-based cloning strategy. Statistical analysis of the expression levels of these candidate genes under different NaCl concentrations by qRT-PCR revealed that qST12.3 (LOC_Os12g25200) was significantly down-regulated with increasing NaCl concentration, and the expression level of the chlorine-transporter-encoding gene LOC_Os12g25200 in HZ was significantly higher than that of Nekken2 under 0 mM NaCl. Sequencing analysis of LOC_Os12g25200 promoter region indicated that the gene expression difference between parents may be due to eight base differences in the promoter region. Through QTL mining and analysis, a plurality of candidate genes related to salt tolerance in rice was obtained, and the results showed that LOC_Os12g25200 might negatively regulate salt tolerance in rice. The results provide the basis for further screening and cultivation of salt-tolerant rice varieties and have laid the foundation for elucidating further molecular regulation mechanisms of salt tolerance in rice.

Entropy and cross-entropy are very vital for information discrimination under complicated Pythagorean fuzzy environment. Firstly, the novel score factors and indeterminacy factors of intuitionistic fuzzy sets (IFSs) are proposed, which are linear transformations of membership functions and non-membership functions. Based on them, the novel entropy measures and cross-entropy measures of an IFS are introduced using Jensen Shannon-divergence (J-divergence). They are more in line with actual fuzzy situations. Then the cases of Pythagorean fuzzy sets (PFSs) are extended. Pythagorean fuzzy entropy, parameterized Pythagorean fuzzy entropy, Pythagorean fuzzy cross-entropy, and weighted Pythagorean fuzzy cross-entropy measures are introduced consecutively based on the novel score factors, indeterminacy factors and J-divergence. Then some comparative experiments prove the rationality and effectiveness of the novel entropy measures and cross-entropy measures. Additionally, the Pythagorean fuzzy entropy and cross-entropy measures are designed to solve pattern recognition and multiple criteria decision making (MCDM) problems. The numerical examples, by comparing with the existing ones, demonstrate the applicability and efficiency of the newly proposed models.

Neurons in the neocortex exhibit astonishing morphological diversity which is critical for properly wiring neural circuits and giving neurons their functional properties. The extent to which the morphological diversity of excitatory neurons forms a continuum or is built from distinct clusters of cell types remains an open question. Here we took a data-driven approach using graph-based machine learning methods to obtain a low-dimensional morphological “bar code” describing more than 30,000 excitatory neurons in mouse visual areas V1, AL and RL that were reconstructed from a millimeter scale serial-section electron microscopy volume. We found a set of principles that captured the morphological diversity of the dendrites of excitatory neurons. First, their morphologies varied with respect to three major axes: soma depth, total apical and basal skeletal length. Second, neurons in layer 2/3 showed a strong trend of a decreasing width of their dendritic arbor and a smaller tuft with increasing cortical depth. Third, in layer 4, atufted neurons were primarily located in the primary visual cortex, while tufted neurons were more abundant in higher visual areas. Fourth, we discovered layer 4 neurons in V1 on the border to layer 5 which showed a tendency towards avoiding deeper layers with their dendrites. In summary, excitatory neurons exhibited a substantial degree of dendritic morphological variation, both within and across cortical layers, but this variation mostly formed a continuum, with only a few notable exceptions in deeper layers.

Neurons in the developing brain undergo extensive structural refinement as nascent circuits adopt their mature form. This physical transformation of neurons is facilitated by the engulfment and degradation of axonal branches and synapses by surrounding glial cells, including microglia and astrocytes. However, the small size of phagocytic organelles and the complex, highly ramified morphology of glia have made it difficult to define the contribution of these and other glial cell types to this crucial process. Here, we used large-scale, serial section transmission electron microscopy (TEM) with computational volume segmentation to reconstruct the complete 3D morphologies of distinct glial types in the mouse visual cortex, providing unprecedented resolution of their morphology and composition. Unexpectedly, we discovered that the fine processes of oligodendrocyte precursor cells (OPCs), a population of abundant, highly dynamic glial progenitors, frequently surrounded small branches of axons. Numerous phagosomes and phagolysosomes (PLs) containing fragments of axons and vesicular structures were present inside their processes, suggesting that OPCs engage in axon pruning. Single-nucleus RNA sequencing from the developing mouse cortex revealed that OPCs express key phagocytic genes at this stage, as well as neuronal transcripts, consistent with active axon engulfment. Although microglia are thought to be responsible for the majority of synaptic pruning and structural refinement, PLs were ten times more abundant in OPCs than in microglia at this stage, and these structures were markedly less abundant in newly generated oligodendrocytes, suggesting that OPCs contribute substantially to the refinement of neuronal circuits during cortical development.

Rationale: Chronic wounds associated with diabetes exact a heavy burden on individuals and society and do not have a specific treatment. Exosome therapy is an extension of stem cell therapy, and RNA interference (RNAi)-based therapy is a type of advanced precision therapy. Based on the discovery of chronic wound-related genes in diabetes, we combined exosome therapy and RNAi therapy through an engineering approach for the treatment of diabetic chronic wounds. Methods: We combined exosome therapy and RNAi therapy to establish a precision therapy for diabetes-associated wounds via an engineered exosome approach. Results: First, chronic diabetic wounds express low levels of miR-31-5p compared with nondiabetic wounds, and an miR-31-5p mimic was shown to be effective in promoting the proliferation and migration of three wound-related cell types in vitro. Second, bioinformatics analysis, luciferase reporter assays and western blotting suggested that miR-31-5p promoted angiogenesis, fibrogenesis and reepithelization by inhibiting factor-inhibiting HIF-1 (HIF1AN, also named FIH) and epithelial membrane protein-1 (EMP-1). Third, engineered miR-31 exosomes were generated as a miR-31-5p RNAi therapeutic agent. In vivo, the engineered miR-31 exosomes promoted diabetic wound healing by enhancing angiogenesis, fibrogenesis and reepithelization. Conclusion: Engineered miR-31 exosomes are an ideal disease pathophysiology-initiated RNAi therapeutic agent for diabetic wounds., Graphical abstract Image 1, Highlights • Diabetic wound is still a tough problem. • MiR-31-5p was identified as a potential precision therapeutic factor in diabetic wounds healing. • Engineered miR-31 exosome was developed to heal diabetic wounds via synergistic effects.

Microbial signatures have emerged as promising biomarkers and targets for disease diagnosis, prognosis, and remission. However, these biomarkers exhibit contradictory results in different studies, necessitating the identification of universally robust microbial biomarkers. Therefore, we introduce xMarkerFinder, a four-stage computational framework for microbial biomarker identification with comprehensive validations from cross-cohort datasets, including differential signature identification, model construction, model validation, and biomarker interpretation. xMarkerFinder enables the identification and validation of reproducible biomarkers for cross-cohort studies, along with the establishment of classification models and potential microbiome-induced mechanisms. Although xMarkerFinder is initially developed for gut microbiome study, it is generalizable to different omics layers, as well as other habitats. Execution time varies depending on the sample size, selected algorithm, and computational resource. xMarkerFinder can be accessed at https://github.com/tjcadd2020/xMarkerFinder. FAQs, detailed tutorials, issue boards, and a ready-to-use Docker image are provided for users with no prior bioinformatics or statistics training.

Hepatocellular carcinoma (HCC) is a major subtype of primary liver cancer with a high mortality rate. Pyroptosis and autophagy are crucial processes in the pathophysiology of HCC. Searching for efficient drugs targeting pyroptosis and autophagy with lower toxicity is useful for HCC treatment. Mallotucin D (MLD), a clerodane diterpenoid from

Serial-section electron microscopy (ssEM) is the method of choice for studying macroscopic biological samples at extremely high resolution in three dimensions. In the nervous system, nanometer-scale images are necessary to reconstruct dense neural wiring diagrams in the brain, so calledconnectomes. In order to use this data, consisting of up to 108individual EM images, it must be assembled into a volume, requiring seamless 2D stitching from each physical section followed by 3D alignment of the stitched sections. The high throughput of ssEM necessitates 2D stitching to be done at the pace of imaging, which currently produces tens of terabytes per day. To achieve this, we present a modular volume assembly software pipelineASAP(Assembly Stitching and Alignment Pipeline) that is scalable to datasets containing petabytes of data and parallelized to work in a distributed computational environment. The pipeline is built on top of theRender[18] services used in the volume assembly of the brain of adultDrosophila melanogaster[2]. It achieves high throughput by operating on the meta-data and transformations of each image stored in a database, thus eliminating the need to render intermediate output. ASAP is modular, allowing for easy incorporation of new algorithms without significant changes in the workflow. The entire software pipeline includes a complete set of tools for stitching, automated quality control, 3D section alignment, and final rendering of the assembled volume to disk. ASAP has been deployed for continuous processing of several large-scale datasets of the mouse visual cortex and human brain samples including one cubic millimeter of mouse visual cortex [1, 25] at speeds that exceed imaging. The pipeline also has multi-channel processing capabilities and can be applied to fluorescence and multi-modal datasets like array tomography.

Mammalian neocortex contains a highly diverse set of cell types. These types have been mapped systematically using a variety of molecular, electrophysiological and morphological approaches. Each modality offers new perspectives on the variation of biological processes underlying cell type specialization. While many morphological surveys focus on branching patterns of individual cells, fewer have been devoted to sub-cellular structure of cells. Electron microscopy (EM) provides dense ultrastructural examination and an unbiased perspective into the subcellular organization of brain cells, including their synaptic connectivity and nanometer scale morphology. Here we present the first systematic survey of the somatic region of nearly 100,000 cortical cells, using quantitative features obtained from EM. This analysis demonstrates a surprising sufficiency of the perisomatic region to recapitulate many known aspects of cortical organization, while also revealing novel relationships. Parameters of cell size, nuclear infolding and somatic synaptic innervation co-vary with distinct patterns across depth and between types. Further, we describe how these subcellular features can be used to create highly accurate predictions of cell-types across large scale EM datasets. More generally, our results suggest that the shifts in cellular physiology and molecular programming seen across cell types accompany profound differences in the fine-scale structure of cells.

Plant lesion mimics refer to necrotic spots spontaneously produced by the plant without mechanical damage, pathogen invasion, and adversity stress. Here, we isolated and characterized two rice (Oryza sativa L) mutants, namely, spl88-1 (spotted leaf88-1) and spl88-2 (spotted leaf88-2), which were identified from an ethyl methanesulfonate-mutagenized japonica cultivar Xiushui 11 population. Physiological and biochemical experiments indicated that more ROS accumulated in spl88-1 and spl88-2 than in wild type. spl88-1 and spl88-2 displayed spontaneous cell death and enhanced their resistance to bacterial blight by affecting the expression of defense-related genes. We isolated SPL88 by map-based cloning, which encoded a highly conserved Cullin protein. A single base deletion was detected in spl88-1 and spl88-2, in which the 132nd base C of SPL88-1 and the 381th base T of SPL88-2 were deleted, causing premature termination of protein translation. SPL88 was expressed in root, stem, leaf, leaf sheath, and panicle. The Cullin protein was localized in the cytoplasm and nucleus. The aforementioned results indicate that SPL88 regulates the growth and development of rice by affecting the expression of defense-related genes.

In order to alleviate the dust pollution in the fully mechanized mining face, the novel negative pressure entrainment dust collector was optimized by the method of orthogonal experimental design and numerical simulation. The influences of nozzle distance, throat diameter and diffusion angle on the atomization efficiency of the proposed dust collector was investigated. The obtained results showed that the optimum ejection dust removal performance of the developed negative pressure entrainment dust collector was obtained for throat diameter 80 mm, throat distance 60 mm and diffusion angle 20 degrees. Under these conditions, air suction rate at the entrance of contraction section was 17.48 m3/min and the average droplet size and mass concentration were 62.99 μm and 0.034 kg/m3, respectively. Here, we have proposed a local closed atomization control dust removal technology for hydraulic support areas based on the optimized negative pressure entrainment dust collector. After the application of the developed system in 2307 fully mechanized mining face in Tangkou Coal Mine, the average total dust of measuring points was decreased from 337.90 to 49.53 mg/m3 and average exhaust dust was decreased from 271.80 to 41.40 mg/m3. The average dust removal rates of total dust and exhaled dust were 85.17% and 84.74% respectively, and dust removal efficiency of the proposed system was obviously confirmed.

Burkitt lymphoma (BL) is an aggressive Epstein-Barr virus (EBV)-driven B-cell lymphoma characterized by the translocation and rearrangement of the c-Myc proto-oncogene. High-intensity multidrug chemotherapy regimens have a limited effect on the survival of refractory or relapsed BL patients, mainly owing to the high EBV load and drug resistance. l-asparaginase ( l-Asp) and etoposide (VP-16) play a beneficial role in EBV-related lymphoproliferative diseases; however, their roles and mechanisms in BL remain unclear. In this study, we found that VP-16 inhibited BL cell proliferation and arrested the cell cycle at the G

The diagnostic utility of poor body composition measures in sarcopenia remains unclear. We hypothesize that the skeletal muscle gauge [combination of skeletal muscle mass index (SMI) and skeletal muscle density (SMD); SMG = SMI × SMD] would have significant diagnostic and predictive value in certain regions and populations.Prospective cross-sectional study.We examined inpatients age ≥60 years with or without cancer and with gastrointestinal disorders.We used computed tomography (CT) image metrics in the 12th thoracic (T12), third lumbar (L3), erector spinae muscle (ESM), and psoas muscle (PM) regions to establish correlations with the 2019 Asian Working Group for Sarcopenia Consensus and used receiver operating characteristic area under the curve (AUC) to compare differences between metrics. Associations between CT metrics and mortality were reported as relative risk after adjustments.We evaluated 385 patients (median age, 69.0 years; 60.8% men) and found consistent trends in cancer (49.6%) and noncancer (50.4%) cohorts. SMG had a stronger correlation with muscle mass than SMD [mean rho: 0.68 (range, 0.59‒0.73) vs 0.39 (range, 0.28‒0.48); all P.05] in T12, L3, and PM regions and a stronger correlation with muscle function than SMI [mean rho: 0.60 (range, 0.50‒0.77) vs 0.36 (range, 0.22‒0.58); all P.05] in T12, ESM, and L3 regions. SMG outperformed SMI in diagnostic accuracy in all regions, particularly for L3 (AUC: 0.87‒0.88 vs 0.80‒0.82; both P.05). PM gauge and L3SMG did not differ, whereas EMG (ESM gauge) or T12SMG and L3SMG did (AUC: 0.80‒0.82 vs 0.87‒0.88; all P.05). L3SMI, L3SMD, T12SMG, EMG, and PM gauge showed no association with 1-year cancer-related mortality after adjusting for confounders; however, L3SMG [relative risk = 0.92 (0.85‒0.99); P = .023) was.L3SMG covers all features of sarcopenia with more diagnostic value than other metrics, allowing a complete sarcopenia assessment with CT alone and not just in populations with cancer.

Generally, the addition of exogenous stem cells and host-to-scaffold immune responses restricts the clinical applications of hydroxyapatite (HA)/chitosan (CS) scaffolds for bone regeneration. To achieve "facilitated endogenous tissue engineering", magnetic M-type hexagonal ferrite (SrFe12O19) nanoparticles were incorporated into bone scaffolds to recruit endogenous stem cells. Then, lanthanum incorporation was utilized to regulate host-to-scaffold immune responses and to provide a pro-regenerative environment for recruited endogenous stem cells. Here, we first fabricated and characterized magnetic lanthanum-doped HA/CS scaffolds. The MLaHA/CS scaffolds were demonstrated to be effective at recruiting rat bone marrow mesenchymal stem cells (rBMSCs) and modulating host-to-scaffold immune responses by promoting macrophage polarization into the anti-inflammatory phenotype (M2) in vitro. By further examining the underlying mechanism, we found that MLaHA/CS scaffolds could promote the osteogenic differentiation of rBMSCs by upregulating the phosphorylation of the Smad 1/5/9 pathway. When MLaHA/CS scaffolds were implanted into rat calvarial defects, the incorporation of magnetic nanoparticles and lanthanum significantly promoted the new bone regeneration, as revealed by micro-CT assays and histological staining. Our findings suggest that MLaHA/CS shows great potential for use as a cell-free and biocompatible scaffold for bone regeneration.

Hepatocellular carcinoma (HCC) is a major subtype of primary liver cancer with a high mortality rate. Pyroptosis and autophagy are crucial processes in the pathophysiology of HCC. Searching for efficient drugs targeting pyroptosis and autophagy with lower toxicity is useful for HCC treatment. Mallotucin D (MLD), a clerodane diterpenoid from Croton crassifolius, has not been previously reported for its anticancer effects in HCC. This study aims to evaluate the inhibitory effects of MLD in HCC and explore the underlying mechanism. We found that the cell proliferation, DNA synthesis, and colony formation of HepG2 cells and the angiogenesis of HUVECs were all greatly inhibited by MLD. MLD caused mitochondrial damage and decreased the TOM20 expression and mitochondrial membrane potential, inducing ROS overproduction. Moreover, MLD promoted the cytochrome C from mitochondria into cytoplasm, leading to cleavage of caspase-9 and caspase-3 inducing GSDMD-related pyroptosis. In addition, we revealed that MLD activated mitophagy by inhibiting the PI3K/AKT/mTOR pathway. Using the ROS-scavenging reagent NAC, the activation effects of MLD on pyroptosis- and autophagy-related pathways were all inhibited. In the HepG2 xenograft model, MLD effectively inhibited tumor growth without detectable toxicities in normal tissue. In conclusion, MLD could be developed as a candidate drug for HCC treatment by inducing mitophagy and pyroptosis via promoting mitochondrial-related ROS production.

Seven new clerodane diterpenoids, crassifolins Q−W (1–7), along with five known analogues (8–12), were isolated from the roots of Croton crassifolius. Their structures were identified by comprehensive spectroscopic analysis (UV, IR, NMR, and HR-ESI-MS), and their absolute configurations were determined by ECD spectra and X-ray crystallography. The activities of compounds 1–5 against inflammatory cytokines IL-6 and TNF-α levels on LPS-induced RAW 264.7 macrophages were assessed, and compound 5 showed the most significant activity with the secretion levels of IL-6 and TNF-α at 32.78 and 12.53%, respectively. Moreover, compounds 1–5 were screened for their anti-angiogenesis using a human umbilical vein endothelial cells in vitro mode; the results showed all of them exhibited obvious anti-angiogenesis activities, in particular, compound 5 showed the strongest anti-angiogenesis effect in the range of 6.25–50 μM.

3D electron microscopy (EM) has been successful at mapping invertebrate nervous systems, but the approach has been limited to small chunks of mammalian brains. To scale up to larger volumes, we have built a computational pipeline for processing petascale image datasets acquired by serial section EM, a popular form of 3D EM. The pipeline employs convolutional nets to compute the nonsmooth transformations required to align images of serial sections containing numerous cracks and folds, detect neuronal boundaries, label voxels as axon, dendrite, soma, and other semantic categories, and detect synapses and assign them to presynaptic and postsynaptic segments. The output of neuronal boundary detection is segmented by mean affinity agglomeration with semantic and size constraints. Pipeline operations are implemented by leveraging distributed and cloud computing. Intermediate results of the pipeline are held in cloud storage, and can be effortlessly viewed as images, which aids debugging. We applied the pipeline to create an automated reconstruction of an EM image volume spanning four visual cortical areas of a mouse brain. Code for the pipeline is publicly available, as is the reconstructed volume.

To understand the brain we must relate neurons’ functional responses to the circuit architecture that shapes them. Here, we present a large functional connectomics dataset with dense calcium imaging of a millimeter scale volume. We recorded activity from approximately 75,000 neurons in primary visual cortex (VISp) and three higher visual areas (VISrl, VISal and VISlm) in an awake mouse viewing natural movies and synthetic stimuli. The functional data were co-registered with a volumetric electron microscopy (EM) reconstruction containing more than 200,000 cells and 0.5 billion synapses. Subsequent proofreading of a subset of neurons in this volume yielded reconstructions that include complete dendritic trees as well the local and inter-areal axonal projections that map up to thousands of cell-to-cell connections per neuron. Here, we release this dataset as an open-access resource to the scientific community including a set of tools that facilitate data retrieval and downstream analysis. In accompanying papers we describe our findings using the dataset to provide a comprehensive structural characterization of cortical cell types1–3and the most detailed synaptic level connectivity diagram of a cortical column to date2, uncovering unique cell-type specific inhibitory motifs that can be linked to gene expression data4. Functionally, we identify new computational principles of how information is integrated across visual space5, characterize novel types of neuronal invariances6and bring structure and function together to decipher a general principle that wires excitatory neurons within and across areas7, 8.

A q-rung orthopair fuzzy set (q-ROFS) is an effective tool for describing uncertainty and fuzziness, and is the promotion of intuitionistic fuzzy sets (IFSs) and Pythagorean fuzzy sets (PFSs). This paper extends q-rung orthopair fuzzy environment to probabilistic q-rung orthopair hesitant fuzzy environment, and proposes the concept of probabilistic q-rung orthopair hesitant fuzzy sets (P-q-ROHFSs). Some desired operational laws and properties of P-q-ROHFSs are studied. And we develop the some aggregation operators for probabilistic q-rung orthopair hesitant fuzzy information. Then the relationship among these operators is discussed by comparing the score function. In order to measure the uncertain information, this paper proposes the four distance measures between two P-q-ROHFSs. Especially, ranking and expansion of P-q-ROHFSs are discussed in detail. Furthermore, we apply them to pattern recognition and multi-attribute group decision making (MAGDM) under probabilistic q-rung orthopair hesitant fuzzy environment. Finally, examples are given to show the rationality and practicability of the proposed method.

To improve the dust suppression efficiency of the external spray systems of shearers, a dust reduction method consisting of shearer external multi-stage atomization and dust removal fan was proposed. Computational fluid dynamics-based numerical simulation was combined with atomization experiments to analyze the migration and distribution of the cutting dust and multi-stage atomization field under airflow at the 2307 fully mechanized mining face of the Tangkou mine. The results show that with adding dust removal fan and multi-stage atomization points, the peak area of wind speed appeared on both sides of the shearer, and the wind speed was greater than 2.7 m/s, the dust concentration on the downside side of the shearer decreased, the spray coverage area increased significantly, and the droplet concentration at the shearer drum was the largest, exceeding 0.05 kg/m3. According to the research results, the multi-stage atomization arrangement of single-fluid water nozzles of shearer was put forward, and the field application was carried out. Compared with the engineering application results of the single-stage atomization dust suppression system, the total dust reduction rate of the synergistic effect of multi-stage atomization external spray with dust removal fan for the shearer is 87.12%, which is 38.59% higher than that of the conventional single-stage atomization dust suppression system.

A gas tank is an important storage facility in chemical enterprises. When an explosion occurs, it can easily cause mass injury and death. This paper takes a 50,000 m3 gas tank as an example to analyze the consequences of an accident. First, a TNT-equivalent explosion model, quantitative risk analysis and FLACS software are used to quantitatively analyze the explosion consequences. The range of casualties caused by the vapor cloud explosion is obtained. The simulation results are then compared with the actual damage range of a gas tank explosion, and the accuracy of the simulation results is verified. Next, the personal and social risks of a gas tank are identified according to China's national standards, and it is concluded that the individual risk can be tolerated, the social risk is within the tolerable range and its area has been reduced as far as possible, and it is necessary to minimize the overall risk as much as possible. Finally, a qualitative analysis of the gas tank explosion accident is carried out and the causes of the accident are analyzed. These analyses can be used to guide practices and effectively prevent the occurrence of similar accidents.

Neurons in the developing brain undergo extensive structural refinement as nascent circuits adopt their mature form1. This transformation is facilitated by the engulfment and degradation of excess axonal branches and inappropriate synapses by surrounding glial cells, including microglia and astrocytes2,3. However, the small size of phagocytic organelles and the complex, highly ramified morphology of glia has made it difficult to determine the contribution of these and other glial cell types to this process. Here, we used large scale, serial electron microscopy (ssEM) with computational volume segmentation to reconstruct the complete 3D morphologies of distinct glial types in the mouse visual cortex. Unexpectedly, we discovered that the fine processes of oligodendrocyte precursor cells (OPCs), a population of abundant, highly dynamic glial progenitors4, frequently surrounded terminal axon branches and included numerous phagolysosomes (PLs) containing fragments of axons and presynaptic terminals. Single- nucleus RNA sequencing indicated that cortical OPCs express key phagocytic genes, as well as neuronal transcripts, consistent with active axonal engulfment. PLs were ten times more abundant in OPCs than in microglia in P36 mice, and declined with age and lineage progression, suggesting that OPCs contribute very substantially to refinement of neuronal circuits during later phases of cortical development.

Neurons in the developing brain undergo extensive structural refinement as nascent circuits adopt their mature form1. This transformation is facilitated by the engulfment and degradation of excess axonal branches and inappropriate synapses by surrounding glial cells, including microglia and astrocytes2,3. However, the small size of phagocytic organelles and the complex, highly ramified morphology of glia has made it difficult to determine the contribution of these and other glial cell types to this process. Here, we used large scale, serial electron microscopy (ssEM) with computational volume segmentation to reconstruct the complete 3D morphologies of distinct glial types in the mouse visual cortex. Unexpectedly, we discovered that the fine processes of oligodendrocyte precursor cells (OPCs), a population of abundant, highly dynamic glial progenitors4, frequently surrounded terminal axon branches and included numerous phagolysosomes (PLs) containing fragments of axons and presynaptic terminals. Single- nucleus RNA sequencing indicated that cortical OPCs express key phagocytic genes, as well as neuronal transcripts, consistent with active axonal engulfment. PLs were ten times more abundant in OPCs than in microglia in P36 mice, and declined with age and lineage progression, suggesting that OPCs contribute very substantially to refinement of neuronal circuits during later phases of cortical development.

The construction of public art landscape at night is a direct symbol of the rapid development of modern cities. It has created a grand, integral and interactive field dominated by lighting environment. Moreover, through individualized, artistic and technological forms, it enriches people's cognition of urban public space and strengthens people's perception and experience of urban landscape environment at night. The night public art landscape combines functionality, artistry and culture, endows the city nightlife with symbolic meaning, and constantly expands the boundaries of art, humanities, society, economy and lifestyle. This paper will take the interactive design of night public art landscape as the research object, and through interpreting the typical cases of night public art landscape practice at home and abroad, summarize its interactive features and presentation types, and dig deep into the publicity and humanity contained in this interactive field. The purpose of this paper is to explore the important role of interactive design in promoting the sustainable development of people and cities from the perspective of public art, taking the night landscape as examples. In my opinion, the interactive design of night public art landscape will inevitably return to the core idea of “people-oriented”, showing a development trend from the coexistence of technical forms and interactive behaviors to the deep-seated emotional symbiotic interaction.

Repair and reconstruction of critical-sized bone defects has always been a difficult task in orthopedics. Hypoxia inducible factor-1α (HIF-1α) plays an important role in bone defect repair, it has the dual function of promoting osteogenesis and vascular regeneration, but it is quickly degraded by the body under normoxic conditions. Previously we prepared mutant HIF-1α, which has been shown to efficiently maintain cellular expression under normoxic conditions. In this study, we evaluated for the first time the role of exosomes of rat bone marrow mesenchymal stem cell carry mutant HIF-1α (BMSC-Exos-HIF1α) in repairing critical-sized bone defects. Evaluation of the effects of BMSC-Exos-HIF1α on bone marrow mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation by cell proliferation assay, alkaline phosphatase activity assay, alizarin red staining, real-time quantitative polymerase chain reaction. BMSC-Exos-HIF1α was loaded onto the β-TCP stent implanted in the bone defect area using a rat cranial critical-sized bone defect model, and new bone formation and neovascularization were detected in vivo by micro-CT, fluorescence labeling analysis, Microfil perfusion, histology and immunohistochemical analysis. In vitro results showed that BMSC-Exos-HIF1α stimulated the proliferation of BMSCs and up-regulated the expression level of bone-related genes, which was superior to bone marrow MSC exosomes (BMSC-Exos). In vivo results showed that BMSC-Exos-HIF1α combined with β-TCP scaffold promoted new bone regeneration and neovascularization in the bone defect area, and the effect was better than that of BMSC-Exos combined with β-TCP scaffold. In this study, the results showed that BMSC-Exos-HIF1α stimulated the proliferation and osteogenic differentiation of BMSCs and that BMSC-Exos-HIF1α combined with β-TCP scaffolds could repair critical-sized bone defects by promoting new bone regeneration and neovascularization.

Since the new century, with the changing and development of the times, cultural characteristics such as informatization, digitalization and consumerization have been continuously highlighted. New science and technology are rapidly flooding urban space, and people’s lifestyle and value orientation have undergone subversive changes. In the field of public art, the works of public art in the city are no longer the aesthetic expression of a single individual, but the reaction medium of the interactive relationships between people and things, person and person, people and natural world. Interactive, experiential and participatory design methods are increasingly valued and become the most direct manifestation of the “publicity” of art. This article will take interactive design in urban public art as the main research object, carry out a local investigation on the practice of urban public art in Shanghai area, relying on the case, focus on analyzing the presentation types, formal characteristics and connotation levels of interactive design, and discuss the construction way of emotional ties and cultural identity among artists, designers and the public. The purpose of this study is to explore the new trend of the development of interactive creative forms and design methods of urban public art, and to recognize that the future practices of urban public art is bound to grow dynamically and is an organic art that includes science and technology, experience and feedback, thoughts and expressions, aesthetic activities and the overall environment of life.

To eliminate the barrier among “designers (students)- virtual environment-users” in interior design teaching, as well as in response to the proposition of experience economy in this era, this study learns from relevant theories of embodied cognition, design thinking and drama theory to formulate the method of role immersion, which is applied in the general procedure of interior design. Through the application in the interior design course of “Regeneration of Old Built Space”, it is verified that “role immersion” can help students to wake up the “body”- a medium which is born to contact and interact with the environment. It can also help to cultivate students’ awareness and ability to carry out design from inside to outside and himself\herself to users to realize users’ positive perception and experience in continuous space and time. At last, the paper summarizes the problems of this method in teaching application and puts forward the developing points.

In order to achieve effective dust suppression during coal cutting process in a fully-mechanized coal mining face by using coal cutter dust removal fans, this study first conducted numerical simulations on the airflow-dustmigration rules. Then, by combining simulation results with experimental measurements and field tests, a novel hydraulic axial-flow dust coal cutter removal fan was developed. Simulation results demonstrated that, during the coal cutting process, high-concentration dust clusters exceeding 1000 mg/m3 were produced 0–20 m away from the coal cutter on the leeward side, which then spread to the operating space along the footway. After using dust removal fans, the concentration of the dust clusters on the leeward side of the coal cutter was reduced to below 500 mg/m3. The dust removal fans were then applied to the 3up705 fully-mechanized coal mining face at seven-five Coal Mine for field measurements. According to the measured results, the use of these dust removal fans can effectively reduce the dust concentration in the operating region around the coal cutter, and the dust removal rates of total dust and respirable dust reached up to 66.5% and 61.8%, respectively. Therefore, the dust removal fans performed well in terms of dust suppression in fully-mechanized coal mining faces.

Background. Platelet-rich plasma (PRP) has been shown to be a promising therapeutic agent against osteoarthritis (OA), whereas its chondroprotection mechanism is not fully elucidated. Autophagy is considered an important biological process throughout the development of OA. Therefore, the objective of the present study is to investigate the role of autophagy in the chondroprotection and compare the effects of releasate between L-PRP and P-PRP. Methods. PRP were prepared from rat blood. Rat chondrocytes pretreated in the presence or absence of interleukin-1 beta (IL-1β) were incubated with PRP releasate. The expressions of OA-related genes and autophagy-related genes were determined by RT-PCR and western blot, respectively. Autophagic bodies were assessed by transmission electron microscopy and the autophagy flux was monitored under the confocal microscopy. The effect of PRP on autophagy was further investigated in the milieu of autophagy activator, rapamycin, or autophagy inhibition by downregulation of Atg5. The effect of PRP on cartilage repair and autophagy was also evaluated in an OA rat model. Results. In vitro, PRP releasate increased the expression of the anabolic genes, COL2 and Aggrecan, and decreased the expression of the catabolic genes, whereas the expression of autophage markers, Atg5 and Beclin-1, as well as the ratio of LC3 II/LC3 I, was not significantly altered in normal or IL-1β-treated chondrocytes. Similar expression pattern was found following the activation (rapamycin) or inhibition (Atg5 silencing) of autophagy. In vivo, PRP releasate ameliorated posttraumatic cartilage degeneration while the expression of LC3 was comparable to that in the vehicle treatment group. Conclusions. PRP releasate promoted the anabolic gene expression, relieved inflammatory stress in chondrocytes, and ameliorated cartilage degeneration, but autophagy was independent of these processes.

CoS nanoplates and nanoparticles films were successfully grown on carbon fibers (CF) via one-step process and used in fiber-shaped dye sensitized solar cells as counter electrodes. The electrocatalytic ability of CF accompanied with CoS nanoplates electrode was comparable with the expensive Pt wire, and obviously superior to the CF covered by CoS nanoparticles film. The results were believed to originate from: (1) the enough void space among CoS nanoplates allows easier redox ion diffusion; (2) the two-dimensional nanoplates favor the longer distance electron transport with less diffusive hindrance than the randomly depositing nanoparticles film, where the electrons have to cross many tiny particle boundaries that can trap electrons.

Resveratrol (trans-3,5,4′-trihydroxystilbene, RSV), a naturally occurring biologically active polyphenol has been observed to induce numerous beneficial effects in diabetic animals and humans. However, its protective effects are somewhat controversial due to low bioavailability and rapid clearance rate. Therefore, we in this study have tried to investigate if its main metabolites, RSV-3-O-glucuronide (R3G) and RSV-4-O-glucuronide (R4G) could ameliorate insulin resistance, similar to RSV in insulin-resistant HepG2 cells. Herein, we first established an insulin-resistant cell model by treating HepG2 cells with 1 × 10−6 mol L−1 insulin for 24 h. Subsequently, the effects of R3G and R4G on insulin resistance inhibition were evaluated in HepG2 cells. Interestingly, our data indicated that R3G and R4G treatment improved cellular glucose uptake and glycogen synthesis contents, and blocked generation of intracellular reactive oxygen species (ROS). Additionally, R3G and R4G also modulated insulin signaling and improved insulin sensitivity by modulating the IRS-1/AMPK signaling pathway. Taken together, our data provided a significant new insight into the effects and molecular mechanism of R3G and R4G on ameliorating insulin resistance in HepG2 cells. Overall, our data supported the hypothesis that despite low bioavailability in vivo, RSV biological effects could be mediated through its metabolites.

Epidemiologic studies have shown alcohol plays a pivotal role in the development of osteonecrosis of the femoral head (ONFH). The aim of this study was to explore the underlying mechanism of alcohol-induced ONFH and the protective effect of pifithrin-α (PFTα). In vitro, we found ethanol treatment significantly activated p53, suppressed Wnt/β-catenin signaling and inhibited osteogenic-related proteins. Furthermore, by separating the cytoplasmic and nuclear proteins, we found ethanol inhibited osteogenesis by impairing the accumulation of β-catenin in both the cytoplasm and nucleus in human bone mesenchymal stem cells (hBMSCs), which resulted from activating glycogen synthase kinase-3β (GSK-3β). Therefore, PFTα, a p53 inhibitor, was introduced in this study to block the ethanol-triggered activation of p53 in hBMSCs and alcohol-induced ONFH in a rat model. In vivo, we established alcohol-induced ONFH in rats and investigated the protective effect of PFTα. Hematoxylin & eosin (H&E) staining combined with TdT-mediated dUTP nick end labeling (TUNEL), cleaved caspase-3 immunohistochemical staining, and micro-CT images revealed substantial ONFH in the alcohol-administered rats, whereas significantly less osteonecrosis developed in the rats injected with PFTα. Osteogenic-related proteins, including osteocalcin, osteopontin and collagen I, were significantly decreased in the alcohol-administered rats, whereas these results were reversed in the PFTα-injected rats. Fluorochrome labeling similarly showed that alcohol significantly reduced the osteogenic activity in the rat femoral head, which was blocked by the injection of PFTα. In conclusion, PFTα had an antagonistic effect against the effects of ethanol on hBMSCs and could be a clinical strategy to prevent the development of alcohol-induced ONFH.

Erythrocyte sedimentation rate (ESR), which reflects the sedimentation rate of platelets, leukocytes and erythrocytes in response to centrifugal force, may influence the cellular composition of platelet-rich plasma (PRP) obtained via centrifugation methods. However, no relevant studies have substantiated this. In the present study, blood was collected from 40 healthy volunteers and used to prepare PRP with two plasma-based preparation systems [YinPRP and Plasma Rich in Growth Factor (PRGF) systems] and two buffy coat-based systems (RegenPRP and WEGOPRP systems) in a single-donor model. Volumes of PRP and platelet-poor plasma (PPP) that were removed in the preparation process were recorded. Analyses of ESR, haematocrit, C-reaction protein, coagulation, serum glucose and serum lipid of the whole blood used for PRP preparation were performed to evaluate the levels of ESR and the factors known to influence it. Whole blood analysis was performed to evaluate the cellular composition of PRP. Results demonstrated that there were marked positive correlations between the ESR of the whole blood used for PRP preparation and PPP removal efficiencies, platelet concentrations, platelet capture efficiencies and platelet enrichment factors of PRP formulations obtained from plasma-based systems, and PRP yield efficiency of RegenPRP and PPP removal efficiency of WEGOPRP. Furthermore, there were marked negative correlations between ESR and concentrations and enrichment factors of platelets, leukocytes and erythrocytes of RegenPRP. Fibrinogen concentration of the whole blood, which had a marked positive correlation with ESR, also influenced the cellular composition of PRP. These findings may increase the understanding of PRP preparation and provide substantial evidence for the individualised optimisation of PRP preparation systems used in clinical practice.

For the clinical application of bone tissue engineering with the combination of biomaterials and mesenchymal stem cells (MSCs), bone scaffolds should possess excellent biocompatibility and osteoinductivity to accelerate the repair of bone defects. Herein, strontium hydroxyapatite [SrHAP, Ca10-xSrx(PO4)6(OH)2]/chitosan (CS) nanohybrid scaffolds were fabricated by a freeze-drying method. The SrHAP nanocrystals with the different x values of 0, 1, 5 and 10 are abbreviated to HAP, Sr1HAP, Sr5HAP and Sr10HAP, respectively. With increasing x values from 0 to 10, the crystal cell volumes and axial lengths of SrHAP become gradually large because of the greater ion radius of Sr2+ than Ca2+, while the crystal sizes of SrHAP decrease from 70.4nm to 46.7nm. The SrHAP/CS nanohybrid scaffolds exhibits three-dimensional (3D) interconnected macropores with pore sizes of 100-400μm, and the SrHAP nanocrystals are uniformly dispersed within the scaffolds. In vitro cell experiments reveal that all the HAP/CS, Sr1HAP/CS, Sr5HAP/CS and Sr10HAP/CS nanohybrid scaffolds possess excellent cytocompatibility with the favorable adhesion, spreading and proliferation of human bone marrow mesenchymal stem cells (hBMSCs). The Sr5HAP nanocrystals in the scaffolds do not affect the adhesion, spreading of hBMSCs, but they contribute remarkably to cell proliferation and osteogenic differentiation. As compared with the HAP/CS nanohybrid scaffold, the released Sr2+ ions from the SrHAP/CS nanohybrid scaffolds enhance alkaline phosphatase (ALP) activity, extracellular matrix (ECM) mineralization and osteogenic-related COL-1 and ALP expression levels. Especially, the Sr5HAP/CS nanohybrid scaffolds exhibit the best osteoinductivity among four groups because of the synergetic effect between Ca2+ and Sr2+ ions. Hence, the Sr5HAP/CS nanohybrid scaffolds with excellent cytocompatibility and osteogenic property have promising application for bone tissue engineering.

OBJECTIVES: Osteoarthritis (OA) is the most common joint disease throughout the world. Exosomes derived from miR-140-5p-overexpressing synovial mesenchymal stem cells (SMSC-140s) may be effective in treating OA. We hypothesized that exosomes derived from SMSC-140 (SMSC-140-Exos) would enhance the proliferation and migration abilities of articular chondrocytes (ACs) without harming extracellular matrix (ECM) secretion. METHODS: SMSCs were transfected with or without miR-140-5p. Exosomes derived from SMSCs or SMSC-140s (SMSC-Exos or SMSC-140-Exos) were isolated and identified. Proliferation, migration and ECM secretion were measured in vitro and compared between groups. The mechanism involving alternative Wnt signalling and activation of Yes-associated protein (YAP) was investigated using lentivirus, oligonucleotides or chemical drugs. The preventative effect of exosomes in vivo was measured using Safranin-O and Fast green staining and immunohistochemical staining. RESULTS: Wnt5a and Wnt5b carried by exosomes activated YAP via the alternative Wnt signalling pathway and enhanced proliferation and migration of chondrocytes with the side-effect of significantly decreasing ECM secretion. Highly-expressed miR-140-5p blocked this side-effect via RalA. SMSC-140-Exos enhanced the proliferation and migration of ACs without damaging ECM secretion in vitro, while in vivo, SMSC-140-Exos successfully prevented OA in a rat model. CONCLUSIONS: These findings highlight the promising potential of SMSC-140-Exos in preventing OA. We first found a potential source of exosomes and studied their merits and shortcomings. Based on our understanding of the molecular mechanism, we overcame the shortcomings by modifying the exosomes. Such exosomes derived from modified cells hold potential as future therapeutic strategies.

Serial-section electron microscopy is the method of choice for studying cellular structure and network connectivity in the brain. We have built a pipeline of parallel imaging using transmission electron automated microscopes (piTEAM) that scales this technology and enables the acquisition of petascale datasets containing local cortical microcircuits. The distributed platform is composed of multiple transmission electron microscopes that image, in parallel, different sections from the same block of tissue, all under control of a custom acquisition software (pyTEM) that implements 24/7 continuous autonomous imaging. The suitability of this architecture for large scale electron microscopy imaging was demonstrated by acquiring a volume of more than 1 mm3 of mouse neocortex spanning four different visual areas. Over 26,500 ultrathin tissue sections were imaged, yielding a dataset of more than 2 petabytes. Our current burst imaging rate is 500 Mpixel/s (image capture only) per microscope and net imaging rate is 100 Mpixel/s (including stage movement, image capture, quality control, and post processing). This brings the combined burst acquisition rate of the pipeline to 3 Gpixel/s and the net rate to 600 Mpixel/s with six microscopes running acquisition in parallel, which allowed imaging a cubic millimeter of mouse visual cortex at synaptic resolution in less than 6 months.