Microglia are the mononuclear phagocytes with various functions in the central nervous system, and the morphologies of microglia imply the different stages and functions. In optical nerve transection model of the retina, the retrograde degeneration of retinal ganglion cells induces microglial activations to a unique morphology termed rod microglia. A few studies described the rod microglia in the cortex and retina; however, the spatial characteristic of rod microglia is not fully understood. In this study, we built a mathematical model to characterize the spatial trait of rod microglia. In addition, we developed a Matlab-based image processing pipeline that consists of log enhancement, image segmentation, mathematical morphology based cell detection, area calculation and angle analysis. This computer program provides researchers a powerful tool to quickly analyze the spatial trait of rod microglia.

With the use of adaptive optics (AO), high-resolution microscopic imaging of living human retina in the single cell level has been achieved. In an adaptive optics confocal scanning laser ophthalmoscope (AOSLO) system, with a small field size (about 1 degree, 280 μm), the motion of the eye severely affects the stabilization of the real-time video images and results in significant distortions of the retina images. In this paper, Scale-Invariant Feature Transform (SIFT) is used to abstract stable point features from the retina images. Kanade-Lucas-Tomasi(KLT) algorithm is applied to track the features. With the tracked features, the image distortion in each frame is removed by the second-order polynomial transformation, and 10 successive frames are co-added to enhance the image quality. Features of special interest in an image can also be selected manually and tracked by KLT. A point on a cone is selected manually, and the cone is tracked from frame to frame.

Quality protein maize (QPM; Zea mays L.) has effectively enhanced levels of the amino acids, lysine, and tryptophan, over normal maize and provided balanced dietary protein for the health and development of monogastric animals and humans. However, as in normal maize, QPM varieties are low in provitamin A (ProVA), a precursor of vitamin A, which can lead to vitamin A deficiency in humans when maize is a significant part of their diet. In this study, maize inbred Hp321-1 carrying the favorable alleles crtRB1-5'TE-2 and crtRB1-3'TE-1 that can enhance levels of ProVA, was used as donor for improving ProVA in QPM inbred lines CML161 and CML171. Functional markers for identifying the favorable alleles crtRB1-5'TE-2 and crtRB1-3'TE-1 were used in foreground selection, and simple sequence repeat markers were used in background selection for the BC1F1, BC2F1, and BC2F2 generations. The background recovery rates were 77.4 and 84.5 % for CML161 and CML171 populations, respectively, in the BC1F1 generation, and 89.9 and 92.1 % in the BC2F2 generation. With foreground and background selection, the mean ProVA concentration has been improved from 1.60 µg g-1 in the parent of CML161 to 5.25 µg g-1 in its BC2F3 offspring, from 1.80 µg g-1 in the parent of CML171 to 8.14 µg g-1 in its BC2F3 offspring while maintaining similar QPM characteristics of the recurrent parents. The success from this study offers maize breeders a procedure for increasing ProVA in QPM lines, which will greatly mitigate vitamin A deficiency and protein-energy malnutrition in developing countries.

It is not clear how Fms-like tyrosine kinase 3-internal tandem duplications (FLT3-ITD) regulates checkpoint kinase 1 (CHK1) in acute myeloid leukemia (AML). In this study, we investigated the regulatory effect of FLT3-ITD on CHK1. Our results showed that CHK1 was highly expressed in FLT3-ITD positive AML. The overall survival rate and disease-free survival rate of AML patients with high CHK1 level were lower than those of patients with low CHK1 level. Mechanistically, FLT3-ITD recruited p300 to the CHK1 promoter and subsequently acetylated H3K27, thereby enhancing the transcription of CHK1. Interfering with the expression of CHK1 significantly inhibited the cell proliferation and induced cell apoptosis in FLT3-ITD positive MV4-11 cells. In addition, CHK1 knockdown promoted the sensitivity of MV4-11 cells to the epigenetic inhibitors JQ1 and C646. This study discovers a new therapeutic target for FLT3-ITD + AML and provided evidence for the combination of epigenetic inhibitors for AML treatment.

Early diagnosis or detection of Alzheimer's disease (AD) from the normal elder control (NC) is very important. However, the computer-aided diagnosis (CAD) was not widely used, and the classification performance did not reach the standard of practical use. We proposed a novel CAD system for MR brain images based on eigenbrains and machine learning with two goals: accurate detection of both AD subjects and AD-related brain regions.

CircRNAs are associated with adriamycin (ADM) resistance in triple‑negative breast cancer (TNBC), but the mechanism is unknown. Reverse transcription‑quantitative PCR was applied to quantify circular RNA (circRNA)_0044556, microRNA (miR)‑145 and NRAS proto‑oncogene, GTPase (NRAS) in TNBC tissues and cells with or without ADM treatment. Following ADM treatment, the effects of circRNA_0044556 on the viability, ADM resistance, apoptosis and migration of TNBC cells were investigated by cell function experiments (Cell Counting Kit‑8, flow cytometry and Transwell assays). The targeting relationship between circRNA_0044556 and miR‑145 was investigated via bioinformatics analysis, dual‑luciferase reporter assay and RNA immunoprecipitation. The effects of the circRNA_0044556/miR‑145 axis on the TNBC cells were revealed by rescue experiments. Correlations among circRNA_0044556, miR‑145 and NRAS were analyzed by Pearson's correlation test. CircRNA_0044556 was highly expressed in TNBC tissues and cells with or without ADM‑resistance. The overexpression of circRNA_0044556 promoted cell viability, ADM‑resistance and migration, while inhibiting the apoptosis by sponging miR‑145. Upregulation of miR‑145 reversed the effects of circRNA_0044556 on the TNBC cells. CircRNA_0044556 was negatively correlated with miR‑145 yet positively correlated with NRAS, the target gene of miR‑145, in addition to the discovery suggesting the negative regulatory effects of circRNA_0044556 on miR‑145. CircRNA_0044556 diminished the sensitivity of TNBC cells to ADM via the miR‑145/NRAS axis.

The wheat blossom midge Sitodiplosis mosellana, one of the most disastrous wheat pests, depends highly on olfactory cues to track suitable plants. To better understand the olfactory recognition mechanisms involved in host selection, in the present study we cloned two S. mosellana adult antenna-specific odorant binding protein (OBP) genes, SmosOBP12 and SmosOBP17, and evaluated bacterially expressed recombinant proteins for their selectivity and sensitivity for host wheat volatiles using the fluorescence-based ligand binding assay. The results showed that both SmosOBPs effectively bound alcohol, ester, ketone, and terpenoid compounds. Particularly, SmosOBP12 had significantly higher affinities (Ki < 10.5 μM) than SmosOBP17 (Ki2 > 0.1 μM) to 3-hexanol, 1-octen-3-ol, D-panthenol, 3-carene, (Z)-3-hexenylacetate, hexyl acetate, methyl salicylate, heptyl acetate, and ethyl heptanoate. Consistently, S. mosellana females were attracted to all these chemicals in a behavioral assay using Y-tube olfactometer. SmosOBP12 also bound aldehyde, but neither bound alkanes. Notably, SmosOBP12 exhibited strong affinity to ocimene (Ki = 8.2 μM) that repelled S. mosellana. SmosOBP17, however, was insensitive to this compound. Taken together, our results indicate that SmosOBP12 may play a greater role than SmosOBP17 in perceiving these biologically active plant volatiles.

Real-time monitoring of rock stability during the mining process is critical. This paper first proposed a RIME algorithm (CCRIME) based on vertical and horizontal crossover search strategies to improve the quality of the solutions obtained by the RIME algorithm and further enhance its search capabilities. Then, by constructing a binary version of CCRIME, the key parameters of FKNN were optimized using a binary conversion method. Finally, a discrete CCRIME-based BCCRIME was developed, which uses an S-shaped function transformation approach to address the feature selection issue by converting the search result into a real number that can only be zero or one. The performance of CCRIME was examined in this study from various perspectives, utilizing 30 benchmark functions from IEEE CEC2017. Basic algorithm comparison tests and sophisticated variant algorithm comparison experiments were also carried out. In addition, this paper also used collected microseismic and blasting data for classification prediction to verify the ability of the BCCRIME-FKNN model to process real data. This paper provides new ideas and methods for real-time monitoring of rock mass stability during deep well mineral resource mining.

In light of the youth mental health crisis, as 1 in 5 children have a mental disorder diagnosis by age 3, identification of transdiagnostic behavioral vulnerability prior to impairing psychopathology must occur at an earlier phase of the clinical sequence. Here, we lay the groundwork for a pragmatic irritability measure to identify at-risk infant-toddlers.

Maternal stress has negative consequences on infant behavioral development, and COVID-19 presented uniquely stressful situations to mothers of infants born during the pandemic. We hypothesized that mothers with higher levels of perceived stress during the pandemic would report higher levels of infant regulatory problems including crying and interrupted sleep patterns.

Human melanomas frequently harbor amplifications of EZH2. However, the contribution of EZH2 to melanoma formation has remained elusive. Taking advantage of murine melanoma models, we show that EZH2 drives tumorigenesis from benign BrafV600E- or NrasQ61K-expressing melanocytes by silencing of genes relevant for the integrity of the primary cilium, a signaling organelle projecting from the surface of vertebrate cells. Consequently, gain of EZH2 promotes loss of primary cilia in benign melanocytic lesions. In contrast, blockade of EZH2 activity evokes ciliogenesis and cilia-dependent growth inhibition in malignant melanoma. Finally, we demonstrate that loss of cilia enhances pro-tumorigenic WNT/β-catenin signaling, and is itself sufficient to drive metastatic melanoma in benign cells. Thus, primary cilia deconstruction is a key process in EZH2-driven melanomagenesis.

Cytochrome P450 2A13 (CYP2A13), an extrahepatic enzyme mainly expressed in the human respiratory system, has been reported to mediate the metabolism and toxicity of cigarette smoke. We previously found that nicotine inhibited 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism by CYP2A13, but its influence on other components of cigarette smoke remains unclear. The nicotine component of cigarette smoke extract (CSE) was separated, purified, and identified using high-performance liquid chromatography (HPLC) and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), splitting CSE into a nicotine section (CSE-N) and nicotine-free section (CSE-O). Cell viability and apoptosis by Cell Counting Kit-8 (CCK-8) and flow cytometry assays were conducted on immortalized human bronchial epithelial (BEAS-2B) cells stably expressing CYP2A13 (B-2A13) or vector (B-V), respectively. Interestingly, CSE and CSE-O were toxic to BEAS-2B cells whereas CSE-N showed less cytotoxicity. CSE-O was more toxic to B-2A13 cells than to B-V cells (IC50 of 2.49% vs. 7.06%), which was flatted by 8-methoxypsoralen (8-MOP), a CYP inhibitor. CSE-O rather than CSE or CSE-N increased apoptosis of B-2A13 cells rather than B-V cells. Accordingly, compared to CSE-N and CSE, CSE-O significantly changed the expression of three pairs of pro- and anti-apoptotic proteins, Bcl-2 Associated X Protein/B cell lymphoma-2 (Bax/Bcl-2), Cleaved Poly (Adenosine Diphosphate-Ribose) Polymerase/Poly (Adenosine Diphosphate-Ribose) Polymerase (C-PARP/PARP), and C-caspase-3/caspase-3, in B-2A13 cells. In addition, recombination of CSE-N and CSE-O (CSE-O/N) showed similar cytotoxicity and apoptosis to the original CSE. These results demonstrate that the nicotine component decreases the metabolic activation of CYP2A13 to CSE and aids in understanding the critical role of CYP2A13 in human respiratory diseases caused by cigarette smoking.

Lipodermatosclerosis (LDS) is a severe skin change accompanied by the development of chronic venous disease of the lower extremities. Its main clinical manifestations are erythema, induration, hyperpigmentation, and rough and thickened skin. It may also eventually lead to refractory ulcers, skin necrosis and even cancer. Conventional treatment methods mainly include the intake of oral anabolic hormones or androgen and pressure therapy. However, patients often refuse due to their drug resistance and intolerance. As a clinical irreplaceable treatment method for LDS, traditional Chinese medicine (TCM) has not been compared of the safety and effectiveness so far. Therefore, we cannot wait to use a method to compare the efficacy of TCM for LDS systematically, such as network meta-analysis (NMA).

Recently, swarm intelligence algorithms have received much attention because of their flexibility for solving complex problems in the real world. Recently, a new algorithm called the colony predation algorithm (CPA) has been proposed, taking inspiration from the predatory habits of groups in nature. However, CPA suffers from poor exploratory ability and cannot always escape solutions known as local optima. Therefore, to improve the global search capability of CPA, an improved variant (OLCPA) incorporating an orthogonal learning strategy is proposed in this paper. Then, considering the fact that the swarm intelligence algorithm can go beyond the local optimum and find the global optimum solution, a novel OLCPA-CNN model is proposed, which uses the OLCPA algorithm to tune the parameters of the convolutional neural network. To verify the performance of OLCPA, comparison experiments are designed to compare with other traditional metaheuristics and advanced algorithms on IEEE CEC 2017 benchmark functions. The experimental results show that OLCPA ranks first in performance compared to the other algorithms. Additionally, the OLCPA-CNN model achieves high accuracy rates of 97.7% and 97.8% in classifying the MIT-BIH Arrhythmia and European ST-T datasets.

Dendritic spines are described as neuronal protrusions. The morphology of dendritic spines and dendrites has a strong relationship to its function, as well as playing an important role in understanding brain function. Quantitative analysis of dendrites and dendritic spines is essential to an understanding of the formation and function of the nervous system. However, highly efficient tools for the quantitative analysis of dendrites and dendritic spines are currently undeveloped. In this paper we propose a novel three-step cascaded algorithm-RTSVM- which is composed of ridge detection as the curvature structure identifier for backbone extraction, boundary location based on differences in density, the Hu moment as features and Twin Support Vector Machine (TSVM) classifiers for spine classification. Our data demonstrates that this newly developed algorithm has performed better than other available techniques used to detect accuracy and false alarm rates. This algorithm will be used effectively in neuroscience research.

Perceptual learning, the improved sensitivity via repetitive practice, is a universal phenomenon in vision and its neural mechanisms remain controversial. A central question is which stage of processing is changed after training. To answer this question, we measured the contrast response functions and electroencephalography (EEG) before and after ten daily sessions of contrast detection training. Behavioral results showed that training substantially improved visual acuity and contrast sensitivity. The learning effect was significant at the trained condition and partially transferred to control conditions. Event-related potential (ERP) results showed that training reduced the latency in both early and late ERPs at the trained condition. Specifically, contrast-gain-related changes were observed in the latency of P1, N1-P2 complex, and N2, which reflects neural changes across the early, middle, and high-level sensory stages. Meanwhile, response-gain-related changes were found in the latency of N2, which indicates stimulus-independent effect in higher-level stages. In sum, our findings indicate that learning leads to changes across different processing stages and the extent of learning and transfer may depend on the specific stage of information processing.

In this study, hotspot regions, QTL clusters, and candidate genes for eight ear-related traits of maize (ear length, ear diameter, kernel row number, kernel number per row, kernel length, kernel width, kernel thickness, and 100-kernel weight) were summarized and analyzed over the past three decades. This review aims to (1) comprehensively summarize and analyze previous studies on QTLs associated with these eight ear-related traits and identify hotspot bin regions located on maize chromosomes and key candidate genes associated with the ear-related traits and (2) compile major and stable QTLs and QTL clusters from various mapping populations and mapping methods and techniques providing valuable insights for fine mapping, gene cloning, and breeding for high-yield and high-quality maize. Previous research has demonstrated that QTLs for ear-related traits are distributed across all ten chromosomes in maize, and the phenotypic variation explained by a single QTL ranged from 0.40% to 36.76%. In total, 23 QTL hotspot bins for ear-related traits were identified across all ten chromosomes. The most prominent hotspot region is bin 4.08 on chromosome 4 with 15 QTLs related to eight ear-related traits. Additionally, this study identified 48 candidate genes associated with ear-related traits. Out of these, five have been cloned and validated, while twenty-eight candidate genes located in the QTL hotspots were defined by this study. This review offers a deeper understanding of the advancements in QTL mapping and the identification of key candidates associated with eight ear-related traits. These insights will undoubtedly assist maize breeders in formulating strategies to develop higher-yield maize varieties, contributing to global food security.

AD-2 (20(R)-dammarane-3β, 12β, 20, 25-tetrol, 25-OH-PPD) was structurally modified to introduce additional amino groups, which can better exert its anti-tumor effects in MCF-7, A549, LoVo, HCT-116, HT -29, and U-87 cell lines. We investigated the cellular activity of 15 different AD-2 amino acid derivatives on HepG2 cells and the possible mechanism of action of the superior derivative 6b. An MTT assay was used to detect the cytotoxicity of the derivatives. Western blotting was used to study the signaling pathways. Flow cytometry was used to detect cell apoptosis and ghost pen peptide staining was used to identify the changes in the cytoskeleton. The AD-2 amino acid derivatives have a better cytotoxic effect on the HepG2 cells than AD-2, which may be achieved by promoting the apoptosis of HepG2 cells and influencing the cytoskeleton. The derivative 6b shows obvious anti-HepG2 cells activity through affecting the expression of apoptotic proteins such as MDM2, P-p53, Bcl-2, Bax, Caspase 3, Cleaved Caspase 3, Caspase 8, and NSD2. According to the above findings, the amino acid derivatives of AD-2 may be developed as HepG2 cytotoxic therapeutic drugs.

Aim. Alzheimer's disease (AD) is a chronic neurodegenerative disease. Recently, computer scientists have developed various methods for early detection based on computer vision and machine learning techniques. Method. In this study, we proposed a novel AD detection method by displacement field (DF) estimation between a normal brain and an AD brain. The DF was treated as the AD-related features, reduced by principal component analysis (PCA), and finally fed into three classifiers: support vector machine (SVM), generalized eigenvalue proximal SVM (GEPSVM), and twin SVM (TSVM). The 10-fold cross validation repeated 50 times. Results. The results showed the "DF + PCA + TSVM" achieved the accuracy of 92.75 ± 1.77, sensitivity of 90.56 ± 1.15, specificity of 93.37 ± 2.05, and precision of 79.61 ± 2.21. This result is better than or comparable with not only the other proposed two methods, but also ten state-of-the-art methods. Besides, our method discovers the AD is related to following brain regions disclosed in recent publications: Angular Gyrus, Anterior Cingulate, Cingulate Gyrus, Culmen, Cuneus, Fusiform Gyrus, Inferior Frontal Gyrus, Inferior Occipital Gyrus, Inferior Parietal Lobule, Inferior Semi-Lunar Lobule, Inferior Temporal Gyrus, Insula, Lateral Ventricle, Lingual Gyrus, Medial Frontal Gyrus, Middle Frontal Gyrus, Middle Occipital Gyrus, Middle Temporal Gyrus, Paracentral Lobule, Parahippocampal Gyrus, Postcentral Gyrus, Posterior Cingulate, Precentral Gyrus, Precuneus, Sub-Gyral, Superior Parietal Lobule, Superior Temporal Gyrus, Supramarginal Gyrus, and Uncus. Conclusion. The displacement filed is effective in detection of AD and related brain-regions.

Staphylococcus aureus (S. aureus) is an opportunistic bacterial pathogen responsible for a diverse spectrum of human diseases, resulting in considerable yearly mortality rates. Due to its rapid acquisition of antibiotic resistance, it becomes increasingly difficult to cure S. aureus infections with conventional antibiotics. Immunotherapy represents a promising alternative strategy to prevent and/or treat the infection. In the present study, passive immunization with polyclonal antibodies targeting three possible S. aureus antigens, Hla, SEB and MntC (termed "SAvac-pcAb") after challenge with lethal dose of S. aureus resulted in reduced bacterial loads, inflammatory cell infiltration and decreased pathology, and was able to provide nearly complete protection in a murine sepsis model. In vitro studies confirmed the direct interaction of SAvac-pcAb with S. aureus bacteria. Additional studies validated that SAvac-pcAb contained both opsonic and neutralizing antibodies that contributed to its protective efficacy. The former mediated opsonophagocytosis in a neutrophil-dependent manner, while the later inhibited the biological functions of Hla and SEB, two major virulence factors secreted by S. aureus. Critically, we demonstrated that SAvac-pcAb was cross-reactive with different clinical strains of S. aureus. These results confirmed the efficacy for treatment of S. aureus infection by passive immunization as an important therapeutic option.