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Abstract This research aims to explore more efficient machine learning (ML) algorithms with better performance for short-term forecasting. Up-to-date literature shows a lack of research on selecting practical ML algorithms for short-term forecasting in real-time industrial applications. This research uses a quantitative and qualitative mixed method combining two rounds of literature reviews, a case study, and a comparative analysis. Ten widely used ML algorithms are selected to conduct a comparative study of gas warning systems in a case study mine. We propose a new assessment visualization tool: a 2D space-based quadrant diagram can be used to visually map prediction error assessment and predictive performance assessment for tested algorithms. Overall, this visualization tool indicates that LR, RF, and SVM are more efficient ML algorithms with overall prediction performance for short-term forecasting. This research indicates ten tested algorithms can be visually mapped onto optimal (LR, RF, and SVM), efficient (ARIMA), suboptimal (BP-SOG, KNN, and Perceptron), and inefficient algorithms (RNN, BP_Resilient, and LSTM). The case study finds results that differ from previous studies regarding the ML efficiency of ARIMA, KNN, LR, LSTM, and SVM. This study finds different views on the prediction performance of a few paired algorithms compared with previous studies, including RF and LR, SVM and RF, KNN and ARIMA, KNN and SVM, RNN and ARIMA, and LSTM and SVM. This study also suggests that ARIMA, KNN, LR, and LSTM should be investigated further with additional prediction error assessments. Overall, no single algorithm can fit all applications. This study raises 20 valuable questions for further research.

Urban transportation is a key contributor to greenhouse gas emissions. Given that metro systems serve as prominent modes of public transportation, it becomes imperative to investigate the alteration in carbon emissions subsequent to the inauguration of new metro lines, along with the determinants influencing the metro commuting choices. Previous research tends to use surveys to collect individual travel data, which may have sample selection and self-reported data problems. This research combines big data and survey method to study commuting carbon emission change and influencing factors of metro adoption. Because COVID-19 also has an impact on individual commuting mode, this research further explores total and per capita carbon emissions before and during the pandemic period. Selecting Shenzhen metro lines as a study case, it is found that the opening of newly extended metro lines leads to an increased proportion of residents commuting by metro and a decreased proportion of car users, resulting in a reduction of commuting carbon emissions. Additionally, during the pandemic, people tended to choose private cars for commuting due to its advantage of independence and privacy, resulting in an increase in commuting carbon emissions. Finally, regarding influencing factors of metro adoption, it is also found that young and middle-aged, highly educated, low-income residents or residents without cars are more likely to choose metro as their commuting mode. This research suggests the local government promote public transit after the pandemic period and tailor transport policies for the various resident groups, including providing subsidies.

Abstract The recent upswing in the integration of spatial multi-omics for conducting multidimensional information measurements is opening a new chapter in biological research. Mapping the landscape of various biomolecules including metabolites, proteins, nucleic acids, etc., and even deciphering their functional interactions and pathways is believed to provide a more holistic and nuanced exploration of the molecular intricacies within living systems. Mass spectrometry imaging (MSI) stands as a forefront technique for spatially mapping the metabolome, lipidome, and proteome within diverse tissue and cell samples. In this review, we offer a systematic survey delineating different MSI techniques for spatially resolved multi-omics analysis, elucidating their principles, capabilities, and limitations. Particularly, we focus on the advancements in methodologies aimed at augmenting the molecular sensitivity and specificity of MSI; and depict the burgeoning integration of MSI-based spatial metabolomics, lipidomics, and proteomics, encompassing the synergy with other imaging modalities. Furthermore, we offer speculative insights into the potential trajectory of MSI technology in the future.

Abstract Background Se (selenium) pollution is an emerging environmental concern. Excessive Se induces phytotoxicity. The endogenous H2S (hydrogen sulfide) was involved in plant adaptation to Se stress, but the signaling player of H2S remains unclear. Methods The study was conducted in a hydroponic system with different chemicals added to the treatment solution. Fluorescent tracking was performed to detect endogenous signaling molecules in plant tissues. Physiological changes were determined based on pharmaceutics and histochemical experiments. Gene expression was analyzed using qRT-PCR. The data were summarized using hierarchical cluster and Pearson correlation analysis. Results Se stress inhibited B. rapa growth (e.g. root elongation, shoot height, and seedling fresh weight and dry weight) in both dose- and time-dependent manners, with approximately 50% of root growth inhibition occurred at 20 µM Se. Se stress induced ROS (reactive oxygen species) accumulation and oxidative injury in B. rapa. Se exposure resulted in the upregulation of LCDs (L-cysteine desulfhydrase) and DCDs (D-cysteine desulfhydrase) encoding enzymes for H2S production in B. rapa at early stage of Se exposure, followed by downregulation of these genes at late stage. This was consistent with the change of endogenous H2S in B. rapa. Enhancing endogenous H2S level with NaHS (H2S donor) stimulates endogenous Ca2+ in B. rapa upon Se exposure, accompanied the attenuation of growth inhibition, ROS accumulation, oxidative injury, and cell death. The beneficial effects of H2S on detoxifying Se were blocked by decreasing endogenous Ca2+ level with Ca2+ channel blocker or Ca2+ chelator. Finally, hierarchical cluster combined with correlation analysis revealed that Ca2+ might acted as downstream of H2S to confer Se tolerance in B. rapa. Conclusion Ca2+ was an important player of H2S in the regulation of plant physiological response upon Se stress. Such findings extend our knowledge of the mechanism for Se-induced phytotoxicity. Graphical Abstract

Regional collaborative governance has become a key strategy for environmental protection, especially in reducing transboundary pollution transfer. This study, set against the backdrop of environmental governance in China's Fen-Wei Plain, employs evolutionary game theory to deeply analyze the strategic choices of local governments in managing haze pollution. We developed a model incorporating 14 key variables to systematically explore the emission reduction strategies of local governments under various policy environments. Through numerical simulations, we not only validate the effectiveness of the model but also focuses on how incentives and punishments from the central government influence the stability of local governments adopting a “strict enforcement” strategy. We find that appropriate incentives from the central government can significantly enhance the tendency of local governments to choose a “strict enforcement” strategy for emission reduction. Under certain conditions, whether adopting “strict enforcement” or “superficial enforcement,” both can lead to an Evolutionarily Stable Strategy (ESS). Moreover, the intensity of rewards and penalties from the central government and the benefits of collaborative governance by local governments are key factors determining the stability of strategies. Our findings underscore the importance of establishing performance-oriented incentive mechanisms, refining reward and punishment measures, and focusing on sustainable and adaptable governance strategies. The strategic recommendations provided by this study offer important guidance for balancing incentives and punishments, thereby stimulating local government enthusiasm for governance, which supports high-quality environmental protection and sustainable development goals.

Abstract Two-dimensional (2D) covalent organic frameworks (COFs) and their derivatives have been widely applied as electrocatalysts owing to their unique nanoscale pore configurations, stable periodic structures, abundant coordination sites and high surface area. This work aims to construct a non-thermodynamically stable Pt-N2 coordination active site by electrochemically modifying platinum (Pt) single atoms into a fully conjugated 2D COF as conductive agent-free and pyrolysis-free electrocatalyst for the hydrogen evolution reaction (HER). In addition to maximizing atomic utilization, single-atom catalysts with definite structures can be used to investigate catalytic mechanisms and structure-activity relationships. In this work, in-situ characterizations and theoretical calculations reveal that a nitrogen-rich graphene analogue COF not only exhibits a favorable metal-support effect for Pt, adjusting the binding energy between Pt sites to H* intermediates by forming unique Pt-N2 instead of the typical Pt-N4 coordination environment, but also enhances electron transport ability and structural stability, showing both conductivity and stability in acidic environments.

Abstract Acceleration of tooth movement during orthodontic treatment is challenging, with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step. Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages, especially adhesion G protein-coupled receptors (aGPCRs), play important roles in force sensing. However, its role in the regulation of osteoclast differentiation remains unclear. Herein, through single-cell analysis, we revealed that CD97, a novel mechanosensitive aGPCR, was expressed in macrophages. Compression upregulated CD97 expression and inhibited osteoclast differentiation; while knockdown of CD97 partially rescued osteoclast differentiation. It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation. RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression. Consistently, we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity, thereby accelerating tooth movement. In conclusion, our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

Hexavalent chromium (Cr[VI]) is a widespread environmental pollutant in air and water that is primarily attributed to industrial pollution. The current maximum contaminant levels (MCLs) for drinking water from the World Health Organization and the U.S. Environmental Protection Agency (0.05 and 0.1 mg/L, respectively) were set based on contact dermatitis and warrant further toxicological investigation. While Cr(VI) is neurotoxic and accumulates in the brain, most animal studies only report whole-brain Cr, leaving large knowledge gaps. Few studies consider differences between ages or sexes, and fewer consider essential metal dyshomeostasis. We sought to investigate where Cr accumulates in the brain, considering sex and age differences, following a 90-day drinking water exposure to current MCLs. Here, we report Cr levels in six brain regions of rats exposed to drinking water Cr(VI). We observed Cr only accumulated in the hippocampus, and only in older females. We further assessed changes to essential metals in the hippocampus, observing opposite effects across sexes and between young rats compared to older rats. In sum, our data indicate drinking water Cr(VI) selectively targeted the hippocampus, with geriatric females accumulating the most Cr, and induced significant essential metal dyshomeostasis even in tissues lacking evident Cr accumulation.

Abstract Background Histologic evaluation of the mucosal changes associated with celiac disease is important for establishing an accurate diagnosis and monitoring the impact of investigational therapies. While the Marsh-Oberhuber classification has been used to categorize the histologic findings into discrete stages (i.e., Type 0-3c), significant variability has been documented between observers using this ordinal scoring system. Therefore, we evaluated whether pathologist-trained machine learning classifiers can be developed to objectively quantitate the pathological changes of villus blunting, intraepithelial lymphocytosis, and crypt hyperplasia in small intestine endoscopic biopsies. Methods A convolutional neural network (CNN) was trained and combined with a secondary algorithm to quantitate intraepithelial lymphocytes (IEL) with 5 classes on CD3 immunohistochemistry whole slide images (WSI) and used to correlate feature outputs with ground truth modified Marsh scores in a total of 116 small intestine biopsies. Results Across all samples, median %CD3 counts (positive cells/enterocytes) from villous epithelium (VE) increased with higher Marsh scores (Type 0%CD3 VE = 13.4; Type 1–3%CD3 VE = 41.9, p

Abstract Purpose By comparing the results of the new self-contained darkroom refractive screener (YD-SX-A) versus table-top autorefractor and cycloplegic retinoscopy, to evaluate the performance of the YD-SX-A in detecting refractive error in children and adolescents and then judge whether it can be used in refractive screening. Methods Cross-sectional study. 1000 participants between the ages of 6 and 18 who visited the Optometry Center of the People's Hospital of Guangxi Zhuang Autonomous Region from June to December 2022 were selected. First, participants were instructed to measure their diopter with a table-top autorefractor (Topcon KR8800) and YD-SX-A in a noncycloplegic setting. After cycloplegia, they were retinoscopy by a professional optometrist. The results measured by three methods were collected respectively. To avoid deviation, only the right eye (1000 eyes) data were used in the statistical analysis. The Bland–Altman plots were used to evaluate the agreement of diopters measured by the three methods. The receiver operating characteristic (ROC) curves was used to analysis effectiveness of detecting refractive error of YD-SX-A. Results The average age of participants was 10.77 ± 3.00 years, including 504 boys (50.4%) and 496 girls (49.6%). When YD-SX-A and cycloplegia retinoscopy (CR) were compared in the myopia group, there was no statistical difference in spherical equivalent (SE) (P > 0.05), but there was a statistical difference in diopter spherical (DS) and diopter cylinder (DC) (P 0.05), but there were significant differences in the SE and DS (P

With the increasing utilization of urban underground space, new tunnels frequently intersect with existing tunnels and operational railways. However, sometimes the excavation and unloading of new tunnels can cause deformation of adjacent existing tunnels and railways, significantly affecting their normal operation. We used finite element software to predict the influence of new tunnel construction on overcrossing existing tunnels and down-traversing operational railways by a dynamic tunneling model based on a connection channel project of the east and west squares of a railway station. This article is not only control the distance between the two tunnels, but the new tunnel and the existing tunnel, as well as the new tunnel and the operation of the railway, the positional relationship between the three, the deformation laws of existing tunnels and operational railways during the construction of new tunnels with different buried depths are analyzed. The results show that the deformation curves of existing tunnels and operational railways present a normal distribution. The maximum deformation position is at the intersection with the new tunnel upon completion of the new tunnel excavation construction. Moreover, an increase in the buried depth of the new tunnel increases the deformation of the operational railway and the existing tunnel. The influence of the depth change of the new tunnel on the settlement of the operational railway is greater than that of the existing tunnel.

We are facing a critical aging crisis, with geriatric populations (65+) growing to unprecedented proportions and ~4 million people (a 6.5-fold increase) expected to become centenarians by 2050. This is compounded by environmental pollution, which affects individuals of all ages and contributes to age-related diseases. As we have a limited understanding of how environmental pollutants affect older populations distinctly from younger populations, these longer-lived geriatric populations present a key knowledge gap. To address this knowledge gap, we employ a “Toxic Aging Coin” approach: heads consider how age impacts chemical toxicity, and tails consider how chemicals act as gerontogens—or how they accelerate biological aging. We employed this approach to investigate hexavalent chromium (Cr[VI]) impacts on female rats exposed to 0.05 or 0.1 mg Cr(VI)/L in drinking water for 90 days; these are the maximum contaminant levels (i.e., the highest levels permitted) from the World Health Organization and U.S. Environmental Protection Agency, respectively. During exposure, rats performed a battery of behavior assays to assess grip strength, locomotor coordination, anxiety, spatial memory, sociability, and social novelty preference. We observed age differences in Cr(VI) neurotoxicity, with grip strength, locomotor function, and spatial memory in middle-aged females being particularly affected. We further compared these results in females to results in males, noting many sex differences, especially in middle-aged rats. These data emphasize the need to consider age and sex as variables in toxicology and to revisit drinking water regulations for Cr(VI).

Abstract Single-cell (SC) analysis provides unique insight into individual cell dynamics and cell-to-cell heterogeneity. Here, we utilize trapped ion mobility separation coupled with dual-polarity ionization mass spectrometry imaging (MSI) to enable high-throughput in situ profiling of the SC lipidome. Multimodal SC imaging, in which dual-polarity-mode MSI is used to perform serial data acquisition runs on individual cells, significantly enhanced SC lipidome coverage. High-spatial resolution SC-MSI identifies both inter- and intracellular lipid heterogeneity; this heterogeneity is further explicated by Uniform Manifold Approximation and Projection and machine learning-driven classifications. We characterize SC lipidome alteration in response to stearoyl-CoA desaturase 1 inhibition and, additionally, identify cell-layer specific lipid distribution patterns in mouse cerebellar cortex. This integrated multimodal SC-MSI technology enables high-resolution spatial mapping of intercellular and cell-to-cell lipidome heterogeneity, SC lipidome remodeling induced by pharmacological intervention, and region-specific lipid diversity within tissue.

Abstract Background To establish a prognostic model to predict the overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC) treated with intensity modulated radiotherapy (IMRT). Methods The unresectable HCC patients treated with IMRT were retrospectively analyzed and randomized into development cohort (n = 237) and validation cohort (n = 103) in a 7:3 ratio. We developed a prognosis model with the multivariate Cox regression analysis in the development cohort to derive the predictive nomogram, which was then validated in the validation cohort. Model performance was evaluated by the c-index, the area under curve(AUC) and the calibration plot. Results A total of 340 patients were enrolled. Tumor numbers > 3 (HR = 1.69, 95% CI = 1.21–2.37), AFP ≥ 400 ng/ml (HR = 1.52, 95% CI = 1.10–2.10), PLT 150U/L (HR = 1.65, 95% CI = 1.15–2.37) and prior surgery (HR = 0.63, 95% CI = 0.43–0.93) were independent prognostic factors. The nomogram based on independent factors was constructed. The c-index for OS prediction was 0.658 (95% CI, 0.647–0.804) and 0.683 (95% CI, 0.580–0.785) in the development and validation cohort, respectively. The nomogram demonstrated good discriminative ability with AUC rates of 0.726, 0.739 and 0.753 at 1-year, 2-year and 3-year models in the development cohort, and 0.715, 0.756 and 0.780 in the validation cohort, respectively. Additionally, good prognostic discrimination of the nomogram is also reflected in stratifying patients into two subgroups with distinct prognosis. Conclusions We constructed a prognostic nomogram for predicting the survival of patients with unresectable HCC treated with IMRT.

To enhance the quality of life and ensure sustainability in crowded cities, safe management of drinking water using cutting-edge technologies is a priority. This study developed an intelligent early warning system (EWS) for alarming and controlling risks from bacteria and disinfection byproducts in a drinking water distribution system (DWDS), named BARCS (Bacterial Risk Controlling System). BARCS adopts an artificial intelligence (AI) approach to data-driven prediction and considers total chlorine (TCl) concentration as the pivot indicator for risk identification and control. First, the machine learning-based AI model in BARCS can provide a reliable prediction of TCl concentration in a DWDS, with an average R2 of 0.64 for the validation set, while offering great flexibility for BARCS to adapt to various conditions. Second, TCl concentration was proven to be a good indicator of bacterial risk in a DWDS, as well as a cost-effective surrogate variable to assess disinfection byproduct risk. Third, the robustness analysis demonstrates that with state-of-the-art water quality monitoring technologies, online implementation of BARCS in real-world settings is feasible. Overall, BARCS represents a promising solution to the safe management of drinking water in future smart cities. HIGHLIGHTS BARCS predicts and regulates bacterial risk in pipelines.; TCl prediction module harvests an average R2 of 0.64 for the validation set.; The relationship between TCl and CFU is quantified.; Online implementation of BARCS in real-world settings is feasible.;

Permanent magnet motors (PMMs) have emerged as key components in numerous industrial applications due to their high efficiency, compact size, and robust performance characteristics. However, to attain optimal performance in PMM drives, accurately predicting and mitigating core losses is paramount. This paper aims to provide a comprehensive review of advancements and methodologies for enhancing the performance of PMM drives by integrating equivalent circuit models (ECMs) that account for core losses. Firstly, the significance of core losses in motor drives is underscored, alongside a survey of research endeavors dedicated to core loss reduction. Notably, emphasis is placed on mathematical models offering both swift computation and reasonable accuracy. Subsequently, the paper delves into the development of ECMs, focusing on approaches adept at capturing core loss effects across diverse operating conditions. Moreover, this paper explores the utilization of these improved ECMs in the design and control of PMMs to achieve enhanced performance. By integrating core loss considerations into design and control strategies, PMM drives can optimize efficiency, torque production, and overall system performance. In summary, this paper may consolidate the current state-of-the-art techniques for enhancing PMM performance through the integration of core-loss-aware ECMs. It highlights key research directions and opportunities for further advancements in this critical area, aiming to foster the development of more efficient and reliable PMM-based systems for a wide range of industrial applications.

Over time, high-temperature superconductor (HTS)-coated conductors (CCs) have proven to be promising candidates for future high-efficiency and high-power density electrical machines. However, their commercialization is handicapped due to the AC dissipative loss that occurs upon exposure to external magnetic fields. In rotating electromagnetic devices, the external magnetic field is a combination of alternating and rotating magnetic fields. Most of the research is devoted to the effect of exposure of the superconductors to alternating magnetic fields only. This article presents an investigation to observe the behavior of HTSCCs under rotating magnetic fields, particularly the AC loss, using a finite-element-based homogeneous H-formulation technique. Our investigation shows that the AC loss could be considerably high when HTSCCs are exposed to rotating magnetic fields and, ultimately, could affect the cooling efficiency of future high-efficiency and high-power density electrical machines.

Monocytes (Mos) are believed to play important roles during the generation of immune response. In our previous study, CVC1302, a complex of PRRs agonists, was demonstrated to recruit Mo into lymph nodes (LNs) in order to present antigen and secret chemokines (CXCL9 and CXCL10), which attracted antigen-specific CD4+ T cells. As it is known that Mos in mice are divided into two main Mo subsets (Ly6C+ Mo and Ly6C− Mo), we aimed to clarify the CVC1302-recruiting Mo subset and functions in the establishment of immunity. In this study, we found that CVC1302 attracted both Ly6C+ Mo and Ly6C− Mo into draining LNs, which infiltrated from different origins, injection muscles and high endothelial venule (HEV), respectively. We also found that the numbers of OVA+ Ly6C+ Mo in the draining LNs were significantly higher compared with OVA+ Ly6C− Mo. However, the levels of CXCL9 and CXCL10 produced by Ly6C− Mo were significantly higher than Ly6C+ Mo, which plays important roles in attracting antigen-specific CD4+ T cells. Under the analysis of their functions in initiating immune responses, we found that the ability of the Ly6C+ monocyte was mainly capturing and presenting antigens, otherwise; the ability of the Ly6C− monocyte was mainly secreting CXCL9 and CXCL10, which attracted antigen-specific CD4+ T cells through CXCR3. These results will provide new insights into the development of new immunopotentiators and vaccines.

Hexavalent chromium [Cr(VI)] is a known human lung carcinogen with widespread exposure in environmental and occupational settings. Despite well-known cancer risks, the molecular mechanisms of Cr(VI)-induced carcinogenesis are not well understood, but a major driver of Cr(VI) carcinogenesis is chromosome instability. Previously, we reported Cr(VI) induced numerical chromosome instability, premature centriole disengagement, centrosome amplification, premature centromere division, and spindle assembly checkpoint bypass. A key regulator of these events is securin, which acts by regulating the cleavage ability of separase. Thus, in this study we investigated securin disruption by Cr(VI) exposure. We exposed human lung cells to a particulate Cr(VI) compound, zinc chromate, for acute (24 h) and prolonged (120 h) time points. We found prolonged Cr(VI) exposure caused marked decrease in securin levels and function. After prolonged exposure at the highest concentration, securin protein levels were decreased to 15.3% of control cells, while securin mRNA quantification was 7.9% relative to control cells. Additionally, loss of securin function led to increased separase activity manifested as enhanced cleavage of separase substrates; separase, kendrin, and SCC1. These data show securin is targeted by prolonged Cr(VI) exposure in human lung cells. Thus, a new mechanistic model for Cr(VI)-induced carcinogenesis emerges with centrosome and centromere disruption as key components of numerical chromosome instability, a key driver in Cr(VI) carcinogenesis.

Background: Signal transducers and activators of transcription (STAT) proteins, well-known cytoplasmic transcription factors, were found to be abnormally expressed in various cancers and play essential parts in the initiation, progression and therapy resistance of cancer. Nevertheless, the functions of different STATs in pancreatic cancer (PC) and their relationship to the prognosis and immune infiltration as well as drug efficacy in PC patients have not been systematically elucidated. Methods: Expression, prognosis, genetic alterations and pathway enrichment analyses of the STAT family were investigated via Oncomine, GEPIA, Kaplan Meier-plotter, cBioPortal, Metascape and GSEA. Analysis of tumor immune microenvironment was conducted by ESTIMATE and TIMER. “pRRophetic” packages were used for analysis of chemotherapeutic response. Finally, the diagnostic and prognostic value of key STATs were further validated through public datasets and immunohistochemistry. Results: In this study, only STAT1 mRNA level was significantly increased in tumor tissues and highly expressed in PC cell lines via multiple datasets. PC patients with higher STAT1/4/6 expression had a worse overall survival (OS) and progression-free survival (PFS), while higher STAT5B expression was correlated with better prognosis in the TCGA cohort. The STATs-associated genes were enriched in pathways about the remodeling of tumor immune microenvironment. The STATs levels were significantly correlated with immune infiltration, except STAT6. The STAT1 was identified as a potential biomarker and its diagnostic and prognostic value were further validated at mRNA and protein levels. GSEA showed that STAT1 may be involved in the progression and immune regulations of PC. Moreover, STAT1 expression was significantly related to the level of immune checkpoint, and predicted immunotherapy and chemotherapy responses. Conclusion: STAT family members were comprehensively analyzed and STAT1 was identified as an effective biomarker for predicting the survival and therapeutic response, which could be beneficial to develop better treatment strategies.

Background: Studies demonstrated that age-related cellular and functional changes of airway significantly contribute to the pathogenesis of many airway diseases. However, our understanding on the age-related molecular alterations of human airway remains inadequate.Methods: Airway (trachea and bronchus) brushing specimens were collected from 14 healthy, female non-smokers with ages ranging from 20 to 60 years. Bulk RNA sequencing was performed on all the specimens (n = 28). Airway cell types and their relative proportions were estimated using CIBERSORTx. The cell type proportions were compared between the younger (age 20–40) and elder group (age 40–60) in the trachea and bronchus respectively. The linear association between cell type proportion and age was assessed using the Pearson correlation coefficient. Differentially expressed genes (DEGs) between the two age groups were identified using DESeq2. Three kinds of enrichment analysis of the age-related DEGs were performed, including Gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and disease enrichment analysis.Results: Sixteen and thirteen cell types were separately identified in tracheal and bronchial brushings, with the airway epithelial cells (including suprabasal, submucosal gland (SMG) goblet, serous, secretory, multiciliated, cycling.basal, basal cells) accounting for 85.1% in the trachea and 92.5% in the bronchus. The lymphatic cell and NK cells had a higher abundance ratio in the trachea, compared with the bronchus. The proportion of basal cells was negatively related to age both in the trachea and bronchus. Thirty-one and fifty-two age-related DEGs (p < 0.1) were identified in the trachea and bronchus, respectively. Among them, five common DEGs (CXCL2, CXCL8, TCIM, P4HA3, AQP10) were identified. Pathway enrichment analysis showed both tracheal and bronchial age-related DEGs were primarily involved in immune regulatory signaling pathways (TNF, NF-kappa B, IL-17 et al.). Disease enrichment analysis suggested that tracheal age-related DEGs significantly related to asthmatic pulmonary eosinophilia, and chronic airflow obstruction et al., and that bronchial age-related DEGs were enriched in airflow obstruction, bronchiectasis, pulmonary emphysema, and low respiratory tract infection et al.Conclusion: We found the proportion of basal cells decreased with age in both the trachea and bronchus, suggesting a weakening of their self-renew ability with age. We identified transcriptomic signature genes associated with the early aging process of the human trachea and bronchus, and provided evidence to support that changes in their immune regulatory function may play critical roles in age-related airway diseases.

Abstract Background High-resolution computed tomography (HRCT) is recommended diagnosing and monitoring connective tissue disease-associated interstitial lung disease (CTD-ILD). Quantitative computed tomography has the potential to precisely assess the radiological severity of CTD-ILD, but has still been under study. Objective To investigate whether dual-energy computed tomography (DECT), a novel quantitative technique, can be used for quantitative severity assessment in CTD-ILD. Methods This cross sectional study recruited adult CTD-ILD patients who underwent DECT scans from the ICE study between October 2019 and November 2021. DECT parameters, including effective atomic number (Zeff), lung (lobe) volume, and monochromatic CT number (MCTN) of each lung lobe, were evaluated. CTD-ILD was classified into extensive CTD-ILD and limited CTD-ILD by staging algorithm using combined forced vital capacity (FVC)%predicted and total extent of ILD (TEI) on CT. Dyspnea, cough, and life quality were scored by Borg dyspnea score, Leicester cough questionnaire (LCQ), and short-form 36 health survey questionnaire (SF-36), respectively. Results There was a total of 147 patients with DECT scans enrolled. Higher Zeff value (3.104 vs 2.256, p

This study found a higher percentage of CD8+ T cells in piglets immunized with a CVC1302-adjuvanted inactivated foot-and-mouth disease virus (FMDV) vaccine. We wondered whether the CVC1302-adjuvanted inactivated FMDV vaccine promoted cellular immunity by promoting the antigen cross-presentation efficiency of ovalbumin (OVA) through dendritic cells (DCs), mainly via cytosolic pathways. This was demonstrated by the enhanced levels of lysosomal escape of OVA in the DCs loaded with OVA and CVC1302. The higher levels of ROS and significantly enhanced elevated lysosomal pH levels in the DCs facilitated the lysosomal escape of OVA. Significantly enhanced CTL activity levels was observed in the mice immunized with OVA-CVC1302. Overall, CVC1302 increased the cross-presentation of exogenous antigens and the cross-priming of CD8+ T cells by alkalizing the lysosomal pH and facilitating the lysosomal escape of antigens. These studies shed new light on the development of immunopotentiators to improve cellular immunity induced by vaccines.

Gray mold infected with Botrytis cinerea frequently appears on fruits and vegetables throughout the supply chain after harvest, leading to economic losses. Biological control of postharvest disease with phytochemicals is a promising approach. CA (cinnamaldehyde) is a natural phytochemical with medicinal and antimicrobial activity. This study evaluated the effect of CA in controlling B. cinerea on fresh pepper fruit. CA inhibited B. cinerea growth in vitro significantly in a dose- (0.1–0.8 mM) and time-dependent (6–48 h) manner, with an EC50 (median effective concentration) of 0.5 mM. CA induced the collapse and breakdown of the mycelia. CA induced lipid peroxidation resulting from ROS (reactive oxygen species) accumulation in mycelia, further leading to cell leakage, evidenced by increased conductivity in mycelia. CA induced mycelial glycerol accumulation, resulting in osmotic stress possibly. CA inhibited sporulation and spore germination resulting from ROS accumulation and cell death observed in spores. Spraying CA at 0.5 mM induced a defense response in fresh pepper fruits, such as the accumulation of defense metabolites (flavonoid and total phenols) and an increase in the activity of defense enzymes (PAL, phenylalanine ammonia lyase; PPO, polyphenol oxidase; POD, peroxidase). As CA is a type of environmentally friendly compound, this study provides significant data on the activity of CA in the biocontrol of postharvest gray mold in peppers.

This paper studies the initial boundary value problem of the Hirota–Satsuma system posed on the half line. ut−αuxxx+6uux=2βvvx,x>0,t>0,vt+vxxx+3uvx=0,x>0,t>0,ux,0=u0x,vx,0=v0x,x>0,u0,t=ft,v0,t=gt,t>0.. For −1/8

With the increasing demand for smaller, lighter, and more affordable electromagnetic devices, there is a growing trend toward developing high-power-density transformers and electrical machines. While increasing the operating frequency is a straightforward approach to achieving high power density, it can lead to significant power loss within a limited volume, resulting in excessive temperature rise and device degradation. Therefore, it is crucial to design high-power-density electromagnetic devices that exhibit low power loss and efficient thermal dissipation to address these challenges. Advanced techniques, such as the utilization of novel and advanced electromagnetic materials, hold great promise for overcoming these issues. Specifically, nanocrystalline and amorphous magnetic materials have emerged as highly effective solutions for reducing power loss and increasing efficiency in electromagnetic devices. This paper aims to provide an overview of the application of nanocrystalline and amorphous magnetic materials in transformers and electrical machines, along with key technologies and the major challenges involved.

Abstract Background Heterosis has been widely used in maize breeding. However, we know little about the heterotic quantitative trait loci and their roles in genomic prediction. In this study, we sought to identify heterotic quantitative trait loci for seedling biomass-related traits using triple testcross design and compare their prediction accuracies by fitting molecular markers and heterotic quantitative trait loci. Results A triple testcross population comprised of 366 genotypes was constructed by crossing each of 122 intermated B73 × Mo17 genotypes with B73, Mo17, and B73 × Mo17. The mid-parent heterosis of seedling biomass-related traits involved in leaf length, leaf width, leaf area, and seedling dry weight displayed a large range, from less than 50 to ~ 150%. Relationships between heterosis of seedling biomass-related traits showed congruency with that between performances. Based on a linkage map comprised of 1631 markers, 14 augmented additive, two augmented dominance, and three dominance × additive epistatic quantitative trait loci for heterosis of seedling biomass-related traits were identified, with each individually explaining 4.1–20.5% of the phenotypic variation. All modes of gene action, i.e., additive, partially dominant, dominant, and overdominant modes were observed. In addition, ten additive × additive and six dominance × dominance epistatic interactions were identified. By implementing the general and special combining ability model, we found that prediction accuracy ranged from 0.29 for leaf length to 0.56 for leaf width. Different number of marker analysis showed that ~ 800 markers almost capture the largest prediction accuracies. When incorporating the heterotic quantitative trait loci into the model, we did not find the significant change of prediction accuracy, with only leaf length showing the marginal improvement by 1.7%. Conclusions Our results demonstrated that the triple testcross design is suitable for detecting heterotic quantitative trait loci and evaluating the prediction accuracy. Seedling leaf width can be used as the representative trait for seedling prediction. The heterotic quantitative trait loci are not necessary for genomic prediction of seedling biomass-related traits.

As we face issues of fossil fuel depletion and environmental pollution, it is becoming increasingly important to transition towards clean renewable energies and electric vehicles (EVs). However, designing electric motors with high power density for EVs can be challenging due to space and weight constraints, as well as issues related to power loss and temperature rise. In order to overcome these challenges, a significant amount of research has been conducted on designing high-power-density electric motors with advanced materials, improved physical and mathematical modeling of materials and the motor system, and system-level multidisciplinary optimization of the entire drive system. These technologies aim to achieve high reliability and optimal performance at the system level. This paper provides an overview of the key technologies for designing high-power-density electric motors for EVs with high reliability and system-level optimal performance, with the focus on advanced magnetic materials and the proper modeling of core losses under two-dimensional or three-dimensional vectorial magnetizations. This paper will also discuss the major challenges associated with designing these motors and the possible future research directions in the field.

Abstract Climate change and human activities have already caused degradation in a large fraction of vegetation on the Qinghai‐Tibetan Plateau (QTP). Many studies report that climate variability instead of overgrazing has been the primary cause for large‐scale vegetation cover changes on the QTP, for example, Lehnert et al., 2016, https://doi.org/10.1038/srep24367. However, it remains unclear how human activities (mainly livestock grazing) regulate vegetation dynamics under climate change. This paper takes the AVHRR/GIMMS Normalized Difference Vegetation Index (NDVI) as an indicator to analyze the growth status of vegetation zones in the QTP, which has highly sensitive to climate change. The spatiotemporal dynamics of vegetation growth between 1981 and 2015 were analyzed. The dual effects of climate change and human activities were examined by correlation analyses of data from 87 meteorological stations and economic statistical data of the QTP. Results show that: (a) The vegetation in central and southwestern QTP with high altitudes was improving due to the warm‐humid climate trend. An increase in temperature and a reduction in the harsh frigid climate at high altitudes due to global warming has resulted in expansions of the vegetated areas, with the NDVI showing a concordant increase. (b) The degraded areas were mainly confined to the northern and eastern QTP, which have high human and livestock population densities. In comparison to gently changing climate regimes, anthropogenic activities such as chronic concentration of population and livestock in the valleys with a less harsh climate exerts a much stronger pressure on vegetation. The study indicates that the anthropogenic pressures are much more intensive than the impact of climate change and are critical for the conservation and sustainable management of the QTP vegetation.

Electric motors play a crucial role in modern industrial and domestic applications. With the trend of more and more electric drives, such as electric vehicles (EVs), the requirements for electric motors become higher and higher, e.g., high power density with good thermal dissipation and high reliability in harsh environments. Many efforts have been made to develop high performance electric motors, such as the application of advanced novel electromagnetic materials, modern control algorithms, advanced mathematical modeling, numerical computation, and artificial intelligence based optimization design techniques. Among many advanced magnetic materials, soft magnetic composite (SMC) appears very promising for developing novel electric motors, thanks to its many unique properties, such as magnetic and thermal isotropies, very low eddy current loss, and the prospect of low-cost mass production. This paper aims to present a comprehensive review about the application of SMC for developing various electric motors for electric drives, with emphasis on those with three-dimensional (3D) magnetic flux paths. The major techniques developed for designing the 3D flux SMC motors are also summarized, such as vectorial magnetic property characterization and system-level multi-discipline robust design optimization. Major challenges and possible future work in this area are also discussed.

High-temperature superconductor (HTS) bulks have demonstrated extremely intriguing potential for industrial and commercial applications due to their capability to trap significantly larger magnetic fields than conventional permanent magnets. The magnetic field in electrical rotating machines is a combination of alternating and rotational fields. In contrast, all previous research on the characterization of electromagnetic properties of HTS have solely engrossed on the alternating AC magnetic fields and the associated AC loss. This research paper gives a thorough examination of the AC loss measurement under various conditions. The obtained results are compared to the finite element-based H-formulation. The AC loss is measured at various amplitudes of circular flux density patterns and compared with the AC loss under one-dimensional alternating flux density. The loss variation has also been studied at other frequencies. The findings in this research paper provide more insights into material characterization, which will be useful in the design of future large-scale HTS applications.

Fusarium oxysporum f. sp. niveum (FON) causes watermelon wilt that is one of the major disease-causing yield losses of watermelon. Sustainable development of agriculture requires controlling watermelon wilt disease with good environmental performance. One important approach is to identify environmental-friendly compounds with inhibitory activity against FON. Thymol is a plant-derived compound that is safe for ecology. Little is known about the application of thymol in agriculture. In this study, we studied the inhibitory activity of thymol against FON by using morphological, physiological, and histochemical approaches. Thymol significantly inhibited colony diameter of FON in a dose-dependent manner, with EC50 at 21 µg/mL. Thymol at 10, 21, and 35 µg/mL decreased the fresh weight of FON mycelia by 29.0%, 50.6%, and 69.5%, respectively. Microscopic observation revealed irregular damage and loss of shape of mycelia upon thymol exposure. Thymol induced the accumulation of superoxide radical in mycelial cells and accompanied increased activity of antioxidative enzymes (SOD, superoxide dismutase; CAT, catalase). Thymol induced membrane permeability was indicated by lipid peroxidation and electrolyte leakage (increased by 29–58%) in mycelial cells. These results suggested that thymol induced oxidative damage in mycelia, which may be one of the possible reasons for thymol-induced mycelial cell death observed with fluorescent detection. Thymol decreased the production of conidia and inhibited the germination of conidia. Thymol induced superoxide radical accumulation, lipid peroxidation, and cell death in conidia as well. All of these results revealed the inhibitory activity of thymol against FON, which may have resulted from the superoxide radical-induced oxidative injury in both conidia and mycelia of FON.

The magnetic properties of magnetic cores are essential for the design of electrical machines, and consequently appropriate mathematical modeling is needed. Usually, the design and analysis of electrical machines consider only the one-dimensional (1D) magnetic properties of core materials, i.e., the relationship of magnetic flux density (B) versus magnetic field strength (H), and their associated power loss under 1D magnetization, in which the B and H are constrained in the same orientation. Some studies have also been performed with the two-dimensional (2D) magnetizations in which the B and H are vectorial, rotating on a plane, and they may not be in the same direction. It has been discovered that the 2D rotational property is very different from its 1D alternating counterpart. However, the magnetic fields in an electrical machine, in particular claw pole and transverse flux machines, are naturally three-dimensional (3D), and the B and H vectors are rotational and may not lie on the same plane. It can be expected that the 3D vectorial property might be different from its 2D or 1D counterpart, and hence it should be investigated for the interests of both academic research and engineering application. This paper targets at a general summary about the magnetic material characterization with 3D vectorial magnetization, and their application prospect in electrical machine design and analysis.

Thymol is a plant-derived natural compound with antimicrobial activity. However, we have little knowledge about the application of thymol in agriculture. One of the limitations is the high volatility and low aqueous solubility of thymol. Tomato gray mold caused by Botrytis cinerea is one of the most devastating postharvest diseases. In this study, we prepared a nano-emulsion of thymol (named as Nano-Thy) to form a stable O/W (oil in water) microemulsion. In vitro experiments showed that Nano-Thy had antifungal activity against B. cinerea by inhibiting mycelial growth and spore germination. Nano-Thy induced ROS accumulation in mycelia, further leading to lipid peroxidation, cell membrane damage, and subsequent cell death. Nano-Thy significantly prevented the infection of B. cinerea on fresh tomato fruits. Finally, we discussed the mechanisms and their significance in controlling postharvest disease of fruit crops.

High-temperature superconducting materials have shown great potential for the design of large-scale industry applications. However, they are complicated under AC conditions, resulting in penalties such as power loss or AC loss. This loss has to be considered in order to design reliable and efficient superconducting devices. Furthermore, when superconductors are used in rotating machines, they may be exposed to rotating magnetic fields, which is critical for the design of such machines. Existing AC loss measuring techniques are limited to measuring under one-dimensional AC magnetic fields or transport currents. Therefore, it is essential to develop and investigate robust experimental techniques to investigate the loss mechanism in HTS machines. In this paper, a new and novel experimental technique has been presented to measure AC loss in rotating magnetic field conditions. The loss under rotating magnetic fields is measured and compared by numerical modeling methods, and the results show a strong correlation with the numerical modeling and show the effectiveness of the experimental setup.

Amorphous metal (AM), specifically amorphous ferromagnetic metal, is considered as a satisfactory magnetic material for exploring electromagnetic devices with high-efficiency and high-power density, such as electrical machines and transformers, benefits from its various advantages, such as reasonably low power loss and very high permeability in medium to high frequency. However, the characteristics of these materials have not been investigated comprehensively, which limits its application prospects to good-performance electrical machines that have the magnetic flux density with generally rotational and non-sinusoidal features. The appropriate characterization of AMs under different magnetizations is among the fundamentals for utilizing these materials in electrical machines. This paper aims to extensively overview AM property measurement techniques in the presence of various magnetization patterns, particularly rotational magnetizations, and AM property modeling methods for advanced electrical machine design and analysis. Possible future research tasks are also discussed for further improving AM applications.

In this paper, we present a novel gain-enhanced sub-harmonic mixer based on 0.5-μm emitter width InGaAs/InP double heterojunction bipolar transistors (InP DHBTs). The proposed mixer consists of a transconductance stage and a gain-enhanced stage. A common-emitter transistor is used in the first stage to realize the sub-harmonic mixing while another common-emitter transistor is used in the second stage to remix the fLO+IF and fIF and also amplify the f2LO+IF. For further verification, a transconductance mixer and a gain-enhanced mixer were designed and fabricated. Compared with the transconductance mixer, the gain-enhanced mixer exhibits a 6.8-dB higher conversion gain with 2-dB lower LO input power and a peak up-conversion gain of 9 dB at 213 GHz with fIF = 1 GHz, fLO = 106 GHz, and PIF = -26 dBm PLO = 3 dBm. To our best knowledge, the gain-enhanced mixing structure is proposed for the first time.

Phytophthora capsici is one of the devastating pathogens, causing foliar blight, root rot, and fruit rot in peppers. Cinnamaldehyde (CA) is a natural compound coming from Cinnamomum cassia. The medicinal properties of CA have been widely identified. Limited knowledge is known about the application of CA in agriculture. In this study, CA significantly inhibited P. capsici, which further suppressed Phytophthora blights in both pepper seedlings and pepper fruits. Treatment with CA resulted in collapsed and fragmented hyphae, accompanying the increase in MDA (malondialdehyde) content and the decrease in intercellular glycerol content in hyphae. CA also inhibited the growth of wild type yeast. The yeast mutant ΔYvc1 with a deletion of Yvc1 (a Ca2+ transporter) showed decreased sensitivity to CA. The transformation of PcNCX1, a sodium/calcium exchanger from P. capsici, into ΔYvc1 restored its sensitivity to CA. The transformant carrying PcNCX1 also showed restored Ca2+ efflux upon CA treatment. RNA-seq analysis showed that CA treatments resulted in the down-regulation of a set of genes encoding for calcium-related proteins. Collectively, our study demonstrates that the antifungal activity of CA against P. capsici may be associated with PcNCX1-mediated Ca2+ efflux. Our results provide crucial insights into the antimicrobial action of CA.

This paper investigates the impact of high-speed railways (HSR) on urban innovation levels by improving intercity accessibility. We employ prefecture city-level data within three megacity regions in China from 2009 to 2018. Using the number of invention patents granted as a proxy for the innovation level of a city, we find that HSR facilities significantly improve urban innovation levels through better regional intercity accessibility and that there is a diminishing effect as commuting time increases. The impact mechanisms of innovation improvement can be explained by an ever-increasing potential of interaction activities among talents and technology investment opportunities among cities. We contribute to the literature by highlighting the spatial attenuation impact of HSR on urban innovation levels as well as the underlying mechanisms. Particularly, talent interaction exerts a larger effect on urban innovation levels than technology investment opportunities. Moreover, we unravel the heterogeneous effects that more innovative cities and cities with double first-class universities gain more from the improved intercity accessibility brought by HSR. This research has policy implications that promoting HSR facilities improves innovation levels of cities with different resources.

High-temperature superconductor (HTS) bulks have shown very promising potential for industrial applications due to the ability to trap much higher magnetic fields compared to traditional permanent magnets. In rotating electrical machines, the magnetic field is a combination of alternating and rotating fields. On the contrary, all studies on electromagnetic characterization of HTS presented in the literature so far have only focused on alternating AC magnetic fields and alternating AC loss due to the unavailability of robust experimental techniques and analytical models. This paper presents a numerical investigation on the characterization of HTS bulks subjected to rotating magnetic fields showing AC loss, current density distribution in three-dimensional axes, and trapped field analysis. A three-dimensional numerical model has been developed using H-formulation based on finite element analysis. An HTS cubic sample is magnetized and demagnetized with two-dimensional magnetic flux density vectors rotating in circular orientation around the XOY, XOZ, and YOZ planes.

Plants are always exposed to the environment, polluted by multiple trace elements. Hydrogen sulfide (H2S), an endogenous gaseous transmitter in plant cells, can help plant combat single elements with excess concentration. Until now, little has been known about the regulatory role of H2S in response to combined stress of multiple elements. Here we found that combined exposure of mercury (Hg) and selenium (Se) triggered endogenous H2S signal in the roots of Brasscia rapa. However, neither Hg nor Se alone worked on it. In roots upon Hg + Se exposure, the defensive role of endogenous H2S was associated to the decrease in reactive oxygen species (ROS) level, followed by alleviating cell death and recovering root growth. Such findings extend our knowledge of plant H2S in response to multiple stress conditions.

Objectives Utilization of self-pay vaccines worldwide is very low, especially in China; the reasons for this are unclear. We aimed to identify factors that impact the decision among Chinese mothers to utilize self-pay vaccines for their children. Methods Mothers who were hospitalized at two hospitals in Zhanjiang City and who agreed to participate by completing the required questionnaire were eligible for this study. Results In total, 7518 respondents (n = 7592) completed the questionnaire and were included in this survey. The self-pay option was largely elected by mothers with one child, compared with those who had two or more children. Similarly, utilization by workers at government agencies and organizations was higher than that among factory workers or unemployed respondents. Mothers with a college degree or above had higher utilization than those with a high school level education or lower. The main issues affecting maternal decisions to utilize self-pay pediatric vaccines were safety, the protective effect, and the high cost. Conclusion Mothers with higher socioeconomic status were more inclined to self-pay for pediatric vaccines. Steps taken to enhance public awareness about the safety and protective benefits of self-pay vaccines, as well as lowering their cost will likely encourage broader utilization of these vaccines.

BackgroundOur aim was to evaluate the clinical utility of non-invasive prenatal testing for pregnant women with different diagnostic indications.MethodsIn eight counties and districts of Yancheng, we studied 13,149 pregnant women with different indications who were offered NIPT for fetal screening, including for sex chromosomal aneuploidies (SCAs), rare autosomal trisomies (RATs), and subchromosomal copy number variations (CNVs). The purpose was to compare the detection of positive predictive values (PPVs) of different indications with the use of NIPT. The results were validated by karyotyping, chromosomal microarray analysis (CMA), or follow-up of pregnancy outcomes.Results13,149 maternal plasma samples were sequenced, among which 28 samples (0.2%) failed the sequencing quality control. The remaining 13,121 samples were analyzed, and birth follow-up missed 2,192 samples (16.7%). The PPVs of NIPT results for trisomy 21 (T21) and trisomy 18 (T18) and SCAs were 96.67, 63.64, and 31.34%, respectively. Among the advanced maternal age (AMA), serum screening high risk (SSHR), serum screening intermediate risk (SSIR), and voluntary screening (VS) groups, the PPVs for the common trisomies were 81.25, 85.71, 100, and 70%, respectively; the PPVs for total chromosomal abnormalities were 55.82, 65.22, 23.08, and 36.59%, respectively.ConclusionNIPT for T21 and T18 and SCAs screening were ideal, and the PPVs for trisomy 13 (T13), RATs, and CNVs were low. For the AMA and VS groups, NIPT could be used as a first-line screening program; for SSHR and SSIR groups, NIPT could be used as a second-line supplementary screening program.

Abstract Background Dormant estrogen receptor positive (ER+) breast cancer micrometastases in the bone marrow survive adjuvant chemotherapy and recur stochastically for more than 20 years. We hypothesized that inflammatory cytokines produced by stromal injury can re-awaken dormant breast cancer cells. Methods We used an established in vitro dormancy model of Michigan Cancer Foundation-7 (MCF-7) breast cancer cells incubated at clonogenic density on fibronectin-coated plates to determine the effects of inflammatory cytokines on reactivation of dormant ER+ breast cancer cells. We measured induction of a mesenchymal phenotype, motility and the capacity to re-enter dormancy. We induced secretory senescence in murine stromal monolayers by oxidation, hypoxia and estrogen deprivation with hydrogen peroxide (H2O2), carbonyl-cyanide m-chlorophenylhydrazzone (CCCP) and Fulvestrant (ICI 182780), respectively, and determined the effects on growth of co-cultivated breast cancer cells. Results Exogenous recombinant human (rh) interleukin (IL)-6, IL-8 or transforming growth factor β1 (TGFβ1) induced regrowth of dormant MCF-7 cells on fibronectin-coated plates. Dormant cells had decreased expression of E-cadherin and estrogen receptor α (ERα) and increased expression of N-cadherin and SNAI2 (SLUG). Cytokine or TGFβ1 treatment of dormant clones induced formation of growing clones, a mesenchymal appearance, increased motility and an impaired capacity to re-enter dormancy. Stromal injury induced secretion of IL-6, IL-8, upregulated tumor necrosis factor alpha (TNFα), activated TGFβ and stimulated the growth of co-cultivated MCF-7 cells. MCF-7 cells induced secretion of IL-6 and IL-8 by stroma in co-culture. Conclusions Dormant ER+ breast cancer cells have activated epithelial mesenchymal transition (EMT) gene expression programs and downregulated ERα but maintain a dormant epithelial phenotype. Stromal inflammation reactivates these cells, induces growth and a mesenchymal phenotype. Reactivated, growing cells have an impaired ability to re-enter dormancy. In turn, breast cancer cells co-cultured with stroma induce secretion of IL-6 and IL-8 by the stroma, creating a positive feedback loop.

In this paper, a new 3-D electromagnetic (EM) simulation approach for heterojunction bipolar transistor (HBT) parameter extraction in terahertz band is presented. We introduce an inter-electrode impedance equivalent-circuit model with the concept of dispersive parameters and a more rigorous 3-D EM simulation parameter extraction method to avoid serious discrepancies between the simulated EM field distribution and the real EM field distribution of the device. Terahertz parasitic effects, including the EM field discretization and multi-finger device field sharing, are observed. Compared with the previous 3-D EM simulation-assisted model, the new model in this paper demonstrates better results for multi-finger indium phosphide HBTs.

The rapid and direct structural characterization of lipids proves to be critical for studying the functional roles of lipids in many biological processes. Among numerous analytical techniques, ambient ionization mass spectrometry (AIMS) allows for a direct molecular characterization of lipids from various complex biological samples with no/minimal sample pretreatment. Over the recent years, researchers have expanded the applications of the AIMS techniques to lipid structural elucidation via a combination with a series of derivatization strategies (e.g., the Paternò–Büchi (PB) reaction, ozone-induced dissociation (OzID), and epoxidation reaction), including carbon–carbon double bond (C=C) locations and sn-positions isomers. Herein, this review summarizes the reaction mechanisms of various derivatization strategies for C=C bond analysis, typical instrumental setup, and applications of AIMS in the structural elucidation of lipids from various biological samples (e.g., tissues, cells, and biofluids). In addition, future directions of AIMS for lipid structural elucidation are discussed.

There has been an increasing number of studies on the interaction between active substances and probiotics to improve disease. Both krill oil (KO) and probiotics have the effect of improving atherosclerotic cardiovascular disease, but the combined effect has not been explored. Therefore, the purpose of this study was to explore the improvement effect of KO combined with probiotics on atherosclerosis. The atherosclerotic plaque area of ApoE−/− mice was detected after the intervention of KO, Bifidobacterium animalis subsp. lactis F1-7 (Bif. animalis F1-7), and KO combined with Bif. animalis F1-7. The results showed that Bif. animalis F1-7, KO, and KO combined with Bif. animalis F1-7 could significantly reduce the area of atherosclerotic plaque and improve the levels of serum lipids and inflammatory factors. They could regulate the farnesoid X receptor (FXR)/cholesterol 7-alpha hydroxylase (CYP7A1) pathway to reduce lipid accumulation. The intervention groups could also improve the inflammatory response by downregulating the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) pathway. The anti-inflammatory effect of the interaction group was significantly better than that of KO. It proved that Bif. animalis F1-7 might play a synergistic effect in the improvement of inflammation by KO to the alleviation of atherosclerosis.

Abstract Background Quinoa (Chenopodium quinoa Willd.) is a balanced nutritional crop, but its breeding improvement has been limited by the lack of information on its genetics and genomics. Therefore, it is necessary to obtain knowledge on genomic variation, population structure, and genetic diversity and to develop novel Insertion/Deletion (InDel) markers for quinoa by whole-genome re-sequencing. Results We re-sequenced 11 quinoa accessions and obtained a coverage depth between approximately 7× to 23× the quinoa genome. Based on the 1453-megabase (Mb) assembly from the reference accession Riobamba, 8,441,022 filtered bi-allelic single nucleotide polymorphisms (SNPs) and 842,783 filtered InDels were identified, with an estimated SNP and InDel density of 5.81 and 0.58 per kilobase (kb). From the genomic InDel variations, 85 dimorphic InDel markers were newly developed and validated. Together with the 62 simple sequence repeat (SSR) markers reported, a total of 147 markers were used for genotyping the 129 quinoa accessions. Molecular grouping analysis showed classification into two major groups, the Andean highland (composed of the northern and southern highland subgroups) and Chilean coastal, based on combined STRUCTURE, phylogenetic tree and PCA (Principle Component Analysis) analyses. Further analysis of the genetic diversity exhibited a decreasing tendency from the Chilean coast group to the Andean highland group, and the gene flow between subgroups was more frequent than that between the two subgroups and the Chilean coastal group. The majority of the variations (approximately 70%) were found through an analysis of molecular variation (AMOVA) due to the diversity between the groups. This was congruent with the observation of a highly significant FST value (0.705) between the groups, demonstrating significant genetic differentiation between the Andean highland type of quinoa and the Chilean coastal type. Moreover, a core set of 16 quinoa germplasms that capture all 362 alleles was selected using a simulated annealing method. Conclusions The large number of SNPs and InDels identified in this study demonstrated that the quinoa genome is enriched with genomic variations. Genetic population structure, genetic core germplasms and dimorphic InDel markers are useful resources for genetic analysis and quinoa breeding.

Abstract Microglia are the resident macrophages of the central nervous system and play complex roles in the milieu of diseases including the primary diseases of myelin. Although mitochondria are critical for cellular functions and survival in the nervous system, alterations in and the roles of mitochondrial dynamics and associated signaling in microglia are still poorly understood. In the present study, by combining immunohistochemistry and 3D ultrastructural analyses, we show that mitochondrial fission/fusion in reactive microglia is differentially regulated from that in monocyte-derived macrophages and the ramified microglia of normal white matter in myelin disease models. Mouse cerebral microglia in vitro demonstrated that stimulation of TLR4 with lipopolysaccharide, widely used to examine microglial reactions, caused the activation of the mitochondrial fission protein, dynamin-related protein 1 (Drp1) and enhanced production of reactive oxygen species (ROS). The increase in the ROS level activated 5′ adenosine monophosphate-activated protein kinase (AMPK), and facilitated elongation of mitochondria along the microtubule tracks. These results suggest that the polymorphic regulation of mitochondrial fission and fusion in reactive microglia is mediated by distinct signaling under inflammatory conditions, and modulates microglial phenotypes through the production of ROS.