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Abstract Background As the population ages, an increasing number of postmenopausal women are donors of adipose stromal cells (ASCs) and may benefit from autologous ASC-related treatments. However, the effect of menopausal status on ASCs has not been investigated. Methods RNA sequencing data were downloaded, and differentially expressed genes (DEGs) were identified. Hierarchical clustering, Gene Ontology, and pathway analyses were applied to the DEGs. Two gene coexpression network analysis approaches were applied to the DEGs to provide a holistic view and preserve gene interactions. Hub genes of the gene coexpression network were identified, and their expression profiles were examined with clinical samples. ASCs from pre- and postmenopausal women were co-cultured with monocytes and T cells to determine their immunoregulatory role. Results In total, 2299 DEGs were identified and presented distinct expression profiles between pre- and postmenopausal women. Gene Ontology and pathway analyses revealed some fertility-, sex hormone-, immune-, aging-, and angiogenesis-related terms and pathways. Gene coexpression networks were constructed, and the top hub genes, including TIE1, ANGPT2, RNASE1, PLVAP, CA2, and MPZL2, were consistent between the two approaches. Expression profiles of hub genes from the RNA sequencing data and clinical samples were consistent. ASCs from postmenopausal women elicit M1 polarization, while their counterparts facilitate CD3/4+ T cell proliferation. Conclusions The present study reveals the transcriptome differences in ASCs derived from pre- and postmenopausal women and provides holistic views by preserving gene interactions via gene coexpression network analysis. The top hub genes identified by this study could serve as potential targets to enhance the therapeutic potential of ASCs.

One major reason for the success of convolutional neural networks (CNNs) is the availability of large-scale labeled data. Effective training of CNNs relies on large annotated data. Unfortunately, large amounts of data with corresponding annotations are too expensive to obtain in some real-world applications. One reasonable alternative is to use data augmentation techniques to automatically generate annotated samples. In this paper, a novel data augmentation framework based on perspective transformation is proposed. This method automatically generates new annotated data without extra manual labeling, thus effectively extends the inadequate dataset. Perspective transformation can produce new images captured from any cameras viewpoints. Therefore, our method can mimic images taken at the angle that the camera cannot reach. Extensive experimental results on several datasets have demonstrated that our perspective transformation data augmentation strategy is an effective tool when using deep CNNs on small or imbalance datasets.

This study is focussed on evaluating and comparing two mediators of osteoclast, osteoprotegerin (OPG) and nuclear factor-κB ligand (RANKL), in plasma and tissue levels in patients with steroid-induced osteonecrosis of femoral head (SIONFH). Subjects were included in this cross-sectional case-control study in 2016. Bone histomorphology, immunohistochemistry, Western blotting, OPG and RANKL plasma levels, post-hoc statistical power and receiver-operating characteristic (ROC) curves were evaluated. Eighty-six patients diagnosed with SIONFH and 51 healthy subjects were included. OPG expression levels in bone samples increased with ARCO stage, and RANKL expression levels decreased with ARCO stages. Plasma OPG and RANKL levels were significantly higher in the SIONFH group compared with the healthy control group. The plasma OPG level and ratio of OPG and RANKL were positively associated with ARCO stages and significantly higher in stages III and IV. Plasma RANKL levels were negatively associated with ARCO stage and were significantly higher in ARCO stages II and III. Plasma OPG and RANKL may represent potential biomarkers during SIONFH at different stages. Higher plasma OPG levels indicated late-stage SIONFH, and higher plasma RANKL levels indicated early stage. Our findings may provide a clue for the development of diagnostic tools and therapies for SIONFH.

Abstract The mitochondrial deoxynucleotide triphosphate (dNTP) is maintained by the mitochondrial deoxynucleoside salvage pathway and dedicated for the mtDNA homeostasis, and the mitochondrial deoxyguanosine kinase (DGUOK) is a rate‐limiting enzyme in this pathway. Here, we investigated the role of the DGUOK in the self‐renewal of lung cancer stem‐like cells (CSC). Our data support that DGUOK overexpression strongly correlates with cancer progression and patient survival. The depletion of DGUOK robustly inhibited lung adenocarcinoma tumor growth, metastasis, and CSC self‐renewal. Mechanistically, DGUOK is required for the biogenesis of respiratory complex I and mitochondrial OXPHOS, which in turn regulates CSC self‐renewal through AMPK‐YAP1 signaling. The restoration of mitochondrial OXPHOS in DGUOK KO lung cancer cells using NDI1 was able to prevent AMPK‐mediated phosphorylation of YAP and to rescue CSC stemness. Genetic targeting of DGUOK using doxycycline‐inducible CRISPR/Cas9 was able to markedly induce tumor regression. Our findings reveal a novel role for mitochondrial dNTP metabolism in lung cancer tumor growth and progression, and implicate that the mitochondrial deoxynucleotide salvage pathway could be potentially targeted to prevent CSC‐mediated therapy resistance and metastatic recurrence.

Squamous cell lung cancer has dismal prognosis due to the dearth of effective treatments. Here, the authors perform an integrated proteogenomic analysis of the disease, revealing three proteomics-based subtypes and suggesting potential therapeutic opportunities.

Farnesoid X receptor (FXR) agonism is emerging as an important potential therapeutic mechanism of action for multiple chronic liver diseases. The bile acid‐derived FXR agonist obeticholic acid (OCA) has shown promise in a phase 2 study in patients with nonalcoholic steatohepatitis (NASH). Here, we report efficacy of the novel nonbile acid FXR agonist tropifexor (LJN452) in two distinct preclinical models of NASH. The efficacy of tropifexor at

BRAF drives MEK/ERK activation to facilitate tumorigenesis. Here, the authors show that in response to pro-inflammatory cytokines, ITCH mediates a non-proteolytic ubiquitination and activation of BRAF, which in turn sustains MEK/ERK signaling to facilitate melanoma cell growth.

Minor elements significantly influence the properties of stainless steel. In this study, a laser-induced breakdown spectroscopy (LIBS) technique combined with a back-propagation artificial intelligence network (BP-ANN) was used to detect nickel (Ni), chromium (Cr), and titanium (Ti) in stainless steel. For data pre-processing, cubic spline interpolation and wavelet threshold transform algorithms were used to perform baseline removal and denoising. The results show that this set of pre-processing methods can effectively improve the signal-to-noise ratio, remove the baseline of spectral baseline, reduce the average relative error, and reduce relative standard deviation of BP-ANN predictions. It indicates that BP-ANN combined with pre-processing methods has promising applications for the determination of Ni, Cr, and Ti in stainless steel with LIBS and improves prediction accuracy and stability.

Based on the concept of high-quality development, this paper constructs an urban ecological welfare evaluation framework, measures the urban ecological welfare performance in Jiangsu Province from 2005 to 2019 using a stochastic frontier production function model, and conducts a spatial and temporal divergence feature analysis, combining a spatial panel econometric model and a threshold panel regression model to explore the spatial effects and mechanisms of urban ecological welfare performance. The results show that: (1) The urban ecological welfare performance in Jiangsu province has been increasing every year, and the spatial divergence between north and south is significant, with the overall trend of southern Jiangsu > central Jiangsu > northern Jiangsu. (2) The differences in urban ecological welfare performance among the three regions are gradually decreasing, with the high values expanding and the low values decreasing, and the urban ecological welfare performance in northern Jiangsu Province is gradually approaching that in southern Jiangsu Province, and the urban ecological welfare performance level tends to be balanced. (3) There are significant negative spillover effects of industrial structure, city scale, and economic development level on urban ecological welfare performance, as well as significant threshold effects of innovation level, industrial structure, foreign trade dependence, and economic development, and significant differences in the degree of influence of urbanization on urban ecological welfare performance under different threshold variables. (4) The urbanization and economic development levels are the fundamental factors driving urban ecological welfare performance improvement. Industrial structure optimization, city scale, technological innovation, and foreign trade dependence positively contribute to urban welfare performance, and government financial pressure constrains the performance level improvement. In the future, a long-term mechanism for high-quality green development should be constructed, spatial spillover channels should be continuously improved, welfare thresholds should be effectively circumvented, and urban ecological welfare performance should be promoted in a concerted manner.

Automatic matching of multimodal remote sensing images remains a vital yet challenging task, particularly for remote sensing and computer vision applications. Most traditional methods mainly focus on key point detection and description of the original image, thus ignoring the deep semantic feature information such as semantic road features, with the result that the traditional method can not effectively resist nonlinear grayscale distortion, and has low matching efficiency and poor accuracy. Motivated by this, this paper proposes a novel automatic matching method named LURF via learned unstructured road features for the multimodal images. There are four main contributions in LURF. To begin with, the semantic road features were extracted from multimodal images based on segmentation model CRESIv2. Next, based on semantic road features, a stable and reliable intersection point detector has been proposed to detect unstructured key points. Moreover, a local entropy descriptor has been designed to describe key points with the local skeleton feature. Finally, a global optimization strategy is adopted to achieve the correct matching. The extensive experimental results demonstrate that the proposed LURF outperforms other state-of-the-art methods in terms of both accuracy and efficiency on different multimodal image data sets.

Summary: A primary goal of the US National Cancer Institute's Ras initiative at the Frederick National Laboratory for Cancer Research is to develop methods to quantify RAS signaling to facilitate development of novel cancer therapeutics. We use targeted proteomics technologies to develop a community resource consisting of 256 validated multiple reaction monitoring (MRM)-based, multiplexed assays for quantifying protein expression and phosphorylation through the receptor tyrosine kinase, MAPK, and AKT signaling networks. As proof of concept, we quantify the response of melanoma (A375 and SK-MEL-2) and colorectal cancer (HCT-116 and HT-29) cell lines to BRAF inhibition by PLX4720. These assays replace over 60 western blots with quantitative mass-spectrometry-based assays of high molecular specificity and quantitative precision, showing the value of these methods for pharmacodynamic measurements and mechanism-of-action studies. Methods, fit-for-purpose validation, and results are publicly available as a resource for the community at assays.cancer.gov. Motivation: A lack of quantitative, multiplexable assays for phosphosignaling limits comprehensive investigation of aberrant signaling in cancer and evaluation of novel treatments. To alleviate this limitation, we sought to develop assays by using targeted mass spectrometry for quantifying protein expression and phosphorylation through the receptor tyrosine kinase, MAPK, and AKT signaling networks. The resulting assays provide a resource for replacing over 60 western blots in examining cancer signaling and tumor biology with high molecular specificity and quantitative rigor.

Most of the critically ill novel coronavirus 2019 pneumonia (NCP) patients progress promptly, and soon match the ARDS diagnostic criteria. When mechanical ventilation and prone position cannot reverse the fatal hypoxia—extra-corporeal-membrane-oxygenation (ECMO) will be applied as a salvage treatment if available. Here, we report a novel coronavirus 2019 pneumonia (NCP) patient, a male, 67 years old, who was treated with ECMO for 30 days. In the midst, bronchoscopy was utilized to comprehend the airway lesions and clear secretions. And computed tomography (CT) scans were performed before and after the treatment of ECMO. In the recovering phase of his disease, the patient experienced multiple times pneumothorax on both sides. Some newly developed lung bullae in the subpleural area and modest bronchiectasis were found by the CT scan. The newly developed lung bullae was the probable cause of pneumothorax. Notably, in the whole process of his illness, the serum IL-6 only had a slight elevation in the early period, there is no typical cytokine storm as that was seen in non-COVID-19 ARDS. After 3-months meticulous treatment, the patient made a full recovery and now is discharged from our hospital. Though COVID-19 may not cause typical cytokine storm, the inflammation in lung may inflict severe damage to lung. Severe NCP may cause lung bullae and bronchiectasis, making the patients hard to be weaned from mechanical ventilation or ECMO.

Hibernators dramatically lower metabolism to save energy while fasting for months. Prolonged fasting challenges metabolic homeostasis, yet small-bodied hibernators emerge each spring ready to resume all aspects of active life, including immediate reproduction. The liver is the body’s metabolic hub, processing and detoxifying macromolecules to provide essential fuels to brain, muscle and other organs throughout the body. Here we quantify changes in liver gene expression across several distinct physiological states of hibernation in 13-lined ground squirrels, using RNA-seq to measure the steady-state transcriptome and GRO-seq to measure transcription for the first time in a hibernator. Our data capture key timepoints in both the seasonal and torpor-arousal cycles of hibernation. Strong positive correlation between transcription and the transcriptome indicates that transcriptional control dominates the known seasonal reprogramming of metabolic gene expression in liver for hibernation. During the torpor-arousal cycle, however, discordance develops between transcription and the steady-state transcriptome by at least two mechanisms: 1) although not transcribed during torpor, some transcripts are unusually stable across the torpor bout; and 2) unexpectedly, on some genes, our data suggest continuing, slow elongation with a failure to terminate transcription across the torpor bout. While the steady-state RNAs corresponding to these read through transcripts did not increase during torpor, they did increase shortly after rewarming despite their simultaneously low transcription. Both of these mechanisms would assure the immediate availability of functional transcripts upon rewarming. Integration of transcriptional, post-transcriptional and RNA stability control mechanisms, all demonstrated in these data, likely initiate a serial gene expression program across the short euthermic period that restores the tissue and prepares the animal for the next bout of torpor.

Mitochondria are vital subcellular organelles that generate most cellular chemical energy, regulate cell metabolism and maintain cell function. Mitochondrial dysfunction is directly linked to numerous diseases including neurodegenerative disorders, diabetes, thyroid squamous disease, cancer and septicemia. Thus, the design of specific mitochondria-targeting molecules and the realization of real-time acquisition of mitochondrial activity are powerful tools in the study and treatment of mitochondria dysfunction in related diseases. Recent advances in mitochondria-targeting agents have led to several important mitochondria chemical probes that offer the opportunity for selective targeting molecules, novel biological applications and therapeutic strategies. This review details the structural and physiological functional characteristics of mitochondria, and comprehensively summarizes and classifies mitochondria-targeting agents. In addition, their pros and cons and their related chemical biological applications are discussed. Finally, the potential biomedical applications of these agents are briefly prospected.

In daily life, there are a variety of complex sound sources. It is important to effectively detect certain sounds in some situations. With the outbreak of COVID-19, it is necessary to distinguish the sound of coughing, to estimate suspected patients in the population. In this paper, we propose a method for cough recognition based on a Mel-spectrogram and a Convolutional Neural Network called the Cough Recognition Network (CRN), which can effectively distinguish cough sounds.

Ships sailing through cold regions frequently encounter floe ice fields. An air-bubble system that reduces friction between the hull and ice floes is thus considered useful for the reduction of ice-induced resistance. In this study, a numerical analysis procedure based on coupled finite volume method (FVM) and discrete element method (DEM) is proposed to simulate complicated hull-water-gas-ice interactions for ice-going ships installed with air-bubble systems. The simulations reveal that after turning on the air-bubble system ice floes in contact with the hull side wall are pushed away from the hull by the gas-water mixture, resulting in an ice-free zone close to the side hull. It is found that the drag reduction rate increases with the increase of ventilation, while the bow ventilation plays a deciding role in the overall ice-resistance reduction. The proposed procedure is expected to facilitate design of new generations of ice-going ships.

The Apalachicola–Chattahoochee–Flint (ACF) basin is arguably the most litigated interstate river system in the eastern United States. Given the complicated demands for water use within this basin, it has been difficult to ascertain if the recent multi-decadal decline in streamflow is a product of human disturbance, changing climate, natural variability, or some combination of the above factors. To overcome these challenges, we examined unimpaired streamflow and precipitation within and adjacent to the ACF basin, upstream of the Apalachicola River at Chattahoochee, and the Florida streamflow station (ARCF), which has historically been identified to be representative of hydrologic variability in the ACF basin. Several of the upstream, unimpaired, streamflow stations selected were identified in rural watersheds where land-cover changes and human disturbance were minimal during the study period. When applying a series of statistical evaluations, ARCF streamflow variability generally reflects the natural variability of the ACF basin. Additionally, unimpaired streamflow variability from the neighboring Choctawhatchee River compared favorably with ARCF variability. The recent multi-decadal decline was consistent in all records, with the 2000s being the most severe in the historic record.

The astrocyte brain-type fatty-acid binding protein (Fabp7) circadian gene expression is synchronized in the same temporal phase throughout mammalian brain. Cellular and molecular mechanisms that contribute to this coordinated expression are not completely understood, but likely involve the nuclear receptor Rev-erbα (NR1D1), a transcriptional repressor. We performed ChIP-seq on ventral tegmental area (VTA) and identified gene targets of Rev-erbα, including Fabp7. We confirmed that Rev-erbα binds to the Fabp7 promoter in multiple brain areas, including hippocampus, hypothalamus, and VTA, and showed that Fabp7 gene expression is upregulated in Rev-erbα knock-out mice. Compared to Fabp7 mRNA levels, Fabp3 and Fabp5 mRNA were unaffected by Rev-erbα depletion in hippocampus, suggesting that these effects are specific to Fabp7. To determine whether these effects of Rev-erbα depletion occur broadly throughout the brain, we also evaluated Fabp mRNA expression levels in multiple brain areas, including cerebellum, cortex, hypothalamus, striatum, and VTA in Rev-erbα knock-out mice. While small but significant changes in Fabp5 mRNA expression exist in some of these areas, the magnitude of these effects are minimal to that of Fabp7 mRNA expression, which was over 6-fold across all brain regions. These studies suggest that Rev-erbα is a transcriptional repressor of Fabp7 gene expression throughout mammalian brain.

Fluorescence-based in vitro assays are highly sensitive, selective and convenient to use, which is suitable for qualitative and quantitative detection of various types of biological samples. Herein, we designed and synthesized a novel fluorogenic probe TPAN-Asn for in vitro l-asparaginase detection. TPAN-Asn exhibited selective and robust response to l-asparaginase over various anions, cations and amino acids. More importantly, we have demonstrated that TPAN-Asn is able to accurately quantify the amount of l-asparaginase in patient serum samples. These results suggest that TPAN-Asn holds great potential in the benchmarking and analysis of l-asparaginase-based cancer therapy.

BackgroundOral propranolol has become the first-line treatment for infantile hemangioma (IH). However, combined therapy with topical timolol and oral propranolol has been proposed as a more effective IH treatment strategy. We aimed to compare the safety and efficacy of topical timolol, oral propranolol, and their combination for treating IH in a meta-analysis.MethodsRelevant randomized controlled trials (RCTs) were obtained after searching the PubMed, Embase, Cochrane’s Library, China National Knowledge Infrastructure, and WanFang databases. A random-effect model was used to pool the results.ResultsEight RCTs with 759 patients with IH were included in this meta-analysis. Treatment with topical timolol alone showed a similar response rate compared to oral propranolol (risk ratio [RR] = 0.97, p = 0.63), but resulted in fewer adverse events (RR = 0.36, p = 0.002). Combined treatment with topical timolol and oral propranolol showed a favorable response rate compared to treatment with oral propranolol (RR = 1.14, p = 0.03) or topical timolol (RR = 1.36, p = 0.01) alone. Moreover, combined treatment showed similar risks of adverse events compared to oral propranolol (RR = 0.80, p = 0.24) or topical timolol (RR = 1.31, p = 0.25) alone.ConclusionsCombined treatment with topical timolol and oral propranolol may be more effective than either single treatment strategy in patients with IH. Topical timolol alone conferred similar efficacy for IH compared to oral propranolol, but with less incidence of adverse events.

Robotic exoskeletons are developed with the aim of enhancing convenience and physical possibilities in daily life. However, at present, these devices lack sufficient synchronization with human movements. To optimize human-exoskeleton interaction, this article proposes a gait recognition and prediction model, called the gait neural network (GNN), which is based on the temporal convolutional network. It consists of an intermediate network, a target network, and a recognition and prediction model. The novel structure of the algorithm can make full use of the historical information from sensors. The performance of the GNN is evaluated based on the publicly available HuGaDB dataset, as well as on data collected by an inertial-based wearable motion capture device. The results show that the proposed approach is highly effective and achieves superior performance compared with existing methods.

Abstract Background Double lumen intubation and one-lung ventilation should be applied without delay in cases of traumatic main bronchial rupture. In most cases, when the patients’ vital signs have been stabilized, the repair can be performed. However, when one-lung ventilation is complicated by traumatic wet lung, the mortality rate is likely to be much higher. Case presentation In this case, the patient experienced a left main bronchial rupture, bilateral traumatic wet lung, and acute respiratory distress syndrome (ARDS) because of severe thoracic trauma. Though the patient was treated with intubation and mechanical ventilation (MV), his oxygenation was still not stable. Thus, veno-venous extracorporeal membrane oxygenation (V-V ECMO) was initiated; upon improvement of oxygenation, the patient received an exploratory thoracotomy. Unfortunately, the rupture proved to be irreparable, resulting in a total left pneumonectomy. As there was severe ARDS caused by trauma, ECMO and ultra-low tidal volume (VT) MV strategy (3 ml/kg) were utilized for lung protection post-op. ECMO was sustained up to the 10th day, and MV until the 20th day, post-operation. With the support of MV, ECMO and other comprehensive measures, the patient made a recovery. Conclusion V-V ECMO and ultra-low VT MV helped this thoracic trauma patient survive the lung edema period and prevented ventilator associated pneumonia (VAP). In extreme situations, with the support of ECMO, the tidal volume may be lowered to 3 ml/kg.

The road marking recognition is an important part of road scene understanding based on computer vision. In road marking recognition, the contour-based algorithm such as generalized Hough transform (GHT) is more effective than the texture-based algorithm for no texture noise effect. However, there are a lot of redundant calculations in template matching which reduces the system efficiency. This paper presents a voting based matching pursuit (VMP) algorithm for locating reference points automatically in solving the sparse optimization problem, which achieves automatic alignment of samples in recognition. Then a dictionary learning method based on VMP algorithm is proposed, which uses a simple strategy to update the dictionary elements. The experimental results from two data sets have shown that the system efficiency is significant improved while ensuring the accuracy rate by the proposed method.

Abstract Background The etiology and pathology osteonecrosis of the femoral head (ONFH) are not completely clarified. As a cytokine participating in systemic inflammation, tumor necrosis factor alpha (TNFα) has been shown to be involved in the pathogenesis of ONFH. However, the role of TNFα in ONFH is not clearly clarified. In the present study, we investigated the effects of TNFα on proliferation, angiogenesis, and osteogenic differentiation of rat bone mesenchymal stem cells (rMSCs) and the underlying mechanisms. Methods All femoral bone tissues were separated in surgeries. After extracting total RNA and protein, we evaluated TNFα content by ELISA and the relative expression levels of genes by quantitative real-time PCR and western blot. Also, immunohistochemistry staining was performed to observe the expression of Runx2 in the bone samples. Chick embryo chorioallantoic membrane (CAM) assay was performed to observe the effect of TNFα on angiogenesis. The genomic DNAs were treated by bisulfite modification, and methylation status of CpG sites in the CpG islands of human and rat Runx2 gene promoter was determined by DNA sequencing. The binding of H3K4me3 and H3K27me3 in Runx2 promoter was checked by ChIP assay. RNA-seq analysis was used to find out the genes and pathways changed by TNFα in rMSCs. Results The results demonstrate TNFα promotes cell proliferation and angiogenesis whereas inhibits osteogenesis. Epigenetic regulations including DNA methylation and histone modifications play important roles in mediating the effect of TNFα on osteogenic differentiation. We find an increased rate of CpG methylation in rat Runx2 promoter in TNFα-treated rMSCs, as well as significantly increased occupancy of H3K27me3 in Runx2 gene promoter. The content of TNFα in necrotic tissue is much lower than that of normal tissue. And relevantly, human Runx2 promoter is demethylated in necrotic tissue using bone samples from patient with ONFH. In addition, we have observed that Wnt signaling pathway is inhibited by TNFα as multiple Wnts are markedly decreased in TNFα-treated rMSCs by RNA-seq analysis. Conclusion Taken together, our study shows that TNFα plays complicated roles in the pathogenesis of ONFH, including proliferation, angiogenesis, and osteogenesis. Targeting TNFα should not be considered as an applicable strategy to inhibit the progression of ONFH.

Electric field controlled magnetism provides an energy efficient way for the operations in the spintronic devices. Here the authors show strain induced, reversible, nonvolatile electric field control of magnetization and magnetoresistance in a magnetic tunnel junction on a ferroelectric substrate at room temperature and zero magnetic field.

Early ducts of breast tumors are unequivocally acidic. High rates of glycolysis combined with poor perfusion lead to a congestion of acidic metabolites in the tumor microenvironment, and pre-malignant cells must adapt to this acidosis to thrive. Adaptation to acidosis selects cancer cells that can thrive in harsh conditions and are capable of outgrowing the normal or non-adapted neighbors. This selection is usually accompanied by phenotypic change. Epithelial mesenchymal transition (EMT) is one of the most important switches correlated to malignant tumor cell phenotype and has been shown to be induced by tumor acidosis. New evidence shows that the EMT switch is not a binary system and occurs on a spectrum of transition states. During confirmation of the EMT phenotype, our results demonstrated a partial EMT phenotype in our acid-adapted cell population. Using RNA sequencing and network analysis we found 10 dysregulated network motifs in acid-adapted breast cancer cells playing a role in EMT. Our further integrative analysis of RNA sequencing and SILAC proteomics resulted in recognition of S100B and S100A6 proteins at both the RNA and protein level. Higher expression of S100B and S100A6 was validated in vitro by Immunocytochemistry. We further validated our finding both in vitro and in patients' samples by IHC analysis of Tissue Microarray (TMA). Correlation analysis of S100A6 and LAMP2b as marker of acidosis in each patient from Moffitt TMA approved the acid related role of S100A6 in breast cancer patients. Also, DCIS patients with higher expression of S100A6 showed lower survival compared to lower expression. We propose essential roles of acid adaptation in cancer cells EMT process through S100 proteins such as S100A6 that can be used as therapeutic strategy targeting both acid-adapted and malignant phenotypes.

A novel variable stiffness soft robotic hand (SRH) consists of three pieces of layer jamming structure (LJS) is proposed. The mechanism is driven by the motor-based tendon along the surface of the pieces that connect to individual gas channel. Each LJS is optimised by adhering a thin layer of hot melt adhesive and overlapping the spring steel sheet as inner layer material. It can be switched between rigid and compliant independently. The structures of variable stiffness and tendon-driven lead to various deformation poses. Then the control system of SRH and the performance analysis of the LJS are introduced. Finally, the experiments are implemented to prove the superiority of the proposed LJS and the demonstrations show that the designed robotic hand has multiple configurations to successfully grasp various objects.

The dislocated development of population, land, and economy will disturb the urban system, cause ecological risk problems, and ultimately affect regional habitat and quality development. Based on social statistics and nighttime lighting data from 2000 to 2018, we used mathematical statistics and spatial analysis methods to analyze the change process of urbanization’s coupling coordination degree and ecological risk response pattern in the Yangtze River Delta. Results show that: ① From 2000 to 2018, the coupling coordination degree of urbanization in the Yangtze River Delta increased, with high values in Suzhou-Wuxi-Changzhou, Shanghai, Nanjing and Hangzhou regions. ② The ecological risk in the Yangtze River Delta weakened, and the vulnerability and disturbance of landscape components together constitute the spatial differentiation pattern of regional ecological risk, which presented homogeneous aggregation and heterogeneous isolation. ③ The overall ecological stress of urbanization in the Yangtze River Delta decreased. ④ The population aggregation degree, socio-economic development level and built-up area expansion trend contributed to the spatiotemporal differentiation of urbanization’s ecological risks through the synergistic effects of factor concentration and diffusion, population quality cultivation and improvement, technological progress and dispersion, industrial structure adjustment and upgrading. This study can provide a reference for regional urbanization to deal with ecological risks reasonably and achieve high-quality development.

The relationship between urbanization and ecology environment is a current research hotspot. Most literature to date focuses on the interaction between urbanization and a single component of the ecosystem (e.g., water, forests, and ecosystem services), while little attention has been given to the relationship between urbanization quality and ecosystem health. Accordingly, this paper used the entropy method and vigor—organization–resilience model to measure the urbanization quality and ecosystem health in Jiangsu Province. Based on the results, this paper analyzed the spatial-temporal pattern and evolution characteristics of the coordination degree between urbanization quality and ecosystem health in Jiangsu Province in 2000, 2005, 2010, 2015, and 2017 and then used the geographic detector and Tobit regression model to explore its internal driving forces and external influencing factors. The results show the following: 1. The changing trend of urbanization quality and ecosystem health in the Jiangsu Province share some traits; it first descends and then ascends; 2. The cities in Jiangsu Province are all between primary coordination and high-quality coordination. Central Jiangsu has the best coupling coordination degree, and Northern Jiangsu has the worst coupling coordination degree, but the overall coordination degree is on the rise; 3. The internal and external factors that drive the coordinated development of urbanization and ecosystem health differ based on periodic and regional characteristics. We need to tailor policies to ensure the sustainable development of the region.

Microrobots can operate in tiny areas that traditional bulk robots cannot reach. The combination of acoustic actuation with microrobots extensively expands the application areas of microrobots due to their desirable miniaturization, flexibility, and biocompatibility features. Herein, an overview of the research and development of acoustics-actuated microrobots is provided. We first introduce the currently established manufacturing methods (3D printing and photolithography). Then, according to their different working principles, we divide acoustics-actuated microrobots into three categories including bubble propulsion, sharp-edge propulsion, and in-situ microrotor. Next, we summarize their established applications from targeted drug delivery to microfluidics operation to microsurgery. Finally, we illustrate current challenges and future perspectives to guide research in this field. This work not only gives a comprehensive overview of the latest technology of acoustics-actuated microrobots, but also provides an in-depth understanding of acoustic actuation for inspiring the next generation of advanced robotic devices.

Background: Numerous studies have reported the relationship between Long non-coding RNAs (LncRNAs) expression and prognosis of osteosarcoma, but less consensus has been reached. Our meta-analysis was conducted to quantitatively assess the relationship between the expression of LncRNAs, prognosis and clinical pathology in osteosarcoma development. Methods: PubMed,Embase,Web of Science,The Cochrane Library,SionMed,CNKI and WanFang databases were carefully searched to identify eligible studies. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the prognostic significance of LncRNAs expression in osteosarcoma. Moreover, meta-regression analysis and subgroup analysis were carried out to explore the potential sources of heterogeneity. Results: A total of 20 studies comprising 1749 patients were included in present meta-analysis. The results showed that the over-expression of LncRNA had a significant correlation with overall survival (OS) (HR = 2.16, 95% CI:1.68–2.79), and was not related to disease free survival (DFS) (HR = 0.71, 95% CI:0.05–9.53). Subgroup analysis further indicated that LncRNA transcription level was significantly associated with alkaline phosphatase (HR = 2.13, 95% CI:1.58–2.88) , tumor size ( 25:HR = 1.01, 95% CI:0.78–1.3), gender(female/male: HR = 1.15, 95% CI: 0.96–1.37), tumor site (femur,tibia/elsewhere:HR = 1.15, 95% CI:0.94–1.4) and chemotherapy (yes/no: HR = 1.45, 95% CI:0.46–4.63). Conclusions: This study demonstrated that abnormal LncRNAs expression might be potential prognostic markers to predict worse overall survival in osteosarcoma patients. However, the cut-off values may be the source of heterogeneity. Keywords: LncRNAs, Osteosarcoma, Prognosis, Meta-analysis

Collapse of the femoral head is the most significant pathogenic complication arising from osteonecrosis of the femoral head. It is related to the disruption of the maintenance of cartilage and bone, and results in an impaired function of the vascular component. A method for predicting the collapse of the femoral head can be treated as a type of clinical index. Efforts in recent years to predict the collapse of the femoral head due to osteonecrosis include multiple methods of radiographic analysis, stress distribution analysis, finite element analysis, and other innovative methods. Prediction methods for osteonecrosis of the femoral head complications originated in Western countries and have been further developed in Asia. Presently, an increasing number of surgeons have chosen to focus on surgical treatments instead of prediction methods to guide more conservative interventions, resulting in a growing reliance on the more prevalent and highly effective total hip arthroplasty, rather than on more conservative treatments. In this review, we performed a literature search of PubMed and Embase using search terms including “osteonecrosis of femoral head,” “prediction,” “collapse,” “finite element,” “radiographic images,” and “stress analysis,” exploring the basic prediction method and prospects for new applications.

Ibrutinib has demonstrated high response rates in B-cell lymphomas but a lot of ibrutinib-treated patients relapse with resistance. This study unified TME-mediatedde novoand acquired drug resistance through B-cell receptor signalling and PI3K-AKT-mTOR axis and provides a combination therapeutic strategy against B-cell malignancies.

Summary: The deregulation of the actin cytoskeleton has been extensively studied in metastatic dissemination. However, the post-dissemination role of the actin cytoskeleton dysregulation is poorly understood. Here, we report that fascin, an actin-bundling protein, promotes lung cancer metastatic colonization by augmenting metabolic stress resistance and mitochondrial oxidative phosphorylation (OXPHOS). Fascin is directly recruited to mitochondria under metabolic stress to stabilize mitochondrial actin filaments (mtF-actin). Using unbiased metabolomics and proteomics approaches, we discovered that fascin-mediated mtF-actin remodeling promotes mitochondrial OXPHOS by increasing the biogenesis of respiratory Complex I. Mechanistically, fascin and mtF-actin control the homeostasis of mtDNA to promote mitochondrial OXPHOS. The disruption of mtF-actin abrogates fascin-mediated lung cancer metastasis. Conversely, restoration of mitochondrial respiration by using yeast NDI1 in fascin-depleted cancer cells is able to rescue lung metastasis. Our findings indicate that the dysregulated actin cytoskeleton in metastatic lung cancer could be targeted to rewire mitochondrial metabolism and to prevent metastatic recurrence. : Lin et. al. show that fascin, a pro-metastasis actin-bundling protein, promotes mitochondrial oxidative phosphorylation and metabolic stress resistance in lung adenocarcinoma by remodeling mitochondrial actin filaments and regulating the homeostasis of mitochondrial DNA. Keywords: fascin, actin, mitochondria, NSCLC, metastasis, metastatic colonization, OXPHOS

The brain–computer interface-based rehabilitation robot has quickly become a very important research area due to its natural interaction. One of the most important problems in brain–computer interface is that large-scale annotated electroencephalography data sets required by advanced classifiers are almost impossible to acquire because biological data acquisition is challenging and quality annotation is costly. Transfer learning relaxes the hypothesis that the training data must be independent and identically distributed with the test data. It can be considered a powerful tool for solving the problem of insufficient training data. There are two basic issues with transfer learning, under transfer and negative transfer. We proposed a novel brain–computer interface framework by using autoencoder-based transfer learning, which includes three main components: an autoencoder framework, a joint adversarial network, and a regularized manifold constraint. The autoencoder framework automatically encodes and reconstructs data from source and target domains and forces the neural network to learn to represent these domains reliably. The joint adversarial network aims to force the network to learn to encode more appropriately for the source domain and target domain simultaneously, thereby overcoming the problem of under transfer. The regularized manifold constraint aims to avoid the problem of negative transfer by avoiding geometric manifold structure in the target domain being destroyed by the source domain. Experiments show that the brain–computer interface framework proposed by us can achieve better results than state-of-the-art approaches in electroencephalography signal classification tasks. This is helpful in aiding our rehabilitation robot to understand the intention of patients and can help patients to carry out rehabilitation exercises effectively.

Clarifying the relationship between land use and farmers’ sense of place on a micro scale is significant for enriching the perspective of research on human–environment relationships. Therefore, this paper analyzed land use change and the sense of place of farmers and further explored the interaction between them in the Yangjuangou catchment of Liqu Town in Baota District, Shaanxi Province from 1984 to 2020. The results indicated that: (1) the change in croplands was the most significant, i.e., its share in the total area decreased by 40%, and the decrease in sloping fields was the highest. The average relative altitude of croplands has decreased. The change in ecological land was also more significant, showing an increasing trend. Overall, the exploitation of land resources has declined; (2) the intensity of the sense of place of local farmers fluctuated downwards. The intensity of place attachment and place dependence decreased, and the intensity of the place identity increased; and (3) the decline in the intensity of the place attachment and place dependence promoted the reduction of sloping fields, the growth of ecological land and abandoned fields. By comparison, the increase in ecological land and check dam land promoted an increase in the intensity of place identity for local farmers. This paper suggested that rural areas in the Loess Hilly and Gully Region should strengthen innovation in land use patterns and focus on sustainability of farmers’ livelihoods, in order to promote the harmonious development of human-environmental relations.

Molecular dynamics simulations were performed to study the evolution of single crystal copper with and without a nanovoid (located at the middle of crystal with a diameter of ~2.9 nm) when loaded with shock waves of different velocities. The simulation results show that the average particle velocity of single crystal copper linearly relates to the velocity of the loaded shock wave for both the systems (crystal with and without a nanovoid). When loaded by the shock wave, the equilibrated temperature and pressure of the system with a nanovoid are found to be slightly larger than those of the system without the nanovoid, while the volume of the system with the nanovoid is found to be lower than that of the void-free system. The single crystal copper undergoes a phase transition from face-centered cubic (FCC) to hexagonal-close packed (HCP) and a dislocation structure forms around the nanovoid. The existence of a nanovoid can induce the rearrangement and deformation of the crystalline structure and eventually lead to the plastic deformation of the system. This work provides molecular-level insight into the effect of nanovoids on the shock plasticity of metals, which can aid in the ultimate application of the control of material structure damage in shock-wave propagation.

Protein arginine methyltransferase-6 participates in a range of biological functions, particularly RNA processing, transcription, chromatin remodeling, and endosomal trafficking. However, it remains unclear whether protein arginine methyltransferase-6 modifies neuropathic pain and, if so, what the mechanisms of this effect. In this study, protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model, chronic constriction injury model and bone cancer pain model, using immunohistochemistry, western blotting, immunoprecipitation, and label-free proteomic analysis. The results showed that protein arginine methyltransferase-6 mostly co-localized with β-tubulin III in the dorsal root ganglion, and that its expression decreased following spared nerve injury, chronic constriction injury and bone cancer pain. In addition, PRMT6 knockout (Prmt6–/–) mice exhibited pain hypersensitivity. Furthermore, the development of spared nerve injury–induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 expression. Moreover, when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury, increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn, and the response to mechanical stimuli was enhanced. Mechanistically, protein arginine methyltransferase-6 appeared to contribute to spared nerve injury–induced neuropathic pain by regulating the expression of heterogeneous nuclear ribonucleoprotein-F. Additionally, protein arginine methyltransferase-6-mediated modulation of heterogeneous nuclear ribonucleoprotein-F expression required amino acids 319 to 388, but not classical H3R2 methylation. These findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target for the treatment of peripheral neuropathic pain.

Objective: Genetic background largely contributes to the complexity of metabolic responses and dysfunctions. Induction of brown adipose features in white fat, known as brown remodeling, has been appreciated as a promising strategy to offset the positive energy balance in obesity and further to improve metabolism. Here we address the effects of genetic background on this process. Methods: We investigated browning remodeling in a depot-specific manner by comparing the response of C57BL/6J, 129/Sv and FVB/NJ mouse strains to cold. Results: Surprisingly, 129/Sv and FVB/NJ mice showed distinct brown remodeling features despite their similar resistance to metabolic disorders in comparison to the obesity-prone C57BL/6J mice. FVB/NJ mice demonstrated a preference of brown remodeling in inguinal subcutaneous white adipose tissue (iWAT), whereas 129/Sv mice displayed robust brown remodeling in visceral epididymal fat (eWAT). We further compared gene expression in different depots by RNA-sequencing and identified Hoxc10 as a novel “brake” of brown remodeling in iWAT. Conclusion: Rodent genetic background determines the brown remodeling of different white fat depots. This study provides new insights into the role of genetic variation in fat remodeling in susceptibility to metabolic diseases. Author Video: Author Video Watch what authors say about their articles Keywords: Genetic background, White adipose tissue, Brown remodeling, Hoxc10, Cold exposure, Browning brake

Nanomagnetic materials allow for the emission and detection of microwave radiation in technological applications by spin excitation. Here, the authors present sensitive room-temperature microwave detectors based on nanoscale magnetic tunnel junctions, enabled via spin torque and injection locking.

In this paper, we propose a novel method for fault diagnosis in micro-electromechanical system (MEMS) inertial sensors using a bidirectional long short-term memory (BLSTM)-based Hilbert–Huang transform (HHT) and a convolutional neural network (CNN). First, the method for fault diagnosis of inertial sensors is formulated into an HHT-based deep learning problem. Second, we present a new BLSTM-based empirical mode decomposition (EMD) method for converting one-dimensional inertial data into two-dimensional Hilbert spectra. Finally, a CNN is used to perform fault classification tasks that use time–frequency HHT spectrums as input. According to our experimental results, significantly improved performance can be achieved, on average, for the proposed BLSTM-based EMD algorithm in terms of EMD computational efficiency compared with state-of-the-art algorithms. In addition, the proposed fault diagnosis method achieves high accuracy in fault classification.

This article introduces a visual–tactile multimodal grasp data set, aiming to further the research on robotic manipulation. The data set was built by the novel designed dexterous robot hand, the Intel’s Eagle Shoal robot hand (Intel Labs China, Beijing, China). The data set contains 2550 sets data, including tactile, joint, time label, image, and RGB and depth video. With the integration of visual and tactile data, researchers could be able to better understand the grasping process and analyze the deeper grasping issues. In this article, the building process of the data set was introduced, as well as the data set composition. In order to evaluate the quality of data set, the tactile data were analyzed by short-time Fourier transform. The tactile data–based slip detection was realized by long short-term memory and contrasted with visual data. The experiments compared the long short-term memory with the traditional classifiers, and generalization ability on different grasp directions and different objects is implemented. The results have proved that the data set’s value in promoting research on robotic manipulation area showed the effective slip detection and generalization ability of long short-term memory. Further work on visual and tactile data will be devoted to in the future.