Neuromorphic computing has been extensively studied to mimic the brain functions of perception, learning, and memory because it may overcome the von Neumann bottleneck. Here, with the light‐induced ...bidirectional photoresponse of the proposed Bi2O2Se/graphene hybrid structure, its potential use in next‐generation neuromorphic hardware is examined with three distinct optoelectronic applications. First, a photodetector based on a Bi2O2Se/graphene hybrid structure presents positive and negative photoresponsibility of 88 and −110 A W−1 achieved by the excitation of visible wavelength and ultraviolet wavelength light at intensities of 1.2 and 0.3 mW cm−2, respectively. Second, this unique photoresponse contributes to the realization of all optically stimulated long‐term potentiation or long‐term depression to mimic synaptic short‐term plasticity and long‐term plasticity, which are attributed to the combined effect of photoconductivity, bolometric, and photoinduced desorption. Third, the devices are applied to perform digital logic functions, such as “AND” and “OR,” using full light modulation. The proposed Bi2O2Se/graphene‐based optoelectronic device represents an innovative and efficient building block for the development of future multifunctional artificial neuromorphic systems.
All‐optical synapses based on a 2D Bi2O2Se/graphene hybrid structure can yield positive photoresponses under visible light and negative photoresponses under 365 nm illumination without the extra electrical control. Contributing to this unique optoelectronic property, the single two‐terminal device with fully optical operations is demonstrated for the photodetector, optoelectronic synapses, and optical logic functions.
The ongoing coronavirus disease 2019 (COVID-19) outbreak expanded rapidly throughout China. Major behavioral, clinical, and state interventions were undertaken to mitigate the epidemic and prevent ...the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, affected COVID-19 spread in China. We used real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation in transmission in cities across China and to ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was explained well by human mobility data. After the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases were still indicative of local chains of transmission outside of Wuhan. This study shows that the drastic control measures implemented in China substantially mitigated the spread of COVID-19.
The modeling of artificial, human-level creativity is becoming more and more achievable. In recent years, neural networks have been successfully applied to different tasks such as image and music ...generation, demonstrating their great potential in realizing computational creativity. The fuzzy definition of creativity combined with varying goals of the evaluated generative systems, however, makes subjective evaluation seem to be the only viable methodology of choice. We review the evaluation of generative music systems and discuss the inherent challenges of their evaluation. Although subjective evaluation should always be the ultimate choice for the evaluation of creative results, researchers unfamiliar with rigorous subjective experiment design and without the necessary resources for the execution of a large-scale experiment face challenges in terms of reliability, validity, and replicability of the results. In numerous studies, this leads to the report of insignificant and possibly irrelevant results and the lack of comparability with similar and previous generative systems. Therefore, we propose a set of simple musically informed objective metrics enabling an objective and reproducible way of evaluating and comparing the output of music generative systems. We demonstrate the usefulness of the proposed metrics with several experiments on real-world data.
In recent decades, chemotherapies targeting apoptosis have emerged and demonstrated remarkable achievements. However, emerging evidence has shown that chemoresistance is mediated by impairing or ...bypassing apoptotic cell death. Several novel types of programmed cell death, such as ferroptosis, necroptosis, and pyroptosis, have recently been reported to play significant roles in the modulation of cancer progression and are considered a promising strategy for cancer treatment. Thus, the switch between apoptosis and pyroptosis is also discussed. Cancer immunotherapy has gained increasing attention due to breakthroughs in immune checkpoint inhibitors; moreover, ferroptosis, necroptosis, and pyroptosis are highly correlated with the modulation of immunity in the tumor microenvironment. Compared with necroptosis and ferroptosis, pyroptosis is the primary mechanism for host defense and is crucial for bridging innate and adaptive immunity. Furthermore, recent evidence has demonstrated that pyroptosis exerts benefits on cancer immunotherapies, including immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell therapy (CAR-T). Hence, in this review, we elucidate the role of pyroptosis in cancer progression and the modulation of immunity. We also summarize the potential small molecules and nanomaterials that target pyroptotic cell death mechanisms and their therapeutic effects on cancer.
Chronic obstructive pulmonary disease (COPD) is a progressive, life-threatening lung disease with increasing prevalence and incidence worldwide. Increasing evidence suggests that lung microbiomes ...might play a physiological role in acute exacerbations of COPD. The objective of this study was to characterize the association of the microbiota and exacerbation risk or airflow limitation in stable COPD patients.
The sputum microbiota from 78 COPD outpatients during periods of clinical stability was investigated using 16S rRNA V3-V4 amplicon sequencing. The microbiome profiles were compared between patients with different risks of exacerbation, i.e., the low risk exacerbator (LRE) or high risk exacerbator (HRE) groups, and with different airflow limitation severity, i.e., mild to moderate (FEV1 ≥ 50; PFT I) or severe to very severe (FEV1 < 50; PFT II).
The bacterial diversity (Chao1 and observed OTUs) was significantly decreased in the HRE group compared to that in the LRE group. The top 3 dominant phyla in sputum were Firmicutes, Actinobacteria, and Proteobacteria, which were similar in the HRE and LRE groups. At the genus level, compared to that in the LRE group (41.24%), the proportion of Streptococcus was slightly decreased in the HRE group (28.68%) (p = 0.007). However, the bacterial diversity and the proportion of dominant bacteria at the phylum and genus levels were similar between the PFT I and PFT II groups. Furthermore, the relative abundances of Gemella morbillorum, Prevotella histicola, and Streptococcus gordonii were decreased in the HRE group compared to those in the LRE group according to linear discriminant analysis effect size (LEfSe). Microbiome network analysis suggested altered bacterial cooperative regulation in different exacerbation phenotypes. The proportions of Proteobacteria and Neisseria were negatively correlated with the FEV1/FVC value. According to functional prediction of sputum bacterial communities through Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis, genes involved in lipopolysaccharide biosynthesis and energy metabolism were enriched in the HRE group.
The present study revealed that the sputum microbiome changed in COPD patients with different risks of exacerbation. Additionally, the bacterial cooperative networks were altered in the HRE patients and may contribute to disease exacerbation. Our results provide evidence that sputum microbiome community dysbiosis is associated with different COPD phenotypes, and we hope that by understanding the lung microbiome, a potentially modifiable clinical factor, further targets for improved COPD therapies during the clinically stable state may be elucidated.
The performance of flexible and stretchable sensors relies on the optimization of both the flexible substrate and the sensing element, and their synergistic interactions. Herein, a novel strategy is ...reported for cost‐effective and scalable manufacturing of a new class of porous materials as 3D flexible and stretchable piezoresistive sensors, by assembling carbon nanotubes onto porous substrates of tunable Poisson ratios. It is shown that the piezoresistive sensitivity of the sensors increases as the substrate's Poisson's ratio decreases. Substrates with negative Poisson ratios (auxetic foams) exhibit significantly higher piezoresistive sensitivity, resulting from the coherent mode of deformation of the auxetic foam and enhanced changes of tunneling resistance of the carbon nanotube networks. Compared with conventional foam sensors, the auxetic foam sensor (AFS) with a Poisson's ratio of –0.5 demonstrates a 300% improvement in piezoresistive sensitivity and the gauge factor increases as much as 500%. The AFS has high sensing capability, is extremely robust, and capable of multimodal sensing, such as large deformation sensing, pressure sensing, shear/torsion sensing, and underwater sensing. AFS shows great potential for a broad range of wearable and portable devices applications, which are described by reporting on a series of demonstrations.
The performance of flexible and stretchable sensors relies on the optimization of both the flexible substrate and the sensing element, along with their synergistic interactions. Herein, a novel strategy for cost‐effective and scalable manufacturing of a new class of porous materials as 3D flexible and stretchable piezoresistive sensors, by assembling carbon nanotubes onto porous substrates of tunable Poisson ratios.
Background & Aims
Differentiation antagonizing non‐protein coding RNA is associated with various types of neoplasms. Hepatitis C virus‐related hepatocellular carcinoma has a high risk of recurrence. ...Here we determined the role of differentiation antagonizing non‐protein coding RNA in hepatitis C virus‐related hepatocarcinogenesis and identified potential therapeutic targets and non‐invasive prognostic markers for long‐term outcome of hepatitis C virus‐related hepatocellular carcinoma after surgical resection.
Methods
Differentiation antagonizing non‐protein coding RNAs relevant to hepatitis C virus‐related hepatocellular carcinoma were identified through comparative RNA‐sequencing of tumour and adjacent non‐tumour (ANT) tissues in a screening set, and were validated using real‐time polymerase chain reaction. Target long non‐coding RNAs (lncRNAs) in tissues and serum exosomes were used to predict the recurrence of hepatitis C virus‐related hepatocellular carcinoma after curative surgical resection in a large application cohort from 2005 to 2012.
Results
We confirmed that differentiation antagonizing non‐protein coding RNA was upregulated following hepatitis C virus infection and identified as the lncRNA most relevant to hepatitis C virus‐related hepatocellular carcinoma in tumour tissues as compared to that in ANT tissues. In 183 hepatitis C virus‐related hepatocellular carcinoma patients followed for 10 years after curative HCC resection, the expression level of circulating exosomal differentiation antagonizing non‐protein coding RNA was positively associated with HCC recurrence and was the most predictive factor associated with HCC recurrence and mortality (hazard ratio/95% confidence intervals: 7.0/4.3‐11.6 and 2.7/1.5‐5.1 respectively).
Conclusions
Differentiation antagonizing non‐protein coding RNA is highly relevant to disease progression of hepatitis C virus‐related hepatocellular carcinoma. Our finding indicated that circulating exosomal differentiation antagonizing non‐protein coding RNA might serve as a non‐invasive prognostic biomarker for hepatitis C virus‐related hepatocellular carcinoma.
Imagine having a knowledge graph that can extract medical health knowledge related to patient diagnosis solutions and treatments from thousands of research papers, distilled using machine learning ...techniques in healthcare applications. Medical doctors can quickly determine treatments and medications for urgent patients, while researchers can discover innovative treatments for existing and unknown diseases. This would be incredible! Our approach serves as an all-in-one solution, enabling users to employ a unified design methodology for creating their own knowledge graphs. Our rigorous validation process involves multiple stages of refinement, ensuring that the resulting answers are of the utmost professionalism and solidity, surpassing the capabilities of other solutions. However, building a high-quality knowledge graph from scratch, with complete triplets consisting of subject entities, relations, and object entities, is a complex and important task that requires a systematic approach. To address this, we have developed a comprehensive design flow for knowledge graph development and a high-quality entities database. We also developed knowledge distillation schemes that allow you to input a keyword (entity) and display all related entities and relations. Our proprietary methodology, multiple levels refinement (MLR), is a novel approach to constructing knowledge graphs and refining entities level-by-level. This ensures the generation of high-quality triplets and a readable knowledge graph through keyword searching. We have generated multiple knowledge graphs and developed a scheme to find the corresponding inputs and outputs of entity linking. Entities with multiple inputs and outputs are referred to as joints, and we have created a joint-version knowledge graph based on this. Additionally, we developed an interactive knowledge graph, providing a user-friendly environment for medical professionals to explore entities related to existing or unknown treatments/diseases. Finally, we have advanced knowledge distillation techniques.
Exosomes are implicated in cancer cell development, migration and invasion. Pigment epithelium-derived factor (PEDF) is a secreted anticancer protein that can regulate lung cancer progression; ...however, the role of PEDF in non-small cell lung cancer (NSCLC), including metastasis and cancer cell-derived exosome secretion, is unclear. In this study, we analyzed the effects of PEDF on exosome-mediated migration, invasion, and tumorigenicity of cultured NSCLC cells. The results showed that PEDF overexpression significantly reduced NSCLC invasion and migration, while inducing cell aggregation, whereas PEDF knockdown had the opposite effects. Exosomes from NSCLC cells treated with recombinant PEDF had a significantly reduced ability to promote cancer cell motility, migration, and invasion compared to exosomes from untreated cells. Exosomes from PEDF-treated cells contained thrombospondin 1 (THBS1), which inhibited cytoskeletal remodeling and exosome-induced lung cancer cell motility, migration, and invasion. Furthermore, PEDF-overexpressing NSCLC cells formed smaller xenograft tumors with higher THBS1 expression compared to control tumors. Our findings indicate that PEDF decreases the metastatic potential of NSCLC cells through regulation of THBS1 release in cancer cell-derived exosomes, thus uncovering a new mechanism of lung cancer progression.
•PEDF induces aggregation and reduces invasion and migration of lung cancer cells.•Exosomes from PEDF-treated cancer cells inhibit metastatic behavior of NSCLC cells.•PEDF-expressing NSCLC cells have reduced tumorigenicity in vivo.•PEDF increases thrombospondin 1 content in lung cancer cell-derived exosomes.•Thrombospondin 1 inhibits exosome-induced lung cancer cell migration and invasion.
Triple-negative breast cancer (TNBC) patients usually lead to poor prognosis and survival because of metastasis. The major sites for TNBC metastasis include the lungs, brain, liver, and bone. Long ...non-coding RNAs (lncRNAs) are non-protein-coding transcripts longer than 200 nucleotides and have been reported as important regulators in BC metastasis. However, the underlying mechanisms for lncRNAs regulating TNBC metastasis are not fully understood. Here we found that linc-ZNF469-3 was highly expressed in lung-metastatic LM2-4175 TNBC cells and overexpression of linc-ZNF469-3 enhanced invasion ability and stemness properties in vitro and lung metastasis in vivo. Furthermore, we found linc-ZNF469-3 physically interacted with miR-574-5p and overexpression of miR-574-5p attenuated ZEB1 expression. Importantly, endogenous high expressions of linc-ZNF469-3 and ZEB1 were correlated with tumor recurrence in TNBC patients with lung metastasis. Taken together, our findings suggested that linc-ZNF469-3 promotes lung metastasis of TNBC through miR-574-5p-ZEB1 signaling axis and may be used as potential prognostic marker for TNBC patients.
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