CRCDB: A comprehensive database for integrating and analyzing multi-omics data of early-onset and late-onset colorectal cancer.

The incidence of early-onset colorectal cancer (EOCRC) has increased significantly worldwide. Uncovering biomarkers that are unique to EOCRC is of great importance to facilitate the prevention and detection of this growing cancer subtype. Although efforts have been made in the data curation about CRC, there is no integrated platform that gives access to data specifically related to young CRC patients. Here, we constructed a user-friendly open integrated resource called CRCDB (URL: http://crcdb-hust.com) which contains multi-omics data of 785 EOCRC, 4898 late-onset CRCs (LOCRC), and 1110 normal control samples from tissue, whole blood, platelets, and serum exosomes. CRCDB manages the differential analysis, survival analysis, co-expression analysis, and immune cell infiltration comparison analysis results in different CRC groups. Meta-analysis results were also provided for users for further data interpretation. Using the resource in CRCDB, we identified that genes associated with the metabolic process were less expressed in EOCRC patients, while up regulated genes most associated with the mitosis process might play an important role in the molecular pathogenesis of LOCRC. Survival-related genes were most enriched in oxidoreduction pathways in EOCRC while in immune-related pathways in LOCRC. With all the data gathered and processed, we anticipate that CRCDB could be a practical data mining platform to help explore potential applications of omics data and develop effective prevention and therapeutic strategies for the specific group of CRC patients.

Ligand-Directed Shape Reconfiguration in Inorganic Materials.

Polymer elastomers with reversible shape-changing capability have led to significant development of artificial muscles, functional devices, and soft robots. By contrast, reversible shape transformation of inorganic nanoparticles is notoriously challenging due to their relatively rigid lattice structure. Here, the authors demonstrate the synthesis of shape-changing nanoparticles via an asymmetrical surface functionalization process. Various ligands are investigated, revealing the essential role of steric hindrance from the functional groups. By controlling the unbalanced structural hindrance on the surface, the as-prepared clay nanoparticles can transform their shape in a fast, facile, and reversible manner. In addition, such flexible morphology-controlled mechanism provides a platform for developing self-propelled shape-shifting nanocollectors. Owing to the ion-exchanging capability of clay, these self-propelled nanoswimmers (NS) are able to autonomously adsorb rare earth elements with ultralow concentration, indicating the feasibility of using naturally occurring materials for self-powered nanomachine.

Deep Learning Dual Neural Networks in the Construction of Learning Models for Online Courses in Piano Education.

The use of deep learning (DL) and artificial intelligence (AI) in teaching children piano lessons promotes modern piano instruction and enhances the overall quality of education. To begin, a more thorough explanation of the teaching environment and the intelligent piano's features is provided. Then, a method for detecting the onset of a piano note using a Dual Neural Network (DNN) is proposed. By transforming the original time-domain waveform of the piano music signal into a frequency distribution that changes with time, the network can analyze the input signal's time-frequency. Finally, the intelligent piano teaching method combines deep learning with artificial intelligence (AI) to produce the best possible results for students learning the piano instrument. For children and their parents alike, it is a favorite, and it significantly impacts their interests. The proposed model has a 94% overall accuracy rate.

Silk sericin patches delivering miRNA-29-enriched extracellular vesicles-decorated myoblasts (SPEED) enhances regeneration and functional repair after severe skeletal muscle injury.

Severe skeletal muscle injuries usually lead to a series of poor recovery issues, such as massive myofibers loss, scar tissue formation, significant muscle function impairment, etc. Here, a silk sericin patch delivering miRNA-29-enriched extracellular vesicles-decorated myoblasts (SPEED) is designed for the rapid regeneration and functional repair after severe skeletal muscle injury. Specifically, miR29-enriched extracellular vesicles (miR29-EVs) are prepared and used to deliver miR29 into primary myoblasts, which promote the myotube formation of myoblasts and increase the expression of myogenic genes while inhibiting the expression of fibrotic genes. Our results indicate that miR29-EVs promote the integration of primary myoblasts and host muscle in a severe mouse tibialis anterior (TA) muscle injury model. Moreover, implantation of SPEED drastically stimulates skeletal muscle regeneration, inhibits fibrosis of injured muscles, and leads to significant improvement of muscle contraction forces and motor ability of mice about 3 weeks after treatment. Subsequently, we further evaluate the transcriptomes of TA muscles and find that SPEED can significantly ameliorate energy metabolism and muscular microenvironment of TA muscles on day 9 after implantation. Additionally, bioinformatic analysis and comprehensive molecular biology studies also reveal that the down-regulation of CDC20-MEF2C signaling axis may participate in the muscle repair process. Together, SPEED may serve as an effective alternative for the rapid repair of severe skeletal muscle injuries in the future.

PltDB: a blood platelets-based gene expression database for disease investigation.

MOTIVATION: Molecular profiling of blood-based liquid biopsies is a promising disease detection method, which overcomes the limitations of invasive diagnostic strategies. Recently, gene expression profiling of platelets reportedly provides valuable resource for developing new biomarkers for the detection of diseases, including cancer. However, there is no database containing RNAs in platelets. RESULTS: In this study, we constructed PltDB (http://www.pltdb-hust.com), a blood platelets-based gene expression database featuring integration and visualization of RNA expression profiles based on RNA-seq and microarray data spanning both normal individuals and patients with different diseases. PltDB currently contains the expression landscape of mRNAs, lncRNAs, circRNAs and miRNAs in platelets from patients with different disease types and healthy controls. Moreover, PltDB provides users with the tools for visualizing results of comparison and correlation analysis and for downloading expression profiles and analysis results. A submission interface for the scientific community is also embraced for uploading novel RNA expression profiles derived from platelet samples. PltDB will offer a comprehensive review of the clinical use of platelets, overcome technical problems when analyzing data from diverse studies and serve as a powerful platform for developing new blood biomarkers. AVAILABILITY AND IMPLEMENTATION: PltDB is accessible at http://www.pltdb-hust.com. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

RNA profiling of blood platelets noninvasively differentiates colorectal cancer from healthy donors and noncancerous intestinal diseases: a retrospective cohort study.

BACKGROUND: The RNA profiles of tumor-educated platelets (TEPs) possess pathological features that could be used for early cancer detection. However, the utility of TEP RNA profiling in detecting early colorectal cancer (CRC) versus noncancerous colorectal diseases has not yet been investigated. This study assesses the diagnostic capacity of TEP RNA profiles in a cohort of patients with CRC and noncancerous diseases. METHODS: Transcriptome sequencing for platelets isolated from 132 patients with CRC at early and late stages and 190 controls consisting of healthy donors and patients with ulcerative disease, Crohn's disease, polyps, and adenomas was performed and analyzed using binary particle swarm optimization coupled with support vector machine to identify genes that contributed to the classification of CRC patients versus controls. The area under the receiver operating curves (AUROCs) and the accuracy of TEP RNA profiles in CRC diagnosis were assessed. RESULTS: TEP RNA profiling achieved high performance in distinguishing and staging CRC patients from the controls. Using the swarm intelligence algorithm, the 921 most contributive genes that classified CRC patients from the controls were identified. AUROCs of 0.928 for the training set via leave-one-out cross-validation and 0.92 for the validation set were achieved, both of which were significantly higher than the clinically utilized serum biomarkers: carcinoembryonic antigen and cancer antigen 19-9. Notably, an AUROC of 0.915 in an external validation set was achieved. For predicting different CRC stages, an AUROC of 0.984 was achieved in the training set and 1.000 in the internal validation set. CONCLUSIONS: RNA profiles of TEPs are of potential diagnostic value for identifying early CRC from noncancerous diseases. Prospective studies are needed to validate its clinical relevance.

Anti-Fogging, Frost-Resistant transparent and flexible silver Nanowire-Ti3C2Tx MXene based composite films for excellent electromagnetic interference shielding ability.

The development of electronics proposes higher requirements for flexible, transparent, and conductive materials with high electromagnetic shielding performance in viewing windows. Flexible transparent films have been fabricated by collaborating one-dimensional silver nanowires (AgNWs) and novel two-dimensional Ti3C2Tx MXene sheets on PET films with an external polymeric coating consisting of poly (vinyl alcohol) (PVA) and poly(styrene sulfonate) (PSS). Especially, the combination of different dimensional nanomaterials effectively establishes a conductive network that exhibits a synergistic effect on excellent electromagnetic interference (EMI) shielding performance, which is superior to that of pure AgNW network or Ti3C2Tx network to some extent. By optimizing the AgNWs content (0.05 mg/cm2) and Ti3C2Tx sheets content (0.01 mg/cm2), the PET/AgNW/Ti3C2Tx/PVA-PSS film exhibits a transmittance of 81% and a desirable EMI SE value of 30.5 dB. In addition, the film shows outstanding anti-fogging and frost-resistant properties due to the remarkable water absorption capacity of PVA and PSS on the external surface. Considering its efficiency and simplicity, this transparent conductive film has promising applications in flexible transparent electronic devices and optical related fields.

Engineered two-dimensional nanomaterials: an emerging paradigm for water purification and monitoring.

Water scarcity has become an increasingly complex challenge with the growth of the global population, economic expansion, and climate change, highlighting the demand for advanced water treatment technologies that can provide clean water in a scalable, reliable, affordable, and sustainable manner. Recent advancements on 2D nanomaterials (2DM) open a new pathway for addressing the grand challenge of water treatment owing to their unique structures and superior properties. Emerging 2D nanostructures such as graphene, MoS2, MXene, h-BN, g-C3N4, and black phosphorus have demonstrated an unprecedented surface-to-volume ratio, which promises ultralow material use, ultrafast processing time, and ultrahigh treatment efficiency for water cleaning/monitoring. In this review, we provide a state-of-the-art account on engineered 2D nanomaterials and their applications in emerging water technologies, involving separation, adsorption, photocatalysis, and pollutant detection. The fundamental design strategies of 2DM are discussed with emphasis on their physicochemical properties, underlying mechanism and targeted applications in different scenarios. This review concludes with a perspective on the pressing challenges and emerging opportunities in 2DM-enabled wastewater treatment and water-quality monitoring. This review can help to elaborate the structure-processing-property relationship of 2DM, and aims to guide the design of next-generation 2DM systems for the development of selective, multifunctional, programmable, and even intelligent water technologies. The global significance of clean water for future generations sheds new light and much inspiration in this rising field to enhance the efficiency and affordability of water treatment and secure a global water supply in a growing portion of the world.

Open resource of clinical data from patients with pneumonia for the prediction of COVID-19 outcomes via deep learning.

Data from patients with coronavirus disease 2019 (COVID-19) are essential for guiding clinical decision making, for furthering the understanding of this viral disease, and for diagnostic modelling. Here, we describe an open resource containing data from 1,521 patients with pneumonia (including COVID-19 pneumonia) consisting of chest computed tomography (CT) images, 130 clinical features (from a range of biochemical and cellular analyses of blood and urine samples) and laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clinical status. We show the utility of the database for prediction of COVID-19 morbidity and mortality outcomes using a deep learning algorithm trained with data from 1,170 patients and 19,685 manually labelled CT slices. In an independent validation cohort of 351 patients, the algorithm discriminated between negative, mild and severe cases with areas under the receiver operating characteristic curve of 0.944, 0.860 and 0.884, respectively. The open database may have further uses in the diagnosis and management of patients with COVID-19.

Eosinopenia and elevated C-reactive protein facilitate triage of COVID-19 patients in fever clinic: A retrospective case-control study.

BACKGROUND: Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a pandemic affecting over 200 countries. Many cities have established designated fever clinics to triage suspected COVID-19 patients from other patients with similar symptoms. However, given the limited availability of the nucleic acid test as well as long waiting time for both the test and radiographic examination, the quarantine or therapeutic decisions for a large number of mixed patients were often not made in time. We aimed to identify simple and quickly available laboratory biomarkers to facilitate effective triage at the fever clinics for sorting suspected COVID-19 patients from those with COVID-19-like symptoms. METHODS: We collected clinical, etiological, and laboratory data of 989 patients who visited the Fever Clinic at Wuhan Union Hospital, Wuhan, China, from Jan 31 to Feb 21. Based on polymerase chain reaction (PCR) nucleic acid testing for SARS-CoV-2 infection, they were divided into two groups: SARS-CoV-2-positive patients as cases and SARS-CoV-2-negative patients as controls. We compared the clinical features and laboratory findings of the two groups, and analyzed the diagnostic performance of several laboratory parameters in predicting SARS-CoV-2 infection and made relevant comparisons to the China diagnosis guideline of having a normal or decreased number of leukocytes (≤9·5 109/L) or lymphopenia (<1·1 109/L). FINDINGS: Normal or decreased number of leukocytes (≤9·5 109/L), lymphopenia (<1·1 109/L), eosinopenia (<0·02 109/L), and elevated hs-CRP (≥4 mg/L) were presented in 95·0%, 52·2%, 74·7% and 86·7% of COVID-19 patients, much higher than 87·2%, 28·8%, 31·3% and 45·2% of the controls, respectively. The eosinopenia produced a sensitivity of 74·7% and specificity of 68·7% for separating the two groups with the area under the curve (AUC) of 0·717. The combination of eosinopenia and elevated hs-CRP yielded a sensitivity of 67·9% and specificity of 78·2% (AUC=0·730). The addition of eosinopenia alone or the combination of eosinopenia and elevated hs-CRP into the guideline-recommended diagnostic parameters for COVID-19 improved the predictive capacity with higher than zero of both net reclassification improvement (NRI) and integrated discrimination improvement (IDI). INTERPRETATION: The combination of eosinopenia and elevated hs-CRP can effectively triage suspected COVID-19 patients from other patients attending the fever clinic with COVID-19-like initial symptoms. This finding would be particularly useful for designing triage strategies in an epidemic region having a large number of patients with COVID-19 and other respiratory diseases while limited medical resources for nucleic acid tests and radiographic examination.

Colorectal Cancer Metastases to Brain or Bone and the Relationship to Primary Tumor Location: a Population-Based Study.

BACKGROUND: The association of primary tumor location with incidence and prognosis of brain or bone metastasis in metastatic colorectal cancer (mCRC) patients remains unclear. We dissect this association across a large population. METHODS: A total of 202,401 CRC patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 were included. For brain metastasis, 9478 cases without brain metastasis information were excluded, leaving 192,923 CRC for incidence analysis and multivariable logistic/Cox regression analyses. Similarly, 193,013 CRC were eligible for bone metastasis analyses. RESULTS: The incidence of brain or bone metastasis at initial diagnosis was 1.38% and 6.12% in mCRC cohort, respectively. Median survival of CRC patients with brain or bone metastasis was 4 and 5 months, respectively. Primary tumor location is not associated with the incidence of brain metastasis but with bone metastasis. For bone metastasis, right-sided colon cancer (RCC) patients exhibited the lowest incidence, whereas rectal cancer (RC) patients had the highest. For both brain and bone metastases, RCC patients always had the shortest median survival, whereas RC patients had the longest. The common risk factors for brain or bone metastasis were grade III and multi-extracerebral or ectosteal metastases. The favorable prognostic factors for brain or bone metastasis were being female, married, insured, and RC. RCC is an unfavorable prognostic factor. CONCLUSIONS: Primary tumor location impacts incidence proportions of bone metastasis and survival of both brain and bone mCRC patients. Primary tumor location should be taken into consideration in clinical practice and prognostic assessment.

Incidence and prognosis of pulmonary metastasis in colorectal cancer: a population-based study.

PURPOSE: It is unclear how primary tumor location affects the pulmonary metastasis in colorectal cancer patients with different primary tumor locations. We aim to explore the relationship between primary tumor location and the incidence and prognosis of colorectal cancer patients with pulmonary metastasis at diagnosis. METHODS: From Surveillance, Epidemiology, and End Results (SEER) database, 9920 out of 192,969 CRC patients were identified with pulmonary metastasis at diagnosis between 2010 and 2015. Patients were classified into three subsets according to primary tumor location. The incidence of pulmonary metastasis and median survival were calculated. Multivariable logistic and Cox regression were performed to identify the risk factors of pulmonary metastasis and prognosis. RESULTS: The incidence of pulmonary metastasis was 5.14% in the entire colorectal cancer cohort and 25.66% in metastatic colorectal cancer patients. The median survival of those patients was 10 months. Rectal cancer patients exhibited the highest incidence of pulmonary metastasis, while they had the longest median survival (15 months). The right-sided colon cancer patients had the lowest incidence of pulmonary metastasis, but the shortest median survival (8 months). 61 to 80 years old, over 80, black, two or three extrapulmonary metastatic sites and CEA-positive had a negative influence both on the incidence and prognosis. CONCLUSIONS: The importance of primary tumor location in affecting the incidence of pulmonary metastasis and prognosis of colorectal cancer patients was highlighted in this study. Primary tumor location should be considered in clinical interference and personalized treatment for colorectal cancer patients with pulmonary metastasis.

A gold-nanodot-decorated hollow carbon nanosphere based nanoplatform for intracellular miRNA imaging in colorectal cancer cells.

We report a new biofunctionalized nanoplatform based on hyaluronic acid-coated gold-nano-dot-decorated hollow carbon nanospheres (AuHCNs-HA) for microRNA imaging in living cells. Importantly, the HA-coated nanoplatform could be internalized into target cells via CD44 receptor-mediated endocytosis. It can be further applied for intracellular miR-21 imaging in CD44-positive colorectal cancer cells.

Iridescence in nematics: Photonic liquid crystals of nanoplates in absence of long-range periodicity.

Photonic materials with positionally ordered structure can interact strongly with light to produce brilliant structural colors. Here, we found that the nonperiodic nematic liquid crystals of nanoplates can also display structural color with only significant orientational order. Owing to the loose stacking of the nematic nanodiscs, such colloidal dispersion is able to reflect a broad-spectrum wavelength, of which the reflection color can be further enhanced by adding carbon nanoparticles to reduce background scattering. Upon the addition of electrolytes, such vivid colors of nematic dispersion can be fine-tuned via electrostatic forces. Furthermore, we took advantage of the fluidity of the nematic structure to create a variety of colorful arts. It was expected that the concept of implanting nematic features in photonic structure of lyotropic nanoparticles may open opportunities for developing advanced photonic materials for display, sensing, and art applications.

Electrostatic-Driven Dynamic Jamming of 2D Nanoparticles at Interfaces for Controlled Molecular Diffusion.

Dynamically engineering the interfacial interaction of nanoparticles has emerged as a new approach for bottom-up fabrication of smart systems to tailor molecular diffusion and controlled release. Janus zwitterionic nanoplates are reported that can be switched between a locked and unlocked state at interfaces upon changing surface charge, allowing manipulation of interfacial properties in a fast, flexible, and switchable manner. Combining experimental and modeling studies, an unambiguous correlation is established among the electrostatic energy, the interface geometry, and the interfacial jamming states. As a proof-of-concept, the well-controlled interfacial jamming of nanoplates enabled the switchable molecular diffusion through liquid-liquid interfaces, confirming the feasibility of using nanoparticle-based surfactants for advanced controlled release.

Toxicity evaluation of boron nitride nanospheres and water-soluble boron nitride in Caenorhabditis elegans.

Boron nitride (BN) nanomaterials have been increasingly explored for potential biological applications. However, their toxicity remains poorly understood. Using Caenorhabditis elegans as a whole-animal model for toxicity analysis of two representative types of BN nanomaterials - BN nanospheres (BNNSs) and highly water-soluble BN nanomaterial (named BN-800-2) - we found that BNNSs overall toxicity was less than soluble BN-800-2 with irregular shapes. The concentration thresholds for BNNSs and BN-800-2 were 100 µg·mL-1 and 10 µg·mL-1, respectively. Above this concentration, both delayed growth, decreased life span, reduced progeny, retarded locomotion behavior, and changed the expression of phenotype-related genes to various extents. BNNSs and BN-800-2 increased oxidative stress levels in C. elegans by promoting reactive oxygen species production. Our results further showed that oxidative stress response and MAPK signaling-related genes, such as GAS1, SOD2, SOD3, MEK1, and PMK1, might be key factors for reactive oxygen species production and toxic responses to BNNSs and BN-800-2 exposure. Together, our results suggest that when concentrations are lower than 10 µg·mL-1, BNNSs are more biocompatible than BN-800-2 and are potentially biocompatible material.

Live-cell confocal microscopy and quantitative 4D image analysis of anchor-cell invasion through the basement membrane in Caenorhabditis elegans.

Cell invasion through basement membrane (BM) barriers is crucial in development, leukocyte trafficking and the spread of cancer. The mechanisms that direct invasion, despite their importance in normal and disease states, are poorly understood, largely because of the inability to visualize dynamic cell-BM interactions in vivo. This protocol describes multichannel time-lapse confocal imaging of anchor-cell invasion in live Caenorhabditis elegans. Methods presented include outline-slide preparation and worm growth synchronization (15 min), mounting (20 min), image acquisition (20-180 min), image processing (20 min) and quantitative analysis (variable timing). The acquired images enable direct measurement of invasive dynamics including formation of invadopodia and cell-membrane protrusions, and removal of BM. This protocol can be combined with genetic analysis, molecular-activity probes and optogenetic approaches to uncover the molecular mechanisms underlying cell invasion. These methods can also be readily adapted by any worm laboratory for real-time analysis of cell migration, BM turnover and cell-membrane dynamics.

MIG-10 (Lamellipodin) stabilizes invading cell adhesion to basement membrane and is a negative transcriptional target of EGL-43 in C. elegans.

Cell invasion through basement membrane (BM) occurs in many physiological and pathological contexts. MIG-10, the Caenorhabditis elegans Lamellipodin (Lpd), regulates diverse biological processes. Its function and regulation in cell invasive behavior remain unclear. Using anchor cell (AC) invasion in C. elegans as an in vivo invasion model, we have previously found that mig-10's activity is largely outside of UNC-6 (netrin) signaling, a chemical cue directing AC invasion. We have shown that MIG-10 is a target of the transcription factor FOS-1A and facilitates BM breaching. Combining genetics and imaging analyses, we report that MIG-10 synergizes with UNC-6 to promote AC attachment to the BM, revealing a functional role for MIG-10 in stabilizing AC-BM adhesion. MIG-10 is also required for F-actin accumulation in the absence of UNC-6. Further, we identify mig-10 as a transcriptional target negatively regulated by EGL-43A (C. elegans Evi-1 proto-oncogene), a transcription factor positively controlled by FOS-1A. The revelation of this negative regulation unmasks an incoherent feedforward circuit existing among fos-1, egl-43 and mig-10. Moreover, our study suggests the functional importance of the negative regulation on mig-10 expression by showing that excessive MIG-10 impairs AC invasion. Thus, we provide new insight into MIG-10's function and its complex transcriptional regulation during cell invasive behavior.