MicroRNAs (miRNAs), small non-coding RNAs, can regulate post-transcriptional gene expressions and silence a broad set of target genes. miRNAs, aberrantly expressed in cancer cells, play an important ...role in modulating gene expressions, thereby regulating downstream signaling pathways and affecting cancer formation and progression. Oncogenes or tumor suppressor genes regulated by miRNAs mediate cell cycle progression, metabolism, cell death, angiogenesis, metastasis and immunosuppression in cancer. Recently, miRNAs have emerged as therapeutic targets or tools and biomarkers for diagnosis and therapy monitoring in cancer. Since miRNAs can regulate multiple cancer-related genes simultaneously, using miRNAs as a therapeutic approach plays an important role in cancer therapy. However, one of the major challenges of miRNA-based cancer therapy is to achieve specific, efficient and safe systemic delivery of therapeutic miRNAs in vivo. This review discusses the key challenges to the development of the carriers for miRNA-based therapy and explores current strategies to systemically deliver miRNAs to cancer without induction of toxicity.
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The pandemic of coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has caused an unprecedented global social and economic impact, and ...high numbers of deaths. Many risk factors have been identified in the progression of COVID‐19 into a severe and critical stage, including old age, male gender, underlying comorbidities such as hypertension, diabetes, obesity, chronic lung diseases, heart, liver and kidney diseases, tumors, clinically apparent immunodeficiencies, local immunodeficiencies, such as early type I interferon secretion capacity, and pregnancy. Possible complications include acute kidney injury, coagulation disorders, thoromboembolism. The development of lymphopenia and eosinopenia are laboratory indicators of COVID‐19. Laboratory parameters to monitor disease progression include lactate dehydrogenase, procalcitonin, high‐sensitivity C‐reactive protein, proinflammatory cytokines such as interleukin (IL)‐6, IL‐1β, Krebs von den Lungen‐6 (KL‐6), and ferritin. The development of a cytokine storm and extensive chest computed tomography imaging patterns are indicators of a severe disease. In addition, socioeconomic status, diet, lifestyle, geographical differences, ethnicity, exposed viral load, day of initiation of treatment, and quality of health care have been reported to influence individual outcomes. In this review, we highlight the scientific evidence on the risk factors of severity of COVID‐19.
Background
Coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has been widely spread. We aim to investigate the clinical ...characteristic and allergy status of patients infected with SARS‐CoV‐2.
Methods
Electronic medical records including demographics, clinical manifestation, comorbidities, laboratory data, and radiological materials of 140 hospitalized COVID‐19 patients, with confirmed result of SARS‐CoV‐2 viral infection, were extracted and analyzed.
Results
An approximately 1:1 ratio of male (50.7%) and female COVID‐19 patients was found, with an overall median age of 57.0 years. All patients were community‐acquired cases. Fever (91.7%), cough (75.0%), fatigue (75.0%), and gastrointestinal symptoms (39.6%) were the most common clinical manifestations, whereas hypertension (30.0%) and diabetes mellitus (12.1%) were the most common comorbidities. Drug hypersensitivity (11.4%) and urticaria (1.4%) were self‐reported by several patients. Asthma or other allergic diseases were not reported by any of the patients. Chronic obstructive pulmonary disease (COPD, 1.4%) patients and current smokers (1.4%) were rare. Bilateral ground‐glass or patchy opacity (89.6%) was the most common sign of radiological finding. Lymphopenia (75.4%) and eosinopenia (52.9%) were observed in most patients. Blood eosinophil counts correlate positively with lymphocyte counts in severe (r = .486, P < .001) and nonsevere (r = .469, P < .001) patients after hospital admission. Significantly higher levels of D‐dimer, C‐reactive protein, and procalcitonin were associated with severe patients compared to nonsevere patients (all P < .001).
Conclusion
Detailed clinical investigation of 140 hospitalized COVID‐19 cases suggests eosinopenia together with lymphopenia may be a potential indicator for diagnosis. Allergic diseases, asthma, and COPD are not risk factors for SARS‐CoV‐2 infection. Older age, high number of comorbidities, and more prominent laboratory abnormalities were associated with severe patients.
Decreased eosinophil count, which was positively correlated with lymphocyte counts, may be a potential biological indicator for diagnosing
COVID‐19 patients. Low prevalence of allergic diseases, COPD and patients with smoking history indicated they may not be the predisposing
factors of COVID‐19. Elder age, high number of comorbidities and more prominent laboratory abnormalities were associated with severe
patientsz.
Intelligent fault diagnosis methods based on signal analysis have been widely used for bearing fault diagnosis. These methods use a pre-determined transformation (such as empirical mode ...decomposition, fast Fourier transform, discrete wavelet transform) to convert time-series signals into frequency domain signals, the performance of dignostic system is significantly rely on the extracted features. However, extracting signal characteristic is fairly time consuming and depends on specialized signal processing knowledge. Although some studies have developed highly accurate algorithms, the diagnostic results rely heavily on large data sets and unreliable human analysis. This study proposes an automatic feature learning neural network that utilizes raw vibration signals as inputs, and uses two convolutional neural networks with different kernel sizes to automatically extract different frequency signal characteristics from raw data. Then long short-term memory was used to identify the fault type according to learned features. The data is down-sampled before inputting into the network, greatly reducing the number of parameters. The experiment shows that the proposed method can not only achieve 98.46% average accuracy, exceeding some state-of-the-art intelligent algorithms based on prior knowledge and having better performance in noisy environments.
Background and aims
The outbreak of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has recently spread worldwide and been ...declared a pandemic. We aim to describe here the various clinical presentations of this disease by examining eleven cases.
Methods
Electronic medical records of 11 patients with COVID‐19 were collected, and demographics, clinical manifestations, outcomes, key laboratory results, and radiological images are discussed.
Results
The clinical course of the eleven cases demonstrated the complexity of the COVID‐19 profile with different clinical presentations. Clinical manifestations range from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Laboratory detection of the viral nucleic acid can yield false‐negative results, and serological testing of virus‐specific IgG and IgM antibodies should be used as an alternative for diagnosis. Patients with common allergic diseases did not develop distinct symptoms and severe courses. Cases with a pre‐existing condition of chronic obstructive pulmonary disease or complicated with a secondary bacterial pneumonia were more severe.
Conclusion
All different clinical characteristics of COVID‐19 should be taken into consideration to identify patients that need to be in strict quarantine for the efficient containment of the pandemic.
Clinical manifestations of COVID‐19 range from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Laboratory detection of the viral nucleic acid can yield false‐negative results, and serological testing of virus‐specific IgG and IgM antibodies should be used as an alternative for diagnosis. Patients with common allergic diseases did not develop distinct symptoms and severe courses. Cases with a pre‐existing condition of chronic obstructive pulmonary disease or complicated with a secondary bacterial pneumonia were more severe.
Recently, the dysregulation of circular RNA (circRNA) have been shown to have important regulatory roles in cancer development and progression, including hepatocellular carcinoma (HCC). However, the ...roles of most circRNAs in HCC are still unknown.
The expression of circular tripartite motif containing 33-12 (circTRIM33-12) in HCC tissues and cell lines was detected by qRT-PCR. The role of circTRIM33-12 in HCC progression was assessed by western blotting, CCK-8, flow cytometry, transwell and a subcutaneous tumor mouse assays both in vitro and in vivo. In vivo circRNA precipitation, RNA immunoprecipitation, luciferase reporter assays were performed to evaluate the interaction between circTRIM33-12 and miR-191.
Here, we found that circTRIM33-12, is downregulated in HCC tissues and cell lines. The downregulation of circTRIM33-12 in HCC was significantly correlated with malignant characteristics and served as an independent risk factor for the overall survival (OS) and recurrence-free survival (RFS) of patients with HCC after surgery. The reduced expression of circTRIM33-12 in HCC cells increases tumor proliferation, migration, invasion and immune evasion. Mechanistically, we demonstrated that circTRIM33-12 upregulated TET1 expression by sponging miR-191, resulting in significantly reduced 5-hydroxymethylcytosine (5hmC) levels in HCC cells.
These results reveal the important role of circTRIM33-12 in the proliferation, migration, invasion and immune evasion abilities of HCC cells and provide a new perspective on circRNAs in HCC progression.
Image steganography based on intelligent devices is one of the effective routes for safely and quickly transferring secret information. However, optical image steganography has attracted far less ...attention than digital one due to the state‐of‐the‐art technology limitations of high‐resolution optical imaging in integrated devices. Optical metasurfaces, composed of ultrathin subwavelength meta‐atoms, are extensively considered for flat optical‐imaging nano‐components with high‐resolutions as competitive candidates for next‐generation miniaturized devices. Here, multiplex imaging metasurfaces composed of single nanorods are proposed under a detailed strategy to realize optical image steganography. The simulation and experimental results demonstrate that an optical steganographic metasurface can simultaneously transfer independent secret image information to two receivers with special keys, without raising suspicions for the general public under the cloak of a cover image. The proposed optical steganographic strategy by metasurfaces can arbitrarily distribute a continuous grayscale image together with a black‐and‐white image in separate channels, implying the distinguishing feature of high‐density information capacity for integration and miniaturization in optical meta‐devices.
Optical image steganography, a technique for hiding information, leads a primary role in securely transferring secret images to receivers on a public channel without raising suspicions. A brand‐new strategy using an ultrathin metasurface can obtain multiplexing image steganography that embeds two secret images into a cover image for independently transferring to different receivers as a kind of miniatured meta‐devices.
For rapid response against the prevailing COVID‐19 (coronavirus disease 19), it is a global imperative to exploit the immunogenicity of existing formulations for safe and efficient vaccines. As the ...most accessible adjuvant, aluminum hydroxide (alum) is still the sole employed adjuvant in most countries. However, alum tends to attach on the membrane rather than entering the dendritic cells (DCs), leading to the absence of intracellular transfer and process of the antigens, and thus limits T‐cell‐mediated immunity. To address this, alum is packed on the squalene/water interphase is packed, forming an alum‐stabilized Pickering emulsion (PAPE). “Inheriting” from alum and squalene, PAPE demonstrates a good biosafety profile. Intriguingly, with the dense array of alum on the oil/water interphase, PAPE not only adsorbs large quantities of SARS‐CoV‐2 (severe acute respiratory syndrome coronavirus 2) antigens, but also harbors a higher affinity for DC uptake, which provokes the uptake and cross‐presentation of the delivered antigens. Compared with alum‐treated groups, more than six times higher antigen‐specific antibody titer and three‐fold more IFN‐γ‐secreting T cells are induced, indicating the potent humoral and cellular immune activations. Collectively, the data suggest that PAPE may provide potential insights toward a safe and efficient adjuvant platform for the enhanced COVID‐19 vaccinations.
The adjuvant‐effect of the licensed alum adjuvant by particulate alum via Pickering emulsion (PAPE) is exploited toward enhanced COVID‐19 vaccines. PAPE mirrors and “inherits” the acknowledged biosafety profile. Additionally, the alum‐packed interphase confers higher affinity for dendritic cell uptake, which provokes the uptake and cross‐presentation of antigens for potent humoral and cellular responses.
Intramyocardial injection of hydrogels offers great potential for treating myocardial infarction (MI) in a minimally invasive manner. However, traditional bulk hydrogels generally lack microporous ...structures to support rapid tissue ingrowth and biochemical signals to prevent fibrotic remodeling toward heart failure. To address such challenges, a novel drug‐releasing microporous annealed particle (drugMAP) system is developed by encapsulating hydrophobic drug‐loaded nanoparticles into microgel building blocks via microfluidic manufacturing. By modulating nanoparticle hydrophilicity and pregel solution viscosity, drugMAP building blocks are generated with consistent and homogeneous encapsulation of nanoparticles. In addition, the complementary effects of forskolin (F) and Repsox (R) on the functional modulations of cardiomyocytes, fibroblasts, and endothelial cells in vitro are demonstrated. After that, both hydrophobic drugs (F and R) are loaded into drugMAP to generate FR/drugMAP for MI therapy in a rat model. The intramyocardial injection of MAP gel improves left ventricular functions, which are further enhanced by FR/drugMAP treatment with increased angiogenesis and reduced fibrosis and inflammatory response. This drugMAP platform represents a new generation of microgel particles for MI therapy and will have broad applications in regenerative medicine and disease therapy.
A novel multimodal drug‐releasing granular microstructured hydrogel system (drugMAP), created from microfluidically generated building blocks, can decouple mechanical support and rapid tissue ingrowth, and endow various pharmacological functions. The drugMAP loaded with the drugs forskolin and Repsox enhance left ventricular function after local injection into infarcted hearts.
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