Melanoma is a malignant tumor that accounts for the deadliest form of skin cancers. Despite the significant efforts made recently for development of immunotherapeutic strategies including using ...immune checkpoint inhibitors and cancer vaccines, the clinical outcomes are unsatisfying. Different factors affect efficient cancer immunotherapy such as side-effects, immunosuppressive tumor microenvironment, and tumor heterogeneity. In the past decades, various nanotechnology-based approaches have been developed to enhance the efficacy of cancer immunotherapy, in addition to diminishing the toxicity associated with it. Several studies have shown that proper application of nanomaterials can revolutionize the outcome of immunotherapy in diverse melanoma models. This review summarizes the recent advancement in the integration of nanotechnology and cancer immunotherapy in melanoma treatment. The importance of nanomaterials and their therapeutic advantages for patients with melanoma are also discussed.
Simultaneous delivery of tumor antigens and adjuvants to antigen presenting cells via nanoparticles activates T cells to attack cancer cells. This causes cancer cell death and release of tumor antigens into the tumor microenvironment, further stimulating the immune system. Display omitted
•Nanoparticles can diminish toxicity associated with free immunotherapeutic drug administration.•Delivery of nanoparticle-based vaccine can elicit a strong immune response against cancer cells.•Nanoparticle-based combination therapies can produce more effective therapeutic results.
Enteroviruses (EVs) are the most common human pathogens worldwide. Recent international outbreaks in North America and South East Asia have emphasized the need for more effective anti-viral ...therapies. As obligate parasites, EVs rely on the host cellular machinery for effective viral propagation. Accumulating evidence has indicated that EVs subvert and disrupt the cellular autophagy pathway to facilitate productive infection, and consequently leading to host pathogenesis. Given that defective autophagy is a common factor in various human diseases, including neurodegeneration, cardiomyopathy, and metabolic disorders, a clear understanding of the relationship between EV infection and autophagy is warranted. In this review, we highlight recent advances in understanding the molecular mechanisms by which EVs exploit the autophagy pathway during different steps of viral life cycle, from entry, replication, and maturation to release. We also provide an overview of recent progress in EV subversion of the autophagy for immune evasion.
Graphene-based nanocarriers not only possess large specific surface area but also prevent drugs from premature release outside the target cells. However, agglomeration in aqueous solution is a ...critical challenge. In this work, graphene oxide (GO) was uniformly embedded into the three-dimensional (3D) porous network of bacterial cellulose (BC) to form a novel BC/GO nanocomposite drug nanocarrier. For the first time, ibuprofen (IBU) was loaded onto the BC/GO nanocomposites. Scanning electron microscope (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) reveal the successful drug loading onto BC/GO nanocomposites. In vitro drug release studies indicate that the drug release of IBU@BC/GO follows a non-Fickian diffusion mechanism. Another important feature of this BC/GO nanocarrier is its better cell viability in comparison to BC. It is believed that this new nanocarrier is a potential choice for drug delivery system.
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•Graphene oxide (GO) was incorporated into 3D porous bacterial cellulose (BC).•Incorporation of GO into BC greatly increases the drug loading capacity of BC.•The BC/GO nanocarrier shows better cell viability than BC does.
In this work, biocompatibility of bacterial cellulose (BC) was assessed as the scaffold for corneal stroma replacement. Biocompatibility was evaluated by examining rabbit corneal epithelial and ...stromal cells cultured on the BC scaffold. The growth of primary cells was assessed by optical microscope, scanning electron microscope (SEM), and transmission electron microscope (TEM). Live/dead viability/cytotoxicity assay and CCK-8 assay were used to evaluate cell survival. BC was surgically implanted in vivo into a stromal pocket. During a 3-month follow-up, the biocompatibility of BC was assessed. We found that epithelial and stromal cells grew well on BC and showed a survival rate of nearly 100%. The SEM examination for both kinds of cell showed abundant leafy protrusions, spherical projections, filopodia, cytoskeletons, and cellular interconnections. The stromal cells cultured on BC arranged regularly. TEM observation revealed normal cellular microstructure and a tight adhesion to the BC membrane. In vivo observation confirmed the optical transparency of BC during 3-month follow-up. The results demonstrated that BC had good biocompatibility for the tissue engineering of corneal stroma.
Axle-box bearings are one of the most critical mechanical components of the high-speed train. Vibration signals collected from axle-box bearings are usually nonlinear and nonstationary, caused by the ...complicated operating conditions. Due to the high reliability and real-time requirement of axle-box bearing fault diagnosis for high-speed trains, the accuracy and efficiency of the bearing fault diagnosis method based on deep learning needs to be enhanced. To identify the axle-box bearing fault accurately and quickly, a novel approach is proposed in this paper using a simplified shallow information fusion-convolutional neural network (SSIF-CNN). Firstly, the time domain and frequency domain features were extracted from the training samples and testing samples before been inputted into the SSIF-CNN model. Secondly, the feature maps obtained from each hidden layer were transformed into a corresponding feature sequence by the global convolution operation. Finally, those feature sequences obtained from different layers were concatenated into one-dimensional as the fully connected layer to achieve the fault identification task. The experimental results showed that the SSIF-CNN effectively compressed the training time and improved the fault diagnosis accuracy compared with a general CNN.
Picornaviruses have evolved to hijack host cellular machinery, including the autophagic pathway. However, the mechanisms remain largely unclear. We use coxsackievirus B3 (CVB3) as a model organism to ...explore the possible role of picornavirus subversion of the autophagic pathway in viral infection. Our in vivo and in vitro experiments demonstrate that CVB3 infection causes a significant, albeit incomplete, inhibition of autophagic flux by limiting the fusion of autophagosomes with lysosomes and/or late endosomes. Furthermore, we show that CVB3 specifically targets SNARE protein SNAP29 and adaptor protein PLEKHM1, two critical proteins known to regulate autophagosome fusion, for cleavage through the catalytic activity of viral proteinase 3C, ultimately impairing the formation of SNARE complexes. Finally, we demonstrate that loss of SNAP29/PLEKHM1 inhibits autophagic flux, resulting in increased viral replication. Collectively, our study reveals a mechanism that supports an emerging model whereby CVB3 hijacks the autophagic machinery to facilitate its own propagation.
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•CVB3 infection inhibits autophagosome-lysosome/late endosome fusion•CVB3 limits autophagic flux via cleavage of SNAP29 and PLEKHM1 by proteinase 3C•Knockdown of SNAP29 and/or PLEKHM1 facilitates viral replication
Mohamud et al. report that coxsackievirus limits autophagosome fusion with lysosomes and/or late endosomes through viral proteinase 3C-mediated cleavage of SNAP29 and PLEKHM1. This leads to the accumulation of autophagosomes that favor viral replication by providing additional membrane scaffolds.
The ongoing pandemic of COVID-19 alongside the outbreaks of SARS in 2003 and MERS in 2012 underscore the significance to understand betacoronaviruses as a global health challenge. SARS-CoV-2, the ...etiological agent for COVID-19, has infected over 50 million individuals’ worldwide with more than ∼1 million fatalities. Autophagy modulators have emerged as potential therapeutic candidates against SARS-CoV-2 but recent clinical setbacks urge for better understanding of viral subversion of autophagy. Using MHV-A59 as a model betacoronavirus, time-course infections revealed significant loss in the protein level of ULK1, a canonical autophagy-regulating kinase, and the concomitant appearance of a possible cleavage fragment. To investigate whether virus-encoded proteases target ULK1, we conducted in-vitro and cellular cleavage assays and identified ULK1 as a novel bona fide substrate of SARS-CoV-2 papain-like protease (PLpro). Mutagenesis studies discovered that ULK1 is cleaved at a conserved PLpro recognition sequence (LGGG) after G499, separating its N-terminal kinase domain from a C-terminal substrate recognition region. Over-expression of SARS-CoV-2 PLpro is sufficient to impair starvation-induced autophagy and disrupt formation of ULK1-ATG13 complex. Finally, we demonstrated a dual role for ULK1 in MHV-A59 replication, serving a pro-viral functions during early replication that is inactivated at late stages of infection. In conclusion, our study identified a new mechanism by which PLpro of betacoronaviruses induces viral pathogenesis by targeting cellular autophagy.
•ULK1 is a novel target of betacoronavirus.•SARS-COV-2 papain-like protease (PLpro) cleaves ULK1 after G499.•PLpro disrupts ULK1 complex and cellular autophagy.•ULK1 is required early but dispensable during late MHV-A59 infection.
The myocardium/heart is the most mitochondria-rich tissue in the human body with mitochondria comprising approximately 30% of total cardiomyocyte volume. As the resident "powerhouse" of cells, ...mitochondria help to fuel the high energy demands of a continuously beating myocardium. It is no surprise that mitochondrial dysfunction underscores the pathogenesis of many cardiovascular ailments, including those of viral origin such as virus-induced myocarditis. Enteroviruses have been especially linked to injuries of the myocardium and its sequelae dilated cardiomyopathy for which no effective therapies currently exist. Intriguingly, recent mechanistic insights have demonstrated viral infections to directly damage mitochondria, impair the mitochondrial quality control processes of the cell, such as disrupting mitochondrial antiviral innate immune signaling, and promoting mitochondrial-dependent pathological inflammation of the infected myocardium. In this review, we briefly highlight recent insights on the virus-mitochondria crosstalk and discuss the therapeutic implications of targeting mitochondria to preserve heart function and ultimately combat viral myocarditis.
Short interfering RNAs (siRNAs) have provided novel insights into the field of cancer treatment in light of their ability to specifically target and silence cancer-associated genes. In recent years, ...numerous studies focus on determining genes that actively participate in tumor formation, invasion, and metastasis in order to establish new targets for cancer treatment. In spite of great advances in designing various siRNAs with diverse targets, efficient delivery of siRNAs to cancer cells is still the main challenge in siRNA-mediated cancer treatment. Recent advancements in the field of nanotechnology and nanomedicine hold great promise to meet this challenge. This review focuses on recent findings in cancer-associated genes and the application of siRNAs to successfully silence them in prostate cancer, as well as recent progress for effectual delivery of siRNAs to cancer cells.
Graphene oxide–bacterial cellulose (GO/BC) nanocomposite hydrogels with well‐dispersed GO in the network of BC are successfully developed using a facile one‐step in situ biosynthesis by adding GO ...suspension into the culture medium of BC. During the biosynthesis process, the crystallinity index of BC decreases and GO is partially reduced. The experimental results indicate that GO nanosheets are uniformly dispersed and well‐bound to the BC matrix and that the 3D porous structure of BC is sustained. This is responsible for efficient load transfer between the GO reinforcement and BC matrix. Compared with the pure BC, the tensile strength and Young's modulus of the GO/BC nanocomposite hydrogel containing 0.48 wt% GO are significantly improved by about 38 and 120%, respectively. The GO/BC nanocomposite hydrogels are promising as a new material for tissue engineering scaffolds.
Graphene oxide–bacterial cellulose (GO/BC) nanocomposite hydrogels with well‐dispersed GO in the network of BC have been successfully developed using a facile one‐step in situ biosynthesis by adding GO suspension into the culture medium of BC. The composites show a significant increase in tensile properties at relatively low GO loadings.
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