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SARS-CoV-2 (severe acute respiratory syndrome) is highly infectious and causes severe acute respiratory distress syndrome (SARD), immune suppression, and multi-organ failure. For SARS-CoV-2, only supportive treatment options are available, such as oxygen supportive therapy, ventilator support, antibiotics for secondary infections, mineral and fluid treatment, and a significant subset of repurposed effective drugs. Viral targeted inhibitors are the most suitable molecules, such as ACE2 (angiotensin-converting enzyme-2) and RBD (receptor-binding domain) protein-based inhibitors, inhibitors of host proteases, inhibitors of viral proteases 3CLpro (3C-like proteinase) and PLpro (papain-like protease), inhibitors of replicative enzymes, inhibitors of viral attachment of SARS-CoV-2 to the ACE2 receptor and TMPRSS2 (transmembrane serine proteinase 2), inhibitors of HR1 (Heptad Repeat 1)–HR2 (Heptad Repeat 2) interaction at the S2 protein of the coronavirus, etc. Targeting the cathepsin L proteinase, peptide analogues, monoclonal antibodies, and protein chimaeras as RBD inhibitors interferes with the spike protein’s ability to fuse to the membrane. Targeting the cathepsin L proteinase, peptide analogues, monoclonal antibodies, and protein chimaeras as RBD inhibitors interferes with the spike protein’s ability to fuse to the membrane. Even with the tremendous progress made, creating effective drugs remains difficult. To develop COVID-19 treatment alternatives, clinical studies are examining a variety of therapy categories, including antibodies, antivirals, cell-based therapy, repurposed diagnostic medicines, and more. In this article, we discuss recent clinical updates on SARS-CoV-2 infection, clinical characteristics, diagnosis, immunopathology, the new emergence of variant, SARS-CoV-2, various approaches to drug development and treatment options. The development of therapies has been complicated by the global occurrence of many SARS-CoV-2 mutations. Discussion of this manuscript will provide new insight into drug pathophysiology and drug development.

The implantable cardioverter-defibrillator (ICD) is an effective method to prevent sudden cardiac death in high-risk patients. However, the transvenous lead is incompatible with large-area electrophysiological mapping and cannot accommodate selective multichannel precision stimulations. Moreover, it involves high-energy shocks, resulting in pain, myocardial damage, and recurrences of ventricular tachyarrhythmia (VTA). We present a method for VTA treatment based on subthreshold electrical stimulations using a stretchable epicardial multichannel electrode array, which does not disturb the normal contraction or electrical propagation of the ventricle. In rabbit models with myocardial infarction, the infarction was detected by mapping intracardiac electrograms with the stretchable epicardial multichannel electrode array. Then, VTAs could be terminated by sequential electrical stimuli from the epicardial multichannel electrode array beginning with low-energy subthreshold stimulations. Last, we used these subthreshold stimulations to prevent the occurrence of additional VTAs. The proposed protocol using the stretchable epicardial multichannel electrode array provides opportunities toward the development of innovative methods for painless ICD therapy.

Background: Pulsed high-power microwave (HPM) has many applications and is constantly being researched to expand its uses in the future. As the number of applications grows, the biological effects and safety level of pulsed HPM become a serious issue, requiring further research.Objective: The brain is regarded as the most vulnerable organ to radiation, raising concerns about determining an acceptable level of exposure. The effect of nanosecond pulses and the mechanisms underlying HPM on the brain has not been studied. For the first time, we observed the effect of pulsed 3.5 GHz HPM on brain normal astrocytes and cancer U87 MG cells, as well as the likely mechanisms involved.Methods: To generate 3.5 GHz HPM, an axial virtual cathode oscillator was constructed on pulsed power generator “Chundoong”. The cells were directly exposed to HPM (10, 25, 40, and 60) pulses (1 mJ/pulse), with each pulse delivered after 1 min of charging time to evaluate the dose dependent effects.Results: A strong electric field (∼23 kV/cm) of HPM irradiation primarily causes the production of reactive oxygen species (ROS), altering cell viability, mitochondrial activity, and cell death rates in U87 and astrocytes at certain dosages. The ROS generation in response to HPM exposure was primarily responsible for DNA damage and p53 activation. The hazardous dosage of 60 pulses is acknowledged as having damaging effects on brain normal cells. Interestingly, the particular 25 pulses exhibited therapeutic effects on U87 cells via p53, Bax, and Caspase-3 activation.Conclusion: HPM pulses induced apoptosis-related events such as ROS burst and increased oxidative DNA damage at higher dosages in normal cells and specific 25 pulses in cancer U87. These findings are useful to understand the physiological mechanisms driving HPM-induced cell death, as well as the safety threshold range for HPM exposure on normal cells and therapeutic effects on cancer U87. As HPM technology advances, we believe this study is timely and will benefit humanity and future research.

Calcium magnesium carbonate nanoparticles (CaMg(CO

Global society has been highly pressured by the COVID-19 pandemic, which has exposed vulnerabilities in supply chains for disinfection products, personal protective equipment, and medical resources worldwide. It is critically necessary to find effective treatments and medications for these viral infections. This review summarizes and emphasizes critical features of recent breakthroughs in vaccines, inhibitors, radiations, and innovative nonthermal atmospheric plasma (NTAP) technologies to inactivate COVID-19. NTAP has emerged as an effective, efficient, and safe method of viral inactivation. NTAP can be used to inactivate viruses in an environmentally friendly manner, as well as activate animal and plant viruses in a variety of matrices. Researchers and engineers desire to help the medical world deal with the ongoing COVID-19 epidemic by establishing techniques that make use of widely available NTAP technologies. NTAP technology is not dependent on viral strain, and it does not necessitate months or years of research to develop specific vaccines for each novel or arising viral disease. We believe the NTAP is a highly promising technique for combating COVID-19 and other viruses. Thus, NTAP technology could be a significant breakthrough in the near future in assisting humans in combating COVID-19 infections. We hope that this review provides a platform for readers to examine the progress made in the fight against COVID-19 through the use of vaccines, inhibitors, radiation, and NTAP.

This study hypothesizes that the application of low-dose nonthermal biocompatible dielectric barrier discharge plasma (DBD-NBP) to human gingival fibroblasts (HGFs) will inhibit colony formation but not cell death and induce matrix metalloproteinase (MMP) expression, extracellular matrix (ECM) degradation, and subsequent cell migration, which can result in enhanced wound healing. HGFs treated with plasma for 3 min migrate to each other across the gap faster than those in the control and 5-min treatment groups on days 1 and 3. The plasma-treated HGFs show significantly high expression levels of the cell cycle arrest-related p21 gene and enhanced MMP activity. Focal adhesion kinase (FAK) mediated attenuation of wound healing or actin cytoskeleton rearrangement, and plasma-mediated reversal of this attenuation support the migratory effect of DBD-NBP. Further, this work performs computer simulations to investigate the effect of oxidation on the stability and conformation of the catalytic kinase domain (KD) of FAK. It is found that the oxidation of highly reactive amino acids (AAs) Cys427, Met442, Cys559, Met571, Met617, and Met643 changes the conformation and increases the structural flexibility of the FAK protein and thus modulates its function and activity. Low-dose DBD-NBP-induces host cell cycle arrest, ECM breakdown, and subsequent migration, thus contributing to the enhanced wound healing process.

Dementia is reported to be common in those with type 2 diabetes mellitus. Type 2 diabetes contributes to common molecular mechanisms and an underlying pathology with dementia. Brain cells becoming resistant to insulin leads to elevated blood glucose levels, impaired synaptic plasticity, microglial overactivation, mitochondrial dysfunction, neuronal apoptosis, nutrient deprivation, TAU (Tubulin-Associated Unit) phosphorylation, and cholinergic dysfunction. If insulin has neuroprotective properties, insulin resistance may interfere with those properties. Risk factors have a significant impact on the development of diseases, such as diabetes, obesity, stroke, and other conditions. Analysis of risk factors of importance for the association between diabetes and dementia is important because they may impede clinical management and early diagnosis. We discuss the pathological and physiological mechanisms behind the association between Type 2 diabetes mellitus and dementia, such as insulin resistance, insulin signaling, and sporadic forms of dementia; the relationship between insulin receptor activation and TAU phosphorylation; dementia and mRNA expression and downregulation of related receptors; neural modulation due to insulin secretion and glucose homeostasis; and neuronal apoptosis due to insulin resistance and Type 2 diabetes mellitus. Addressing these factors will offer clinical outcome-based insights into the mechanisms and connection between patients with type 2 diabetes and cognitive impairment. Furthermore, we will explore the role of brain insulin resistance and evidence for anti-diabetic drugs in the prevention of dementia risk in type 2 diabetes.

Thin, sensitive skin electronics The properties of the human sense of touch, including high sensitivity to differences in temperature, pressure, or surface roughness, are challenging to replicate in robotics because skin materials must be highly conductive, stretchable, and thin. Jung et al . developed a process to assemble nanomaterials as a monolayer that is partially embedded in an ultrathin elastomer. The process works by depositing a mixed solvent containing nanostructured silver and/or gold, along with elastomer, onto deionized water. This results in a layer of nanoparticles residing at the interface coating with elastomer, which is further densified by the addition of surfactant. The process is scalable, and the resulting elastomer membranes can be transferred to other substrates. —MSL

With the emergence of new drug-resistant microorganisms, the development of effective antimicrobial agents is urgently required. Core-shell-structured nanomaterials have received considerable attention as antibacterial agents. We prepared a bioactive core-shell-structured silicon-based NiOOH nanoflower (Si@NiOOH) targeted against various bacteria using a modified chemical bath deposition method. Further, we investigated its potential antibacterial mechanism by evaluating electrochemical properties in a redox reaction with ascorbic acid, measuring metal ion release, and analyzing the surface area. The bactericidal rate of Si@NiOOH at 200 μg/mL towards Pseudomonas aeruginosa, Klebsiella pneumoniae, and methicillin-resistant Staphylococcus aureus was as high as 99.9%. Si@NiOOH maintained its original morphology after killing the bacteria and exhibited negligible cytotoxicity towards mouse embryonic fibroblasts. The excellent antibacterial activities of Si@NiOOH are possibly derived from its high surface area, providing a wide active site attached to the cell wall, and the high oxidative potency of the Ni(III) cations existing on its surface. The high antibacterial activity and low cytotoxicity of the nanoflower make it a promising tool for promoting wound healing and for use with medical devices and implants.

Modern humanity wades daily through various radiations, resulting in frequent exposure and causing potentially important biological effects. Among them, the brain is the organ most sensitive to electromagnetic radiation (EMR) exposure. Despite numerous correlated studies, critical unknowns surround the different parameters used, including operational frequency, power density (i.e., energy dose), and irradiation time that could permit reproducibility and comparability between analyses. Furthermore, the interactions of EMR with biological systems and its precise mechanisms remain poorly characterized. In this review, recent approaches examining the effects of microwave radiations on the brain, specifically learning and memory capabilities, as well as the mechanisms of brain dysfunction with exposure as reported in the literature, are analyzed and interpreted to provide prospective views for future research directed at this important and novel medical technology for developing preventive and therapeutic strategies on brain degeneration caused by microwave radiation. Additionally, the interactions of microwaves with biological systems and possible mechanisms are presented in this review. Treatment with natural products and safe techniques to reduce harm to organs have become essential components of daily life, and some promising techniques to treat cancers and their radioprotective effects are summarized as well. This review can serve as a platform for researchers to understand the mechanism and interactions of microwave radiation with biological systems, the present scenario, and prospects for future studies on the effect of microwaves on the brain.

Noble metal nanomaterials have been studied as conductive fillers for stretchable, conductive, and biocompatible nanocomposites. However, their performance as conductive filler materials is far from ideal because of their high percolation threshold and low intrinsic conductivity. Moreover, the difficulty in large-scale production is another critical hurdle in their practical applications. Here we report a method for the facile and scalable synthesis of whiskered gold nanosheets (W-AuNSs) for stretchable, conductive, and biocompatible nanocomposites and their application to stretchable bioelectrodes. W-AuNSs show a lower percolation threshold (1.56 vol %) than those of gold nanoparticles (5.02 vol %) and gold nanosheets (2.74 vol %), which enables the fabrication of W-AuNS-based stretchable nanocomposites with superior conductivity and high stretchability. Addition of platinum-coated W-AuNSs (W-AuNSs@Pt) to the prepared nanocomposite significantly reduces the impedance and improved charge storage capacity. Such enhanced performance of the stretchable nanocomposite enables us to fabricate stretchable bioelectrodes whose performance is demonstrated through animal experiments including electrophysiological recording and electrical stimulation

Summary Recent advances in bioelectronics, such as skin-mounted electroencephalography sensors, multi-channel neural probes, and closed-loop deep brain stimulators, have enabled electrophysiological brain activities to be both monitored and modulated. Despite this remarkable progress, major challenges remain, which stem from the inherent mechanical, chemical, and electrical differences that exist between brain tissues and bioelectronics. New approaches are therefore required to address these mismatches between biotic and abiotic systems. Here, we review recent technological advances that minimize such mismatches by using unconventional soft materials, such as silicon/metal nanowires, functionalized hydrogels, and stretchable conductive nanocomposites, as well as customized fabrication processes and novel device designs. The resulting novel, soft bioelectronic devices provide new opportunities for brain research and clinical neuroengineering.

In this study, zinc sulphide nanomaterial (ZnS NM) powders were prepared with the assistance of an atmospheric pressure soft jet plasma (APPJ) device. Regular approaches to ZnS preparation mainly resulted in aggregated powders, thus plasma methods were investigated to obtain controlled morphological structures. The APPJ plasma-assisted ZnS exhibited unique surface architectures, such as nanorods, layers and spherical aggregates, that were controllably obtained by changing the reactant concentration and type of precursor. The prepared ZnS showed good thermal stability by no changes in its composition up to 400 °C. The APPJ plasma-assisted ZnS showed sphalerite and wurtzite crystal structures and resulted in excellent chemical purity. The simple and handy APPJ plasma method shows good potential for shape-controlled ZnS NMs preparation without addition of surfactant chemicals, mechanical stirring, external heating or any other tedious procedures. This capability showcases the scientific and technological merit of this technique. The prepared ZnS NMs were utilized as antibacterial agents and evaluated the activity using three techniques against the human pathogens of E. coli, S. aureus and K. pneumoniae. The ZnS NMs showed effective concentration and shape-dependent activity when used as an antibacterial material.

The application of non-thermal bio-compatible plasma (NBP) for stem cell differentiation is promising in tissue engineering. However, the differentiation efficiency of NBP treatment on various types of human tissue-derived stem cells and the underlying mechanisms is yet understood. This study is the first time to investigate the role of NBP in inducing differentiation and its potential molecular mechanism by using human bone marrow-derived stem cells (hBMSCs) and human periodontal ligament-derived stem cells (hPDLSCs). Our results showed that NBP promote osteogenic differentiation of hPDLSCs more effectively than hBMSCs under the same treatment condition, indicating a tissue-dependent manner of NBP interacts with stem cells. Furthermore, an increase of intracellular reactive oxygen species (ROS) production of hPDLSCs and antioxidant enzymes activation was observed after NBP treatment. Particularly, mitogen-activated protein kinases (MAPKs) level was also increased and in consistent with ROS level increase. Taken together, this study revealed that with NBP induction, hPDLSCs is a more suitable stem cell source than hBMSCs for bone regeneration and tissue engineering, and ROS-induced activation of MAPKs are possibly involved in the osteogenic differentiation process.

Graphical abstract, Coronaviruses are a group of enveloped RNA viruses that are diversely found in humans and now declared a global pandemic by the World Health Organization in March 2020. The population's susceptibility to these highly pathogenic coronaviruses has contributed to large outbreaks, evolved into public health events, and rapidly transmitted globally. Thus, there is an urgent need to develop effective therapies and vaccines against this disease. In the primary stage of severe acute respiratory syndrome coronavirus (SARS-COV-2) infection, the signs and symptoms are nonspecific, and many more cases have been observed than initially expected. Genome sequencing is performed regularly to identify genetic changes to SARS-COV-2, and vaccine development is focused on manufacture, production, and based on specific problems, and very few are available on recent developments in the prevention of outbreaks. The aim of this review article to explore recent updates on SARS-COV-2 in the context of pathogenesis during disease progression, and innate acquired mechanisms of defense, This includes advances in diagnostics, susceptibility, and severity of host-virus genome interactions, modes of transmission, active compounds being used in pre-clinical and clinical trials for the treatment of patients, vaccine developments, and the effectiveness of SARS-COV-2 prevention and control measures. We have summarized the importance of pathophysiology immune response, Diagnostics, vaccine development currently approaches explored for SARS-COV-2.

Vaginal cancer is a rare and uncommon disease that is rarely discussed. Although vaginal cancer traditionally occurs in older postmenopausal women, the incidence of high-risk human papillomavirus (HPV)-induced cancers is increasing in younger women. Cervical cancer cells contain high-risk human papillomavirus (HPV) E6 and E7 proteins and inhibiting HPV gene expression leads the cells to stop proliferating and enter senescence. As E6, and E7 protein promoted the carcinogenesis mechanism, and here not only regulate the cellular degradation of P53, and pRb but also enhances the cell proliferation along with E6 protein targets the p53 for breakdown and subsequently promote the apoptotic cell death, and DNA repair inhibition, that is indispensable to the continue the lifecycle of the HPV. As a synchronous or metachronous tumor, vaginal cancer is frequently found in combination with cervical cancer. It is uncertain what causes invasive female vaginal organ cancer. HPV type 16 is the most often isolated HPV type in female vaginal organ cancers. Due to cancer’s rarity, case studies have provided the majority of etiologic findings. Many findings demonstrate that ring pessaries, chronic vaginitis, sexual behavior, birth trauma, obesity, vaginal chemical exposure, and viruses are all risk factors. Because of insufficient understanding and disease findings, we are trying to find the disease’s mechanism with the available data. We also address different risk factors, therapy at various stages, diagnosis, and management of vaginal cancer in this review.

An urgent need in chemodynamic therapy (CDT) is to achieve high Fenton catalytic efficiency at small doses of CDT agents. However, simple general promotion of the Fenton reaction increases the risk of damaging normal cells along with the cancer cells. Therefore, a tailored strategy to selectively enhance the Fenton reactivity in tumors, for example, by taking advantage of the characteristics of the tumor microenvironment (TME), is in high demand. Herein, a heterogeneous CDT system based on copper-iron peroxide nanoparticles (CFp NPs) is designed for TME-mediated synergistic therapy. CFp NPs degrade under the mildly acidic conditions of TME, self-supply H

Recent advances in atmospheric plasmas have led to the formation of nonthermal plasma (NTP). In recent decades, a number of novel plasma diagnostic approaches have been implemented and reported in order to better understand the physics of NTP. The use of NTP is a novel approach to producing reactive oxygen and nitrogen species. Plasma technology has many applications, including electrical device microfabrication, biomedicine, dentistry, agriculture, ozone generation, chemical synthesis, surface treatment, coating, and disease therapy. Furthermore, NTP is thought to be a successful strategy for the degradation of hazardous pollutants in the environment, making it a future hope. Recent studies showed that various operating parameters affect the yield of NTP-based technology. Especially, the presence of a catalyst, properly placed in an NTP reactor, leads to a significant increase in process performance as compared to NTP alone. Scientists have looked at using NTP in conjunction with catalysts to remove various sorts of pollutants from the environment. In this context, review articles are crucial due to the prevalence of NTP-based applications and ongoing developments. This review will describe recent advancements in NTP-based biomedical applications, bacterial inactivation, food preservation and storage, and environmental catalytic formulations. This review could be useful in providing a platform for advancements in biological applications and environmental protection through the use of NTP technology.

We investigated the characteristics of a rollable dielectric barrier discharge (RDBD) and evaluate its effects on seed germination rate and water uptake. The RDBD source was composed of a polyimide substrate and copper electrode, and it was mounted in a rolled-up structure for omnidirectional and uniform treatment of seeds with flowing synthetic air gas. The rotational and vibrational temperatures were measured to be 342 K and 2860 K, respectively, using optical emission spectroscopy. The chemical species analysis via Fourier-transform infrared spectroscopy and 0D chemical simulation showed that O3 production was dominant and NOx production was restrained at the given temperatures. The water uptake and germination rate of spinach seeds by 5 min treatment of RDBD was increased by 10% and 15%, respectively, and the standard error of germination was reduced by 4% in comparison with the controls. RDBD enables an important step forward in non-thermal atmospheric-pressure plasma agriculture for omnidirectional seed treatment.

Bacteria employ numerous resistance mechanisms against structurally distinct drugs by the process of multidrug resistance. A study was planned to discover the antibacterial potential of a graphene oxide nanosheet (GO), a graphene oxide–zinc oxide nanocomposite (GO/ZnO), a graphene oxide-chitosan nanocomposite (GO–CS), a zinc oxide decorated graphene oxide–chitosan nanocomposite (GO–CS/ZnO), and zinc oxide nanoparticles (ZnO) alone and in a blend with antibiotics against a PS-2 isolate of Pseudomonas aeruginosa. These nanocomposites reduced the MIC of tetracycline (TET) from 16 folds to 64 folds against a multidrug-resistant clinical isolate. Efflux pumps were interfered, as evident by an ethidium bromide synergy study with nanocomposites, as well as inhibiting biofilm synthesis. These nanoparticles/nanocomposites also decreased the mutant prevention concentration (MPC) of TET. To the best of our knowledge, this is the first report on nanomaterials as a synergistic agent via inhibition of efflux and biofilm synthesis.

The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin family that is overexpressed in several cancers. RAGE is highly expressed in the lung, and its expression increases proportionally at the site of inflammation. This receptor can bind a variety of ligands, including advanced glycation end products, high mobility group box 1, S100 proteins, adhesion molecules, complement components, advanced lipoxidation end products, lipopolysaccharides, and other molecules that mediate cellular responses related to acute and chronic inflammation. RAGE serves as an important node for the initiation and stimulation of cell stress and growth signaling mechanisms that promote carcinogenesis, tumor propagation, and metastatic potential. In this review, we discuss different aspects of RAGE and its prominent ligands implicated in cancer pathogenesis and describe current findings that provide insights into the significant role played by RAGE in cancer. Cancer development can be hindered by inhibiting the interaction of RAGE with its ligands, and this could provide an effective strategy for cancer treatment.

Pelvic organ prolapse (POP) is a chronic disorder that affects quality of life in women. Several POP treatments may be accompanied by abrasion, constant infection, and severe pain. Therefore, new treatment methods and improvements in current treatments for POP are required. Non-thermal atmospheric-pressure plasma is a rising biomedical therapy that generates a mixed cocktail of reactive species by different mechanisms. In this study, we applied a cylinder-type dielectric barrier discharge plasma device to create a plasma-treated liquid (PTL). The PTL was added to primary cultured human uterosacral ligament fibroblast (hUSLF) cells from POP patients at each stage. Surprisingly, treatment with diluted PTL increased hUSLF cell viability but decreased ovarian cancer cell viability. PTL also decreased cell apoptosis in hUSLF cells but increased it in SKOV3 cells. Our results suggest that PTL protects hUSLF cells from cell apoptosis by controlling the p53 pathway and improves cell viability, implying that PTL is a promising application for POP therapy.

Nonthermal biocompatible plasma (NBP) sources operating in atmospheric pressure environments and their characteristics can be used for plasma bioscience, medicine, and hygiene applications, especially for COVID-19 and citizen. This review surveyed the various NBP sources, including a plasma jet, micro-DBD (dielectric barrier discharge) and nanosecond discharged plasma. The electron temperatures and the plasma densities, which are produced using dielectric barrier discharged electrode systems, can be characterized as 0.7 ~ 1.8 eV and (3-5) × 10

As a new approach of creating the photo-exited electron (e-) and hole (h+) mediation zone for highly selective singlet oxygen (1O2) production, the rod-type graphitic carbon nitride (NCN) has been synthesized from the nitric acid-modified melamine followed by the calcination. The NCN exhibited a higher surface area and surface oxygen adsorption ability than bulk graphitic carbon nitride (BCN). The increment of C O and NHx groups on NCN corresponded to e- and h+ mediation groups, respectively, resulting in higher production of 1O2 than BCN. Moreover, those mediation groups on NCN result in higher recombination efficiency and longer e- decay time. As a result, the optimized NCN-0.5 (derived from 0.5 M of nitric acid-modified melamine) displayed 5.8 times higher kinetic rate constant of atrazine (ATZ) removal under UVA-LED irradiation compared to BCN. This study also evaluated the ATZ degradation pathways and toxicity effect of by-products. In addition, continuous flow experiments using NCN-0.5 showed superior ATZ removal performance with a hybrid concept between a slurry photocatalysis and a continuous stirred tank reactor system using actual effluent obtained from a wastewater treatment plant. Thus, this work provides an insight into the strategy for highly selective 1O2 production and the potential for water purification application.

Highly conductive and intrinsically stretchable electrodes are vital components of soft electronics such as stretchable transistors and circuits, sensors and actuators, light-emitting diode arrays, and energy harvesting devices. Many kinds of conducting nanomaterials with outstanding electrical and mechanical properties have been integrated with elastomers to produce stretchable conductive nanocomposites. Understanding the characteristics of these nanocomposites and assessing the feasibility of their fabrication are therefore critical for the development of high-performance stretchable conductors and electronic devices. We herein summarise the recent advances in stretchable conductors based on the percolation networks of nanoscale conductive fillers in elastomeric media. After discussing the material-, dimension-, and size-dependent properties of conductive fillers and their implications, we highlight various techniques that are used to reduce the contact resistance between the conductive filler materials. Furthermore, we categorize elastomer matrices with different stretchabilities and mechanical properties based on their polymeric chain structures. Then, we discuss the fabrication techniques of stretchable conductive nanocomposites toward their use in soft electronics. Finally, we provide representative examples of stretchable device applications and conclude the review with a brief outlook for future research.

Neuropathic pain is a chronic and pathological pain caused by injury or dysfunction in the nervous system. Pro-inflammatory microglial activation with aberrant reactive oxygen species (ROS) generation in the spinal cord plays a critical role in the development of neuropathic pain. However, the efficacy of current therapeutic methods for neuropathic pain is limited because only neurons or neural circuits involved in pain transmission are targeted. Here, an effective strategy to treat pain hypersensitivity using microglia-targeting ceria-zirconia nanoparticles (CZ NPs) is reported. The CZ NPs are coated with microglia-specific antibodies to promote their delivery to microglia, and thus to improve their therapeutic efficacy. The targeted delivery facilitates the elimination of both pro-inflammatory cytokines and ROS in microglia, enabling the rapid and effective inhibition of microglial activation. As a result, greatly ameliorated mechanical allodynia is achieved in a spinal nerve transection (SNT)-induced neuropathic pain mouse model, proving the potent analgesic effect of the microglia-targeting CZ NPs. Given the generality of the approach used in this study, the microglia-targeting CZ NPs are expected to be useful for the treatment of not only neuropathic pain but also other neurological diseases associated with the vicious activation of microglia.

Graphical abstract, Highlights • Triple-negative breast cancer (TNBC) is a breast cancer subtype characterized by the loss of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor--2. • Aberrant gene expression and protein degradation are considered to underlie the onset of tumorigenesis and metastasis. Early detection in asymptomatic patients is the key to improving survival outcomes. • Potential applications of CRISPR/Cas9 and its variants in deciphering or engineering intricate molecular and epigenetic mechanisms associated with TNBC. • CRISPR/Cas9 based editing is a potential application for diagnosis and Drug Resistance in of TNBC., Breast cancer (BC) is the most common type of cancer in women at the global level and the highest mortality rate has been observed with triple-negative breast cancer (TNBC). Accumulation of genetic lesions an aberrant gene expression and protein degradation are considered to underlie the onset of tumorigenesis and metastasis. Therefore, the challenge to identify the genes and molecules that could be potentially used as potent biomarkers for personalized medicine against TNBC with minimal or no associated side effects. Discovery of the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) arrangement and an increasing repertoire of its new variants has provided a much-needed fillip towards editing TNBC genomes. In this review, we discuss the CRISPR/Cas9 genome editing, CRISPR Technology for diagnosis of (Triple-negative breast cancer) TNBC, Drug Resistance, and potential applications of CRISPR/Cas9 and its variants in deciphering or engineering intricate molecular and epigenetic mechanisms associated with TNBC. Furthermore, we have also explored the TNBC and CRISPR/Cas9 genome editing potential for repairing, genetic modifications in TNBC.

Metal-organic frameworks (MOFs) can be applied in biology and medicine as drug delivery systems by carrying drugs on their surfaces or releasing bioactive ligands. To investigate the therapeutic potential of hydrogels that contain MOFs, three MOFs containing glutarate and 1,2-bis(4-pyridyl)ethylene ligands were synthesized by the previously reported hydrothermal or solvothermal reactions: Cu-MOF 1, Co-MOF 2, and Zn-MOF 3. Bioactive MOF-embedded hydrogels (hydrogel@Cu-MOF 1, hydrogel@Co-MOF 2, and hydrogel@Zn-MOF 3) were prepared by UV light-mediated thiol-ene photopolymerization using diacrylated polyethylene glycol (PEG), 4-arm-thiolated PEG, and MOFs. The activities of the MOF-embedded hydrogels were tested against the Gram-negative bacterium Escherichia coli and the Gram-positive bacterium Staphylococcus aureus. These MOF-embedded hydrogels were observed to be very stable, based on the release test of MII ions, and both hydrogel@Cu-MOF 1 and hydrogel@Co-MOF 2 showed excellent antibacterial activity. Although, in human dermal fibroblasts, hydrogel@Cu-MOF 1 showed no cytotoxic effects, it exhibited 99.9% antibacterial effects at the minimum bactericidal concentration. Physical properties such as the surface area and dimension of MOFs with different central metals appeared to be more important than the chemical properties of the ligands in determining the effects on bacteria. These MOF-embedded hydrogels may be useful in antibacterial applications such as cosmetics, treatment of skin diseases, and drug delivery owing to their low cytotoxicity and high bactericidal activity.

Nanomaterials with antioxidant properties are promising for treating reactive oxygen species (ROS)-related diseases. However, maintaining efficacy at low doses to minimize toxicity is a critical for clinical applications. Tuning the surface strain of metallic nanoparticles can enhance catalytic reactivity, which has rarely been demonstrated in metal oxide nanomaterials. Here, it is shown that inducing surface strains of CeO

Malignant melanoma is considered to be a heterogeneous disease that arises from altered genes and transformed melanocytes. In this study, special softjet cold atmospheric plasma was used to treat three different human melanoma cells using air and N2 gases to check the anti-melanoma activity. The physical effects by plasma revealed an increase in the temperature with the gradual reduction in pH at 60 sec, 180 sec and 300 sec air and N2 plasma treatment. Cellular toxicity revealed a decreased in cell survival (~50% cell survival using air gas and 2 gas at 60 sec plasma treatment in G-361 cells). Gene analysis by q-PCR revealed that 3 min and 5 min air and N2 plasma treatment activated apoptotic pathways by triggering apoptotic genes in all three melanoma cell lines. The apoptosis was confirmed by DAPI staining and its related pathways were further explored according to protein-protein docking, and their probable activation mechanism was revealed. The pathways highlighted that activation of apoptosis which leads to cellular cascades and hence stimulation ASK1 (docking method) revealed that softjet plasma can be an effective modality for human melanoma treatment.

Wearable and implantable devices require conductive, stretchable and biocompatible materials. However, obtaining composites that simultaneously fulfil these requirements is challenging due to a trade-off between conductivity and stretchability. Here, we report on Ag–Au nanocomposites composed of ultralong gold-coated silver nanowires in an elastomeric block-copolymer matrix. Owing to the high aspect ratio and percolation network of the Ag–Au nanowires, the nanocomposites exhibit an optimized conductivity of 41,850 S cm−1 (maximum of 72,600 S cm−1). Phase separation in the Ag–Au nanocomposite during the solvent-drying process generates a microstructure that yields an optimized stretchability of 266% (maximum of 840%). The thick gold sheath deposited on the silver nanowire surface prevents oxidation and silver ion leaching, making the composite biocompatible and highly conductive. Using the nanocomposite, we successfully fabricate wearable and implantable soft bioelectronic devices that can be conformally integrated with human skin and swine heart for continuous electrophysiological recording, and electrical and thermal stimulation. A highly conductive, biocompatible and stretchable nanocomposite based on ultralong gold-coated silver nanowires allows for the realization of wearable and implantable bioelectronics.

Here the underlying role of CNOT2, a subunit of CCR4-NOT complex, was elucidated in cancer progression. CNOT2 was overexpressed in HIT-T15, ASPC-1, BXPC-3, PC-3, LNCaP, MCF-7 and MDA-MB-231 cell lines, which was confirmed by Tissue array in various human tumor tissues. Also, CNOT2 depletion suppressed proliferation and colony formation of MDA-MB-231 cells. Of note, microarray revealed decreased expression of CNOT2, VEGF-A, HIF2 alpha (0.5 fold) and increased expression of UMOD1, LOC727847, MMP4, hCG and other genes (2.0 fold) in CNOT2 depleted MDA-MB-231 cells compared to untreated control. Consistently, downregulation of VEGF, CNOT2 and HIF2 alpha was verified in CNOT2 depleted MDA-MB-231 cells by RT-qPCR. Additionally, CNOT2 depletion inhibited VEGF induced tube formation in HUVECs and reduced neovascularization in CAM assay. Furthermore, the growth of CNOT2 depleted MDA-MB-231 cells was significantly reduced in Balb/c nude mice along with decreased expression of VEGF and PCNA by immunohistochemistry compared to untreated control group. Overall, our findings provide evidences that CNOT2 promotes proliferation and angiogenesis via VEGF signaling in MDA-MB-231 breast cancer cells as a potent molecular target for breast cancer treatment.

The appearance IoT (Internet-of-Things) applications such as environmental monitoring, smart cities, and home automation has realized the IoT concept to reality at a massive scale. Mission critical event data dissemination in massive IoT networks imposes constraints on the message transfer delay between devices. Due to low power and communication range of IoT devices, event data is predicted to be relayed over multiple D2D (device-to-device) links before reaching the destination. The coexistence of a massive number of IoT devices poses a challenge in maximizing the successful transmission capacity of the overall network alongside reducing the multi-hop transmission delay in order to support mission critical applications. In this paper, we first propose an extended s-grid quorum: the xS-grid quorum and the ┣-shaped grid quorum, which are quorum structures that can be used in many different applications including decentralized consensus, distributed mutual exclusion, and replica control. Next, we propose a quorum-based hierarchical dissemination algorithm for critical event data executed on the edge-fog environment in massive IoTs. The proposed algorithm constructs xS-grid and ┣-shaped grid quorums in the overlay network on the edge nodes of the lower layer and the fog servers of the upper layer to support event dissemination, respectively. It supports reliable and guaranteed real-time data dissemination using the proposed algorithm. Then, the performance of quorum and algorithm which are proposed is evaluated through an analytical model.

Soft neuroprosthetics that monitor signals from sensory neurons and deliver motor information can potentially replace damaged nerves. However, achieving long-term stability of devices interfacing peripheral nerves is challenging, since dynamic mechanical deformations in peripheral nerves cause material degradation in devices. Here, a durable and fatigue-resistant soft neuroprosthetic device is reported for bidirectional signaling on peripheral nerves. The neuroprosthetic device is made of a nanocomposite of gold nanoshell (AuNS)-coated silver (Ag) flakes dispersed in a tough, stretchable, and self-healing polymer (SHP). The dynamic self-healing property of the nanocomposite allows the percolation network of AuNS-coated flakes to rebuild after degradation. Therefore, its degraded electrical and mechanical performance by repetitive, irregular, and intense deformations at the device-nerve interface can be spontaneously self-recovered. When the device is implanted on a rat sciatic nerve, stable bidirectional signaling is obtained for over 5 weeks. Neural signals collected from a live walking rat using these neuroprosthetics are analyzed by a deep neural network to predict the joint position precisely. This result demonstrates that durable soft neuroprosthetics can facilitate collection and analysis of large-sized in vivo data for solving challenges in neurological disorders.

Despite cyanoacrylate’s numerous advantages such as good cosmetic results and fast application for first aid, drawbacks such as brittleness and local tissue toxicity have limited their application. In this study, to improve both the biocompatibility and mechanical properties of cyanoacrylate, allyl 2-cyanocarylate was pre-polymerized and mixed with poly(L-lactide-co-e-caprolactone) (PLCL, 50:50) as biodegradable elastomer and mixed with hydroxyapatite (HA) as multifunctional bio-glue for variety body application. Hybridized allyl 2-cyanoacrylate (Hybridized Cy) was mixed with pre-polymerization allyl 2-cynaocarylate and PLCL. For the evaluation of various properties of hybridized Cy/HA bio-glue mixtures, bond strength, surface analysis (SEM, XRD), cell viability, and biocompatibility were confirmed. Especially, optimal condition for hybridized Cy/HA bio-glue was determined as 1.2 wt% HA mixture ratio through bond strength. Surface morphology has smooth form to increase HA mixture ratio. Cell viabi...

Brain tumor is one of the most lethal forms of cancer to human beings, among which Glioblastoma astrocytoma is the most familiar and quickly progressing type of astrocytic brain tumor in adults with poor prognosis are still a therapeutic challenge. Current therapy options at diagnosis are multimodal and include surgical resection, radiation, and chemotherapy but difficulty to failure of drug delivery through the blood-brain barrier, tumor response to chemotherapy and intrinsic resistance of tumor cells. Therefore new therapy is needed that can afford selective targeting of proliferating cells to promote current therapies. Non-thermal plasma can be considered as a potential cancer therapy for the alteration of biological and clinical applications by generating reactive oxygen species (ROS) and reactive nitrogen species (RNS). In our study, we designate the effects of a NBP-J device to U87MG cell line. Previous research work established that jet plasma could induce apoptosis of various cancer cells, in particular indicative the selective cytotoxicity of cancer cells over normal cells. In this study, we assessed the effects of NBP-J on the U87MG brain cancer cell line including different effects and the physicochemical and biological correlation between the RONS cascade and p38/MAPK signaling pathway on the dose (time) dependent manner. The results of this study shows that the soft jet plasma significantly inhibits cell proliferation, inhibit survival pathway and induce apoptosis by p38/MAPK pathway in U87MG cells. The current results reveal that soft jet plasma has a powerful cytotoxic effect against brain cancer cells. Taken together, our results showed that NBP-J can become potential applications for effective and safe clinical trials for cancer therapy. Keywords: Non-thermal atmospheric-pressure plasma, soft jet plasma, Human glioblastoma, Cancer therapy. Acknowledgement This work was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF- 2016K1A4A3914113) funded by the Ministry of Science, ICT, and Future Planning (MSIP) of the Korean Government for EH. Choi, I. Han. Also this work was supported by the Basic Science Research Program through the Ministry of Science ICT of Korea (2019R1H1A2101686) for I. Han. Citation Format: Ihn Han. Apoptosis induced by non-thermal atmospheric pressure bio-compatible soft jet plasma on brain tumor through p38/MAPK signaling pathways [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2402.

Nanomaterials with antioxidant properties are promising for treating reactive oxygen species (ROS)-related diseases. However, maintaining efficacy at low doses to minimize toxicity is a critical for clinical applications. Tuning the surface strain of metallic nanoparticles can enhance catalytic reactivity, which has rarely been demonstrated in metal oxide nanomaterials. Here, it is shown that inducing surface strains of CeO2 /Mn3 O4 nanocrystals produces highly catalytic antioxidants that can protect tissue-resident stem cells from irradiation-induced ROS damage. Manganese ions deposited on the surface of cerium oxide (CeO2 ) nanocrystals form strained layers of manganese oxide (Mn3 O4 ) islands, increasing the number of oxygen vacancies. CeO2 /Mn3 O4 nanocrystals show better catalytic activity than CeO2 or Mn3 O4 alone and can protect the regenerative capabilities of intestinal stem cells in an organoid model after a lethal dose of irradiation. A small amount of the nanocrystals prevents acute radiation syndrome and increases the survival rate of mice treated with a lethal dose of total body irradiation.

Nonthermal plasma is a promising novel therapy for the alteration of biological and clinical functions of cells and tissues, including apoptosis and inhibition of tumor progression. This therapy generates reactive oxygen and nitrogen species (RONS), which play a major role in anticancer effects. Previous research has verified that plasma jets can selectively induce apoptosis in various cancer cells, suggesting that it could be a potentially effective novel therapy in combination with or as an alternative to conventional therapeutic methods. In this study, we determined the effects of nonthermal air soft plasma jets on a U87 MG brain cancer cell line, including the dose- and time-dependent effects and the physicochemical and biological correlation between the RONS cascade and p38/mitogen-activated protein kinase (MAPK) signaling pathway, which contribute to apoptosis. The results indicated that soft plasma jets efficiently inhibit cell proliferation and induce apoptosis in U87 MG cells but have minimal effects on astrocytes. These findings revealed that soft plasma jets produce a potent cytotoxic effect via the initiation of cell cycle arrest and apoptosis. The production of reactive oxygen species (ROS) in cells was tested, and an intracellular ROS scavenger, N-acetyl cysteine (NAC), was examined. Our results suggested that soft plasma jets could potentially be used as an effective approach for anticancer therapy.

Introduction Although mesenchymal stem cells (MSCs) have antitumor potential in hepatocellular carcinoma and breast cancer cells, the antitumor mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) in prostate cancer cells still remains unclear. Thus, in the present study, we elucidated the antitumor activity of hUCMSCs in PC-3 prostate cancer cells in vitro and in vivo. Methods hUCMSCs were isolated from Wharton jelly of umbilical cord and characterized via induction of differentiations, osteogenesis, and adipogenesis. Antitumor effects of UCMSCs on tumor growth were evaluated in a co-culture condition with PC-3 prostate cancer cells. PC-3 cells were subcutaneously (sc) injected into the left flank of nude mice, and UCMSCs were sc injected into the right flank of the same mouse. Results We found that hUCMSCs inhibited the proliferation of PC-3 cells in the co-culture condition. Furthermore, co-culture of hUCMSCs induced the cleavage of caspase 9/3 and PARP, activated c-jun NH2-terminal kinase (JNK), and Bax, and attenuated the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/ AKT, extracellular signal-regulated kinase (ERK), and the expression of survival genes such as Bcl-2, Bcl-xL, Survivin, Mcl-1, and cIAP-1 in PC-3 cells in Western blotting assay. Conversely, we found that treatment of specific JNK inhibitor SP600125 suppressed the cleavages of caspase 9/3 and PARP induced by hUCMSCs in PC-3 cells by Western blotting and immunofluorescence assay. The homing of hUCMSCs to, and TUNEL-positive cells on, the K562 xenograft tumor region were detected in Nu/nu-BALB/c mouse. Conclusions These results suggest that UCMSCs inhibit tumor growth and have the antitumor potential for PC-3 prostate cancer treatment.

Information-centric networking (ICN) has emerged as a promising candidate for the architecture of the future Internet of Things (IoT). ICN provides unique and location-independent content names, in-network caching and name-based routing. Consequently, locating the demanded device or content is one of the major challenges in ICN-based IoT networks. In this paper, we propose a BFH2M2: Bloom Filter based Hierarchical Hybrid Mobility Management that works in IoT with Edge-Fog Cloud architecture. The proposed BFH2M2 uses the hybrid location scheme that combines direct location with indirect location schemes depending on a moving device characteristics. Also, BFH2M2 uses time-based location update mixed with geographic-based location update, and it uses various Bloom filters: counting Bloom filter (CBF), mapping Bloom filter information base (MaBFIB) and attenuated Bloom filter (ABF) as data structures to effectively store and query the location and routing information of a node name. The performance of BFH2M2 is evaluated through an analytical model.