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Sanitation is becoming more crucial as urban populations rise, making waste management a crucial issue in smart cities. Accurate waste material identification and classification are necessary because the waste items vary as they deteriorate. Furthermore, traditional methods do not overcome the risk of contamination when non-recyclable or hazardous products are improperly disposed of with ordinary waste, and there is an issue of identifying the waste that deteriorates over time. Hence a novel method ''Simplified White Shark with Multivariate Deep Belief Network'' is proposed, it improves system effectiveness and efficiency by identifying waste things that deteriorate with time using an object detection algorithm called Simplified White Shark Object. In addition, a Nearest Centroid Deep Belief Network classification technique for precise waste classification in smart cities is also proposed. The suggested algorithm considerably boosts waste management performance by increasing classification accuracy, efficiency and sensitivity which reaches a maximum of 99.78 %, 99.34 %, 97.69 %, and the minimum error rate of 0.182.

Abstract Receptor-interacting protein kinases (RIPK)-1 and -3 play crucial roles in cell fate decisions and are regulated by multiple checkpoint controls. Previous studies have identified IKK1/2- and p38/MK2-dependent checkpoints that phosphorylate RIPK1 at different residues to inhibit its activation. In this study, we investigated TNF-induced death in MAPK-activated protein kinase 2 (MK2)-deficient cells and found that MK2 deficiency or inactivation predominantly leads to necroptotic cell death, even without caspase inhibition. While RIPK1 inhibitors can rescue MK2-deficient cells from necroptosis, inhibiting RIPK3 seems to switch the process to apoptosis. To understand the underlying mechanism of this switch, we screened a library of 149 kinase inhibitors and identified the adenosine analog 5-Iodotubercidin (5-ITu) as the most potent compound that sensitizes MK2-deficient MEFs to TNF-induced cell death. 5-ITu also enhances LPS-induced necroptosis when combined with MK2 inhibition in RAW264.7 macrophages. Further mechanistic studies revealed that 5-ITu induces RIPK1-dependent necroptosis by suppressing IKK signaling in the absence of MK2 activity. These findings highlight the role for the multitarget kinase inhibitor 5-ITu in TNF-, LPS- and chemotherapeutics-induced necroptosis and its potential implications in RIPK1-targeted therapies.

Abstract Background Gingivobuccal complex oral squamous cell carcinoma (GBC-OSCC) is an aggressive malignancy with high mortality often preceded by premalignant lesions, including leukoplakia. Previous studies have reported genomic drivers in OSCC, but much remains to be elucidated about DNA methylation patterns across different stages of oral carcinogenesis. Results There is a serious lack of biomarkers and clinical application of biomarkers for early detection and prognosis of gingivobuccal complex cancers. Hence, in search of novel biomarkers, we measured genome-wide DNA methylation in 22 normal oral tissues, 22 leukoplakia, and 74 GBC-OSCC tissue samples. Both leukoplakia and GBC-OSCC had distinct methylation profiles as compared to normal oral tissue samples. Aberrant DNA methylation increases during the different stages of oral carcinogenesis, from premalignant lesions to carcinoma. We identified 846 and 5111 differentially methylated promoters in leukoplakia and GBC-OSCC, respectively, with a sizable fraction shared between the two sets. Further, we identified potential biomarkers from integrative analysis in gingivobuccal complex cancers and validated them in an independent cohort. Integration of genome, epigenome, and transcriptome data revealed candidate genes with gene expression synergistically regulated by copy number and DNA methylation changes. Regularised Cox regression identified 32 genes associated with patient survival. In an independent set of samples, we validated eight genes (FAT1, GLDC, HOXB13, CST7, CYB5A, MLLT11, GHR, LY75) from the integrative analysis and 30 genes from previously published reports. Bisulfite pyrosequencing validated GLDC (P = 0.036), HOXB13 (P

Microneedle arrays are minimally invasive devices that have been extensively investigated for the transdermal/intradermal delivery of drugs/bioactives. Here, we demonstrate the release of bioactive molecules (estradiol, melatonin and meropenem) from poly(2-hydroxyethyl methacrylate), pHEMA, hydrogel-based microneedle patches in vitro. The pHEMA hydrogel microneedles had mechanical properties that were sufficiently robust to penetrate soft tissues (exemplified here by phantom tissues). The bioactive release from the pHEMA hydrogel-based microneedles was fitted to various models (e.g., zero order, first order, second order). Such pHEMA microneedles have potential application in the transdermal delivery of bioactives (exemplified here by estradiol, melatonin and meropenem) for the treatment of various conditions.

Abstract The TNF receptor-interacting protein kinases (RIPK)-1 and 3 are regulators of extrinsic cell death response pathways, where RIPK1 makes the cell survival or death decisions by associating with distinct complexes mediating survival signaling, caspase activation or RIPK3-dependent necroptotic cell death in a context-dependent manner. Using a mass spectrometry-based screen to find new components of the ripoptosome/necrosome, we discovered the protein-arginine methyltransferase (PRMT)-5 as a direct interaction partner of RIPK1. Interestingly, RIPK3 but not RIPK1 was then found to be a target of PRMT5-mediated symmetric arginine dimethylation. A conserved arginine residue in RIPK3 (R486 in human, R415 in mouse) was identified as the evolutionarily conserved target for PRMT5-mediated symmetric dimethylation and the mutations R486A and R486K in human RIPK3 almost completely abrogated its methylation. Rescue experiments using these non-methylatable mutants of RIPK3 demonstrated PRMT5-mediated RIPK3 methylation to act as an efficient mechanism of RIPK3-mediated feedback control on RIPK1 activity and function. Therefore, this study reveals PRMT5-mediated RIPK3 methylation as a novel modulator of RIPK1-dependent signaling.

Autophagy plays an important role in recognizing and protecting cells from invading intracellular pathogens such as Salmonella. In this work, we investigated the role of p38MAPK/MK2 in modulating the host cell susceptibility to Salmonella infection. Inhibition of p38MAPK or MK2 led to a significant increase of bacterial counts in Salmonella infected mouse embryonic fibroblasts (MEFs), as well as in MK2-deficient (Mk2-/-) cells. Furthermore, western blot analysis showed that Mk2-/- cells have lower level of LC3 lipidation, which is the indicator of general autophagy compared to Mk2-rescued cells. In Mk2-/- cells, we also observed lower activated TANK-binding kinase-1 phosphorylation on Ser172 and p62/SQTM1-Ser403 phosphorylation, which are important to promote the translocation of p62 to ubiquitinated microbes and required for efficient autophagy of bacteria. Furthermore, immunofluorescence analysis revealed reduced colocalization of Salmonella with LC3 and p62 in MEFs. Inhibition of autophagy with bafilomycin A1 showed increased bacterial counts in treated cells compared to control cell. Overall, these results indicate that p38MAPK/MK2-mediated protein phosphorylation modulates the host cell susceptibility to Salmonella infection by affecting the autophagy pathways.

Abstract The release of metformin, a drug used in the treatment of cancer and diabetes, from poly(2‐hydroxyethyl methacrylate), pHEMA, hydrogel‐based microneedle patches is demonstrated in vitro. Tuning the composition of the pHEMA hydrogels enables preparation of robust microneedle patches with mechanical properties such that they would penetrate skin (insertion force of a single microneedle to be ≈40 N). Swelling experiments conducted at 20, 35, and 60 °C show temperature‐dependent degrees of swelling and diffusion kinetics. Drug release from the pHEMA hydrogel‐based microneedles is fitted to various models (e.g., zero order, first order, second order). Such pHEMA microneedles have potential application for transdermal delivery of metformin for the treatment of aging, cancer, diabetes, etc.

Abstract The overexpression of Epidermal Growth Factor Receptor (EGFR) and dysregulation of its downstream effector pathways are important molecular hallmarks of oral cancers. Present study investigates the chemopreventive potential of polymeric black tea polyphenols (PBPs)/thearubigins (TRs) in the hamster model of oral carcinogenesis as well as determine the effect of PBPs on EGFR and the molecular players in the EGFR pathway. In dose-dependent manner, pre and concurrent treatment with PBPs (1.5%, 5%, 10%) decreased the number and volume of macroscopic tumors as well as the number and area of microscopic lesions. Interestingly, at 10% dose of PBPs, no macroscopic or microscopic tumors were observed. We observed PBPs mediated dose-dependent decrease in oxidative DNA damage (8OHdG); inflammation (COX-2); proliferation (PCNA, Cyclin D1); expression of EGFR, and its downstream signaling kinases (pAkt, Akt, and mTOR); hypoxia (HIF1α) and angiogenesis (VEGF). There was also a PBPs mediated dose-dependent increase in apoptosis (Bax). Thus, our data clearly indicate that the observed chemopreventive potential of PBPs was due to modulation in the EGFR pathway associated with cell proliferation, hypoxia, and angiogenesis. Taken together, our results demonstrate preclinical chemopreventive efficacy of PBPs and give an insight into its mechanistic role in the chemoprevention of experimental oral cancer.

Abstract Over the past decades, there has been an escalating rise in the need for chemicals and catalytic materials to keep up with global demands. Addressing those issues by conventional methods often becomes inefficient, with myriad operational risks. Process intensification methods through procedural and equipment‐based modifications have been considered greener, have higher heat and mass transfer rates, and operate with lower costs. In this review, research using ultrasonic reactors and microreactors, along with developments through an integrated external energy source, for synthesizing acrylic microspheres is covered extensively. Acrylic microspheres have garnered much interest for their biocompatibility, affinity toward functionalization, and wide range of applications. Core–shell, composite, functional‐group modified, and porous acrylic microspheres are used for enzyme immobilization and as catalyst carriers. The use of acrylic support has provided huge improvements in catalytic activity, reusability, recyclability, and overall stability. Finally, various other process intensification methods and alternate support materials are covered to help enhance future developments in the field of catalysis.

We present a composite Compressed Sensing system for the acquisition and recovery of compressible signals, where a sparse Binary Sensing Matrix aids Sparsity Order Estimation, and a Gaussian Sensing Matrix aids reconstruction. The Binary Sensing Matrix is deterministic and is adapted according to the varying nature of the sparsity order. We estimate the sparsity order by exploiting the sparse structure of the Binary Sensing Matrix and the statistics of the obtained measurements. We refine the estimates of the sparsity order using a Kalman filter with a discrete Markov model that characterizes the sparsity order variation. A Binary Sensing Matrix-Aided Orthogonal Matching Pursuit is developed for faster recovery of compressible signals. Simulation results on real-world and synthetic data demonstrate the merits of the proposed sparsity order estimation and recovery methods compared to other existing methods. Our proposed methods are practical and recover compressible signals at least 25% faster than the existing methods.

Macroautophagy (hereafter referred to as autophagy), a highly conserved metabolic process, regulates cellular homeostasis by degrading dysfunctional cytosolic constituents and invading pathogens via the lysosomal system. In addition, autophagy selectively recycles specific organelles such as damaged mitochondria (via mitophagy), and lipid droplets (LDs; via lipophagy) or eliminates specialized intracellular pathogenic microorganisms such as hepatitis B virus (HBV) and coronaviruses (via virophagy). Selective autophagy, particularly mitophagy, plays a key role in the preservation of healthy liver physiology, and its dysfunction is connected to the pathogenesis of a wide variety of liver diseases. For example, lipophagy has emerged as a defensive mechanism against chronic liver diseases. There is a prominent role for mitophagy and lipophagy in hepatic pathologies including non-alcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC), and drug-induced liver injury. Moreover, these selective autophagy pathways including virophagy are being investigated in the context of viral hepatitis and, more recently, the coronavirus disease 2019 (COVID-19)-associated hepatic pathologies. The interplay between diverse types of selective autophagy and its impact on liver diseases is briefly addressed. Thus, modulating selective autophagy (e.g., mitophagy) would seem to be effective in improving liver diseases. Considering the prominence of selective autophagy in liver physiology, this review summarizes the current understanding of the molecular mechanisms and functions of selective autophagy (mainly mitophagy and lipophagy) in liver physiology and pathophysiology. This may help in finding therapeutic interventions targeting hepatic diseases via manipulation of selective autophagy.

Abstract This work investigates the effect of a modified nickel‐doped metal‐organic framework (Ni‐ZIF‐67) as a filler on thermal, mechanical, and water vapor permeability properties of environmentally friendly waterborne polyurethane (WPU). The facile and greener ultrasound (sonochemical) technique is developed to prepare multifunctional Ni‐ZIF‐67@WPU nanocomposites, exhibiting superior crystallinity and uniform distribution. The resultant Ni‐ZIF‐67 nanoparticles and Ni‐ZIF‐67@WPU films are characterized by various techniques, including powder XRD, FE‐SEM, FTIR, TGA, UTM, contact angle, and antibacterial properties. Ni‐ZIF‐67@WPU nanocomposites exhibited excellent three‐fold mechanical performance (tensile strength ≈22 MPa) at a very low 5 wt.% filler loading and high thermal stability compared to pristine WPU. In addition, Ni‐ZIF‐67@WPU exhibited optimum water vapor permeability performance at 5.0 wt.% filler with the potential antibacterial application. Demonstrate that the rapid and facile synthesis approach can enhance the interaction of filler and matrix, high surface area, and tuneable pore size of filler material. This new insight has a new green approach for fabricating advanced nanocomposites toward practical utilization.

ABSTRACT Clinical and in vivo studies have demonstrated a role for hepatitis B virus (HBV)-encoded HBsAg (hepatitis B surface antigen) in HBV-related hepatocellular carcinoma (HCC); however, the underlying mechanisms remain largely unknown. Here, we investigated the role of HBsAg in regulating long noncoding RNAs (lncRNAs) involved in HCC progression. Our analysis of microarray data sets identified LINC00665 as an HBsAg-regulated lncRNA. Furthermore, LINC00665 is upregulated in liver samples from HBV-infected patients as well as in HCC, specifically in HBV-related HCC liver samples. These findings were supported by our in vitro data demonstrating that HBsAg, as well as HBV, positively regulates LINC00665 in multiple HBV cell culture models. Next, we evaluated the oncogenic potential of LINC00665 by its overexpression and CRISPR interference (CRISPRi)-based knockdown in various cell-based assays. LINC00665 promoted cell proliferation, migration, and colony formation but inhibited cell apoptosis in vitro. We then identified the underlying mechanism of HBsAg-mediated regulation of LINC00665. We used immunofluorescence assays to show that HBsAg enhanced the nuclear translocation of NF-κB factors in HepG2 cells, confirming that HBsAg activates NF-κB. Inhibition of NF-κB signaling nullified HBsAg-mediated LINC00665 upregulation, suggesting that HBsAg acts through NF-κB to regulate LINC00665. Furthermore, the LINC00665 promoter contains NF-κB binding sites, and their disruption abrogated HBsAg-induced LINC00665 upregulation. Finally, HBsAg facilitated the enrichment of the NF-κB factors NF-κB1, RelA, and c-Rel in the LINC00665 promoter. Taken together, this work shows that HBsAg can drive hepatocarcinogenesis by upregulating oncogenic LINC000665 through the NF-κB pathway, thereby identifying a novel mechanism in HBV-related HCC. IMPORTANCE Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Numerous reports indicate an oncogenic role for HBV-encoded HBsAg; however, the underlying mechanisms are not well understood. Here, we studied the role of HBsAg in regulating lncRNAs involved in hepatocarcinogenesis. We demonstrate that HBsAg, as well as HBV, positively regulates oncogenic lncRNA LINC00665. The clinical significance of this lncRNA is highlighted by our observation that LINC00665 is upregulated in liver samples during HBV infection and HBV-related HCC. Furthermore, we show LINC00665 can drive hepatocarcinogenesis by promoting cell proliferation, colony formation, and cell migration and inhibiting apoptosis. Taken together, this work identified LINC00665 as a novel gene through which HBsAg can drive hepatocarcinogenesis. Finally, we show that HBsAg enhances LINC00665 levels in hepatocytes by activating the NF-κB pathway, thereby identifying a novel mechanism by which HBV may contribute to HCC.

In the present work, the effect of various discontinuities like voids, soft inclusions and hard inclusions of the mixed-mode stress intensity factor (MMSIF), crack growth and energy release rate (ERR) of an edge crack isotropic plate under different loading like tensile, shear, combine and exponential by various numerical examples is investigated. The basic formulation is based on the extended finite element method (XFEM) through the M interaction approach using the level set method. The effect of single and multi voids and inclusions with position variation on MMSIF and crack growth are also investigated. The presented results would be applicable to enhancing the better fracture resistance of cracked structures and various loading conditions.