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The ubiquitin–proteasome system (UPS) controls protein homeostasis to maintain cell functionality and survival. Neurogenesis relies on proteasome function, and a defective proteasome system during brain development leads to neurological disorders. An endocrine-disrupting xenoestrogen bisphenol-A (BPA) used in plastic products adversely affects human health and causes neurotoxicity. Previously, we reported that BPA reduces neural stem cells (NSCs) proliferation and differentiation, impairs myelination and mitochondrial protein import, and causes excessive mitochondrial fragmentation leading to cognitive impairments in rats. Herein, we examined the effect(s) of prenatal BPA exposure on UPS functions during NSCs proliferation and differentiation in the hippocampus. Rats were orally treated with 40 µg/kg body weight BPA during day 6 gestation to day 21 postnatal. BPA significantly reduced proteasome activity in a cellular extract of NSCs. Immunocytochemistry exhibited a significant reduction of 20S proteasome/Nestin + and PSMB5/Nestin + cells in NSCs culture. BPA decreased 20S/Tuj1 + and PSMB5/Tuj1 + cells, indicating disrupted UPS during neuronal differentiation. BPA reduced the expression of UPS genes, 20S, and PSMB5 protein levels and proteasome activity in the hippocampus. It significantly reduced overall protein synthesis by the loss of Nissl substances in the hippocampus. Pharmacological activation of UPS by a bioactive triterpenoid 18α-glycyrrhetinic acid (18α GA) caused increased proteasome activities, significantly increased neurosphere size and number, and enhanced NSCs proliferation in BPA exposed culture, while proteasome inhibition by MG132 further aggravates BPA-mediated effects. In silico studies demonstrated that BPA strongly binds to catalytic sites of UPS genes (PSMB5, TRIM11, Parkin, and PSMD4) which may result in UPS inactivation. These results suggest that BPA significantly reduces NSCs proliferation by impairing UPS, and UPS activation by 18α GA could suppress BPA-mediated neurotoxicity and exerts neuroprotection.

Consistently emerging variants and the life-threatening consequences of SARS-CoV-2 have prompted worldwide concern about human health, necessitating rapid and accurate point-of-care diagnostics to limit the spread of COVID-19. Still, However, the availability of such diagnostics for COVID-19 remains a major rate-limiting factor in containing the outbreaks. Apart from the conventional reverse transcription polymerase chain reaction, loop-mediated isothermal amplification-based (LAMP) assays have emerged as rapid and efficient systems to detect COVID-19. The present study aims to develop RT-LAMP-based assay system for detecting multiple targets in N, ORF1ab, E, and S genes of the SARS-CoV-2 genome, where the end-products were quantified using spectrophotometry, paper-based lateral-flow devices, and electrochemical sensors. The spectrophotometric method shows a LOD of 10 agµL−1 for N, ORF1ab, E genes and 100 agµL−1 for S gene in SARS-CoV-2. The developed lateral-flow devices showed an LOD of 10 agµL−1 for all four gene targets in SARS-CoV-2. An electrochemical sensor developed for N-gene showed an LOD and E-strip sensitivity of log 1.79 ± 0.427 pgµL−1 and log 0.067 µA/pg µL−1/mm2, respectively. The developed assay systems were validated with the clinical samples from COVID-19 outbreaks in 2020 and 2021. This multigene target approach can effectively detect emerging COVID-19 variants using combination of various analytical techniques at testing facilities and in point-of-care settings.

Aggregation of α-synuclein (α-syn) is associated with the manifestation of various pathogenic synucleinopathies, including Parkinson’s disease attributed to both genetic and environmental stress factors. The initial events triggering α-syn aggregation and disease initiation due to environmental stress factors are still largely unknown. Here, to understand the mechanism of misfolding and aggregation initiation, we induced α-syn aggregation with rotenone, an established chemical inducer of PD like symptoms. We found that rotenone accelerates the formation of structurally distinct oligomers and fibrils that act as templates and increase the formation of conformers capable of spreading to the neighboring neuronal cells. Molecular dynamics simulations and NMR studies revealed the involvement of NAC region and formation of helical conformations resulting in structural variations in oligomers and fibrils. These structural variations affect the cytotoxic potential of oligomers and fibrils, where, the beta sheet rich oligomers and fibrils alter the membrane potential of neuronal cells and lead to early apoptosis. Our results describe the initial mechanistic events in pathogenic protein aggregation, where initial structural alterations in response to external stress factors dictate the toxicity of resulting conformers. This information will further provide insights in the understanding of protein aggregation, disease progression and pathogenesis.

Chaperonins are cage-like complexes in which nonnative polypeptides prone to aggregation are thought to reach their native state optimally. However, they also may use ATP to unfold stably bound misfolded polypeptides and mediate the out-of-cage native refolding of large proteins. Here, we show that even without ATP and GroES, both GroEL and the eukaryotic chaperonin containing t-complex polypeptide 1 (CCT/TRiC) can unfold stable misfolded polypeptide conformers and readily release them from the access ways to the cage. Reconciling earlier disparate experimental observations to ours, we present a comprehensive model whereby following unfolding on the upper cavity, in-cage confinement is not needed for the released intermediates to slowly reach their native state in solution. As over-sticky intermediates occasionally stall the catalytic unfoldase sites, GroES mobile loops and ATP are necessary to dissociate the inhibitory species and regenerate the unfolding activity. Thus, chaperonin rings are not obligate confining antiaggregation cages. They are polypeptide unfoldases that can iteratively convert stable off-pathway conformers into functional proteins.

Engineered nanoparticles (ENPs) are artificially synthesized particles with unique physicochemical properties. ENPs are being extensively used in several consumer items, elevating the probability of ENP exposure to biological systems. ENPs interact with various biomolecules like lipids, proteins, nucleic acids, where proteins are most susceptible. The ENP-protein interactions are mostly studied for corona formation and its effect on the bio-reactivity of ENPs, however, an in-depth understanding of subsequent interactive effects on proteins, such as alterations in their structure, conformation, free energy, and folding is still required. The present review focuses on ENP-protein interactions and the subsequent effects on protein structure and function followed by the therapeutic potential of ENPs for protein misfolding diseases.

Protein misfolding under stressful environmental conditions cause several cellular problems owing to the disturbed cellular protein homeostasis, which may further lead to neurological disorders like Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyloid lateral sclerosis and Huntington disease (HD). The presence of cellular defense mechanisms like molecular chaperones and proteasomal degradation systems prevent protein misfolding and aggregation. Molecular chaperones plays primary role in preventing protein misfolding by mediating proper native folding, unfolding and refolding of the polypeptides along with vast number of cellular functions. In past few years, the understanding of molecular chaperone mechanisms has been expanded enormously although implementation to prevent protein aggregation diseases is still deficient. We in this review evaluated major classes of molecular chaperones and their mechanisms relevant for preventing protein aggregation, specific case of α-synuclein aggregation. We also evaluate the molecular chaperone function as a novel therapeutic approach and the chaperone inhibitors or activators as small molecular drug targets.

The immense applications of titanium dioxide nanoparticles (TiO2 NPs) in consumer products have raised concerns about their health effects especially because TiO2 NPs can interact with various biomolecules. Out of these, proteins are more prone to alterations owing to their dynamic nature. Different protein conformers co-exist in cellular systems, and studying the interaction of protein conformers with nanoparticles becomes crucial for mechanistic understanding and therapeutic applications of TiO2 NPs. In the present study, the effect of TiO2 NPs on native, unfolded, and misfolded luciferase has been investigated. TiO2 NPs were found to destabilize native luciferase, interfere with the spontaneous refolding of unfolded luciferase, and promote luciferase misfolding; however, minor structural alterations were observed indicating weak interactions between the TiO2 NPs and luciferase. Morphological analysis of TiO2 NPs showed an average size of 24.57 ± 4.94 nm that increased to 50.52 ± 16.71 nm upon adsorption of luciferase on to TiO2 NPs. This study provides an understanding on the implication of nanoparticle-protein interaction on structural and conformational changes in various protein conformers.

In both developing and developed countries, cancer has become one of the most fearsome health ailments in the 21st century. Among the different variants of cancer, colon cancer is the 3rd most prevalent cancer globally and the 2nd deadliest form of cancer. Early diagnosis is very critical for the successful treatment of colon cancer. In recent times, machine-learning approaches have made significant strides in IoT-assisted healthcare systems. Computer-aided diagnostic systems driven by deep learning algorithms can detect colon cancer with great accuracy, assisting the medical profession in quick diagnosis and developing quick remedies against it. In our approach, we have developed a deep learning model based on convolutional neural network architecture to accurately classify and detect colon cancer. The developed model has been trained with 10,000 histopathological images of the colon, divided into two classes: colon adenocarcinoma and colon benign tissues, each containing 5000 images. We have also employed various performance metrics in our research to monitor the performance of our machine-learning model. The proposed model has been trained for 30 epochs with a batch size of 32 and achieved an overall accuracy of 98.79%.

Purpose The purpose of this paper is to investigate the influencing factors of generation Z (Gen Z) consumers’ revisit intentions to robotic restaurants in the post-pandemic times. Design/methodology/approach Using a sample of Gen Z consumers with dining experiences in an Indian restaurant using service robots, the study empirically tests a research framework based on stimulus–organism–response theory. Findings The study explains how Gen Z consumer’s perceptions of functional attributes (i.e. perceived usefulness and perceived ease of use), socio-emotional attribute (i.e. perceived safety) and relational attribute (i.e. trust) shape their attitude, which in turn leads to their evaluations of performance outcomes and intention to revisit the robotic restaurants. The findings also indicate that perceived risk reduction of viral infection moderates the impact of performance outcomes on revisit intention. Originality/value Due to the outbreak of COVID-19 pandemic, the changing preferences of consumers have resulted in an increase in demand for restaurants offering robotic services. To support the long-term viability of service robots in restaurant services, the current study investigates what elements of service robots can determine consumers’ intentions to revisit the robotic restaurants during post-pandemic times.

Purpose This study aims to explore the role of virtual tours in determining the Indian young consumers’ hotel booking intentions. The study’s framework is grounded in the stimulus organism response (SOR) theory and technology acceptance model (TAM). Design/methodology/approach The data collected through a survey generated 352 usable customer responses that were analysed using Structural Equation Modelling (SEM). Findings Young consumers’ perceptions of the hedonic and utilitarian attributes of virtual tours (stimulus) shape their attitude (organism), which in turn influences their behavioural intentions of online hotel booking (response). Originality/value Integrating the SOR and TAM frameworks, the study empirically examines the key determinants of potential consumers’ behavioural intentions in the context of an emerging country.