Unravelling the benefits of transition-metal-co-doping in lanthanide upconversion nanoparticles.

Recent advances reveal that upconversion (UC) luminescent materials are highly important not just from a scientific, but also from a future application standpoint. Although significant progress has been made in this field in recent decades, still their versatile applications are hindered by the low upconversion luminescence intensity and low tuneability, which has hampered further implementation in real life applications. We find it highly beneficial to compile a summary of recent relevant literature and propose ways to enhance upconversion efficiency in lanthanide nanomaterials. One very promising way to tackle this problem is through implementing transition metal ion co-dopants into the materials, which is the focus of this tutorial review. In this review, the recent studies related to the tailored design of UC materials with transition metal ion co-dopants have been summarized, and the desirable functionality of transition metal ions in the host matrixes has been discussed. Apart from improving the upconversion efficiency, the implementation of transition metal-co-dopants into lanthanide upconversion materials has recently sparked interest in applications such as in vivo imaging, drug delivery or nanothermometers.

Application of Nanoscale Materials and Nanotechnology Against Viral Infection: A Special Focus on Coronaviruses.

INTRODUCTION: In recent years, viral infections and associated diseases have become a big challenge for humanity due to high morbidity rates globally. However, timely, accurate, and rapid detection of viral infection may lead to the control of morbidity as well as provide enough time for vaccine preparation and early antiviral therapy. Existing virus detection methods based on immunological and molecular diagnosis found drawbacks, such as its time-consuming and costly one. Recently, the introduction of nanomaterials having multiple unique properties with a series of smart and innovative nano-based technologies have been under investigation for rapid viral detection. This chapter aims to critically review recent literature to illustrate the encompassing applications of nano-engineered materials and further highlighting the role of their active surface in improving the virus detection with high sensitivity and detection range, and in a short time. METHODS: The authors review the research findings related to emerging nanotechnology-based virus detection systems and their applicability for diagnostics of infectious viruses. RESULTS: Recent advances in nanotechnology allow for the development of robust, rapid, and sensitive detection of infectious virus to overcome deficiencies of conventional detection technologies. Nanoparticles have several distinctive physical and chemical characteristics such as unique optical, electronic, and magnetic properties compared to their bulk form enabling them the detection of biological agents like viruses. Further, high surface area to volume ratios of nanoparticles also provides a platform for multi-functionalization with various organic or biological ligands for the selective binding and detection of biological targets like viruses. For instance, colloidal gold nanoparticle-based lateral-flow (AuNP-LF) provides rapid diagnosis and on-site diagnosis of SARS-CoV-2 virus via the IgM detection using the indirect immune-chromatography method. CONCLUSION: The distinct properties of nanomaterials such as plasmon resonance absorption, conductivity, redox behavior, etc. along with surface functionalization might be used in the development of the nano-sensing system with high accuracy and rapid detection of infectious viral diagnosis at the point of care application.

Label-free gold nanorod-based plasmonic sensing of arsenic(iii) in contaminated water.

In this paper, we report a strategy based on unmodified gold nanorods for sensitive and selective detection of arsenic(iii) in contaminated water for the first time. The strategy relies on the inhibitory effect of arsenic(iii) on iron(iii)-mediated oxidative shortening of gold nanorods (Au-NRs) in acidic pH and at increased temperature. The arsenic(iii)-mediated inhibition of Au-NR oxidation is demonstrated by the red-shift of the longitudinal surface plasmon resonance (LSPR) band of Au-NRs. The novelty of our sensing strategy is the fact that it is label-free as it doesn't include any arsenic(iii) selective functionalization of Au-NRs. Moreover, this strategy can detect the arsenic(iii) content in water down to 10 ppb, which is the maximum permissible limit of the arsenic trace in drinking water according to the World Health Organization (WHO) guidelines. The effect of H2O2 in controlling the selectivity of our sensing strategy is investigated. It is found that in the absence of H2O2, the strategy is selective for arsenic(iii) with a broad dynamic response range (10-500 ppb), except for the interference from copper(ii). However, the interference of copper(ii) is efficiently eliminated by selective removal of copper(ii) from water via magnetic separation using polyethyleneimine-functionalized cobalt ferrite nanoparticles. The morphology of Au-NRs and the shift of the LSPR band during the sensing of arsenic(iii) are established by electron microscopy images and Vis-NIR absorption spectroscopy. This strategy is successfully applied for the estimation of arsenic(iii) in the real water sample and this paves the way for the implementation of our strategy for the real-time estimation of arsenic(iii) contamination levels found across prevalent drinking water sources, which are otherwise difficult to achieve with traditional sensors.

The Interplay between Heat Shock Proteins and Cancer Pathogenesis: A Novel Strategy for Cancer Therapeutics.

Heat shock proteins (HSPs) are developmentally conserved families of protein found in both prokaryotic and eukaryotic organisms. HSPs are engaged in a diverse range of physiological processes, including molecular chaperone activity to assist the initial protein folding or promote the unfolding and refolding of misfolded intermediates to acquire the normal or native conformation and its translocation and prevent protein aggregation as well as in immunity, apoptosis, and autophagy. These molecular chaperonins are classified into various families according to their molecular size or weight, encompassing small HSPs (e.g., HSP10 and HSP27), HSP40, HSP60, HSP70, HSP90, and the category of large HSPs that include HSP100 and ClpB proteins. The overexpression of HSPs is induced to counteract cell stress at elevated levels in a variety of solid tumors, including anticancer chemotherapy, and is closely related to a worse prognosis and therapeutic resistance to cancer cells. HSPs are also involved in anti-apoptotic properties and are associated with processes of cancer progression and development, such as metastasis, invasion, and cell proliferation. This review outlines the previously mentioned HSPs and their significant involvement in diverse mechanisms of tumor advancement and metastasis, as well as their contribution to identifying potential targets for therapeutic interventions.

Proteins and their functionalization for finding therapeutic avenues in cancer: Current status and future prospective.

Despite the remarkable advancement in the health care sector, cancer remains the second most fatal disease globally. The existing conventional cancer treatments primarily include chemotherapy, which has been associated with little to severe side effects, and radiotherapy, which is usually expensive. To overcome these problems, target-specific nanocarriers have been explored for delivering chemo drugs. However, recent reports on using a few proteins having anticancer activity and further use of them as drug carriers have generated tremendous attention for furthering the research towards cancer therapy. Biomolecules, especially proteins, have emerged as suitable alternatives in cancer treatment due to multiple favourable properties including biocompatibility, biodegradability, and structural flexibility for easy surface functionalization. Several in vitro and in vivo studies have reported that various proteins derived from animal, plant, and bacterial species, demonstrated strong cytotoxic and antiproliferative properties against malignant cells in native and their different structural conformations. Moreover, surface tunable properties of these proteins help to bind a range of anticancer drugs and target ligands, thus making them efficient delivery agents in cancer therapy. Here, we discuss various proteins obtained from common exogenous sources and how they transform into effective anticancer agents. We also comprehensively discuss the tumor-killing mechanisms of different dietary proteins such as bovine α-lactalbumin, hen egg-white lysozyme, and their conjugates. We also articulate how protein nanostructures can be used as carriers for delivering cancer drugs and theranostics, and strategies to be adopted for improving their in vivo delivery and targeting. We further discuss the FDA-approved protein-based anticancer formulations along with those in different phases of clinical trials.

Detergent induced structural perturbations in peanut agglutinin: insights from spectroscopic and molecular dynamic simulation studies.

The three dimensional structure of a protein is very important for its structure. Studies relating to protein structure have been numerous and the effect of denaturants on proteins can help understand the process of protein folding and misfolding. Detergents are important denaturants and play important roles in various fields. Here we explored the effect of sodium dodecyl sulphate (SDS) and cetyltrimethylammonium bromide (CTAB) on the structure of peanut agglutinin (PNA). The protein was purified from its natural source and impact of SDS and CTAB was studied by circular dichroism, intrinsic fluorescence, 8-anilino-1-napthalenesulfonic acid, molecular docking and molecular dynamics simulation. Pure peanut agglutinin showed a trough at 220 nm and positive ellipticity peak at 195 nm, specific for lectins. Results from the experimental and simulation studies suggest how oppositely charged detergents can interact differently and lead to varied structural perturbations in PNA. Both the surfactants induce all α protein-like circular dichroism in the protein, above its critical micelle concentrations, with significant change in accessible surface area that became more hydrophobic upon the treatment. Major interactions between the surfactants and protein, resulting in PNA conformational rearrangement, are electrostatic and van der Waals interactions. However, CTAB, a cationic surfactant, has similar effects as anionic surfactant (SDS) but at significantly very low concentration. Though the effects followed same pattern in both the surfactant treatment, i.e. above respective CMC, the surfactants were inducing all α protein-like conformation in PNA.Communicated by Ramaswamy H. Sarma.

Turning 3D Covalent Organic Frameworks into Luminescent Ratiometric Temperature Sensors.

In this study, we report hybrid crystalline lanthanide-containing 3D covalent organic framework (Ln@3D COF) materials that are suitable for temperature sensing applications. Different routes to obtain these hybrid materials were tested and compared for material quality and thermometric properties. In the first approach, a bipyridine-containing 3D COF (Bipy COF) was grafted with a range of visible emitting lanthanide (Eu3+, Tb3+, Dy3+, and Eu3+/Tb3+) ß-diketonate complexes. In the second approach, a novel nanocomposite material was prepared by embedding NaYF4:Er,Yb nanoparticles on the surface of a nonfunctionalized 3D COF (COF-300). To the best of our knowledge, the luminescent materials developed here are the first 3D COFs to be tested as ratiometric temperature sensors. In fact, for the Bipy COF, two different types of thermometers were tested (the Eu3+/Tb3+ system and a rare Dy3+ system), with both showing excellent temperature sensing properties. The reported NaYF4:Er,Yb/COF-300 nanocomposite material combines upconverting nanoparticles with 3D COFs, similar to previously reported metal organic framework (MOF) nanocomposite materials; however, this type of hybrid material has not yet been explored for COFs. As such, our findings open a new pathway toward potential multifunctional materials that can combine thermometry with other modalities, such as catalysis or drug delivery, in just one nanocomposite material.

Comparative functional analysis of the Caenorhabditis elegans and Drosophila melanogaster proteomes.

The nematode Caenorhabditis elegans is a popular model system in genetics, not least because a majority of human disease genes are conserved in C. elegans. To generate a comprehensive inventory of its expressed proteome, we performed extensive shotgun proteomics and identified more than half of all predicted C. elegans proteins. This allowed us to confirm and extend genome annotations, characterize the role of operons in C. elegans, and semiquantitatively infer abundance levels for thousands of proteins. Furthermore, for the first time to our knowledge, we were able to compare two animal proteomes (C. elegans and Drosophila melanogaster). We found that the abundances of orthologous proteins in metazoans correlate remarkably well, better than protein abundance versus transcript abundance within each organism or transcript abundances across organisms; this suggests that changes in transcript abundance may have been partially offset during evolution by opposing changes in protein abundance.

Identification and functional characterization of N-terminally acetylated proteins in Drosophila melanogaster.

Protein modifications play a major role for most biological processes in living organisms. Amino-terminal acetylation of proteins is a common modification found throughout the tree of life: the N-terminus of a nascent polypeptide chain becomes co-translationally acetylated, often after the removal of the initiating methionine residue. While the enzymes and protein complexes involved in these processes have been extensively studied, only little is known about the biological function of such N-terminal modification events. To identify common principles of N-terminal acetylation, we analyzed the amino-terminal peptides from proteins extracted from Drosophila Kc167 cells. We detected more than 1,200 mature protein N-termini and could show that N-terminal acetylation occurs in insects with a similar frequency as in humans. As the sole true determinant for N-terminal acetylation we could extract the (X)PX rule that indicates the prevention of acetylation under all circumstances. We could show that this rule can be used to genetically engineer a protein to study the biological relevance of the presence or absence of an acetyl group, thereby generating a generic assay to probe the functional importance of N-terminal acetylation. We applied the assay by expressing mutated proteins as transgenes in cell lines and in flies. Here, we present a straightforward strategy to systematically study the functional relevance of N-terminal acetylations in cells and whole organisms. Since the (X)PX rule seems to be of general validity in lower as well as higher eukaryotes, we propose that it can be used to study the function of N-terminal acetylation in all species.

Dual-mode vehicles with simultaneous thermometry and drug release properties based on hollow Y2O3:Er,Yb and Y2O2SO4:Er,Yb spheres.

Employing luminescence thermometry in the biomedical field is undeniably appealing as many health conditions are accompanied by temperature changes. In this work, we show our ongoing efforts and results at designing novel vehicles for dual-mode thermometry and pH-dependent drug release based on hollow spheres. Hereby for that purpose, we exploit the hollow Y2O3 and Y2O2SO4 host materials. These two inorganic hollow phosphors were investigated and showed to have excellent upconversion Er3+-Yb3+ luminescence properties and could be effectively used as optical temperature sensors in the physiological temperature range when induced by near-infrared CW light (975 nm). Further, doxorubicin was exploited as a model anti-cancer drug to monitor the pH-dependent drug release of these materials showing that they can be used for simultaneous thermometry and drug delivery applications.

"Update vision on COVID-19: Structure, immune pathogenesis, treatment and safety assessment".

The on-going SARS-CoV-2 causing COVID-19 discovered in December 2019, is responsible for a global pandemic. The virus belongs to the group of enveloped viruses containing linear, non-segmented, single stranded, positive sense strand RNA as genetic material. Already six different strains Coronaviruses are being reported to infect humans, however the seventh one is genetically similar to the SARS Coronavirus and termed as SARS-CoV-2. Specific crucial macromolecules such as membrane, nuclear, spike and enveloped proteins including HE esterase are present in the virus that interact with ACE2, APN, NEU-5, 9SC2 moiety of humans plays significant role in occurrence and transmission of the devastating disease. This review article summarizes the structure, histopathology, transmission of novel Coronavirus, its symptoms with preventive measures & currently prescribed drugs. Though various drugs and therapy have been administrated or implemented to restrict COVID-19, however it is imperative to develop an antidote against SARS-CoV-2 by the scientific or research community to save life.

A high-quality catalog of the Drosophila melanogaster proteome.

Understanding how proteins and their complex interaction networks convert the genomic information into a dynamic living organism is a fundamental challenge in biological sciences. As an important step towards understanding the systems biology of a complex eukaryote, we cataloged 63% of the predicted Drosophila melanogaster proteome by detecting 9,124 proteins from 498,000 redundant and 72,281 distinct peptide identifications. This unprecedented high proteome coverage for a complex eukaryote was achieved by combining sample diversity, multidimensional biochemical fractionation and analysis-driven experimentation feedback loops, whereby data collection is guided by statistical analysis of prior data. We show that high-quality proteomics data provide crucial information to amend genome annotation and to confirm many predicted gene models. We also present experimentally identified proteotypic peptides matching approximately 50% of D. melanogaster gene models. This library of proteotypic peptides should enable fast, targeted and quantitative proteomic studies to elucidate the systems biology of this model organism.

Tailoring the Design of a Lanthanide Complex/Magnetic Ferrite Nanocomposite for Efficient Photoluminescence and Magnetic Hyperthermia Performance.

In this work, we have designed a magnetoluminescent nanocomposite as a single platform for optical imaging and safe magnetic hyperthermia therapy by optimizing the composition of magnetic nanoparticles and controlling the conjugation strategy of the luminescent lanthanide complex. We have synthesized CoxMn1-xFe2O4 nanoferrites, with x = 0 to 1 in 0.25 steps, from soft (MnFe2O4) to hard (CoFe2O4) ferrites of size (∼20 nm) following a one-pot oxidative hydrolysis method. We have performed the induction heating study with an aqueous dispersion of nanoferrites using an alternating magnetic field (AMF) of 12 kAm-1, 335 kHz. This shows an enhancement of heating efficiency with the increment of manganese content and attains the highest intrinsic loss power (ILP) of 6.47 nHm2 kg-1 for MnFe2O4 nanoparticles. We have then fabricated a magnetoluminescent nanocomposite employing MnFe2O4 nanoparticles as it shows outstanding heating performance within the threshold limit of AMF (≤5 × 109 Am-1 s-1). A layer-by-layer coating strategy is followed, where a pure silica coating of thickness ∼10 nm on MnFe2O4 nanoparticles is achieved before encapsulation of the luminescent complex of europium(III), 2-thenoyltrifluoroacetone, and 1,10-phenanthroline in the second layer of silica. This is to ensure the optimal distance between the magnetic core and Eu(III)-complex to pertain significant luminescence in the composite (Eu-MnFe2O4). The photoluminescence spectra of an aqueous dispersion of Eu-MnFe2O4 by excitation in the UV region show a narrow and strong emission at 612 nm, which is stable even after 72 h. The induction heating study of an aqueous dispersion of Eu-MnFe2O4 in 12 kAm-1, 335 kHz AMF shows an ILP as 4.02 nHm2 kg-1, which is remarkably higher than the hyperthermia efficiency of reported magnetoluminescent nanoparticles.

Epigenetic reprogramming in Mist1(-/-) mice predicts the molecular response to cerulein-induced pancreatitis.

Gene expression is affected by modifications to histone core proteins within chromatin. Changes in these modifications, or epigenetic reprogramming, can dictate cell fate and promote susceptibility to disease. The goal of this study was to determine the extent of epigenetic reprogramming in response to chronic stress that occurs following ablation of MIST1 (Mist1(-/-) ), which is repressed in pancreatic disease. Chromatin immunoprecipitation for trimethylation of lysine residue 4 on histone 3 (H3K4Me3) in purified acinar cells from wild type and Mist1(-/-) mice was followed by Next Generation sequencing (ChIP-seq) or ChIP-qPCR. H3K4Me3-enriched genes were assessed for expression by qRT-PCR in pancreatic tissue before and after induction of cerulein-induced pancreatitis. While most of H3K4Me3-enrichment is restricted to transcriptional start sites, >25% of enrichment sites are found within, downstream or between annotated genes. Less than 10% of these sites were altered in Mist1(-/-) acini, with most changes in H3K4Me3 enrichment not reflecting altered gene expression. Ingenuity Pathway Analysis of genes differentially-enriched for H3K4Me3 revealed an association with pancreatitis and pancreatic ductal adenocarcinoma in Mist1(-/-) tissue. Most of these genes were not differentially expressed but several were readily induced by acute experimental pancreatitis, with significantly increased expression in Mist1(-/-) tissue relative to wild type mice. We suggest that the chronic cell stress observed in the absence of MIST1 results in epigenetic reprogramming of genes involved in promoting pancreatitis to a poised state, thereby increasing the sensitivity to events that promote disease.

GPR56 Regulates VEGF production and angiogenesis during melanoma progression.

Angiogenesis is a critical step during cancer progression. The VEGF is a major stimulator for angiogenesis and is predominantly contributed by cancer cells in tumors. Inhibition of the VEGF signaling pathway has shown promising therapeutic benefits for cancer patients, but adaptive tumor responses are often observed, indicating the need for further understanding of VEGF regulation. We report that a novel G protein-coupled receptor, GPR56, inhibits VEGF production from the melanoma cell lines and impedes melanoma angiogenesis and growth, through the serine threonine proline-rich segment in its N-terminus and a signaling pathway involving protein kinase Cα. We also present evidence that the two fragments of GPR56, which are generated by autocatalyzed cleavage, played distinct roles in regulating VEGF production and melanoma progression. Finally, consistent with its suppressive roles in melanoma progression, the expression levels of GPR56 are inversely correlated with the malignancy of melanomas in human subjects. We propose that components of the GPR56-mediated signaling pathway may serve as new targets for antiangiogenic treatment of melanoma.

Experimental metastasis assay.

Metastasis is the leading cause of death in cancer patients. To understand the mechanism of metastasis, an experimental metastasis assay was established using immunodeficient mice. This article delineates the procedures involved in this assay, including sample preparation, intravenous injection, and culturing cells from lung metastases. Briefly, a pre-determined number of human cancer cells were prepared in vitro and directly injected into the circulation of immunodeficient mice through their tail veins. A small number of cells survive the turbulence in the circulation and grow as metastases in internal organs, such as lung. The injected mice are dissected after a certain period. The tissue distribution of metastases is determined under a dissecting microscope. The number of metastases in a specific tissue is counted and it directly correlates with the metastatic ability of the injected cancer cells. The arisen metastases are isolated and cultured in vitro as cell lines, which often show enhanced metastatic abilities than the parental line when injected again into immunodeficient mice. These highly metastatic derivatives become useful tools for identifying genes or molecular pathways that regulate metastatic progression.

A combined proteomic and genetic analysis identifies a role for the lipid desaturase Desat1 in starvation-induced autophagy in Drosophila.

Autophagy is a lysosomal-mediated degradation process that promotes cell survival during nutrient-limiting conditions. However, excessive autophagy results in cell death. In Drosophila, autophagy is regulated nutritionally, hormonally and developmentally in several tissues, including the fat body, a nutrient-storage organ. Here we use a proteomics approach to identify components of starvation-induced autophagic responses in the Drosophila fat body. Using cICAT labeling and mass spectrometry, differences in protein expression levels of normal compared to starved fat bodies were determined. Candidates were analyzed genetically for their involvement in autophagy in fat bodies deficient for the respective genes. One of these genes, Desat1, encodes a lipid desaturase. Desat1 mutant cells fail to induce autophagy upon starvation. The desat1 protein localizes to autophagic structures after nutrient depletion and is required for fly development. Lipid analyses revealed that Desat1 regulates the composition of lipids in Drosophila. We propose that Desat1 exerts its role in autophagy by controlling lipid biosynthesis and/or signaling necessary for autophagic responses.

Optimized peptide separation and identification for mass spectrometry based proteomics via free-flow electrophoresis.

Multidimensional LC-MS based shotgun proteomics experiments at the peptide level have traditionally been carried out by ion exchange in the first dimension and reversed-phase liquid chromatography in the second. Recently, it has been shown that isoelectric focusing (IEF) is an interesting alternative approach to ion exchange separation of peptides in the first dimension. Here we present an improved protocol for peptide separation by continuous free-flow electrophoresis (FFE) as the first dimension in a two-dimensional peptide separation work flow. By the use of a flat pI gradient and a mannitol and urea based separation media we were able to perform high-throughput proteome analysis with improved interfacing between FFE and RPLC-MS/MS. The developed protocol was applied to a cytosolic fraction from Schneider S2 cells from Drosophila melanogaster, resulting in the identification of more than 10,000 unique peptides with high probability. To improve the accuracy of the peptide identification following FFE-IEF we incorporated the pI information as an additional parameter into a statistical model for discrimination between correct and incorrect peptide assignments to MS/MS spectra.