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Autophagy-the lysosomal degradation of cytoplasmic components via their sequestration into double-membraned autophagosomes-has not been detected non-invasively. Here we show that the flux of autophagosomes can be measured via magnetic resonance imaging or serial near-infrared fluorescence imaging of intravenously injected iron oxide nanoparticles decorated with cathepsin-cleavable arginine-rich peptides functionalized with the near-infrared fluorochrome Cy5.5 (the peptides facilitate the uptake of the nanoparticles by early autophagosomes, and are then cleaved by cathepsins in lysosomes). In the heart tissue of live mice, the nanoparticles enabled quantitative measurements of changes in autophagic flux, upregulated genetically, by ischaemia-reperfusion injury or via starvation, or inhibited via the administration of a chemotherapeutic or the antibiotic bafilomycin. In mice receiving doxorubicin, pre-starvation improved cardiac function and overall survival, suggesting that bursts of increased autophagic flux may have cardioprotective effects during chemotherapy. Autophagy-detecting nanoparticle probes may facilitate the further understanding of the roles of autophagy in disease.

Post-transcriptional RNA modifications (PTxMs) present in small RNA species, specifically circulating extracellular RNAs, were recently identified as clinically relevant readouts, often more indicative of disease severity than the classical up and down changes in their copy number alone. While identification of PTxMs requires multiple and complex sample preparation steps, microgram-range amounts of RNA, followed by expensive and protracted bioinformatics analyses, the clinically relevant information is usually a yes/no for a particular genetic variant(s), and an up/down answer for relevant biomarkers. We have previously shown that molecular beacons (MBs) can identify specific nucleic acid sequences with picomolar sensitivity and single nucleotide specificity by exploiting the target-dependent change in their electrophoretic mobility profile. We now present a method for direct identification of miRNAs and isomiRs in cells and extracellular vesicles using gel electrophoresis, without the need for RNA isolation and purification. The detection is based on discreet changes in the hydrodynamic surface profile, the overall size, charge and charge distribution of the MB-target hybrid. Furthermore, using an RNA tertiary structure prediction algorithm (iFoldRNA) and a custom molecular dynamics simulation (DMD), we designed modified MBs specific for m6A-modified nucleotides in target RNA sequences. The sample preparation method coupled to the software package affords the design of specific MBs and sensitive, multiplex-type detection of targets in a wide variety of biofluids and cells, in a simple mix and read approach.

This century has observed unusual improvements in green materials through the development of biocomposites due to anxieties about the atmosphere and sustainability issues. These biocomposites can be effectively disposed of at the final existence without harming the environment, which is impossible with man-made fiber-based polymer composites. The natural fiber is not a problem-free option, and they maintain some shortfall features that are the considerable moisture assimilation and very anisotropicity. This review paper intends to give a short outline of various surface modification methods to improve the fiber–matrix adhesion influencing the significant enhancement of the mechanical properties of the biocomposites.

Recently, researchers and scientists are trying to overcome the environmental burden by using biocomposites in engineering applications as far as possible. The main source of biocomposites is cellulosic fibres which is a class of natural fibres. Instead of many advantages of cellulosic fibres, they and their polymer composites suffer from some limitations as well. The environmental conditions are one of the most important issues to degradation behavior of the cellulosic fibres polymer composites (CFPCs). Among the environmental conditions, water absorption is an important ground to degradation in the mechanical performance of the CFPCs, which resists them to be used in outdoor applications. Several studies have been presented on water absorption characteristics of cellulosic fibres and its polymer-based biocomposites. Further, the consequence of water uptake on the mechanical performance of biocomposites was also reported in many studies. In most of the cases, a negative effect of water absorption was observed, whereas in a few cases a positive effect was also seen. In the present study, mechanics and kinetics of water absorption for CFPCs are discussed. Further, a detailed literature review on water absorption of cellulosic fibres and their different types of polymer-based biocomposites has also been carried out. Furthermore, studies reported on the effect of water absorption on the mechanical properties were also systematically presented. Moreover, all the possible remedies to lower the water absorption capacity were also discussed in the present review paper.

Due to the dominating advantages of natural fibres such as biodegradability, eco-friendliness, nominal cost, low density and high specific strength, they are being used opposite to synthetic fibres in many industrial applications. Despite many advantages, these fibres face some limitations such as higher moisture uptake, quality variations, low thermal stability, and poor compatibility with polymeric matrix. To overcome these limitations, chemical treatments of these fibres were found to be the most suitable method to improve adhesion with polymers, increase their strength and water absorption resistance, and improve their composite properties also. Among chemical treatments, alkali treatment is the most widely used and versatile surface modification method of the natural fibres. A good number of research works have been carried out on effect of alkali treatment on the properties of natural fibres and its composites, which motivated for this review. In this paper, the effect of alkali treatment on the properties of natural fibres has been reviewed. In addition, the physical and mechanical properties, thermal analysis and tribological behaviour of its biocomposites are also reviewed. It was concluded that alkali treatment of natural fibres could provide enhanced properties of various bio-composites up to a great extent.

Background Cell therapy is one of the most promising therapeutic interventions for retinitis pigmentosa. In the current study, we aimed to assess if peripheral blood-derived monocytes which are highly abundant and accessible could be utilized as a potential candidate for phenotypic differentiation into neuron-like cells. Methods The peripheral blood-derived monocytes were reconditioned phenotypically using extrinsic growth factors to induce pluripotency and proliferation. The reconditioned monocytes (RM) were further incubated with a cocktail of growth factors involved in retinal development and growth to induce retinal neuron-like properties. These cells, termed as retinal neuron-like cells (RNLCs) were characterized for their morphological, molecular and functional behaviour in vitro and in vivo. Results The monocytes de-differentiated in vitro and acquired pluripotency with the expression of prominent stem cell markers. Treatment of RM with retinal growth factors led to an upregulation of neuronal and retinal lineage markers and downregulation of myeloid markers. These cells show morphological alterations resembling retinal neuron-like cells and expressed photoreceptor (PR) markers. The induced RNLCs also exhibited relative membrane potential change upon light exposure suggesting that they have gained some neuronal characteristics. Further studies showed that RNLCs could also integrate in an immune-deficient retinitis pigmentosa mouse model NOD.SCID-rd1 upon sub-retinal transplantation. The RNLCs engrafted in the inner nuclear layer (INL) and ganglion cell layer (GCL) of the RP afflicted retina. Mice transplanted with RNLCs showed improvement in depth perception, exploratory behaviour and the optokinetic response. Conclusions This proof-of-concept study demonstrates that reconditioned monocytes can be induced to acquire retinal neuron-like properties through differentiation using a defined growth media and can be a potential candidate for cell therapy-based interventions and disease modelling for ocular diseases.

Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein involved in redox signalling and programmed cell death. The role of AIF has been well recognized in diabetes and obesity. However, the aspect of AIF deficiency in the development of hepatic steatosis and liver injury is unknown. Therefore, in the current study, Harlequin (Hq mutant) mouse with markedly reduced content of AIF was investigated to explore the role of AIF on the initiation of liver injury. The wild type (WT) developed physiological and pathological features of non-alcoholic fatty liver disease (NAFLD) that were not seen in the Hq mice with AIF deficiency, when fed on high fat high fructose (HFHF) diet. Following bile duct ligation (BDL), the liver associated pathological changes were less conspicuous in Hq mice as compared to WT mice. The expression of AIF protein and apoptosis was markedly lesser as compared to their respective control in Hq mice on HFHF diet. Furthermore, the genes involved in fatty acid metabolism were also altered in the group of treated Hq mice. In conclusion, Hq mice failed to develop diet induced hepatic steatosis, suggestive of a role of AIF mediated pathway in the initiation and progression of liver inflammation. Thus, partial loss of AIF appears to be hepatoprotective. SIGNIFICANCE OF THE STUDY: AIF deficiency has multiple roles in altered pathology processes and cellular metabolism, thereby compromising the cellular homeostasis. Considering the molecular functions of AIF in other organ pathology little is known about its role in diet induced liver injury. Hence, the aim of the current study was to investigate the role of AIF deficiency in liver injury and diseases with focus on NAFLD. The study will help to deliniate the mechanisms of NAFLD using Harliquin Mice.

An integrated thermodynamic approach for selecting a suitable hydrate former for desalination prior to process design is presented. From amongst the various formers reported in literature, methane, carbon dioxide (CO2), ethane, propane and iso-butane were chosen for this investigation. Simulation studies related to formation of hydrates in pure and saline water (2–8 wt% salt) for the 5 chosen formers have been conducted to predict phase equilibria along with gas solubility in the aqueous phase. A commercial software HydraFLASH was used for this purpose. In addition, the hydration number and phase change enthalpy associated with hydrate formation/dissociation has been calculated, the latter determined using the Clapeyron equation. Simulation results wherever appropriate were validated with experimental data and good agreement was observed. The implications of the thermodynamic data obtained on desalination process design have been discussed to arrive at a suitable choice of former. The results favor propane and ethane as preferred candidates for hydrate based desalination.

The aim of present study is to overcome the limitations of natural fibres and its polymer based composites. In present work, a new approach as PLA coating of sisal fibres has been used. Hand lay up technique was used to fabricate the polyester based composites using alkali treated and PLA coated sisal fibres. Static analysis in terms of tensile and flexural test, and dynamic mechanical analysis in terms of storage modulus (E’), loss modulus (E”), damping (Tanδ) and glass transition temperature (Tg) was carried out. In addition, morphological analysis of fractured surface of the composites was performed using scanning electron microscopy (SEM). The results revealed that composite with PLA coated sisal fibres showed better mechanical performance than alkali treated and untreated sisal composites.

Nowadays, it has been global demand to overcome the abundant use of synthetic fibres with respect to save the environment. Sisal fibre is one of the widely used natural fibre and being used as rein...

Hepatitis B virus infection is a common cause of liver cirrhosis and hepatocellular carcinoma leading to about one million deaths annually. The disease pathogenesis is complex and incompletely understood, especially when it turns chronic. Among various factors known to be responsible for the disease progression, the immune system has the most important role to play. Viral clearance is largely T cells dependent, and progression to a chronic state is due to insufficient T cells response, partly due to T-regulatory cells. In chronic infections, functions of important immune cells like natural killer cells and dendritic cells are impaired, which enables the viral persistence and promotes the pathogenesis in the host body. Similarly, the virus is reported to modulate functions of monocytes, macrophages, and Kupffer cells to promote an immune-tolerant local environment in the liver. Though B cells are expected to be central to the humoral immune response that clears the virus, its role in chronic HBV is still obscure. This chapter would elaborate on the significant roles of immune cells in pathogenesis and in clearance of the hepatitis B virus.

The influence of pre-straining process on dynamic fracture behavior of Cu-strengthened high-strength low-alloy (HSLA) of varied amount of pre-straining has been investigated in the current study. The influence of pre-straining on deformation due to tensile loading and on ductile fracture behavior of the steel has been carried out with the help of instrumented Charpy test and standard fracture test. Study of microstructure, its hardness, and tensile properties has been done to understand and correlate these properties with Charpy and dynamic fracture behavior of the investigated steel. Prior to the machining of the specimen, the stock materials are pre-strained at different levels. All the Charpy V notch (CVN) specimens are fatigue pre-cracked to generate natural crack. The pre-crack length was restricted to 5 mm (a/w = 0.5). Force–time behavior curve and the force–displacement curve is determined by double numerical integration of force–time curve. In the investigated steel, normalized energy increased slightly up to a level of 2% pre-strain and then decreased by increasing pre-strain level greater than 2%. The dynamic fracture toughness first increases up to 2% and then decreases beyond 2% pre-strain indicating the influence of pre-strain on dynamic fracture toughness behavior of steel. The fracture surface of investigated steel has been examined under scanning electron microscopy. This study has been also focused to understand (i) The nature of the stretch zone—a featureless band that forms prior to initiation of ductile fracture and (ii) the micromechanism of slow stable crack growth.

Concentrated brines and bitterns rejected from various processes contain mineral salts of economic value. For example, sulphate-rich bittern generated at saltworks in the Rajasthan state of India exceeds 3 million tons annually and requires adequate treatment. Resource recovery from such unutilized by-products presents a sustainable waste management approach. This work presents the development and evaluation of a process for sodium-sulphate (Na2SO4) recovery from sulphate-rich bitterns using an integrated process combining cooling crystallization, filtration, and drying as major unit operations. A parametric study has been conducted to investigate the effect of various operating parameters on product (anhydrous sodium-sulphate) yield and quality. Chemical analysis, TGA, P-XRD, and SEM-EDX techniques were used to characterize the product quality and purity. Based on the parametric studies, a sodium-sulphate production process was designed, and material & energy balance was established. The mass balance calculations have shown that 1 ton of anhydrous Na2SO4 (~97 wt% purity) can be produced from 6.31 tons of bittern having a sulphate ion concentration of about 140.8 ± 6.94 g/l. Subsequently, the economic feasibility of a 5 ton/day anhydrous Na2SO4 capacity plant has been evaluated using the cost and profitability analysis. The engineering-economic calculations suggest that the sodium-sulphate production from bittern can be economically favourable, achieving a payback period of 3.5 years. The optimized parameters and economics presented in this paper could significantly help implement an actual sodium-sulphate recovery unit using sulphate-rich bittern as feed.

Clathrate hydrates are gaining interest in their applications in the area of energy and the environment. They are also being considered for recovering clean water from brackish water, seawater, wastewater, and industrial effluents. Water reclamation via clathrate hydrate is based on the formation, separation, and dissociation of hydrate crystals devoid of salt and metal ions from saline/wastewater. A comprehensive review of studies undertaken to date on the application of clathrate hydrates as promising carrier for water desalination/treatment is presented. Both fundamental and technological advancements in the clathrate hydrate technology are reported to establish its feasibility and potential for producing quality water from waste effluents. The hydrate forming agent and kinetic promoters have been found to be important factors for faster hydrate formation and subsequent water recovery. Several developments towards novel reactor design, efficient separation & washing methods, hybrid hydrate-membrane processes, multi-functional devices etc. present a strong case for considering the clathrate hydrate technique as an available alternative for water reclamation in near future.

Ice based Freeze Desalination (FD) offers a potential alternative to recover fresh water from seawater. There has been increased interest over the years in the development of continuous crystallizer configurations to address the combined challenge of ice yield and salinity reduction in FD. In this work, experimental studies have been conducted to establish the potential of a novel continuously operated U-shaped crystallizer for ice based Freeze Desalination (FD). Unlike conventional FD crystallizers researched till date, this crystallizer integrates pre-cooling, chilling and freezing of saline water in a single unit along with in-situ ice removal. Preliminary experiments were carried out using synthetic salt water to investigate the effect of salt water flow rate and coolant temperature on product water yield and salinity. Salinity was found to increase with water yield. The overall phase change heat transfer coefficient has also been estimated. Subsequently test runs were carried out using seawater samples under prescribed operating conditions identified from the synthetic salt water runs. Salinity reduction was observed to increase with an increase in number of washing steps and wash water requirement. The results obtained provide a strong case to promote the use of the U-shaped crystallizer for ice based FD.

Background With the aim of preparing a more effective, safe and economical vaccine for tuberculosis, inhalable live mycobacterium formulations were evaluated. Methods Alginate particles in the size range of 2–4 μm were prepared by encapsulating live Bacille Calmette–Guérin (BCG) and “Mycobacterium indicus pranii” (MIP). These particles were characterized for their size, stability and release profile. Mice were immunized with liquid aerosol or dry powder aerosol (DPA) alginate encapsulated mycobacterium particles and their in-vitro recall response and infection with mycobacterium H37Rv were investigated. Results It was found that the DPA of alginate encapsulated mycobacterium particles invoked superior immune response and provided higher protection in mice than the liquid aerosol. The BCG encapsulated in alginate particles (BEAP) and MIP encapsulated in alginate particles (MEAP) were engulfed by bone marrow dendritic cells (BMDCs) and co-localized with lysosome. The MEAP/BEAP activated BMDCs exhibited higher chemotaxis movement and had enhanced ability of antigen presentation to T cells. The in-vitro recall response of BEAP/MEAP immunized mice when compared in terms of proliferation index and Interferon gamma (IFN-gamma) released by splenocytes and mediastinal lymph node cells was found to be higher than mice immunized by liquid aerosol of BCG/MIP. Finally, different groups of immunized mice were infected with M. tb H37Rv and after 16 weeks the Colony forming units (CFUs) in lung and spleen estimated. The bacilli burden in the BEAP/MEAP immunized mice was significantly less than the respective liquid aerosol immunized mice and the histopathology of BEAP/MEAP immunized mice lungs showed very little damage. Conclusions These inhale-able vaccines formulation of alginate coated live mycobacterium are more immunogenic as compared to the aerosol of bacilli and they provide better protection in mice when infected with H37Rv. Electronic supplementary material The online version of this article (10.1186/s12879-019-4157-2) contains supplementary material, which is available to authorized users.

The social behaviour of bacteria for the fulfilment of different physiological activities is defined as Quorum Sensing (QS). This ranges from conjugation, symbiosis, virulence, antibiotic production, sporulation and biofilm formation. Streptococcus pyogenes which is also named as group A streptococcus (GAS) is a Gram-positive bacteria, is reported to cause diseases strictly in human. The different QS mechanisms in GAS (group A streptococcus) reported till date include Rgg-SHP quorum sensing pathway, SilC (streptococcal invasion locus) quorum-sensing pathway, Lantibiotic regulatory systems, LuxS and AI-2. The proteins of Rgg family are conserved transcription factors, which is modulated by short peptides, thus involve in the biofilm formation and virulence of bacteria. The SilC mechanism involved in the invasive tissue disease and also in the biofilm formation, Lantibiotic regulatory systems aids bacteria in adopting different immune evasion strategies and thus allow them to persist in the harsh hostile environment. Lastly, LuxS and AI-2 are the common mechanisms in all the different bacterial species including streptococcus for the virulence, motility and bio-film formation. The current chapter focuses on the detail mechanism of all the four different pathways along with the role of Quorum Sensing for the establishment of disease in the host, the immune evasion strategies of bacteria using Quorum sensing (QS) and future clinical perspective with possible applications. This may help to increase our vision towards putative vaccine targets by exploiting the mechanisms involved in Quorum Sensing.

Candida albicans a polymorphic fungus can cause wide range of disease in humans, its potential to transform between yeast to hypha form and biofilm formation is associated with its virulence. The regulated expression of virulence genes plays a critical role during pathogenesis and immune evasion. The synchronized expression of genes in accordance with the population density is define as Quorum sensing (QS).There are enormous information about prokaryotic QS but the eukaryotic QS was concealed till the discovery of farnesol in Candida albicans. Farnesol is a sesquiterpine alcohol produce endogenously in plants, animals and fungi. It inhibits the initiation of hyphal formation. Apart from farnesol other quorum sensing molecule (QSM) in fungal kingdom includes aromatic amino acid derived alcohols like tyrosol, tryptophol and phenylethanol. This chapter emphasizes more on the various types of mechanisms involved in the fungal Quorum sensing, elaborating their physiological effects and quorum sensing involved during the host-pathogen interactions. Understanding of Quorum sensing mechanisms in Candida albicans may open the door of various therapeutic possibilities.

The intercellular communication, commonly called as Quorum Sensing (QS) or auto induction, has been attributed for various coordinative and community phenomena in Gram positive and Gram negative bacteria. The signalling is facilitated by diffusible signal, auto inducers, in response to population of neighbouring bacteria. Consequently, QS influences bacterial phenotype such as the production of antibiotics. Current understanding of how bacteria mediate antibiotic synthesis in the natural environment is limited to classical quorum sensing receptors and ‘orphan’ quorum sensing receptors. The genetic studies and biochemical investigation of carbapenem synthesis in Serratia and Erwinia carotovora have acknowledged a group of nine genes complex in the assembly namely carRABCDEFGH which are responsible for antibiotic assembly. N-(3oxohexanoyl)-L-homoserine lactone (OHHL) is produced as a product of the independent carI gene activates CarR transcription factor. This OHHL reliant transcriptional activation permits the cells to synchronise expression of carbapenem with cell density. An orphan quorum-sensing receptor, discovered as the soil bacterium Burkholderia thailandensis, differs from classical quorum sensing as this receptor does not respond to characteristic quorum sensing signalling partners. The orphan receptor however responds to antibiotics, such as trimethoprim and sulfamethoxazole. Consequently, eliciting the expression of the genes malA-M which is involved in synthesis of the cytotoxic antibiotic malleilactone. This controlling pathway might be vital to sense and compete in mixed communities. The synthesis of antibiotic is very expensive for the bacteria therefore the induction and modus of induction is tightly regulated. This work is an understanding of the current view of quorum sensing and their function in modulating antibiotics synthesis.

Natural fibres are gaining attention day by day in industrial applications. The aim of current investigation is to enhance the performance of sisal fibre by its surface modifications. The surface modifications include alkali treatment with varying concentrations (2, 5, 10, 15 & 20 %) and coating of PLA with varying concentrations (2, 4, 6, 8 & 10 %). Treated and untreated sisal fibres were subjected to tensile test and thermo gravimetric analysis (TGA). In addition to this, sisal fibres were characterized by X-ray diffraction (XRD), and its structural morphology was studied by scanning electron microscope (SEM). Moreover, FTIR spectroscope analysis was also carried out to see the removal of hemicelluloses and lignin from sisal fibre by alkali treatment. It was observed that surface modifications had much influenced the performance of sisal fibre. On other hand, PLA coated fibre had a better performance than alkali treated fibre.