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Conductive polymers and their composite materials have attracted considerable interest due to their potential applications in sensors, actuators, drug delivery systems, and energy storage devices. Despite their wide range of applications, many challenges remain primarily with respect to the complex synthesis and time-consuming manufacturing steps that are often required in the fabrication process of various devices with conductive polymers. Here, we demonstrate the novel use of cold atmospheric plasma (CAP)-assisted deposition technologies as a solvent-free and scalable approach for in situ polymerization and direct deposition of conductive polypyrrole-silver (PPy-Ag) nanocomposites onto the desired substrates under atmospheric conditions. In this study, a systematic approach with different precursor composition mixtures containing pyrrole as the monomer and AgNO3as the photoinitiator was investigated to assess the effect of precursor composition on the final chemical, electrical, and mechanical properties of the PPy-Ag nanocomposite thin-film coatings which were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and cyclic bending tests. The characterizations indicated the possibility of fabricating PPy-Ag nanocomposite films with tunable degrees of polymerization and Ag nanoparticle loading by simply varying the percentage of AgNO3in precursor composition mixtures. Finally, as a proof of concept, the potential use of the PPy-Ag nanocomposite films with different Ag nanoparticle loading percentages was assessed for humidity sensing by measuring their level of change in electrical resistance in the relative humidity range of 12–60%. It is envisioned that the developed CAP-assisted deposition technology can provide a new stepping stone toward scalable additive manufacturing of various functional nanocomposite films for different low-cost and flexible electronic applications.

Despite remarkable progress during the past decade, eradication of established tumors by targeted cancer therapy and cancer immunotherapy remains an uphill task. Herein, we report on a combination approach for eradicating established mouse melanoma. Our approach employs the use of tumor selective chemotherapy in combination with in vivodendritic cell (DC) targeted DNA vaccination. Liposomes of a newly synthesized lipopeptide containing a previously reported tumor-targeting CGKRK-ligand covalently grafted in its polar head-group region were used for tumor selective delivery of cancer therapeutics. Liposomally co-loaded STAT3siRNA and WP1066 (a commercially available inhibitor of the JAK2/STAT3 pathway) were used as cancer therapeutics. In vivotargeting of a melanoma antigen (MART-1) encoded DNA vaccine (p-CMV-MART1) to dendritic cells was accomplished by complexing it with a previously reported mannose-receptor selective in vivoDC-targeting liposome. Liposomes of the CGKRK-lipopeptide containing encapsulated FITC-labeled siRNA, upon intravenous administration in B16F10 melanoma bearing mice, showed remarkably higher accumulation in tumors 24 h post i.v.treatment, compared to their degree of accumulation in other body tissues including the lungs, liver, kidneys, spleen and heart. Importantly, the findings in tumor growth inhibition studies revealed that only in vivoDC-targeted genetic immunization or only tumor-selective chemotherapy using the presently described systems failed to eradicate the established mouse melanoma. The presently described combination approach is expected to find future applications in combating various malignancies (with well-defined surface antigens).

This study investigates ceramic fused filament fabrication (CF3) 3D printing of alumina with an emphasis on the impact of particle morphology on feedstock preparation and printability. Spherical powder displayed superior flow with higher apparent density, tap density, and powder packing fraction compared to irregular powder. A 55 vol % powder loading was chosen to ensure good flowability during printing. Irregular powder-based feedstocks had 40X higher viscosity than spherical powder feedstocks at 400 s−1shear rate, posing potential printing challenges. Slow printing speed maintained low feed-rates for consistent material flow. The debinding and sintering process produced macroscopically defect-free alumina components with relative densities above 89 % for both powder morphologies. The focus of the work is on comparing two different powder particle morphologies influencing feedstock behavior, printing fidelity, and sintered part properties.

In the present study, Mg alloys were prepared with different strontium contents and investigated for applications as resorbable implants (screws, plates, stents etc.). Microstructural characterisation and phase analysis were performed by optical microscopy, scanning electron microscopy, X-ray diffraction, and transmission electron microscopy. Alloy with 0.5 wt-% strontium results in a microstructure with fine grains (179 ± 22 µm) and the highest second phase precipitates (area-fraction ∼1.55%). The immersion and electrochemical measurements were performed at different times in Hanks’ solution. The corrosion rate decreased with increasing strontium amount owing to precipitate barrier and protective corrosion products. In vitrobiocompatibility test was carried out by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The cell viability decreases with an increase in strontium content owing to presumably higher fraction of the Mg17Sr2phase.

In the present study, Mg alloys were prepared with different strontium contents and investigated for applications as resorbable implants (screws, plates, stents etc.). Microstructural characterisation and phase analysis were performed by optical microscopy, scanning electron microscopy, X-ray diffraction, and transmission electron microscopy. Alloy with 0.5?wt-% strontium results in a microstructure with fine grains (179?±?22?µm) and the highest second phase precipitates (area-fraction ~1.55%). The immersion and electrochemical measurements were performed at different times in Hanks’ solution. The corrosion rate decreased with increasing strontium amount owing to precipitate barrier and protective corrosion products. In vitrobiocompatibility test was carried out by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The cell viability decreases with an increase in strontium content owing to presumably higher fraction of the Mg17Sr2phase.

Water shortage has become a crucial problem in many regions of the world. The study has been conducted on the Taraphini river basin, situated at the plateau fringe in the western part of West Bengal, India. This is a hard rock region under a dry tropical sub-humid climate facing intense water shortages during dry seasons, increasing pressure on groundwater. Thus, the occurrence of groundwater becomes a concern. The groundwater potential regions are identified by applying the Analytical Hierarchy Process (AHP) and Multi-Influencing Factor (MIF) methods with an integrated Remote Sensing and Geographical Information System approach. Eight influencing factors- Geomorphology, Lineament density, Hydrogeology, Rainfall, Drainage density, Land use land cover, Slope and Soil types were analysed and assigned scores and weights according to their influence on groundwater and prepared two maps by integrating these factors in GIS system. The resultant groundwater potential maps are validated using groundwater level data of 50 groundwater wells in the region and the accuracy of the models is assessed through Receiver Operating Characteristics (ROC). The maps were divided into five classes. More than 55% of the area has very low and low groundwater potentiality, where, settlement is compact and developed in small patches and they practice rain-fed agriculture. Whereas, only 7% and 11% area of the region has very good and good groundwater potentiality, where, agriculture is irrigation-based and bigger and more compact settlements developed. The results of the study will benefit sustainable groundwater resource management in the hard rock region of the study area.

Purpose:Despite the reported high prevalence of dysphagia and reflux, patients with obstructive sleep apnea (OSA) are not routinely screened for dysphagia or reflux during conventional OSA management. The purpose of this exploratory study was to (a) identify prevalences of dysphagia and reflux self-reported symptoms in patients with OSA and (b) determine associations between dysphagia and reflux symptoms and demographic and clinical variables.Method:A chart review was completed on 75 patients with treated OSA during routine medical management at a university-affiliated sleep center. All participants completed the 10-Item Eating Assessment Tool (EAT-10) and Reflux Symptom Index (RSI) questionnaires, which are patient-reported outcome measures (PROMs) of swallowing and reflux symptoms, respectively. Relevant demographic and clinical variables were extracted. A binary logistic regression was computed to examine the relationships between dysphagia and reflux PROMs and demographic and clinical variables.Result:Sixty-three participants met eligibility criteria (Mage= 64 years). In addition, 14% (n= 9) and 11% (n= 7) of patients with OSA syndrome reported swallowing and reflux symptoms, respectively. Among the demographic and clinical variables investigated, there were no significant predictive factors for EAT-10 scores. Age and apnea–hypopnea index were significant predictive factors for RSI scores.Conclusions:To our knowledge, this is the first preliminary study to investigate swallowing and reflux symptoms concurrently in OSA, as well as potential mitigating factors. Although our findings suggest a relatively low percentage of patients with OSA report dysphagia and reflux symptoms, the true prevalences of swallowing and reflux disorders may be higher based on previous evidence suggesting that pharyngeal afferent (sensory) dysfunction may cause patients to underestimate their symptoms.

The process of angiogenesis, involving generation of new blood vessels from the existing ones, is vital for the supply of oxygen and nutrients to various tissues of body system. Angiogenesis is directly associated with several physiological and pathological processes. It is well-established that impairment in angiogenesis process results in various fatal conditions. Recently, few research groups including ours demonstrated therapeutic angiogenesis through nanomedicine approach using metal oxide/hydroxide nanoparticles. However, there is still a thorough necessity for the development of novel, eco-friendly, pro-angiogenic nanomaterials. Hence, in the present study we demonstrate the in vitro and in vivo pro-angiogenic properties of terbium hydroxide nanorods (THNRs) synthesized using an advanced microwave irradiation method, along with the detailed molecular signaling cascade underlying THNRs induced angiogenesis. The in vivo wound healing and nonimmunogenicity of the THNRs have been validated in the mouse models. We thus strongly believe that the present study establishing the pro-angiogenic properties of THNRs will aid in the development of alternative treatment strategies for wound healing along with cardiovascular and ischemic diseases, where angiogenesis is the chief target.

Although doped bioceramics have been widely investigated for biomedical applications, the codoped bioceramics remain mostly unexplored for bone regeneration applications. For example, the impact of codoping of Sr2+and Fe3+ions on the phase stability and cytocompatibility is not explored so far. In this perspective, the objective of the present study is to quantitatively understand this aspect in case of Fe/Sr codoped biphasic calcium phosphate (BCP). Following sol–gel synthesis, codoped BCP samples with Sr/Fe dopant concentrations of 2, 10, 20, 30, and 40 mol % as well as doped BCPs with single dopant (Sr or Fe) with similar compositions were calcined at 800 °C in air. Using extensive Rietveld analysis, the dopant content dependent crystallographic properties (e.g lattice parameters) and phase stability of HA/TCP are quantitatively assessed. In vitro cytocompatibility of codoped samples has been assessed using mouse osteoblast cells. An important observation is that, while singular dopant of Sr/Fe at 20 mol % or higher amount reduces cell viability significantly, osteoblast viability is not compromised to any significant extent on Sr/Fe codoped BCP, compared to undoped BCP. Our results indicate that one can tailor osteoblast functionality by controlling the codopant content. More importantly, all the codoped BCPs support cell proliferation, when single doped BCP exhibits significant reductionin cell viability, at dopant content of 10 mol % or higher. Cell morphological analysis supports extensive cell spreading on codoped BCPs. An attempt has been made to correlate the variation in cellular response with HA/TCP ratio and ion dissolution behavior. Taken together, the present work establishes unique advantage of Sr/Fe codoping approach toward realizing their bone replacement application.

Background: The importance of inhibiting the kinases of the DDR pathway for radiosensitizing cancer cells is well established. Cancer cells exploit these kinases for their survival, which leads to the development of resistance towards DNA damaging therapeutics. Objective: In this article, the focus is on targeting the key mediator of the DDR pathway, the ATM kinase. A new set of quinoline-3-carboxamides, as potential inhibitors of ATM, is reported. Methods: Quinoline-3-carboxamide derivatives were synthesized and cytotoxicity assay was performed to analyze the effect of molecules on different cancer cell lines like HCT116, MDA-MB-468, and MDA-MB-231. Results: Three of the synthesized compounds showed promising cytotoxicity towards a selected set of cancer cell lines. Western Blot analysis was also performed by pre-treating the cells with quercetin, a known ATM upregulator, by causing DNA double-strand breaks. SAR studies suggested the importance of the electron-donating nature of the R group for the molecule to be toxic. Finally, Western-Blot analysis confirmed the down-regulation of ATM in the cells. Additionally, the PTEN negative cell line, MDA-MB-468, was more sensitive towards the compounds in comparison with the PTEN positive cell line, MDA-MB-231. Cytotoxicity studies against 293T cells showed that the compounds were at least three times less toxic when compared with HCT116. Conclusion: In conclusion, these experiments will lay the groundwork for the evolution of potent and selective ATM inhibitors for the radio- and chemo-sensitization of cancer cells.

Capillary-driven ink infiltration through a porous powder bed in three-dimensional (3D) binder jet printing (inkjet printing onto a powder bed) controls the printing resolution and as-printed “green” strength of the resulting object. However, a full understanding of the factors controlling the kinetics of the infiltration remains incomplete. Here, high-resolution in situsynchrotron radiography provides time-resolved imaging of the penetration of an aqueous solution of eythylene glycol through a porous alumina powder bed, used as a model system. A static drop-on-demand inkjet printer was used to dispense liquid droplets onto a powder surface. The subsequent migration of the liquid front and its interactions with powder particles were tracked using fast synchrotron X-radiography in the Diamond Synchrotron, with phase-contrast imaging at a frame rate of 500 Hz. Image processing and analysis reveal that both the time-dependent increment in the wetting area and the propagation of the “interface leading edge” exhibit heterogeneous behavior in both temporal and spatial domains. However, mean infiltration kinetics are shown to be consistent with existing infiltration models based on the Washburn equation modified to account for the spreading of the liquid drop on the powder surface and using a modified term for the bed porosity.

Neuritogenesis, a complex process of the sprouting of neurites, plays a vital role in the structural and functional restoration of cerebral ischemia-injured neuronal tissue. Practically, there is no effective long-term treatment strategy for cerebral ischemia in clinical practice to date due to several limitations of conventional therapies, facilitating the urgency to develop new alternative therapeutic approaches. Herein, for the first time we report that pro-angiogenic nanomaterials, zinc oxide nanoflowers (ZONF), exhibit neuritogenic activity by elevating mRNA expression of different neurotrophins, following PI3K/Akt-MAPK/ERK signaling pathways. Further, ZONF administration to global cerebral ischemia-induced Fischer rats shows improved neurobehavior and enhanced synaptic plasticity of neurons via upregulation of Neurabin-2 and NT-3, revealing their neuroprotective activity. Altogether, this study offers the basis for exploitation of angio-neural cross talk of other pro-angiogenic nano/biomaterials for future advancement of alternative treatment strategies for cerebral ischemia, where neuritogenesis and neural repair are highly critical.

We have investigated the effect of piezoelectric actuating voltage on cell behavior after drop on demand inkjet printing using mouse 3T3 cells as a model cell line. Cell viability after printing was assessed using a live/dead assay, Alamar Blue as an assay for cell proliferation, and propidium iodide (PI) and Texas Red labeled dextran molecular probes to assess cell membrane integrity. No significant difference was found for the cell death rate compared between an unprinted control population and after printing at 80, 90, and 100 V, respectively. However, cell proliferation was lower than that of the control population at all time points postprinting. Cell membrane integrity was quantified using PI and dextran probes of mean molecular weight of 3, 10, 40, and 70 kDa. Total membrane damage (assessed by PI) increased with increasing piezoelectric actuator driving voltage, and this was always greater than the unprinted control cells. The uptake of the labeled dextran only occurs after inkjet printing and was never observed with the control cells. The largest dextran molecular probe of 70 kDa was only taken up by cells after printing using the lower printing voltages of 80 and 90 V and was absent after printing at 100 V. At the two lower printing voltages, the membrane damage is recovered, and no dextran molecule penetrated the cells 2 h after printing. However, printing at 100 V leads to an increased uptake of 3 and 10 kDa dextran molecules, the retention of membrane porosity, and continued uptake of these 3 and 10 kDa dextran for greater than 2 h postprinting. We hypothesize that the change in membrane porosity with increasing actuation voltage can be explained by distinct nucleation and growth stages for pore formation in response to printing stress.

Tissue engineering has been a subject of extensive scientific exploration in the last two decades making gradual inroads into clinical studies as well. Along with regenerative cells and growth factors, biomaterial scaffolds are integral to the development of a tissue engineered construct. It is now appreciated that scaffolds should mimic the target tissue properties intimately in order to provide a micro-environment milieu that allows the seeded cells to differentiate into the desired tissue. Even from a structural viewpoint, mismatch between scaffold and native matrix properties can cause cell necrosis through mechanisms such as stress shielding. One of the key properties of most body tissues is that they exhibit anisotropy. However, most fabrication methods generate isotropic scaffolds and require specific modifications to produce anisotropic scaffolds. In the last decade, the advent of additive manufacturing and bioprinting has provided facile tools to fabricate scaffolds with desired anisotropy. On the other hand, a biomimetic scaffold can be designed only when target tissue anisotropy is well known to the tissue engineer. This review presents an overview of the anisotropic properties of different tissues, which will be critical for developing biomimetic engineered constructs. The traditional anatomical records do not adequately present these properties from the perspective of designing tissue engineering scaffolds. Subsequently, present state-of-the art in development of anisotropic scaffolds as well as tissue constructs using different conventional and emerging fabrication techniques is discussed. It is expected that the readers will obtain a comprehensive reference on the research area by examining these two aspects juxtaposed to each other and gain key trends for fabrication of anisotropic scaffolds, plausibly with improved regenerative outcomes.

Combination of bioceramics with polymers to fabricate nanofibrous scaffolds holds enormous potential for bone tissue regeneration. In this study, we aim to incorporate HAp nanoparticles in trace doping amount in PVA-chitosan nanofiber matrix to fabricate PVA-chitosan composite nanofibers with improved performance for application as a bone tissue regeneration material. The diameter of the fabricated composite nanofibrous mat is estimated as 300 ± 121 nm. Beads free nanofibers mat with uniform morphology was ascertained for all sample groups by scanning electron microscopy (SEM) and the overall composition was assessed using Fourier transform infrared spectroscopy (FTIR) and energy dispersive X-ray spectroscopy (EDX). SEM images showed a homogeneous distribution of HAp nanoparticles in the composite nanofibers matrix. Further, X-ray diffraction (XRD) was performed to determine the crystallinity of the fabricated scaffolds. Swelling behavior and hydrolytic degradation of nanofibrous mats were subsequently evaluated by immersing in PBS buffer at pH 7.4 at physiological temperature (37 °C). The biocompatibility study of nanofiber scaffolds was performed with MC3T3 cells. Significantly higher cellular viability was observed on HAp nanoparticles incorporated composite nanofibrous scaffold surface after 7 days of culture in comparison to scaffolds without HAp.

Automated identification of healing progression in lower limb wounds is an important clinical challenge since such wounds fail to heal in an orderly and timely manner. Selection of suitable target features and employment of appropriate analytical tool are critical for the precise monitoring of the healing progression through automated diagnostic method. The present study aims at automated detection of healing trend based on characteristics of epithelial rete pegs, which is considered as an important parameter for monitoring and hence healing progression of epithelial maturation. To this aim, the applicability of various segmentation methods namely, watershed, marker-controlled watershed, k-means clustering and active contour method and comprehensive characterization of rete-pegs are studied and compared. Among them active contour provided better performance in terms of non-linear objective assessments including performance metrics like-peak-signal-to-noise-ratio, processing speed and Mean Square Error. Further, support vector machine is trained for classification of the rete-peg features at different time points of clinically diagnosed non-healing wounds treated with a specific protocol. Kappa scoring tests inter-rater agreement between applied segmentation protocol and ground truth images. The overall accuracy of the system has been found to be 95%. It is thus concluded that with the aid of the proposed segmentation and classification method an automated detection system can be developed for precise monitoring of lower limb wound healing progression.

Clitocybula albidais described from West Bengal, India. A comprehensive description, photographs, and comparisons with morphologically similar and phylogenetically related species are provided. Molecular phylogenetic analyses based on ITS sequences coupled with morphology confirmed the placement of this species inClitocybula.

Abstract

The polysaccharide alginate has received most extensive attention as bioink in bioprinting applications due to its ability to undergo gelation under cell-friendly conditions. However, absence of cell-binding motifs and the erratic degradation of alginate hydrogels have remained their persistent limitations. Honey is a conveniently available natural material, known for its role in wound healing and skin tissue regeneration. However, honey blending to improve biological response of alginate-based bioprinted scaffolds has not been yet reported. In the present work, honey-alginate bioinks were evaluated for their printability property (shape fidelity). It was found that honey blending reduced alginate viscosity, which gradually affected bioprinting fidelity. Therefore, the concentration that provides for acceptable bioprinting along with improvement in cell proliferations is determined. It is concluded that honey blending improves cell response of alginate bioinks and can be a facile approach to obtain bioinks especially for in situ skin tissue engineering applications.

The aim of this study was to microencapsulate the reuterin produced by Lactobacillus reuteriBPL-36 strain for its long-term efficacy against food-borne pathogen Listeria monocytogenes. Lactobacillus reuteriBPL-36 strain previously isolated from a human infant fecal sample in lab was selected for the present study based on its ability to produce reuterin. The organism displayed a broad-spectrum antimicrobial activity. Reuterin concentration of 89.63 mM was obtained in the MRS–glycerol medium after 16 h incubation at 37 °C. The reuterin concentration required to inhibit the growth of Pseudomonas aeruginosa, Escherichia coliO157: H7, Salmonella typhi, Staphylococcus aureus,and Listeria monocytogeneswas found to be 1.0, 2.0, 2.0, 4.0, and 10.0 AU/mL, respectively. Microencapsulation of reuterin to enhance long-term efficacy against food-borne pathogens was done. Results in this study indicated that the release characteristics of reuterin from the encapsulated particles were pH dependent. The release characteristics were unaffected by the storage of encapsulated reuterin at 4 °C for 2 weeks. The anti-listerial efficacy of the encapsulated reuterin was tested against L. monocytogenesin the BHI medium adjusted to pH 5.0 with a reuterin content equivalent to 16 mM, similar to un-encapsulated (free) reuterin. Encapsulated reuterin demonstrated enhanced efficacy against L. monocytogenesfor longer duration of time when compared with un-encapsulated (free) reuterin. The present work demonstrated a novel antimicrobial delivery system that ensured much better capability of inhibiting the growth of L. monocytogenesthroughout 24 h incubation at 37 °C.

This article reviews the current status and contemporary challenges involved in 3D inkjet powder printing of metallic biomaterials. The process physics, comprising of drop-on-demand methodology and binder-powder interaction are briefly discussed. For the later, various dimensionless numbers (Re, Oh and We) are emphasized as they govern the morphology and travel of the binder droplet. The post-impact interaction with powder particles are described into three sequential stages as, impact driven, capillary driven and equilibrium attainment. A review of several binder formulations to 3D print metallic biomaterials is presented along with the guidelines. Non-destructive 3D structural analysis, using advanced X Ray micro-computed tomography (XCT) technique is emphasized for porous architecture assessment (pore volume fraction, pore shape and size distribution, % interconnectivity) and dimensional tolerance. Finally, the processing and post-processing related challenges in terms of the suitable models for real time powder-binder interaction study, limitations in depowdering, heat treatment strategy, surface roughness are emphasized.

Despite quantum leaps, the biomimetic regeneration of cartilage and osteochondral regeneration remains a major challenge, owing to the complex and hierarchical nature of compositional, structural and functional properties. In this review, an account of the prevailing challenges in biomimicking the gradients in porous microstructure, cells and extracellular matrix (ECM) orientation is presented. Further, the spatial arrangement of the cues in inducing vascularization in the subchondral bone region while maintaining the avascular nature of the adjacent cartilage layer is highlighted. With rapid advancement in biomaterials science, biofabrication tools and strategies, the state-of-the-art in osteochondral regeneration since the last decade has expansively elaborated. This includes conventional and additive manufacturing of synthetic/natural/ECM-based biomaterials, tissue-specific/mesenchymal/progenitor cells, growth factors and/or signaling biomolecules. Beyond the laboratory-based research and development, the underlying challenges in translational research are also provided in a dedicated section. A new generation of biomaterial-based acellular scaffold systems with uncompromised biocompatibility and osteochondral regenerative capability is necessary to bridge the clinical demand and commercial supply. Encompassing the basic elements of osteochondral research, this review is believed to serve as a standalone guide for early career researchers, in expanding the research horizon to improve the quality of life of osteoarthritic patients affordably.

Despite different nanomaterials were developed so far against cancer, their potential drawbacks are still scarcely considered. The off-target delivery of a therapeutic compound, as well as the non-specific uptake of these nanomaterials by healthy tissues or organs, and their potential immunogenicity are some of the major issues that still have to be faced prior to a successful clinical translation. This work aims to develop an innovative theranostic, biocompatible, and drug-loaded nanoconstruct based on Gadolinium-doped Zinc Oxide (ZnO-Gd) nanocrystals (NCs), focusing on one of the most lethal diseases, i.e., pancreatic cancer. The use of zinc oxide is motivated by the huge potential of this nanomaterial already demonstrated for in vitro and in vivo applications, while the Gadolinium doping confers magnetic properties useful for diagnostics. Furthermore, an innovative biomimetic shell is here used to coat the NCs: it is composed of a lipid bilayer made from extracellular vesicles (EVs) combined with other synthetic lipids and a peptide targeting the pancreatic tumor microenvironment. To complete the nanoconstruct therapeutic function, Gemcitabine, a first-line drug for pancreatic cancer treatment, was adsorbed on the ZnO-Gd NCs prior to the coating with the above-mentioned lipidic shell. The aim of this work is thus to strongly enhance the therapeutic capability of the final nanoconstruct, providing it with high biocompatibility, colloidal stability in biological media, efficient cargo loading and release properties, as well as active targeting for site-selective drug delivery. Furthermore, the magnetic properties of the ZnO-Gd NCs core can in future allow efficient in situ bioimaging capabilities based on Magnetic Resonance Imaging technique. The obtained nanoconstructs were tested on two different pancreatic cancer cell lines, i.e., BxPC-3 and the metastatic AsPC-1, proving high cell internalization levels, mediated by the targeting peptide exposed on the nanoconstruct. Cellular cytotoxicity assay performed on both cell lines dictated ~ 20% increased cell killing efficacy of Gemcitabine when delivered through the nanoconstruct rather than as a free drug. Taken together, our designed theranostic nanoconstruct can have a significant impact on the standard treatment of pancreatic cancer.

Prior studies reported significant anticancer activities of ceramides. However, anticancer activities of homoserine based ceramides have not been tested. With a view to compare the anticancer activity of ceramides and homoceramides, in the present study, we have synthesized four serine based and four homoserine based C8-ceramide analogues. Since many cancer cells have shown resistance to ceramides, curcumin is now being used in combination with ceramides because of its ability to reverse multidrug resistance. Aimed at targeting curcumin–ceramide combination to tumor endothelial cells, herein we have used a tumor vasculature targeting liposomes of a newly synthesized pegylated RGDGWK-lipopeptide. Importantly, the liposomal formulations of the homoserine based C8-ceramide analogue containing oleyl chain showed more promising antineoplastic activities under both in vitroand systemic settings than the liposomal formulations of commercially available C8-ceramide. Findings in the mouse tumor growth inhibition study revealed synergistic therapeutic benefit from simultaneous delivery of curcumin and a homoserine based ceramide containing oleyl chain to tumor vasculature. Results in RT-PCR and Western blot experiments suggest that inhibition of solid tumor growth is mediated via inhibition of PI3K-Akt signaling pathway. The present structure–activity study is the first report to demonstrate therapeutic promise of curcumin–homoserine based ceramide combination in antiangiogenic cancer therapy.

In the present study, we report the delivery of anti-cancer drug curcumin to cancer cells using mesoporous silica materials. A series of mesoporous silica material based drug delivery systems (S2, S4and S6) were first designed and developed through the amine functionalization of KIT-6, MSU-2 and MCM-41 followed by the loading of curcumin. The curcumin loaded materials were characterized with several physico-chemical techniques and thoroughly screened on cancer cells to evaluate their in vitrodrug delivery efficacy. All the curcumin loaded silica materials exhibited higher cellular uptake and inhibition of cancer cell viability compared to pristine curcumin. The effective internalization of curcumin in cancer cells through the mesoporous silica materials initiated the generation of intracellular reactive oxygen species and the down regulation of poly ADP ribose polymerase (PARP) enzyme levels compared to free curcumin leading to the activation of apoptosis. This study shows that the anti-cancer activity of curcumin can be potentiated by loading onto mesoporous silica materials. Therefore, we strongly believe that mesoporous silica based curcumin loaded drug delivery systems may have future potential applications for the treatment of cancers.

In this paper, we propose a stochastic approximation to the well-studied expectation–maximization (EM) algorithm for finding the maximum likelihood (ML)-type estimates in situations where missing data arise naturally and a proportion of individuals are immune to the event of interest. A flexible family of three parameter exponentiated Weibull (EW) distributions is assumed to characterize lifetimes of the non-immune individuals as it accommodates both monotone (increasing and decreasing) and non-monotone (unimodal and bathtub) hazard functions. To evaluate the performance of the proposed algorithm, an extensive simulation study is carried out under various parameter settings. Using likelihood ratio tests, we also carry out model discrimination within the EW family of distributions. Furthermore, we study the robustness of the proposed algorithm with respect to outliers in the data and the choice of initial values to start the algorithm. In particular, we show that our proposed algorithm is less sensitive to the choice of initial values when compared to the EM algorithm. For illustration, we analyze a real survival data on cutaneous melanoma. Through this data, we illustrate the applicability of the likelihood ratio test toward rejecting several well-known lifetime distributions that are nested within the wider class of the proposed EW distributions.

Increasing incidents of diabetes (mellitus) induced non-healing lower extremity wounds and disease associated amputations have raised significant concerns related to quality of life of afflicted patients. High glucose level in diabetic wounds inhibits the transactivation of angiogenesis related molecules resulting delayed healing progression. Present study investigates the impact of a natural medicine like honey in angiogenesis of non-healing diabetic lower limb wounds. Quantitative assessment of different vessel parameters was performed on in vitroCAM model for validation of angiogenic potential of honey. Further the upregulation of angiogenesis related prime molecular markers like HIF-1α, VEGFA, VEGFR2 is under the therapeutic intervention of honey indicated improved angiogenesis which in turn promote the healing rate. These results may facilitate in determining the healing impact of this natural product in treatment of diabetic wounds and it may also help in developing alternative cost effective therapeutic modality.

A reflective intensity modulated fiber optic displacement sensor with self-referencing method is studied and the effect of varying source power on the sensor response is investigated in this paper. The advantages and practical limitations of the rather simple referencing technique are experimented and reported. Calibration aspects of the sensor for different target materials are discussed. Also the effect of varying source power is experimented. The various issues on sensitivity and dynamic range are reported.

The present investigation attempts to formulate the analytical quality assessment criteria of lifting hooks made of 4140 grade (400 °C temper) high-strength steel using linear elastic fracture mechanics (LEFM) procedures. According to the existing standard specifications, the proof load test is mandatory for the acceptance/rejection of these components. Also, there is a provision that the hooks should be checked by nondestructive testing (NDT) techniques and must be free from obvious defects, but there is no stipulation of acceptance limit of defect, if any. It is therefore not realistic and is insufficient, because sometimes tested hooks are found to fail in actual service. In the present paper, acceptance limit that is, the maximum allowable defect sizes for dynamic loads with various stress ratios are quantitatively estimated from the computed defect growth curves. The maximum allowable operating cycles for nondestructively detectable minimum defects are tabulated, from which a logical quality assessment criteria has been formulated for the assessment of the fatigue life of the hooks. This investigation is helpful for the safe operation of the hooks.

Intramural aeromycological survey was performed at the Central Milk Dairy, Calcutta, covering eight locations within the Dairyusing Burkard personal volumetric air sampler. The locations were butter cold storage (−2 °C), cold store (8 °C), packaging section (23 °C), milk processing section (24 °C), reconstituent of skimmed milk (24 °C), quality control lab (25 °C), raw milk reception (28 °C) and loading dock (26 °C). A number of fungal spores, conidia and mycelia were recorded in different rooms: the highest spore quantity was recorded in the packaging section (23 °C) and the minimum at the butter cold store (−2 °C). The dominant spores consisted of Aspergillus niger, A flavus,Cladosporiumsp., Fusariumsp., Curvulariasp.,Alternariasp., Torulasp., Myrotheciumsp., Helminthosporiumsp., Periconiasp.,Nigrosporasp. and Pithomycessp.

The influence of post-combustion, heat transfer efficiency, and the degree of metallisation is studied with regard to coal saving and export gas in the COREX process using a thermochemical model. An increase in post-combustion ratio decreases the coal rate and the amount of reduction gas, which influences the achievable degree of metallisation, when no additional reduction gas is added to the system. Further post-combustion with oxygen generates a higher temperature than that with air at all post-combustion ratios. A higher heat transfer rate is necessary to keep the temperature of the gas within the refractoriness limits of the lining material. It is asserted that the post-combustion ratio, the degree of metallisation, and the medium for post-combustion must be adjusted according to the refractoriness of the lining material of the melter–gasifier, the efficiency of heat transfer mechanisms from the post-combustion zone to the bath, the gas handling efficiency, and the thermal energy requirement of the surplus gas, when considering the use of post-combustion in the COREX process.

The mortality rate of cervical cancer is increasing alarmingly. Conventional cytological methods are not always efficient to diagnose cancer at an early stage. Several label-free, quantitative screening approaches are emerging rapidly for fast and accurate detection of cervical cancer. Differential interference contrast (DIC) imaging is one of such label-free methods for the detection of cellular abnormality. The combination of DIC imaging and prediction algorithm enables the development of an efficient computer-aided diagnosis (CAD) system for cervical cancer detection at an early stage. In the present study, the DIC dataset is categorized into 2-classes (abnormal and normal) and 3-classes (normal, precancer, and squamous cell carcinoma). After segmentation of the cells using the modified valley-based Otsu thresholding method, three classifiers, namely support vector machine (SVM), multilayer perceptron (MLP), and k-nearest neighbour (k-NN) are applied. Further, to improve the classification performances, principal component analysis (PCA) is applied for feature selection. The experimental results reveal that the SVM classifier has the greatest accuracy of 0.97 (2-class classification) and 0.90 (3-class classification).