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The past decade has witnessed a phenomenal rise in nanotechnology research due to its broad range of applications in diverse fields including food safety, transportation, sustainable energy, environmental science, catalysis, and medicine. The distinctive properties of nanomaterials (nano-sized particles in the range of 1 to 100 nm) make them uniquely suitable for such wide range of functions. The nanoparticles when manufactured using green synthesis methods are especially desirable being devoid of harsh operating conditions (high temperature and pressure), hazardous chemicals, or addition of external stabilizing or capping agents. Numerous plants and microorganisms are being experimented upon for an eco–friendly, cost–effective, and biologically safe process optimization. This review provides a comprehensive overview on the green synthesis of metallic NPs using plants and microorganisms, factors affecting the synthesis, and characterization of synthesized NPs. The potential applications of metal NPs in various sectors have also been highlighted along with the major challenges involved with respect to toxicity and translational research.

Plastics i.e. polymers are long chains or networks of monomer molecules which can be fabricated in desired shape, colour and specifications. The multi-functionality of this macromolecule has made it an integral part of society. Due to being given immense importance in various industrial sectors, like information technology, electrical, as well as electronics industries, intelligent, smart and advanced packaging systems, agriculture, automobiles, biomedical applications, etc., they are quite indispensable for the modern generation. The huge demand and high frequency usage have alarmed a number of countries littered with plastic wastes which need to be attended immediately. The effects of plastic solid waste on environmental living and non-living components are noticeable in the ever-increasing level of plastic pollution both on land and in the oceans globally. This paper compiles the various aspects and prospects of disposal methods like landfilling, recycling, progress in recovery and management of plastic waste (i.e. primary, secondary, tertiary and quaternary) in order to minimize its huge volumes. The depolymerisation process is the key technology behind its success which provides a high yield of product and a minimal amount of waste. Few innovative methods other than recycling published by different researchers are also discussed in this paper.

The similarities and differences between normal tissue stem cells and cancer stem cells (CSCs) have been the source of much contention, with some recent studies calling into question the very existence of CSCs. An examination of the literature indicates, however, that the CSC model rests on firm experimental foundations and that differences in the observed frequencies of CSCs within tumors reflect the various cancer types and hosts used to assay these cells. Studies of stem cells and the differentiation program termed the epithelial-mesenchymal transition (EMT) point to the possible existence of plasticity between stem cells and their more differentiated derivatives. If present, such plasticity would have major implications for the CSC model and for future therapeutic approaches.

Malignant carcinomas that recur following therapy are typically de-differentiated and multidrug resistant (MDR). De-differentiated cancer cells acquire MDR by up-regulating reactive oxygen species (ROS)-scavenging enzymes and drug efflux pumps, but how these genes are up-regulated in response to de-differentiation is not known. Here, we examine this question by using global transcriptional profiling to identify ROS-induced genes that are already up-regulated in de-differentiated cells, even in the absence of oxidative damage. Using this approach, we found that the Nrf2 transcription factor, which is the master regulator of cellular responses to oxidative stress, is preactivated in de-differentiated cells. In de-differentiated cells, Nrf2 is not activated by oxidation but rather through a noncanonical mechanism involving its phosphorylation by the ER membrane kinase PERK. In contrast, differentiated cells require oxidative damage to activate Nrf2. Constitutive PERK-Nrf2 signaling protects de-differentiated cells from chemotherapy by reducing ROS levels and increasing drug efflux. These findings are validated in therapy-resistant basal breast cancer cell lines and animal models, where inhibition of the PERK-Nrf2 signaling axis reversed the MDR of de-differentiated cancer cells. Additionally, analysis of patient tumor datasets showed that a PERK pathway signature correlates strongly with chemotherapy resistance, tumor grade, and overall survival. Collectively, these results indicate that de-differentiated cells up-regulate MDR genes via PERK-Nrf2 signaling and suggest that targeting this pathway could sensitize drug-resistant cells to chemotherapy.

PERK signaling is required for cancer invasion and there is interest in targeting this pathway for therapy. Unfortunately, chemical inhibitors of PERK’s kinase activity cause on-target side effects that have precluded their further development. One strategy for resolving this difficulty would be to target downstream components of the pathway that specifically mediate PERK’s pro-invasive and metastatic functions. Here we identify the transcription factor CREB3L1 as an essential mediator of PERK’s pro-metastatic functions in breast cancer. CREB3L1 acts downstream of PERK, specifically in the mesenchymal subtype of triple-negative tumors, and its inhibition by genetic or pharmacological methods suppresses cancer cell invasion and metastasis. In patients with this tumor subtype, CREB3L1 expression is predictive of distant metastasis. These findings establish CREB3L1 as a key downstream mediator of PERK-driven metastasis and a druggable target for breast cancer therapy. PERK stress signaling is an important driver of cancer invasion and metastasis, but chemical inhibitors of PERK cause side effects. Here, the authors find that CREB3L1 is required for PERK's pro-metastatic function in breast cancer, and its inhibition suppresses cancer invasion and metastasis.

Cognitive rehabilitation, STEM (science, technology, engineering, and math) skill acquisition, and coaching games such as chess often require tutoring decision-making strategies. The advancement of AI-driven tutoring systems for facilitating human learning requires an understanding of the impact of evaluative feedback on human decision-making and skill development. To this end, we conduct human experiments using Amazon Mechanical Turk to study the influence of evaluative feedback on human decision-making in sequential tasks. In these experiments, participants solve the Tower of Hanoi puzzle and receive AI-generated feedback while solving it. We examine how this feedback affects their learning and skill transfer to related tasks. Additionally, treating humans as noisy optimal agents, we employ maximum entropy inverse reinforcement learning to analyze the effect of feedback on the implicit human reward structure that guides their decision making. Lastly, we explore various computational models to understand how people incorporate evaluative feedback into their decision-making processes. Our findings underscore that humans perceive evaluative feedback as indicative of their long-term strategic success, thus aiding in skill acquisition and transfer in sequential decision-making tasks. Moreover, we demonstrate that evaluative feedback fosters a more structured and organized learning experience compared to learning without feedback. Furthermore, our results indicate that providing intermediate goals alone does not significantly enhance human learning outcomes.

Inhibition of DOT1L, the H3K79 histone methyltransferase, increases cell reprogramming and substituted for KLF4 and c-Myc, showing that chromatin-modifying enzymes act not only as facilitators but also as barriers to reprogramming. Chromatin in iPS-cell formation A study of the role of chromatin-modifying enzymes in the reprogramming of human fibroblasts to induced pluripotent stem (iPS) cells suggests that such enzymes can act as facilitators — but also as barriers — to epigenetic remodelling. By knocking down 22 selected genes involved in DNA and histone methylation pathways, George Daley and colleagues identified both positive and negative regulators of iPS-cell generation. In particular, inhibition of DOT1L, the H3K79 histone methyltransferase, increased reprogramming and substituted for KLF4 and c-Myc, two of the factors needed in the reprogramming cocktail. The effect of DOT1L inhibition seems to be associated with increase in the reprogramming factors NANOG and LIN28. This work demonstrates that specific chromatin modifiers can be modulated to generate iPS cells more efficiently and with fewer exogenously introduced transcription factors. Generation of induced pluripotent stem cells (iPSCs) by somatic cell reprogramming involves global epigenetic remodelling 1 . Whereas several proteins are known to regulate chromatin marks associated with the distinct epigenetic states of cells before and after reprogramming 2 , 3 , the role of specific chromatin-modifying enzymes in reprogramming remains to be determined. To address how chromatin-modifying proteins influence reprogramming, we used short hairpin RNAs (shRNAs) to target genes in DNA and histone methylation pathways, and identified positive and negative modulators of iPSC generation. Whereas inhibition of the core components of the polycomb repressive complex 1 and 2, including the histone 3 lysine 27 methyltransferase EZH2, reduced reprogramming efficiency, suppression of SUV39H1, YY1 and DOT1L enhanced reprogramming. Specifically, inhibition of the H3K79 histone methyltransferase DOT1L by shRNA or a small molecule accelerated reprogramming, significantly increased the yield of iPSC colonies, and substituted for KLF4 and c-Myc (also known as MYC). Inhibition of DOT1L early in the reprogramming process is associated with a marked increase in two alternative factors, NANOG and LIN28, which play essential functional roles in the enhancement of reprogramming. Genome-wide analysis of H3K79me2 distribution revealed that fibroblast-specific genes associated with the epithelial to mesenchymal transition lose H3K79me2 in the initial phases of reprogramming. DOT1L inhibition facilitates the loss of this mark from genes that are fated to be repressed in the pluripotent state. These findings implicate specific chromatin-modifying enzymes as barriers to or facilitators of reprogramming, and demonstrate how modulation of chromatin-modifying enzymes can be exploited to more efficiently generate iPSCs with fewer exogenous transcription factors.

The epithelial-to-mesenchymal transition (EMT) produces cancer cells that are invasive, migratory, and exhibit stem cell characteristics, hallmarks of cells that have the potential to generate metastases. Inducers of the EMT include several transcription factors (TFs), such as Goosecoid, Snail, and Twist, as well as the secreted TGF-β1. Each of these factors is capable, on its own, of inducing an EMT in the human mammary epithelial (HMLE) cell line. However, the interactions between these regulators are poorly understood. Overexpression of each of the above EMT inducers up-regulates a subset of other EMT-inducing TFs, with Twist, Zeb1, Zeb2, TGF-β1, and FOXC2 being commonly induced. Up-regulation of Slug and FOXC2 by either Snail or Twist does not depend on TGF-β1 signaling. Gene expression signatures (GESs) derived by overexpressing EMT-inducing TFs reveal that the Twist GES and Snail GES are the most similar, although the Goosecoid GES is the least similar to the others. An EMT core signature was derived from the changes in gene expression shared by up-regulation of Gsc, Snail, Twist, and TGF-β1 and by down-regulation of E-cadherin, loss of which can also trigger an EMT in certain cell types. The EMT core signature associates closely with the claudin-low and metaplastic breast cancer subtypes and correlates negatively with pathological complete response. Additionally, the expression level of FOXC1, another EMT inducer, correlates strongly with poor survival of breast cancer patients.

Background Three-dimensional (3D) cultures have proven invaluable for expanding human tissues for basic research and clinical applications. In both contexts, 3D cultures are most useful when they (1) support the outgrowth of tissues from primary human cells that have not been immortalized through extensive culture or viral infection and (2) include defined, physiologically relevant components. Here we describe a 3D culture system with both of these properties that stimulates the outgrowth of morphologically complex and hormone-responsive mammary tissues from primary human breast epithelial cells. Methods Primary human breast epithelial cells isolated from patient reduction mammoplasty tissues were seeded into 3D hydrogels. The hydrogel scaffolds were composed of extracellular proteins and carbohydrates present in human breast tissue and were cultured in serum-free medium containing only defined components. The physical properties of these hydrogels were determined using atomic force microscopy. Tissue growth was monitored over time using bright-field and fluorescence microscopy, and maturation was assessed using morphological metrics and by immunostaining for markers of stem cells and differentiated cell types. The hydrogel tissues were also studied by fabricating physical models from confocal images using a 3D printer. Results When seeded into these 3D hydrogels, primary human breast epithelial cells rapidly self-organized in the absence of stromal cells and within 2 weeks expanded to form mature mammary tissues. The mature tissues contained luminal, basal, and stem cells in the correct topological orientation and also exhibited the complex ductal and lobular morphologies observed in the human breast. The expanded tissues became hollow when treated with estrogen and progesterone, and with the further addition of prolactin produced lipid droplets, indicating that they were responding to hormones. Ductal branching was initiated by clusters of cells expressing putative mammary stem cell markers, which subsequently localized to the leading edges of the tissue outgrowths. Ductal elongation was preceded by leader cells that protruded from the tips of ducts and engaged with the extracellular matrix. Conclusions These 3D hydrogel scaffolds support the growth of complex mammary tissues from primary patient-derived cells. We anticipate that this culture system will empower future studies of human mammary gland development and biology.

Background The water supplies are hindered because aquatic resources have constrained with natural and man-made pollution activities in terms of releasing huge amounts of contaminants from different point and non-point sources across the globe. The industries like metal plating, batteries, paint, fertilizers, tanneries, textile industries, dyeing industries, mining operations, and paper industries discharge their effluents into the environment directly or indirectly, and hence, they are considered as the key sources of heavy metals contamination in water resources. Heavy metals are inorganic, non-biodegradable, persistent, and having a tendency to get accumulated in biotic and abiotic components of environment as compared to organic pollutants. Some heavy metal cations, for example, mercury, arsenic, cadmium, zinc, lead, nickel, copper, and chromium, are carcinogenic in nature and so, lethal. There are growing health concerns due to toxic impacts of heavy metals on every genre of ecosystem. To deal with the bottleneck situation, it is highly imperative to search a feasible solution for heavy metal remediation in water in context of preventing amalgamation of noxious contaminants in food web. Different methods are exercised for the remediation of such impurities from its solutions. One method, i.e. adsorption is found to be the simplest, economical, efficient, and eco-friendly in this context. Main body Geopolymers exhibit heterogeneous amorphous microstructure and wide surface area. The compatibility for depollution and the performance of these materials mainly depend upon their preparation methods, composition, and microstructure. Fly ash-based geopolymer may serve as a better alternate to various cost-effective adsorbents and it will be a proven environmentally viable, waste to money solution by consuming heaps of fly ash waste for the adsorbent modified by using fly ash. The possible utilization of wastes from several industries is a matter of concerned sustainability benefits. This study shows that fly ash-based geopolymers have the potential to cope up with the problems and risk factors associated with the fly ash waste management and it would be the utmost scientific panacea in the field of removing toxins from aqueous medium and maintain environmental health in the future. Short conclusions The literature available in different databases is very limited pertaining to heavy metal remediation using fly ash-based geopolymers . Keeping all the factors in mind, this article is an attempt to summarize relevant informations related to work done on fly ash-based geopolymers for treating aqueous solutions comprising heavy metals.