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Refugees from another world, the Visionaries' startling magical abilities could make them powerful allies... or dangerous enemies. It turns out there are some of each. When Virulina, leader of the Darkling Lords, discovers that the Transformers are vulnerable to magic, she uses that weakness to try and gain control of Cybertron! Leoric of the Spectral Knights teams up with Ironhide to stop her, but they quickly find themselves facing not just the Lords, but all of New Prysmos itself.

Mammalian development demands precision. Millions of molecules must be properly located in temporal order, and their function regulated, to orchestrate important steps in cell cycle progression, apoptosis, migration and differentiation, to shape developing embryos. Ubiquitin and its associated enzymes act as cellular guardians to ensure precise spatio-temporal control of key molecules during each of these important cellular processes. Loss of precision results in numerous examples of embryological disorders or even cancer. This Review discusses the crucial roles of E3 ubiquitin ligases during key steps of early mammalian development and their roles in human disease, and considers how new methods to manipulate and exploit the ubiquitin regulatory machinery — for example, the development of molecular glues and PROTACs — might facilitate clinical therapy.E3 ubiquitin ligases ensure the precise spatiotemporal control of key molecules during important cellular processes. This Review discusses the crucial roles of E3 ligases during early mammalian development and their roles in human disease, and considers how new methods to manipulate the ubiquitin regulatory machinery — for example, the development of molecular glues and PROTACs — might facilitate clinical therapy.

Background Structural descriptions of complete genomes have elucidated evolutionary processes in angiosperms. In Cactaceae (Caryophyllales), a high structural diversity of the chloroplast genome has been identified within and among genera. In this study, we assembled the first mitochondrial genome (mtDNA) for the short-globose cactus Mammillaria huitzilopochtli . For comparative purposes, we used the published genomes of 19 different angiosperms and the gymnosperm Cycas taitungensis as an external group for phylogenetic issues. Results The mtDNA of M. huitzilopochtli was assembled into one linear chromosome of 2,052,004 bp, in which 65 genes were annotated. These genes account for 57,606 bp including 34 protein-coding genes (PCGs), 27 tRNAs, and three rRNAs. In the non-coding sequences, repeats were abundant, with a total of 4,550 (179,215 bp). In addition, five complete genes ( psaC and four tRNAs) of chloroplast origin were documented. Negative selection was estimated for most (23) of the PCGs. The phylogenetic tree showed a topology consistent with previous analyses based on the chloroplast genome. Conclusions The number and type of genes contained in the mtDNA of M. huitzilopochtli were similar to those reported in 19 other angiosperm species, regardless of their phylogenetic relationships. Although other Caryophyllids exhibit strong differences in structural arrangement and total size of mtDNA, these differences do not result in an increase in the typical number and types of genes found in M. huitzilopochtli . We concluded that the total size of mtDNA in angiosperms increases by the lengthening of the non-coding sequences rather than a significant gain of coding genes.

Bimetallic silver/gold nanosystems are expected to significantly improve therapeutic efficacy compared to their monometallic counterparts by maintaining the general biocompatibility of gold nanoparticles (AuNPs) while, at the same time, decreasing the relatively high toxicity of silver nanoparticles (AgNPs) toward healthy human cells. Thus, the aim of this research was to establish a highly reproducible one-pot green synthesis of colloidal AuNPs and bimetallic Ag/Au alloy nanoparticles (NPs; Ag/AuNPs) using starch as reducing and capping agent. The optical properties, high reproducibility, stability and particle size distribution of the colloidal NPs were analyzed by ultraviolet (UV)-visible spectroscopy, dynamic light scattering (DLS) and -potential. The presence of starch as capping agent was determined by Fourier transform infrared (FT-IR) spectroscopy. The structural properties were studied by X-ray diffraction (XRD). Transmission electron microscopy (TEM) imaging was done to determine the morphology and size of the nanostructures. The chemical composition of the nanomaterials was determined by energy-dispersive X-ray spectroscopy (EDS) and inductively coupled plasma mass spectrometry (ICP-MS) analysis. To further study the biomedical applications of the synthesized nanostructures, antibacterial studies against multidrug-resistant (MDR) and methicillin-resistant (MRSA) were conducted. In addition, the NPs were added to the growth media of human dermal fibroblast (HDF) and human melanoma cells to show their cytocompatibility and cytotoxicity, respectively, over a 3-day experiment. UV-visible spectroscopy confirmed the highly reproducible green synthesis of colloidal AuNPs and Ag/AuNPs. The NPs showed a face-centered cubic crystal structure and an icosahedral shape with mean particle sizes of 28.5 and 9.7 nm for AuNPs and Ag/AuNPs, respectively. The antibacterial studies of the NPs against antibiotic-resistant bacterial strains presented a dose-dependent antimicrobial behavior. Furthermore, the NPs showed cytocompat-ibility towards HDF, but a dose-dependent anticancer effect was found when human melanoma cells were grown in presence of different NP concentrations for 72 hours. In this study, mono- and bimetallic NPs were synthesized for the first time using a highly reproducible, environmentally friendly, cost-effective and quick method and were successfully characterized and tested for several anti-infection and anticancer biomedical applications.

We extend the theory of Rubio de Francia extrapolation, including off-diagonal, limited range and A∞A_\\infty extrapolation, to the weighted variable Lebesgue spaces Lp(⋅)(w)L^{p(\\cdot )}(w). As a consequence we are able to show that a number of different operators from harmonic analysis are bounded on these spaces. The proofs of our extrapolation results are developed in a way that outlines a general approach to proving extrapolation theorems on other Banach function spaces.

The rise of nanotechnology has brought to the world a new potential and broader perspective of what humanity can achieve through material manipulation at the nanoscale. As a consequence, the use of different nanomaterials has revolutionized both the industrial and biomedical worlds. Metallic and metal-oxide nanostructures have shown great potential due to their high surface to volume ratio and high reactivity. Among them, zinc oxide (ZnO) has revealed wider applicability, including in nanomedicine, where ZnO nanomaterials have shown great potential leading to effective interactions with biological membranes and exhibiting antibacterial and/or anticancer behaviors. However, consistent with several other nanostructures, the synthesis of ZnO nanomaterials is not devoid of drawbacks, such as the production of harmful and toxic byproducts, the use of toxic reagents, the employment of expensive instruments, and the lack of biocompatibility, all of which need to be overcome before extensive use. As a solution, green nanotechnology has allowed the production of ZnO nanostructures using environmentally friendly and cost-effective methods, which are based on the use of living organisms, natural biomolecules and waste materials. Once produced, green-synthesized ZnO nanoparticles have shown enhancements in terms of their cytocompatibility and biomedical properties compared to their traditionally produced counterparts, becoming excellent antibacterial or anticancer agents. These ZnO nanoparticles have also proven to be valuable materials in combination with wound healing processes and biosensing elements in order to trace small amounts of biomarkers associated with different diseases. As a consequence, there is a synergy between green nanotechnology and ZnO nanomaterials, which is leading to an exciting flourishment in the field, presenting a wide variety of biomedical applications for these nanostructures. This review compares and contrasts recent approaches and examples of the use of green-synthesized ZnO nanomaterials with traditionally synthesized structures, demonstrating a remarkable potential for their use as a powerful biomedical agent.

Protein–polysaccharide composites have been known to show a wide range of applications in biomedical and green chemical fields. These composites have been fabricated into a variety of forms, such as films, fibers, particles, and gels, dependent upon their specific applications. Post treatments of these composites, such as enhancing chemical and physical changes, have been shown to favorably alter their structure and properties, allowing for specificity of medical treatments. Protein–polysaccharide composite materials introduce many opportunities to improve biological functions and contemporary technological functions. Current applications involving the replication of artificial tissues in tissue regeneration, wound therapy, effective drug delivery systems, and food colloids have benefited from protein–polysaccharide composite materials. Although there is limited research on the development of protein–polysaccharide composites, studies have proven their effectiveness and advantages amongst multiple fields. This review aims to provide insight on the elements of protein–polysaccharide complexes, how they are formed, and how they can be applied in modern material science and engineering.

Breast cancer remains as a concerning global health issue, being the second leading cause of cancer deaths among women in the United States (US) in 2019. Therefore, there is an urgent and substantial need to explore novel strategies to combat breast cancer. A potential solution may come from the use of cancer nanotechnology, an innovative field of study which investigates the potential of nanomaterials for cancer diagnosis, therapy, and theranostic applications. Consequently, the theranostic functionality of cancer nanotechnology has been gaining much attention between scientists during the past few years and is growing exponentially. The use of biosynthesized gold nanoparticles (AuNPs) has been explored as an efficient mechanism for the treatment of breast cancer. The present study supposed a global systematic review to evaluate the effectiveness of biogenic AuNPs for the treatment of breast cancer and their anticancer molecular mechanisms through in vitro studies. Online electronic databases, including Cochrane, PubMed, Scopus, Web of Science, Science Direct, ProQuest, and Embase, were searched for the articles published up to July 16, 2019. Our findings revealed that plant-mediated synthesis was the most common approach for the generation of AuNPs. Most of the studies reported spherical or nearly spherical-shaped AuNPs with a mean diameter less than 100 nm in size. A significantly larger cytotoxicity was observed when the biogenic AuNPs were tested towards breast cancer cells compared to healthy cells. Moreover, biogenic AuNPs demonstrated significant synergistic activity in combination with other anticancer drugs through in vitro studies. Although we provided strong and comprehensive preliminary in vitro data, further in vivo investigations are required to show the reliability and efficacy of these NPs in animal models.

Precise and efficient manipulation of genes is crucial for understanding the molecular mechanisms that govern human hematopoiesis and for developing novel therapies for diseases of the blood and immune system. Current methods do not enable precise engineering of complex genotypes that can be easily tracked in a mixed population of cells. We describe a method to multiplex homologous recombination (HR) in human hematopoietic stem and progenitor cells and primary human T cells by combining rAAV6 donor delivery and the CRISPR/Cas9 system delivered as ribonucleoproteins (RNPs). In addition, the use of reporter genes allows FACS-purification and tracking of cells that have had multiple alleles or loci modified by HR. We believe this method will enable broad applications not only to the study of human hematopoietic gene function and networks, but also to perform sophisticated synthetic biology to develop innovative engineered stem cell-based therapeutics. Our DNA contains thousands of sections called genes that encode the information needed to make all the cells in the human body. To understand what the genes do and how they contribute to diseases, it is crucial for researchers to be able to switch individual genes on or off or make precise changes to the ‘letters’ in their code. Since most genes act in complicated networks it would be very useful to be able to edit several genes at the same time, especially when studying cancer and other diseases that are caused by defects in multiple genes. CRISPR/Cas9 is a relatively new technique that allows the code of individual genes to be precisely edited. To edit a gene, CRISPR/Cas9 first breaks the DNA at the site of interest and this break is subsequently repaired using new DNA templates that introduce the desired change in the code. In this way, the letters of the code can be changed with the same precision that one edits the letters and words of a document. This technique has been successfully used to edit the code of single genes, but it is much more difficult to use it to edit several genes at the same time. To import new DNA repair templates into human and other mammalian cells, researchers have used harmless virus-like particles called rAAV vectors. Researchers load the DNA templates into rAAV vectors, which are able to enter the cells and carry the templates to the DNA of the cells. Bak, Dever, Reinisch et al. combined CRISPR/Cas9 with rAAV template delivery to precisely edit several genes in human cells, including blood stem cells. In this new system, CRISPR/Cas9 directs the insertion of new pieces of DNA carried by rAAV6 vectors into specific genes. The system developed by Bak, Dever, Reinisch et al. allows several genes to be precisely edited at the same time. Furthermore, the system includes fluorescent markers that enable successfully edited cells to be identified and tracked. In the future, this technique could be used to study how genes work together to control various characteristics, and how cancer and other diseases develop.

The increase in garbage generated in modern societies demands the implementation of a more sustainable model as well as new methods for efficient waste management. This article describes the development and implementation of a prototype of a smart bin that automatically sorts waste using a multi-agent system and blockchain integration. The proposed system has sensors that identify the type of waste (organic, plastic, paper, etc.) and uses collaborative intelligent agents to make instant sorting decisions. Blockchain has been implemented as a technology for the immutable and transparent control of waste registration, favoring traceability during the classification process, providing sustainability to the process, and making the audit of data in smart urban environments transparent. For the computer vision algorithm, three versions of YOLO (YOLOv8, YOLOv11, and YOLOv12) were used and evaluated with respect to their performance in automatic detection and classification of waste. The YOLOv12 version was selected due to its overall performance, which is superior to others with mAP@50 values of 86.2%, an overall accuracy of 84.6%, and an average F1 score of 80.1%. Latency was kept below 9 ms per image with YOLOv12, ensuring smooth and lag-free processing, even for utilitarian embedded systems. This allows for efficient deployment in near-real-time applications where speed and immediate response are crucial. These results confirm the viability of the system in both accuracy and computational efficiency. This work provides an innovative solution in the field of ambient intelligence, characterized by low equipment cost and high scalability, laying the foundations for the development of smart waste management infrastructures in sustainable cities.