The chromium-catalyzed hydrogenation of alkynes is reported herein, demonstrating selective E- and Z-olefin synthesis, controlled by the presence of two carbene ligands. Employing a cyclic (alkyl)(amino)carbene ligand with a phosphino anchor, alkynes undergo trans-addition hydrogenation to selectively produce E-olefins. Implementing a carbene ligand featuring an imino anchor permits the control of stereoselectivity, causing a main outcome of Z-isomers. A single metal catalyst, coupled with a specific ligand, offers a novel method of geometrical stereoinversion, exceeding standard two-metal approaches in E/Z selectivity control, achieving highly efficient and on-demand access to both stereocomplementary E- and Z-olefins. The selective formation of E- or Z-olefins, in terms of stereochemistry, is primarily governed by the differing steric effects of these two carbene ligands, as ascertained through mechanistic investigations.
The heterogeneity of cancer represents a persistent and substantial hurdle to current cancer treatment approaches, highlighting the critical issue of repeated heterogeneity between and within individuals. Recent and future years have seen personalized therapy rise as a significant area of research interest, owing to this. Advances in cancer treatment are yielding new models, exemplified by cell lines, patient-derived xenografts, and particularly, organoids. Organoids, a three-dimensional in vitro model developed over the past decade, successfully reproduce the cellular and molecular characteristics of the original tumor. These advantages showcase the considerable potential of patient-derived organoids to develop personalized anticancer therapies, encompassing preclinical drug screening and the anticipation of patient treatment responses. The critical role of the microenvironment in cancer treatment strategies cannot be denied, and its modification allows organoids to integrate with various technologies, among which organs-on-chips serves as a prominent example. This review analyzes the clinical efficacy predictability of colorectal cancer treatments using the complementary approaches of organoids and organs-on-chips. In addition, we examine the limitations of each methodology and their effective combination.
Non-ST-segment elevation myocardial infarction (NSTEMI), with its increasing incidence and consequent significant long-term mortality, requires urgent clinical consideration. Unfortunately, research into possible interventions to manage this condition is severely limited by the non-reproducibility of the pre-clinical model. Certainly, the current animal models of myocardial infarction (MI), encompassing both small and large species, predominantly simulate full-thickness, ST-segment elevation (STEMI) infarcts, thereby limiting their application to investigations focused on treatments and interventions specific to this particular MI subtype. Therefore, a model of ovine NSTEMI is created by tying off the myocardial muscle at specific intervals that align with the left anterior descending coronary artery. Post-NSTEMI tissue remodeling exhibited distinctive features, as observed via RNA-seq and proteomics, in a comparative study of the proposed model with the STEMI full ligation model, confirming the findings through histological and functional analysis. Pathway analyses of the transcriptome and proteome, performed at 7 and 28 days post-NSTEMI, pinpoint specific changes in the cardiac extracellular matrix following ischemia. NSTEMI ischemic regions showcase unique compositions of complex galactosylated and sialylated N-glycans within cellular membranes and the extracellular matrix, correlating with the emergence of recognized inflammation and fibrosis markers. The discovery of changes in molecular structures that can be targeted by infusible and intra-myocardial injectable drugs is critical in devising specific pharmacological solutions to address harmful fibrotic remodeling.
Recurringly, epizootiologists examine the haemolymph (blood equivalent) of shellfish and discover symbionts and pathobionts. Among the dinoflagellates, the genus Hematodinium comprises several species, each capable of causing debilitating diseases in decapod crustaceans. The shore crab, Carcinus maenas, functions as a mobile repository for microparasites, such as Hematodinium sp., which consequently presents a threat to other economically significant species found in the same locale, for example. A prominent inhabitant of the coastal waters is the Necora puber, or velvet crab. Given the recognized seasonal pattern and widespread occurrence of Hematodinium infection, the host-parasite interaction, specifically Hematodinium's ability to evade the host's defenses, continues to elude scientific understanding. We investigated the haemolymph of Hematodinium-positive and Hematodinium-negative crabs for extracellular vesicle (EV) profiles, a marker of cellular communication, alongside proteomic signatures reflecting post-translational citrullination/deimination by arginine deiminases, which can signal a pathological state. Microscopes and Cell Imaging Systems Hemolymph exosome circulation within parasitized crabs decreased substantially, coupled with a smaller modal size distribution of the exosomes, although the difference from non-infected controls did not reach statistical significance. A comparative examination of citrullinated/deiminated target proteins in the haemolymph of parasitized and control crabs revealed observable variations, with fewer of these proteins identified in the haemolymph of the parasitized crabs. Specific to parasitized crab haemolymph, three deiminated proteins, namely actin, Down syndrome cell adhesion molecule (DSCAM), and nitric oxide synthase, participate in the innate immune system. Newly reported findings indicate that Hematodinium sp. may disrupt the generation of extracellular vesicles, proposing that protein deimination is a possible mechanism influencing immune responses in crustaceans infected with Hematodinium.
Despite its crucial role in the global transition to sustainable energy and a decarbonized society, green hydrogen currently lacks economic competitiveness compared to fossil fuel-based hydrogen. We propose a strategy to overcome this limitation by linking photoelectrochemical (PEC) water splitting to the hydrogenation of chemicals. By coupling the hydrogenation of itaconic acid (IA) within a photoelectrochemical water splitting apparatus, we evaluate the potential for co-generating hydrogen and methylsuccinic acid (MSA). The device's generation of hydrogen alone is projected to result in a negative net energy balance, though energy breakeven is possible through the application of a small amount (approximately 2%) of the hydrogen in-situ for IA-to-MSA conversion. The simulated coupled device demonstrates a noticeably lower cumulative energy demand when producing MSA than traditional hydrogenation procedures. The hydrogenation coupling strategy proves attractive for enhancing the feasibility of PEC water splitting, concomitantly achieving decarbonization in the valuable chemical production sector.
Corrosion is a universal failure mechanism for materials. A common observation is the formation of porosity in materials, previously known to be either three-dimensional or two-dimensional, as localized corrosion progresses. Using new tools and analytical techniques, we've come to realize that a more localized form of corrosion, which we've now defined as '1D wormhole corrosion', had been misclassified in a number of previous situations. Through electron tomography, we demonstrate the prevalence of this 1D, percolating morphology. We sought to determine the origin of this mechanism in a molten salt-corroded Ni-Cr alloy by merging energy-filtered four-dimensional scanning transmission electron microscopy with ab initio density functional theory calculations. This allowed us to establish a nanometer-resolution vacancy mapping procedure. This procedure identified an extraordinarily high concentration of vacancies, reaching 100 times the equilibrium value at the melting point, in the diffusion-driven grain boundary migration zone. Determining the origins of 1D corrosion plays a critical role in developing structural materials that exhibit superior resistance to corrosion.
Within Escherichia coli, the 14-cistron phn operon, which encodes carbon-phosphorus lyase, enables the utilization of phosphorus derived from a diverse array of stable phosphonate compounds that incorporate a C-P bond. The PhnJ subunit, within a multi-step, intricate pathway, was observed to cleave the C-P bond through a radical mechanism. Nevertheless, the details of this reaction were incompatible with the crystal structure of the 220 kDa PhnGHIJ C-P lyase core complex, leaving a critical gap in our knowledge of phosphonate breakdown in bacterial systems. Through single-particle cryogenic electron microscopy, we observe PhnJ's involvement in the binding of a double dimer composed of PhnK and PhnL ATP-binding cassette proteins to the core complex. ATP hydrolysis prompts a dramatic restructuring of the core complex, resulting in its opening and a rearrangement of the metal-binding site and the proposed active site, which is situated at the interface between the PhnI and PhnJ subunits.
Characterizing the functional attributes of cancer clones can explain the evolutionary strategies that fuel cancer's spread and recurrence. learn more The functional status of cancer as a whole is demonstrably shown by single-cell RNA sequencing data; however, extensive research is necessary to pinpoint and reconstruct clonal relationships to properly characterize the functional shifts within individual clones. PhylEx, integrating bulk genomics data with mutation co-occurrences from single-cell RNA sequencing, reconstructs high-fidelity clonal trees. PhylEx is evaluated using datasets of synthetic and well-defined high-grade serous ovarian cancer cell lines. maternal infection The reconstruction of clonal trees and the identification of clones are handled more effectively by PhylEx than by any existing state-of-the-art methods. High-grade serous ovarian and breast cancer datasets are used to highlight PhylEx's aptitude for leveraging clonal expression profiles, surpassing the limitations of expression-based clustering. This allows for accurate clonal tree inference and robust phylo-phenotypic assessment in cancer.