Circulating tumor cells (CTCs) are tumor cells that have sloughed off the primary tumor and extravasate into and circulate in the blood. Understanding of the metastatic cascade of CTCs has tremendous potential for the identification of targets against cancer metastasis. Detecting these very rare CTCs among the massive blood cells is challenging. However, emerging technologies for CTCs detection have profoundly contributed to deepening investigation into the biology of CTCs and have facilitated their clinical application. Current technologies for the detection of CTCs are summarized herein, together with their advantages and disadvantages. The detection of CTCs is usually dependent on molecular markers, with the epithelial cell adhesion molecule being the most widely used, although molecular markers vary between different types of cancer. Properties associated with epithelial-to-mesenchymal transition and stemness have been identified in CTCs, indicating their increased metastatic capacity. Only a small proportion of CTCs can survive and eventually initiate metastases, suggesting that an interaction and modulation between CTCs and the hostile blood microenvironment is essential for CTC metastasis. Single-cell sequencing of CTCs has been extensively investigated, and has enabled researchers to reveal the genome and transcriptome of CTCs. Herein, we also review the clinical applications of CTCs, especially for monitoring response to cancer treatment and in evaluating prognosis. Hence, CTCs have and will continue to contribute to providing significant insights into metastatic processes and will open new avenues for useful clinical applications.
Herein we describe the use of synergistic Pd and Cu catalysis for stereodivergent coupling reactions between 1,3-dienes and aldimine esters. By using different enantiomers of the two metal catalysts, all four stereoisomers of the coupling products, which have two vicinal stereocenters, could be accessed with high diastereo-and enantioselectivity. This atom-economical cross-coupling reaction has a wide substrate scope and good functional group tolerance. Our work highlights the power of synergistic catalysis for asymmetric coupling reactions involving Pd-hydride catalysts.A s an atom-economical strategy for C−C bond formation, coupling reactions between enols/enolates and unsaturated hydrocarbons with catalysis by transition-metal hydrides (M-H) have been attracting increasing attention. 1 These reactions are initiated by addition of M-H to the unsaturated hydrocarbon to form an electrophilic π-allyl metal intermediate, which reacts with the enolizable carbonyl compound to form a C−C bond (Scheme 1A). Substantial progress on asymmetric versions of these reactions has been made. 2−4 However, controlling the stereochemistry when two contiguous stereocenters are generated by these methods remains a formidable challenge; Dong and co-workers reported the only successful example to date. 5 These investigators developed a cooperative system involving Rh−H and Jacobsen's amine for stereodivergent coupling of aldehydes with alkynes. Inspired by this work, as well as recent advances in Ir-catalyzed stereodivergent allylic alkylation reactions, 6−8 we herein report a protocol for asymmetric coupling reactions between 1,3-dienes and aldimine esters with synergistic catalysis 9 by Pd and Cu; all four possible stereoisomers of the coupling products could be obtained regio-, enantio-, and diastereoselectively by using various combinations of different enantiomers of the two catalysts.Pioneering work by Malcolmson and co-workers demonstrated that Pd-phosphinooxazoline (Pd-PHOX) catalysts can be used to accomplish the addition of various activated Cpronucleophiles to 1,3-dienes with high enantioselectivity. 2d,e However, these investigators did not evaluate less reactive pronucleophiles, 10,11 such as amino acid derivatives. Zhou et al. reported a Ni(0)-catalyzed coupling of 1,3-dienes with simple ketones, but nearly 1:1 mixtures of diastereomers were obtained when two stereocenters were generated. 4 We
Acute central nervous system (CNS) injuries, such as stroke, traumatic brain injury (TBI), and spinal cord injury (SCI) present a grave health care challenge worldwide due to high morbidity and mortality, as well as limited clinical therapeutic strategies. Established literature has shown that oxidative stress (OS), inflammation, excitotoxicity, and apoptosis play important roles in the pathophysiological processes of acute CNS injuries. Recently, there have been many studies on the topic of ferroptosis, a form of regulated cell death characterized by the accumulation of iron-dependent lipid peroxidation. Some studies have revealed an emerging connection between acute CNS injuries and ferroptosis. Ferroptosis, induced by the abnormal metabolism of lipids, glutathione (GSH), and iron, can accelerate acute CNS injuries. However, pharmaceutical agents, such as iron chelators, ferrostatin-1 (Fer-1), and liproxstatin-1 (Lip-1), can inhibit ferroptosis and may have neuroprotective effects after acute CNS injuries. However, the specific mechanisms underlying this connection has not yet been clearly elucidated. In this paper, we discuss the general mechanisms of ferroptosis and its role in stroke, TBI, and SCI. We also summarize ferroptosis-related drugs and highlight the potential therapeutic strategies in treating various acute CNS injuries. Additionally, this paper suggests a testable hypothesis that ferroptosis may be a novel direction for further research of acute CNS injuries by providing corresponding evidence.
1H NMR chemical shift, spin−lattice relaxation time, spin−spin relaxation time, and two-dimensional nuclear Overhauser enhancement (2D NOESY) measurements show that Triton X-100 (TX-100) molecules coaggregate with cetyl trimethylammonium bromide (CTAB) molecules in aqueous solutions. The concentration of TX-100 in the mixed solutions of this study is 3 mM, with varying molar ratios of CTAB/TX-100 (C/T) ranging from 0.5 to 2.9. The results give information about the structure of the mixed micelles. The α-methylene group of CTAB is in the near vicinity of the phenoxy ring of TX-100. The trimethyl group attached to the polar head of CTAB locates between the first oxyethylene group next to the phenoxy ring of TX-100, and the end methyl group of CTAB is close to those of TX-100. The closely packed (coiled) hydrophilic polyoxyethylene chains in the exterior part of the mixed micelles gradually extend with an increase in C/T in the mixed solution. CTAB and TX-100 molecules are uniformly mixed in the micelles in each mixed solution.
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