The NLRP3 inflammasome is a critical component of the innate immune system that mediates caspase-1 activation and the secretion of proinflammatory cytokines IL-1β/IL-18 in response to microbial ...infection and cellular damage. However, the aberrant activation of the NLRP3 inflammasome has been linked with several inflammatory disorders, which include cryopyrin-associated periodic syndromes, Alzheimer's disease, diabetes, and atherosclerosis. The NLRP3 inflammasome is activated by diverse stimuli, and multiple molecular and cellular events, including ionic flux, mitochondrial dysfunction, and the production of reactive oxygen species, and lysosomal damage have been shown to trigger its activation. How NLRP3 responds to those signaling events and initiates the assembly of the NLRP3 inflammasome is not fully understood. In this review, we summarize our current understanding of the mechanisms of NLRP3 inflammasome activation by multiple signaling events, and its regulation by post-translational modifications and interacting partners of NLRP3.
Recent interest has surged in using heterogeneous carriers to boost synergistic photocatalysis for organic transformations. Heterogeneous catalysts not only facilitate synergistic enhancement of ...distinct catalytic centers compared to their homogeneous counterparts, but also allow for the easy recovery and reuse of catalysts. This mini‐review summarizes recent advancements in developing heterogeneous carriers, including metal–organic frameworks, covalent–organic frameworks, porous organic polymers, and others, for synergistic catalytic reactions. The advantages of porous materials in heterogeneous catalysis originate from their ability to provide a high surface area, facilitate enhanced mass transport, offer a tunable chemical structure, ensure the stability of active species, and enable easy recovery and reuse of catalysts. Both photosensitizers and catalysts can be intricately incorporated into suitable porous carriers to create heterogeneous dual photocatalysts for organic transformations. Notably, experimental evidence from reported cases has shown that the catalytic efficacy of heterogeneous catalysts often surpasses that of their homogeneous analogues. This enhanced performance is attributed to the proximity and confinement effects provided by the porous nature of the carriers. It is expected that porous carriers will provide a versatile platform for integrating diverse catalysts, thus exhibiting superior performance across a range of organic transformations and appealing prospect for industrial applications.
Porous materials including metal–organic frameworks (MOFs), covalent–organic frameworks (COFs), and porous organic polymers (POPs) have recently been established as an ideal platform to enhance synergistic photocatalysis for organic transformations. Benefitting from the designability of these molecular materials, both photosensitizers and catalysts can be intricately incorporated into the porous carriers, leading to greatly enhanced performance over their homogeneous counterparts.
Members of the nucleotide-binding domain and leucine-rich repeat (LRR)-containing (NLR) family and the pyrin and HIN domain (PYHIN) family can form multiprotein complexes termed ‘inflammasomes’. The ...biochemical function of inflammasomes is to activate caspase-1, which leads to the maturation of interleukin 1 beta (IL-1β) and IL-18 and the induction of pyroptosis, a form of cell death. Unlike other inflammasomes, the NLRP3 inflammasome can be activated by diverse stimuli. The importance of the NLRP3 inflammasome in immunity and human diseases has been well documented, but the mechanism and regulation of its activation remain unclear. In this review we summarize current understanding of the mechanism and regulation of NLRP3 inflammasome activation as well as recent advances in the noncanonical and alternative inflammasome pathways.
The NLRP3 inflammasome is an essential mediator of host immune responses through the activation of caspase-1 and interleukin 1 beta (IL-1β)/IL-18.
The NLRP3 inflammasome is thought to sense the disturbance of cellular homeostasis rather than directly recognizing a common motif present in its activators, and multiple cellular signals have been proposed to trigger its activation, including K+ efflux, Ca2+ signaling, mitochondrial dysfunction, and lysosomal rupture.
Noncanonical and alternative inflammasome pathways were recently shown to activate the NLRP3 inflammasome.
Nek7 has emerged as an essential regulator of NLRP3 inflammasome activation.
A one‐step procedure for the self‐switchable block copolymerization of monomer mixtures of epoxides, cyclic anhydrides, and lactide (LA) was developed by using simple organocatalysts without an ...external stimulus. This multicomponent polymerization bridges two catalytic cycles involving ring‐opening alternating copolymerization of epoxides with anhydrides and ring‐opening polymerization (ROP) of LA, in which the presence/absence of anhydrides in mixed feedstocks switched the ROP of LA off/on. The self‐switchable terpolymerization showed distinct noncoordinating and living nature, as well as perfect chemoselectivity. Different combinations of epoxides, anhydrides, and initiators enabled the generation of a variety of new block polyester polyols.
Admirable self‐control: A self‐switchable route to multiblock copolymers from three‐component feedstocks (see picture) was developed with commercially accessible organocatalysts. The one‐step procedure showed perfect chemoselectivity, living nature, and applicability to a wide range of monomers.
Nonbiaryl N-C atropisomer is an important structural scaffold, which is present in natural products, medicines and chiral ligands. However the direct enantioselective C-H amination to access ...optically pure N-C atropisomer is still difficult and rare. Here we report a π-π interaction and dual H-bond concerted control strategy to develop the chiral phosphoric acids (CPAs) catalyzed direct intermolecular enantioselective C-H amination of N-aryl-2-naphthylamines with azodicarboxylates as amino sources for the construction of atroposelective naphthalene-1,2-diamines. This type of N-C atropisomers is stabilized by intramolecular hydrogen bond and the method features a broad range of substrates, high yields and ee values, providing a strategy to chirality transfer via the modification of N-C atropisomers.
In this paper, we perform a further investigation on the Apostol–Bernoulli and Apostol–Euler functions introduced by Luo. By using the Fourier expansions of the Apostol–Bernoulli and Apostol–Euler ...polynomials, we establish some symmetric identities for the Apostol–Bernoulli and Apostol–Euler functions. As applications, some known results, for example, Raabe’s multiplication formula and Hermite’s identity, are deduced as special cases.
Exo‐Selective Diels–Alder Reactions Li, Yuan‐He; Chen, Jia‐Hua; Yang, Zhen
Chemistry : a European journal,
March 20, 2024, Volume:
30, Issue:
17
Journal Article
Peer reviewed
The Diels–Alder reaction stands as one of the most pivotal transformations in organic chemistry. Its efficiency, marked by the formation of two carbon‐carbon bonds and up to four new stereocenters in ...a single step, underscores its versatility and indispensability in synthesizing natural products and pharmaceuticals. The most significant stereoselectivity feature is the “endo rule”. While this rule underpins the predictability of the stereochemical outcomes, it also underscores the challenges in achieving the opposite diastereoselectivity, making the exo‐Diels–Alder reactions often considered outliers. This review delves into recent examples of exo‐Diels–Alder reactions, shedding light on the factors inverting the intrinsic tendency. We explore the roles of steric, electrostatic, and orbital interactions, as well as thermodynamic equilibriums in influencing exo/endo selectivity. Furthermore, we illustrate strategies to manipulate these factors, employing approaches such as bulky substituents, s‐cis conformations, transient structural constraints, and innovative control physics. Through these analyses, our aim is to provide a comprehensive understanding of how to predict and design exo‐Diels–Alder reactions, paving the way for new diastereoselective catalyst systems and expanding the chemical scope of Diels–Alder reactions.
This review examines the uncommon exo‐selectivity of Diels–Alder reactions, exploring strategies like using bulky structures, s‐cis conformations, α‐substitutions, transient constraints, and thermodynamic equilibriums. The aim is to understand, predict, and guide the creation of new catalysts for exo‐Diels–Alder reactions, expanding the scope of synthetic chemistry.
The interplay between thermal and quantum fluctuations controls the competition between phases of matter in strongly correlated electron systems. We study finite-temperature properties of the ...strongly coupled two-dimensional doped Hubbard model using the minimally entangled typical thermal states method on width-four cylinders. We discover that a phase characterized by commensurate short-range antiferromagnetic correlations and no charge ordering occurs at temperatures above the half-filled stripe phase extending to zero temperature. The transition from the antiferromagnetic phase to the stripe phase takes place at temperatureT/t≈0.05and is accompanied by a steplike feature of the specific heat. We find the single-particle gap to be smallest close to the nodal point atk=(π/2,π/2)and detect a maximum in the magnetic susceptibility. These features bear a strong resemblance to the pseudogap phase of high-temperature cuprate superconductors. The simulations are verified using a variety of different unbiased numerical methods in the three limiting cases of zero temperature, small lattice sizes, and half filling. Moreover, we compare to and confirm previous determinantal quantum Monte Carlo results on incommensurate spin-density waves at finite doping and temperature.
Radar, as one of the sensors for human activity recognition (HAR), has unique characteristics such as privacy protection and contactless sensing. Radar-based HAR has been applied in many fields such ...as human–computer interaction, smart surveillance and health assessment. Conventional machine learning approaches rely on heuristic hand-crafted feature extraction, and their generalization capability is limited. Additionally, extracting features manually is time–consuming and inefficient. Deep learning acts as a hierarchical approach to learn high-level features automatically and has achieved superior performance for HAR. This paper surveys deep learning based HAR in radar from three aspects: deep learning techniques, radar systems, and deep learning for radar-based HAR. Especially, we elaborate deep learning approaches designed for activity recognition in radar according to the dimension of radar returns (i.e., 1D, 2D and 3D echoes). Due to the difference of echo forms, corresponding deep learning approaches are different to fully exploit motion information. Experimental results have demonstrated the feasibility of applying deep learning for radar-based HAR in 1D, 2D and 3D echoes. Finally, we address some current research considerations and future opportunities.
Dendritic cells (DCs) are central for the initiation and regulation of innate and adaptive immunity in the tumor microenvironment. As such, many kinds of DC-targeted vaccines have been developed to ...improve cancer immunotherapy in numerous clinical trials. Targeted delivery of antigens and adjuvants to DCs in vivo represents an important approach for the development of DC vaccines. However, nonspecific activation of systemic DCs and the preparation of optimal immunodominant tumor antigens still represent major challenges.
We loaded the immunogenic cell death (ICD) inducers human neutrophil elastase (ELANE) and Hiltonol (TLR3 agonist) into α-lactalbumin (α-LA)-engineered breast cancer-derived exosomes to form an in situ DC vaccine (HELA-Exos). HELA-Exos were identified by transmission electron microscopy, nanoscale flow cytometry, and Western blot analysis. The targeting, killing, and immune activation effects of HELA-Exos were evaluated in vitro. The tumor suppressor and immune-activating effects of HELA-Exos were explored in immunocompetent mice and patient-derived organoids.
HELA-Exos possessed a profound ability to specifically induce ICD in breast cancer cells. Adequate exposure to tumor antigens and Hiltonol following HELA-Exo-induced ICD of cancer cells activated type one conventional DCs (cDC1s) in situ and cross-primed tumor-reactive CD8
T cell responses, leading to potent tumor inhibition in a poorly immunogenic triple negative breast cancer (TNBC) mouse xenograft model and patient-derived tumor organoids.
HELA-Exos exhibit potent antitumor activity in both a mouse model and human breast cancer organoids by promoting the activation of cDC1s in situ and thus improving the subsequent tumor-reactive CD8
T cell responses. The strategy proposed here is promising for generating an in situ DC-primed vaccine and can be extended to various types of cancers. Scheme 1. Schematic illustration of HELA-Exos as an in situ DC-primed vaccine for breast cancer. (A) Allogenic breast cancer-derived exosomes isolated from MDA-MB-231 cells were genetically engineered to overexpress α-LA and simultaneously loaded with the ICD inducers ELANE and Hiltonol (TLR3 agonist) to generate HELA-Exos. (B) Mechanism by which HELA-Exos activate DCs in situ in a mouse xenograft model ofTNBC. HELA-Exos specifically homed to the TME and induced ICD in cancer cells, which resulted in the increased release of tumor antigens, Hiltonol, and DAMPs, as well as the uptake of dying tumor cells by cDC1s. The activated cDC1s then cross-primed tumor-reactive CD8+ T cell responses. (C) HELA-Exos activated DCs in situ in the breast cancer patient PBMC-autologous tumor organoid coculture system.
DCs: dendritic cells; α-LA: α-lactalbumin; HELA-Exos: Hiltonol-ELANE-α-LA-engineered exosomes; ICD: immunogenic cell death; ELANE: human neutrophil elastase; TLR3: Toll-like receptor 3; TNBC: triple-negative breast cancer; TME: tumor microenvironment; DAMPs: damage-associated molecular patterns; cDC1s: type 1 conventional dendritic cells; PBMCs: peripheral blood mononuclear cells.
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