Platinum‐catalyzed formal 5+2 and 4+2 annulations of isoxazoles with heterosubstituted alkynes enabled the atom‐economical synthesis of valuable 1,3‐oxazepines and 2,5‐dihydropyridines, respectively. ...Importantly, this Pt catalysis not only led to unique reactivity dramatically divergent from that observed under Au catalysis, but also proceeded via unprecedented α‐imino platinum carbene intermediates.
Gold's deviant relative: Platinum‐catalyzed formal 5+2 and 4+2 annulations of isoxazoles and heterosubstituted alkynes provided valuable 1,3‐oxazepines and 2,5‐dihydropyridines (see scheme). This reactivity deviates dramatically from that observed under gold catalysis and involves the generation of an α‐imino platinum carbene. A computational study provided evidence for the proposed mechanism of this unusual tandem sequence.
Charge-Swapping Q-balls and Their Lifetimes Xie, Qi-Xin; Saffin, Paul M.; Zhou, Shuang-Yong
The journal of high energy physics,
07/2021, Letnik:
2021, Številka:
7
Journal Article
Recenzirano
Odprti dostop
A
bstract
For scalar theories accommodating spherically symmetric Q-balls, there are also towers of quasi-stable composite Q-balls, called charge swapping Q-balls (CSQs). We investigate the ...properties, particularly the lifetimes, of these long-lived CSQs in 2+1D and 3+1D using numerical simulations with efficient second order absorbing boundary conditions. We find that the evolution of a CSQ typically consists of 4 distinct stages: initial relaxation, first plateau (CSQ stage), fast decay and second plateau (oscillon stage). We chart the lifetimes of CSQs for different parameters of the initial conditions and of the potential, and show the attractor behavior and other properties of the CSQs.
Medium‐sized N,S‐heterocycles have received tremendous interest due to their biological activities and potential medical applications. However, asymmetric synthesis of these compounds are extremely ...rare. Described herein is a catalyst‐dependent 3,3‐sigmatropic rearrangement of sulfoxide‐ynamides, enabling divergent and atom‐economic synthesis of a series of valuable medium‐sized N,S‐heterocycles in moderate to good yields with broad substrate scope. Importantly, excellent enantioselectivities have been achieved via an unprecedented chirality‐transfer. Moreover, theoretical calculations are employed to elucidate the origins of the catalyst‐dependent stereospecific 3,3‐rearrangement.
A catalyst‐dependent 3,3‐sigmatropic rearrangement of sulfoxide‐ynamides enables the divergent and atom‐economic synthesis of a series of valuable medium‐sized N,S‐heterocycles in moderate to good yields with broad substrate scope. Excellent enantioselectivities were achieved with this chirality‐transfer strategy, which was studied by theoretical calculations.
An efficient yttrium‐catalyzed intramolecular hydroalkoxylation/Claisen rearrangement sequence has been achieved, thus enabling facile access to a diverse array of valuable medium‐sized lactams. ...Furthermore, a mechanistic rationale for this novel cascade reaction is well supported by a variety of control experiments.
Ring maker: An efficient yttrium‐catalyzed tandem intramolecular hydroxyalkylation/Claisen rearrangement has been achieved, enabling facile access to a diverse array of valuable medium‐sized lactams. A mechanistic rationale for this novel reaction sequence is well supported by a variety of control experiments.
Ynamides are special alkynes bearing an electron-withdrawing group on the nitrogen atom, and they have been extensively studied over the past decade. However, the addition of functional groups across ...ynamides in these transformations typically occurs at the α-position of the ynamide because of the strong polarization of the alkynyl moiety. Studies of umpolung transformations in ynamide chemistry may not only discover organic reactions but also lead to divergent organic syntheses, thus significantly enriching ynamide chemistry. This review summarizes four main strategies utilized to achieve reversal of the regioselectivity, including the ring strain factor, metal–carbonyl (or sulfonyl) chelation, and base-mediated and radical-initiated addition.
(CoxZn1–x)TiNb2O8 (x = 0.2–0.8) microwave dielectric ceramics were synthesized via the conventional solid‐state reaction route, and the correlation of microwave dielectric properties on the crystal ...structure was discussed. Crystal structures of ceramic samples were systematically investigated by X‐ray powder diffraction. Moreover, composition‐induced phase transitions were confirmed via the following sequence: for x ≤ 0.2, single‐phase orthorhombic ixiolite (ZnTiNb2O8) was formed, whereas for 0.3 ≤ x<0.8, ixiolite and rutile coexisted. When x ≥ 0.8, only single‐phase rutile was detected. For the (CoxZn1–x)TiNb2O8 ceramics, the microwave dielectric properties were changed with the crystal structural transitions: the dielectric constant (εr) and the temperature coefficient of resonant frequency (τf) increased upon increasing the Co2+, but the quality factor (Q) decreased. A near‐zero τf = +1.6 ppm/°C was obtained in the Co0.38Zn0.62TiNb2O8 ceramics with εr = 40.7 and high Q × f = 16 790 GHz. These research outcomes are expected to have great significance for developing microwave dielectric ceramics in practical applications.
AP2S1 is the sigma 2 subunit of adaptor protein 2 (AP2) that is essential for endocytosis. In this study, we investigated the potential role of AP2S1 in intracellular processing of amyloid precursor ...protein (APP), which contributes to the pathogenesis of Alzheimer disease (AD) by generating the toxic β‐amyloid peptide (Aβ). We found that knockdown or overexpression of AP2S1 decreased or increased the protein levels of APP and Aβ in cells stably expressing human full‐length APP695, respectively. This effect was unrelated to endocytosis but involved lysosomal degradation. Morphological studies revealed that silencing of AP2S1 promoted the translocalization of APP from RAB9‐positive late endosomes (LE) to LAMP1‐positive lysosomes, which was paralleled by the enhanced LE‐lysosome fusion. In support, silencing of vacuolar protein sorting‐associated protein 41 (VPS41) that is implicated in LE‐lyso fusion prevented AP2S1‐mediated regulation of APP degradation and translocalization. In APP/PS1 mice, an animal model of AD, AAV‐mediated delivery of AP2S1 shRNA in the hippocampus significantly reduced the protein levels of APP and Aβ, with the concomitant APP translocalization, LE‐lyso fusion and the improved cognitive functions. Taken together, these data uncover a LE‐lyso fusion mechanism in APP degradation and suggest a novel role for AP2S1 in the pathophysiology of AD.
Fission events at endo‐lyso interface could be favored in the presence of AP2S1, which is reminiscent of membrane fission during endocytosis. In contrast, lack of AP2S1 may inhibit this process, and alternatively facilitate endo‐lyso fusion and content exchange, leading to lysosomal degradation of APP.
Polarization of microglia, the resident retinal immune cells, plays important roles in mediating both injury and repair responses post-retinal ischemia-reperfusion (I/R) injury, which is one of the ...main pathological mechanisms behind ganglion cell apoptosis. Aging could perturb microglial balances, resulting in lowered post-I/R retinal repair. Young bone marrow (BM) stem cell antigen 1-positive (Sca-1
) cells have been demonstrated to have higher reparative capabilities post-I/R retinal injury when transplanted into old mice, where they were able to home and differentiate into retinal microglia.
Exosomes were enriched from young Sca-1
or Sca-1
cells, and injected into the vitreous humor of old mice post-retinal I/R. Bioinformatics analyses, including miRNA sequencing, was used to analyze exosome contents, which was confirmed by RT-qPCR. Western blot was then performed to examine expression levels of inflammatory factors and underlying signaling pathway proteins, while immunofluorescence staining was used to examine the extent of pro-inflammatory M1 microglial polarization. Fluoro-Gold labelling was then utilized to identify viable ganglion cells, while H&E staining was used to examine retinal morphology post-I/R and exosome treatment.
Sca-1
exosome-injected mice yielded better visual functional preservation and lowered inflammatory factors, compared to Sca-1
, at days 1, 3, and 7 days post-I/R. miRNA sequencing found that Sca-1
exosomes had higher miR-150-5p levels, compared to Sca-1
exosomes, which was confirmed by RT-qPCR. Mechanistic analysis found that miR-150-5p from Sca-1
exosomes repressed the mitogen-activated protein kinase kinase kinase 3 (MEKK3)/JNK/c-Jun axis, leading to IL-6 and TNF-α downregulation, and subsequently reduced microglial polarization, all of which contributes to reduced ganglion cell apoptosis and preservation of proper retinal morphology.
This study elucidates a potential new therapeutic approach for neuroprotection against I/R injury, via delivering miR-150-5p-enriched Sca-1
exosomes, which targets the miR-150-5p/MEKK3/JNK/c-Jun axis, thereby serving as a cell-free remedy for treating retinal I/R injury and preserving visual functioning.
Autophagy is considered to be another restorative focus for the treatment of brain tumors. Although several research have demonstrated that melatonin induces autophagy in colon cancer and hepatoma ...cells, there has not been any direct evidence of whether melatonin is capable of inducing autophagy in human glioma cells.
In the present research, we report that melatonin or its agonist, agomelatine, induced autophagy in A172 and U87-MG glioblastoma cells for a concentration-and time-dependent way, which was significantly attenuated by treatment with luzindole, a melatonin receptor antagonist. Furthermore, by suppressing autophagy at the late-stage with bafilomycin A1 and early stage with 3-MA, we found that the melatonin-induced autophagy was activated early, and the autophagic flux was complete. Melatonin treatment alone did not induce any apoptotic changes in the glioblastoma cells, as measured by flow cytometry. Western blot studies confirmed that melatonin alone prominently upregulated the levels of Beclin 1 and LC3 II, which was accompanied by an increase in the expression of Bcl-2, whereas it had no effect on the expression of Bax in the glioblastoma cells. Remarkably, co-treatment with 3-MA and melatonin significantly enhanced the apoptotic cell population in the glioblastoma cells, along with a prominent decrease in the expression of bcl-2 and increase in the Bax expression levels, which collectively indicated that the disruption of autophagy triggers the melatonin-induced apoptosis in glioblastoma cells.
These results provide information indicating that melatonin may act as a common upstream signal between autophagy and apoptosis, which may lead to the development of new therapeutic strategies for glioma.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Quantum corrected Q-ball dynamics Xie, Qi-Xin; Saffin, Paul M.; Tranberg, Anders ...
The journal of high energy physics,
01/2024, Letnik:
2024, Številka:
1
Journal Article
Recenzirano
Odprti dostop
A
bstract
The physics of individual Q-balls and interactions between multiple Q-balls are well-studied in classical numerical simulations. Interesting properties and phenomena have been discovered, ...involving stability, forces, collisions and swapping of charge between different components of multi-Q-ball systems. We investigate these phenomena in quantum field theory, including quantum corrections to leading order in a 2PI coupling expansion, the inhomogeneous Hartree approximation. The presence of quantum modes and new decay channels allows the mean-field Q-ball to exchange charge with the quantum modes, and also alters the charge swapping frequencies of the composite Q-balls. It is also observed that the periodic exchanges between the mean-field and quantum modes tend to be quenched by collisions between Q-balls. We illustrate how the classical limit arises through a scaling of the Q-ball potential, making quantum corrections negligible for large-amplitude Q-balls.
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