Elucidating the structural and conformational preferences of bioactive chromone and its monohydrate through advanced rotational spectroscopy.

Chromones are a class of naturally occurring compounds, renowned for their diverse biological activities with significant relevance in medicine and biochemistry. This study marks the first analysis of rotational spectra of both the chromone monomer and its monohydrate through Fourier transform microwave spectroscopy. The observation of nine mono-substituted 13C isotopologues facilitated a semi-experimental determination of the equilibrium structure of the chromone monomer. In the case of chromone monohydrate, two distinct isomers were identified, each characterized by a combination of O-H⋯O and C-H⋯O hydrogen bonds involving the chromone's carbonyl group. This study further delved into intermolecular non-covalent interactions, employing different theoretical approaches. The relative population ratio of the two identified isomers was estimated to be about 2:1 within the supersonic jet.

HfOx /AlOy Superlattice-Like Memristive Synapse.

The adjustable conductance of a two-terminal memristor in a crossbar array can facilitate vector-matrix multiplication in one step, making the memristor a promising synapse for efficiently implementing neuromorphic computing. To achieve controllable and gradual switching of multi-level conductance, important for neuromorphic computing, a theoretical design of a superlattice-like (SLL) structure switching layer for the multi-level memristor is proposed and validated, refining the growth of conductive filaments (CFs) and preventing CFs from the abrupt formation and rupture. Ti/(HfOx /AlOy )SLL /TiN memristors are shown with transmission electron microscopy , X-ray photoelectron spectroscopy , and ab initio calculation findings corroborate the SLL structure of HfOx /AlOy film. The optimized SLL memristor achieves outstanding conductance modulation performance with linearly synaptic weight update (nonlinear factor α = 1.06), and the convolutional neural network based on the SLL memristive synapse improves the handwritten digit recognition accuracy to 94.95%. Meanwhile, this improved synaptic device has a fast operating speed (30 ns), a long data retention time (≥ 104 s at 85 â„ƒ), scalability, and CMOS process compatibility. Finally, its physical nature is explored and the CF evolution process is characterized using nudged elastic band calculations and the conduction mechanism fitting. In this work, as an example the HfOx /AlOy SLL memristor provides a design viewpoint and optimization strategy for neuromorphic computing.

Reconfigurable and Efficient Implementation of 16 Boolean Logics and Full-Adder Functions with Memristor Crossbar for Beyond von Neumann In-Memory Computing.

The rise of emerging technologies such as Big Data, the Internet of Things, and artificial intelligence, which requires efficient power schemes, is driving brainstorming in data computing and storage technologies. In this study, merely relying on the fundamental structure of two memristors and a resistor, arbitrary Boolean logic can be reconfigured and calculated in two steps, while no additional voltage sources are needed beyond "±VP " and 0, and all state reversals are based on memristor set switching. Utilizing the proposed logic scheme in an elegant form of unity structure and minimum cost, the implementation of a 1-bit adder is demonstrated economically, and a promising circuit scheme for the N-bit adder is exhibited. Some critical issues including the crosstalk problem, energy consumption, and peripheral circuits are further simulated and discussed. Compared with existing works on memristive logic, such methods support building a memristor-based digital in-memory calculation system with high functional reconfigurability, simple voltage sources, and low power and area consumption.

O-Acetylation of Capsular Polysialic Acid Enables Escherichia coli K1 Escaping from Siglec-Mediated Innate Immunity and Lysosomal Degradation of E. coli-Containing Vacuoles in Macrophage-Like Cells.

Escherichia coli K1 causes bacteremia and meningitis in human neonates. The K1 capsule, an α2,8-linked polysialic acid (PSA) homopolymer, is its essential virulence factor. PSA is usually partially modified by O-acetyl groups. It is known that O-acetylation alters the antigenicity of PSA, but its impact on the interactions between E. coli K1 and host cells is unclear. In this study, a phase variant was obtained by passage of E. coli K1 parent strain, which expressed a capsule with 44% O-acetylation whereas the capsule of the parent strain has only 3%. The variant strain showed significantly reduced adherence and invasion to macrophage-like cells in comparison to the parent strain. Furthermore, we found that O-acetylation of PSA enhanced the modulation of trafficking of E. coli-containing vacuoles (ECV), enabling them to avoid fusing with lysosomes in these cells. Intriguingly, by using quartz crystal microbalance, we demonstrated that the PSA purified from the parent strain interacted with human sialic acid-binding immunoglobulin-like lectins (Siglecs), including Siglec-5, Siglec-7, Siglec-11, and Siglec-14. However, O-acetylated PSA from the variant interacted much less and also suppressed the production of Siglec-mediated proinflammatory cytokines. The adherence of the parent strain to human macrophage-like cells was significantly blocked by monoclonal antibodies against Siglec-11 and Siglec-14. Furthermore, the variant strain caused increased bacteremia and higher lethality in neonatal mice compared to the parent strain. These data elucidate that O-acetylation of K1 capsule enables E. coli to escape from Siglec-mediated innate immunity and lysosomal degradation; therefore, it is a strategy used by E. coli K1 to regulate its virulence. IMPORTANCE Escherichia coli K1 is a leading cause of neonatal meningitis. The mortality and morbidity of this disease remain significantly high despite antibiotic therapy. One major limitation on advances in prevention and therapy for meningitis is an incomplete understanding of its pathogenesis. E. coli K1 is surrounded by PSA, which is observed to have high-frequency variation of O-acetyl modification. Here, we present an in-depth study of the function of O-acetylation in PSA at each stage of host-pathogen interaction. We found that a high level of O-acetylation significantly interfered with Siglec-mediated bacterial adherence to macrophage-like cells, and blunted the proinflammatory response. Furthermore, the O-acetylation of PSA modulated the trafficking of ECVs to prevent them from fusing with lysosomes, enabling them to escape degradation by lysozymes within these cells. Elucidating how subtle modification of the capsule enhances bacterial defenses against host innate immunity will enable the future development of effective drugs or vaccines against infection by E. coli K1.

An ultrasensitive molybdenum-based double-heterojunction phototransistor.

Two-dimensional (2D) materials are promising for next-generation photo detection because of their exceptional properties such as a strong interaction with light, electronic and optical properties that depend on the number of layers, and the ability to form hybrid structures. However, the intrinsic detection ability of 2D material-based photodetectors is low due to their atomic thickness. Photogating is widely used to improve the responsivity of devices, which usually generates large noise current, resulting in limited detectivity. Here, we report a molybdenum-based phototransistor with MoS2 channel and α-MoO3-x contact electrodes. The device works in a photo-induced barrier-lowering (PIBL) mechanism and its double heterojunctions between the channel and the electrodes can provide positive feedback to each other. As a result, a detectivity of 9.8 × 1016 cm Hz1/2 W-1 has been achieved. The proposed double heterojunction PIBL mechanism adds to the techniques available for the fabrication of 2D material-based phototransistors with an ultrahigh photosensitivity.

Synthesis and biological evaluation of novel ligustrazine-chalcone derivatives as potential anti-triple negative breast cancer agents.

A series of novel ligustrazine-chalcone hybrids were synthesized and evaluated for their in vitro and in vivo antitumor activities. The results showed that most of these compounds exhibited significant in vitro cytotoxicity against MDA-MB-231, MCF-7, A549 and HepG2 cell lines with IC50 values as low as sub-micromole. Among them, compounds 6c and 6f possessed better comprehensive characteristics for the antiproliferation effects on both MDA-MB-231 (IC50: 6c, 1.60 ± 0.21 µM; 6f, 1.67 ± 1.25 µM) and MCF-7 (IC50: 6c, 1.41 ± 0.23 µM; 6f, 1.54 ± 0.30 µM). They also exhibited the potent colony-formation inhibitory abilities on above two cell lines in both concentration and time dependent manners, as well as the significantly suppression capabilities against the migration of such cell lines in a concentration dependent manner by wound-healing assay. Of note, compound 6c could significantly induce the apoptosis of MDA-MB-231 cells in a concentration dependent manner and inhibited the transformation of the growth cycle of MDA-MB-231 cells and blocked the cell growth cycle in G0/G1 phase. Moreover, the in vivo antiproliferation assay of compound 6c on TNBC model indicated such compound had a remarkable potency against tumor growth with a widely safety window. Further immunohistochemistry analysis illustrated that compound 6c was provided with a potent capacity to significantly reduce the Ki-67 positive rate in a dose dependent manner. All the results suggested that these hybrids presented both in vitro and in vivo proliferation inhibition potency against breast cancer and further development with good therapeutic potential should be of great interest.

Synergistic effects of colchicine combined with atorvastatin in rats with hyperlipidemia.

BACKGROUND: Inflammation and endothelial dysfunction is implicated in the atherosclerosis initiation and progression in the setting of hyperlipidemia. Colchicine is a potent anti-inflammatory agent and whether colchicine combined with atorvastatin has synergistic effects on inflammation amelioration and endothelial function improvement is unknown. METHODS: Hyperlipidemic rat model was produced by high-fat and high-cholesterol diet for 6 weeks. Rats with normal diet were served as shame group. In hyperlipidemic group, normal saline, atorvastatin (10 mg/kg body weight/day), colchicines (0.5 mg/kg body weight/day), or atorvastatin combined with colchicines (same dosages) were prescribed for 2 weeks. Serum levels of lipid profile, C-reactive protein (CRP), liver enzyme, lipoprotein associated phospholipase A2 (Lp-PLA2) and nitric oxide (NO) production were serially assessed. RESULTS: Before the beginning of the study, all laboratory variables were comparable among each group. After 6 weeks of hyperlipidemic model production, serum levels of cholesterols, CRP and Lp-PLA2 were significantly increased when compared to sham group, whereas NO production was reduced. With 2 weeks of colchicine therapy, serum levels of CRP and Lp-PLA2 were decreased and NO production was enhanced in the colchicine group in a lipid-lowering independent manner. Added colchicine into atorvastatin therapy further improved NO production and decreased CRP and Lp-PLA2 levels, indicating a potential synergism of colchicine and atorvastatin. CONCLUSION: Colchicine combined with atorvastatin may have stronger protective effects on improving endothelial function and ameliorating inflammation in rats with hyperlipidemia.