Nickel-catalyzed cross-electrophile allylation of vinyl bromides and the modification of anti-tumour natural medicine β-elemene

Herein, we present a facile and efficient allylation method via Ni-catalyzed cross-electrophile coupling of readily available allylic acetates with a variety of substituted alkenyl bromides using zinc as the terminal reductant. This Ni-catalyzed modular approach displays excellent functional group tolerance and a broad substrate scope, which the creation of a series of 1,4-dienes including several structurally complex natural products and pharmaceutical motifs. Moreover, the coupling strategy has the potential to realize enantiomeric control. The practicality of this transformation is demonstrated through the potent modification of the naturally antitumor active molecule β-elemene.

Herein, we present a facile and efficient allylation method via Ni-catalyzed cross-electrophile coupling of readily available allylic acetates with a variety of substituted alkenyl bromides using zinc as the terminal reductant.     

Dynamic Deformation of Frozen Soil at a High Strain Rate:Experiments and Damage-Coupled Constitutive Model

The dynamic compressive deformation of frozen soil was investigated by conduct-ing the split-Hopkinson pressure bar (SHPB) experiments at three temperatures and...     

The Extracts of Polygonum cuspidatum Root and Rhizome Block the Entry of SARS-CoV-2 Wild-Type and Omicron Pseudotyped Viruses via Inhibition of the S-Protein and 3CL Protease

COVID-19, resulting from infection by the SARS-CoV-2 virus, caused a contagious pandemic. Even with the current vaccines, there is still an urgent need to develop effective pharmacological treatments against this deadly disease. Here, we show that the water and ethanol extracts of the root and rhizome of Polygonum cuspidatum (Polygoni Cuspidati Rhizoma et Radix), a common Chinese herbal medicine, blocked the entry of wild-type and the omicron variant of the SARS-CoV-2 pseudotyped virus into fibroblasts or zebrafish larvae, with IC₅₀ values ranging from 0.015 to 0.04 mg/mL. The extracts were shown to inhibit various aspects of the pseudovirus entry, including the interaction between the spike protein (S-protein) and the angiotensin-converting enzyme II (ACE2) receptor, and the 3CL protease activity. Out of the chemical compounds tested in this report, gallic acid, a phytochemical in P. cuspidatum, was shown to have a significant anti-viral effect. Therefore, this might be responsible, at least in part, for the anti-viral efficacy of the herbal extract. Together, our data suggest that the extracts of P. cuspidatum inhibit the entry of wild-type and the omicron variant of SARS-CoV-2, and so they could be considered as potent treatments against COVID-19.     

Repurposing of intestinal defensins as multi-target,dual-function amyloid inhibitors via cross-seeding

Amyloid formation and microbial infection are the two common pathological causes of neurogenerative diseases, including Alzheimer''s disease (AD), type II diabetes (T2D), and medullary thyroid carcinoma (MTC). While significant efforts have been made to develop different prevention strategies and preclinical hits for these diseases, conventional design strategies of amyloid inhibitors are mostly limited to either a single prevention mechanism (amyloid cascade vs. microbial infection) or a single amyloid protein (Aβ, hIAPP, or hCT), which has prevented the launch of any successful drug on the market. Here, we propose and demonstrate a new “anti-amyloid and anti-bacteria” strategy to repurpose two intestinal defensins, human α-defensin 6 (HD-6) and human β-defensin 1 (HBD-1), as multiple-target, dual-function, amyloid inhibitors. Both HD-6 and HBD-1 can cross-seed with three amyloid peptides, Aβ (associated with AD), hIAPP (associated with T2D), and hCT (associated with MTC), to prevent their aggregation towards amyloid fibrils from monomers and oligomers, rescue SH-SY5Y and RIN-m5F cells from amyloid-induced cytotoxicity, and retain their original antimicrobial activity against four common bacterial strains at sub-stoichiometric concentrations. Such sequence-independent anti-amyloid and anti-bacterial functions of intestinal defensins mainly stem from their cross-interactions with amyloid proteins through amyloid-like mimicry of β-sheet associations. In a broader view, this work provides a new out-of-the-box thinking to search and repurpose a huge source of antimicrobial peptides as amyloid inhibitors, allowing the blocking of the two interlinked pathological pathways and bidirectional communication between the central nervous system and intestines via the gut–brain axis associated with neurodegenerative diseases.

Amyloid formation and microbial infection are the two common pathological causes of neurogenerative diseases. Here, we proposed a new “anti-amyloid and anti-bacteria” strategy to repurpose two intestinal defensins as multiple-target, dual-function amyloid inhibitors.     

CFD-DEM-VDGM method for simulation of particle fluidization behavior in multi-ring inclined-hole spouted fluidized bed

The simulation of particle fluidization behavior in a complex geometry with a large number of particles is challenging owing to the complexity of unstructured c...     

Mesoporous sodium four-coordinate aluminosilicate nanoparticles modulate dendritic cell pyroptosis and activate innate and adaptive immunity

Pyroptosis is a programmed cell death widely studied in cancer cells for tumour inhibition, but rarely in dendritic cell (DC) activation for vaccine development. Here, we report the synthesis of sodium stabilized mesoporous aluminosilicate nanoparticles as DC pyroptosis modulators and antigen carriers. By surface modification of sodium-stabilized four-coordinate aluminium species on dendritic mesoporous silica nanoparticles, the resultant Na-^IVAl-DMSN significantly activated DC through caspase-1 dependent pyroptosis via pH responsive intracellular ion exchange. The released proinflammatory cellular contents further mediated DC hyperactivation with prolonged cytokine release. In vivo studies showed that Na-^IVAl-DMSN induced enhanced cellular immunity mediated by natural killer (NK) cells, cytotoxic T cells, and memory T cells as well as humoral immune response. Our results provide a new principle for the design of next-generation nanoadjuvants for vaccine applications.

Na-^IVAl-DMSN acts as both antigen carriers and modulators to “hyperactivate” dendritic cells (DCs) via potassium (K⁺) efflux dependent pyroptosis, eventually leading to enhanced adaptive and innate immunity.     

Phenothiazine-based covalent organic frameworks with low exciton binding energies for photocatalysis

Designing delocalized excitons with low binding energy (E_b) in organic semiconductors is urgently required for efficient photochemistry because the excitons in most organic materials are localized with a high E_b of >300 meV. In this work, we report the achievement of a low E_b of ∼50 meV by constructing phenothiazine-based covalent organic frameworks (COFs) with inherent crystallinity, porosity, chemical robustness, and feasibility of bandgap engineering. The low E_b facilitates effective exciton dissociation and thus promotes photocatalysis by using these COFs. As a demonstration, we subject these COFs to photocatalytic polymerization to synthesize polymers with remarkably high molecular weight without any requirement of the metal catalyst. Our results can facilitate the rational design of porous materials with low E_b for efficient photocatalysis.

We report the construction of phenothiazine-based covalent organic frameworks, which exhibited diverse structures, the feasibility of bandgap engineering, and unprecedented ultralow exciton binding energy of ∼50 meV for photocatalytic polymerization.     

Improved Stretchable and Sensitive Fe Nanowire-Based Strain Sensor by Optimizing Areal Density of Nanowire Network

Flexible strain sensors, when considering high sensitivity and a large strain range, have become a key requirement for current robotic applications. However, it is still a thorny issue to take both factors into consideration at the same time. Here, we report a sandwich-structured strain sensor based on Fe nanowires (Fe NWs) that has a high GF (37–53) while taking into account a large strain range (15–57.5%), low hysteresis (2.45%), stability, and low cost with an areal density of Fe NWs of 4.4 mg/cm². Additionally, the relationship between the contact point of the conductive network, the output resistance, and the areal density of the sensing unit is analyzed. Microscopically, the contact points of the conductive network directly affect the sensor output resistance distribution, thereby affecting the gauge factor (GF) of the sensor. Macroscopically, the areal density and the output resistivity of the strain sensor have the opposite percolation theory, which affects its linearity performance. At the same time, there is a positive correlation between the areal density and the contact point: when the stretching amount is constant, it theoretically shows that the areal density affects the GF. When the areal density reaches this percolation threshold range, the sensing performance is the best. This will lay the foundation for rapid applications in wearable robots.     

Spectrum analysis of all parameter noises in repetition-rate laser pulse train

The theoretical investigation of all parameter noises in repetition-rate laser pulse train was presented. The expression of power spectrum of laser pulse trains with all parameter noises was derived, and the power spectra of pulse trains with different noise parameters were numerically simulated. By comparing the power spectra with and without pulse-width jitter, we noted that pulse-width jitter could not be neglected compared with amplitude noise and timing jitter and contributed a great amount of noise into the power spectrum under the condition that the product of pulse width and angular frequency was larger than 1.