Size, shape, and protein corona play a key role in cellular uptake and removal mechanisms of gold nanoparticles (Au NPs). The 15 nm nanoparticles (NP1), the 45 nm nanoparticles (NP2), and the ...rod‐shaped nanoparticles (NR) enter into cells via a receptor‐mediated endocytosis (RME) pathway. The star‐shaped nanoparticles (NS) adopt not only clathrin‐mediated, but also caveolin‐mediated endocytosis pathways. However, the 80 nm nanoparitcles (NP3) mainly enter into the cells by macropinocytosis pathway due to the big size. Furthermore, the results indicate that the presence of protein corona can change the uptake mechanisms of Au NPs. The endocytosis pathway of NP1, NP2, and NS changes from RME to macropinocytosis pathway and NR changes from RME to clathrin and caveolin‐independent pathway under the non‐fetal bovine serun (FBS)‐coated condition. Both FBS‐coated and non‐FBS‐coated of five types of Au NPs are released out through the lysosomal exocytosis pathway. The size, shape, and protein corona have an effect on the exocytosis ratio and amount, but do not change the exocytosis mechanism. The systematic study of the endocytosis and exocytosis mechanism of Au NPs with different sizes and shapes will benefit the toxicology evaluation and nanomedicine application of Au NPs.
Size, shape, and protein corona play the key role in cellular uptake and removal mechanisms of gold nanoparticles (Au NPs). The uptake mechanisms of five types of Au NPs are different. Size, shape, and protein corona decrease the uptake amount and affect the endocytosis mechanism. However, all of them are released through the lysosomal exocytosis pathway.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
In-situ, wide-angle, and ultra-wideband inverse synthetic aperture radar (ISAR) imaging of vehicles and drones is demonstrated using a portable ultra-wideband radar. In order to form well-focused ...ISAR images, motion compensation is performed before applying the
-space imaging algorithm. While the same basic motion compensation methodology is applied to both types of targets, a more complex motion model is needed to better capture the flight path of the drone. The resulting ISAR images clearly show the geometrical outline of the targets and highlight locations of prominent backscattering. The ISAR images are also assessed against images generated through instrumented targets or laboratory measurements, and the image quality is shown to be comparable.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Summary
2′‐Fucosyllactose (2′‐FL), one of the most abundant human milk oligosaccharides (HMOs), is used as a promising infant formula ingredient owing to its multiple health benefits for newborns. ...However, limited availability and high‐cost preparation have restricted its extensive use and intensive research on its potential functions. In this work, a powerful Escherichia coli cell factory was developed to ulteriorly increase 2′‐FL production. Initially, a modular pathway engineering was strengthened to balance the synthesis pathway through different plasmid combinations with a resulting maximum 2′‐FL titre of 1.45 g l−1. To further facilitate the metabolic flux from GDP‐l‐fucose towards 2′‐FL, the CRISPR‐Cas9 system was utilized to inactivate the genes including lacZ and wcaJ, increasing the titre by 6.59‐fold. Notably, the co‐introduction of NADPH and GTP regeneration pathways was confirmed to be more conducive to 2′‐FL formation, achieving a 2′‐FL titre of 2.24 g l−1. Moreover, comparisons of various exogenous α1,2‐fucosyltransferase candidates revealed that futC from Helicobacter pylori generated the highest titre of 2′‐FL. Finally, the viability of scaled‐up production of 2′‐FL was evidenced in a 3 l bioreactor with a maximum titre of 22.3 g l−1 2′‐FL and a yield of 0.53 mole 2′‐FL mole−1 lactose.
A powerful Escherichia coli cell factory was developed to enhance 2′‐FL production. The systematic engineering strategies included modular combinatorial optimization, enhancement of NADPH and GTP supply, gene knockout and screening for α1,2‐fucosyltransferase. The final titre of 2′‐FL was 22.3 g l−1 by fed‐batch in a 3 l bioreactor.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
A general efficient protocol was developed for the synthesis of carboxylic acids, esters, and amides through oxidation of alkynyl boronates, generated directly from terminal alkynes. This protocol ...represents the first example of C(sp)−B bond oxidation. This approach displays a broad substrate scope, including aryl and alkyl alkynes, and exhibits excellent functional group tolerance. Water, primary and secondary alcohols, and amines are suitable nucleophiles for this transformation. Notably, amino acids and peptides can be used as nucleophiles, providing an efficient method for the synthesis and modification of peptides. The practicability of this methodology was further highlighted by the preparation of pharmaceutical molecules.
A general efficient protocol for the synthesis of carboxylic acids, esters, and amides through oxidation of alkynyl boronates was developed. This approach displays a broad substrate scope, including aryl and alkyl alkynes, and exhibits excellent functional group tolerance. Water, primary and secondary alcohols, and amines are suitable nucleophiles for this transformation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Cancer immunotherapy is a major breakthrough in the history of tumor therapy in the last decade. Immune checkpoint inhibitors blocking CTLA-4/B7 or PD-1/PD-L1 pathways have greatly prolonged the ...survival of patients with different cancers. Long non-coding RNAs (lncRNAs) are abnormally expressed in tumors and play an important role in tumor immunotherapy through immune regulation and immunotherapy resistance. In this review, we summarized the mechanisms of lncRNAs in regulating gene expression and well-studied immune checkpoint pathways. The crucial regulatory function of immune-related lncRNAs in cancer immunotherapy was also described. Further understanding of the underlying mechanisms of these lncRNAs is of great importance to the development of taking lncRNAs as novel biomarkers and therapeutic targets for immunotherapy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Radar signatures of several small consumer drones are investigated by laboratory measurement. The drones are rotated on a turntable, and backscattered data are collected at two different frequency ...bands. The data are post-processed into inverse synthetic aperture radar images. The effects of frequency, aspect, polarization, dynamic blade rotation, camera mount, and drone types are presented.
Heavy metals are non-biodegradable and carcinogenic pollutants with great bio-accumulation potential. Their ubiquitous occurrence in water and soils has caused serious environmental concerns. ...Effective strategies that can eliminate the heavy metal pollution are urgently needed. Here the adsorption potential of seven heavy metal cations (Cd2+, Cu2+, Fe3+, Hg2+, Mn2+, Ni2+ and Zn2+) with 20 amino acids was systematically investigated with Density Functional Theory method. The binding energies calculated at B3LYP-D3/def2TZVP level showed that the contribution order of amino acid side chains to the binding affinity was carboxyl > benzene ring > hydroxyl > sulfhydryl > amino group. The affinity order was inversely proportional to the radius and charge transfer of heavy metal cations, approximately following the order of: Ni2+ > Fe3+ > Cu2+ > Hg2+ > Zn2+ > Cd2+ > Mn2+. Compared to the gas-phase in other researches, the water environment has a significant influence on structures and binding energies of the heavy metal and amino acid binary complexes. Collectively, the present results will provide a basis for the design of a chelating agent (e.g., adding carboxyl or a benzene ring) to effectively remove heavy metals from the environment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Rett syndrome (RTT) arises from loss-of-function mutations in methyl-CpG binding protein 2 gene (Mecp2), but fundamental aspects of its physiological mechanisms are unresolved. Here, by whole-cell ...recording of synaptic responses in MeCP2 mutant mice in vivo, we show that visually driven excitatory and inhibitory conductances are both reduced in cortical pyramidal neurons. The excitation-to-inhibition (E/I) ratio is increased in amplitude and prolonged in time course. These changes predict circuit-wide reductions in response reliability and selectivity of pyramidal neurons to visual stimuli, as confirmed by two-photon imaging. Targeted recordings reveal that parvalbumin-expressing (PV⁺) interneurons in mutant mice have reduced responses. PV-specific MeCP2 deletion alone recapitulates effects of global MeCP2 deletion on cortical circuits, including reduced pyramidal neuron responses and reduced response reliability and selectivity. Furthermore, MeCP2 mutant mice show reduced expression of the cation-chloride cotransporter KCC2 (K⁺/Cl⁻ exporter) and a reduced KCC2/NKCC1 (Na⁺/K⁺/Cl⁻ importer) ratio. Perforated patch recordings demonstrate that the reversal potential for GABA is more depolarized in mutant mice, but is restored by application of the NKCC1 inhibitor bumetanide. Treatment with recombinant human insulin-like growth factor-1 restores responses of PV⁺ and pyramidal neurons and increases KCC2 expression to normalize the KCC2/NKCC1 ratio. Thus, loss of MeCP2 in the brain alters both excitation and inhibition in brain circuits via multiple mechanisms. Loss of MeCP2 from a specific interneuron subtype contributes crucially to the cell-specific and circuit-wide deficits of RTT. The joint restoration of inhibition and excitation in cortical circuits is pivotal for functionally correcting the disorder.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Neurological disorders are a group of disorders with motor, sensory or cognitive damage, caused by dysfunction of the central or peripheral nervous system. Cyclin-dependent kinases 5 (Cdk5) is of ...vital significance for the development of the nervous system, including the migration and differentiation of neurons, the formation of synapses, and axon regeneration. However, when the nervous system is subject to pathological stimulation, aberrant activation of Cdk5 will induce abnormal phosphorylation of a variety of substrates, resulting in a cascade signaling pathway, and thus lead to pathological changes. Cdk5 is intimately related to the pathological mechanism of a variety of neurological disorders, such as A-β protein formation in Alzheimer’s disease, mitochondrial fragmentation in cerebral ischemia, and apoptosis of dopaminergic neurons in Parkinson’s disease. It is worth noting that Cdk5 inhibitors have been reported to have neuroprotective effects by inhibiting related pathological processes. Therefore, in this review, we will briefly introduce the physiological and pathological mechanisms of Cdk5 in the nervous system, focusing on the recent advances of Cdk5 in neurological disorders and the prospect of targeted Cdk5 for the treatment of neurological disorders.
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