High magnetic order temperature, sustainable polar insulating state, and tolerance to device integrations are substantial advantages for applications in next-generation spintronics. However, ...engineering such functionality in a single-phase system remains a challenge owing to the contradicted chemical and electronic requirements for polar nature and magnetism, especially with an ordering state highly above room temperature. Perovskite-related oxides with unique flexibility allow electron-unpaired subsystems to merge into the polar lattice to induce magnetic interactions, combined with their inherent asymmetry, thereby promising polar magnet design. Herein, by atomic-level composition assembly, a family of Ti/Fe co-occupied perovskite oxide films Pb(Ti1–x ,Fe x )O3 (PFT(x)) with a Ruddlesden–Popper superstructure are successfully synthesized on several different substrates, demonstrating exceptional adaptability to different integration conditions. Furthermore, second-harmonic generation measurements convince the symmetry-breaking polar character. Notably, a ferromagnetic ground state up to 600 K and a steady insulating state far beyond room temperature were achieved simultaneously in these films. This strategy of constructing layered modular superlattices in perovskite oxides could be extended to other strongly correlated systems for triggering nontrivial quantum physical phenomena.
The backbone of Dendrobium officinale polysaccharide (DOP) was reported to be glucomannan. But the dispute continues due to the limitation of conventional analysis methods (e.g., the overlapped NMR ...signals). Herein, we describe an oligosaccharide sequencing analysis that successfully corrects the backbone to mannan. This analysis involves producing oligosaccharide fragments from mild acid hydrolysis of DOP followed by p-aminobenzoic ethyl ester (ABEE) derivatization. Then, a series of oligosaccharides with varied polymerization degrees (DP = 2–10) were isolated and identified by LC-MS profiling, monosaccharide composition analysis, linkage analysis, and 1D-/2D-NMR elucidation. Finally, we conclude that the backbone of DOP is a β-D-1,4-mannan which is confirmed by other analysis such as comparison with reference mannan. This oligosaccharide analysis is more straightforward and reliable by transforming the complicated polymers into oligomers which have more accurate and convincing MS and NMR data.
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•An oligosaccharide analysis method was proposed to characterize the DOP.•A series of oligomers and isomers from hydrolyzed DOP were isolated and identified.•An LC-MS method was established to test the oligomers' sugar sequence.•The backbone structure of DOP was corrected to be a β-D-1,4-Mannan.
Epidermal growth factor receptor (EGFR) plays a significant role in promoting breast cancer progression. However, targeting EGFR as a single treatment only resulted in moderate efficacy to the ...disease. The underlying mechanism of low responsiveness to EGFR inhibition remains largely unclear. Tumor-secreted extracellular vesicles (EVs) play a crucial role in mediating intercellular communication between tumor and stromal cells in local microenvironment and distant metastatic niche. Extracellular vesicles mediate cell-to-cell transfer of lipids, nucleic acids, and proteins. Although numerous recent studies have demonstrated exchanges of extracellular vesicles between cancer cells and the recipient cells contribute to tumor proliferation, invasion, and metastasis, yet little is known how the exosomal compartment responds to targeted therapies and their role in promoting drug resistance. In the current study we used a triple-negative breast cancer model to show that EV-encapsulated EGFR is protected from targeted inhibitors of EGFR and can trigger signaling pathway in recipient cancer cells, promoting proliferation and migration ability in vitro. Taken together, our study suggested a novel mechanism of drug resistance entailing the EV compartment, such as exosomes, as a target shelter which when released can signal for tumor promotion in the recipient cancer cells.
•EGFR inhibitors suppress autophosphorylation of cellular EGFR but not EV-carried EGFR.•EV-carried EGFR stimulated cancer cell growth which is resistant to inhibition of EGFR and MAPK of the EV-producing cells.•Cancer cell-secreted EVs can stimulate cell migration through EGFR-independent mechanisms.•Our results suggest a novel mechanism that EV can shelter RTKs to signal growth promotion in the recipient cancer cells.
Pancreatic fibrosis, a prominent feature of chronic pancreatitis (CP), induces persistent and permanent damage in the pancreas. Pancreatic stellate cells (PSCs) provide a major source of ...extracellular matrix (ECM) deposition during pancreatic injury, and persistent activation of PSCs plays a vital role in the progression of pancreatic fibrosis. Retinoic acid (RA), a retinoid, has a broad range of biological functions, including regulation of cell differentiation and proliferation, attenuating progressive fibrosis of multiple organs. In the present study, we investigated the effects of RA on fibrosis in experimental CP and cultured PSCs. CP was induced in mice by repetitive cerulein injection in vivo, and mouse PSCs were isolated and activated in vitro. Suppression of pancreatic fibrosis upon administration of RA was confirmed based on reduction of histological damage, α-smooth muscle actin (α-SMA) expression and mRNA levels of β-catenin, platelet-derived growth factor (PDGF)-Rβ transforming growth factor (TGF)-βRII and collagen 1α1 in vivo. Wnt 2 and β-catenin protein levels were markedly down-regulated, while Axin 2 expression level was up-regulated in the presence of RA, both in vivo and in vitro. Nuclear translation of β-catenin was significantly decreased following RA treatment, compared with cerulein-induced CP in mice and activated PSCs. Furthermore, RA induced significant PSC apoptosis, inhibited proliferation, suppressed TCF/LEF-dependent transcriptional activity and ECM production of PSC via down-regulation of TGFβRII, PDGFRβ and collagen 1α1 in vitro. These results indicate a critical role of the Wnt/β-catenin signaling pathway in RA-induced effects on CP and PSC regulation and support the potential of RA as a suppressor of pancreatic fibrosis in mice.
•Rapid authentication of EBN in minutes based on an oligosaccharide was established.•The oligosaccharide marker was identified to be Neu5Ac (2–3) Gal by MS and NMR.•The marker content could be ...associated with the quality of EBN products.
Edible bird’s nest (EBN) is a popular and expensive food material. The limited supply and great demand result in the use of adulterants. The authenticity concern is raised due to the lack of appropriate quality markers. Herein, this study aims to provide a specific oligosaccharide marker for rapid EBN authentication. Comparing the benzocaine (ABEE)-labeled saccharide profiles of multiple batches of EBN and adulterants indicates seven unique EBN oligosaccharides. The most abundant one, named BNM001, was selected as a marker and characterized to be Neu5Ac (2–3) Gal by MS and NMR spectra. This new oligosaccharide marker enables a rapid authentication of EBN within 10 min. ABEE labelling of this marker further upgraded the accuracy and sensitivity of the LC-qTOF-MS quantitative analysis. The relative marker content was associated with the quality of EBN products. These results suggest a specific and efficient quality marker for rapid authentication of EBN and related products.
Chronic cerebral hypoperfusion (CCH)-mediated cognitive impairment is a serious problem worldwide. However, given its complexity, the underlying mechanisms by which CCH induces cognitive dysfunction ...remain unclear, resulting in a lack of effective treatments. In this study, we aimed to determine whether changes in the expression of RasGRF1, an important protein associated with cognition and synaptic plasticity, underlie the associated impairments in cognition after CCH. We found that RasGRF1 levels markedly decreased following CCH. Through prediction and validation studies, we observed that miRNA-323-3p was upregulated after CCH and could bind to the 3'-untranslated region of
mRNA and regulate its expression
. Moreover, the inhibition of miRNA-323-3p upregulated
expression in the hippocampus after CCH, which was reversed by
siRNA. This suggests that miRNA-323-3p is an important regulator of Rasgrf1. The Morris water maze and Y maze tests showed that miRNA-323-3p inhibition and
upregulation improved spatial learning and memory, and electrophysiological measurements revealed deficits in long-term potentiation after CCH that were reversed by
upregulation. Dendritic spine density and mature mushroom spine density were also improved after miRNA-323-3p inhibition and
upregulation. Furthermore,
upregulation by miRNA-323-3p inhibition improved dendritic spine density and mature mushroom spine density and ameliorated the deterioration of synapses and postsynaptic density. Overall, RasGRF1 regulation attenuated cognitive impairment, helped maintain structural and functional synaptic plasticity, and prevented synapse deterioration after CCH. These results suggest that
downregulation by miRNA-323-3p plays an important role in cognitive impairment after CCH. Thus, RasGRF1 and miRNA-323-3p may represent potential therapeutic targets for cognitive impairment after CCH.
The comparison between the mini-midvastus (mini-MV) and mini-parapatellar (mini-MPP) approach in total knee arthroplasty (TKA) remains a subject of debate. The present study compared quadriceps ...activation, pain levels, and clinical outcomes between the two approaches; quadricep activation was assessed using surface electromyography (sEMG).
This retrospective cross-sectional study comprised a total of 78 patients aged between 50 and 85 years with primary osteoarthritis. Patients were divided into a mini-MV (n = 38) group and a mini-MPP (n = 40) group according to the surgical approach.
The two groups exhibited no significant differences in sEMG for the vastus medialis (VM) or rectus femoris (RF) at the follow-up time points, with the exception that the mini-MV group exhibited superior strength of RF during extensions at the 2-week follow-up. However, the mini-MPP group had superior Western Ontario and McMaster Universities Index (WOMAC) total and function scores at the 2- and 6-week follow-ups. The mini-MPP group also had superior WOMAC stiffness scores at the 2-week follow-up. The two groups did not differ significantly in terms of pain levels or morphine consumption.
The sEMG data of quadriceps muscle would not differ significantly between the mini-MV and mini-MPP approaches for TKA. Moreover, the mini-MPP approach may yield superior WOMAC scores when compared with the mini-MV approach.
Chronic high-dose alcohol consumption impairs bone remodeling, reduces bone mass, and increases the risk of osteoporosis and bone fracture. However, the mechanisms underlying alcohol-induced ...osteoporosis are yet to be elucidated. In this study, we showed that excess intake of ethyl alcohol (EtOH) resulted in osteopenia and osteoblast necroptosis in mice that led to necrotic lesions and reduced osteogenic differentiation in bone marrow mesenchymal stem cells (BMMSCs). We found that EtOH treatment led to the activation of the RIPK1/RIPK3/MLKL signaling, resulting in increased osteoblast necroptosis and decreased osteogenic differentiation and bone formation both in vivo and in vitro. We further discovered that excessive EtOH treatment-induced osteoblast necroptosis might partly depend on reactive oxygen species (ROS) generation; concomitantly, ROS contributed to necroptosis of osteoblasts through a positive feedback loop involving RIPK1/RIPK3. In addition, blocking of the RIPK1/RIPK3/MLKL signaling by necrostatin-1 (Nec-1), a key inhibitor of RIPK1 kinase in the necroptosis pathway, or antioxidant N-acetylcysteine (NAC), an inhibitor of ROS, could decrease the activation of osteoblast necroptosis and ameliorate alcohol-induced osteopenia both in vivo and in vitro. Collectively, we demonstrated that chronic high-dose alcohol consumption induced osteopenia via osteoblast necroptosis and revealed that RIPK1 kinase may be a therapeutic target for alcohol-induced osteopenia.
In this paper, a novel complex Fe
II
4
L
4
8+
was designed and synthesized from subcomponent self-assembly of
C
3
-symmetric 2,4,6-tris(4-aminophenoxy)triazine, 3-methylpyridine-2-carboxaldehyde and ...iron(II) trifluoromethanesulfonate in CH
3
CN solution. The structure of target compound was confirmed by
1
H NMR and ESI-MS measurements as a tetrahedral cage, and the host–guest interactions between the complex and a series of guest molecules were studied. The results show that the intermolecular interactions are relatively weak by comparison with other similar ligand’s complexes, which may be due to the steric effect of methyl groups adjacent to the peripheral apertures of the cage.
Flexible electronics are a possible alternative for portable consumer applications and have many advantages. However, the circuit design for flexible electronics is still challenging, especially for ...sensitive analog circuits. Due to the different properties of flexible thin-film transistors (TFTs), conventional CMOS design techniques cannot be used directly on flexible electronics. Significant parameter variations and degradation effects of flexible TFTs further increase difficulties for circuit designers. In this paper, a reliability-aware circuit sizing approach is proposed for the analog circuits with flexible TFTs. The process variation, bending, and degradation effects of flexible TFTs in the optimization flow are considered simultaneously. Instead of optimizing the fresh yield and lifetime yield separately, a unified optimization approach is proposed to consider the two yield issues simultaneously. As shown in the experimental results, the proposed approach can further improve the lifetime yield and significantly reduce the design overhead with a fast computation time.
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