The nature of molecule-electrode interface is critical for the integration of atomically precise molecules as functional components into circuits. Herein, we demonstrate that the electric field ...localized metal cations in outer Helmholtz plane can modulate interfacial Au-carboxyl contacts, realizing a reversible single-molecule switch. STM break junction and I-V measurements show the electrochemical gating of aliphatic and aromatic carboxylic acids have a conductance ON/OFF behavior in electrolyte solution containing metal cations (i.e., Na
, K
, Mg
and Ca
), compared to almost no change in conductance without metal cations. In situ Raman spectra reveal strong molecular carboxyl-metal cation coordination at the negatively charged electrode surface, hindering the formation of molecular junctions for electron tunnelling. This work validates the critical role of localized cations in the electric double layer to regulate electron transport at the single-molecule level.
Abstract
Background
We previously demonstrated that pregnant women with a history of cervical insufficiency had a softer anterior cervical lip, shorter cervical length and wider endocervical canal in ...the first trimester. The aim of this study was to investigate changes in cervical elastography, cervical length, and endocervical canal width in the second trimester after cerclage, and further discuss whether these ultrasound parameters are predictive of preterm delivery.
Methods
This was a secondary analysis of cervical changes in singleton pregnancies after cerclage from January 2016 to June 2018. Cervical elastography, cervical length, and endocervical canal width were measured during the second trimester in the cervical insufficiency group and control group without cervical insufficiency. Strain elastography under transvaginal ultrasound was used to assess cervical stiffness and presented as percentage (strain rate).
Results
Among the 339 pregnant women enrolled, 24 had a history of cervical insufficiency and underwent cerclage. Both anterior and posterior cervical lips were significantly softer in the cervical insufficiency group even though they received cerclage (anterior strain rate: 0.18 ± 0.06% vs. 0.13 ± 0.04%;
P
= 0.001; posterior strain rate: 0.11 ± 0.03% vs. 0.09 ± 0.04%;
P
= 0.017). Cervical length was also shorter in the cervical insufficiency group (36.3 ± 3.6 mm vs. 38.3 ± 4.6 mm;
P
= 0.047). However, there was no significant difference in endocervical canal width between the two groups (5.4 ± 0.7 mm vs. 5.6 ± 0.7 mm;
P
= 0.159). Multivariate logistic regression analysis also revealed significant differences in anterior cervical lip strain rate (adjusted odds ratio OR, 7.32, 95% confidence interval CI, 1.70-31.41;
P
= 0.007), posterior cervical lip strain rate (adjusted OR, 5.22, 95% CI, 1.42–19.18;
P
= 0.013), and cervical length (adjusted OR, 3.17, 95% CI,1.08–9.29;
P
= 0.035). Among the four ultrasound parameters, softer anterior cervical lip (
P
= 0.024) and shorter cervical length (
P
< 0.001) were significantly related to preterm delivery.
Conclusions
Cervical cerclage can prevent widening of the endocervical canal, but not improve cervical elasticity or cervical length. Measuring anterior cervical elastography and cervical length may be valuable to predict preterm delivery.
Oral squamous cell carcinoma (OSCC) is an extremely common head and neck cancer with a poor 5‐year survival rate, especially in cases of metastatic disease. Interleukin (IL)‐11 reportedly promotes ...cell growth and the epithelial–mesenchymal transition process in metastasis. However, the molecular mechanisms of IL‐11 in OSCC metastasis are unclear. This study found that IL‐11 upregulates matrix metalloproteinase 13 (MMP‐13) expression in OSCC via the IL‐11 receptor alpha subunit/glycoprotein 130 receptors that activate phosphatidyl‐inositol 3‐kinase, Ak strain transforming, and activator protein 1 signaling, which subsequently enhance MMP‐13‐induced tumor metastasis. TIMER2.0 analysis revealed a positive correlation between MMP‐13 and IL‐11 levels (r = 0.454). Moreover, a strong positive association was observed between higher levels of IL‐11 expression in OSCC tissue (p < 0.01), lymph node metastasis (p = 0.0154), and clinical disease stage (p = 0.0337). IL‐11 knockdown suppressed the migration of OSCC cells (p < 0.05). The evidence indicates that IL‐11 can serve as a new molecular therapeutic target in OSCC metastasis.
The clinical translation of bioactive scaffolds for the treatment of large segmental bone defects remains a grand challenge. The gene‐activated matrix (GAM) combining gene therapy and tissue ...engineering scaffold offers a promising strategy for the restoration of structure and function of damaged or dysfunctional tissues. Herein, a gene‐activated biomimetic composite scaffold consisting of an electrospun poly(ε‐caprolactone) fiber sheath and an alginate hydrogel core which carried plasmid DNA encoding bone morphogenetic protein 2 (pBMP2) and vascular endothelial growth factor (pVEGF), respectively, is developed. A peptide‐modified polymeric nanocarrier with low cytotoxicity and high efficiency serves as the nonviral DNA delivery vector. The obtained GAM allows spatiotemporal release of pVEGF and pBMP2 and promotes osteogenic differentiation of preosteoblasts in vitro. In vivo evaluation using a critical‐sized segmental femoral defect model in rats shows that the dual gene delivery system can significantly accelerate bone healing by activating angiogenesis and osteogenesis. These findings demonstrate the effectiveness of the developed dual gene‐activated core–sheath structured fiber‐hydrogel composite scaffold for critical‐sized bone defect regeneration and the potential of cell‐free scaffold‐based gene therapy for tissue engineering.
A dual gene‐activated biomimetic composite scaffold consisting of an electrospun poly(ε‐caprolactone) fiber sheath carrying plasmid DNA encoding bone morphogenetic protein 2 and an alginate hydrogel core carrying plasmid DNA encoding vascular endothelial growth factor is developed to enable spatiotemporally defined gene delivery for critical‐sized vascularized bone defect regeneration.
TGF-β superfamily signaling is indispensable for bone homeostasis. However, the global expression profiles of all the genes that make up this signaling module in bone and bone-related diseases have ...not yet been well characterized.
Transcriptomic datasets from human bone marrows, bone marrow-derived mesenchymal stem cells (MSCs) and MSCs of primary osteoporotic patients were used for expression profile analyses. Protein treatments, gene quantification, reporter assay and signaling dissection in MSC lines were used to clarify the interactive regulations and feedback mechanisms between TGF-β superfamily ligands and antagonists. Ingenuity Pathway Analysis was used for network construction.
We identified TGFB1 in the ligand group that carries out SMAD2/3 signaling and BMP8A, BMP8B and BMP2 in the ligand group that conducts SMAD1/5/8 signaling have relatively high expression levels in normal bone marrows and MSCs. Among 16 antagonist genes, the dominantly expressed TGF-β superfamily ligands induced only NOG, GREM1 and GREM2 via different SMAD pathways in MSCs. These induced antagonist proteins further showed distinct antagonisms to the treated ligands and thus would make up complicated negative feedback networks in bone. We further identified TGF-β superfamily signaling is enriched in MSCs of primary osteoporosis. Enhanced expression of the genes mediating TGF-β-mediated SMAD3 signaling and the genes encoding TGF-β superfamily antagonists served as significant features to osteoporosis.
Our data for the first time unveiled the transcription landscape of all the genes that make up TGF-β superfamily signaling module in bone. The feedback mechanisms and regulatory network prediction of antagonists provided novel hints to treat osteoporosis. Video Abstract.
Procalcitonin, as a medium of inflammation, has become a new marker of the identification of severe bacterial infections in recent years and has received high attention due to its most ideal ...diagnostic indicators of specificity with major types of organism systemic inflammation of bacterial infection in the early stages. Thus, a novel method for the determination of procalcitonin (PCT) was developed based on a sandwich-type electrochemical immunosensor, which combined a simple immunosensor array as well as an effectively designed trace tag. The immunosensor was fabricated by layer-by-layer coating graphene (GC), carbon nanotubes (MWCNTs), chitosan (CS), glutaraldehyde (GA) composite on the working electrode, which can increase the electronic transfer rate and improve the surface area to capture a large number of primary antibodies (Ab1). The trace tag was prepared by loading high-content signal horseradish peroxidase labeled secondary PCT antibody (HRP-Ab2) with AuNPs, which were coated with mesoporous silica nanoparticles (MCM-41) through thionine linking. In comparison with conventional methods, the proposed immunosensor for PCT provided a better linear response range from 0.01 to 350ng/mL and a lower limit of detection (LOD) of 0.5pg/mL under optimal experimental conditions. In addition, the immunosensor exhibited convenience, low cost, rapidity, good specificity, acceptable stability and reproducibility. Moreover, satisfactory results were obtained for the determination of PCT in real human serum samples, indicating that the developed immunoassay has the potential to find application in clinical detection of PCT and other tumor markers as an alternative approach.
•We designed a novel sandwich-type electrochemical immunosensor for Procalcitonin.•Combining by a simple immunosensor array and an effectively designed trace tag.•This proposed method shows better accuracy, stability, reproducibility, and sensitivity.•The LOD for PCT was remarkably lower compared with other current techniques.•The proposed system can provide a further platform for other immunoassays.
Understanding the structure‐activity relationship of catalytic reactions at a molecular level still remains a great challenge. Herein, shell‐isolated nanoparticle‐enhanced Raman spectroscopy ...(SHINERS) is employed to in‐situ study the catalytic hydrogenation of para‐nitrothiophenol (pNTP) on Pt‐based nanocatalysts with different size and composition. The nanocatalysts are assembled on pinhole‐free shell‐isolate nanoparticles (SHINs), which work as Raman amplifiers to enhance the Raman signals of species on the catalysts, allowing the in‐situ monitoring of catalytic reactions carried out on the catalysts. Using this strategy, we find that the catalytic activity of the Pt nanocatalysts shows a volcanic trend with the Pt size, and that PtM (M=Ni or Cu) bimetallic nanocatalysts display much higher performance compared with Pt due to better activation of the nitro group. This work demonstrates that SHINERS is a promising technique for in‐situ study of nanocatalysis thus can deepen the understanding of the behaviors of different catalysts.
Shine like a diamond! Shell‐isolated nanoparticles enhanced Raman spectroscopy (SHINERS) has been employed to reveal the size and composition effect of Pt‐based nanocatalysts towards the hydrogenation of pNTP.
Chondrosarcoma is a malignant bone tumor that is characterized by high metastatic potential and marked resistance to radiation and chemotherapy. The knowledge that adipokines facilitate the ...initiation, progression, metastasis, and treatment resistance of various tumors has driven several in vitro and in vivo investigations into the effects of adipokines resistin, leptin, and adiponectin upon the development and progression of chondrosarcomas. Another adipokine, visfatin, is known to regulate tumor progression and metastasis, although how this molecule may affect chondrosarcoma metastasis is unclear. Here, we found that visfatin facilitated cellular migration via matrix metalloproteinase-2 (MMP-2) production in human chondrosarcoma cells and overexpression of visfatin enhanced lung metastasis in a mouse model of chondrosarcoma. Visfatin-induced stimulation of MMP-2 synthesis and activation of the AP-1 transcription factor facilitated chondrosarcoma cell migration via the ERK, p38, and JNK signaling pathways. This evidence suggests that visfatin is worth targeting in the treatment of metastatic chondrosarcoma.
Osteosarcoma, one of primary bone tumor in children and young adults, has poor prognosis and drug resistances to chemotherapy. In order to reinforce the conventional therapies and antagonize the ...osteosarcoma in patients, a novel strategy is required for developing a new treatment. In this study, surfactin, a natural product from Bacillus subtilis, showed the efficiency of cell death in osteosarcoma, but not in normal cells. Surfactin triggers ER stress mechanism by promoting the aberrant Ca2+ release from ER lumen and ER‐signaling to mitochondrial dysfunction following caspases activation mediating cell apoptosis. Surfactin‐induced ER stress not only upregulated of glucose‐regulated protein 78/94 and IRE1‐ASK1‐JNK pathway but also leading to calpains and Bcl‐2 proteins family involving the release of cytochrome c. The releases into cytosol trigger the cleavage of caspase‐9 and caspase‐3 to induce cell apoptosis. In this study, surfactin demonstrated the potential functions to trigger the ER stress, ER stress‐associated IRE1‐ASK1‐JNK signaling pathway, mitochondrial dysfunction, and caspase activations leading to programmed cell apoptosis. Importantly, implicating the signaling pathway that regulates the connection between ER stress and mitochondrial dysfunction causing apoptosis associated with surfactin. These results indicated a potential application of surfactin strengthen current conventional therapies.
Background
Colorectal cancer (CRC) is one of the most common cancers worldwide. Comprehensive data on the economic burden of CRC at a population‐level is critical in informing policymaking, but such ...data are currently limited in China.
Methods
From a societal perspective, the economic burden of CRC in 2019 was estimated, including direct medical and nonmedical expenditure, disability, and premature‐death‐related indirect expenditure. Data on disease burden was taken from the GBD 2019 and analyzed using a prevalence‐based approach. The per‐person direct expenditure and work loss days were from a multicenter study; the premature‐death‐related expenditure was estimated using a human capital approach. Projections were conducted in different simulated scenarios. All expenditure data were in Chinese Yuan (CNY) and discounted to 2019.
Results
In 2019, the estimated overall economic burden of CRC in China was CNY170.5 billion (0.189% of the local GDP). The direct expenditure was CNY106.4 billion (62.4% of the total economic burden), 91.4% of which was a direct medical expenditure. The indirect expenditure was CNY64.1 billion, of which 63.7% was related to premature death. The predicted burden would reach CNY560.0 billion in 2030 given constant trends for disease burden; however, it would be alternatively reduced to <CNY515.2 billion if the cancer prevention and control goals set by the United Nations and China for 2030 are achieved.
Conclusions
The population‐level economic burden of CRC in China in 2019 seemed noteworthy, with the direct expenditure accounting for more than half. Without effectively reducing exposure to modifiable factors and expanding screening coverage, the burden would continue increasing.
PDF
