The biomimetic structure and composition of biomaterials are recognized as critical factors that determine their biological performance. A bioinspired nano-micro structured octacalcium phosphate ...(OCP)/silk fibroin (SF) composite coating on titanium was achieved through a mild electrochemically induced deposition method. Findings indicate that SF plays a critical role in constructing the unique biomimetic hierarchical structure of OCP/SF composite coating layers. In vitro cell culture tests demonstrate that the presence of OCP/SF composite coatings, with highly ordered and hierarchically porous structure, greatly enhance cellular responses. The coatings developed in this study have considerable potential for various hard tissue engineering and applications.
Cancer‐associated mesenchymal stem cells (MSCs) play a pivotal role in modulating tumor progression. However, the interactions between liver cancer‐associated MSCs (LC‐MSCs) and hepatocellular ...carcinoma (HCC) remain unreported. Here, we identified the presence of MSCs in HCC tissues. We also showed that LC‐MSCs significantly enhanced tumor growth in vivo and promoted tumor sphere formation in vitro. LC‐MSCs also promoted HCC metastasis in an orthotopic liver transplantation model. Complementary DNA (cDNA) microarray analysis showed that S100A4 expression was significantly higher in LC‐MSCs compared with liver normal MSCs (LN‐MSCs) from adjacent cancer‐free tissues. Importantly, the inhibition of S100A4 led to a reduction of proliferation and invasion of HCC cells, while exogenous S100A4 expression in HCC cells resulted in heavier tumors and more metastasis sites. Our results indicate that S100A4 secreted from LC‐MSCs can promote HCC cell proliferation and invasion. We then found the expression of oncogenic microRNA (miR)‐155 in HCC cells was significantly up‐regulated by coculture with LC‐MSCs and by S100A4 ectopic overexpression. The invasion‐promoting effects of S100A4 were significantly attenuated by a miR‐155 inhibitor. These results suggest that S100A4 exerts its effects through the regulation of miR‐155 expression in HCC cells. We demonstrate that S100A4 secreted from LC‐MSCs promotes the expression of miR‐155, which mediates the down‐regulation of suppressor of cytokine signaling 1, leading to the subsequent activation of STAT3 signaling. This promotes the expression of matrix metalloproteinases 9, which results in increased tumor invasiveness. Conclusion: S100A4 secreted from LC‐MSCs is involved in the modulation of HCC progression, and may be a potential therapeutic target. (HEPATOLOGY 2013)
Abstract
The lung is the prophylaxis target against SARS-CoV-2 infection, and neutralizing antibodies are a leading class of biological products against various infectious viral pathogen. In this ...study, we develop a safe and cost-effective platform to express neutralizing antibody in the lung with replicating mRNA basing on alphavirus replicon particle (VRP) delivery system, to prevent SARS-CoV-2 infections. First, a modified VEEV replicon with two subgenomic (sg) promoters was engineered to translate the light and heavy chains of antibody simultaneously, for expression and assembly of neutralizing anti-SARS-CoV-2 antibody CB6. Second, the feasibility and protective efficacy of replicating mRNA against SARS-CoV-2 infection were demonstrated through both in vitro and in vivo assays. The lung target delivery with the help of VRP system resulted in efficiently block SARS-CoV-2 infection with reducing viral titer and less tissue damage in the lung of mice. Overall, our data suggests that expressing neutralizing antibodies in the lungs with the help of self-replicating mRNA could potentially be a promising prophylaxis approach against SARS-CoV-2 infection.
In this work, the Mn0.2Cd0.8S/NiCo2O4 composite modified with Ni2P as a co-catalyst was fabricated via a simple two-step hydrothermal method. The as-prepared ternary Mn0.2Cd0.8S/NiCo2O4/Ni2P ...composite displayed excellent H2 production performance. The ternary composite loaded with 5 wt% NiCo2O4 and 2 wt% Ni2P obtained the optimal H2 production performance of 24.47 mmol g−1 h−1 and a maximum AQE of 23.75%. The enhanced H2 production activity was assigned firstly to efficient spatial charge separation through the p−n Mn0.2Cd0.8S/NiCo2O4 heterojunction and secondly to sufficient surface active sites provided by Ni2P co-catalysts. This research provides a new approach to design effective ternary heterojunction.
Mn0.2Cd0.8S/NiCo2O4/Ni2P ternary heterojunction was prepared and displayed a superior photocatalytic H2 evolution activity under visible light illumination (λ ≥ 420 nm), which was attributed to the synergistic effect of p−n Mn0.2Cd0.8S/NiCo2O4 heterojunction and modification with Ni2P co-catalyst. Display omitted
•Mn0.2Cd0.8S/NiCo2O4/Ni2P was firstly designed and constructed.•Mn0.2Cd0.8S coupling with NiCo2O4 formed a p–n heterojunction.•Ni2P acted as co-catalyst and provided abundant active sites.•The ternary composite exhibited an enhanced H2 production activity.•H2 production mechanism of ternary composite was discussed.
Purpose
Ammonia oxidation, the first and rate-limiting step of nitrification, can be strongly influenced by agricultural practices, but little is known about the effects of fertilization and ...irrigation combination on ammonia oxidizers in agricultural soils. This study was designed to reveal how fertilizer type and irrigation frequency affect the ammonia-oxidizing archaea (AOA) and bacteria (AOB) communities in a northern Chinese wheat-maize rotation soil.
Materials and methods
Soil samples were collected from a long-term field experiment under different fertilization and irrigation regimes located in Wuqiao Experimental Station of China Agricultural University in June 2016. The abundance, diversity, and composition of AOA and AOB in the soils were investigated by using real-time PCR and Illumina Miseq sequencing approaches.
Results and discussion
The abundance of AOA was higher in the irrigated treatments, but lower in the treatments without irrigation, than that of AOB. The AOA abundance was positively correlated with soil moisture, pH, and NO
3
−
-N, while the AOB abundance was positively correlated with TN and NO
3
−
-N. Soil potential nitrification activity (PNA) was significantly positively correlated with the AOB abundance. Both fertilizer type and irrigation frequency significantly affected Shannon, ACE, and Chao1 indices of the AOB community, while only irrigation frequency had a significant impact on Shannon index of the AOA community. PCoA analysis results indicated that irrigation frequency greatly affected the AOA community structure, while fertilizer type played a more important role in affecting the AOB community structure. Mantel test and correlation heatmap analysis results indicated that soil moisture, pH, and NH
4
+
-N were significantly correlated to the AOA community structure, and TN and SOC were significantly correlated to the AOB community structure.
Conclusions
This study demonstrated that irrigation frequency greatly influenced the AOA community, while fertilizer type had a stronger effect on the AOB community. It was AOB but not AOA played a more important role in soil nitrification. Moreover, soil moisture, pH, and TN were the main determinants in driving the AOA community and TN and SOC were the main factors in influencing the AOB community.
Interleukin-37b (hereafter called IL-37) was identified as fundamental inhibitor of natural and acquired immunity. The molecular mechanism and function of IL-37 in colorectal cancer (CRC) has been ...elusive. Here, we found that IL-37 transgenic (IL-37tg) mice were highly susceptible to colitis-associated colorectal cancer (CAC) and suffered from dramatically increased tumor burdens in colon. Nevertheless, IL-37 is dispensable for intestinal mutagenesis, and CRC cell proliferation, apoptosis, and migration. Notably, IL-37 dampened protective cytotoxic T cell-mediated immunity in CAC and B16-OVA models. CD8
T cell dysfunction is defined by reduced retention and activation as well as failure to proliferate and produce cytotoxic cytokines in IL-37tg mice, enabling tumor evasion of immune surveillance. The dysfunction led by IL-37 antagonizes IL-18-induced proliferation and effector function of CD8
T cells, which was dependent on SIGIRR (single immunoglobulin interleukin-1 receptor-related protein). Finally, we observed that IL-37 levels were significantly increased in CRC patients, and positively correlated with serum CRC biomarker CEA levels, but negatively correlated with the CD8
T cell infiltration in CRC patients. Our findings highlight the role of IL-37 in harnessing antitumor immunity by inactivation of cytotoxic T cells and establish a new defined inhibitory factor IL-37/SIGIRR in cancer-immunity cycle as therapeutic targets in CRC.
Background
The Prognostic Nutritional Index (PNI) has been reported to be correlated with long-term outcomes after gastrointestinal tumor surgery. However, to our knowledge, only a few studies have ...shown that the PNI is related to cardiovascular diseases. Therefore, we aimed to assess the association between the PNI and long-term outcomes in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI).
Methods
This was retrospective observational study. A total of 3561 patients with CAD after PCI were retrospectively enrolled in the CORFCHD-ZZ study from January 2013 to December 2017. The patients (3519) were divided into three groups according to PNI tertiles: the first tertile (PNI < 47.12, n = 1173), the second tertile (47.12 ≤ PNI < 51.50, n = 1185), and the third tertile (PNI ≥ 51.50, n = 1161). The mean follow-up time was 37.59 ± 22.24 months. The primary endpoint long-term mortality, including all-cause mortality (ACM) and cardiac mortality (CM).Secondary endpoints were major adverse cardiovascular events (MACEs) and major adverse cardiovascular and cerebrovascular events (MACCEs).
Result
In our study, the incidences of ACM in the first, second, and third tertiles were 3.8%, 1.8% and 1.4%, respectively (P < 0.001). The incidences of CM occurring in the first, second, and third tertiles were 1.7%, 3.1% and 2.1%, respectively (P < 0.001).There was statistically significant different in primary endpoints incidence. MACEs occurred in 139 patients (11.8%) in the first tertile, 121 patients(11.1%) in the second tertile and 123 patients(10.8%) in the third tertile(P = 0.691). MACCEs occurred in 183 patients (15.6%) in the first tertile, 174 patients(14.7%) in the second tertile and 160 patients(13.85%) in the third tertile(P = 0.463).There was no statistically significant different in secondary endpoints incidence. Kaplan–Meier analyses showed that elevated PNI was significantly related to long-term CM (log rank, P < 0.001) and long-term ACM (log-rank, P < 0.001). Cox regression analyses suggested that compared with the patients in the first tertile, the risk of ACM was decreased to 60.9% (HR = 0.609, 95% CI: 0.398–0.932, P = 0.029) in the second tertile and 40.3%(HR = 0.403, 95% CI: 0.279–0.766, P = 0.003) in the third tertile, while the risk of CM was decreased to 58.8%(HR = 0.588, 95% CI: 0.321–0.969, P = 0.038) in the second tertile and 46.6%(HR = 0.466, 95% CI: 0.250–0.870, P = 0.017) in the third tertile. Multivariate Cox regression analyses showed that the PNI was an independent predictor of long-term ACM and CM.
Conclusion
Our finding shown that PNI is an independent predictor in CAD patients after PCI，the higher the PNI, the less occurring adverse event. Therefore，PNI may be an new biomarker to predict long-term outcome of CAD patients after PCI.
Background:
Hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) in the immune-tolerant (IT) phase is significantly associated with high risk for hepatocellular carcinoma, suggesting ...requirement for antiviral therapy, particularly for those with histological liver injury. This study aimed to establish a non-invasive panel to assess significant liver fibrosis in IT chronic hepatitis B.
Patients and methods:
One hundred and thirteen IT-phase CHB patients were retrospectively recruited and divided into two histopathological groups according to their histological profiles: necroinflammatory score <4 (N <4)/fibrosis score ⩽1 (F0-1), and necroinflammatory score ⩾4 (N ⩾4)/fibrosis score ⩾2 (F2-4). Multivariate analysis was conducted to assess the predictive value of the non-invasive model for significant liver fibrosis.
Results:
IT-phase CHB patients with N <4/F0-1 had significantly higher HBsAg levels than those with N ⩾4/F2-4. The optimal HBsAg level of log 4.44 IU/mL for significant liver fibrosis (F ⩾2) gave an area under the curve (AUC) of 0.83, sensitivity of 81.1%, specificity of 81.6%, positive predictive value (PPV) of 68.2%, and negative predictive value (NPV) of 89.9%. An IT model with HBsAg and gamma glutamyl transpeptidase (GGT) in combination was established, and it had an AUC of 0.86, sensitivity of 86.5%, specificity of 81.6%, PPV of 69.6, NPV of 92.5, and accuracy of 83.2% to predict F ⩾2 in the IT-phase CHB patients. Notably, the IT model exhibited higher predictive value than the existing aspartate aminotransferase-to-platelet ratio index, Fibrosis-4 score, and GGT to platelet ratio.
Conclusion:
The established IT model combining HBsAg and GGT has good performance in predicting significant liver fibrosis in IT-phase CHB patients.
Neurofibrillary tangles of hyperphosphorylated tau protein (p-tau) are a key pathological feature of Alzheimer's disease (AD). Tau phosphorylation is suggested to be secondary to amyloid-beta (Aβ) ...accumulation. However, the mechanism by which Aβ induces tau phosphorylation in neurons remains unclear. Neurotrophin receptor p75 (p75NTR) is a receptor for Aβ and mediates Aβ neurotoxicity, implying that p75NTR may mediate Aβ-induced tau phosphorylation in AD. Here, we showed that Aβ-induced tau hyperphosphorylation and neurodegeneration, including tau phosphorylation, synaptic disorder and neuronal loss, in the brains of both male wild-type (Wt) mice and male P301L transgenic mice (a mouse model of human tauopathy) were alleviated by genetic knockout of p75NTR in the both mouse models. We further confirmed that the activation or inhibition of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase-3β (GSK3β) significantly changed Aβ/p75NTR-mediated p-tau levels in neurons. Treatment of male P301L mice with soluble p75NTR extracellular domain (p75ECD-Fc), which antagonizes the binding of Aβ to p75NTR, suppressed tau hyperphosphorylation. Taken together, our findings suggest that p75NTR meditates Aβ-induced tau pathology and is a potential druggable target for AD and other tauopathies.
•p75NTR mediates Aβ-induced neuronal tau hyperphosphorylation.•The calpain/CDK5 and AKT/GSK3β pathways are involved in Aβ/p75NTR-induced tau hyperphosphorylation.•Modulation of p75NTR is a potential therapeutic approach to rescue brain tau pathology in AD.
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