Objective
This study was undertaken to uncover the pathophysiologic role of discoidin domain receptor 2 (DDR‐2), a putative fibrillar collagen receptor, in inflammation promotion and joint ...destruction in rheumatoid arthritis (RA).
Methods
In synovial tissue from patients with RA and from mice with collagen antibody–induced arthritis (CAIA) (using Ddr2−/− and DBA/1 mice), gene and protein expression levels of DDR‐2, interleukin‐15 (IL‐15), and Dkk‐1 were measured by quantitative reverse transcription–polymerase chain reaction, Western blotting, and immunohistochemistry. Gene knockdown of DDR2 in human RA fibroblast‐like synoviocytes (FLS) was conducted via small interfering RNA. Interaction between the long noncoding RNA H19 and microRNA 103a (miR‐103a) was assessed in RA FLS using RNA pulldown assays. Cellular localization of H19 was examined using fluorescence in situ hybridization assays. Chromatin immunoprecipitation and dual luciferase reporter assays were applied to verify H19 transcriptional and posttranscriptional regulation by miR‐103a.
Results
DDR2 messenger RNA (mRNA) expression was significantly associated with the levels of IL‐15 and Dkk‐1 mRNA in the synovial tissue of RA patients (r2 = 0.2022–0.3293, all P < 0.05; n = 33) and with the serum levels of IL‐15 and Dkk‐1 in mice with CAIA (P < 0.05). In human RA FLS, activated DDR‐2 induced the expression of H19 through c‐Myc. Moreover, H19 directly interacted with and promoted the degradation of miR‐103a.
Conclusion
These results indicate a novel role for activated DDR‐2 in RA FLS, showing that DDR‐2 is responsible for regulating the expression of IL‐15 and Dkk‐1 in RA FLS and is involved in the promotion of inflammation and joint destruction during pathophysiologic development of RA. Moreover, DDR‐2 inhibition, acting through the H19–miR‐103a axis, leads to reductions in the inflammatory reaction and severity of joint destruction in mice with CAIA, suggesting that inhibition of DDR‐2 may be a potential therapeutic strategy for RA.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The cost-effectiveness and abundance of sodium make sodium-ion batteries a compelling alternative to lithium-ion batteries. The hurdle is adapting the widely used graphite anodes in lithium-ion ...batteries for use in sodium-ion battery anodes, given the larger size of sodium. Macroporous carbon materials emerge as promising anode candidates for sodium-ion batteries due to their favorable electrolyte penetration and structural stability. In this research, an economical and readily available high-temperature coal pitch serves as the precursor for the anode material. Sodium chloride acts as the templating agent, while phosphorus atoms are intentionally introduced through disodium hydrogen phosphate to induce defects. The phosphorus-doped macroporous carbon demonstrates noteworthy specific capacity and cycling stability, even under high current density conditions, making it a viable choice for application in sodium-ion batteries: after 1000 cycles at a current density of 5 A g
−1
, the reversible specific capacity still reaches 135 mA h g
−1
with a capacity retention rate of 94.4%; after increasing the current density to 10 A g
−1
, the reversible specific capacity still exceeds 100 mA h g
−1
after 3500 cycles.
The cost-effectiveness and abundance of sodium make sodium-ion batteries a compelling alternative to lithium-ion batteries.
Tooth loss is suggested to be associated with an increased risk of dementia in many studies. But the relationship between tooth loss and dementia is not yet fully understood. This systematic review ...and meta-analysis aimed to determine the relative effect of tooth loss on dementia risk.
An electronic search of PubMed, Scopus, Embase, and Web of Knowledge was conducted in March 2018 to identify relevant observational studies with the English language restriction. Studies were included if they assessed the relationship between tooth loss and risk of dementia. Study quality was detected by the modified Downs and Black scale. Odds risks (ORs) were pooled using a random-effects model in the crude model.
The literature search initially yielded 1574 articles, and 21 observational studies published between 1994 and 2017 were finally included for the analyses. The crude results with random-effects model showed that patients with multiple tooth loss had higher incidence of dementia (OR 2.62, 95% CI 1.90-3.61, P < 0.001, I
= 90.40%). The association remained noted when only adjusted results were pooled from 18 studies (OR 1.55, 95% CI 1.41-1.70, P = 0.13, I
= 28.00%). Meta-regression analysis showed that study design explained about 16.52% of heterogeneity in the crude model. The overall quality rating scores of studies ranged from 11 to 16.
Findings from this review evidenced that tooth loss is positively associated with an increased risk of dementia in adults. Future well-designed longitudinal researches examining the direct and indirect relationship between tooth loss and dementia risk are encouraged.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Novel multi‐stimuli‐responsive microcapsules with adjustable controlled‐release characteristics are prepared by a microfluidic technique. The proposed microcapsules are composed of crosslinked ...chitosan acting as pH‐responsive capsule membrane, embedded magnetic nanoparticles to realize “site‐specific targeting”, and embedded temperature‐responsive sub‐microspheres serving as “micro‐valves”. By applying an external magnetic field, the prepared smart microcapsules can achieve targeting aggregation at specific sites. Due to acid‐induced swelling of the capsule membranes, the microcapsules exhibit higher release rate at specific acidic sites compared to that at normal sites with physiological pH. More importantly, through controlling the hydrodynamic size of sub‐microsphere “micro‐valves” by regulating the environment temperature, the release rate of drug molecules from the microcapsules can be flexibly adjusted. This kind of multi‐stimuli‐responsive microcapsules with site‐specific targeting and adjustable controlled‐release characteristics provides a new mode for designing “intelligent” controlled‐release systems and is expected to realize more rational drug administration.
Multi‐stimuli‐responsive microcapsules with adjustable controlled‐release characteristics are successfully prepared by embedding magnetic nanoparticles and temperature‐responsive sub‐microspheres into pH‐responsive chitosan microcapsule membranes. This kind of microcapsules can simultaneously achieve targeted delivery by applying an external magnetic field, self‐regulated drug release according to pH difference at pathological sites, and adjustable controlled‐release depending on temperature regulation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The growing knowledge of ferroptosis has suggested the role and therapeutic potential of ferroptosis in cancer, but has not been translated into effective therapy. Liver cancer, primarily ...hepatocellular carcinoma (HCC), is highly lethal with limited treatment options. LIFR is frequently downregulated in HCC. Here, by studying hepatocyte-specific and inducible Lifr-knockout mice, we show that loss of Lifr promotes liver tumorigenesis and confers resistance to drug-induced ferroptosis. Mechanistically, loss of LIFR activates NF-κB signaling through SHP1, leading to upregulation of the iron-sequestering cytokine LCN2, which depletes iron and renders insensitivity to ferroptosis inducers. Notably, an LCN2-neutralizing antibody enhances the ferroptosis-inducing and anticancer effects of sorafenib on HCC patient-derived xenograft tumors with low LIFR expression and high LCN2 expression. Thus, anti-LCN2 therapy is a promising way to improve liver cancer treatment by targeting ferroptosis.
In this study, we aimed to compare the radiation-induced hepatic toxicity (RIHT) outcomes of radiotherapy (RT) plus antibodies against programmed cell death protein 1 (anti-PD1) versus RT alone in ...patients with hepatocellular carcinoma (HCC), evaluate prognostic factors of non-classic radiation-induced liver disease (ncRILD), and establish a nomogram for predicting the probability of ncRILD.
Patients with unresectable HCC treated with RT and anti-PD1 (RT + PD1, n = 30) or RT alone (n = 66) were enrolled retrospectively. Patients (n = 30) in each group were placed in a matched cohort using propensity score matching (PSM). Treatment-related hepatotoxicity was evaluated and analyzed before and after PSM. The prognostic factors affecting ncRILD were identified by univariable logistic analysis and Spearman's rank test in the matched cohort to generate a nomogram.
There were no differences in RIHT except for increased aspartate aminotransferase (AST) ≥ grade 1 and increased total bilirubin ≥ grade 1 between the two groups before PSM. After PSM, AST ≥ grade 1 occurred more frequently in the RT + PD1 group (p = 0.020), and there were no significant differences in other hepatotoxicity metrics between the two groups. In the matched cohort, V25, tumor number, age, and prothrombin time (PT) were the optimal prognostic factors for ncRILD modeling. A nomogram revealed a good predictive performance (area under the curve = 0.82).
The incidence of RIHT in patients with HCC treated with RT + PD1 was acceptable and similar to that of RT treatment. The nomogram based on V25, tumor number, age, and PT robustly predicted the probability of ncRILD.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The incidence of classic radiation-induced liver disease (cRILD) has been significantly reduced. However, non-classic radiation-induced liver disease (ncRILD) remains a major concern following ...radiotherapy in patients with hepatocellular carcinoma (HCC). This study evaluated the incidence of ncRILD following intensity-modulated radiotherapy (IMRT) for Child-Pugh grade B (CP-B) patients with locally advanced HCC and established a nomogram for predicting ncRILD probability.
Seventy-five CP-B patients with locally advanced HCC treated with IMRT between September 2014 and July 2021 were included. The max tumor size was 8.39 cm ± 5.06, and the median prescribed dose was 53.24 Gy ± 7.26. Treatment-related hepatotoxicity was evaluated within three months of completing IMRT. A nomogram model was formulated to predict the probability of ncRILD, using univariate and multivariate analysis.
Among CP-B patients with locally advanced HCC, ncRILD occurred in 17 (22.7%) patients. Two patients (2.7%) exhibited a transaminase elevation of ≥ G3, fourteen (18.7%) exhibited a Child-Pugh score increase of ≥ 2, and one (1.3%) demonstrated both a transaminase elevation of ≥ G3 and a Child-Pugh score increase of ≥ 2. No cRILD cases were observed. A mean dose to the normal liver of ≥ 15.1 Gy was used as the cutoff for ncRILD. Multivariate analysis revealed that the prothrombin time before IMRT, tumour number, and mean dose to the normal liver were independent risk factors for ncRILD. The nomogram established on the basis of these risk factors displayed exceptional predictive performance (AUC = 0.800, 95% CI 0.674-0.926).
The incidence of ncRILD following IMRT for CP-B patients with locally advanced HCC was acceptable. A nomogram based on prothrombin time before IMRT, tumour number, and mean dose to the normal liver accurately predicted the probability of ncRILD in these patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This paper estimates the effects of trade liberalization on household income inequality and investigates whether trade liberalization or domestic reforms are the main factors influencing increasing ...inequality in Taiwan, a middle‐income open economy. We construct an empirical model by decomposing the sources of household disposable income in the quintile ratio and separate trade partners into OECD (Organisation for Economic Co‐operation and Development) and non‐OECD countries. Using time‐series data to estimate the long‐run effect, we find that net exports to OECD countries increase inequality, whereas net exports to non‐OECD countries insignificantly decrease inequality. This finding diverges from the prediction based on the Stolper–Samuelson theorem. Overall, trade liberalization increases income inequality, and the effect is mainly attributed to net exports to OECD countries. Moreover, we provide evidence that domestic reforms, particularly technological progress in favor of skilled labor and industrial structural change, rather than trade liberalization, are the main driving forces of income inequality.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
•NMC-Co is a mesoporous carbon microsphere consisting of carbon nanosheets.•Co nanoparticles obviously limited the dissolution and generation of polyselenide.•Carbon nanosheets can shorten ion ...transport and enhance electrochemical kinetics.•Se@NMC-Co has excellent rate capability of 462.0 mA h g−1 at 2C.
To solve the volume expansion and the dissolution of high-order polyselenide of selenium cathode during discharge process, herein, a cobalt nanoparticles inlayed N-doped mesoporous carbon material (NMC-Co) consisting of carbon nanosheets was synthesized to apply as a selenium host for high performance Lithium-Selenium (Li-Se) battery. The obtained material with high specific surface area and high porosity has an excellent structure combining mesopores and inlayed cobalt nanoparticles, which provides favorable conditions for electrolyte infiltration and alleviation of cathode volume expansion, and also effectively restricts the generation and dissolution of polyselenide. As expected, when using NMC-Co as a host for the selenium cathode, Se50@NMC-Co loading with 50% of Se can deliver a high reversible capacity of 419.1 mA h g−1 at a current rate of 0.2C after 100 cycles (1C = 675 mA h g−1) and an excellent cycling stability of only 0.024% capacity decay per cycle after 200 cycles at 1C is demonstrated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objectives
Preoperative differentiation between benign parotid gland tumors (BPGT) and malignant parotid gland tumors (MPGT) is important for treatment decisions. The purpose of this study was to ...develop and validate an MRI-based radiomics nomogram for the preoperative differentiation of BPGT from MPGT.
Methods
A total of 115 patients (80 in training set and 35 in external validation set) with BPGT (
n
= 60) or MPGT (
n
= 55) were enrolled. Radiomics features were extracted from T1-weighted and fat-saturated T2-weighted images. A radiomics signature model and a radiomics score (Rad-score) were constructed and calculated. A clinical-factors model was built based on demographics and MRI findings. A radiomics nomogram model combining the Rad-score and independent clinical factors was constructed using multivariate logistic regression analysis. The diagnostic performance of the three models was evaluated and validated using ROC curves on the training and validation datasets.
Results
Seventeen features from MR images were used to build the radiomics signature. The radiomics nomogram incorporating the clinical factors and radiomics signature had an AUC value of 0.952 in the training set and 0.938 in the validation set. Decision curve analysis showed that the nomogram outperformed the clinical-factors model in terms of clinical usefulness.
Conclusions
The above-described radiomics nomogram performed well for differentiating BPGT from MPGT, and may help in the clinical decision-making process.
Key Points
•
Differential diagnosis between BPGT and MPGT is rather difficult by conventional imaging modalities.
•
A radiomics nomogram integrated with the radiomics signature, clinical data, and MRI features facilitates differentiation of BPGT from MPGT with improved diagnostic efficacy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
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