The effects of Cr addition on microstructures, mechanical properties and deformation behavior of near-rapidly solidified low-density Fe-20Mn-9Al-1.2C (wt. %) steel strips were investigated. It was ...found that Cr addition increased the volume fraction and size of δ-ferrite, and decreased the precipitation of κ-carbides in this low-density steel strip. The yield strength of the near-rapidly solidified steel strips was decreased significantly, but the ultimate tensile strength and the total elongation didn't obviously change. However, after cold rolling with 20% reduction, the yield strength and ultimate tensile strength of Cr-containing steel strips were significantly higher than that of the Cr-free steel strip. It was attributed to the fact that the decrease of κ-carbides caused by Cr addition facilitated the formation of high-density slip bands during cold rolling deformation. The ultimate tensile strength and total elongation of cold-rolled 3Cr (wt. %) steel strip were 1270 MPa and 21%, respectively. A double (Slip-band and Microband) hardening mechanism was proposed for the strain hardening behavior of the low-density steel strips, and the number of nanoscale κ-carbides played a crucial role in the strain hardening rate at the early strain stage.
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•Cr addition increases δ-ferrite content and decreases nano-scale κ-carbide content in low-density Fe-20Mn-9Al-1.2C steel.•The decrease of nano-scale κ-carbide promotes generation of the slip bands and increases its strain hardening rate.•A double (Slip-band and Microband) hardening mechanism is proposed for strain hardening of the low-density steel strips.
New strategies for the construction of versatile nanovehicles to overcome the multiple challenges of targeted delivery are urgently needed for cancer therapy. To address these needs, we developed a ...novel targeting-clickable and tumor-cleavable polyurethane nanomicelle for multifunctional delivery of antitumor drugs. The polyurethane was synthesized from biodegradable poly(ε-caprolactone) (PCL) and l-lysine ethyl ester diisocyanate (LDI), further extended by a new designed l-cystine-derivatized chain extender bearing a redox-responsive disulfide bond and clickable alkynyl groups (Cys-PA), and finally terminated by a detachable methoxyl-poly(ethylene glycol) with a highly pH-sensitive benzoic-imine linkage (BPEG). The obtained polymers show attractive self-assembly characteristics and stimuli-responsiveness, good cytocompatibility, and high loading capacity for doxorubicin (DOX). Furthermore, folic acid (FA) as a model targeting ligand was conjugated to the polyurethane micelles via an efficient click reaction. The decoration of FA results in an enhanced cellular uptake and improved drug efficacy toward FA-receptor positive HeLa cancer cells in vitro. As a proof-of-concept, this work provides a facile approach to the design of extracellularly activatable nanocarriers for tumor-targeted and programmed intracellular drug delivery.
Background The current risk stratification methods for Pediatric Differentiated Thyroid Carcinoma (DTC) are deemed inadequate due to the high recurrence rates observed in this demographic. This study ...investigates alternative clinicopathological factors, specifically the Central Lymph Node Ratio (CLNR), for improved risk stratification in pediatric DTC. Methods A retrospective review of 100 pediatric DTC patients, aged 19 or younger, treated between December 2012 and January 2021 at the First Affiliated Hospital of Guangxi Medical University was conducted. Clinicopathological variables were extracted, and univariate logistic regression identified factors correlated with recurrence. Kaplan-Meier (KM) survival analysis and subsequent statistical tests were used to assess the significance of these factors. Results The CLNR, with a cutoff value of 77.78%, emerged as a significant predictor of recurrence. Patients with a CLNR above this threshold had a 5.467 times higher risk of recurrence. The high CLNR group showed a higher proportion of male patients, clinically lymph node positivity (cN1), and extrathyroidal extension (ETE) compared to the low-risk group (p<0.05). Conclusion CLNR is a valuable predictor for recurrence in pediatric DTC and aids in stratifying patients based on Recurrence-Free Survival (RFS). For patients with a high CLNR, aggressive iodine-131 therapy, stringent TSH suppression, and proactive postoperative surveillance are recommended to mitigate recurrence risk and facilitate timely detection of recurrent lesions.
Angiogenesis is considered as an important process in the development of malignancies and is associated with cancer progression and metastasis. Hepatocellular carcinoma (HCC) is the most common ...primary tumor of the liver and is recognized as a typical angiogenic tumor. Thus, it is of great importance to study the underlying mechanism of angiogenesis in HCC. The long non-coding RNA (lncRNA) ubiquitin conjugating enzyme E2C pseudogene 3 (UBE2CP3) has been reported as an oncogene that promotes tumor metastasis in HCC. However, the role and underlying mechanisms of UBE2CP3 in HCC angiogenesis are still unclear.
We measured the expression levels of UBE2CP3 by in situ hybridization (ISH) and quantitative real-time polymerase chain reaction (qRT-PCR) in HCC patient samples. We also concomitantly used CD31/PAS double-staining to measure endothelial vessel (EV) density and used qRT-PCR to measure the CD31 mRNA level. HepG2 and SMMC-7721 cells were transfected with Lv-UBE2CP3 or Sh-UBE2CP3 virus to obtain stably over-expressing or knocking-down UBE2CP3 cell lines. The indirect effects of UBE2CP3 on ECs were studied by establishing a co-culture system using Transwell chambers with a 0.4-μm pore size. HCC cells and ECs in the co-culture system were separated, but the cytokines and growth factors were able to communicate with each other. Following exposed to HCC cells, ECs were collected for functional studies. Finally, we studied the function of UBE2CP3 in vivo by chick embryo chorioallantoic membrane (CAM) angiogenesis assays and nude mouse tumorigenicity assays.
In this study, we found that UBE2CP3 expression was higher in HCC tissues than in para-tumor tissues and was up-regulated in tissues with high EV density. Functionally, we found that in the co-culture systems, HCC cells overexpressing UBE2CP3 promoted HUVEC proliferation, migration and tube formation via the activation of ERK/HIF-1α/p70S6K/VEGFA signalling, increasing the level of VEGFA in HCC cell supernatant. In addition, the opposite results appeared when the expression of UBE2CP3 in HCC cells was knocked down. Consistent with these results, CAM angiogenesis assays and nude mouse tumorigenicity assays showed that UBE2CP3 expression up-regulated EV density in vivo.
Our study suggests that UBE2CP3 can enhance the interaction between HCC tumor cells and HUVECs and promote HCC tumorigenicity by facilitating angiogenesis.
To obtain a pH-sensitive multifunctional polyurethane micelle drug carrier, a novel pH-sensitive macrodiol containing acid-cleavable hydrazone linkers, poly(ε-caprolactone)−hydrazone−poly(ethylene ...glycol)−hydrazone−poly(ε-caprolactone) diol (PCL−Hyd−PEG−Hyd−PCL), was synthesized and characterized with proton nuclear magnetic resonance spectra (1H NMR). A series of pH-sensitive biodegradable polyurethanes (pHPUs) were designed and synthesized using pH-sensitive macrodiol, l-lysine ethyl ester diisocyanate (LDI) and l-lysine derivative tripeptide as chain extender, which can provide an active reaction site for the development of positive target polyurethane micelles for drug delivery. The bulk structures of the prepared polyurethanes were carefully characterized with 1H NMR, gel permeation chromatograph (GPC), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The polyurethanes could be cleaved in acidic media (pH ∼ 4−6) as well as degraded in PBS and enzymatic solution, as demonstrated by 1H NMR and weight loss, respectively. The cytotoxicity of their degradation products was evaluated using methylthiazoletetrazolium (MTT) assay in vitro, resulting in no apparent inhibition effect on the fibroblasts. These polyurethanes could self-assemble into micelles in aqueous solutions, as verified using dynamic light-scattering (DLS). Our present work provides a new method for the preparation of amphiphilic multiblock polyurethanes with pH-sensitivity and biodegradability. It could be a good candidate as biodegradable multifunctional carrier for active intracellular drug delivery.
Myocardial infarction (MI) is a severe coronary artery disease resulted from substantial and sustained ischemia. Abnormal upregulation of calcium and integrin binding protein 1 (CIB1) has been found ...in several cardiovascular diseases. In this study, we established a mouse model of MI by permanent ligation of the left anterior descending coronary artery. CIB1 was upregulated in the heart of MI mice. Notably, CIB1 knockdown by intramuscular injection of lentivirus-mediated short hairpin RNA (shRNA) targeting Cib1 improved cardiac function and attenuated myocardial hypertrophy and infarct area in MI mice. MI-induced upregulation of α-SMA, vimentin, Collagen I, and Collagen III, which resulted in collagen production and myocardial fibrosis, were regressed by CIB1 silencing. In vitro, cardiac fibroblasts (CFs) isolated from mice were subjected to angiotensin II (Ang II) treatment. Inhibition of CIB1 downregulated the expression of α-SMA, vimentin, Collagen I, and Collagen III in Ang II-treated CFs. Moreover, CIB1 knockdown inhibited Ang II-induced phosphorylation of PI3K-p85 and Akt in CFs. The effect of CIB1 knockdown on Ang II-induced cellular injury was comparable to that of LY294002, a specific inhibitor of the PI3K/Akt pathway. We demonstrated that MI-induced cardiac hypertrophy, myocardial fibrosis, and cardiac dysfunction might be attributed to the upregulation of CIB1 in MI mice. Downregulation of CIB1 alleviated myocardial fibrosis and cardiac dysfunction by decreasing the expression of α-SMA, vimentin, Collagen I, and Collagen III via inhibiting the PI3K/Akt pathway. Therefore, CIB1 may be a potential target for MI treatment.
Lymph node metastasis (LNM) is an important factor for thyroid cancer patients' treatment and prognosis. The aim of this study was to explore the clinical value of ultrasound features and radiomics ...analysis in predicting LNM in thyroid cancer patients before surgery.
The characteristics of ultrasound images of 150 thyroid nodules were retrospectively analysed. All nodules were confirmed as thyroid cancer. Among the assessed patients, only one hundred and twenty-six patients underwent lymph node dissection. All patients underwent an ultrasound examination before surgery. In the radiomic analysis, the area of interest was identified from selected ultrasound images by using ITK-SNAP software. The radiomic features were extracted by using Ultrosomics software. Then, the data were classified into a training set and a validation set. Hypothetical tests and bagging were used to build the model. The diagnostic performance of different ultrasound features was assessed, a radiomic analysis was conducted, and a receiver operating characteristic (ROC) curve analysis was performed to explore the diagnostic accuracy.
Regarding the prediction of LNM, the ROC curves showed that the area under the curve (AUC) values of an irregular shape and microcalcification were 0.591 (P = 0.059) and 0.629 (P = 0.007), respectively. In the radiomics analysis, in the training set, the AUC value of LNM was 0.759, with a sensitivity of 0.90 and a specificity of 0.860. In the verification set, the AUC was 0.803, with a sensitivity of 0.727 and a specificity of 0.800.
Microcalcification and an irregular shape are predictors of LNM in thyroid carcinoma patients. In addition, radiomics analysis has promising value in screening meaningful ultrasound features in thyroid cancer patients with LNM. Therefore, the prediction of LNM based on ultrasound features and radiomic features is useful for making appropriate decisions regarding surgery and interventions before thyroid carcinoma surgery.
This article presents the electric field waveforms of natural return strokes recorded by Foshan Total Lightning Location System. The distance ranges from 10 to 300 km. The evolution of parameters for ...positive first and negative first and subsequent return stroke electric field waveforms along with distance change is analyzed. The results show that the risetime, fall time, half-peak width, and zero-crossing time become longer with longer distance, and these four parameters of the negative return strokes show more clear linear relation with distance than the positive return strokes. For the overshoot duration, the values for both positive and negative return strokes increase with distance at 10-200 km, but when the distance is larger, the distance dependence becomes less obvious. The values of the initial peak normalized to 100 km and 20 kA remain the same in general for all the return strokes. For the overshoot amplitude and the ratio of overshoot to initial peak, the values for both positive and negative return strokes increase with distance. The return stroke electric field waveforms at far distances are more likely to show clear opposite polarity overshoot.
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•Particle engulfment was facilitated via ultrasonic-assisted solidification.•It is attributed to the vigorous movement of particles towards the s/l interface.•The secondary dendrites ...are refined due to the enhanced disturbance.
Particle engulfment plays a vital role in the application of particulate reinforced metal matrix composites fabricated by ingot metallurgy. During solidification, particles are nevertheless pushed by an advancing front. As a model system, TiB2p/Al composites were used to investigate the particle engulfment facilitated by acoustic cavitation. The implosion of bubbles drives the particles plunging towards the solid/liquid interface, which increases the engulfment probability. The secondary dendrite arms are refined from 271.2 μm to 98.0 μm as a result of the forced movements of TiB2 particles. Owing to the particle engulfment and dendrite refinement, the composite with ultrasound vibration treatment shows a more rapid work-hardening rate and higher strength.
In magnesium alloys with aluminum as an alloying component, zirconium loses its grain refinement effect as a grain refiner. Instead of zirconium, Mg3N2 can be used, and promising results have already ...been obtained. However, the duration of action of Mg3N2 has not been elucidated yet. The aim of this work is therefore to determine the grain size of the AZ80 alloy as a function of the duration of action of Mg3N2 and thus the economically reasonable duration of use. It was found that the Mg3N2 reaches its full effect from 30 min after a complete remelting and does not lose this grain refinement effect even after 90 min. It thus proves to be a stable and reliable grain refiner. A grain size of 146.3 ± 10.3 µm was achieved. Furthermore, a minimum tensile strength of 205 MPa with a break elongation of 5.99% was achieved.
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