To construct a lentiviral vector (Lenti-GPER-shRNA) targeting G-protein coupled estrogen receptor (GPER) and explore the role of GPER in the effect of tamoxifen on cell proliferation and apoptosis in ...breast cancer associated fibroblasts (BCAFs).
The target sequence of GPER gene and negative control were cloned into lentiviral vectors. The recombinant lentivirus and control were extracted after HEK293T cells were transfected with the recombinant vector and helper vectors. After infection of BCAFs with the GPER lentiviral vector under the best interfering condition, GPER expression was detected by real-time quantitative PCR and Western blotting. BCAFs were divided into negative control group, GPER-RNAi group, negative control combined with tamoxifen (10(-8) mmol/L) group and GPER-RNAi combined with tamoxifen (10(-8) mmol/L) group. CCK-8 assay was used to detect the proliferation and annexin V-fluorescein isothiocyanate/propidium iodide (annexin V-FITC/PI) combined with flow cytometry was used to detect the apop
Renal cell carcinoma (RCC) is the most common renal tumor, with lung, bone, and liver being the primary sites of metastasis. Thyroid metastasis, on the other hand, is relatively uncommon. Metastatic ...tumors in the thyroid gland typically manifest as multiple or isolated nodules, which can be easily overlooked due to the lack of specific clinical and imaging features. However, the identification of thyroid metastasis suggests the presence of systemic metastasis and is indicative of a poor prognosis for patients. In this paper, we present two cases of thyroid metastasis following nephrectomy, with the objective of enhancing understanding among medical community regarding the diagnosis and treatment of thyroid metastasis originating from renal cell carcinoma. By raising awareness about this phenomenon, we emphasize the importance of early detection and diagnosis to improve patient prognoses. The implementation of standardized treatment protocols at the earliest possible stage is also emphasized. Through this research, we aim to contribute to the early identification and management of thyroid metastasis in patients with renal cell carcinoma, ultimately leading to improved outcomes.
Abnormal proliferation is one characteristic of cancer-associated fibroblasts (CAFs), which play a key role in tumorigenesis and tumor progression. Oxidative stress (OS) is the root cause of CAFs ...abnormal proliferation. ATM (ataxia-telangiectasia mutated protein kinase), an important redox sensor, is involved in DNA damage response and cellular homeostasis. Whether and how oxidized ATM regulating CAFs proliferation remains unclear. In this study, we show that there is a high level of oxidized ATM in breast CAFs in the absence of double-strand breaks (DSBs) and that oxidized ATM plays a critical role in CAFs proliferation. The effect of oxidized ATM on CAFs proliferation is mediated by its regulation of cellular redox balance and the activity of the ERK, PI3K-AKT, and Wnt signaling pathways. Treating cells with antioxidant N-acetyl-cysteine (NAC) partially rescues the proliferation defect of the breast CAFs caused by ATM deficiency. Administrating cells with individual or a combination of specific inhibitors of the ERK, PI3K-AKT, and Wnt signaling pathways mimics the effect of ATM deficiency on breast CAF proliferation. This is mainly ascribed to the β-catenin suppression and down-regulation of c-Myc, thus further leading to the decreased cyclinD1, cyclinE, and E2F1 expression and the enhanced p21
Cip1
level. Our results reveal an important role of oxidized ATM in the regulation of the abnormal proliferation of breast CAFs. Oxidized ATM could serve as a potential target for treating breast cancer.
The challenge of mitigating adverse climatic conditions is a critical issue that affects worker safety and operational efficiency in underground engineering. This study introduces an innovative ...approach using pumping wet shotcrete as an insulating material, incorporated with microencapsulated phase change materials (MPCMs) and filled within fluorine rubber tubes to address this concern. The MPCMs were synthesized via suspension polymerization, utilizing paraffin as the core material and modified SiO2-poly (lauryl methacrylate) as the shell material. To determine the optimal composition for practical application, an orthogonal experimental design was employed, complemented by comprehensive performance testing. The results indicated that a mix of 1375 kg/m3 of sand, 120 kg/m3 of ceramsite, and 1 g/cm of SiO2-MPCMs in each fluorine rubber tube having an inner diameter of 13 mm, provided the best balance between multiple properties. Notably, the insulation performance improved by 60–75 % compared to traditional pumping wet shotcrete, demonstrating a significant enhancement in thermal management capabilities. The findings contribute substantially to the field of thermal management in mines, presenting a novel technique that could be instrumental in improving safety and efficiency in deep underground operations.
The use of biomass as a binder for the development of high-performance wood products has become a popular research topic in the context of sustainable development. In this work, wood flour obtained ...from agroforestry processing residues was used as an active functional filler. The wood flour was oxidized and chemically cross-linked with hyperbranched polyamines and used as a binder matrix. By applying the same oxidative treatment to the wood surface, a chemically activated bonding interface was formed. Analysis by FTIR, 13C NMR, XPS and XRD characterization showed that the key to the improved bonding property was the formation of multiple covalent cross-linked networks during hot pressing of the plywood. It is clear that the specimens with untreated wood surfaces showed no water resistance and the dry strength was only above the standard value. On the contrary, after activation of the veneer surfaces, the bond strength and water resistance were significantly improved, meeting the requirements of GB/T 17657–2013 for Class I panels. Activation of the chemically active adhesive interface by oxidation of wood materials is an effective means of improving the performance of plywood, and also provides a new idea for high-value utilization of biomass resources.
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•A bio-based wood adhesive was prepared using renewable wood flour.•The adhesive exhibited excellent wet bonding performance.•The triplex cross-linked network structure improved the adhesive adhesion.•The water resistance of the adhesive was significantly improved.
Background and Objective
GB221 is a recombinant humanized anti-HER2 monoclonal antibody. The purpose of this study was to evaluate the pharmacokinetic, safety, and immunogenicity of GB221 in healthy ...Chinese adults in comparison to trastuzumab (Herceptin
®
).
Methods
In this randomized, double-blind, parallel-group phase I clinical trial, 88 subjects were randomized 1:1 to receive a single intravenous infusion (90-100 min) of GB221 or trastuzumab (6 mg/kg). The primary pharmacokinetic parameters—maximum observed serum concentration (
C
max
), area under the serum concentration–time curve from zero to the last quantifiable concentration at time
t
(AUC
0–
t
), and area under the serum concentration–time curve from time zero to infinity (AUC
0–∞
)—of GB221 and trastuzumab were compared to establish whether the 90% confidence interval (CI) attained the 80–125% bioequivalence standard. Safety and immunogenicity were also evaluated.
Results
The GB221 group (
n
= 43) and the trastuzumab group (
n
= 44) showed similar pharmacokinetic characteristics. The geometric mean ratios (90% CI) of
C
max
, AUC
0–
t
,
and AUC
0–∞
between the two groups were 107.53% (102.25–113.07%), 108.31% (103.57–113.26%), and 108.34% (103.57–113.33%), respectively. The incidence of treatment-emergent adverse events (TEAEs) was 83.7% (36/43) of the subjects in the GB221 group and 95.5% (42/44) of the subjects in the trastuzumab group. No subjects withdrew from the trial due to TEAEs, and there were no occurrences of serious adverse events. All subjects tested negative for antidrug antibodies (ADA).
Conclusion
GB221 demonstrated similar pharmacokinetics to trastuzumab and comparable safety and immunogenicity in healthy Chinese adults.
We report on the investigation of perpendicular exchange bias in FePt(001)/NiO(111) orthogonal exchange couple with FePt partially L1 sub(0) ordered. From initial magnetization curve measurement and ...magnetic domain imaging, we find that, for the as-grown bilayer structure, the FePt layer experiences a small-angle magnetization rotation when it is magnetized near to saturation in film normal direction. After field cooling, the bilayer structure shows a significant enhancement of perpendicular magnetic anisotropy, indicating the field mediated coupling between the spins across the FePt/NiO interface. According to Koon's theoretical calculation on the basis of lowest energy ferromagnetic/antiferromagnetic coupling configuration for compensated spins at antiferromagnetic side, we consider slightly slanted Ni spins at the interface off the (111) easy plane can stabilize the spin coupling between FePt and NiO and result in the observed exchange bias in this paper. This consideration was further confirmed by stripe domain width calculation.
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