Macroscopic and Microscopic Investigation of Gypsum Slag Cement-Stabilized Recycled Aggregate Base Layers.

The purpose of this study is to investigate the macro and micro properties of stabilized recycled aggregate base layers using gypsum slag cement (GSC) and compare them with ordinary Portland cement (OPC). To achieve this, four levels of recycled aggregate content (0%, 50%, 60%, 70%) and three levels of binder materials (3.5%, 4.5%, 5.5%) were designed, where the binding materials included OPC and GSC. When GSC is used as the binding material with 0% recycled content, two scenarios for the ratio of slag to activator are considered: 4:1 and 4:2. For recycled content of 50%, 60%, and 70%, only the 4:1 ratio is considered. The macro-mechanical properties of the composite material were studied through compaction tests, unconfined compressive strength tests, and indirect tensile strength tests. Microscopic properties were investigated through X-ray diffraction (XRD) and scanning electron microscopy (SEM). Macroscopic test results indicate that, at an equal binder content, GSC exhibits a higher moisture content and maximum dry density compared to OPC. Moreover, the unconfined compressive strength and indirect tensile strength of GSC are higher than those of OPC. Microscopic test results reveal that the hydration products of both binding materials are essentially similar; however, under identical curing conditions, the hydration products of GSC are more abundant than those of OPC.

Shrink polymer based electrochemical sensor for point-of-care detection of prostate-specific antigen.

There is a growing but unmet need for point-of-care detection of prostate-specific antigen (PSA) in body fluid which may facilitate early diagnosis and therapy of prostate cancer in a cost-effective and user-friendly way. Low sensitivity and narrow detection range limits applications of point-of-care testing in practice. Here, an immunosensor is first presented based on shrink polymer and integrated into a miniaturized electrochemical platform for detecting PSA in clinical samples. The sensing electrode was prepared by sputtering a gold film on shrink polymer, followed by heating to shrink the electrode to a small size with wrinkles from nano-scale to micro-scale. These wrinkles can be directly regulated by the thickness of the gold film with high specific areas for enhancement of antigen-antibody binding (3.9 times). A distinct difference between electrochemical active surface area (EASA) and response to PSA of shrink electrodes was observed and discussed. The electrode was treated with air plasma and modified with self-assembled graphene to further enhance the sensor's sensitivity (10.4 times). The shrink sensor with gold 200 nm thick integrated into the portable system was validated by a label-free immunoassay for detection of PSA in 20 µL serum within 35 mins. It exhibited a limit of detection of 0.38 fg/mL, the lowest among label-free PSA sensors, and a wide linear response from 10 fg/mL to 1000 ng/mL. Moreover, the sensor demonstrated reliable assay results in clinical serums, comparable to the commercial chemiluminescence instrument, confirming its feasibility for clinical diagnosis.

Exploring the effect and mechanism of Aloin A against cancer cachexia-induced muscle atrophy via network pharmacology, molecular docking, molecular dynamics and experimental validation.

80% of advanced cancer patients suffer from cachexia, but there are no FDA-approved drugs. Therefore, it is imperative to discover potential drugs. OBJECTIVE: This study aims at exploring the effect and targets of Aloin A against cancer cachexia (CC)-induced muscle atrophy. METHODS: Network pharmacology, molecular docking, molecular dynamics (MD) and animal model of CC-induced muscle atrophy with a series of behavior tests, muscle quality, HE staining and RT-PCR were performed to investigate the anticachectic effects and targets of Aloin A and its molecular mechanism. RESULTS: Based on network pharmacology, 51 potential targets of Aloin A on CC-induced muscle atrophy were found, and then 10 hub genes were predicted by the PPI network. Next, KEGG and GO enrichment analysis showed that the anticachectic effect of Aloin A is associated with PI3K-AKT, MAPK, TNF, TLR, etc., pathways, and biological processes like inflammation, apoptosis and cell proliferation. Molecular docking and MD results showed good binding ability between the Aloin A and key targets. Moreover, experiments in vivo demonstrated that Aloin A effectively rescued muscle function and wasting by improving muscle quality, mean CSA, and distribution of muscle fibers by regulating HSP90AA1/AKT signaling in tumor-bearing mice. CONCLUSION: This study offers new insights for researchers to understand the effect and mechanism of Aloin A against CC using network pharmacology, molecular docking, MD and experimental validation, and Aloin A retards CC-induced muscle wasting through multiple targets and pathways, including HSP90AA1/AKT signaling, which provides evidence for Aloin A as a potential therapy for cancer cachexia in clinic.

circ_0067934: A Potential Biomarker and Therapeutic Target for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a high-level invasive and metastatic malignancy with a low survival rate. Accumulating evidence has proved that circular RNAs (cirRNAs) function as potential biomarkers for diagnosis or prognosis in various cancer, including HCC. In the present study, we aimed to explore a novel biomarker, circ_0067934 for diagnosis and prognosis of HCC so as to contribute to therapeutic strategies. In the present study, the expression levels of circ_0067934 in HCC patients and paired controls were determined by real-time quantitative polymerase chain reaction (qRT-PCR) analysis. The correlation between different circ_0067934 expressions with clinicopathological factors of HCC patients was analyzed by one-way analysis of variance (ANOVA). Then, we examined the potential diagnostic value of circ_0067934 by measuring the receiver operating characteristic (ROC) curves. Finally, the overall survival rate evaluated by Spearman's rank correlation coefficient of HCC patients with different circ_0067934 was compared in order to present the prognostic value of circ_0067934 in HCC. From the results, qRT-PCR analysis revealed that circ_0067934 was significantly up-regulated in HCC tissues compared with adjacent non-tumor tissues. Moreover, circ_0067934 positively correlated with tumor size (P=0.0025), TNM stage (P<0.0001) and microvascular invasion (P<0.0001). However, there were no significant differences in gender, age, family history, diabetes, ALT, AST, AFP and AKP. Meanwhile, the ROC curves presented that circ_0067934 had favorable specificity and sensitivity with the area under the curves of 0.8412 (95% CI=0.7881 to 0.8943). Furthermore, the upregulation of circ_0067934 was associated with unfavorable prognosis in patients with HCC. In conclusion, circ_0067934 may function as a potential biomarker for the diagnosis and prognosis of HCC.

miR-24-3p stimulates migration, invasion and proliferation of prostate cancer cells by targeting suppressor of cytokine signaling 6.

Prostate cancer is among the most widespread malignancies affecting men in the world. Its aggressive evolution has been associated with altered expression of suppressor of cytokine signaling 6 (SOCS6) but very little is known about the mechanism by which this alteration occurs. The purpose of this study was to explore the role of SOCS6 in prostate cancer cells and the involvement of its regulating microRNA (miR), miR-24-3p. Prostate cancer cell lines were used to determine the transcription level of miR-24-3p and SOCS6 by quantitative reverse-transcriptase-polymerase chain reaction (qRT-PCR) and Western blot. Cell proliferation and cell migration assays were doneto determine the effect of miR-24-3p mimics and inhibitors on cell proliferation, invasion and migration. Luciferase reporter assay with SOCS6 3'-UTR was performed to confirm the control of SOCS6 expression by the miR. The results showed that miR-24-3p was up-regulated in prostate cancer cells whereas SOCS6 protein was downregulated. Overexpression of miR-24-3p in prostate cancer cells promoted cell proliferation, inhibited apoptosis, and increased cell migration and invasion. Luciferase reporter assays showed that SOCS6 is a direct target of its negative regulator miR-24-3p and overexpression of SOCS6 reverses the effects of miR-24-3p on the metastatic phenotype of prostate cancer cells. These results show case miR-24-3p up-regulation in prostate cancer and a mechanism for inhibition of SOCS6 expression. Thus, the miR-24-3p/SOCS6 pathway could be a relevant avenue for prostate cancer treatment.

[Five-year therapeutic experience of sorafenib for patients with advanced renal cell carcinoma].

OBJECTIVE: To explore the tolerability and safety of sorafenib for patients with advanced renal cell carcinoma. METHODS: Among 63 cases of advanced renal cell carcinoma, there were 45 males and 18 females with a median age of 57 years. And 48 patients had recurrence or metastasis after nephrectomy. And cytokine therapy was offered for 36 of them before recurrence or metastasis. Postoperative recurrence or metastasis occurred <1 year (n = 11) and ≥ 1 year (n = 37). And 15 cases of primary non-resectable renal lesions received biopsy. The pathological types were clear cell carcinoma (n = 49) and papillary carcinoma (n = 14). The pre-dosing Karnofsky performance scores were all ≥ 70 points. Sorafenib was used as a first-line single drug at 400 mg twice daily until disease progression or an onset of intolerable adverse reactions. RESULTS: Follow-ups ended in February 2013. The median follow-up period was 20 (6-42) months. Twenty-four patients died. The outcomes were complete remission (n = 2), partial remission (n = 8), stable disease (n = 30) and disease progression (n = 23). The overall objective response rate was 15.9% (10/63) and disease control rate 63.5% (40/63) . Hand-foot skin reaction (70.0%), alopecia (62.5%), rash (52.5%), diarrhea (37.5%), loss of appetite (32.5%) and fatigue (27.5%) were noted. Most adverse reactions occurred at 2-4 weeks and subsided after symptomatic measures. And medication was not disrupted. CONCLUSION: Sorafenib has a high disease control rate for advanced renal cell carcinoma. And its adverse reactions are generally mild and similar to those reported in the literature. It has excellent profiles of tolerability and safety.

Enhanced therapeutic effect of cisplatin on the prostate cancer in tumor-bearing mice by transfecting the attenuated Salmonella carrying a plasmid co-expressing p53 gene and mdm2 siRNA.

Prostate cancer urgently needs an efficient therapy. Here we demonstrated that cisplatin combined with gene therapy by transfecting the attenuated Salmonella that carry a plasmid containing p53 gene and MDM2 siRNA provided a super-synergistic effect on the inhibition of prostate cancer growth in vivo. This synergistic therapy was associated with the induction of apoptotic cell death with a decreased Bcl2 to Bax expression ratio and increased expression of cleaved caspase 3 and caspase 9 in the prostate cancer xenograft. These results indicate that cisplatin-chemotherapy in combination with targeting the MDM2/p53 axis is an attractive strategy to treat prostate cancer.