The Piezocatalytic Degradation of Sulfadiazine by Lanthanum-Doped Barium Titanate.

Piezocatalysis, a heterogeneous catalytic technique, leverages the periodic electric field changes generated by piezoelectric materials under external forces to drive carriers for the advanced oxidation of organic pollutants. Antibiotics, as emerging trace organic pollutants in water sources, pose a potential threat to animals and drinking water safety. Thus, piezoelectric catalysis can be used to degrade trace organic pollutants in water. In this work, BaTiO3 and La-doped BaTiO3 were synthesized using an improved sol-gel-hydrothermal method and used as piezocatalytic materials to degrade sulfadiazine (SDZ) with ultrasound activation. High-crystallinity products with nano cubic and spherical morphologies were successfully synthesized. An initial concentration of SDZ ranging from 1 to 10 mg/L, a catalysis dosage range from 1 to 2.5 mg/mL, pH, and the background ions in the water were considered as influencing factors and tested. The reaction rate constant was 0.0378 min-1 under the optimum working conditions, and the degradation efficiency achieved was 89.06% in 60 min. La-doped BaTiO3 had a better degradation efficiency, at 14.98% on average, compared to undoped BaTiO3. Further investigations into scavengers revealed a partially piezocatalytic process for the degradation of SDZ. In summary, our work provides an idea for green environmental protection in dealing with new types of environmental pollution.

Broadband transverse unidirectional scattering and large range nanoscale displacement measuring based on the interaction between a tightly focused azimuthally polarized beam and a silicon hollow nanostructure.

We theoretically propose a broadband transverse unidirectional scattering scheme based on the interaction between a tightly focused azimuthally polarized beam (APB) and a silicon hollow nanostructure. When the nanostructure is located at a specific position in the focal plane of the APB, the transverse scattering fields can be decomposed into contributions from transverse components of the electric dipoles, longitudinal components of magnetic dipoles and magnetic quadrupole components. In order to satisfy the transverse Kerker conditions for these multipoles within a wide infrared spectrum, we design a novel nanostructure with hollow parallelepiped shape. Through numerical simulations and theoretical calculations, this scheme exhibits efficient transverse unidirectional scattering effects in the wavelength range of 1440 nm to 1820 nm (380 nm). In addition, by adjusting the position of the nanostructure on the x-axis, efficient nanoscale displacement sensing with large measuring ranges can be achieved. After analyses, the results prove that our research may have potential applications in the field of high-precision on-chip displacement sensors.

Downregulation of c-Myc expression confers sensitivity to CHK1 inhibitors in hematologic malignancies.

Checkpoint kinase 1 inhibitors (CHK1i) have shown impressive single-agent efficacy in treatment of certain tumors, as monotherapy or potentiators of chemotherapy in clinical trials, but the sensitive tumor types and downstream effectors to dictate the therapeutic responses to CHK1i remains unclear. In this study we first analyzed GDSC (Genomics of Drug Sensitivity in Cancer) and DepMap database and disclosed that hematologic malignancies (HMs) were relatively sensitive to CHK1i or CHK1 knockdown. This notion was confirmed by examining PY34, a new and potent in-house selective CHK1i, which exhibited potent anti-HM effect in vitro and in vivo, as single agent. We demonstrated that the downregulation of c-Myc and its signaling pathway was the common transcriptomic profiling response of sensitive HM cell lines to PY34, whereas overexpressing c-Myc could partially rescue the anticancer effect of PY34. Strikingly, we revealed the significant correlations between downregulation of c-Myc and cell sensitivity to PY34 in 17 HM cell lines and 39 patient-derived cell (PDC) samples. Thus, our results demonstrate that HMs are more sensitive to CHK1i than solid tumors, and c-Myc downregulation could represent the CHK1i efficacy in HMs.

Activation of unfolded protein response overcomes Ibrutinib resistance in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most widespread type of non-Hodgkin lymphoma (NHL). As the most aggressive form of the DLBCL, the activated B-cell-like (ABC) subtype is often resistant to standard chemotherapies. Bruton's tyrosine kinase (BTK) inhibitor ibrutinib provides a potential therapeutic approach for the DLBCL but fails to improve the outcome in the phase III trial. In the current study, we investigated the molecular mechanisms underlying ibrutinib resistance and explored new combination therapy with ibrutinib. We generated an ibrutinib-resistant ABC-DLBCL cell line (OCI-ly10-IR) through continuous exposure to ibrutinib. Transcriptome analysis of the parental and ibrutinib-resistant cell lines revealed that the ibrutinib-resistant cells had significantly lower expression of the unfolded protein response (UPR) marker genes. Overexpression of one UPR branch-XBP1s greatly potentiated ibrutinib-induced apoptosis in both sensitive and resistant cells. The UPR inhibitor tauroursodeoxycholic acid (TUDCA) partially reduced the apoptotic rate induced by the ibrutinib in sensitive cells. The UPR activator 2-deoxy-D-glucose (2-DG) in combination with the ibrutinib triggered even greater cell growth inhibition, apoptosis, and stronger calcium (Ca2+) flux inhibition than either of the agents alone. A combination treatment of ibrutinib (15 mg·kg-1·d-1, po.) and 2-DG (500 mg/kg, po, b.i.d.) synergistically retarded tumor growth in NOD/SCID mice bearing OCI-ly10-IR xenograft. In addition, ibrutinib induced the UPR in the sensitive cell lines but not in the resistant cell lines of the DLBCL. There was also a combined synergistic effect in the primary resistant DLBCL cell lines. Overall, our results suggest that targeting the UPR could be a potential combination strategy to overcome ibrutinib resistance in the DLBCL.

ADAM17 promotes the invasion of hepatocellular carcinoma via upregulation MMP21.

BACKGROUND: The upregulation of ADAM17 has been reported to be associated with invasion and metastasis in various tumors, however the molecular mechanism of ADAM17 in the progression of hepatocellular carcinoma (HCC) remain to be clarified. Human matrix metalloproteinase 21 (MMP21), the newest member of the MMP gene family, has been suggested to play an important role in embryogenesis and tumor progression. So far, nothing is known about the relationship between ADAM17 and MMP21. METHODS: In this study, the expression level of ADAM17 and MMP21 in HCC tissues was measured by immunohistochemistry. The Scratch wounding assay and Transwell were used to identify the invasion and metastasis ability. ELISA was used to evaluate the production of MMP21. Coimmunoprecipitation experiments demonstrated a direct association between ADAM17 and MMP21. HPLC was used to confirmed that ADAM17 participated in the maturation of MMP21. RESULTS: Our present data indicated that ADAM17 and MMP21 was significantly upregulated in human HCC tissues. Knockdown of ADAM17 in HCC inhibited cell invasion and metastasis. Moreover, ADAM17 regulates the secretion and expression of MMP21. Furthermore we discovered a direct association between ADAM17 and MMP21, and we also found MMP21 prodomain could be cleaved by ADAM17. CONCLUSION: Our data suggest that ADAM17 plays an important role in the development of HCC invasion and metastasis and this function may be implement by MMP21.

Electronic Characteristics, Stability and Water Oxidation Selectivity of High-Index BiVO4 Facets for Photocatalytic Application: A First Principle Study.

Some high-index facets of BiVO4, such as (012), (210), (115), (511), (121), (132) and (231), exhibit much better photocatalytic performance than conventional (010) and (110) surfaces for water splitting. However, the detailed mechanisms and stability of improved photocatalytic performance for these high-index BiVO4 surfaces are still not clear, which is important for designing photocatalysts with high efficiency. Here, based on first principle calculation, we carried out a systematic theoretical research on BiVO4 with different surfaces, especially high-index facets. The results show that all of the high-index facets in our calculated systems show an n-type behavior, and the band edge positions indicate that all of the high-index facets have enough ability to produce O2 without external bias. Electronic structures, band alignments and formation enthalpy indicate that (012), (115) and (132) could be equivalent to (210), (511) and (231), respectively, in the calculation. Oxidation and reduction potential show that only (132)/(231) is stable without strongly oxidative conditions, and the Gibbs free energy indicates that (012)/(210), (115)/(511), (121) and (132)/(231) have lower overpotential than (010) and (110). Our calculation is able to unveil insights into the effects of the surface, including electronic structures, overpotential and stability during the reaction process.

Vacancy defect engineered BiVO4 with low-index surfaces for photocatalytic application: a first principles study.

BiVO4 has been widely investigated as a photocatalyst material for water splitting due to its outstanding photocatalytic properties. In order to further improve its photocatalytic efficiency, it is necessary to conduct an in-depth study of improvement strategies, such as defect engineering. By focusing on the (001) and (011) surfaces, we carried out a systematic theoretical research on pristine and defective systems, including Bi, V and O vacancies. Based on density functional theory (DFT), the electronic properties, band alignments and Gibbs free energy of pristine and defective BiVO4 have been analyzed. The electronic structures of the (001) and (011) surfaces show different band gaps, and O vacancies make the BiVO4 become an n-type semiconductor, while Bi and V vacancies tend to form a p-type semiconductor. Moreover, the band edge positions indicate that holes are indeed easily accumulated on the (011) surface while electrons tend to accumulate on (001). However, the (011) surface with Bi and V vacancies does not have enough oxidation potential to oxidize water. The reaction free energy shows that O and Bi vacancies could lower the overpotential to some extent.

Tankyrases/ß-catenin Signaling Pathway as an Anti-proliferation and Anti-metastatic Target in Hepatocarcinoma Cell Lines.

Objective: The Wnt/ß-catenin pathway is involved in the development of hepatocellular carcinoma (HCC) and malignant events such as the epithelial-mesenchymal transition (EMT), metastasis, and invasion. Studies have illustrated that the inhibition of tankyrases (TNKS) antagonizes Wnt/ß-catenin signaling in many cancer cells. Methods: The expression levels of proteins related to the Wnt/ß-catenin pathway and EMT were analyzed by immunohistochemistry in HCC tissue and paired adjacent normal tissue (n = 10), and in an analysis of The Cancer Genome Atlas (TCGA) data. Additionally, after treatment of HCC cell lines with TNKS1/2 small interfering RNA (siRNA) and a novel TNKS inhibitor (NVP-TNKS656), cell viability, cell clone formation, wound-healing, and cell invasion assays were performed. Results: Higher expression of ß-catenin, TNKS, vimentin, and N-cadherin was observed in HCC tissue compared to adjacent normal tissue, but lower expression of E-cadherin was found in HCC tissue. These findings were also observed in the TCGA analysis. In addition, TNKS inhibition (using TNKS1/2 siRNA and NVP-TNKS656) not only abrogated the proliferation of the HCC cell lines but also suppressed metastasis, invasion, and EMT phenotypic features. Moreover, the mechanisms related to TNKS inhibition in HCC probably involved the stabilization of AXIN levels and the downregulation of ß-catenin, which mediates EMT marker expression. Conclusion: The TNKS/ß-catenin signaling pathway is a potential anti-proliferation and anti-metastatic target in HCC.