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Metal halide perovskites have fascinated the research community over the past decade, and demonstrated unprecedented success in optoelectronics. In particular, perovskite single crystals have emerged as promising candidates for ionization radiation detection, due to the excellent opto-electronic properties. However, most of the reported crystals are grown in organic solvents and require high temperature. In this work, we develop a low-temperature crystallization strategy to grow CsPbBr 3 perovskite single crystals in water. Then, we carefully investigate the structure and optoelectronic properties of the crystals obtained, and compare them with CsPbBr 3 crystals grown in dimethyl sulfoxide. Interestingly, the water grown crystals exhibit a distinct crystal habit, superior charge transport properties and better stability in air. We also fabricate X-ray detectors based on the CsPbBr 3 crystals, and systematically characterize their device performance. The crystals grown in water demonstrate great potential for X-ray imaging with enhanced performance metrics. Perovskite single crystals are commonly grown in organic solvents, which require relatively high temperature condition. Here, the authors develop a low-temperature crystallisation strategy to grow CsPbBr 3 single crystals in water with improved charge transport properties and stability.

Large single crystals serve as an ideal platform for investigating intrinsic material properties and optoelectronic applications. Here we develop a method, namely, room-temperature liquid diffused separation induced crystallization that uses silicone oil to separate the solvent from the perovskite precursors, to grow high-quality perovskite single crystals. The growth kinetics of perovskite single crystals using this method is elucidated, and their structural and optoelectronic properties are carefully characterized. The resultant perovskite single crystals, taking CH 3 NH 3 PbBr 3 as an example, exhibit approximately 1 µs lifetime, a low trap density of 4.4 × 10 9  cm −3 , and high yield of 92%, which are appealing for visible light or X-ray detection. We hope our findings will be of great significance for the continued advancement of high-quality perovskite single crystals, through a better understanding of growth mechanisms and their deployment in various optoelectronics. The diffused separation induced crystallization strategy presents a major step forward for advancing the field on perovskite single crystals. Perovskites are appealing for optoelectronics, but high-quality perovskite single crystals should be grown at low temperature to minimize trap density. Here, the authors report a room-temperature liquid-diffused-induced crystallization for growth of high-quality hybrid perovskite single crystals.

High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy. However, the molecular mechanisms underlying HGSOC development, progression, chemotherapy insensitivity and resistance remain unclear. Two independent GEO datasets, including the gene expression profile of primary ovarian carcinoma and normal controls, were analyzed to identify genes related to HGSOC development and progression. A KEGG pathway analysis of the differentially expressed genes (DEGs) revealed that the cell cycle pathway was the most enriched pathway, among which TTK protein kinase (TTK) was the only gene with a clinical-grade inhibitor that has been investigated in a clinical trial but had not been studied in HGSOC. TTK was also upregulated in cisplatin-resistant ovarian cancer cells from two other datasets. TTK is a regulator of spindle assembly checkpoint signaling, playing an important role in cell cycle control and tumorigenesis in various cancers. However, the function and regulatory mechanism of TTK in HGSOC remain to be determined. In this study, we observed TTK upregulation in patients with HGSOC. High TTK expression was related to a poor prognosis. Genetic and pharmacological inhibition of TTK impeded the proliferation of ovarian cancer cells by disturbing cell cycle progression and increasing apoptosis. TTK silencing increased cisplatin sensitivity by activating the mammalian target of rapamycin (mTOR) complex to further suppress cisplatin-induced autophagy in vitro. In addition, the enhanced sensitivity was partially diminished by rapamycin-mediated inhibition of mTOR in TTK knockdown cells. Furthermore, TTK knockdown increased the toxicity of cisplatin in vivo by decreasing autophagy. These findings suggest that the administration of TTK inhibitors in combination with cisplatin may lead to improved response rates to cisplatin in patients with HGSOC presenting high TTK expression. In summary, our study may provide a theoretical foundation for using the combination therapy of cisplatin and TTK inhibitors as a treatment for HGSOC in the future.

Poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) resistance remains a therapeutic challenge in ovarian cancer. High-mobility group box 3 (HMGB3) plays significant roles in the development of drug resistance of many cancers. However, the function of HMGB3 in PARPi resistance is poorly understood. In the current study, we clarified that HMGB3 was aberrantly overexpressed in high-grade serous ovarian carcinoma (HGSOC) tissues, and high HMGB3 levels indicated shorter overall survival and drug resistance in HGSOC. The overexpression of HMGB3 increased the insensitivity of ovarian cancer to PARPi, whereas HMGB3 knockdown reduced PARPi resistance. Mechanistically, PARP1 was identified as a novel interaction partner of HMGB3, which could be blocked using olaparib and was enhanced upon DNA damage conditions. We further showed that loss of HMGB3 induced PARP1 trapping at DNA lesions and inhibited the PARylation activity of PARP1, resulting in an increased DNA damage response and cell apoptosis. The PARPi-resistant role of HMGB3 was also verified in a xenograft mouse model. In conclusion, HMGB3 promoted PARPi resistance via interacting with PARP1, and the targeted inhibition of HMGB3 might overcome PARPi resistance in ovarian cancer therapy.

The high-voltage oxygen redox activity of Li-rich layered oxides enables additional capacity beyond conventional transition metal (TM) redox contributions and drives the development of positive electrode active materials in secondary Li-based batteries. However, Li-rich layered oxides often face voltage decay during battery operation. In particular, although Li-rich positive electrode active materials with a high nickel content demonstrate improved voltage stability, they suffer from poor discharge capacity. Here, via physicochemical and electrochemical measurements, we investigate the correlation between oxygen redox activity and superstructure units in Li-rich layered oxides, specifically the fractions of LiMn 6 and Ni 4+ -stabilized LiNiMn 5 within the TM layer. We prove that an excess of LiNiMn 5 hinders the extraction/insertion of lithium ions during Li metal coin cell charging/discharging, resulting in incomplete oxygen redox activity at a cell potential of about 3.3 V. We also demonstrate that lithium content adjustment could be a beneficial approach to tailor the superstructure units. Indeed, we report an improved oxygen redox reversibility for an optimized Li-rich layered oxide with fewer LiNiMn 5 units. The high-voltage oxygen redox activity of Li-rich layered oxides enables additional capacity beyond conventional transition metal redox contributions. Here, authors investigate the correlation between oxygen redox activity and superstructure units. They prove that an excess of LiNiMn5 hinders the extraction/insertion of lithium ions.

Cervical cancer is the fourth most common cancer and the leading cause of mortality among women worldwide. Tumor metastasis is an important cause of poor prognosis. Determining the exact mechanisms of metastasis and potential targeted therapies is urgently needed. Junctional adhesion molecule 3 (JAM3) is an important member of the TJ tight junction (TJ) family, and its biological function in cervical cancer needs to be further clarified. We found that JAM3 was highly expressed in cervical cancer patients with lymph node metastasis and that high expression of JAM3 promoted cervical cancer cell metastasis both in vitro and in vivo. In addition, overexpression of JAM3 induces epithelial–mesenchymal transition (EMT). Moreover, silencing JAM3 suppressed cervical cancer cell migration and invasion in vitro. Finally, JAM3 overexpression activated the HIF-1α/VEGFA pathway. In conclusion, our results suggested that JAM3 promotes cervical cancer cell migration and invasion by activating the HIF-1α/VEGFA pathway. JAM3 may be a promising biomarker and effective therapeutic target for cervical cancer.

Background DNA damage and repair (DDR) is involved in the antitumor immune response, however, the correlation between DNA damage response with immunotherapy in NSCLC remain unclear. We examined the relationship between DDR alterations and expression of PD-L1 in non-small cell lung cancer. Methods Tumor tissues, para-carcinoma and normal tissues, were obtained from 54 patients who were surgically resected NSCLC tumors. Patient characteristics, neoplasm staging and pathological information were collected. Immunohistochemical analysis of tissue samples was analyzed for γH2AX、RAD51, PARP-1 and PD-L1 protein expression. Results A total of 54 patients with non-small cell lung cancer were included in this study, including 24 males and 30 females with ages ranging from 45 to 79 years (mean, 63.5 years). The high expression rate of γH2AX staining in lung cancer was 81.5%(44/54)and the expression levels of γH2AX protein were significantly higher in NSCLC than those in paired para-carcinoma 50%(27/54) and normal tissues 42.6%(23/54). The expression levels of RAD51 protein were significantly higher in lung cancer tissue 68.5%(37/54) than those in paired para-carcinoma 48.1%(26/54) and normal tissues 40.7%(22/54). There was a significant correlation between high RAD51 expression and male patients 87.5%(21/24) ( p  = 0.009) and a history of smoking 90%(18/20) ( p  = 0.014). The presence of any DDR alteration was showed with PD-L1. (1) HigherγH2AX expression was observed in the PD-L1 positive cases 90.6% (29/32) compared to the PD-L1 negative cases 68.2% (15/22). Lung cancers with higher γH2AX expression were associated with the higher expression of PD-L1 ( p  = 0.046, r  = 0.284). (2) There was no statistically significant correlation between expression of PD-L1 and RAD51 ( p  = 0.221, r  = 0.168). (3) Higher PARP-1 expression was observed in the PD-L1 negative cases 59.1% (13/22) compared to the PD-L1 positive cases 25% (8/32). Lung cancers with higher PARP-1 expression were associated with the lower expression of PD-L1 ( p  = 0.009, r =-0.344). (4) No statistically significant association was observed in relationship between expression of DDR Expression (γH2AX、RAD51) and PARP-1 of patients ( p  = 0.507 and p  = 0.817,respectively). Conclusion Overall, our study shows that high expression of γH2AX, RAD51, and PARP1 proteins display in NSCLC and proves that DNA damage repair may be closely related to the occurrence and development of NSCLC. γH2AX could be a predictor of the adaptation of ICIs as an alternative to PD-L1, and NSCLC is expected to benefit from PARP-1 inhibitors combined with immunotherapy.

Facile formation of carbon-heteroatom bonds is a long-standing objective in synthetic organic chemistry. However, direct cross-coupling with readily accessible alkenyl acetates via inert C‒O bond-cleavage for the carbon-heteroatom bond construction remains challenging. Here we report a practical preparation of stereoselective tri- and tetrasubstituted alkenyl silanes and stannanes by performing cobalt-catalyzed C‒O silylation and stannylation of alkenyl acetates using silylzinc pivalate and stannylzinc chloride as the nucleophiles. This protocol features a complete control of chemoselectivity, stereoselectivity, as well as excellent functional group compatibility. The resulting alkenyl silanes and stannanes show high reactivities in arylation and alkenylation by Hiyama and Stille reactions. The synthetic utility is further illustrated by the facile late-stage modifications of natural products and drug-like molecules. Mechanistic studies suggest that the reaction might involve a chelation-assisted oxidative insertion of cobalt species to C‒O bond. We anticipate that our findings should prove instrumental for potential applications of this technology to organic syntheses and drug discoveries in medicinal chemistry. Carbon-heteroatom bond formation reactions are of high interest in synthetic organic chemistry. Here, the authors report the cobalt-catalyzed synthesis of tri- and tetrasubstituted alkenyl silanes and stannanes via C–O functionalization of vinyl acetates using silylzinc pivalate and stannylzinc chloride as the nucleophiles.

Background Ovarian cancer, particularly epithelial ovarian cancer (EOC), is the leading cause of cancer-related mortality among women. Our previous study revealed that high HMGB3 levels are associated with poor prognosis and lymph node metastasis in patients with high-grade serous ovarian carcinoma; however, the role of HMGB3 in EOC proliferation and metastasis remains unknown. Methods MTT, clonogenic, and EdU assays were used to assess cell proliferation. Transwell assays were performed to detect cell migration and invasion. Signaling pathways involved in HMGB3 function were identified by RNA sequencing (RNA-seq). MAPK/ERK signaling pathway protein levels were evaluated by western blot. Results HMGB3 knockdown inhibited ovarian cancer cell proliferation and metastasis, whereas HMGB3 overexpression facilitated these processes. RNA-seq showed that HMGB3 participates in regulating stem cell pluripotency and the MAPK signaling pathway. We further proved that HMGB3 promotes ovarian cancer stemness, proliferation, and metastasis through activating the MAPK/ERK signaling pathway. In addition, we demonstrated that HMGB3 promotes tumor growth in a xenograft model via MAPK/ERK signaling. Conclusions HMGB3 promotes ovarian cancer malignant phenotypes and stemness through the MAPK/ERK signaling pathway. Targeting HMGB3 is a promising strategy for ovarian cancer treatment that may improve the prognosis of women with this disease. 2qup1eeBfJMNesoTGXbg-C Video Abstract

Resistance to PARP inhibitors (PARPi) remains a therapeutic challenge in ovarian cancer patients. PDZ-binding kinase (PBK) participates in the chemoresistance of many malignancies. However, the role of PBK in PARPi resistance of ovarian cancer is obscure. In the current study, we demonstrated that overexpression of PBK contributed to olaparib resistance in ovarian cancer cells. Knockdown of PBK sensitized olaparib-resistant SKOV3 cells to olaparib. Inhibition of PBK using a specific inhibitor enhanced the therapeutic efficiency of olaparib. Mechanically, PBK directly interacted with TRIM37 to promote its phosphorylation and nuclear translocation. which subsequently activates the NFκB pathway. Additionally, PBK enhanced olaparib resistance of ovarian cancer by regulating the NFκB/TRIM37 axis in vitro and in vivo. In conclusion, PBK confers ovarian cancer resistance to PARPi through activating the TRIM37-mediated NFκB pathway, and targeted inhibition of PBK provided the new therapy to improve PARPi treatment outcomes for ovarian cancer patients. Cancer: Enzyme confers resistance to targeted chemotherapy An enzyme implicated in tumor progression also helps cancers thwart a commonly used type of targeted drug therapy. Beihua Kong and colleagues from Shandong University, Jinan, China, showed how PDZ-binding kinase (PBK), an enzyme that promotes the proliferation and spread of cancer cells, activates a signaling pathway that renders tumors resistant to treatment with olaparib. This precision anti-cancer drug works by blocking a protein called PARP that normally helps cells repair damaged DNA. The researchers showed how PBK interacts with another protein to stimulate a transcription factor previously shown to reduce the effectiveness of radiation and chemotherapy. Blocking the activity of PBK, either pharmacologically or genetically, enhanced the sensitivity of ovarian cancer cells to olaparib. A similar drug strategy could help improve outcomes for cancer patients undergoing PARP inhibitor treatment.