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As an advanced amorphous material, sp3 amorphous carbon exhibits exceptional mechanical, thermal and optical properties, but it cannot be synthesized by using traditional processes such as fast cooling liquid carbon and an efficient strategy to tune its structure and properties is thus lacking. Here we show that the structures and physical properties of sp3 amorphous carbon can be modified by changing the concentration of carbon pentagons and hexagons in the fullerene precursor from the topological transition point of view. A highly transparent, nearly pure sp3−hybridized bulk amorphous carbon, which inherits more hexagonal-diamond structural feature, was synthesized from C70 at high pressure and high temperature. This amorphous carbon shows more hexagonal-diamond-like clusters, stronger short/medium-range structural order, and significantly enhanced thermal conductivity (36.3 ± 2.2 W m−1 K−1) and higher hardness (109.8 ± 5.6 GPa) compared to that synthesized from C60. Our work thus provides a valid strategy to modify the microstructure of amorphous solids for desirable properties. sp3 amorphous carbon exhibits exceptional mechanical, thermal, and optical properties, but cannot be synthesized using traditional processes. Here authors report a nearly pure sp3−hybridized amorphous carbon synthesized from C70 which shows more short/medium-range order and enhanced thermal conductivity compared to C60. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy targeting PD-1/PD-L1 has been proven to be effective for cervical cancer treatment. To explore non-invasive examinations for assessing the PD-L1 status in cervical cancer, we performed a retrospective study to investigate the predictive value of 18F-FDG PET/CT. Methods: The correlations between PD-L1 expression, clinicopathological characteristics and 18F-FDG PET/CT metabolic parameters were evaluated in 74 cervical cancer patients. The clinicopathological characteristics included age, histologic type, tumor differentiation, FIGO stage and tumor size. The metabolic parameters included maximum standard uptake (SUVmax), mean standard uptake (SUVmean), total lesion glycolysis (TLG) and tumor metabolic volume (MTV). Results: In univariate analysis, SUVmax, SUVmean, TLG, tumor size and tumor differentiation were obviously associated with PD-L1 status. SUVmax (rs = 0.42) and SUVmean (rs = 0.40) were moderately positively correlated with the combined positive score (CPS) for PD-L1 in Spearman correlation analysis. The results of multivariable analysis showed that the higher SUVmax (odds ratio = 2.849) and the lower degree of differentiation (Odds Ratio = 0.168), the greater probability of being PD-L1 positive. The ROC curve analysis demonstrated that when the cut-off values of SUVmax, SUVmean and TLG were 10.45, 6.75 and 143.4, respectively, the highest accuracy for predicting PD-L1 expression was 77.0%, 71.6% and 62.2%, respectively. The comprehensive predictive ability of PD-L1 expression, assessed by combining SUVmax with tumor differentiation, showed that the PD-L1-negative rate was 100% in the low probability group, whereas the PD-L1-positive rate was 84.6% in the high probability group. In addition, we also found that the H-score of HIF-1α was moderately positively correlated with PD-L1 CPS (rs = 0.51). Conclusions: The SUVmax and differentiation of the primary lesion were the optimum predictors for PD-L1 expression in cervical cancer. There was a great potential for 18F-FDG PET/CT in predicting PD-L1 status and selecting cervical cancer candidates for PD1/PD-L1 immune checkpoint therapy. [ABSTRACT FROM AUTHOR]

Hypoxia is an important tumor feature and hypoxia-inducible factor 1 (HIF-1) is a master regulator of cell response to hypoxia. Mouse double minute 2 homolog (MDM2) promotes cancer cell survival in retinoblastoma (RB), with the underlying mechanism remaining elusive. In this study, we investigated the role of MDM2 and its relation to HIF-1α in RB. Expression analysis on primary human RB samples showed that MDM2 expression was positively correlated with that of HIF-1α while negatively correlated with von Hippel-Lindau protein (pVHL), the regulator of HIF-1α. In agreement, RB cells with MDM2 overexpression showed increased expression of HIF-1α and decreased expression of pVHL, while cells with MDM2 siRNA knockdown or MDM2-specific inhibitor showed the opposite effect under hypoxia. Further immuno-precipitation analysis revealed that MDM2 could directly interact with pVHL and promotes its ubiquitination and degradation, which consequently led to the increase of HIF-1α. Inhibition of MDM2 and/or HIF-1α with specific inhibitors induced RB cell death and decreased the stem cell properties of primary RB cells. Taken together, our study has shown that MDM2 promotes RB survival through regulating the expression of pVHL and HIF-1α, and targeting MDM2 and/or HIF-1α represents a potential effective approach for RB treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Xu, Li, Ji, Jin, Chen, Gan, Tao and Chai.)

Objective: To explore the effect of whole brain irradiation (WBI) on neurogenesis in hippocampus and its relationship with histone acetylation., Methods: A signal dose of 30Gy 4MeV electron beam was offered to male Sprague-Dawley rats (150 - 200 g). At Days 7 and 30, immunohistochemistry and Western blot were used to analyze the effects of WBI on neurogenesis and the expression of acetyl-H3 and histone deacetylase 1 (HDAC1) in hippocampus. Finally trichostatin A (TSA), a HDAC1 inhibitor, was used to verify whether H3 acetylation was associated with neurogenesis impairment., Results: Immunofluorescence showed that, at Day 7 post-irradiation, the number of BrdU + NeuN + cells reduced by 67% (P < 0. 01) and it approached zero at Day 30 (P < 0. 01). Meanwhile, a significant decrease of HDAC1-dependent H3 acetylation was observed. Western blot showed 30% (P <0. 05) and 61% (P < 0. 01) reductions in H3 acetylation at Days 7 and 30 post-irradiation respectively. These results were further confirmed by immunofluorescent staining. Also HDAC1 levels significantly increased in a time-dependent manner at Days 7 and 30 post-irradiation. And TSA rescued neurogenesis impairment after WBI., Conclusion: Radiation-induced HDAC1-dependent H3 acetylation decline is associated with long-term neurogenesis impairment in dentate gyrus.