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Introduction Lung tumor growth and metastasis requires angiogenesis--the formation of new blood vessels (1, 2). Angiogenesis is typically triggered by hypoxia, which stabilizes hypoxia-inducible transcription factors (HIFs) including HIF1[alpha] and [...], Lung cancer progression relies on angiogenesis, which is a response to hypoxia typically coordinated by hypoxia- inducible transcription factors (HIFs), but growing evidence indicates that transcriptional programs beyond HIFs control tumor angiogenesis. Here, we show that the redox-sensitive transcription factor BTB and CNC homology 1 (BACH1) controls the transcription of a broad range of angiogenesis genes. BACH1 is stabilized by lowering ROS levels; consequently, angiogenesis gene expression in lung cancer cells, tumor organoids, and xenograft tumors increased substantially following administration of vitamins C and E and N-acetylcysteine in a BACH1-dependent fashion under normoxia. Moreover, angiogenesis gene expression increased in endogenous BACH1-overexpressing cells and decreased in SACH7-knockout cells in the absence of antioxidants. BACH1 levels also increased upon hypoxia and following administration of prolyl hydroxylase inhibitors in both HfF7A-knockout and WT cells. BACH1 was found to be a transcriptional target of HIF1[alpha], but BACH1's ability to stimulate angiogenesis gene expression was HIF1[alpha] independent. Antioxidants increased tumor vascularity in vivo in a BACH1- dependent fashion, and overexpressing BACH1 rendered tumors sensitive to antiangiogenesis therapy. BACH1 expression in tumor sections from patients with lung cancer correlated with angiogenesis gene and protein expression. We conclude that BACH1 is an oxygen- and redox-sensitive angiogenesis transcription factor.

The test of the fatigue crack growth rate under five stress ratios（ R = 0. 1,0. 2,0. 3,0. 4 and 0. 5） is completed used the compact tensile specimen. The test data are processed by using incremental polynomial method and the expressions and curves of crack growth rate under different stress ratios are obtained. The effect of stress ratio on crack growth rate and two important parameters in Paris formula are analyzed. Moreover,the fatigue fractures under different stress ratios are analyzed,and discussed the mechanism of effect on crack propagation rate under different stress ratios.

Early intervention services to young children with developmental delays in China have experienced significant growth since 1978, the beginning of the period of Reform and Opening. This article described the present situation of early intervention practices in mainland China, framed around the key components and guiding principles of Guralnick's Developmental Systems Approach (DSA). The overarching purpose of this to overview is to develop a nationwide, integrated, and coordinated early intervention system, one that will develop in spite of the diversity inherent in the current practices and the dominant tradition of professionals as authority around the country. Extensive evidence demonstrates that early intervention practices in China have addressed some of the guiding principles of DSA and made significant progress in developing some components of DSA. Nevertheless, there still remains a great deal of work to be done to bring China's practices for the care and intervention of families and children up to the quality standards of the DSA for early intervention. Implications within the Chinese context for incorporating the key elements of DSA with strong connections between research, policy, and practices to further develop and strengthen early intervention system are discussed.

This article describes the background and findings of a research project on school effectiveness and evaluation in one regional education authority in China. The study was the outcome of a China/UK academic link aiming to improve research capacity and the evaluation of educational quality in China, funded by the British Council in Beijing, on behalf of the UK Department for International Development (DFID). With reference to the Chinese context, the paper also provides an overview and critique of relevant school effectiveness and school evaluation research, as well as approaches to assessing pupils' educational outcomes in China. In line with previous research in other country contexts, the findings of the study showed that significant differences in "value added" measures of school effectiveness appear to exist between senior secondary schools in China, and also that some schools are differentially effective (i.e., more effective in one academic subject than another). Recommendations are outlined in terms of how the results could be used to enhance school self-evaluation and the findings are also discussed in relation to the future quality in education research agenda in China. (Contains 3 tables, 2 figures, and 5 notes.)

Background: Although immune checkpoint blockade (ICB) has been proven to achieve a persistent therapeutic response in various tumor types, only 20%-40% of patients benefit from this treatment. Radiotherapy (RT) can enhance tumor immunogenicity and improve the ICB response, but the outcome achieved by combining these two modalities remains clinically unsatisfactory. We previously uncovered that lysine-specific demethylase 4C (KDM4C) is a regulator of radiosensitivity in lung cancer. However, the role of KDM4C in antitumor immunity has not yet been investigated., Methods: Infiltrating immune cells in our mouse tumor model were screened by flow cytometry. An in vivo subcutaneous transplanted tumor model and in vitro conditioned culture model were constructed to detect the quantitative and functional changes in CD8 + T cells. RNA sequencing and chromatin immunoprecipitation-PCR assays were used to explore the downstream regulatory mechanism of KDM4C in antitumor immunity. A C57BL/6 mouse tumor model was developed to evaluate the efficacy and safety of a triple therapy (the KDM4C-specific inhibitor SD70 plus RT and an anti-PD-L1 antibody) in lung cancer in vivo., Results: Genetical or pharmacological inhibition of KDM4C specifically increased CD8 + T cell infiltration; promoted the proliferation, migration and activation of CD8 + T cells; and alleviated CD8 + T cell exhaustion in mouse tumor tissues. Mechanistically, KDM4C inhibition increased the binding of H3K36me3 to the CXCL10 promoter region, thus inducing CXCL10 transcription and enhancing the CD8 + T cell mediated antitumor immune response. More importantly, among the tested regimens, the triple therapy achieved the best therapeutic efficacy with tolerable toxicity in lung cancer., Conclusions: Our data reveal a crucial role for KDM4C in antitumor immunity in lung cancer and indicate that targeting KDM4C in combination with radioimmunotherapy might be a promising synergistic strategy in lung cancer., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)