335 research outputs found
sj-docx-1-tah-10.1177_20406207221085197 – Supplemental material for A multicenter phase II study on the efficacy and safety of hetrombopag in patients with severe aplastic anemia refractory to immunosuppressive therapy
No full textSupplemental material, sj-docx-1-tah-10.1177_20406207221085197 for A multicenter phase II study on the efficacy and safety of hetrombopag in patients with severe aplastic anemia refractory to immunosuppressive therapy by Guangxin Peng, Guangsheng He, Hong Chang, Sujun Gao, Xinjian Liu, Tong Chen, Pei Li, Bing Han, Miao Miao, Zheng Ge, Xiaoyan Ge, Fei Li, Yingmei Li, Shunqing Wang, Yi Wang, Yaqi Shen, Tao Zhang, Jianjun Zou and Fengkui Zhang in Therapeutic Advances in Hematology</p
Effect of thermal cycles on the laser beam welded joint of AA2060 alloys
No full textThe effects of the thermal cyclic aging treatment on the microstructure and mechanical properties of 2060 Al-Li alloy laser beam welded joints were investigated. Aging treatments were conducted at different temperatures and for different cycles. Test results showed that the tensile strength of the weld joints increased and the elongation slightly decreased after the thermal cycling treatment. It was also found that the heat affected zone (HAZ) of the welds exhibited a significant increase in microhardness, whilst the microhardness variation of the nondendrite equiaxed zone (EQZ) can be neglected. The strengthening effect of the thermal cycling became more obvious as the temperature and cycles increased. The highest strength of around 513 MPa (96% of the base metal) was obtained at the temperature of 180 degrees C. Reprecipitation of strengthening phases such as T1 in the HAZ at 180 degrees C was observed by TEM, which can be considered as the main reason for the strengthening effect of the aging treatment.</p
Unveiling novel participants in the DNA damage response
No full textThe human genome is constantly challenged by DNA damage resulting from environmental factors and metabolic processes. To safeguard the integrity of the genome, a complex defence system known as the DNA damage response (DDR) has evolved. The DDR comprises intricate mechanisms, including DNA repair pathways, damage tolerance processes, cell cycle checkpoints and programmed cell death, together aimed at maintaining genomic stability. Among the various types of DNA lesions, interstrand crosslinks (ICLs) pose a significant threat as they impede DNA replication and transcription. Inadequate repair of ICLs is closely linked to Fanconi anaemia (FA), a genetic disorder associated with severe health consequences. Moreover, ICL-inducing agents have a broad clinical application in cancer therapy, although the emergence of drug resistance poses a challenge. Therefore, comprehending the mechanisms involved in ICL repair is critical for developing alternative treatment strategies and enhancing drug sensitivity.
The focus of this DPhil thesis is to investigate the participation and function of two novel proteins in the cellular response to ICL-induced DNA damage. Rapid accumulation of the first protein at ICL sites is observed, and its knockout results in heightened cellular sensitivity to ICL-inducing agents, indicating its positive contribution to cell survival against ICLs. Further investigations revealed that this protein operates independently of the established FA and NEIL3 pathway for ICL repair, suggesting its potential role in alternative repair mechanisms or early-stage DDR processes. The second novel protein exhibits a distinct relocation from the nucleoplasm to the peripheral nucleoli, forming a ring-shaped accumulation pattern in response to ICLs. Additional experiments demonstrate that this protein translocates into the nucleolar cap under nucleolar stress induced by various types of DNA damage and transcription inhibition. These findings support the notion that the nucleolus acts as a stress sensor, and the nucleolar translocation of this novel protein potentially contributes to cellular fate decisions or the interplay between DDR and nucleolar function. Together, the research presented in this thesis provides insights into the roles of two new protein players in preserving genomic stability. Understanding their interactions with established repair pathways and their potential therapeutic implications in FA and cancer treatment will pave the way for developing targeted interventions and improving patient outcomes
Research on the combined heating method using dual subsonic gas flow of high and middle temperature for thermal test of tip wedge structure
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