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"Li, Jie"
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Cdc25A inhibits autophagy-mediated ferroptosis by upregulating ErbB2 through PKM2 dephosphorylation in cervical cancer cells
Cervical cancer is the leading cause of cancer-related deaths in women, and treatment for cervical cancer is very limited. Emerging evidence suggests that targeting ferroptosis is a promising way to treat cancer. Here, we investigated the role of ferroptosis in cervical cancer, with a focus on the Cdc25A/PKM2/ErbB2 axis. Cervical cancer cells were treated with sorafenib to induce ferroptosis. Cellular MDA/ROS/GSH/iron detection assays were used to measure ferroptosis. MTT assays were performed to assess cell viability. qRT-PCR, western blot, and immunostaining assays were performed to measure the levels of proteins. Autophagy was monitored by fluorescence microscopy. Nuclear and cytosolic fractions were isolated to examine the location of PKM2 modifications. Co-IP experiments were conducted to determine the Cdc25A/PKM2 interaction. ChIP assays were performed to measure the binding affinity between H3K9Ac and the ErbB3 promoter, and a dual luciferase assay was performed to examine the transcriptional activity of ErbB2. A nude mouse xenograft model was used to examine the effects of the Cdc25A/ErbB2 axis on tumour growth in vivo. Cdc25A was elevated in human cervical cancer tissues but was reduced during sorafenib-induced ferroptosis of cervical cancer cells. Overexpression of Cdc25A inhibited sorafenib-induced ferroptosis by dephosphorylating nuclear PKM2 and suppressing autophagy. Cdc25A regulated autophagy-induced ferroptosis by increasing ErbB2 levels via the PKM2–pH3T11–H3K9Ac pathway. Cdc25A increased the resistance of cervical cancer to sorafenib, while knockdown of ErbB2 blocked these effects. Cdc25A suppressed autophagy-dependent ferroptosis in cervical cancer cells by upregulating ErbB2 levels through the dephosphorylation of PKM2. These studies revealed that Cdc25A/PKM2/ErbB2 pathway-regulated ferroptosis could serve as a therapeutic target in cervical cancer.
Journal Article
Strengthening in multi-principal element alloys with local-chemical-order roughened dislocation pathways
High-entropy and medium-entropy alloys are presumed to have a configurational entropy as high as that of an ideally mixed solid solution (SS) of multiple elements in near-equal proportions. However, enthalpic interactions inevitably render such chemically disordered SSs rare and metastable, except at very high temperatures. Here we highlight the wide variety of local chemical ordering (LCO) that sets these concentrated SSs apart from traditional solvent-solute ones. Using atomistic simulations, we reveal that the LCO of the multi-principal-element NiCoCr SS changes with alloy processing conditions, producing a wide range of generalized planar fault energies. We show that the LCO heightens the ruggedness of the energy landscape and raises activation barriers governing dislocation activities. This influences the selection of dislocation pathways in slip, faulting, and twinning, and increases the lattice friction to dislocation motion via a nanoscale segment detrapping mechanism. In contrast, severe plastic deformation reduces the LCO towards random SS.
Multi-principal-element alloys have been assumed to have the configurational entropy of an ideal solution. Here, the authors use atomistic simulations to show that instead NiCoCr exhibits local chemical order, raising the activation barriers of dislocation activities to elevate mechanical strength.
Journal Article
Antibody responses to SARS-CoV-2 in patients with COVID-19
We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT–PCR results and for the identification of asymptomatic infections.
A cross-sectional study of hospitalized patients with COVID-19 and a longitudinal follow-up study of patients with COVID-19 suggest that SARS-CoV2-specific IgG or IgM seroconversion occurs within 20 days post symptom onset.
Journal Article
Modern emergency management
This book provides essential information on emergency management. It is composed of two parts, addressing the basic theory and related methods of emergency management, including risk management, coordination management, crisis management and disaster management. By putting the emphasis on interdisciplinary, systematic perspectives and building a bridge between basic knowledge and further research, it is well suited as an emergency management textbook and offers a valuable guide to prepare readers for their future emergency management careers.
Book
Changes in notifiable infectious disease incidence in China during the COVID-19 pandemic
Nationwide nonpharmaceutical interventions (NPIs) have been effective at mitigating the spread of the novel coronavirus disease (COVID-19), but their broad impact on other diseases remains under-investigated. Here we report an ecological analysis comparing the incidence of 31 major notifiable infectious diseases in China in 2020 to the average level during 2014-2019, controlling for temporal phases defined by NPI intensity levels. Respiratory diseases and gastrointestinal or enteroviral diseases declined more than sexually transmitted or bloodborne diseases and vector-borne or zoonotic diseases. Early pandemic phases with more stringent NPIs were associated with greater reductions in disease incidence. Non-respiratory diseases, such as hand, foot and mouth disease, rebounded substantially towards the end of the year 2020 as the NPIs were relaxed. Statistical modeling analyses confirm that strong NPIs were associated with a broad mitigation effect on communicable diseases, but resurgence of non-respiratory diseases should be expected when the NPIs, especially restrictions of human movement and gathering, become less stringent.
Non-pharmaceutical interventions implemented to mitigate COVID-19 transmission are likely to have impacted spread of other infectious diseases. Here, the authors investigate changes in the incidence of 31 notifiable infectious diseases using surveillance data from China.
Journal Article
الإنسان
أصدرت مؤسسة بيت الحكمة، حديثا، سلسلة \"قصص الرموز الصينية\"، وهي أول سلسلة تثقيفية وتعليمية مترجمة تتناول البحث في قصص الرموز الصينية، والكشف عن أصل الرموز والحكايات التاريخية التى خلفها، حيث تعتمد على مقولات مبسطة تقود القارئ لمعرفة منابع الرموز الصينية وتاريخ تطورها. وتتشكل السلسلة من خمسة كتب، وهي : \"الإنسان، والحيوان، والنبات، والطبيعة، والحياة\"، ويتناول كل منها عددا من الرموز التي يحكي أصلها وطرق كتابتها على مر العصور وصولا لشكلها الحالي، بالإضافة إلى التعريف بأشكال النقوش وأنواع الخطوط الصينية ونماذج لكل منها، والطرق الأساسية لابتكار الرموز الصينية إما المعبرة عن الأشياء، أو المشتقة من معنى أجزائها، كما تتناول السلسلة، الكلمات والعبارات التي تدخل الرموز في تكوينها، والأمثال والحكم والقصص التراثية التي تستخدم الرمز أو مدلولاته في إطار أدبي شيق.
BOOK
Hsp90 up-regulates PD-L1 to promote HPV-positive cervical cancer via HER2/PI3K/AKT pathway
Background
HPV16 is the predominant cancer-causing strain that is responsible for over 50% of all cervical cancers. In this study, we aim to investigate the therapeutic effect of heat shock protein 90 (Hsp90) knockdown on HPV16
+
cervical cancer progression and the underlying mechanism.
Methods
The transcript and protein expression of Hsp90 in normal cervical and HPV16
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cervical cancer tissues and cell lines were detected by qRT-PCR, immunohistochemistry staining and Western blot. Hsp90 knockdown clones were established using HPV16
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cervical cancer cell line Caski and SiHa cells. The effect of Hsp90 knockdown on HER2/PI3K/AKT pathway and PD-L1 expression was characterized using qRT-PCR and Western blot analysis. Cell proliferation and migration were determined using MTT and transwell assays. Using mouse xenograft tumor model, the impact of Hsp90 knockdown and PD-L1 overexpression on tumor progression was evaluated.
Results
Hsp90 expression was up-regulated in HPV16
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cervical cancer tissues and cells. Knockdown of Hsp90 inhibited proliferation and migration of Caski and SiHa cells. PD-L1 expression in cervical cancer tissues was positively correlated with Hsp90 expression, and Hsp90 regulated PD-L1 expression via HER2/PI3K/AKT signaling pathway. The results of mouse xenograft tumor model demonstrated Hsp90 knockdown suppressed tumor formation and overexpression of PD-L1 simultaneously eliminated the cancer-suppressive effect of Hsp90 knockdown.
Conclusion
In this study, we demonstrated a promising tumor-suppressive effect of Hsp90 knockdown in HPV16
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cervical cancers, and investigated the underlying molecular pathway. Our results suggested that Hsp90 knockdown holds great therapeutic potential in treating HPV16
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cervical cancers.
Journal Article