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Emerging roles of podoplanin in vascular development and homeostasis

null

《医学前沿（英文）》 2015年 第9卷 第4期   页码 421-430 doi: 10.1007/s11684-015-0424-9

摘要：

Podoplanin (PDPN) is a mucin-type O-glycoprotein expressed in diverse cell types, such as lymphatic endothelial cells (LECs) in the vascular system and fibroblastic reticular cells (FRCs) in lymph nodes. PDPN on LECs or FRCs activates CLEC-2 in platelets, triggering platelet activation and/or aggregation through downstream signaling events, including activation of Syk kinase. This mechanism is required to initiate and maintain separation of blood and lymphatic vessels and to stabilize high endothelial venule integrity within lymph nodes. In the vascular system, normal expression of PDPN at the LEC surface requires transcriptional activation of Pdpn by Prox1 and modification of PDPN with core 1-derived O-glycans. This review provides a comprehensive overview of the roles of PDPN in vascular development and lymphoid organ maintenance and discusses the mechanisms that regulate PDPN expression related to its function.

关键词： podoplanin     CLEC-2     Prox1     O-glycosylation     lymphatic vascular development and maintenance     lymphoid organ homeostasis    

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Paradoxical role of Id proteins in regulating tumorigenic potential of lymphoid cells

null

《医学前沿（英文）》 2018年 第12卷 第4期   页码 374-386 doi: 10.1007/s11684-018-0652-x

摘要：

A family of transcription factors known as Id proteins, or inhibitor of DNA binding and differentiation, is capable of regulating cell proliferation, survival and differentiation, and is often upregulated in multiple types of tumors. Due to their ability to promote self-renewal, Id proteins have been considered as oncogenes, and potential therapeutic targets in cancer models. On the contrary, certain Id proteins are reported to act as tumor suppressors in the development of Burkitt’s lymphoma in humans, and hepatosplenic and innate-like T cell lymphomas in mice. The contexts and mechanisms by which Id proteins can serve in such contradictory roles to determine tumor outcomes are still not well understood. In this review, we explore the roles of Id proteins in lymphocyte development and tumorigenesis, particularly with respect to inhibition of their canonical DNA binding partners known as E proteins. Transcriptional regulation by E proteins, and their antagonism by Id proteins, act as gatekeepers to ensure appropriate lymphocyte development at key checkpoints. We re-examine the derailment of these regulatory mechanisms in lymphocytes that facilitate tumor development. These mechanistic insights can allow better appreciation of the context-dependent roles of Id proteins in cancers and improve considerations for therapy.

关键词： Id proteins     lymphoma     leukemia     T cells     B cells     tumor suppressor     oncogene    

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Clinical characteristics and prognostic factors of patients with mature T-cell lymphoid malignancies:

null

《医学前沿（英文）》 2015年 第9卷 第4期   页码 468-477 doi: 10.1007/s11684-015-0419-6

摘要：

Mature T-cell lymphoid malignancies comprise a group of heterogeneous diseases that vary in clinicopathological features, biological behavior, treatment response, and prognosis. Bone marrow (BM) infiltration is more commonly present in mature T-cell lymphoid malignancies compared with their B-cell counterparts and hence important for differential diagnosis. In this study, clinical characteristics and prognostic factors were analyzed in 225 patients with mature T-cell lymphoid malignancies treated in a single institution. These included 29 cases of T-cell lymphoproliferative disorders (T-LPD, all with BM infiltration) and 196 cases of T-/natural-killer-cell lymphoma (T/NKCL, 56 with BM infiltration and 140 without BM infiltration). The estimated 5-year overall survival (OS) rates of T-LPD and T/NKCL were 96.6% and 37.3%, respectively. T-LPD patients were less likely to exhibit poor performance status, advanced disease stage, presence of B symptoms, or abnormal level of serum β-2 microglobulin. With similar pathological characteristics, T/NKCL patients with BM infiltration showed significantly lower response rates and shorter OS than those without BM infiltration (P = 0.0264 and P<0.0001, respectively). Multivariate analysis indicated that poor performance status, advanced disease stage, elevated serum lactate dehydrogenase level, and BM involvement were independent unfavorable prognostic factors. The Glasgow Prognostic Score may be more efficient than the International Prognostic Index in predicting disease outcome in T/NKCL. In conclusion, clinical characteristics may be useful in more effectively stratifying patients with mature T-cell lymphoid malignancies.

关键词： mature T-cell lymphoid malignancies     clonal T-cell population     bone marrow infiltration     prognostic factors    

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Toll-like receptor signaling in hematopoietic homeostasis and the pathogenesis of hematologic diseases

null

《医学前沿（英文）》 2015年 第9卷 第3期   页码 288-303 doi: 10.1007/s11684-015-0412-0

摘要：

Toll-like receptors (TLRs), which are found in innate immune cells, are essential mediators of rapid inflammatory responses and appropriate T-cell activation in response to infection and tissue damage. Accumulating evidence suggests that TLR signaling is involved in normal hematopoiesis and specific hematologic pathologies. Particular TLRs and their downstream signaling mediators are expressed not only in terminally differentiated innate immune cells but also in early hematopoietic progenitors. Sterile activation of TLR signaling is required to generate early embryonic hematopoietic progenitor cells. In adult animals, TLR signaling directly or indirectly promotes differentiation of myeloid cells at the expense of that of lymphoid cells and the self-renewal of hematopoietic stem cells during infection and tissue damage. Activating mutations of the MyD88 gene, which codes for a key adaptor involved in TLR signaling, are commonly detected in B-cell lymphomas and other B-cell hematopathologies. Dysregulated TLR signaling contributes to the pathogenesis of many hematopoietic disorders, including bone marrow failure, myelodysplastic syndrome, and acute myeloid leukemia. Complete elucidation of the molecular mechanisms by which TLR signaling mediates the regulation of both normal and pathogenic hematopoiesis will prove valuable to the development of targeted therapies and strategies for improved treatment of hematopoietic disorders.

关键词： TLR     MyD88     hematopoiesis     bone marrow failure     leukemia     myelodysplastic syndrome    

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Zinc homeostasis in the metabolic syndrome and diabetes

null

《医学前沿（英文）》 2013年 第7卷 第1期   页码 31-52 doi: 10.1007/s11684-013-0251-9

摘要：

Zinc (Zn) is an essential mineral that is required for various cellular functions. Zn dyshomeostasis always is related to certain disorders such as metabolic syndrome, diabetes and diabetic complications. The associations of Zn with metabolic syndrome, diabetes and diabetic complications, thus, stem from the multiple roles of Zn: (1) a constructive component of many important enzymes or proteins, (2) a requirement for insulin storage and secretion, (3) a direct or indirect antioxidant action, and (4) an insulin-like action. However, whether there is a clear cause-and-effect relationship of Zn with metabolic syndrome, diabetes, or diabetic complications remains unclear. In fact, it is known that Zn deficiency is a common phenomenon in diabetic patients. Chronic low intake of Zn was associated with the increased risk of diabetes and diabetes also impairs Zn metabolism. Theoretically Zn supplementation should prevent the metabolic syndrome, diabetes, and diabetic complications; however, limited available data are not always supportive of the above notion. Therefore, this review has tried to summarize these pieces of available information, possible mechanisms by which Zn prevents the metabolic syndrome, diabetes, and diabetic complications. In the final part, what are the current issues for Zn supplementation were also discussed.

关键词： zinc     zinc transporters     metallothionein     diabetes     diabetic complications     insulin resistance     antioxidant    

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post-transplantation cyclophosphamide for allogeneic peripheral stem cell transplantation for adult patients with lymphoid

Ling Wang, Lining Wang, Xing Fan, Wei Tang, Jiong Hu

《医学前沿（英文）》 2021年 第15卷 第1期   页码 108-115 doi: 10.1007/s11684-019-0730-8

摘要： Post-transplantation cyclophosphamide (PT-Cy) alone or in combination with other immunosuppressive drugs has emerged as a promising strategy in the setting of allogeneic hematopoietic stem cell transplantation. Improved survival rate was reported in lymphoid malignancies following PT-Cy strategy compared with myeloid disease in non-myeloablative bone marrow transplant setting. Thus, we aimed to evaluate the safety and efficacy of PT-Cy combined with cyclosporine as graft-versus-host disease (GVHD) prophylaxis after myeloablative conditioning and T cell-replete peripheral stem cell transplantation in lymphoid malignancies. This single-arm phase II clinical trial (NCT01435447) involving 31 adult patients was conducted from January 2013 to June 2018. The donor-type neutrophil engraftment rate was 100%, and the overall incidence of grade II to IV and grade III to IV acute GVHD was 39% and 24%, respectively. The cumulative incidence rates of chronic GVHD (35%), including moderate to severe forms (10%), were reduced compared with those of the historical group ( =0.03 and =0.04, respectively). With a median follow-up of 18 months, the estimated 2-year overall and event-free survival was 64.8% (95% confidence interval: 47.8%–86.7%) and 58.4% (95% CI: 41.9%–81.7%), respectively. The 2-year cumulative incidence rate of relapse was 19.5% (95% CI: 9.0%–35.8%), whereas the non-relapse mortality rate was 21.8% (95% CI: 11.3%–38.1%). These results demonstrated the feasibility of PT-Cy as GVHD prophylaxis in this clinical setting. This strategy could significantly reduce the incidence of chronic GVHD and its moderate to severe forms but not of acute GVHD and results in similar survival outcomes compared with the historical group. A prospective study with additional patients is warranted to confirm the role of PT-Cy in lymphoid malignancy.

关键词： post-transplantation cyclophosphamide     allogeneic hematopoietic stem cell transplantation     lymphoid malignancies    

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Low-carbohydrate diets lead to greater weight loss and better glucose homeostasis than exercise: a randomized

《医学前沿（英文）》 2021年 第15卷 第3期   页码 460-471 doi: 10.1007/s11684-021-0861-6

摘要： Lifestyle interventions, including dietary adjustments and exercise, are important for obesity management. This study enrolled adults with overweight or obesity to explore whether either low-carbohydrate diet (LCD) or exercise is more effective in metabolism improvement. Forty-five eligible subjects were randomly divided into an LCD group (n=22) and an exercise group (EX, n=23). The subjects either adopted LCD (carbohydrate intake<50 g/day) or performed moderate-to-vigorous exercise (≥30 min/day) for 3 weeks. After the interventions, LCD led to a larger weight loss than EX (−3.56±0.37 kg vs. −1.24±0.39 kg, P<0.001), as well as a larger reduction in fat mass (−2.10±0.18 kg vs. −1.25±0.24 kg, P=0.007) and waist circumference (−5.25±0.52 cm vs. −3.45±0.38 cm, P=0.008). Both interventions reduced visceral and subcutaneous fat and improved liver steatosis and insulin resistance. Triglycerides decreased in both two groups, whereas low-density lipoprotein cholesterol increased in the LCD group but decreased in the EX group. Various glycemic parameters, including serum glycated albumin, mean sensor glucose, coefficient of variability (CV), and largest amplitude of glycemic excursions, substantially declined in the LCD group. Only CV slightly decreased after exercise. This pilot study suggested that the effects of LCD and exercise are similar in alleviating liver steatosis and insulin resistance. Compared with exercise, LCD might be more efficient for weight loss and glucose homeostasis in people with obesity.

关键词： low-carbohydrate diet     obesity     nonalcoholic fatty liver disease     continuous glucose monitoring     mean sensor glucose    

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alleviates myocardial diastolic dysfunction by modulating Drp1-mediated mitochondrial fission and Ca homeostasis

《医学前沿（英文）》 doi: 10.1007/s11684-023-0983-0

摘要： Berberine alleviates myocardial diastolic dysfunction by modulating Drp1-mediated mitochondrial fission and Ca homeostasis in a murine model of HFpEF

关键词： mitochondrial fission Ca     Berberine alleviates myocardial     murine model HFpEF    

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Zfyve16 regulates the proliferation of B-lymphoid cells

Xuemei Zhao, Donghe Li, Qingsong Qiu, Bo Jiao, Ruihong Zhang, Ping Liu, Ruibao Ren

《医学前沿（英文）》 2018年 第12卷 第5期   页码 559-565 doi: 10.1007/s11684-017-0562-3

摘要：

Zfyve16 (a.k.a. endofin or endosome-associated FYVE-domain protein), a member of the FYVE-domain protein family, is involved in endosomal trafficking and in TGF-β, BMP, and EGFR signaling. The FYVE protein SARA regulates the TGF-β signaling pathway by recruiting Smad2/3 and accelerating their phosphorylation, thereby altering their susceptibility to TGF-β-mediated T cell suppression. Zfyve16 binds to Smad4 and their binding affects the formation of Smad2/3-Smad4 complex in TGF-β signaling. However, the in vivo function of Zfyve16 remains unknown. In this study, we generated a Zfyve16 knockout mouse strain (Zfyve16KO) and examined its hematopoietic phenotypes and hematopoietic reconstruction ability. The proportion of T cells in the peripheral blood of Zfyve16KO mice increases compared with that in wild-type mice. This finding is consistent with the role of Zfyve16 in facilitating TGF-β signaling. Unpredictably, B cell proliferation is inhibited in Zfyve16KO mice. The proliferation potential of Zfyve16KO B-lymphoid cells also significantly decreases in vitro. These results suggest that Zfyve16 inhibits the proliferation of T cells, possibly through the TGF-β signaling, but upregulates the proliferation of B-lymphoid cells.

关键词： Zfyve16     endofin     hematopoiesis     TGF-β     lymphocytes    

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Planetary Homeostasis of Reactive Nitrogen Through Anaerobic Ammonium Oxidation

Guibing Zhu,Bangrui Lan,Shuci Liu,Cameron M. Callbeck,Shanyun Wang,Liping Jiang,Asheesh Kumar Yadav,Jan Vymazal,Mike S. M. Jetten,Ganlin Zhang,Yongguan Zhu,

《工程（英文）》 doi: 10.1016/j.eng.2023.09.013

摘要： The availability of nitrogen (N) is crucial for both the productivity of terrestrial and aquatic ecosystems globally. However, the overuse of artificial fertilizers and the energy required to fix nitrogen have pushed the global nitrogen cycle (N-cycle) past its safe operating limits, leading to severe nitrogen pollution and the production of significant amounts of greenhouse gas nitrous oxide (N2O). The anaerobic ammonium oxidation (anammox) mechanism can counteract the release of ammonium and N2O in many oxygen-limited situations, assisting in the restoration of the homeostasis of the Earth’s N biogeochemistry. In this work, we looked into the characteristics of the anammox hotspots’ distribution across various types of ecosystems worldwide. Anammox hotspots are present at diverse oxic–anoxic interfaces in terrestrial systems, and they are most prevalent at the oxic–anoxic transition zone in aquatic ecosystems. Based on the discovery of an anammox hotspot capable of oxidizing ammonium anoxically into N2 without N2O by-product, we then designed an innovative concept and technical routes of nature-based anammox hotspot geoengineering for climate change, biodiversity loss, and efficient utilization of water resources. After 15 years of actual use, anammox hotspot geoengineering has proven to be effective in ensuring clean drinking water, regulating the climate, fostering plant and animal diversity, and enhancing long-term environmental quality. The sustainable biogeoengineering of anammox could be a workable natural remedy to resolve the conflicts between environmental pollution and food security connected to N management.

关键词： biogeochemical N-cycle     oxic–anoxic interface     nature-based solution     biogeoengineering     nitrogen sustainable development    

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用于器官芯片的工程化血管系统 Review

Abdellah Aazmi, 周竑钊, 李雨亭, 俞梦飞, 许晓斌, 吴钰桐, 马梁, 张斌, 杨华勇

《工程（英文）》 2022年 第9卷 第2期   页码 131-147 doi: 10.1016/j.eng.2021.06.020

摘要：

器官芯片技术是一种很有前途的三维（3D）动态培养方法，可确保准确高效的细胞培养，在临床前试验中具有替代动物模型的巨大潜力。血管系统是人体内最丰富的器官，在氧气交换和物质传递中起着至关重要的作用，是组织器官生存的决定性因素。因此，必须将血管系统集成到器官芯片中，以重建组织和器官微环境及其生理功能。本文讨论了血管与新兴器官芯片技术之间的协同作用，为复现生理学和疾病特征提供了更好的可能性。此外，回顾了血管化的器官芯片制造过程的不同步骤，包括使用不同生物制造策略的结构制造和组织构建。最后，概述了这项技术在器官和肿瘤培养这个有极具吸引力且快速发展的领域的适用性。

关键词： 器官芯片     血管     生物打印     肿瘤芯片    

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A literature review of perishable medical resource management

《工程管理前沿（英文）》   页码 710-726 doi: 10.1007/s42524-023-0278-9

摘要： In recent decades, healthcare providers have faced mounting pressure to effectively manage highly perishable and limited medical resources. This article offers a comprehensive review of supply chain management pertaining to such resources, which include transplantable organs and healthcare products. The review encompasses 93 publications from 1990 to 2022, illustrating a discernible upward trajectory in annual publications. The surveyed literature is categorized into three levels: Strategic, tactical, and operational. Key problem attributes and methodologies are analyzed through the assessment of pertinent publications for each problem level. Furthermore, research on service innovation, decision analytics, and supply chain resilience elucidates potential areas for future research.

关键词： perishable medical resources     organ transplant     healthcare products     decision analytics     operations management    

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ECRG4: a new potential target in precision medicine

Xin Qin, Ping Zhang

《医学前沿（英文）》 2019年 第13卷 第5期   页码 540-546 doi: 10.1007/s11684-018-0637-9

摘要： Given the rapid development in precision medicine, tremendous efforts have been devoted to discovering new biomarkers for disease diagnosis and treatment. Esophageal cancer-related gene-4 ( ), which is initially known as a new candidate tumor suppressor gene, is emerging as a sentinel molecule for gauging tissue homeostasis. ECRG4 is unique in its cytokine-like functional pattern and epigenetically-regulated gene expression pattern. The gene can be released from the cell membrane upon activation and detected in liquid biopsy, thus offering considerable potential in precision medicine. This review provides an updated summary on the biology of ECRG4, with emphasis on its important roles in cancer diagnosis and therapy. The future perspectives of ECRG4 as a potential molecular marker in precision medicine are also discussed in detail.

关键词： ECRG4     tumor suppressor gene     sentinel molecule     precision medicine     cell senescence     epithelium homeostasis    

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Piezoelectric pump with flexible venous valves for active cell transmission

《机械工程前沿（英文）》 2022年 第17卷 第4期 doi: 10.1007/s11465-022-0712-4

摘要： The development of organ-on-a-chip systems demands high requirements for adequate micro-pump performance, which needs excellent performance and effective transport of active cells. In this study, we designed a piezoelectric pump with a flexible venous valve inspired by that of humans. Performance test of the proposed pump with deionized water as the transmission medium shows a maximum output flow rate of 14.95 mL/min when the input voltage is 100 V, and the pump can transfer aqueous solutions of glycerol with a viscosity of 10.8 mPa·s. Cell survival rate can reach 97.22% with a yeast cell culture solution as the transmission medium. A computational model of the electric-solid-liquid multi-physical field coupling of the piezoelectric pump with a flexible venous valve is established, and simulation results are consistent with experimental results. The proposed pump can help to construct the circulating organ-on-a-chip system, and the simple structure and portable application can enrich the design of microfluidic systems. In addition, the multi-physical field coupling computational model established for the proposed piezoelectric pump can provide an in-depth study of the characteristics of the flow field, facilitating the optimal design of the micro-pump and providing a reference for the further study of active cell transport in organ-on-a-chip systems.

关键词： venous valve     flexible venous valve     cell transmission     organ-on-a-chip system     piezoelectric device    

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The relevance of James Lovelock’s research and philosophy to environmental science and academia

《环境科学与工程前沿（英文）》 2023年 第17卷 第3期 doi: 10.1007/s11783-023-1639-7

摘要： James E. Lovelock, famed for his Gaia hypothesis, which views the Earth as a living integrated and interconnected self-regulating system whose equilibrium comes about from complex energy-based interactions and feedback loops, ultimately sustaining life, passed away at the end of July, 2022 at the age of 103. Not only are the adaptive mechanisms of Gaia central to the conversation of environmental homeostasis, they lie at the heart of climate change and global warming. Lovelock is also remembered as the co-inventor of the electron capture detector that eventually allowed for the sensitive detection of chlorofluorocarbons and pesticides. Finally, Lovelock’s free-spirited nature and research independence allow academia to rethink current research’s modus operandi.

关键词： Academic independence     Climate change     Electron capture detector     Environmental equilibrium     Global warming     Homeostasis    

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标题 作者 时间 类型 操作

Emerging roles of podoplanin in vascular development and homeostasis

null

期刊论文

Paradoxical role of Id proteins in regulating tumorigenic potential of lymphoid cells

null

期刊论文

Clinical characteristics and prognostic factors of patients with mature T-cell lymphoid malignancies:

null

期刊论文

Toll-like receptor signaling in hematopoietic homeostasis and the pathogenesis of hematologic diseases

null

期刊论文

Zinc homeostasis in the metabolic syndrome and diabetes

null

期刊论文

post-transplantation cyclophosphamide for allogeneic peripheral stem cell transplantation for adult patients with lymphoid

Ling Wang, Lining Wang, Xing Fan, Wei Tang, Jiong Hu

期刊论文

Low-carbohydrate diets lead to greater weight loss and better glucose homeostasis than exercise: a randomized

期刊论文

alleviates myocardial diastolic dysfunction by modulating Drp1-mediated mitochondrial fission and Ca homeostasis

期刊论文

Zfyve16 regulates the proliferation of B-lymphoid cells

Xuemei Zhao, Donghe Li, Qingsong Qiu, Bo Jiao, Ruihong Zhang, Ping Liu, Ruibao Ren

期刊论文

Planetary Homeostasis of Reactive Nitrogen Through Anaerobic Ammonium Oxidation

Guibing Zhu,Bangrui Lan,Shuci Liu,Cameron M. Callbeck,Shanyun Wang,Liping Jiang,Asheesh Kumar Yadav,Jan Vymazal,Mike S. M. Jetten,Ganlin Zhang,Yongguan Zhu,

期刊论文

用于器官芯片的工程化血管系统

Abdellah Aazmi, 周竑钊, 李雨亭, 俞梦飞, 许晓斌, 吴钰桐, 马梁, 张斌, 杨华勇

期刊论文

A literature review of perishable medical resource management

期刊论文

ECRG4: a new potential target in precision medicine

Xin Qin, Ping Zhang

期刊论文

Piezoelectric pump with flexible venous valves for active cell transmission

期刊论文

The relevance of James Lovelock’s research and philosophy to environmental science and academia

期刊论文