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Integrated analysis of gut microbiome and host immune responses in COVID-19

《医学前沿（英文）》 2022年第16卷第2期页码 263-275 doi: 10.1007/s11684-022-0921-6

摘要： Emerging evidence indicates that the gut microbiome contributes to the host immune response to infectious diseases. Here, to explore the role of the gut microbiome in the host immune responses in COVID-19, we conducted shotgun metagenomic sequencing and immune profiling of 14 severe/critical and 24 mild/moderate COVID-19 cases as well as 31 healthy control samples. We found that the diversity of the gut microbiome was reduced in severe/critical COVID-19 cases compared to mild/moderate ones. We identified the abundance of some gut microbes altered post-SARS-CoV-2 infection and related to disease severity, such as Enterococcus faecium, Coprococcus comes, Roseburia intestinalis, Akkermansia muciniphila, Bacteroides cellulosilyticus and Blautia obeum. We further analyzed the correlation between the abundance of gut microbes and host responses, and obtained a correlation map between clinical features of COVID-19 and 16 severity-related gut microbe, including Coprococcus comes that was positively correlated with CD3⁺/CD4⁺/CD8⁺ lymphocyte counts. In addition, an integrative analysis of gut microbiome and the transcriptome of peripheral blood mononuclear cells (PBMCs) showed that genes related to viral transcription and apoptosis were up-regulated in Coprococcus comes low samples. Moreover, a number of metabolic pathways in gut microbes were also found to be differentially enriched in severe/critical or mild/moderate COVID-19 cases, including the superpathways of polyamine biosynthesis II and sulfur oxidation that were suppressed in severe/critical COVID-19. Together, our study highlighted a potential regulatory role of severity related gut microbes in the immune response of host.

关键词： COVID-19 SARS-COV-2 gut microbiome immune response

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Innate immune responses in RNA viral infection

Qian Xu, Yuting Tang, Gang Huang

《医学前沿（英文）》 2021年第15卷第3期页码 333-346 doi: 10.1007/s11684-020-0776-7

摘要： RNA viruses cause a multitude of human diseases, including several pandemic events in the past century. Upon viral invasion, the innate immune system responds rapidly and plays a key role in activating the adaptive immune system. In the innate immune system, the interactions between pathogen-associated molecular patterns and host pattern recognition receptors activate multiple signaling pathways in immune cells and induce the production of pro-inflammatory cytokines and interferons to elicit antiviral responses. Macrophages, dendritic cells, and natural killer cells are the principal innate immune components that exert antiviral activities. In this review, the current understanding of innate immunity contributing to the restriction of RNA viral infections was briefly summarized. Besides the main role of immune cells in combating viral infection, the intercellular transfer of pathogen and host-derived materials and their epigenetic and metabolic interactions associated with innate immunity was discussed. This knowledge provides an enhanced understanding of the innate immune response to RNA viral infections in general and aids in the preparation for the existing and next emerging viral infections.

关键词： innate immune viral infection intercellular signaling metabolic changes epigenetic changes

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Critical roles of chemokines and cytokines in antiviral innate immune responses during rabies virus infection

Ying HUANG, Clement Wesley GNANADURAI, Zhenfang FU

《农业科学与工程前沿（英文）》 2017年第4卷第3期页码 260-267 doi: 10.15302/J-FASE-2016116

摘要： The innate immune response is the first line of defense against viral invasion and pro-inflammatory chemokines and cytokines have a critical function in the innate immune responses against virus infections. The ability of a rabies virus (RABV) to induce the expression of chemokines and cytokines can lead to viral clearance from the central nervous system (CNS), whereas the ability to evade such expression and activation contributes to virulence and pathogenicity. In this review, the crucial contribution of chemokines/cytokines to clearing RABV from the CNS is discussed, including recruiting leukocytes into the CNS, enhancement of blood brain barrier permeability and activation of various immune cells that are essential for viral clearance. In addition, recombinant RABV expressing cytokines and chemokines can induce elevated innate and adaptive immune responses which result in clearing an established wild-type RABV infection in the CNS.

关键词： antiviral blood brain barrier chemokines and cytokines innate immunity rabies virus

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Decitabine induces -mediated immune responses in p53-mutated triple-negative breast cancer: a clinical

《医学前沿（英文）》 doi: 10.1007/s11684-023-1016-8

摘要： p53 is mutated in half of cancer cases. However, no p53-targeting drugs have been approved. Here, we reposition decitabine for triple-negative breast cancer (TNBC), a subtype with frequent p53 mutations and extremely poor prognosis. In a retrospective study on tissue microarrays with 132 TNBC cases, DNMT1 overexpression was associated with p53 mutations (P = 0.037) and poor overall survival (OS) (P = 0.010). In a prospective DEciTabinE and Carboplatin in TNBC (DETECT) trial (NCT03295552), decitabine with carboplatin produced an objective response rate (ORR) of 42% in 12 patients with stage IV TNBC. Among the 9 trialed patients with available TP53 sequencing results, the 6 patients with p53 mutations had higher ORR (3/6 vs. 0/3) and better OS (16.0 vs. 4.0 months) than the patients with wild-type p53. In a mechanistic study, isogenic TNBC cell lines harboring DETECT-derived p53 mutations exhibited higher DNMT1 expression and decitabine sensitivity than the cell line with wild-type p53. In the DETECT trial, decitabine induced strong immune responses featuring the striking upregulation of the innate immune player IRF7 in the p53-mutated TNBC cell line (upregulation by 16-fold) and the most responsive patient with TNBC. Our integrative studies reveal the potential of repurposing decitabine for the treatment of p53-mutated TNBC and suggest IRF7 as a potential biomarker for decitabine-based treatments.

关键词： p53 mutation triple-negative breast cancer decitabine DNMT1 IRF7 innate immune response

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Anti-biofouling strategies for implantable biosensors of continuous glucose monitoring systems

《化学科学与工程前沿（英文）》 2023年第17卷第12期页码 1866-1878 doi: 10.1007/s11705-023-2340-x

摘要： Continuous glucose monitoring (CGM) systems play an increasingly vital role in the glycemic control of patients with diabetes mellitus. However, the immune responses triggered by the implantation of poorly biocompatible sensors have a significant impact on the accuracy and lifetime of CGM systems. In this review, research efforts over the past few years to mitigate the immune responses by enhancing the anti-biofouling ability of sensors are summarized. This review divided these works into active immune engaging strategy and passive immune escape strategy based on their respective mechanisms. In each strategy, the various biocompatible layers on the biosensor surface, such as drug-releasing membranes, hydrogels, hydrophilic membranes, anti-biofouling membranes based on zwitterionic polymers, and bio-mimicking membranes, are described in detail. This review, therefore, provides researchers working on implantable biosensors for CGM systems with vital information, which is likely to aid in the research and development of novel CGM systems with profound anti-biofouling properties.

关键词： implantable glucose biosensor anti-biofouling continuous glucose monitoring immune responses

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Advances on immune-related adverse events associated with immune checkpoint inhibitors

Yong Fan, Yan Geng, Lin Shen, Zhuoli Zhang

《医学前沿（英文）》 2021年第15卷第1期页码 33-42 doi: 10.1007/s11684-019-0735-3

摘要： Immunotherapy has recently led to a paradigm shift in cancer therapy, in which immune checkpoint inhibitors (ICIs) are the most successful agents approved for multiple advanced malignancies. However, given the nature of the non-specific activation of effector T cells, ICIs are remarkably associated with a substantial risk of immune-related adverse events (irAEs) in almost all organs or systems. Up to 90% of patients who received ICIs combination therapy experienced irAEs, of which majority were low-grade toxicity. Cytotoxic lymphocyte antigen-4 and programmed cell death protein-1/programmed cell death ligand 1 inhibitors usually display distinct features of irAEs. In this review, the mechanisms of action of ICIs and how they may cause irAEs are described. Some unsolved challenges, however really engrossing issues, such as the association between irAEs and cancer treatment response, tumor response to irAEs therapy, and ICIs in challenging populations, are comprehensively summarized.

关键词： cancer immunotherapy immune checkpoint inhibitors immune-related adverse events review

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Natural killer cells in liver diseases

null

《医学前沿（英文）》 2018年第12卷第3期页码 269-279 doi: 10.1007/s11684-018-0621-4

摘要：

The liver has been characterized as a frontline lymphoid organ with complex immunological features such as liver immunity and liver tolerance. Liver tolerance plays an important role in liver diseases including acute inflammation, chronic infection, autoimmune disease, and tumors. The liver contains a large proportion of natural killer (NK) cells, which exhibit heterogeneity in phenotypic and functional characteristics. NK cell activation, well known for its role in the immune surveillance against tumor and pathogen-infected cells, depends on the balance between numerous activating and inhibitory signals. In addition to the innate direct “killer” functions, NK cell activity contributes to regulate innate and adaptive immunity (helper or regulator). Under the setting of liver diseases, NK cells are of great importance for stimulating or inhibiting immune responses, leading to either immune activation or immune tolerance. Here, we focus on the relationship between NK cell biology, such as their phenotypic features and functional diversity, and liver diseases.

关键词： natural killer cell phenotype immune activation immune tolerance liver diseases

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SUPEROXIDE DISMUTASE FAMILY GENES IN WATERMELON AND THEIR RESPONSES TO DIFFERENT ABIOTIC STRESSES

《农业科学与工程前沿（英文）》 2021年第8卷第4期页码 645-658 doi: 10.15302/J-FASE -2020350

摘要：

Superoxide dismutase (SOD) is an important enzyme in the antioxidant system of plants and plays a vital role in stress responses by maintaining the dynamic balance of reactive oxygen species (ROS) concentrations. Genome-wide analysis of the SOD gene family in various plant species has been conducted but little is known about this gene family in watermelon (Citrullus lanatus). Here, eight SOD genes were identified in the watermelon genome and are designated ClCSD1-5, ClFSD1-2 and ClMSD according to their metal cofactors. Phylogenetic analysis shows that SOD proteins from various plant species can be classified into five groups and members in the same group possess the same metal cofactor and similar subcellular localizations. Expression analysis of the ClSOD genes indicates that they had tissue-specific expression patterns with high expression in different tissues including the leaves, flowers and fruit. In addition, the expression of ClSOD genes differed appreciably under salinity, drought and abscisic acid (ABA) treatments, indicating that they may be involved in ROS scavenging under different abiotic stresses via an ABA-dependent signaling pathway. These results lay the foundation for elucidating the function of ClSOD genes in stress tolerance and fruit development in watermelon.

关键词： abiotic stress / expression analysis / phylogeny / SOD / superoxide dismutase / watermelon

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Persistence of humoral and cellular immune response after SARS-CoV-2 infection: opportunities and challenges

Tangchun Wu

《医学前沿（英文）》 2020年第14卷第6期页码 816-819 doi: 10.1007/s11684-020-0823-4

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Heterogeneity of the tumor immune microenvironment and clinical interventions

《医学前沿（英文）》 2023年第17卷第4期页码 617-648 doi: 10.1007/s11684-023-1015-9

摘要： Heterogeneity of the tumor immune microenvironment and clinical interventions

关键词： Heterogeneity tumor immune

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重组治疗性乙型肝炎疫苗（YIC）的实验研究

闻玉梅,何丽芳,瞿涤,马张妹,姚忻

《中国工程科学》 1999年第1卷第1期页码 38-42

摘要：

研制了抗原-抗体复合物型乙肝治疗性疫苗。用小鼠实验证明这一治疗性疫苗的作用机理为：通过复合物中抗体Fc段与抗原呈递细胞表面的Fc受体结合，促进了细胞摄取抗原。复合物中的抗原经呈递后可比单纯抗原更有效地激活T细胞增殖，释放更多的γ-干扰素和白细胞介素-2，属TH1类型应答。复合物可在小鼠中诱生较单纯抗原诱生的抗-HBs高10倍以上。复合物还可诱生更强的细胞免疫，表现为经特异的抗原刺激后，γ-干扰素的mRNA量增多。还发现复合物可在对HBsAg低应答鼠系中（B 10.S）诱生与正常应答鼠相当的抗体效价。在HBsAg阳性转基因鼠中，复合物可使部分鼠的HBsAg转为阴性，并可产生抗-HBs，反映这一疫苗具有疗效。为制备人用乙肝治疗性疫苗建立了用重组酵母菌表达的HBsAg与人高效价抗乙肝免疫球蛋白组建治疗性疫苗的工艺，以及产品标化及效力的参比实验技术。

关键词：乙型肝炎治疗性疫苗抗原抗体复合物免疫应答

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Molecular classification and precision therapy of cancer: immune checkpoint inhibitors

null

《医学前沿（英文）》 2018年第12卷第2期页码 229-235 doi: 10.1007/s11684-017-0581-0

摘要：

On May 23, 2017, the US Food and Drug Administration (FDA) approved a treatment for cancer patients with positive microsatellite instability-high (MSI-H) markers or mismatch repair deficient (dMMR) markers. This approach is the first approved tumor treatment using a common biomarker rather than specified tumor locations in the body. FDA previously approved Keytruda for treatment of several types of malignancies, such as metastatic melanoma, metastatic non-small-cell lung cancer, recurrent or metastatic head and neck cancer, refractory Hodgkin lymphoma, and urothelial carcinoma, all of which carry positive programmed death-1/programmed death-ligand 1 biomarkers. Therefore, indications of Keytruda significantly expanded. Several types of malignancies are disclosed by MSI-H status due to dMMR and characterized by increased neoantigen load, which elicits intense host immune response in tumor microenvironment, including portions of colorectal and gastric carcinomas. Currently, biomarker-based patient selection remains a challenge. Pathologists play important roles in evaluating histology and biomarker results and establishing detection methods. Taking gastric cancer as an example, its molecular classification is built on genome abnormalities, but it lacks acceptable clinical characteristics. Pathologists are expected to act as “genetic interpreters” or “genetic translators” and build a link between molecular subtypes with tumor histological features. Subsequently, by using their findings, oncologists will carry out targeted therapy based on molecular classification.

关键词： molecular classification precision medicine pembrolizumab PD-1/PD-L1 MSI-H

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Microbial responses to the use of NaClO in sediment treatment

《环境科学与工程前沿（英文）》 2022年第16卷第2期 doi: 10.1007/s11783-021-1451-1

摘要：

• Chlorine addition enhanced the release of TOC, TN from the sediment.

关键词： Sediment chlorination Substance mobility Microbial response Community composition Function

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The critical role of autophagy in plant responses to abiotic stresses

Yu WANG,Jie ZHOU,Jingquan YU

《农业科学与工程前沿（英文）》 2017年第4卷第1期页码 28-36 doi: 10.15302/J-FASE-2017130

摘要： Autophagy is an evolutionary conserved recycling process in eukaryotes whereby intracellular components are engulfed by autophagosomes, which are subsequently transferred to the vacuoles for further degradation and reuse. In organisms like yeast and metazoans, autophagy is actively engaged during environmental perturbation either by degrading denatured proteins and organelles or by interfacing with stress related signaling molecules. Studies over the last decade have also revealed numerous important mechanisms where autophagy is widely involved in plant abiotic stress responses. Autophagy serves as a pivotal route for nutrient remobilization by the degradation of superfluous or damaged cellular cytoplasmic material and organelles. It is also reported to regulate the accumulation of reactive oxygen species, to maintain the cellular redox balance of plants under stressful conditions. Furthermore, autophagy is essential in regulating cellular toxicity by removing aggregated and/or denatured proteins and thereby improving plant stress tolerance. In this review, recent advances in our understanding of autophagy, along with pathways and regulatory networks through which it influences many aspects of plant growth and development in response to nutrient starvation, oxidative stress, osmotic stress and extreme temperatures are discussed.

关键词： abiotic stresses autophagy extreme temperature nutrient starvation osmotic stress oxidative stress

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Hyperthermia on skin immune system and its application in the treatment of human papillomavirus-infected

null

《医学前沿（英文）》 2014年第8卷第1期页码 1-5 doi: 10.1007/s11684-014-0309-3

摘要：

Hyperthermia is a condition characterized by increased body temperature as a consequence of failed thermoregulation. Hyperthermia occurs when a body produces or absorbs more heat than it dissipates. Hyperthermia also elicits various effects on the physiology of living cells. For instance, fever-range temperature (39β°C to 40β°C) can modulate the activities of immune cells, including antigen-presenting cells, T cells, and natural killer cells. Heat shock temperature (41β°C to 43β°C) can increase the immunogenicity of tumor cells. Cytotoxic temperature (>43β°C) can create an antigen source to induce an anti-tumor immune response. The immunomodulatory effect of hyperthermia has promoted an interest in hyperthermia-aided immunotherapy, particularly against tumors. Hyperthermia has also been used to treat deep fungal, bacterial, and viral skin infections. We conducted a series of open or controlled trials to treat skin human papillomavirus infection by inducing local hyperthermia. More than half of the patients were significantly cured compared with those in the control trial. A series of challenging clinical cases, such as large lesions in pregnant patients or patients with diabetes mellitus, were also successfully and safely managed using the proposed method. However, further studies should be conducted to clarify the underlying mechanisms and promote the clinical applications of hyperthermia.

关键词： hyperthermia HPV immune response virus tumor