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Cytokine storm and translating IL-6 biology into effective treatments for COVID-19

《医学前沿（英文）》 doi: 10.1007/s11684-023-1044-4

摘要： As of May 3, 2023, the coronavirus disease 2019 (COVID-19) pandemic has resulted in more than 760 million confirmed cases and over 6.9 million deaths. Several patients have developed pneumonia, which can deteriorate into acute respiratory distress syndrome. The primary etiology may be attributed to cytokine storm, which is triggered by the excessive release of proinflammatory cytokines and subsequently leads to immune dysregulation. Considering that high levels of interleukin-6 (IL-6) have been detected in several highly pathogenic coronavirus-infected diseases, such as severe acute respiratory syndrome in 2002, the Middle East respiratory syndrome in 2012, and COVID-19, the IL-6 pathway has emerged as a key in the pathogenesis of this hyperinflammatory state. Thus, we review the history of cytokine storm and the process of targeting IL-6 signaling to elucidate the pivotal role played by tocilizumab in combating COVID-19.

关键词： SARS-CoV-2     COVID-19     cytokine storm     interleukin-6     tocilizumab    

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Keratin 5-Cre-driven deletion of

Jun Yang, Lianqing Wang, Yingzhi Huang, Keqiang Liu, Chaoxia Lu, Nuo Si, Rongrong Wang, Yaping Liu, Xue Zhang

《医学前沿（英文）》 2020年 第14卷 第3期   页码 305-317 doi: 10.1007/s11684-019-0722-8

摘要： Familial acne inversa (AI) is an autoinflammatory disorder that affects hair follicles and is caused by loss-of-function mutations in -secretase component genes. We and other researchers showed that ( ) is the most frequently mutated gene in familial AI. In this study, we generated a keratin 5-Cre-driven epidermis-specific conditional knockout mutant in mice. We determined that this mutant recapitulated the major phenotypes of AI, including hyperkeratosis of hair follicles and inflammation. In mice, the IL-36a expression level markedly increased starting from postnatal day 0 (P0), and this increase occurred much earlier than those of TNF- , IL-23A, IL-1 and TLR4. RNA-Seq analysis indicated that Sprr2d, a member of the small proline-rich protein 2 family, in the skin tissues of the mice was also upregulated on P0. Quantitative reverse-transcription polymerase chain reaction showed that other genes had a similar expression pattern. Our findings suggested that IL-36a might be a key inflammatory cytokine in the pathophysiology of AI and involved in the malfunction of the skin barrier in the pathogenesis of AI.

关键词： acne inversa mouse model     interleukin 1 family     member 6     small proline rich protein 2D     key inflammatory cytokine    

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Beneficial metabolic activities of inflammatory cytokine interleukin 15 in obesity and type 2 diabetes

null

《医学前沿（英文）》 2015年 第9卷 第2期   页码 139-145 doi: 10.1007/s11684-015-0377-z

摘要：

In obesity, chronic inflammation is believed to induce insulin resistance and impairs adipose tissue function. Although this view is supported by a large body of literature, it has been challenged by growing evidence that pro-inflammatory cytokines may favor insulin sensitivity through induction of energy expenditure. In this review article, interleukin 15 (IL-15) is used as a new example to explain the beneficial effects of the pro-inflammatory cytokines. IL-15 is secreted by multiple types of cells including macrophages, neutrophils and skeletal muscle cells. IL-15 expression is induced in immune cells by endotoxin and in muscle cells by physical exercise. Its transcription is induced by transcription factor NF-κB. IL-15 binds to its receptor that contains three different subunits (α, β and γ) to activate JAK/STAT, PI3K/Akt, IKK/NF-κB and JNK/AP1 pathways in cells. In the regulation of metabolism, IL-15 reduces weight gain without inhibiting food intake in rodents. IL-15 suppresses lipogenesis, stimulates brown fat function, improves insulin sensitivity through weight loss and energy expenditure. In human, circulating IL-15 is negatively associated with body weight. In the immune system, IL-15 stimulates proliferation and differentiation of T cells, NK cells, monocytes and neutrophils. In the anti-obesity effects of IL-15, T cells and NK cells are not required, but leptin receptor is required. In summary, evidence from human and rodents supports that the pro-inflammatory cytokine IL-15 may enhance energy expenditure to protect the body from obesity and type 2 diabetes. The mechanism of IL-15 action remains to be fully uncovered in the regulation of energy expenditure.

关键词： inflammation     obesity     cytokine     energy expenditure     insulin resistance    

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murine pancreatic carcinoma by β-elemene combined with dendritic cells modified with genes encoding interleukin

TAN Guang, WANG Zhongyu, CHE Luanqing, YIN Shuo

《医学前沿（英文）》 2007年 第1卷 第1期   页码 41-45 doi: 10.1007/s11684-007-0008-4

摘要： The dendritic cell vaccine is a treatment vaccine with potent clinical applications. Functional cytokines can enhance dendritic cell anti-tumor immune responses. This experiment was conducted to study the effects of bone marrow-deriv

关键词： Functional     experiment     anti-tumor     dendritic     clinical    

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微波辐射下离子液体［RMIm］PF6（R=P, B, C6）的合成及其电导率研究

何永福

《中国工程科学》 2008年 第10卷 第9期   页码 92-95

摘要： 1－溴己烷)在80 ℃回流加热10 min，可制得咪唑类离子液体的中间体溴代1－丁基－3－甲基咪唑（［BMIm］Br）、溴代1－丙基－3－甲基咪唑（［PMIm］Br）、溴代1－己基－3－甲基咪唑（［C6MIm］Br），进一步与HPF6在室温搅拌反应4 h，制得憎水性的咪唑类离子液体［BMIm］PF6，［PMIm］PF6和［C6MIm］PF6。

关键词： 离子液体     微波辐射     电导率     [BMIm]PF6     [PMIm]PF6     [C6MIm]PF6    

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FERM domain-containing protein FRMD6 activates the mTOR signaling pathway and promotes lung cancer progression

《医学前沿（英文）》 2023年 第17卷 第4期   页码 714-728 doi: 10.1007/s11684-022-0959-5

摘要： FRMD6, a member of the 4.1 ezrin–radixin–moesin domain-containing protein family, has been reported to inhibit tumor progression in multiple cancers. Here, we demonstrate the involvement of FRMD6 in lung cancer progression. We find that FRMD6 is overexpressed in lung cancer tissues relative to in normal lung tissues. In addition, the enhanced expression of FRMD6 is associated with poor outcomes in patients with lung squamous cell carcinoma (n = 75, P = 0.0054) and lung adenocarcinoma (n = 94, P = 0.0330). Cell migration and proliferation in vitro and tumor formation in vivo are promoted by FRMD6 but are suppressed by the depletion of FRMD6. Mechanistically, FRMD6 interacts and colocalizes with mTOR and S6K, which are the key molecules of the mTOR signaling pathway. FRMD6 markedly enhances the interaction between mTOR and S6K, subsequently increasing the levels of endogenous pS6K and downstream pS6 in lung cancer cells. Furthermore, knocking out FRMD6 inhibits the activation of the mTOR signaling pathway in Frmd6−/− gene KO MEFs and mice. Altogether, our results show that FRMD6 contributes to lung cancer progression by activating the mTOR signaling pathway.

关键词： FRMD6     lung cancer     mTOR pathway    

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Association of miRNA-122-binding site polymorphism at the interleukin-1 α gene and its interaction with

null

《医学前沿（英文）》 2014年 第8卷 第2期   页码 217-226 doi: 10.1007/s11684-014-0326-2

摘要：

This study was designed to investigate the contribution of miRNA-122-binding site polymorphism at the IL-1A gene and its multiplicative interactions with hepatitis B virus (HBV) mutations in the risk of hepatocellular carcinoma (HCC). A total of 1021 healthy controls, 302 HBV surface antigen (HBsAg) seroclearance subjects, and 2011 HBsAg-positive subjects (including 1021 HCC patients) were enrolled in this study. Quantitative PCR was used to genotype rs3783553. HBV mutations were determined by direct sequencing. Multivariate logistic regression analyses were performed to test the associations of rs3783553, mutations, and their interactions with the risk of HCC. No significant association was found between rs3783553 and the risk of HCC among healthy controls, HBsAg seroclearance subjects, HBsAg-positive subjects without HCC, and all controls. Additionally, rs3783553 was not significantly associated with chronic HBV infection, liver cirrhosis, HBV e antigen seroconversion, abnormal alanine aminotransferase, and high viral load (>104 copies/ml). However, the TTCA insertion allele of rs3783553 was significantly associated with an increased frequency of HBV C7A mutation compared with homozygous TTCA deletion carriers [(del/ins+ ins/ins) vs. del/del, adjusted odds ratio (OR)=1.48, 95% confidence interval (CI)=1.09-2.02, P=0.013]. Multiplicative interaction of rs3783553 with HBV preS deletion significantly reduced the risk of HCC in males, with an adjusted OR of 0.64 (95% CI=0.42-0.98; P=0.041) after age and HBV genotype were adjusted. Although rs3783553 did not significantly affect genetic susceptibility to HBV-related HCC, its variant allele may predispose the host to selecting HBV C7A mutation during evolution and significantly reduce the risk of HCC caused by HBV preS deletion. This study provides an insight into the complex host-virus interaction in HBV-induced hepatocarcinogenesis and is helpful in determining HBsAg-positive subjects who are likely to develop HCC.

关键词： hepatocellular carcinoma (HCC)     interaction     miRNA-122-binding site     IL-1A     rs3783553     hepatitis B virus (HBV) mutations    

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RNA m6A modification and its function in diseases

null

《医学前沿（英文）》 2018年 第12卷 第4期   页码 481-489 doi: 10.1007/s11684-018-0654-8

摘要：

N6-methyladenosine (m6A) is the most common post-transcriptional RNA modification throughout the transcriptome, affecting fundamental aspects of RNA metabolism. m6A modification could be installed by m6A “writers” composed of core catalytic components (METTL3/METTL14/WTAP) and newly defined regulators and removed by m6A “erasers” (FTO and ALKBH5). The function of m6A is executed by m6A “readers” that bind to m6A directly (YTH domain-containing proteins, eIF3 and IGF2BPs) or indirectly (HNRNPA2B1). In the past few years, advances in m6A modulators (“writers,” “erasers,” and “readers”) have remarkably renewed our understanding of the function and regulation of m6A in different cells under normal or disease conditions. However, the mechanism and the regulatory network of m6A are still largely unknown. Moreover, investigations of the m6A physiological roles in human diseases are limited. In this review, we summarize the recent advances in m6A research and highlight the functional relevance and importance of m6A modification in in vitro cell lines, in physiological contexts, and in cancers.

关键词： RNA modification     m6A     immunity     cancer     epigenetics    

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Antibacterial and anti-flaming PA6 composite with metathetically prepared nano AgCl@BaSO

Wei Zhang, Boren Xu, Caihong Gong, Chunwang Yi, Shen Zhang

《化学科学与工程前沿（英文）》 2021年 第15卷 第2期   页码 340-350 doi: 10.1007/s11705-020-1942-9

摘要： In this study, a facile and environmentally friendly method with low energy consumption for preparing nanoscale AgCl and BaSO co-precipitates (AgCl@BaSO co-precipitates) was developed based on the metathetical reaction. Then, the dried co-precipitates were melt-compounded with polyamide 6 (PA6) resins at a specified mass ratio in a twin-screw extruder. The results demonstrated that in the absence of any coating agent or carrier, the nanoparticles of AgCl@BaSO co-precipitates were homogeneously dispersed in the PA6 matrix. Further analysis showed that after the addition of AgCl@BaSO co-precipitates, the antibacterial performance, along with the flame-retardance and anti-dripping characteristics of PA6, was enhanced significantly. In addition, the PA6 composites possessed high spinnability in producing pre-oriented yarn.

关键词： nano AgCl@BaSO4 co-precipitates     antibacterial     flame resistance     PA6 composite     PA6 yarn    

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A systematic survey of LU domain-containing proteins reveals a novel human gene, LY6A, which encodesthe candidate ortholog of mouse Ly-6A/Sca-1 and is aberrantly expressed in pituitary tumors

《医学前沿（英文）》 2023年 第17卷 第3期   页码 458-475 doi: 10.1007/s11684-022-0968-4

摘要： The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon‒intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.

关键词： LU domain-containing protein family     novel human gene     LY6A     pituitary tumor     biomarker     nonsynonymous SNP     GPI-anchored protein    

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A rolling 6U parallel mechanism

Zhihuai MIAO, Yanan YAO

《机械工程前沿（英文）》 2011年 第6卷 第1期   页码 96-98 doi: 10.1007/s11465-011-0214-2

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G protein-coupled receptor LGR6 is an independent risk factor for colon adenocarcinoma

Wenjing Wang, Shigang Ding, Hejun Zhang, Jun Li, Jun Zhan, Hongquan Zhang

《医学前沿（英文）》 2019年 第13卷 第4期   页码 482-491 doi: 10.1007/s11684-018-0633-0

摘要： LGR6 is a member of the G protein-coupled receptor family that plays a tumor-suppressive role in colon cancer. However, the relationship between LGR6 expression in patients and clinicopathological factors remains unclear. This study aimed to clarify whether the expression level of LGR6 is correlated with colon adenocarcinoma progression. Immunohistochemistry was used to detect LGR6 expression in colon adenoma tissues ( = 21), colon adenocarcinoma tissues ( = 156), and adjacent normal tissues ( = 124). The expression levels of LGR6 in colon adenoma and adenocarcinoma were significantly higher than those in normal colon epithelial tissues ( <0.001). Low LGR6 expression predicted a short overall survival in patients with colon adenocarcinoma (log-rank test, = 0.016). Univariate and multivariate survival analyses showed that, in addition to N and M classification, LGR6 expression served as an independent prognostic factor. Thus, low expression of LGR6 can be used as an independent prognostic parameter in patients with colon adenocarcinoma.

关键词： LGR6     colon adenocarcinoma     immunohistochemistry     prognosis    

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Single and joint effects of HHCB and cadmium on zebrafish (

Lei ZHANG, Jing AN, Qixing ZHOU

《环境科学与工程前沿（英文）》 2012年 第6卷 第3期   页码 360-372 doi: 10.1007/s11783-011-0353-z

摘要： As an important type of emerging pollutants, ecological toxicity and risk of artificial musks are increasingly concerned. Thus, single and joint toxic effects of 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8- hexamethylcyclopenta-gamma-2-benzopyran (HHCB) as one of the most widely applied artificial musks and cadmium (Cd) as an toxic metal on zebrafish ( ) were investigated by the exposure of zebrafish to various concentrations of HHCB or/and Cd in feculent water containing bedloads. The results indicated that the joint effect of HHCB and Cd changed during different exposure times within 120 h. The index of the antioxidant enzyme system including superoxide dismutase (SOD) and peroxidase (POD), and malondialdehyde (MDA) were sensitive and induced in the zebrafish stressed by Cd, and content of soluble protein (SP) was sensitive to HHCB and could be used as a biomarker for HHCB. Joint effects on antioxidant enzymes depended more on the effect of single Cd in the first one or two days. However, in the rest exposure days, the effect of HHCB began to dominate in the joint effect during the exposure process.

关键词： 1     3     4     6     7     8-hexahydro-4     6     6     7     8     8-hexamethylcyclopenta-gamma-2-benzopyran (HHCB)     cadmium (Cd)     antioxidant biomarker     feculent water containing bedloads    

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后5G与6G天线系统技术演进与创新 Editorial

Bao-yan DUAN

《信息与电子工程前沿（英文）》 2020年 第21卷 第1期   页码 1-3 doi: 10.1631/FITEE.2010000

摘要： 同时，第六代（6G）移动通信系统已成为备受学术界和工业界瞩目的重要领域，前景广阔。与5G相比，6G可实现更快的接入速率（10～100倍以上）、更低的接入延迟、更广泛深入的通信覆盖以及更优的能量和频谱效率，使得天线和射频（RF）系统的材料、工艺、技术及形式不断演进。在此背景下，中国工程院院刊《信息与电子工程前沿（英文）》（FITEE）特组织并刊发了“后5G与6G天线系统技术演进与创新”专刊。该专刊涵盖天线、无源和有源器件及系统、传播和信道以及材料和算法等方面，频率涵盖6 GHz乃至太赫兹。专刊旨在回顾天线相关技术发展现状，明确未来发展趋势。作为5G技术演进的延续，6G以其高数据速率、低延迟等特点备受关注。张建华等通过分析几种新兴6G技术和应用，阐述了6G信道模型的发展趋势，展望了6G信道测量和建模的未来发展方向。

关键词： None    

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All-inorganic TiO/CsAgBiBr composite as highly efficient photocatalyst under visible light irradiation

《化学科学与工程前沿（英文）》 2023年 第17卷 第12期   页码 1925-1936 doi: 10.1007/s11705-023-2344-6

摘要： In recent years, limited photocatalysis efficiency and wide band gap have hindered the application of TiO2 in the field of photocatalysis. A leading star in photocatalysis has been revealed as lead-free Cs2AgBiBr6 double halide perovskite nanocrystals, owing to its strong visible light absorption and tunable band gap. In this work, this photocatalytic process was facilitated by a unique TiO2/Cs2AgBiBr6 composite, which was identified as an S-cheme heterojunction. TiO2/Cs2AgBiBr6 composite was investigated for its structure and photocatalytic behavior. The results showed that when the perovskite dosage is 40%, the photocatalytic rate of TiO2 could be boosted to 0.1369 min–1. This paper discusses and proposes the band gap matching, carrier separation, and photocatalytic mechanism of TiO2/Cs2AgBiBr6 composites, which will facilitate the generation of new ideas for improving TiO2’s photocatalytic performance.

关键词： Cs2AgBiBr6 nanocrystals     visible-light photocatalyst     Cs2AgBiBr6/TiO2 heterojunction    

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标题 作者 时间 类型 操作

Cytokine storm and translating IL-6 biology into effective treatments for COVID-19

期刊论文

Keratin 5-Cre-driven deletion of

Jun Yang, Lianqing Wang, Yingzhi Huang, Keqiang Liu, Chaoxia Lu, Nuo Si, Rongrong Wang, Yaping Liu, Xue Zhang

期刊论文

Beneficial metabolic activities of inflammatory cytokine interleukin 15 in obesity and type 2 diabetes

null

期刊论文

murine pancreatic carcinoma by β-elemene combined with dendritic cells modified with genes encoding interleukin

TAN Guang, WANG Zhongyu, CHE Luanqing, YIN Shuo

期刊论文

微波辐射下离子液体［RMIm］PF6（R=P, B, C6）的合成及其电导率研究

何永福

期刊论文

FERM domain-containing protein FRMD6 activates the mTOR signaling pathway and promotes lung cancer progression

期刊论文

Association of miRNA-122-binding site polymorphism at the interleukin-1 α gene and its interaction with

null

期刊论文

RNA m6A modification and its function in diseases

null

期刊论文

Antibacterial and anti-flaming PA6 composite with metathetically prepared nano AgCl@BaSO

Wei Zhang, Boren Xu, Caihong Gong, Chunwang Yi, Shen Zhang

期刊论文

A systematic survey of LU domain-containing proteins reveals a novel human gene, LY6A, which encodesthe candidate ortholog of mouse Ly-6A/Sca-1 and is aberrantly expressed in pituitary tumors

期刊论文

A rolling 6U parallel mechanism

Zhihuai MIAO, Yanan YAO

期刊论文

G protein-coupled receptor LGR6 is an independent risk factor for colon adenocarcinoma

Wenjing Wang, Shigang Ding, Hejun Zhang, Jun Li, Jun Zhan, Hongquan Zhang

期刊论文

Single and joint effects of HHCB and cadmium on zebrafish (

Lei ZHANG, Jing AN, Qixing ZHOU

期刊论文

后5G与6G天线系统技术演进与创新

Bao-yan DUAN

期刊论文

All-inorganic TiO/CsAgBiBr composite as highly efficient photocatalyst under visible light irradiation

期刊论文