The MabHLH11 transcription factor interacting with MaMYB4 acts additively in increasing plant scopolin biosynthesis

The plant natural product scopolin,a coumarin secondary metabolite,has been extensively exploited in flavor,cosmetic,medicine,and other industrial fields.Melilotus albus,a leguminous rotation crop,contains high concentrations of coumarin.The transcriptional regulatory network that controls the flow through the scopolin biosynthesis pipeline in M.albus remains poorly understood.MabHLH11 encodes a basic helix–loop–helix(bHLH)transcription factor whose transcription is positively associated with scopolin accumulation and with the expression of MaMYB4,the bHLH partner of the MYB-bHLH complex.Phylogenetic analysis grouped MabHLH11 in the TRANSPARENT TESTA 8(TT8)clade of the bHLH IIIf subgroup.The MabHLH11 protein contained an MYB-interacting region and physically interacted with MaMYB4 in yeast and tobacco leaves.Co-overexpression of MabHLH11 with MaMYB4 in M.albus additively increased the expression of UDP-glucosyltransferase(MaUGT79)and induced more scopolin accumulation than occurred under the expression of MabHLH11 alone.MabHLH11 directly targeted the promoter of MaUGT79 and the activation of MabHLH11 was strengthened by the presence of MaMYB4.Thus,MaMYB4 enhanced the function of MabHLH11 in upregulating scopolin biosynthesis in M.albus,providing a theoretical basis for scalable production of a high-value plant natural product.

甲壳素纳米纤维/碳纳米管复合凝胶膜的制备与性能

将甲壳素纳米纤维与碳纳米管在水性条件下混合,建立甲壳素纳米纤维均匀分散的碳纳米管混合体系;利用真空抽滤制备甲壳素纳米纤维/碳纳米管复合膜,通过20%氢氧化钠低温处理制备具有连续三维纳米网络结构的复合凝胶膜,并对比凝胶化前后样品微观结构、导电性能及电化学性能等。结果表明,凝胶化处理有助于在凝胶膜内部构建三维纳米导电网络,当甲壳素纳米纤维与碳纳米管的质量比为1∶1时,凝胶膜的导电率和质量比电容较复合膜提高了2倍;2000次循环测试后,凝胶膜的比电容量仍能保持为起始比电容量的92.5%,循环稳定性较好。

Assessment of hepatic VX_2 tumors with combined percutaneous transhepatic lymphosonography and contrast-enhanced ultrasonographic imaging

AIM: To evaluate the feasibility and efficacy of per-cutaneous transhepatic lymphosonography (PTL) as a novel method for the detection of tumor lymphan-giogenesis in hepatic VX2 of rabbits and to evaluate combined PTL and routine contrast-enhanced ultraso-nographic imaging for the diagnosis of liver cancer. METHODS: Ten rabbits with VX2 tumor were included in this study. SonoVue (0.1 mL/kg) was injected into each rabbit via an ear vein for contrast-enhanced ul-trasonographic imaging,and 0.5 mL SonoVue was injected into the normal liver parenchyma near the VX2 tumor for PTL. Images and/or movie clips were stored for further analysis. RESULTS: Ultrasonographic imaging showed VX2 tumors ranging 5-19 mm in the liver of rabbits. The VX2 tumor was hyperechoic and hypoechoic to liver parenchyma at the early and later phase,respectively. The hepatic lymph vessels were visualized immediately after injection of contrast medium and continuously vi-sualized with SonoVue during PTL. The boundaries of VX2 tumors were hyperechoic to liver parenchyma and the tumors. There was a signifi cant difference in the values for the boundaries of VX2 tumors after injection compared with the liver normal parenchyma and the tumor parenchyma during PTL.CONCLUSION: PTL is a novel method for the detec-tion of tumor lymphangiogenesis in hepatic VX2 of rabbits. Combined PTL and contrast-enhanced ultraso-nographic imaging can improve the diagnosis of liver cancer.

谷固醇血症的临床特征及生化和基因诊断

目的对谷固醇血症患儿的临床特征及生化和基因检测结果进行分析,以提高临床对该病的认识和诊疗水平。方法对2016年11月至2021年6月,因皮肤黄瘤病伴高胆固醇血症来复旦大学附属儿科医院就诊的4例患儿,回顾其临床特征及常规生化检测结果,并采用气相色谱-质谱联用技术测定患儿血清中的植物固醇谱。采用全外显子测序方法,分析其致病基因,对所发现的ABCG5基因变异,采用Sanger测序方法进一步验证。结果4例患儿中,男性2例,女性2例,年龄为15月龄~10岁6月。患儿关节伸侧面等处皮肤有线样或结节状多发黄色瘤,血总胆固醇均高于正常。4例患儿的菜油固醇为129.83~325.37μmol/L(正常范围0.01~17.96μmol/L),豆固醇为23.54~40.10μmol/L(正常范围0.01~10.25μmol/L),谷固醇为152.49~531.71μmol/L(正常范围0.01~15.44μmol/L)。4例患儿的基因检测结果提示均为ABCG5基因的复合杂合变异,共检出6种不同的变异类型。结论谷固醇血症患儿以关节附近皮肤皱褶处的黄色瘤为主要表现,常规生化提示血胆固醇升高,建议完善血清植物固醇谱分析并结合基因测序,以便尽早饮食指导和药物干预,改善预后。

贞芪扶正胶囊辅助治疗艾滋病作用机制的网络药理学分析及分子对接验证

目的利用网络药理学方法及分子对接技术分析贞芪扶正胶囊辅助治疗艾滋病的分子机制。方法通过TCMSP获取贞芪扶正胶囊组方药物活性成分及作用靶点,通过GeneCards、OMIM及DrugBank数据库获取艾滋病相关靶点;通过STRING 11.5数据库构建交集靶点PPI网络,并采用Cytoscape 3.9.1软件进行网络拓扑分析;采用Metascape数据库对核心靶点进行GO功能和KEGG通路富集分析;运用Cytoscape 3.9.1构建贞芪扶正胶囊成分-靶点-通路网络;利用Autodock Tools软件对核心靶点与活性成分进行分子对接。结果获得贞芪扶正胶囊31个活性成分及180个作用靶点,确定TNF、IL6、AKT1、IL1B、TP53、VEGFA、RELA、EGFR、CASP3为核心靶点。GO功能富集分析获得生物过程1436条、细胞组分53条、分子功能117条。KEGG通路富集分析获得167条通路,与癌症、糖尿病并发症的AGE-RAGE信号通路、IL-17信号通路等密切相关。分子对接结果显示,AKT1、TNF等核心靶点与槲皮素、山柰酚、木犀草素等成分有良好的结合活性。结论贞芪扶正胶囊治疗艾滋病的主要活性成分为槲皮素、山柰酚、木犀草素,可能通过IL-17信号通路辅助治疗艾滋病。

Intestinal dysbiosis exacerbates the pathogenesis of psoriasis-like phenotype through changes in fatty acid metabolism

The intestinal microbiota has been associated with host immunity as well as psoriasis;however,the mechanism of intestinal microbiota regulating psoriasis needs to be demonstrated systematically.Here,we sought to examine its role and mechanism of action in the pathogenesis of psoriasis.We found that the severity of psoriasis-like skin phenotype was accompanied by changes in the composition of the intestinal microbiota.We performed co-housing and fecal microbial transplantation(FMT)experiments using the K14-VEGF transgenic mouse model of psoriasis and demonstrated that the transfer of intestinal microbiota from mice with severe psoriasis-like skin phenotype exacerbated psoriasiform skin inflammation in mice with mild symptoms,including increasing the infiltration and differentiation of Th17,and increased the abundance of Prevotella,while decreasing that of Parabacteroides distasonis,in the colon.These alterations affected fatty acid metabolism,increasing the abundance of oleic and stearic acids.Meanwhile,gentamicin treatment significantly reduced the abundance of Prevotella and alleviated the psoriasis-like symptoms in both K14-VEGF mice and imiquimod(IMQ)-induced psoriasis-like mice.Indeed,administration of oleic and stearic acids exacerbated psoriasis-like symptoms and increased Th17 and monocyte-derived dendritic cell infiltration in the skin lesion areas in vivo,as well as increased the secretion of IL-23 by stimulating DCs in vitro.At last,we found that,treatment of PDE-4 inhibitor alleviated psoriasis-like phenotype of K14-VEGF mice accompanied by the recovery of intestinal microbiota,including the decrease of Prevotella and increase of Parabacteroides distasonis.Overall,our findings reveal that the intestinal microbiota modulates host metabolism and psoriasis-like skin inflammation in mice,suggesting a new target for the clinical diagnosis and treatment of psoriasis.

A modelling method for large-scale open spaces orientated toward coordinated control of multiple air-terminal units

The temperature distribution is always assumed to be homogeneous in a traditional singleinput-single-output(SISO)air conditioning control strategy.However,the airflow inside is more complicated and unpredictable.This study proposes a zonal temperature control strategy with a thermal coupling effect integrated for air-conditioned large-scale open spaces.The target space was split into several subzones based on the minimum controllable air terminal units in the proposed method,and each zone can be controlled to its own set-point while considering the thermal coupling effect from its adjacent zones.A numerical method resorting to computational fluid dynamics was presented to obtain the heat transfer coefficients(HTCs)under different air supply scenarios.The relationship between heat transfer coefficient and zonal temperature difference was linearized.Thus,currently available zonal models in popular software can be used to simulate the dynamic response of temperatures in large-scale indoor open spaces.Case studies showed that the introduction of HTCs across the adjacent zones was capable of enhancing the precision of temperature control of large-scale open spaces.It could satisfy the temperature requirements of different zones,improve thermal comfort and at least 11%of energy saving can be achieved by comparing with the conventional control strategy.

过表达基因elo1和ole1增强光滑球拟酵母△med15B菌株的低pH耐受能力

【目的】研究中介体亚基Med15B(ORF CAGL0H06215g)介导的脂肪酸代谢影响光滑球拟酵母(Candida glabrata)耐受低pH胁迫的生理机制。【方法】在菌株Δmed15B中过量表达脂肪酸延伸酶基因elo1(ORF CAGL0L08184g)和Δ9去饱和酶基因ole1(ORF CAGL0I00418g),构建过表达菌株Δmed15B/elo1-ole1,然后与菌株Δmed15B和亲本菌株ATCC55对比分析基因elo1和ole1的表达水平、脂肪酸组分比例、细胞膜完整性和耐受能力在pH 2.0和pH 6.0条件下的差异。【结果】发现,在pH 2.0条件下过表达菌株Δmed15B/elo1-ole1:(1)基因elo1和ole1表达水平比菌株Δmed15B分别上调了4.1倍和3.3倍,与亲本菌株ATCC55相比分别上调了2.5倍和2.2倍;(2)脂肪酸平均链长延长至17.4,高于菌株Δmed15B的16.8和亲本菌株ATCC55的17.1;不饱和脂肪酸与饱和脂肪酸的比值比菌株Δmed15B和亲本菌株ATCC55分别提高了53.1%和41.5%;(3)碘化丙啶(PI)染色细胞数占总检测细胞数的比例,与菌株Δmed15B和亲本菌株ATCC55比较分别下降了60.8%和37.7%;(4)细胞半抑制pH(胁迫)(IC_(50))值达到pH 2.3,比菌株Δmed15B的pH 3.7和亲本菌株ATCC55的pH 3.1具有更强的耐受能力。【结论】在菌株Δmed15B中过表达基因elo1和ole1能通过提高长链脂肪酸和不饱和脂肪酸含量,增强细胞对低pH胁迫的耐受能力。

^(18)F-DOPA-PET CT显像辅助诊断高胰岛素血症性低血糖患儿临床特点

目的总结经^(18)氟-多巴正电子发射断层扫描CT(^(18)F-DOPA-PET CT)辅助诊断的高胰岛素血症性低血糖(HH)患儿的临床特征和治疗转归。方法回顾性分析2016年1月至2020年12月复旦大学附属儿科医院内分泌遗传代谢科采用综合临床诊断流程诊断的123例HH患儿的临床资料,依次收集患儿的性别、发病年龄等一般情况,低血糖时同步测定的血清胰岛素水平,^(18)F-DOPA-PET CT胰腺扫描的病灶类型,基因检测结果,治疗等临床资料。比较胰腺局灶型和弥漫型两组不同类型病灶患儿的临床特征和治疗转归。组间比较采用t检验、秩和检验和χ^(2)检验。结果123例HH患儿(男72例、女51例)发病年龄为3(1~4860)日龄,分别来自24个省份,低血糖时同步血清胰岛素水平7.1(0.4~303.0)mU/L。^(18)F-DOPA-PET CT扫描显示25.2%(31/123)为局灶型病变,74.8%(92/123)为弥漫型病变。64.2%(79/123)的HH患儿发现相关基因致病性变异,其中88.6%(70/79)为KATP相关通道基因(61例ABCC8基因致病性变异,9例KCNJ11基因致病性变异)。37例(17例局灶型、20例弥漫型)接受了手术治疗,手术成功率为67.6%(25/37)。弥漫型患儿二氮嗪治疗有效率显著高于局灶型患儿[28.3%(26/92)比9.7%(3/31),χ^(2)=10.31,P=0.001]。结论^(18)F-DOPA-PET CT扫描能提高手术成功率。遗传学分析联合^(18)F-DOPA-PET CT扫描对HH患儿进行全面的病因诊断将有助于更好地治疗和预后。

Effects of plant species coexistence on soil enzyme activities and soil microbial community structure under Cd and Pb combined pollution

The relationship between plant species coexistence and soil microbial communities under heavy metal pollution has attracted much attention in ecology.However,whether plant species coexistence could offset the impacts of heavy metal combined pollution on soil microbial community structure and soil enzymes activities is not well studied.The modified ecological dose model and PCR-RAPD method were used to assess the effects of two plant species coexistence on soil microbial community and enzymes activities subjected to Cd and Pb combined stress.The results indicated that monoculture and mixed culture would increased microbe populations under Cd and Pb combined stress,and the order of sensitivity of microbial community responding to heavy metal stress was:actinomycetes > bacteria > fungi.The respirations were significantly higher in planted soil than that in unplanted soil.The plant species coexistence could enhance soil enzyme activities under Cd and Pb combined.Furthermore,planted soil would be helpful to enhance soil genetic polymorphisms,but Cd and Pb pollution would cause a decrease on soil genetic polymorphisms.Mixed culture would increase the ecological dose 50%(ED50) values,and the ED50 values for soil enzyme activities decreased with increasing culture time.The dehydrogenase was most sensitive to metal addition and easily loses activity under low dose of heavy metal.However,it was difficult to fully inhibit the phoshpatase activity,and urease responded similarly with phosphatase.

Plant diversity reduces the effect of multiple heavy metal pollution on soil enzyme activities and microbial community structure

It is unclear whether certain plant species and plant diversity could reduce the impacts of multiple heavy metal pollution on soil microbial structure and soil enzyme activities. Random amplified polymorphic DNA （RAPD） was used to analyze the genetic diversity and microbial similarity in planted and unplanted soil under combined cadmium （Cd） and lead （Pb） pollution. A metal hyper- accumulator, Brassica juncea, and a common plant, Festuca arundinacea Schreb, were used in this research. The results showed that microorganism quantity in planted soil significantly increased, compared with that in unplanted soil with Cd and Pb pollution. The order of microbial community sensitivity in response to Cd and Pb stress was as follows： actinomycetes 〉 bacteria 〉 fungi. Respiration, phosphatase, urease and dehydrogenase activity were significantly inhibited due to Cd and Pb stress. Compared with unplanted soil, planted soils have frequently been reported to have higher rates of microbial activity due to the presence of additional surfaces for microbial colonization and organic compounds released by the plant roots. Two coexisting plants could increase microbe population and the activity of phosphatases, dehydrogenases and, in particular, ureases. Soil enzyme activity was higher in B. juncea phytoremediated soil than in F. arundinacea planted soil in this study. Heavy metal pollution decreased the richness of the soil microbial community, but plant diversity increased DNA sequence diversity and maintained DNA sequence diversity at highlevels. The genetic polymorphism under heavy metal stress was higher in B. juncea phytoremediated soil than in F. arundinacea planted soil.

Skin friction reduction characteristics of variable ovoid non-smooth surfaces

目的:仿生非光滑表面具有降低表面摩擦阻力的作用,传统的非光滑结构有沟槽和凹坑等。本文旨在研究变异卵圆形凹坑非光滑表面的气动摩擦减阻特性及其减阻机理。创新点:1.以仿生学理论为基础,提出变异卵圆形凹坑结构模型,突破现有非光滑结构类型的局限;2.采用参数构造的方法研究变异卵圆形各构造参数对表面摩擦阻力减阻的影响。方法:1.采用半径、半轴和坑深3个尺寸参数对变异卵圆凹坑结构进行几何定义,并将非光滑结构以一定纵向间距按矩形排布布置在仿真模型底部;2.以3个尺寸参数和纵向间距设计"三水平四因素"正交实验,在不同气流流速下进行数值模拟仿真;3.通过速度矢量、边界层厚度变化和压力分布研究变异卵圆形凹坑非光滑表面的气动摩擦减阻机理。结论:1.变异卵圆形非光滑表面具有一定的气动摩擦减阻效果,和光滑表面相比,在空气来流速度为24 m/s时,有10%的减阻效果;2.正交实验分析表明,4个试验因素对减阻效果的影响从大到小排列分别为:半径、坑深、半轴和纵向间距;3.变异卵圆形凹坑表面增加了边界层的厚度,降低了近壁面区域的速度梯度,减少了剪切力,从而起到了减少摩擦阻力的效果。

Advances in fungal-assisted phytoremediation of heavy metals:A review

Trace metals such as manganese(Mn),copper(Cu),zinc(Zn),and iron(Fe)are essential for many biological processes in plant life cycles.However,in excess,they can be toxic and disrupt plant growth processes,which is economically undesirable for crop production.For this reason,processes such as homeostasis and transport control of these trace metals are of constant interest to scientists studying heavily contaminated habitats.Phytoremediation is a promising cleanup technology for soils polluted with heavy metals.However,this technique has some disadvantages,such as the slow growth rate of metal-accumulating plant species,low bioavailability of heavy metals,and long duration of remediation.Microbial-assisted phytoremediation is a promising strategy for hyperaccumulating,detoxifying,or remediating soil contaminants.Arbuscular mycorrhizal fungi(AMF)are found in association with almost all plants,contributing to their healthy performance and providing resistance against environmental stresses.They colonize plant roots and extend their hyphae to the rhizosphere region,assisting in mineral nutrient uptake and regulation of heavy metal acquisition.Endophytic fungi exist in every healthy plant tissue and provide enormous services to their host plants,including growth enhancement by nutrient acquisition,detoxification of heavy metals,secondary metabolite regulation,and enhancement of abiotic/biotic stress tolerance.The aim of the present work is to review the recent literature regarding the role of AMF and endophytic fungi in plant heavy metal tolerance in terms of its regulation in highly contaminated conditions.

Evidence for the paternal mitochondrial DNA in the crucian carp-like fish lineage with hybrid origin

In terms of taxonomic status,common carp(Cyprinus carpio,Cyprininae)and crucian carp(Carassius auratus,Cyprininae)are different species;however,in this study,a newborn homodiploid crucian carp-like fish(2n=100)(2nNCRC)lineage(F1–F3)was established from the interspecific hybridization of female common carp(2n=100)×male blunt snout bream(Megalobrama amblycephala,Cultrinae,2n=48).The phenotypes and genotypes of 2 n NCRC differed from those of its parents but were closely related to those of the existing diploid crucian carp.We further sequenced the whole mitochondrial(mt)genomes of the 2n NCRC lineage from F1 to F3.The paternal mt DNA fragments were stably embedded in the mt-genomes of F1–F3 generations of 2n NCRC to form chimeric DNA fragments.Along with this chimeric process,numerous base sites of F1–F3 generations of 2 n NCRC underwent mutations.Most of these mutation sites were consistent with the existing diploid crucian carp.Moreover,the mt DNA organization and nucleotide composition of 2n NCRC were more similar to those of the existing diploid crucian carp than those of the parents.The inheritable chimeric DNA fragments and mutant loci in the mt-genomes of different generations of 2nNCRC provided important evidence of the mt DNA change process in the newborn lineage derived from hybridization of different species.Our findings demonstrated for the first time that the paternal mt DNA were transmitted into the mt-genomes of homodiploid lineage,which provided new insights into the existence of paternal mt DNA in the mt DNA inheritance.

Import of Rift Valley fever to China:a potential new threat?

Several recent studies in Virologica Sinica and other journals have highlighted the enormous international challenge of emerging arboviral diseases,such as Zika virus disease,dengue,and chikungunya(Islam et al.,2015;Maurice et al.,2015;Dai et al.,2016;Deng et al.,2016;Song et al.,2016;Wang et al.,2016;Xu et al.,2016;Zhang et al.,2016;Zhou

Mutualistic fungus Piriformospora indica modulates cadmium phytoremediation properties of host plant via concerted action of enzymatic and non-enzymatic biochemicals

Soils and ecosystems contaminated with cadmium (Cd) threaten human health and adversely affect morphological,physiological,and biochemical parameters of plants.The symbiotic association of endophytic fungi with their host plants is the best strategy to improve various plant characteristics and remediate soils polluted with heavy metal(loid)s (HMs).Being a well-known plant growth-promoting fungus,Piriformospora indica confers resistance against a number of abiotic stresses,including HM stress.This pot experiment explored the potential and ameliorative effects of P.indica on Artemisia annua L.plants treated with different concentrations (0,40,80,and 120 mg kg-1) of Cd.Inoculation with P.indica significantly increased plant performance,especially by enhancing chlorophyll concentration and water potential and by decreasing electrolytic leakage,when compared with un-inoculated plants,despite the high Cd levels.Similarly,P.indica enhanced antioxidant enzyme activities,thereby reducing the drastic effects of Cd in inoculated plants.In addition,P.indica accumulated Cd in the roots of colonized plants,as revealed by atomic absorption spectroscopy,and restricted Cd translocation to aerial parts.Furthermore,P.indica showed in vitro resistance (up to a certain level) to Cd stress;however,fungus growth was inhibited at very high Cd concentrations,proving it an excellent candidate for use as a potential phytoremediator in fields affected by Cd contamination.The transcriptional analysis showed that the signaling genes and artemisinin and flavonoid biosynthetic pathway genes were significantly upregulated in P.indica-co-cultivated plants when compared with un-inoculated plants,suggesting a fine collaboration between primary and secondary metabolisms to modulate resistance capacity and to enhance the phytoremediation capability of A.annua against Cd toxicity.

基于核苷酸配合物的多级手性的研究进展

手性是自然界中普遍存在的一种特殊对称性.生物体展示了跨多尺度的手性信息与传递的功能.研究多级手性的传递、诱导与放大是涉及化学、生物、物理、材料等多个学科的基本科学问题.从分子手性到宏观手性可在不同的长度与尺度下分为四个层级:构型(分子)手性(一级)、构象手性(二级)、相手性(三级)、宏观手性(四级).基于核苷酸配位超分子组装体的X射线单晶结构研究并结合固(晶)态圆二色谱分析方法是研究多级手性问题的有效途径.深刻认识与理解多尺度的手性组装、手性诱导与手性传递不仅有助于我们认识生物体的结构与功能的关系,而且还为合理设计与合成手性功能材料与人工分子机器提供理论基础.本文基于本课题组在核苷酸手性配位超分子组装体方面的研究成果,阐述了一种有效研究构象手性与相手性的方法,即X射线单晶衍射技术与固态圆二色光谱相关联的手性研究方法.首次将有机化学中的轴手性拓展至一维配位聚合物中而创新地提出“拓展轴手性”的概念.在精确晶体结构数据分析的基础上,揭示了金属配位键、氢键、π-π堆积作用等在手性诱导、手性组装和手性传递等方面的作用.同时,对未来手性研究提出了展望.

Beagle Dogs Have Low Susceptibility to Florida Clade 2 H3N8 Equine Avian Influenza

Dear Editor,Dogs were long considered refractory to influenza viruses until the equine-origin H3N8 canine influenza virus(CIV)was first isolated in the United States of America(U.S.A)in 2004(Crawford et al.2005).Since then,H3N8 CIV of equine-origin strains has been circulating in dogs in the U.S.A.In 2006,another CIV of avian origin H3N2 subtype was isolated from dogs in China(Li et al.2010).Recently,H3N2 CIV strains have become endemic in dog populations in China,South Korea,and North America(Borland et al.2020).

Interleukin-37 promotes colitis-associated carcinogenesis via SIGIRR-mediated cytotoxic T cells dysfunction

Interleukin-37b(hereafter called IL-37)was identified as fundamental inhibitor of natural and acquired immunity.The molecular mechanism and function of IL-37 in colorectal cancer(CRC)has been elusive.Here,we found that IL-37 transgenic(IL-37tg)mice were highly susceptible to colitis-associated colorectal cancer(CAC)and suffered from dramatically increased tumor burdens in colon.Nevertheless,IL-37 is dispensable for intestinal mutagenesis,and CRC cell proliferation,apoptosis,and migration.Notably,IL-37 dampened protective cytotoxic T cell-mediated immunity in CAC and B16-OVA models.CD8^(+)T cell dysfunction is defined by reduced retention and activation as well as failure to proliferate and produce cytotoxic cytokines in IL-37tg mice,enabling tumor evasion of immune surveillance.The dysfunction led by IL-37 antagonizes IL-18–induced proliferation and effector function of CD8+T cells,which was dependent on SIGIRR(single immunoglobulin interleukin-1 receptor-related protein).Finally,we observed that IL-37 levels were significantly increased in CRC patients,and positively correlated with serum CRC biomarker CEA levels,but negatively correlated with the CD8+T cell infiltration in CRC patients.Our findings highlight the role of IL-37 in harnessing antitumor immunity by inactivation of cytotoxic T cells and establish a new defined inhibitory factor IL-37/SIGIRR in cancerimmunity cycle as therapeutic targets in CRC.