Characterization and evaluation of rice blast resistance of Chinese indica hybrid rice parental lines

The development of resistant varieties and hybrid combinations has been the most effective and economical strategy to control blast disease caused by Magnaporthe oryzae.However, the distribution of major R genes and blast resistance characterization in hybrid rice parents has not been well investigated, resulting in their limited use in hybrid rice blast-resistance breeding. In the present study, 88 elite indica hybrid rice parental lines were evaluated with 30 isolates of M. oryzae collected from the main planting area of indica hybrid rice in China and were characterized for the presence of 11 major resistance genes using molecular markers. The pathogenicity assays showed that four types of hybrid rice parent line showed some resistance to M. oryzae. However, the proportions of highly resistant lines and the mean resistance frequency(RF) varied among the four types, with resistance in decreasing order shown by three-line restorer lines, three-line maintainer lines, two-line sterile lines, and two-line restorer lines. All 88 hybrid rice parental lines carried more than one R gene, but none carried the R genes Pi1 and Pi2. Although Pid3 and Pi9 were present only in three-line restorer lines and Pigm only in three-line maintainer lines, the remaining six R genes(Pib, Pid2, Pi5, Pia, Pi54, and Pita) were present in the four types of hybrid rice parent with significantly different distribution frequencies. The correlation between R genes and resistance reactions was investigated. The results are expected to provide useful information for rational utilization of major R genes in hybrid rice breeding programs.

Preliminary outcome of rituximab-containing salvage regimens on relapsed or refractory B-cell non-Hodgkin’s lymphoma: single institution experience

Objective： The prognosis of relapsed or refractory B-cell lymphoma is poor, with a short-term survival after conventional second-line chemotherapy, Rituximab, a chimeric anti-CD20 antigen, in combination with CHOP or CHOP-like chemotherapy may improve both disease free survival （DFS） and overall survival （OS） of naive patients, but its role in the second-line therapy for relapsed non-Hodgkin＇s Lymphoma （NHL） remains to be defined, This study aimed to evaluate the efficacy of rituximab-containing salvage regimens for relapsed or refractory NHL, and observe the toxicities. Methods： The clinical data of 54 patients, who were with relapsed or refractory NHL and treated in the Cancer Center of Sun Yat-sen University, were analyzed retrospectively, Of the 54 patients, 29 were man, 25 were women, with a median age of 52.5 years old （range 18 to 75）; 50 patients （92.6%） scored 0-1 for the ECOG performance status; for second-line international prognostic index （slPI）, 21 （38.9%） scored 0-1,30 （55.6%） scored 2 to 3, and 3 （5.6%） scored 4-5; 40 cases were diffuse large B-cell lymphoma （DLBCL）, accounting for 74.1% of all subtypes, Rituximab was administered intravenously at a dose of 375 mg/m^2 at the day before each chemotherapy cycle, The second or third-line salvage regimens included EPOCH, CHOP, DHAP, DICE, IVAC, IMVP-16 and FND, Results： Of the 54 patients, 49 received retuximab-containing salvage regimens, The objective response rate of the 45 evaluable cases was 68,8%, with a complete remission （CR） rate of 37.7%; 3 patients achieved CR after radiotherapy following rituximab-based regimens and 3 achieved CR after autologous hematopoietic stem cell transplantation, The most frequent adverse events were leucopenia, nausea and alopecia. The addition of rituximab to chemotherapy only elevated the occurrence of mild infusion-related reactions, such as chills, fever and pruritus. The median follow-up time was 18 months （range 2-86 months）; 5 patients were lost, 24 were dead （23 died of lymphoma, and 1 died of severe hepatitis）, the other patients remained alive. The median survival time was 32 months （range 2-86 months, 95% confidential interval 16-48 months）. The 1-, 2- and 3-year OS rates were 70.6%, 53,6% and 41,5%, respectively, The median TTP was 6 months （range 0-52 months）, The median PFS was 10 months （range 0-47 months, 95% CI 0-26 months）, The 1- and 2-year PFS were 49,3% and 41,3%. Conclusion： Rituximab-containing salvage regimens are effective and well tolerated therapy for patients with relapsed or refractory B-cell NHL, even those were extensively treated.

A Mobility Management Solution Based on ID/Locator Separation

Current mobility management solutions based on ID/Locator separation are not easily deployed and cannot solve routing scalability and mobility problems. This paper proposes a novel network architecture based on ID/Locator separation and suggests a new mobility management solution. This solution solves the problem of scalability in the network and also provides better support for mobility. It can be easily deployed because no modification of the mobile host’s protocol stack is required. The identifier contains some routing information; so the solution provides intrinsic interworking with traditional mobile hosts. Because the mapping systems are distributed to the edge networks, robustness of the whole system is enhanced and handover delay is decreased.

Effect of fertility history and parity on Alzheimer’s disease:a mini review from animal to human studies

More women than men have Alzheimer's disease(AD)or other dementias.There are a number of potential biological and social reasons for the sex difference in the risk of AD,such as women live longer than men on average,and estrogen depletion after menopause in women,biological or genetic variations,and education,occupation or rates of heart disease.Recent studies showed a link between reproductive history and dementia risk in women.Women with fertility history showed lower risk of dementia compared to women with no child.Other studies also suggested that women's pregnancy history may influence AD's risk.In this review,we will focus on the relationship between women fertility and cognition and discuss the potential role of sex hormones in the brain and cognition,especially on AD pathogenesis.

Malignant ovarian tumors during pregnancy:Diagnostic evaluation,optimal treatment,and future perspective

To the Editor:Malignant ovarian tumors during pregnancy(MOTP)rank second after cervical cancer among gynecological malignancies diagnosed during pregnancy,and most women today hope to maintain pregnancy and preserve fertility,which complicates oncologic treatment,as all potential complications and prognoses should be carefully considered for both the mother and fetus.A coordinated approach from a multidisciplinary team involving gynecological oncologists,obstetricians,and pathologists is recommended.

Pijx confers broad-spectrum seedling and panicle blast resistance by promoting the degradation of ATP b subunit and OsRbohC-mediated ROS burst in rice

(Molecular Plant 16,1832-1846,November 62023)The originally published version of this manuscript contained several small mistakes in the labels and legends of main and supplemental figures,along with a few small mistakes in the main text,that have now been corrected.Specifically,in Figure 6G,the label“NILGY31^(Pijx)”has been corrected to“NIL^(Pijx)”,and in the legend of Figure 6H,“PPL^(Pijx Piz-t)”and“PPL^(Pijx Pigm)”have been corrected to“NIL^(Piz-t Pijx)”and“PPL^(Pigm Pijx).”In Figure S8A。

部分还原二氧化钛的NMR和EPR研究

部分还原TiO2纳米材料由于具备可见光催化及降解活性而引起广泛研究关注。本研究采用17O和1H魔角旋转固体核磁共振(MAS NMR)谱学,结合电子顺磁共振(EPR)谱学研究了锐钛矿型部分还原TiO2(Re-A-TiO2)纳米颗粒的表面结构,并与非还原样品(A-TiO2)作了对比。EPR结果显示,Re-A-TiO2的顺磁物种(氧空位(OV)和Ti^3+)含量远高于A-TiO2,并且EPR信号的强度受吸附水含量的显著影响,我们结合1H NMR数据,探讨了这一过程中的结构变化。17O NMR谱中,两种样品除了表面2配位氧(μ2-O)的信号有明显差异外,还发现在Re-A-TiO2表面有更多的羟基(OH),显示该样品表面有较高比例的(001)晶面暴露。综合EPR和NMR数据,可推断羟基主要来源于顺磁中心与吸附水分子反应。1H→17O交叉极化(CP)-MAS和二维异核相关(2D HETCOR)NMR谱确认了强吸附的水物种和一种羟基的归属,另外位于约11 ppm的1H NMR信号可归属为分子内氢键中的氢物种。这些表面结构的差异应与两种材料光降解甲基橙性能差别直接相关。

Protective effect of Jiaweibugan decoction against diabetic peripheral neuropathy

Oxygen free radical damage is regarded as a direct or indirect common pathway associated with diabetic neuropathy and is the main cause of complications in peripheral neuropathies. We speculate that Jiaweibugan decoction has a significant effect in treating diabetic peripheral neuropathy through an anti-oxidative stress pathway. In this study, a diabetic rat model was established by intraperitoneal injection of streptozotocin. Rats were treated with Jiaweibugan decoction via intragastric administration. The levels of malondialdehyde and glutathione, which are indirect indexes of oxidative stress, in serum were determined using a colorimetric method. The expression levels of nuclear factor kappa B p65 mRNA and p38 mitogen-activated protein kinase, which are oxidative stress associated factors, in the dorsal root ganglion of spinal $4-6 segments were evaluated by reverse-transcriptase polymerase chain reaction and immunohistochemistry. Results showed that, Jiaweibugan decoction significantly ameliorated motor nerve conduction velocity in diabetic rats, effectively decreased malondialdehyde levels in serum and the expression of nuclear factor kappa B p65 mRNA and p38 mitogen-activated protein kinase mRNA in the dorsa root ganglion, and increased glutathione levels in serum. Therefore, our experimental findings indicate that Jiaweibugan decoction plays an anti-oxidative stress role in the diabetic peripheral neuropathy process, which has a protective effect on peripheral nerve injury.

Molecularly tagged genes and quantitative trait loci in cucumber with recommendations for QTL nomenclature

Cucumber,Cucumis sativus L.(2n=2x=14),is an important vegetable crop worldwide.It was the first specialty crop with a publicly available draft genome.Its relatively small,diploid genome,short life cycle,and selfcompatible mating system offers advantages for genetic studies.In recent years,significant progress has been made in molecular mapping,and identification of genes and QTL responsible for key phenotypic traits,but a systematic review of the work is lacking.Here,we conducted an extensive literature review on mutants,genes and QTL that have been molecularly mapped or characterized in cucumber.We documented 81 simply inherited trait genes or major-effect QTL that have been cloned or fine mapped.For each gene,detailed information was compiled including chromosome locations,allelic variants and associated polymorphisms,predicted functions,and diagnostic markers that could be used for marker-assisted selection in cucumber breeding.We also documented 322 QTL for 42 quantitative traits,including 109 for disease resistances against seven pathogens.By alignment of these QTL on the latest version of cucumber draft genomes,consensus QTL across multiple studies were inferred,which provided insights into heritable correlations among different traits.Through collaborative efforts among public and private cucumber researchers,we identified 130 quantitative traits and developed a set of recommendations for QTL nomenclature in cucumber.This is the first attempt to systematically summarize,analyze and inventory cucumber mutants,cloned or mapped genes and QTL,which should be a useful resource for the cucurbit research community.

Corrosion behavior of high-level waste container materials Ti and Ti-Pd alloy under long-term gamma irradiation in Beishan groundwater

Titanium and titanium-palladium alloys are important potential materials for nuclear waste container,which will endure both intenseγ-irradiation and groundwater erosion.Therefore,it is very important to investigate the corrosion behavior of the container materials.In this research,the cumulative dose effect of TA8-1 type titanium-palladium alloy(TA8-1)and TA2-type pure titanium(TA2)underγ-irradiation was studied based on the geological disposal of nuclear wastes.The irradiation experiments were performed at room temperature using^(60)Co gamma sources with a 5.0-kGy·h^(-1)intensity for 40,80 or 160 days,respectively.The pH value and conductivity of Beishan groundwater were investigated.The results showed that the pH value changed from alkaline(8.22)to acidic(2.46 for TA8-1 and 2.44 for TA2),while the un-irradiated solution remained alkaline(8.17 for TA8-1 and 8.20 for TA2)after 160 days.With the increase of irradiation dose,the conductivity increases rapidly and then tends to become stable,which indicates that the titanium dioxide corrosion layer formed on the surface of the sample surface effectively prevents further corrosion.Meanwhile,XRD and SEM-EDS analysis results show that the main components of corrosion products are TiO_(2) and TiO.The titanium on the surface of the sample is oxidized,resulting in slight uneven local corrosion.The results show that TA8-1 and TA2 are suitable to be used as candidate materials for high-level waste(HLW)disposal containers due to their excellent performance under long-term and high-dose irradiation corrosion.

Identification of key long noncoding RNAs and their biological functions in hepatocellular carcinoma

Long noncoding RNAs(lncRNAs)are vital regulators in tumorigenesis and metastasis.However,the pathological role of lncRNAs in hepatocellular carcinoma(HCC)is still unclear.In this study,we filtered out three lncRNAs from The Cancer Genome Atlas(TCGA)data that were screened for basic expression and clinical research.We selected lncRNA-NEAT1 for further study to explore its function in HCC progression and its regulatory mechanism.We identified three differentially expressed lncRNAs(DElncRNAs)in tumor and adjacent normal tissues from the TCGA library using data mining methods:lncRNA-NEAT1,lncRNA-MAGI2-AS3 and lncRNA-HCG11.Their basic expression levels were detected by qPCR.Then,we selected lncRNA-NEAT1 as a potentially important lncRNA to verity its biological function and mechanism in HCC cell lines.lncRNA-NEAT1,lncRNA-MAGI2-AS3 and lncRNA-HCG11 were overexpressed in liver cancer tissues and cell lines.We found that silencing NEAT1 in vitro can inhibit the proliferation of HuH-7 and Li-7 cells,inhibit cell migration,and induce apoptosis as well as significantly increase the level of miR-16-5p.We also confirmed that miR-16-5p has a significant correlation with Bcl-2.When NEAT1 is silenced,the expression of Bcl-2 decreases.Inhibiting miR-16-5p can restore Bcl-2 to its original level.We conclude that miR-16-5p1/lncRNA NEAT1 plays a crucial role in regulating the delivery of Bcl-2 in HCC.Overall,the miR-16-5p/lncRNA-NEAT1/Bcl-2 signaling axis may be a promising target for HCC treatment.

Androgen receptor inhibits the hair follicle induction potential of dermal papilla cells by binding with Tcf4 at the A574 binding site

Androgenic alopecia(AGA)is the most common type of clinical alopecia.Androgen receptor(AR)is the most logical candidate gene for regulating the occurrence of AGA.Dermal papilla cells(DPCs)are a special kind of mesenchymal cells,located in the hair bulb of hair follicles.DPCs play a role in maintaining and inducing the periodic cycling of hair follicles,and are considered as a key cell target of androgen in hair follicles.

Pijx confers broad-spectrum seedling and panicle blast resistance by promoting the degradation of ATP β subunit and OsRbohC-mediated ROS burst in rice

Rice blast,caused by the fungal pathogen Magnaporthe oryzae,is one of the most important diseases of rice.Utilization of blast-resistance genes is the most economical,effective,and environmentally friendly way to control the disease.However,genetic resources with broad-spectrum resistance(BSR)that is effective throughout the rice growth period are rare.In this work,using a genome-wide association study,we identify a new blast-resistance gene,Pijx,which encodes a typical CC-NBS-LRR protein.Pijx is derived from a wild rice species and confers BSR to M.oryzae at both the seedling and panicle stages.The functions of the resistant haplotypes of Pijx are confirmed by gene knockout and overexpression experiments.Mechanistically,the LRR domain in Pijx interacts with and promotes the degradation of the ATP synthase β subunit(ATPb)via the 26S proteasome pathway.ATPb acts as a negative regulator of Pijx-mediated panicle blast resistance,and interacts with OsRbohC to promote its degradation.Consistently,loss of ATPb function causes an increase in NAPDH content and ROS burst.Remarkably,when Pijx is introgressed into two japonica rice varieties,the introgression lines show BSR and increased yields that are approximately 51.59%and 79.31%higher compared with those of their parents in a natural blast disease nursery.In addition,we generate PPL^(Pijx Pigm) and PPL^(Pijx Piz-t) pyramided lines and these lines also have higher BSR to panicle blast compared with Pigm-or Piz-t-containing rice plants.Collectively,this study demonstrates that Pijx not only confers BSR to M.oryzae but also maintains high and stable rice yield,providing new genetic resources and molecular targets for breeding rice varieties with broad-spectrum blast resistance.

Wnt4 increases the thickness of the epidermis in burn wounds by activating canonical Wnt signalling and decreasing the cell junctions between epidermal cells

Background:Burn wound healing is a complex process and the role of Wnt ligands varies in this process.Whether and how Wnt4 functions in burn wound healing is not well understood.In this study,we aim to reveal the effects and potential mechanisms of Wnt4 in burn wound healing.Methods:First,the expression of Wnt4 during burn wound healing was determined by immunoflu-orescence,Western blotting and qPCR.Then,Wnt4 was overexpressed in burn wounds.The healing rate and healing quality were analysed by gross photography and haematoxyline and eosin staining.Collagen secretion was observed by Masson staining.Vessel formation and fibroblast distribution were observed by immunostaining.Next,Wnt4 was knocked down in HaCaT cells.The migration of HaCaT cells was analysed by scratch healing and transwell assays.Next,the expression ofβ-catenin was detected by Western blotting and immunofluorescence.The binding of Frizzled2 and Wnt4 was detected by coimmunoprecipitation and immunofluorescence.Finally,the molecular changes induced by Wnt4 were analysed by RNA sequencing,immunofluorescence,Western blotting and qPCR in HaCaT cells and burn wound healing tissues.Results:The expression of Wnt4 was enhanced in burn wound skin.Overexpression of Wnt4 in burn wound skin increased the thickness of epidermis.Collagen secretion,vessel formation and fibroblast distribution were not significantly impacted by Wnt4 overexpression.When Wnt4 was knocked down in HaCaT cells,the ratio of proliferating cells decreased,the ratio of apoptotic cells increased and the ratio of the healing area in the scratch healing assay to the number of migrated cells in the transwell assay decreased.The nuclear translocation ofβ-catenin decreased in shRNA of Wnt4 mediated by lentivirus-treated HaCaT cells and increased in Wnt4-overexpressing epidermal cells.RNA-sequencing analysis revealed that cell junction-related signalling pathways were significantly impacted by Wnt4 knockdown.The expression of the cell junction proteins was decreased by the overexpression of Wnt4.Conclusions:Wnt4 promoted the migration of epidermal cells.Overexpression of Wnt4 increased the thickness of the burn wound.A potential mechanism for this effect is that Wnt4 binds with Frizzled2 and increases the nuclear translocation ofβ-catenin,thus activating the canonical Wnt signalling pathway and decreasing the cell junction between epidermal cells.

Voluntary resignation of independent directors and auditor responses:Empirical evidence from Chinese A-share listed firms

We examine auditor responses to the voluntary resignation of independent directors.We show that auditors respond by increasing audit fees or rescinding engagement with their clients,but not by increasing their audit effort.Mechanism tests reveal that independent directors’voluntary resignation leads to increased regulatory sanctions and negative media coverage,these relationships are more pronounced after the New Securities Law.Auditor response strategies follow an order of priority:at an acceptable level of perceived risk,auditors increase audit fees;when perceived risk exceeds this level,auditors will discontinue the client relationship.Auditors associate greater risk with firms that have(vs.have not)experienced consecutive voluntary resignations by independent directors.Mandatory resignation has no such effect.

Cretaceous-Neogene Exhumation of the Daqing Shan,North China Constrained by Apatite Fission Track Thermochronology

The Daqing Shan(DQS)located in the Yinshan-Yanshan Orogenic Belt plays an important role in the Mesozoic to Cenozoic evolution of the North China Craton.However,the cooling and exhumation history since the Cretaceous is still controversial.Integrating the apatite fission track(AFT)data in both this study and previous works,a three-stage exhumation history from Cretaceous to Neogene of the DQS is proposed.(1)The first stage is composed of the early exhumation during Early Cretaceous driven by the collision between the North China and Siberia cratons(ca.148-132 Ma)and the far-field effect of the subduction of the Pacific Plate(ca.132-114 Ma).(2)Due to the subsidence of the Hetao Basin and the subsequent compensation between the DQS and the Hetao Basin,the DQS experienced the second rapid exhumation from Early Eocene to Early Oligocene(ca.54-29 Ma).(3)Since the Late Miocene(ca.13.5 Ma),the third rapid cooling and exhumation of the DQS occurred due to the far-field effect of the uplift of the Tibetan Plateau and the subduction of the Pacific Plate.

Phenylboronic-tannin nanocolloids that scavenge subchondral reactive oxygen microenvironment and inhibit RANKL induced osteoclastogenesis for osteoarthritis treatment

The excessive reactive oxygen species (ROS) accumulation and overactivated osteoclastogenesis in subchondral bone has proved to be a major cause of osteoarthritis (OA). Scavenging of ROS microenvironment to inhibit the osteoclastogenesis is highly valued in the therapeutic process of osteoarthritis. Despite the excellent ability of polyphenolic colloidal to scavenge reactive oxygen species and its affinity for macrophages, the preparation of polyphenolic colloidal nanoparticles is limited by the complex intermolecular forces between phenol molecules and the lack of understanding of polymerization/sol-gel chemistry. Herein, our work introduces a novel poly-tannin-phenylboronic colloidal nanoparticle (PTA) exclusively linked by ROS-responsive bondings. Nanocolloidal PTA has a uniform particle size, is easy and scalable to synthesize, has excellent scavenging of ROS, and can be slowly degraded. For in vitro experiments, we demonstrated that, PTA could eliminate ROS within RAW264.7 cells and impede osteoclastogenesis and bone resorption. RNA sequencing results of PTA-treated RAW264.7 cells further reveal the promotion of antioxidant activity and inhibition of osteoclastogenesis. For in vivo experiments, PTA could eliminate the ROS environment and reduce the number of osteoclasts in the subchondral bone, thereby alleviating the damage of subchondral bone and symptoms of osteoarthritis. Our research, by delving into the formation of polyphenol colloidal nanoparticles and validating their role in ROS scavenging to inhibit osteoclastogenesis in subchondral bone, may open new avenues for OA treatment in the future.

The SWi2/SNF2 Chromatin-Remodeling ATPase BRAHMA Regulates Chlorophyll Biosynthesis in Arabidopsis

Chlorophyll biosynthesis is critical for chloroplast development and photosynthesis in plants. Although reactions in the chlorophyll biosynthetic pathway have been largely known, little is known about the regu-latory mechanisms of this pathway. In this study, we found that the dark-grown knockout and knockdown mutants as well as RNA-interference transgenic seedlings of BRAHMA （BRM）, which encodes an SWI2/ SNF2 chromatin-remodeling ATPase, had iligher greening rates, accumulated less protochlorophyllide, and produced less reactive oxygen species than Arabidopsis wild-type plants did upon light exposure. The expression of NADPH：protochlorophyilide oxidoreductase A （PORA）, PORB, and PORC, which catalyze a key step in chlorophyll biosynthesis, was increased in the brm mutants. We found that BRM physically interacted with the bHLH transcription factor PHYTOCHRONIE-iNTERACTING FACTOR 1 （PIF1） through its N-terminal domains. Furthermore, we demonstrated that BRM was directly recruited to the cis-regula-tory regions of PORC, but not of PORA and PORB, at least partially in a PIF1-dependent manner and the level of histone H3 lysine 4 tri-methylation （H3K4me3） at PORC loci was increased in the brm mutant. Taken together, our data indicate that the chromatino-remodeling enzyme BRM modulates PORC expression through interacting with PIF1, providing a novel regulatory mechanism by which plants fine-tune chloro-phyll biosynthesis during the transition from heterotrophic to autotrophic growth.

Distribution of Helium Resources in Weihe Basin,Central China:Insight from 3D Magnetic Inversion

There is promising indication of helium-rich natural gas in Weihe Basin.However,the lack of a detailed investigation on the origin and the spatial distribution of helium source rocks(mainly Yanshanian granites)limits the helium potentiality evaluation in Weihe Basin(WB).We performed three-dimensional(3 D)inversions of magnetic data in Weihe Basin and its adjacent areas to figure out the crustal thermal structure and the temporal-spatial distribution of deep granite in the basin.Based on this,we have proposed a geological model of helium accumulation and predicted the potential area of helium distribution.The results of 3 D magnetic inversion indicate that the granites in the deep Weihe Basin are mostly located at the central and southern parts of the basin,which are connected spatially with the granites in the North Qinling Orogenic Belt.These granites were all derived from largescale intra-continental orogeny in the Qinling area during the mid-Mesozoic,providing a good material basis for crust-derived helium in the basin.The local uplift of the Curie surface makes the thermal fluid more actively,which contributes to helium accumulation.The faults developed in the WB are the migration pathway of crust-derived helium and the upward migration of the mantle-derived helium.The wells with high percentage helium are mostly located near the Weihe fault and the areas on the south of it.The Wugong-Xi’an-Lantian area in the central and the Lintong-Weinan-Tongguan area in the eastern Weihe Basin are the most promising helium distribution areas.Furthermore,the region from the north of Taibai Mountain to Baoji City in the western Weihe Basin may also be another potential area of Helium resource.

Circ-Smad5 retards the G1/S transition of cell cycle via inhibiting the activity of wnt/lef/cyclind1 signaling in JB6 cells

Circular RNAs are a large class of noncoding RNAs.Smad5 functions in cell differentiation,cell proliferation and metastasis.It has been reported that lnc-Smad5 can inhibit the proliferation of diffuse large B cell lymphoma.However,the function of circ-Smad5 has not yet been reported.Lentivirus vectors were constructed to establish circ-Smad5 upregulated and circ-Smad5 downregulated cell models.A CCK-8 assay was used to detect the proliferation of JB6 cells.FACS was used to analyze the cell cycle in the cell models.Western blot,immunofluorescence staining and TOP/FOP flash dual luciferase activity assays were used to determine the activity of the Wnt signaling pathway.The results revealed that the expression level of circ-Smad5 in JB6 cells was significantly lower than the expression level of linearizedSmad5.Compared with the control group,the percentage of S phase cells and the expression level of cyclin D1 protein were significantly higher in the sh-circ-Smad5 group.In the sh-circSmad5 group,b-catenin and LEF-1 were significantly increased,p-b-catenin was significantly decreased,and the relative activity of the TOP/FOP reporter gene was higher compared to the control group levels.These phenomena could be reversed by treating with Wnt signaling inhibitor PNU-74654.We conclude that the circ-Smad5 retards the proliferation and the cell cycle progression of JB6 cells.Thus,circ-Smad5 may function by inhibiting the activation of Wnt/b-catenin/Lef 1 signaling,which inhibits the expression of cyclin D1.To the best of our knowledge,we are the first to report the function of circ-Smad5.