Background:Hepatocellular carcinoma(HCC)has a poor long-term prognosis.The competition of circular RNAs(circRNAs)with endogenous RNA is a novel tool for predicting HCC prognosis.Based on the alterations of circRNA reg...Background:Hepatocellular carcinoma(HCC)has a poor long-term prognosis.The competition of circular RNAs(circRNAs)with endogenous RNA is a novel tool for predicting HCC prognosis.Based on the alterations of circRNA regulatory networks,the analysis of gene modules related to HCC is feasible.Methods:Multiple expression datasets and RNA element targeting prediction tools were used to construct a circRNA-microRNA-mRNA network in HCC.Gene function,pathway,and protein interaction analyses were performed for the differentially expressed genes(DEGs)in this regulatory network.In the proteinprotein interaction network,hub genes were identified and subjected to regression analysis,producing an optimized four-gene signature for prognostic risk stratification in HCC patients.Anti-HCC drugs were excavated by assessing the DEGs between the low-and high-risk groups.A circRNA-microRNA-hub gene subnetwork was constructed,in which three hallmark genes,KIF4A,CCNA2,and PBK,were subjected to functional enrichment analysis.Results:A four-gene signature(KIF4A,CCNA2,PBK,and ZWINT)that effectively estimated the overall survival and aided in prognostic risk assessment in the The Cancer Genome Atlas(TCGA)cohort and International Cancer Genome Consortium(ICGC)cohort was developed.CDK inhibitors,PI3K inhibitors,HDAC inhibitors,and EGFR inhibitors were predicted as four potential mechanisms of drug action(MOA)in high-risk HCC patients.Subsequent analysis has revealed that PBK,CCNA2,and KIF4A play a crucial role in regulating the tumor microenvironment by promoting immune cell invasion,regulating microsatellite instability(MSI),and exerting an impact on HCC progression.Conclusions:The present study highlights the role of the circRNA-related regulatory network,identifies a four-gene prognostic signature and biomarkers,and further identifies novel therapy for HCC.展开更多
BACKGROUND Achalasia is associated with high risk of esophageal carcinoma.However,the optimal endoscopic surgery for patients with early esophageal carcinoma concomitant with achalasia remains unclear.CASE SUMMARY A c...BACKGROUND Achalasia is associated with high risk of esophageal carcinoma.However,the optimal endoscopic surgery for patients with early esophageal carcinoma concomitant with achalasia remains unclear.CASE SUMMARY A combination of concurrent endoscopic submucosal dissection(ESD)and modified peroral endoscopic myotomy(POEM)was performed on a 62-year-old male,who presented with multiple early esophageal carcinomas concomitant with achalasia.The patient exhibited an improvement in feeding obstruction,and presented no evidence of disease during the 3-year follow-up.CONCLUSION The combination of ESD and POEM is a feasible treatment modality for patients with early esophageal carcinoma concomitant with achalasia.展开更多
AIM: To evaluate the role of baicalin in ulcerative colitis (UC) with regard to the CD4<sup>+</sup>CD29<sup>+</sup> T helper cell, its surface markers and serum inflammatory cytokines.
BACKGROUND Cervical lymph node metastasis in papillary thyroid carcinoma(PTC) affects the treatment and prognosis of patients. Ultrasound is a common imaging method for detecting cervical lymph nodes in PTC patients; ...BACKGROUND Cervical lymph node metastasis in papillary thyroid carcinoma(PTC) affects the treatment and prognosis of patients. Ultrasound is a common imaging method for detecting cervical lymph nodes in PTC patients; however, it is not accurate in determining lymph node metastasis.AIM To evaluate the value of contrast-enhanced ultrasound combined with elastography in evaluating cervical lymph node metastasis in PTC.METHODS A total of 94 patients with PTC were recruited. According to pathological results,lymph nodes were divided into two groups: metastatic group(n = 50) and reactive group(n = 63). The routine ultrasound findings, contrast-enhanced ultrasound and elastography data were recorded and compared. Logistic regression was used to generate predictive probability distributions for the diagnosis of lymph node metastasis with different indicators. Receiver operating characteristic curve analysis was used to test the efficacy of contrast-enhanced ultrasound combined with elastography based on routine ultrasound in evaluating PTC cervical lymph node metastasis.RESULTS The ratio of long diameter/short diameter(L/S) ≤ 2, irregular marginal morphology, missing lymphatic portal, peripheral or mixed blood flow distribution, peak intensity(PI), non-uniform contrast distribution and elasticity score in the metastatic group were significantly higher than those in the reactive group(P < 0.05). L/S ratio, missing lymphatic portal, PI and elasticity score had a significant influence on the occurrence of PTC cervical lymph node metastasis(P< 0.05). Furthermore, the area under the curve(AUC) for lymph node metastasis diagnosed using the combination of PI ratio, elasticity score, missing lymphatic portal and LS was 0.936, which was significantly higher than the AUC for PI ratio alone. The difference was statistically significant(P < 0.05). The fitting equation for the combined diagnosis was logit(P) =-12.341 + 1.482 × L/S ratio + 3.529 ×missing lymphatic portal + 0.392 × PI + 3.288 × elasticity score.CONCLUSION Based on the gray-scale ultrasound, the combination of contrast-enhanced ultrasound and elastography can accurately assess PTC cervical lymph node metastasis.展开更多
Background: Previous research suggested that insulin-like growth factor binding protein related protein 1(IGFBPrP1), as a novel mediator, contributes to hepatic fibrogenesis. Matrix metalloproteinases(MMP) and tissue ...Background: Previous research suggested that insulin-like growth factor binding protein related protein 1(IGFBPrP1), as a novel mediator, contributes to hepatic fibrogenesis. Matrix metalloproteinases(MMP) and tissue inhibitors of metalloproteinases(TIMP) play an essential role in hepatic fibrogenesis by regulating homeostasis and remodeling of the extracellular matrix(ECM). However, the interaction between IGFBPrP1 and MMP/TIMP is not clear. The present study was to knockdown IGFBPrP1 to investigate the correlation between IGFBPrP1 and MMP/TIMP in hepatic fibrosis. Methods: Hepatic fibrosis was induced by thioacetamide(TAA) in mice. Knockdown of IGFBPrP1 expression by ultrasound-targeted microbubble destruction-mediated CMB-shRNA-IGFBPrP1 delivery, or inhibition of the Hedgehog(Hh) pathway by cyclopamine treatment, was performed in TAA-induced liver fibrosis mice. Hepatic fibrosis was determined by hematoxylin and eosin and Sirius red staining. Hepatic expression of IGFBPrP1, α-smooth muscle actin( α-SMA), transforming growth factor β 1(TGF β1), collagen I, MMPs/TIMPs, Sonic Hedgehog(Shh), and glioblastoma family transcription factors(Gli1) were investigated by immunohistochemical staining and Western blotting analysis. Results: We found that hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I were increased longitudinally in mice with TAA-induced hepatic fibrosis, concomitant with MMP2/TIMP2 and MMP9/TIMP1 imbalance and Hh pathway activation. Knockdown of IGFBPrP1 expression, or inhibition of the Hh pathway, reduced the hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I and re-established MMP2/TIMP2 and MMP9/TIMP1 balance. Conclusions: Our findings suggest that IGFBPrP1 knockdown attenuates liver fibrosis by re-establishing MMP2/TIMP2 and MMP9/TIMP1 balance, concomitant with the inhibition of hepatic stellate cell activation, down-regulation of TGF β1 expression, and degradation of the ECM. Furthermore, the Hh pathway mediates IGFBPrP1 knockdown-induced attenuation of hepatic fibrosis through the regulation of MMPs/TIMPs balance.展开更多
AIM: To study differences in the visceral sensitivity of the colonic mucosa between patients with diarrheapredominant irritable bowel syndrome(IBS-D) and those with ulcerative colitis(UC) in remission and to relate th...AIM: To study differences in the visceral sensitivity of the colonic mucosa between patients with diarrheapredominant irritable bowel syndrome(IBS-D) and those with ulcerative colitis(UC) in remission and to relate these differences with changes in the 5-hydroxytryptophan(5-HT) signaling pathway. METHODS: Gastrointestinal symptoms were used to determine the clinical symptom scores and rectal visceral sensitivity of patients with IBS-D and patients with UC in remission. Blood levels of 5-HT and5-hydroxyindoleacetic acid(5-HIAA) were measured using an HPLC-electrochemical detection system. The levels of 5-HT 3 receptor(3R), 4R, and 7R m RNAs in colonic biopsy samples were detected using reverse transcription-polymerase chain reaction. The protein expression of TPH1 was analyzed by Western blot and immunohistochemistry.RESULTS: Abdominal pain or discomfort, stool frequency, and the scores of these symptoms in combination with gastrointestinal symptoms were higher in the IBS-D and UC groups than in the control groups. However, no significant differences were observed between the IBS-D and UC remission groups. With respect to rectal visceral sensitivity, the UC remission and IBS-D groups showed a decrease in the initial perception threshold, defecating threshold and pain threshold. However, these groups exhibited significantly increased anorectal relaxation pressure. Tests examining the main indicators of the 5-HT signaling pathway showed that the plasma 5-HT levels, 5-HIAA concentrations, TPH1 expression in the colonic mucosa, and 5-HT3 R and 5-HT5 R expression were increased in both the IBS-D and the UC remission groups; no increases were observed with respect to 5-HT7 R expression.CONCLUSION: The IBS-D and UC groups showed similar clinical symptom scores, visceral sensitivity, and levels of serotonin signaling pathway indicators in the plasma and colonic mucosa. However, the pain threshold and 5-HT7 R expression in the colonic mucosa were significantly different between these groups. The results reveal that(1) IBS-D and UC are related to visceral sensitivity pathogenesis and the clinical manifestations of these conditions and(2) the observed differences in visceral hypersensitivity are possibly due to differences in levels of the 5-HT7 receptor, a component of the 5-HT signaling pathway.展开更多
AIM:To investigate the efficacy and molecularmechanisms of induced heme oxygenase(HO)-1 in protecting liver from warm ischemia/reperfusion(I/R)injury.METHODS:Partial warm ischemia was produced in the left and middle h...AIM:To investigate the efficacy and molecularmechanisms of induced heme oxygenase(HO)-1 in protecting liver from warm ischemia/reperfusion(I/R)injury.METHODS:Partial warm ischemia was produced in the left and middle hepatic lobes of SD rats for 75min,followed by 6 h of reperfusion.Rats were treated with saline,cobalt protoporphyrin(Co PP)or zinc protoporphyrin(Zn PP)at 24 h prior to the ischemia insult.Blood and samples of ischemic lobes subjected to ischemia were collected at 6 h after reperfusion.Serum transaminases level,plasma lactate dehydrogenase and myeloperoxidase activity in liver were measured.Liver histological injury and inflammatory cell infiltration were evaluated by tissue section and liver immunohistochemical analysis.We used quantitative reverse transcription polymerase chain reaction to analyze liver expression of inflammatory cytokines and chemokines.The cell lysates were subjected to immunoprecipitation with anti-Toll-IL-1R-containing adaptor inducing interferon-β(TRIF)and anti-myeloid differentiation factor 88(My D88),and then the immunoprecipitates were analyzed by SDS-PAGE and immunoblotted with the indicated antibodies.RESULTS:HO-1 protected livers from I/R injury,as evidenced by diminished liver enzymes and wellpreserved tissue architecture.In comparison with Zn PP livers 6 h after surgery,Co PP treatment livers showed a significant increase inflammatory cell infiltration of lymphocytes,plasma cells,neutrophils and macrophages.The Toll-like receptor(TLR)-4 and TANK binding kinase1 protein levels of rats treated with Co PP significantly reduced in TRIF-immunoprecipitated complex,as compared with Zn PP treatment.In addition,pretreatment with Co PP reduced the expression levels of TLR2,TLR4,IL-1R-associated kinase(IRAK)-1 and tumor necrosis factor receptor-associated factor 6 in My D88-immunoprecipitated complex.The inflammatory cytokines and chemokines m RNA expression rapidly decreased inCo PP-pretreated liver,compared with the Zn PP-treated group.However,the expression of negative regulators Tollinteracting protein,suppressor of cytokine signaling-1,IRAK-M and Src homology 2 domain-containing inositol-5-phosphatase-1 in Co PP treatment rats were markedly up-regulated as compared with Zn PP-treated rats.CONCLUSION:HO-1 protects liver against I/R injury by inhibiting TLR2/TLR4-triggered My D88-and TRIFdependent signaling pathways and increasing expression of negative regulators of TLR signaling in rats.展开更多
The superplastic deformation diffusion bonding of 00Cr25Ni7Mo3N duplex stainless steel was performed on a hot simulator. The microstructure of the bonding interface was characterized by scanning electron microscopy （...The superplastic deformation diffusion bonding of 00Cr25Ni7Mo3N duplex stainless steel was performed on a hot simulator. The microstructure of the bonding interface was characterized by scanning electron microscopy （SEM） and electron backscatter diffraction （EBSD）. The mechanical properties of the specimen were investigated by a shear strength test. The results indicated that the shear strength was improved with the increase of superplastic deformation reduction. When the deformation reduction was up to 50%, the shear strength of the specimen achieved 417 Mpa, approaching to that of the base metal. In addtion, the superplastic diffusion bonding technique was not very sensitive to surface roughness levels. When the surface roughness of the bonding specimen surpassed 0.416 pan （level G2）, the shear strength achieved at least 381 MPa.展开更多
AIM: To investigate the role and mechanism of insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) in the development of liver fibrosis.
As the most sensitive single-dish radio telescope,the Five-hundred Aperture Spherical radio Telescope(FAST)is very susceptive to radio frequency interference(RFI)from active radio services.Moreover,due to the rapid de...As the most sensitive single-dish radio telescope,the Five-hundred Aperture Spherical radio Telescope(FAST)is very susceptive to radio frequency interference(RFI)from active radio services.Moreover,due to the rapid development of space applications and research,satellite interference has become one of the main RFI sources for FAST,particularly at the L band.Therefore,we have developed several measures to mitigate satellite RFI.On the one hand,an antenna with 4.5-meter diameter has been constructed and installed at the FAST site to detect the satellite interference in the frequency band between 1 to 5 GHz.Meanwhile,we have developed a satellite RFI database based on the FAST sky coverage,the observing frequency bands,and known satellite systems.By combining the satellite RFI monitoring antenna and the database,we have established a satellite RFI mitigation system.With this system,we can not only track satellites to collect their characteristics and update the database but also help the observer to program the observing plan by predicting satellite interference.During the practical observation of FAST at the L band,the feasibility of this system to mitigate satellite RFI has been proved.In particular,the system effectively avoids strong satellite interference from entering the main beam of the telescope and causing receiver saturation.展开更多
BACKGROUND: We previously showed that insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) is a novel mediator in liver fibrosis. Transforming growth factor beta 1 (TGF beta 1) is known as the stron...BACKGROUND: We previously showed that insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) is a novel mediator in liver fibrosis. Transforming growth factor beta 1 (TGF beta 1) is known as the strongest effector of liver fibrosis. Therefore, we aimed to investigate the detailed interaction between IGFBPrP1 and TGF beta 1 in primary hepatic stellate cells (HSCs). METHODS: We overexpressed TGF beta 1 or IGFBPrP1 and inhibited TGF beta 1 expression in primary HSCs for 6, 12, 24, 48, 72, and 96 hours to investigate their interaction and observe the accompanying expressions of a-smooth muscle actin (alpha-SMA), collagen I, fibronectin, and phosphorylated-mothers against decapentaplegic homolog 2/3 (p-Smad2/3). RESULTS: We found that the adenovirus vector encoding the TGF beta 1 gene (AdTGF beta 1) induced IGFBPrP1 expression while that of alpha-SMA, collagen I, fibronectin, and TGF beta 1 increased gradually. Concomitantly, AdIGFBPrP1 upregulated TGF beta 1, alpha-SMA, collagen I, fibronectin, and p-Smad2/3 in a time-dependent manner while IGFBPrP1 expression was decreased at 96 hours. Inhibition of TGF beta 1 expression reduced the IGFBPrP1-stimulated expression of alpha-SMA, collagen I, fibronectin, and p-Smad2/3. CONCLUSIONS: These findings for the first time suggest the existence of a possible mutually regulation between IGFBPrP1 and TGF beta 1, which likely accelerates liver fibrosis progression. Furthermore, IGFBPrP1 likely participates in liver fibrosis in a TGF beta 1-depedent manner, and may act as an upstream regulatory factor of TGF beta 1 in the Smad pathway.展开更多
Radio Frequency Interference(RFI)mitigation is essential for supporting the science output of Five-hundred-meter Aperture Spherical radio Telescope(FAST)due to its high sensitivity.In order to protect FAST from RFI,an...Radio Frequency Interference(RFI)mitigation is essential for supporting the science output of Five-hundred-meter Aperture Spherical radio Telescope(FAST)due to its high sensitivity.In order to protect FAST from RFI,an Electromagnetic Compatibility(EMC)study has been carried out and the operation of a Radio Quiet Zone(RQZ)is ongoing.RFI measurements of the telescope instruments and monitoring of the active radio services outside the site have revealed the radiation properties of the RFI sources.Based on the measurement results and theoretical analysis,various EMC methods have been implemented for the telescope to decrease the RFIs.Meanwhile,the main RFI sources in the FAST RQZ,such as mobile stations,broadcast stations and navigation instruments,have been identified,and the technical measures have been adopted to protect the quiet radio environment around the site.The early science outputs of FAST have demonstrated the efficiency of RFI mitigation methods.展开更多
The Hefei Advanced Light Facility(HALF)proposed by the National Synchrotron Radiation Laboratory(NSRL)is a diffraction-limited storage ring(DLSR),which plans to use a full energy linac as the injector.To ensure inject...The Hefei Advanced Light Facility(HALF)proposed by the National Synchrotron Radiation Laboratory(NSRL)is a diffraction-limited storage ring(DLSR),which plans to use a full energy linac as the injector.To ensure injection efficiency,the injection beam needs to have low emittance.Therefore,a photocathode radio frequency(RF)gun was developed in the HALF R&D project.The gun is designed to deliver high-quality electron bunches with a typically 0.5 nC charge and~4.5 MeV energy with low emittance.The initial system commission with an electron beam was completed at the end of 2020,and a stable 1.2–1.4 mm.mrad emittance with a bunch charge of 500 pC was demonstrated.In this paper,we report the experimental results and experience obtained during the commission,including the RF gun,drive laser system,and beam diagnostics.展开更多
Invasive species have profound negative impacts on native ranges.Unraveling the mechanisms employed by invasive plant species is crucial to controlling invasions.One important approach that invasive plants use to outc...Invasive species have profound negative impacts on native ranges.Unraveling the mechanisms employed by invasive plant species is crucial to controlling invasions.One important approach that invasive plants use to outcompete native plants is to disrupt mutualistic interactions between native roots and mycorrhizal fungi.However,it remains unclear how differences in the competitive ability of invasive plants affect native plant associations with mycorrhizae.Here,we examined how a native plant,Xanthium strumarium,responds to invasive plants that differed in competitive abilities(i.e.,as represented by aboveground plant biomass)by measuring changes in root nitrogen concentration(root nutrient acquisition)and mycorrhizal colonization rate.We found that both root nitrogen concentration and mycorrhizal colonization rate in the native plant were reduced by invasive plants.The change in mycorrhizal colonization rate of the native plant was negatively correlated with both aboveground plant biomass of the invasive plants and the change in aboveground plant biomass of the native plant in monocultures relative to mixed plantings.In contrast,the change in root nitrogen concentration of the native plant was positively correlated with aboveground plant biomass of the invasive plants and the change in aboveground plant biomass of the native plant.When we compared the changes in mycorrhizal colonization rate and root nitrogen concentration in the native plant grown in monocultures with those of native plants grown with invasive plants,we observed a significant tradeoff.Our study shows that invasive plants can suppress native plants by reducing root nutrient acquisition rather than by disrupting symbiotic mycorrhizal associations,a novel finding likely attributable to a low dependence of the native plant on mycorrhizal fungi.展开更多
SOX9(SRY-related HMG box gene 9)is an essential regulator of male sex determination and testis differentiation in many vertebrate species.However,the functional role of Sox9 in testis differentiation has not yet been ...SOX9(SRY-related HMG box gene 9)is an essential regulator of male sex determination and testis differentiation in many vertebrate species.However,the functional role of Sox9 in testis differentiation has not yet been identified in any reptilian species.Herein,Sox9 knockdown in the red-eared slider turtle(Trachemys scripta)embryos at a male-producing temperature led to complete male-to-female sex reversal,characterized by the formation of an ovary-like structure,disappearance of male marker AMH,and ectopic expression of ovarian regulator FOXL2,as well as a female distribution pattern of germ cells.Conversely,in-ovo overexpression of Sox9 at a female-producing temperature resulted in partial masculinization of putative female embryos,with the coexistence of AMH and FOXL2.Our study provides the first direct evidence that Sox9 is indispensable for testicular differentiation in a reptilian species,further confirming the conserved role of Sox9 in vertebrate sexual development.展开更多
The discovery of ubiquitous habitable extrasolar planets,combined with revolutionary advances in instrumentation and observational capabilities,has ushered in a renaissance in the search for extraterrestrial intellige...The discovery of ubiquitous habitable extrasolar planets,combined with revolutionary advances in instrumentation and observational capabilities,has ushered in a renaissance in the search for extraterrestrial intelligence(SETI).Large scale SETI activities are now underway at numerous international facilities.The Five-hundred-meter Aperture Spherical radio Telescope(FAST)is the largest single-aperture radio telescope in the world,and is well positioned to conduct sensitive searches for radio emission indicative of exo-intelligence.SETI is one of the five key science goals specified in the original FAST project plan.A collaboration with the Breakthrough Listen Initiative was initiated in 2016 with a joint statement signed both by Dr.Jun Yan,the then director of National Astronomical Observatories,Chinese Academy of Sciences(NAOC),and Dr.Peter Worden,Chairman of the Breakthrough Prize Foundation.In this paper,we highlight some of the unique features of FAST that will allow for novel SETI observations.We identify and describe three different signal types indicative of a technological source,namely,narrow band,wide-band artificially dispersed and modulated signals.Here,we propose observations with FAST to achieve sensitivities never before explored.For nearby exoplanets,such as TESS targets,FAST will be sensitive to an EIRP of 1.9×1011 W,well within the reach of current human technology.For the Andromeda Galaxy,FAST will be able to detect any Kardashev type II or more advanced civilization there.展开更多
A method of combining Green’s function retrieval theory and ultrasonic array imaging using Lamb waves is presented to solve near filed defects in thin aluminum plates.The defects are close to the ultrasonic phased ar...A method of combining Green’s function retrieval theory and ultrasonic array imaging using Lamb waves is presented to solve near filed defects in thin aluminum plates.The defects are close to the ultrasonic phased array and satisfy the near field calculation formula.Near field acoustic information of defects is obscured by the nonlinear effects of initial wave signal in a directly acquired response using the full matrix capture mode.A reconstructed full matrix of inter-element responses is produced from cross-correlation of directly received ultrasonic signals between sensor pairs.This new matrix eliminates the nonlinear interference and restores the near-field defect information.The topological imaging method that was developed in recent ultrasonic inspection is used for displaying the scatterers.The experiments are conducted on both thin aluminum plates containing two and four defects, respectively.The results show that these defects are clearly identified when using a reconstructed full matrix.The spatial resolution is equal to about one wavelength of the selectively excited mode and the identifiable defect is about one fifth of the wavelength.However, in a conventional directly captured image,the images of defects overlap together and cannot be distinguished.The proposed method reduces the background noise and allows for effective topological imaging of near field defects.展开更多
基金This study was supported by grants from the High-level Preresearch Program of Zhejiang Shuren University 2019(KXJ121860)Zhejiang Provincial Natural Science Foundation of China(LQ20H190004)。
文摘Background:Hepatocellular carcinoma(HCC)has a poor long-term prognosis.The competition of circular RNAs(circRNAs)with endogenous RNA is a novel tool for predicting HCC prognosis.Based on the alterations of circRNA regulatory networks,the analysis of gene modules related to HCC is feasible.Methods:Multiple expression datasets and RNA element targeting prediction tools were used to construct a circRNA-microRNA-mRNA network in HCC.Gene function,pathway,and protein interaction analyses were performed for the differentially expressed genes(DEGs)in this regulatory network.In the proteinprotein interaction network,hub genes were identified and subjected to regression analysis,producing an optimized four-gene signature for prognostic risk stratification in HCC patients.Anti-HCC drugs were excavated by assessing the DEGs between the low-and high-risk groups.A circRNA-microRNA-hub gene subnetwork was constructed,in which three hallmark genes,KIF4A,CCNA2,and PBK,were subjected to functional enrichment analysis.Results:A four-gene signature(KIF4A,CCNA2,PBK,and ZWINT)that effectively estimated the overall survival and aided in prognostic risk assessment in the The Cancer Genome Atlas(TCGA)cohort and International Cancer Genome Consortium(ICGC)cohort was developed.CDK inhibitors,PI3K inhibitors,HDAC inhibitors,and EGFR inhibitors were predicted as four potential mechanisms of drug action(MOA)in high-risk HCC patients.Subsequent analysis has revealed that PBK,CCNA2,and KIF4A play a crucial role in regulating the tumor microenvironment by promoting immune cell invasion,regulating microsatellite instability(MSI),and exerting an impact on HCC progression.Conclusions:The present study highlights the role of the circRNA-related regulatory network,identifies a four-gene prognostic signature and biomarkers,and further identifies novel therapy for HCC.
文摘BACKGROUND Achalasia is associated with high risk of esophageal carcinoma.However,the optimal endoscopic surgery for patients with early esophageal carcinoma concomitant with achalasia remains unclear.CASE SUMMARY A combination of concurrent endoscopic submucosal dissection(ESD)and modified peroral endoscopic myotomy(POEM)was performed on a 62-year-old male,who presented with multiple early esophageal carcinomas concomitant with achalasia.The patient exhibited an improvement in feeding obstruction,and presented no evidence of disease during the 3-year follow-up.CONCLUSION The combination of ESD and POEM is a feasible treatment modality for patients with early esophageal carcinoma concomitant with achalasia.
基金Supported by National Natural Science Foundation of Chinunder Grant No.30772701
文摘AIM: To evaluate the role of baicalin in ulcerative colitis (UC) with regard to the CD4<sup>+</sup>CD29<sup>+</sup> T helper cell, its surface markers and serum inflammatory cytokines.
基金Supported by Shenzhen Science and Technology Plan Funding Project,No.201102125
文摘BACKGROUND Cervical lymph node metastasis in papillary thyroid carcinoma(PTC) affects the treatment and prognosis of patients. Ultrasound is a common imaging method for detecting cervical lymph nodes in PTC patients; however, it is not accurate in determining lymph node metastasis.AIM To evaluate the value of contrast-enhanced ultrasound combined with elastography in evaluating cervical lymph node metastasis in PTC.METHODS A total of 94 patients with PTC were recruited. According to pathological results,lymph nodes were divided into two groups: metastatic group(n = 50) and reactive group(n = 63). The routine ultrasound findings, contrast-enhanced ultrasound and elastography data were recorded and compared. Logistic regression was used to generate predictive probability distributions for the diagnosis of lymph node metastasis with different indicators. Receiver operating characteristic curve analysis was used to test the efficacy of contrast-enhanced ultrasound combined with elastography based on routine ultrasound in evaluating PTC cervical lymph node metastasis.RESULTS The ratio of long diameter/short diameter(L/S) ≤ 2, irregular marginal morphology, missing lymphatic portal, peripheral or mixed blood flow distribution, peak intensity(PI), non-uniform contrast distribution and elasticity score in the metastatic group were significantly higher than those in the reactive group(P < 0.05). L/S ratio, missing lymphatic portal, PI and elasticity score had a significant influence on the occurrence of PTC cervical lymph node metastasis(P< 0.05). Furthermore, the area under the curve(AUC) for lymph node metastasis diagnosed using the combination of PI ratio, elasticity score, missing lymphatic portal and LS was 0.936, which was significantly higher than the AUC for PI ratio alone. The difference was statistically significant(P < 0.05). The fitting equation for the combined diagnosis was logit(P) =-12.341 + 1.482 × L/S ratio + 3.529 ×missing lymphatic portal + 0.392 × PI + 3.288 × elasticity score.CONCLUSION Based on the gray-scale ultrasound, the combination of contrast-enhanced ultrasound and elastography can accurately assess PTC cervical lymph node metastasis.
基金supported by grants from National Natural Science Foundation of China(81670559)Key Research and Development Project of Shanxi Province(201603D421023)+2 种基金Youth Fund of Shanxi Medical University(02201514)Graduate Student Education Innovation Project of Shanxi(2016BY077)Youth Fund of Ap-plied Basic Research Program of Shanxi(201701D221175)
文摘Background: Previous research suggested that insulin-like growth factor binding protein related protein 1(IGFBPrP1), as a novel mediator, contributes to hepatic fibrogenesis. Matrix metalloproteinases(MMP) and tissue inhibitors of metalloproteinases(TIMP) play an essential role in hepatic fibrogenesis by regulating homeostasis and remodeling of the extracellular matrix(ECM). However, the interaction between IGFBPrP1 and MMP/TIMP is not clear. The present study was to knockdown IGFBPrP1 to investigate the correlation between IGFBPrP1 and MMP/TIMP in hepatic fibrosis. Methods: Hepatic fibrosis was induced by thioacetamide(TAA) in mice. Knockdown of IGFBPrP1 expression by ultrasound-targeted microbubble destruction-mediated CMB-shRNA-IGFBPrP1 delivery, or inhibition of the Hedgehog(Hh) pathway by cyclopamine treatment, was performed in TAA-induced liver fibrosis mice. Hepatic fibrosis was determined by hematoxylin and eosin and Sirius red staining. Hepatic expression of IGFBPrP1, α-smooth muscle actin( α-SMA), transforming growth factor β 1(TGF β1), collagen I, MMPs/TIMPs, Sonic Hedgehog(Shh), and glioblastoma family transcription factors(Gli1) were investigated by immunohistochemical staining and Western blotting analysis. Results: We found that hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I were increased longitudinally in mice with TAA-induced hepatic fibrosis, concomitant with MMP2/TIMP2 and MMP9/TIMP1 imbalance and Hh pathway activation. Knockdown of IGFBPrP1 expression, or inhibition of the Hh pathway, reduced the hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I and re-established MMP2/TIMP2 and MMP9/TIMP1 balance. Conclusions: Our findings suggest that IGFBPrP1 knockdown attenuates liver fibrosis by re-establishing MMP2/TIMP2 and MMP9/TIMP1 balance, concomitant with the inhibition of hepatic stellate cell activation, down-regulation of TGF β1 expression, and degradation of the ECM. Furthermore, the Hh pathway mediates IGFBPrP1 knockdown-induced attenuation of hepatic fibrosis through the regulation of MMPs/TIMPs balance.
基金Supported by The Natural Science Foundation of Guangdong,No.S2012040006557
文摘AIM: To study differences in the visceral sensitivity of the colonic mucosa between patients with diarrheapredominant irritable bowel syndrome(IBS-D) and those with ulcerative colitis(UC) in remission and to relate these differences with changes in the 5-hydroxytryptophan(5-HT) signaling pathway. METHODS: Gastrointestinal symptoms were used to determine the clinical symptom scores and rectal visceral sensitivity of patients with IBS-D and patients with UC in remission. Blood levels of 5-HT and5-hydroxyindoleacetic acid(5-HIAA) were measured using an HPLC-electrochemical detection system. The levels of 5-HT 3 receptor(3R), 4R, and 7R m RNAs in colonic biopsy samples were detected using reverse transcription-polymerase chain reaction. The protein expression of TPH1 was analyzed by Western blot and immunohistochemistry.RESULTS: Abdominal pain or discomfort, stool frequency, and the scores of these symptoms in combination with gastrointestinal symptoms were higher in the IBS-D and UC groups than in the control groups. However, no significant differences were observed between the IBS-D and UC remission groups. With respect to rectal visceral sensitivity, the UC remission and IBS-D groups showed a decrease in the initial perception threshold, defecating threshold and pain threshold. However, these groups exhibited significantly increased anorectal relaxation pressure. Tests examining the main indicators of the 5-HT signaling pathway showed that the plasma 5-HT levels, 5-HIAA concentrations, TPH1 expression in the colonic mucosa, and 5-HT3 R and 5-HT5 R expression were increased in both the IBS-D and the UC remission groups; no increases were observed with respect to 5-HT7 R expression.CONCLUSION: The IBS-D and UC groups showed similar clinical symptom scores, visceral sensitivity, and levels of serotonin signaling pathway indicators in the plasma and colonic mucosa. However, the pain threshold and 5-HT7 R expression in the colonic mucosa were significantly different between these groups. The results reveal that(1) IBS-D and UC are related to visceral sensitivity pathogenesis and the clinical manifestations of these conditions and(2) the observed differences in visceral hypersensitivity are possibly due to differences in levels of the 5-HT7 receptor, a component of the 5-HT signaling pathway.
基金Supported by National Natural Science Foundation of China,No.81360079Yunnan Provincial Science and Technology Department and Kunming Medical University Collaborative Fund,No.2013FB142
文摘AIM:To investigate the efficacy and molecularmechanisms of induced heme oxygenase(HO)-1 in protecting liver from warm ischemia/reperfusion(I/R)injury.METHODS:Partial warm ischemia was produced in the left and middle hepatic lobes of SD rats for 75min,followed by 6 h of reperfusion.Rats were treated with saline,cobalt protoporphyrin(Co PP)or zinc protoporphyrin(Zn PP)at 24 h prior to the ischemia insult.Blood and samples of ischemic lobes subjected to ischemia were collected at 6 h after reperfusion.Serum transaminases level,plasma lactate dehydrogenase and myeloperoxidase activity in liver were measured.Liver histological injury and inflammatory cell infiltration were evaluated by tissue section and liver immunohistochemical analysis.We used quantitative reverse transcription polymerase chain reaction to analyze liver expression of inflammatory cytokines and chemokines.The cell lysates were subjected to immunoprecipitation with anti-Toll-IL-1R-containing adaptor inducing interferon-β(TRIF)and anti-myeloid differentiation factor 88(My D88),and then the immunoprecipitates were analyzed by SDS-PAGE and immunoblotted with the indicated antibodies.RESULTS:HO-1 protected livers from I/R injury,as evidenced by diminished liver enzymes and wellpreserved tissue architecture.In comparison with Zn PP livers 6 h after surgery,Co PP treatment livers showed a significant increase inflammatory cell infiltration of lymphocytes,plasma cells,neutrophils and macrophages.The Toll-like receptor(TLR)-4 and TANK binding kinase1 protein levels of rats treated with Co PP significantly reduced in TRIF-immunoprecipitated complex,as compared with Zn PP treatment.In addition,pretreatment with Co PP reduced the expression levels of TLR2,TLR4,IL-1R-associated kinase(IRAK)-1 and tumor necrosis factor receptor-associated factor 6 in My D88-immunoprecipitated complex.The inflammatory cytokines and chemokines m RNA expression rapidly decreased inCo PP-pretreated liver,compared with the Zn PP-treated group.However,the expression of negative regulators Tollinteracting protein,suppressor of cytokine signaling-1,IRAK-M and Src homology 2 domain-containing inositol-5-phosphatase-1 in Co PP treatment rats were markedly up-regulated as compared with Zn PP-treated rats.CONCLUSION:HO-1 protects liver against I/R injury by inhibiting TLR2/TLR4-triggered My D88-and TRIFdependent signaling pathways and increasing expression of negative regulators of TLR signaling in rats.
文摘The superplastic deformation diffusion bonding of 00Cr25Ni7Mo3N duplex stainless steel was performed on a hot simulator. The microstructure of the bonding interface was characterized by scanning electron microscopy （SEM） and electron backscatter diffraction （EBSD）. The mechanical properties of the specimen were investigated by a shear strength test. The results indicated that the shear strength was improved with the increase of superplastic deformation reduction. When the deformation reduction was up to 50%, the shear strength of the specimen achieved 417 Mpa, approaching to that of the base metal. In addtion, the superplastic diffusion bonding technique was not very sensitive to surface roughness levels. When the surface roughness of the bonding specimen surpassed 0.416 pan （level G2）, the shear strength achieved at least 381 MPa.
基金Supported by National Natural Science Foundation of China,No.30871146 and No.81141049Shanxi Provincial Key Scientific Research Projects for the Returned Scholars,2012-4
文摘AIM: To investigate the role and mechanism of insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) in the development of liver fibrosis.
基金the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB23000000)the National Key Research and Development Program(No.2019YFB1312704)+2 种基金the National Natural Science Foundation of China(Program No.U1831128)the International Partnership Program of Chinese Academy of Sciences(Program No.114A11KYSB20160008)supported by the National Development and Reform Commission,the Key Laboratory of FAST of CAS。
文摘As the most sensitive single-dish radio telescope,the Five-hundred Aperture Spherical radio Telescope(FAST)is very susceptive to radio frequency interference(RFI)from active radio services.Moreover,due to the rapid development of space applications and research,satellite interference has become one of the main RFI sources for FAST,particularly at the L band.Therefore,we have developed several measures to mitigate satellite RFI.On the one hand,an antenna with 4.5-meter diameter has been constructed and installed at the FAST site to detect the satellite interference in the frequency band between 1 to 5 GHz.Meanwhile,we have developed a satellite RFI database based on the FAST sky coverage,the observing frequency bands,and known satellite systems.By combining the satellite RFI monitoring antenna and the database,we have established a satellite RFI mitigation system.With this system,we can not only track satellites to collect their characteristics and update the database but also help the observer to program the observing plan by predicting satellite interference.During the practical observation of FAST at the L band,the feasibility of this system to mitigate satellite RFI has been proved.In particular,the system effectively avoids strong satellite interference from entering the main beam of the telescope and causing receiver saturation.
基金supported by a grant from the Shanxi Province Foundation for Returness(2012-4)
文摘BACKGROUND: We previously showed that insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) is a novel mediator in liver fibrosis. Transforming growth factor beta 1 (TGF beta 1) is known as the strongest effector of liver fibrosis. Therefore, we aimed to investigate the detailed interaction between IGFBPrP1 and TGF beta 1 in primary hepatic stellate cells (HSCs). METHODS: We overexpressed TGF beta 1 or IGFBPrP1 and inhibited TGF beta 1 expression in primary HSCs for 6, 12, 24, 48, 72, and 96 hours to investigate their interaction and observe the accompanying expressions of a-smooth muscle actin (alpha-SMA), collagen I, fibronectin, and phosphorylated-mothers against decapentaplegic homolog 2/3 (p-Smad2/3). RESULTS: We found that the adenovirus vector encoding the TGF beta 1 gene (AdTGF beta 1) induced IGFBPrP1 expression while that of alpha-SMA, collagen I, fibronectin, and TGF beta 1 increased gradually. Concomitantly, AdIGFBPrP1 upregulated TGF beta 1, alpha-SMA, collagen I, fibronectin, and p-Smad2/3 in a time-dependent manner while IGFBPrP1 expression was decreased at 96 hours. Inhibition of TGF beta 1 expression reduced the IGFBPrP1-stimulated expression of alpha-SMA, collagen I, fibronectin, and p-Smad2/3. CONCLUSIONS: These findings for the first time suggest the existence of a possible mutually regulation between IGFBPrP1 and TGF beta 1, which likely accelerates liver fibrosis progression. Furthermore, IGFBPrP1 likely participates in liver fibrosis in a TGF beta 1-depedent manner, and may act as an upstream regulatory factor of TGF beta 1 in the Smad pathway.
基金supported by the National Development and Reform Commission,and the Key Laboratory of FAST of CAS
文摘Radio Frequency Interference(RFI)mitigation is essential for supporting the science output of Five-hundred-meter Aperture Spherical radio Telescope(FAST)due to its high sensitivity.In order to protect FAST from RFI,an Electromagnetic Compatibility(EMC)study has been carried out and the operation of a Radio Quiet Zone(RQZ)is ongoing.RFI measurements of the telescope instruments and monitoring of the active radio services outside the site have revealed the radiation properties of the RFI sources.Based on the measurement results and theoretical analysis,various EMC methods have been implemented for the telescope to decrease the RFIs.Meanwhile,the main RFI sources in the FAST RQZ,such as mobile stations,broadcast stations and navigation instruments,have been identified,and the technical measures have been adopted to protect the quiet radio environment around the site.The early science outputs of FAST have demonstrated the efficiency of RFI mitigation methods.
基金supported by Hefei Advanced Light Facility R&D project and the National Natural Science Foundation of China (No.11775216)
文摘The Hefei Advanced Light Facility(HALF)proposed by the National Synchrotron Radiation Laboratory(NSRL)is a diffraction-limited storage ring(DLSR),which plans to use a full energy linac as the injector.To ensure injection efficiency,the injection beam needs to have low emittance.Therefore,a photocathode radio frequency(RF)gun was developed in the HALF R&D project.The gun is designed to deliver high-quality electron bunches with a typically 0.5 nC charge and~4.5 MeV energy with low emittance.The initial system commission with an electron beam was completed at the end of 2020,and a stable 1.2–1.4 mm.mrad emittance with a bunch charge of 500 pC was demonstrated.In this paper,we report the experimental results and experience obtained during the commission,including the RF gun,drive laser system,and beam diagnostics.
基金supported by the National Natural Science Foundation of China(31870522,32171746 and 32171662)the Scientific Research Foundation of Henan Agricultural University(30500854),Research Funds for overseas returnee in Henan Province,China.
文摘Invasive species have profound negative impacts on native ranges.Unraveling the mechanisms employed by invasive plant species is crucial to controlling invasions.One important approach that invasive plants use to outcompete native plants is to disrupt mutualistic interactions between native roots and mycorrhizal fungi.However,it remains unclear how differences in the competitive ability of invasive plants affect native plant associations with mycorrhizae.Here,we examined how a native plant,Xanthium strumarium,responds to invasive plants that differed in competitive abilities(i.e.,as represented by aboveground plant biomass)by measuring changes in root nitrogen concentration(root nutrient acquisition)and mycorrhizal colonization rate.We found that both root nitrogen concentration and mycorrhizal colonization rate in the native plant were reduced by invasive plants.The change in mycorrhizal colonization rate of the native plant was negatively correlated with both aboveground plant biomass of the invasive plants and the change in aboveground plant biomass of the native plant in monocultures relative to mixed plantings.In contrast,the change in root nitrogen concentration of the native plant was positively correlated with aboveground plant biomass of the invasive plants and the change in aboveground plant biomass of the native plant.When we compared the changes in mycorrhizal colonization rate and root nitrogen concentration in the native plant grown in monocultures with those of native plants grown with invasive plants,we observed a significant tradeoff.Our study shows that invasive plants can suppress native plants by reducing root nutrient acquisition rather than by disrupting symbiotic mycorrhizal associations,a novel finding likely attributable to a low dependence of the native plant on mycorrhizal fungi.
基金This study was supported by the National Key Research and Development Program(2018YFD0900203)National Natural Science Foundation of China(31922084,31872960)+1 种基金Natural Science Foundation of Zhejiang Province for Distinguished Young Scholars(LR19C190001)Key Agricultural Project of Ningbo(2019C10018)。
文摘SOX9(SRY-related HMG box gene 9)is an essential regulator of male sex determination and testis differentiation in many vertebrate species.However,the functional role of Sox9 in testis differentiation has not yet been identified in any reptilian species.Herein,Sox9 knockdown in the red-eared slider turtle(Trachemys scripta)embryos at a male-producing temperature led to complete male-to-female sex reversal,characterized by the formation of an ovary-like structure,disappearance of male marker AMH,and ectopic expression of ovarian regulator FOXL2,as well as a female distribution pattern of germ cells.Conversely,in-ovo overexpression of Sox9 at a female-producing temperature resulted in partial masculinization of putative female embryos,with the coexistence of AMH and FOXL2.Our study provides the first direct evidence that Sox9 is indispensable for testicular differentiation in a reptilian species,further confirming the conserved role of Sox9 in vertebrate sexual development.
文摘The discovery of ubiquitous habitable extrasolar planets,combined with revolutionary advances in instrumentation and observational capabilities,has ushered in a renaissance in the search for extraterrestrial intelligence(SETI).Large scale SETI activities are now underway at numerous international facilities.The Five-hundred-meter Aperture Spherical radio Telescope(FAST)is the largest single-aperture radio telescope in the world,and is well positioned to conduct sensitive searches for radio emission indicative of exo-intelligence.SETI is one of the five key science goals specified in the original FAST project plan.A collaboration with the Breakthrough Listen Initiative was initiated in 2016 with a joint statement signed both by Dr.Jun Yan,the then director of National Astronomical Observatories,Chinese Academy of Sciences(NAOC),and Dr.Peter Worden,Chairman of the Breakthrough Prize Foundation.In this paper,we highlight some of the unique features of FAST that will allow for novel SETI observations.We identify and describe three different signal types indicative of a technological source,namely,narrow band,wide-band artificially dispersed and modulated signals.Here,we propose observations with FAST to achieve sensitivities never before explored.For nearby exoplanets,such as TESS targets,FAST will be sensitive to an EIRP of 1.9×1011 W,well within the reach of current human technology.For the Andromeda Galaxy,FAST will be able to detect any Kardashev type II or more advanced civilization there.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11674214 and 11874255)
文摘A method of combining Green’s function retrieval theory and ultrasonic array imaging using Lamb waves is presented to solve near filed defects in thin aluminum plates.The defects are close to the ultrasonic phased array and satisfy the near field calculation formula.Near field acoustic information of defects is obscured by the nonlinear effects of initial wave signal in a directly acquired response using the full matrix capture mode.A reconstructed full matrix of inter-element responses is produced from cross-correlation of directly received ultrasonic signals between sensor pairs.This new matrix eliminates the nonlinear interference and restores the near-field defect information.The topological imaging method that was developed in recent ultrasonic inspection is used for displaying the scatterers.The experiments are conducted on both thin aluminum plates containing two and four defects, respectively.The results show that these defects are clearly identified when using a reconstructed full matrix.The spatial resolution is equal to about one wavelength of the selectively excited mode and the identifiable defect is about one fifth of the wavelength.However, in a conventional directly captured image,the images of defects overlap together and cannot be distinguished.The proposed method reduces the background noise and allows for effective topological imaging of near field defects.
