TuBG1 promotes hepatocellular carcinoma via ATR/P53-apoptosis and cycling pathways

Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate the relationship between TuBG1 and clinical parameters and survival in HCC patients.Methods:The correlation between TuBG1 and clinical parameters and survival in HCC patients was ex-plored by bioinformatics analysis.Immunohistochemistry was used for the verification.The molecular function of TuBG1 was measured using colony formation,scratch assay,trans-well assay and flow cytometry.Gene set enrichment analysis(GSEA)was used to pick up the enriched pathways,followed by investigating the target pathways using Western blotting.The tumor-immune system interactions and drug bank database(TISIDB)was used to evaluate TuBG1 and immunity.Based on the TuBG1-related immune genes,a prognostic model was constructed and was further validated internally and externally.Results:The bioinformatic analysis found high expressed TuBG1 in HCC tissue,which was confirmed us-ing immunohistochemistry and Western blotting.After silencing the TuBG1 in HCC cell lines,more G1 arrested cells were found,cell proliferation and invasion were inhibited,and apoptosis was promoted.Furthermore,the silence of TuBG1 increased the expressions of Ataxia-Telangiectasia and Rad-3(ATR),phospho-P38 mitogen-activated protein kinase(P-P38MAPK),phospho-P53(P-P53),B-cell lymphoma-2 associated X protein(Bax),cleaved caspase 3 and P21;decreased the expressions of B-cell lymphoma-2(Bcl-2),cyclin D1,cyclin E2,cyclin-dependent kinase 2(CDK2)and CDK4.The correlation analysis of immunohistochemistry and clinical parameters and survival data revealed that TuBG1 was negatively corre-lated with the overall survival.The constructed immune prognosis model could effectively evaluate the prognosis.Conclusions:The increased expression of TuBG1 in HCC is associated with poor prognosis,which might be involved in the occurrence and development of HCC.

Gut microbiota contributes to the distinction between two traditional Chinese medicine syndromes of ulcerative colitis

BACKGROUND Ulcerative colitis(UC)is considered to be closely associated with alteration of intestinal microorganisms.According to the traditional Chinese medicine(TCM)theory,UC can be divided into two disease syndromes called Pi-Xu-Shi-Yun(PXSY)and Da-Chang-Shi-Re(DCSR).The relationships among gut microbiota,TCM syndromes,and UC pathogenesis have not been well investigated.AIM To investigate the role of gut microbiota in UC and the distinction of microbiota dysbiosis between PXSY and DCSR syndromes.METHODS From May 2015 to February 2016,UC patients presenting to LongHua Hospital who met the established inclusion and exclusion criteria were enrolled in this retrospective study.Fresh stool specimens of UC patients with PXSY or DCSR were collected.The feces of the control group came from the health examination population of Longhua Hospital.The composition of gut bacterial communities in stool samples was determined by the pyrosequencing of 16S ribosomal RNA.The high-throughput sequencing reads were processed with QIIME,and biological functions were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States.RESULTS The composition of gut bacterial communities in 93 stool samples(30 healthy controls,32 patients with PXSY syndrome,and 31 patients with DCSR syndrome)was determined by the pyrosequencing of 16S ribosomal RNA.Beta diversity showed that the composition of the microbiota was different among the three groups.At the family level,Porphyromonadaceae,Rikeneliaceae,and Lachnospiraceae significantly decreased while Enterococcus,Streptococcus,and other potential pathogens significantly increased in UC patients compared to healthy subjects.At the genus level,Parabacteroides,Dorea,and Ruminococcus decreased while Faeca-libacterium showed increased abundance in UC compared to healthy controls.Five differential taxa were identified between PXSY and DCSR syndromes.At the genus level,a significantly increased abundance of Streptococcus was observed in DCSR patients,while Lachnoclostridium increased in PXSY patients.The differential functional pathways of the gut microbiome between the PXSY and DCSR groups mainly included lipid metabolism,immunity,and the metabolism of polypeptides.CONCLUSION Our study suggests that the gut microbiota contributes to the distinction between the two TCM syndromes of UC.

A Heterologous Fibrin Glue Enhances the Closure Effect of Surgical Suture on the Repair of Annulus Fibrous Defect in a Sheep Model

Improving the closure effect of surgical suture for repair of annulus fibrosus defects remains an unsolved problem.A new type of porcine fibrin glue was reported for the repair of annulus fibrous defects in sheep models in this study.Continuous axial loading test showed that this glue could effectively improve the closure effect of surgical suture for annulus fibrous defect.Magnetic resonance imaging (MRI) of the lumbar spine confirmed that,compared with nonfibrin glue treated intervertebral discs,it contributed to preservation of the nucleus pulposus and maintained the physiological hydration of the intervertebral discs.Moreover,histomorphology evaluation showed that the porcine fibrin glue could partially reverse degeneration of the injured intervertebral discs.Taken together,porcine fibrin glue can effectively enhance the closure effect of surgical suture on annulus fibrosus,improve the repair effect and slow down the degeneration of the intervertebral disc,and provide a potential therapeutic strategy for degenerative intervertebral disc disease.

Bio-compatibility and cytotoxicity studies of water-soluble CuInS_2-ZnS-AFP fluorescence probe in liver cancer cells

BACKGROUND： The oncogenesis of hepatocellular carcinoma（HCC） is not clear. The current methods of the pertinent studies are not precise and sensitive. The present study was to use liver cancer cell line to explore the bio-compatibility and cytotoxicity of ternary quantum dots（QDs） probe and to evaluate the possible application of QDs in HCC.METHODS： CuInS_2-ZnS-AFP fluorescence probe was designed and synthesized to label the liver cancer cell HepG 2. The cytotoxicity of CuInS_2-ZnS-AFP probe was evaluated by MTT experiments and flow cytometry. RESULTS： The labeling experiments indicated that CuInS_2-ZnS QDs conjugated with AFP antibody could enter HepG 2 cells effectively and emit intensive yellow fluorescence by ultraviolet excitation without changing cellular morphology. Toxicity tests suggested that the cytotoxicity of CuInS_2-ZnS-AFP probe was significantly lower than that of CdT e-ZnS-AFP probe（t test, F=0.8, T=-69.326, P〈0.001）. For CuInS_2-ZnS-AFP probe, timeeffect relationship was presented in intermediate concentration（〉20%） groups（P〈0.05） and dose-effect relationship was presented in almost all of the groups（P〈0.05）. CONCLUSION： CuInS_2-ZnS-AFP QDs probe had better biocompatibility and lower cytotoxicity compared with CdT e-ZnS-AFP probe, and could be used for imaging the living cells in vitro.

Au@SiO2 @CuInS2–ZnS/Anti-AFP fluorescent probe improves HCC cell labeling

Background: Clear tumor imaging is essential to the resection of hepatocellular carcinoma(HCC). This study aimed to create a novel biological probe to improve the HCC imaging. Methods: Au nano-flower particles and CuInS2 –Zn S core-shell quantum dots were synthesized by hydrothermal method. Au was coated with porous SiO2 and combined with anti-AFP antibody. HCC cell line HepG2 was used to evaluate the targeting efficacy of the probe, while flow cytometry and MTT assay were used to detect the cytotoxicity and bio-compatibility of the probe. Probes were subcutaneously injected to nude mice to explore light intensity and tissue penetration. Results: The fluorescence stability of the probe was maintained 100% for 24 h, and the brightness value was 4 times stronger than that of the corresponding CuInS2 –Zn S quantum dot. In the targeting experiment, the labeled HepG2 emitted yellow fluorescence. In the cytotoxicity experiments, MTT and flow cytometry results showed that the bio-compatibility of the probe was fine, the inhibition rate of HepG2 cell with 60% Cu-QDs/Anti-AFP probe and Au-QDs/Anti-AFP probe solution for 48 h were significantly different(86.3%±7.0% vs. 4.9%±1.3%, t = 19.745, P < 0.05), and the apoptosis rates were 83.3%±5.1% vs. 4.4%±0.8%( P < 0.001). In the animal experiment, the luminescence of the novel probe can penetrate the abdominal tissues of a mouse, stronger than that of CuInS2 –ZnS quantum dot. Conclusions: The Au@SiO2 @CuInS2 –ZnS/Anti-AFP probe can targetedly recognize and label HepG2 cells with good bio-compatibility and no toxicity, and the strong tissue penetrability of luminescence may be helpful to surgeons.

High-quality reference genomes of swallowtail butterflies provide insights into their coloration evolution

Swallowtail butterflies(Papilionidae)are a historically significant butterfly group due to their colorful wing patterns,extensive morphological diversity,and phylogenetically important position as a sister group to all other butterflies and have been widely studied regarding ecological adaption,phylogeny,genetics,and evolution.Notably,they contain a unique class of pigments,i.e.,papiliochromes,which contribute to their color diversity and various biological functions such as predator avoidance and mate preference.To date,however,the genomic and genetic basis of their color diversity and papiliochrome origin in a phylogenetic and evolutionary context remain largely unknown.Here,we obtained high-quality reference genomes of 11 swallowtail butterfly species covering all tribes of Papilioninae and Parnassiinae using long-read sequencing technology.Combined with previously published butterfly genomes,we obtained robust phylogenetic relationships among tribes,overcoming the challenges of incomplete lineage sorting(ILS)and gene flow.Comprehensive genomic analyses indicated that the evolution of Papilionidae-specific conserved non-exonic elements(PSCNEs)and transcription factor binding sites(TFBSs)of patterning and transporter/cofactor genes,together with the rapid evolution of transporters/cofactors,likely promoted the origin and evolution of papiliochromes.These findings not only provide novel insights into the genomic basis of color diversity,especially papiliochrome origin in swallowtail butterflies,but also provide important data resources for exploring the evolution,ecology,and conservation of butterflies.

Erratum to: A Heterologous Fibrin Glue Enhances the Closure Effect of Surgical Suture on the Repair of Annulus Fibrous Defect in a Sheep Model

The original version of this article unfortunately contained one mistake.The institutions of the authors are wrong.The corrected institutions are given below.

Propensity score matching study of 325 patients with spontaneous rupture of hepatocellular carcinoma

Background:This study aims to find out the possible optimal therapy and assess the prognosis properly for patient with spontaneous rupture of hepatocellular carcinoma(HCC).Methods:Propensity score matching(PSM)analysis was used to study the data from 325 patients with ruptured HCC(RHCC)and 2,291 patients with non-RHCC.Results:The incidence and hospital mortality of RHCC were 5.1%and 0.8%respectively,with a median overall survival(OS)time of 17 months.There was no difference between ruptured and non-RHCC patients undergoing conservation treatment in terms of OS.Trans-arterial embolization(TAE)was carried out in 69(21.2%)cases with RHCC,with a median OS of 7 months,which was no difference from that of non-RHCC(pre-and post-PSM).One hundred and sixty-nine(52.0%)RHCC cases underwent one-stage hepatectomy,with a median OS and disease-free survival(DFS)of 30 and 6 months respectively,which were shorter than that of non-RHCC(post-PSM).TAE plus two-stage hepatectomy was performed in 30 RHCC cases,with a median OS and DFS of 28 and 10 months respectively;these outcomes were better than that from RHCC patients undergoing TAE alone or one-stage hepatectomy(post-PSM),which were no difference from that of non-RHCC patients undergoing hepatectomy.The risk of death for RHCC patient undergoing one-stage hepatectomy is 1.545 times higher than that of one undergoing TAE+two-stage hepatectomy.Conclusions:TAE plus two-stage hepatectomy might be the optimal treatment for RHCC patient.Under the premise of the same pathological properties,there is no difference in prognosis between ruptured and non-RHCC patients if the therapy is appropriate.

Revision and addendum to the manuscript titled“Propensity score matching study of 325 patients with spontaneous rupture of hepatocellular carcinoma”

We gratefully receive the comment entitled“Is transarterial embolization plus two-stage hepatectomy the optimal strategy for the treatment of spontaneous rupture of hepatocellular carcinoma?”(1).We apologize for the two typing errors in the paper:mortality rate of rupture of hepatocellular carcinoma(RHCC)patients was“0.8%”in the abstract should be changed as“0.9%”;“TNM stage”in the discussion should be replaced by“tumor diameter”.Thanks for the careful reading.