Cell division cyclin 25C knockdown inhibits hepatocellular carcinoma development by inducing endoplasmic reticulum stress

BACKGROUND Cell division cyclin 25C(CDC25C)is a protein that plays a critical role in the cell cycle,specifically in the transition from the G2 phase to the M phase.Recent research has shown that CDC25C could be a potential therapeutic target for cancers,particularly for hepatocellular carcinoma(HCC).However,the specific regulatory mechanisms underlying the role of CDC25C in HCC tumorigenesis and development remain incompletely understood.AIM To explore the impact of CDC25C on cell proliferation and apoptosis,as well as its regulatory mechanisms in HCC development.METHODS Hepa1-6 and B16 cells were transduced with a lentiviral vector containing shRNA interference sequences(LV-CDC25C shRNA)to knock down CDC25C.Subsequently,a xenograft mouse model was established by subcutaneously injecting transduced Hepa1-6 cells into C57BL/6 mice to assess the effects of CDC25C knockdown on HCC development in vivo.Cell proliferation and migration were evaluated using a Cell Counting Kit-8 cell proliferation assays and wound healing assays,respectively.The expression of endoplasmic reticulum(ER)stress-related molecules(glucose-regulated protein 78,X-box binding protein-1,and C/EBP homologous protein)was measured in both cells and subcutaneous xenografts using quantitative real-time PCR(qRT-PCR)and western blotting.Additionally,apoptosis was investigated using flow cytometry,qRT-PCR,and western blotting.RESULTS CDC25C was stably suppressed in Hepa1-6 and B16 cells through LV-CDC25C shRNA transduction.A xenograft model with CDC25C knockdown was successfully established and that downregulation of CDC25C expression significantly inhibited HCC growth in mice.CDC25C knockdown not only inhibited cell proliferation and migration but also significantly increased the ER stress response,ultimately promoting ER stress-induced apoptosis in HCC cells.CONCLUSION The regulatory mechanism of CDC25C in HCC development may involve the activation of ER stress and the ER stress-induced apoptosis signaling pathway.

Prognostic significance of lymphovascular invasion in colorectal cancer and its association with genomic alterations

BACKGROUND Lymphovascular invasion (LVI) is suggested to be an early and important step in tumor progression toward metastasis, but its prognostic value and genetic mechanisms in colorectal cancer (CRC) have not been well investigated. AIM To investigate the prognostic value of LVI in CRC and identify the associated genomic alterations. METHODS We performed a retrospective analysis of 1219 CRC patients and evaluated the prognostic value of LVI for overall survival by the Kaplan-Meier method and multivariate Cox regression analysis. We also performed an array-based comparative genomic hybridization analysis of 47 fresh CRC samples to examine the genomic alterations associated with LVI. A decision tree model was applied to identify special DNA copy number alterations (DCNAs) for differentiating between CRCs with and without LVI. Functional enrichment and protein-protein interaction network analyses were conducted to explore the potential molecular mechanisms of LVI. RESULTS LVI was detected in 150 (12.3%) of 1219 CRCs, and the presence was positively associated with higher histological grade and advanced tumor stage (both P < 0.001). Compared with the non-LVI group, the LVI group showed a 1.77-fold (95% confidence interval: 1.40-2.25, P < 0.001) increased risk of death and a significantly lower 5-year overall survival rate (P < 0.001). Based on the comparative genomic hybridization data, 184 DCNAs (105 gains and 79 losses) were identified to be significantly related to LVI (P < 0.05), and the majority were located at 22q, 17q, 10q, and 6q. We further constructed a decision tree classifier including seven special DCNAs, which could distinguish CRCs with LVI from those without it at an accuracy of 95.7%. Functional enrichment and proteinprotein interaction network analyses revealed that the genomic alterations related to LVI were correlated with inflammation, epithelial-mesenchymal transition, angiogenesis, and matrix remodeling. CONCLUSION LVI is an independent predictor for survival in CRC, and its development may correlate with inflammation, epithelial-mesenchymal transition, angiogenesis, and matrix remodeling.

Laparoscopic lateral lymph node dissection in two fascial spaces for locally advanced lower rectal cancer

BACKGROUND The procedure for lateral lymph node(LLN)dissection(LLND)is complicated and can result in complications.We developed a technique for laparoscopic LLND based on two fascial spaces to simplify the procedure.AIM To clarify the anatomical basis of laparoscopic LLND in two fascial spaces and to evaluate its efficacy and safety in treating locally advanced low rectal cancer(LALRC).METHODS Cadaveric dissection was performed on 24 pelvises,and the fascial composition related to LLND was observed and described.Three dimensional-laparoscopic total mesorectal excision with LLND was performed in 20 patients with LALRC,and their clinical data were analyzed.RESULTS The cadaver study showed that the fascia propria of the rectum,urogenital fascia,vesicohypogastric fascia and parietal fascia lie side by side in a medial-lateral direction constituting the dissection plane for curative rectal cancer surgery,and the last three fasciae formed two spaces(Latzko's pararectal space and paravesical space)which were the surgical area for LLND.Laparoscopic LLND in two fascial spaces was performed successfully in all 20 patients.The median operating time,blood loss and postoperative hospitalization were 178(152-243)min,55(25-150)mL and 10(7-20)d,respectively.The median number of harvested LLNs was 8.6(6-12),and pathologically positive LLN metastasis was confirmed in 7(35.0%)cases.Postoperative complications included lower limb pain in 1 case and lymph leakage in 1 case.CONCLUSION Our preliminary surgical experience suggests that laparoscopic LLND based on fascial spaces is a feasible,effective and safe procedure for treating LALRC.

Brain tumors:Cancer stem-like cells interact with tumor microenvironment

Cancer stem-like cells(CSCs)with potential of self-renewal drive tumorigenesis.Brain tumor microenvironment(TME)has been identified as a critical regulator of malignancy progression.Many researchers are searching new ways to characterize tumors with the goal of predicting how they respond to treatment.Here,we describe the striking parallels between normal stem cells and CSCs.We review the microenvironmental aspects of brain tumors,in particular composition and vital roles of immune cells infiltrating glioma and medulloblastoma.By highlighting that CSCs cooperate with TME via various cellular communication approaches,we discuss the recent advances in therapeutic strategies targeting the components of TME.Identification of the complex and interconnected factors can facilitate the development of promising treatments for these deadly malignancies.

Passively stabilized single-photon interferometer

A single-photon interferometer is a fundamental element in quantum information science.In most previously reported works,single-photon interferometers use an active feedback locking system to stabilize the relative phase between two arms of the interferometer.Here,we use a pair of beam displacers to construct a passively stable single-photon interferometer.The relative phase stabilization between the two arms is achieved by stabilizing the temperature of the beam displacers.A purely polarized single-photon-level pulse is directed into the interferometer input port.By analyzing and measuring the polarization states of the single-photon pulse at the output port,the achieved polarization fidelity of the interferometer is about 99.1±0.1%.Our passively stabilized single-photon interferometer provides a key element for generating highfidelity entanglement between a photon and atomic memory.

New classification system for radical rectal cancer surgery based on membrane anatomy

BACKGROUND Total mesorectal excision along the“holy plane”is the only radical surgery for rectal cancer,regardless of tumor size,localization or even tumor stage.However,according to the concept of membrane anatomy,multiple fascial spaces around the rectum could be used as the surgical plane to achieve radical resection.AIM To propose a new membrane anatomical and staging-oriented classification system for tailoring the radicality during rectal cancer surgery.METHODS A three-dimensional template of the member anatomy of the pelvis was established,and the existing anatomical nomenclatures were clarified by cadaveric dissection study and laparoscopic surgical observation.Then,we suggested a new and simple classification system for rectal cancer surgery.For simplification,the classification was based only on the lateral extent of resection.RESULTS The fascia propria of the rectum,urogenital fascia,vesicohypogastric fascia and parietal fascia lie side by side around the rectum and form three spaces(medial,middle and lateral),and blood vessels and nerves are precisely positioned in the fascia or space.Three types of radical surgery for rectal cancer are described,as are a few subtypes that consider nerve preservation.The surgical planes of the proposed radical surgeries(types A,B and C)correspond exactly to the medial,middle,and lateral spaces,respectively.CONCLUSION Three types of radical surgery can be precisely defined based on membrane anatomy,including nerve-sparing procedures.Our classification system may offer an optimal tool for tailoring rectal cancer surgery.

Phospho-proteomics identifies a critical role of ATF2 in pseudorabies virus replication

Pseudorabies virus(PRV),an etiological agent of pseudorabies in livestock,has negatively affected the porcine industry all over the world.Epithelial cells are reported as the first site of PRV infection.However,the role of host proteins and its related signaling pathways in PRV replication is largely unclear.In this study,we performed a quantitative phosphoproteomics screening on PRV-infected porcine kidney(PK-15)epithelial cells.Totally 5723phosphopeptides,corresponding to 2180 proteins,were obtained,and the phosphorylated states of 810 proteins were significantly different in PRV-infected cells compared with mock-infected cells(P<0.05).GO and KEGG analysis revealed that these differentially expressed phosphorylated proteins were predominantly related to RNA transport and MAPK signaling pathways.Further functional studies of NF-κB,transcription activator factor-2(ATF2),MAX and SOS genes in MAPK signaling pathway were analyzed using RNA interference(RNAi)knockdown.It showed that only ATF2-knockdown reduces both PRV titer and viral genome copy number.JNK pathway inhibition and CRISPR/Cas9 gene knockout showed that ATF2 was required for the effective replication of PRV,especially during the biogenesis of viral genome DNA.Subsequently,by overexpression of the ATF2 gene and point mutation of the amino acid positions 69/71 of ATF2,it was further demonstrated that the phosphorylation of ATF2 promoted PRV replication.These findings suggest that ATF2 may provide potential therapeutic target for inhibiting PRV infection.

Determination of continuous constitutive relationship of weld zone of high-strength steel rectangular welded tube

For QSTE700 high-strength steel rectangular welded tube,the mechanical properties of the weld zone vary with the distancefrom the centerline of the weld.Therefore,the accurate description of constitutive relationship of the weld zone is of greatsignificance for the study of formability of QSTE700 rectangular welded tube.Firstly,the mechanical properties of parentand mixed specimens containing weld zone and parent zone were obtained by uniaxial tensile test.And based on the micro-hardness test,the width and the microhardness distribution of the weld zone were determined.Secondly,by subdividingthe weld zone into several small areas,and combining with the rule of mixtures and nanoindentation test,the continuous functional relationships of strength coefficient K,hardening coeffecient n and elastic modulus E were obtained,and then,the continuous constitutive relationship of QSTE700 rectangular welded tube was established.Finally,the validity and reliability of the continuous constitutive relationship of welded tube were verified by nanoindentation fest and rotary drawbending of rectangular welded tubc.Besides,it was found that the finite element model of rotary draw bending of QSTE700 rectangular welded tube established by using the continuous constitutive relationship can well simulate the cross sectiondeformation and wall thickness variation.

Astrocyte elevated gene-1 serves as a target of miR542 to promote glioblastoma proliferation and invasion

Background:Epithelial to mesenchymal transition (EMT) is strongly linked with tumor invasion and metastasis, which performs a vital role in carcinogenesis and cancer progression. Emerging evidence suggests that microRNAs (miRNAs) expression are closely associated to EMT by regulating targeted genes. MiR542 has been found to be involved in the EMT program and bound up with various cancers. However, the functions of miR542 and its underlying mechanism in glioblastoma multiforme (GBM) remain largely unknown. In the current study, we investigated the effect of astrocyte elevated gene-1 ( AEG-1) on U251 cells aggressiveness, proliferation, apoptosis, and cell cycle. Methods:The screening of targeted miRNAs was performed, as well as the functional roles and mechanisms of miR542 were explored.Results:MiR542 was selected as the target because of the most significantly differential expression and this high level of expression negatively correlated with cell migration and proliferation, which suggested that miR542 could be a novel tumor suppressor. Moreover, we confirmed that AEG-1 was a direct targeted gene of miR542 by luciferase activity assay, reverse transcription-polymerase chain reaction, and immunoblotting analysis. Furthermore, miR542 suppressed the expression of AEG-1, which upgraded the level of E-cadherin and degraded Vimentin expression contributing to retraining EMT. Conclusion:The in vitro findings demonstrated that miR542 inhibited the migration and proliferation of U251 cells and suppressed EMT through targeting AEG-1, indicating that miR542 may be a potential anti-cancer target for GBM.

Improvement in irradiation resistance of FeCu alloy by pre-deformation through introduction of dense point defect sinks

The irradiation resistance of pre-deformed FeCu alloy was studied using a 3 MeV Fe ion irradiation experiment at room temperature in comparison with that of the as-received sample.Nanoindentation and atom probe tomography(APT) were used to characterize the mechanical properties and solute distribution.The stress-strain curve obtained by nanoindentation shows that the yield strength(σ0.2) of the pre-deformed sample is unexpectedly reduced with an increase in the irradiation dose to five displacements per atom(dpa).We suggest that it results both from the decrease in the dislocation density and the suppression of defects during irradiation.APT shows that the nucleation of the Cu cluster is suppressed;however,its growth is promoted in the pre-deformed sample,resulting in the formation of sparse and coarse clusters at 1 dpa irradiation.These coarse Cu clusters were then unexpectedly refined to finer grains with an increase in the irradiation dose to 5 dpa.Theoretically,the improvement in the resistance to irradiation in the pre-deformed sample is attributed to the dense point-defect sinks,that is,the dislocations and grain boundaries introduced by pre-deformation.In addition,the contributions of the dislocations and grain boundaries to the sink strength are estimated for both the as-received and pre-deformed samples.The results indicate that dislocations,rather than grain boundaries,play a major role after deformation.