Oxygen tension modulates cell function in an in vitro three-dimensional glioblastoma tumor model

Hypoxia is a typical feature of the tumor microenvironment,one of the most critical factors affecting cell behavior and tumor progression.However,the lack of tumor models able to precisely emulate natural brain tumor tissue has impeded the study of the effects of hypoxia on the progression and growth of tumor cells.This study reports a three-dimensional(3D)brain tumor model obtained by encapsulating U87MG(U87)cells in a hydrogel containing type I collagen.It also documents the effect of various oxygen concentrations(1%,7%,and 21%)in the culture environment on U87 cell morphology,proliferation,viability,cell cycle,apoptosis rate,and migration.Finally,it compares two-dimensional(2D)and 3D cultures.For comparison purposes,cells cultured in flat culture dishes were used as the control(2D model).Cells cultured in the 3D model proliferated more slowly but had a higher apoptosis rate and proportion of cells in the resting phase(G0 phase)/gap I phase(G1 phase)than those cultured in the 2D model.Besides,the two models yielded significantly different cell morphologies.Finally,hypoxia(e.g.,1%O2)affected cell morphology,slowed cell growth,reduced cell viability,and increased the apoptosis rate in the 3D model.These results indicate that the constructed 3D model is effective for investigating the effects of biological and chemical factors on cell morphology and function,and can be more representative of the tumor microenvironment than 2D culture systems.The developed 3D glioblastoma tumor model is equally applicable to other studies in pharmacology and pathology.

Three-dimensional structural models,evolution and petroleum geological significances of transtensional faults in the Ziyang area,central Sichuan Basin,SW China

With drilling and seismic data of Transtensional(strike-slip)Fault System in the Ziyang area of the central Sichuan Basin,SW China plane-section integrated structural interpretation,3-D fault framework model building,fault throw analyzing,and balanced profile restoration,it is pointed out that the transtensional fault system in the Ziyang 3-D seismic survey consists of the northeast-trending F_(I)19 and F_(I)20 fault zones dominated by extensional deformation,as well as 3 sets of northwest-trending en echelon normal faults experienced dextral shear deformation.Among them,the F_(I)19 and F_(I)20 fault zones cut through the Neoproterozoic to Lower Triassic Jialingjiang Formation,presenting a 3-D structure of an“S”-shaped ribbon.And before Permian and during the Early Triassic,the F_(I)19 and F_(I)20 fault zones underwent at least two periods of structural superimposition.Besides,the 3 sets of northwest-trending en echelon normal faults are composed of small normal faults arranged in pairs,with opposite dip directions and partially left-stepped arrangement.And before Permian,they had formed almost,restricting the eastward growth and propagation of the F_(I)19 fault zone.The F_(I)19 and F_(I)20 fault zones communicate multiple sets of source rocks and reservoirs from deep to shallow,and the timing of fault activity matches well with oil and gas generation peaks.If there were favorable Cambrian-Triassic sedimentary facies and reservoirs developing on the local anticlinal belts of both sides of the F_(I)19 and F_(I)20 fault zones,the major reservoirs in this area are expected to achieve breakthroughs in oil and gas exploration.

Differential gene expression during capillary morphogenesis in a microcarrier-based three-dimensional in vitro model of angiogenesis with focus on chemokines and chemokine receptors

AIM:To globally compare the gene expression profiles during the capillary morphogenesis of human microvascular endothelial cells (HMVECs) in an in vitro angiogeness system with affymetrix oligonucleotide array. METHODS: A microcarrier-based in vitro angiogenesis system was developed, in which ECs migrated into the matrix, proliferated, and formed capillary sprouts. The sprouts elongated, branched and formed networks. The total RNA samples from the HMVECs at the selected time points (0.5, 24, and 72 h) during the capillary morphogenesis were used for microarray analyses, and the data were processed with the softwares provided by the manufacturers. The expression patterns of some genes were validated and confirmed by semi-quantitative RT-PCR. The regulated genes were grouped based on their molecular functions and expression patterns, and among them the expression of chemokines and chemokine receptors was specially examined and their functional implications were analyzed. RESULTS: A total of 1 961 genes were up- or downreg-ulated two-folds or above, and among them, 468 genes were up- or down-regulated three-folds or above. The regulated genes could be grouped into categories based on their molecular functions, and were also clustered into six groups based on their patterns of expression. As for chemokines and chemokine receptors, CXCL1/GRO-α, CXCL2/GRO-β, CXCL5/ENA-78, CXCL6/GCP2, IL-8/CXCL8, CXCL12/SDF-1, CXCL9/Mig, CXC11/ITAC, OOCL1/fractalkine, CCL2/MCP-1, CCL3, CCL5/RANTES, CCL7, CCL15, CCL21, CCL23, CCL28, and CCR1, CCR9, CXCR4 were identified. Moreover, these genes demonstrated different changing patterns during the capillary morphogenesis, which implied that they might have different roles in the sequential process. Among the chemokines identified, CCL2/MCP-1, CCL5/RANTES and CX3CL1 were specially up-regulated at the 24-h time point when the sprouting characterized the morphological change. It was thus suggested that they might exert crucial roles at the early stage of angiogenesis. CONCLUSION: The present study demonstrates a global profile of gene expression during endothelial capillary morphogenesis, and the results provide us much information about the molecular mechanisms of angiogenesis, with which further evaluation of individual genes can be conducted.

Effects of three-dimensional quality assessment nursing intervention on efficacy and disease management of patients undergoing esophageal cancer surgery

BACKGROUND Esophageal cancer is one of the most common malignant tumors.The three-dimensional quality structure model is a quality assessment theory that includes three dimensions:Structure,process,and results.AIM To investigate the effects of nursing interventions with three-dimensional quality assessment on the efficacy and disease management ability of patients undergoing esophageal cancer surgery.METHODS In this prospective study,the control group received routine nursing,and the intervention group additionally received a three-dimensional quality assessment intervention based on the above routine care.Self-efficacy and patient disease management abilities were evaluated using the General Self-Efficacy Scale(GSES)and Exercise of Self-Care Agency scale,respectively.IBM SPSS Statistics for Windows,version 17.0,was used for the data processing.RESULTS This study recruited 112 patients who were assigned to the control and experi-mental groups(n=56 per group).Before the intervention,there was no significant difference in GSES scores between the two groups(P>0.05).After the inter-vention,the GSES scores of both groups increased,with the experimental group showing higher values(P<0.05).At the time of discharge and three months after discharge,the scores for positive attitudes,self-stress reduction,and total score of health promotion in the experimental group were higher than those in the control group(P<0.05).CONCLUSION The implementation of a three-dimensional quality structure model for postoperative patients with esophageal cancer can effectively improve their self-management ability and self-efficacy of postoperative patients.

Research on Three-Dimensional Simulation of the Internal Arc Gear Skiving

Aiming at the problems that the simulation accuracy which is reduced due to the simplification of the model,a three-dimensional simulation method based on solid modeling is being proposed.By analyzing the motion relationship and positional relationship between the caries knife and the workpiece,the coordinate system of the caries machining was established.With the MATLAB software,the cutting edge model and the blade sweeping surface model of the boring cutter are sequentially established.Boolean operation is performed on the blade swept surface formed by the tooth cutter teeth with time t and the workpiece tooth geometry as well as the undeformed three-dimensional chip geometry model and the instantaneous cogging geometry model are obtained at different times.Through the compare between gear end face simulation tooth profile and the theoretical inner arc tooth profile,we verified the accuracy and rationality of the proposed method.

Study of the geomagnetic field's regional gradients in Chinese continent using three-dimensional surface Spline model

We combined domestic ground-based and satellite magnetic measurements to create a regional three-dimensional surface Spline(3DSS)gradient model of the main geomagnetic field over the Chinese continent.To improve the precision of the model,we considered the data gap between the ground and satellite data.We compared and analyzed the results of the Taylor polynomial,surface Spline,and CHAOS-6(the CHAMP,?rsted and SAC-C model of Earth’s magnetic field)gradient models.Results showed that the gradients in the south-north and east-west directions of the four models were consistent.The 3DSS model was able to express not only gradients at different altitudes,but also average gradients inside the research area.The two Spline models were able to capture more information on gradient anomalies than were the fitted models.Strong local anomalies were observed in northern Xinjiang,Beijing,and the junction area between Jiangsu and Zhejiang,and the total intensity F decreased whereas the altitude increased.The gradient decreased by 21.69%in the south-north direction and increased by 11.78%in the east-west direction.In addition,the altitude gradient turned from negative to positive while the altitude increased.The Spline model and the two fitted models differed mainly in the field sources they expressed and the modeling theory.

Can preoperative planning using IRIS™three-dimensional anatomical virtual models predict operative findings during robot-assisted partial nephrectomy?

Objective To evaluate the predictive validity of IRIS™(Intuitive Surgical®,Sunnyvale,CA,USA)as a planning tool for robot-assisted partial nephrectomy(RAPN)by assessing the degree of overlap with intraoperative execution.Methods Thirty-one patients scheduled for RAPN by four experienced urologists were enrolled in a prospective study.Prior to surgery,urologists reviewed the IRIS™three-dimensional model on an iphone Operating System(iOS)app and completed a questionnaire outlining their surgical plan including surgical approach,and ischemia technique as well as confidence in executing this plan.Postoperatively,questionnaires assessing the procedural approach,clinical utility,efficiency,and effectiveness of IRIS™were completed.The degree of overlap between the preoperative and intraoperative questionnaires and between the planned approach and actual execution of the procedure was analyzed.Questionnaires were answered on a 5-point Likert scale and scores of 4 or greater were considered positive.Results Mean age was 65.1 years with a mean tumor size of 27.7 mm(interquartile range 17.5-44.0 mm).Hilar tumors consisted of 32.3%;48.4%of patients had R.E.N.A.L.nephrometry scores of 7-9.On preoperative questionnaires,the surgeons reported that in 67.7%cases they were confident that they can perform the procedure successfully,and on intraoperative questionnaires,the surgeons reported that in 96.8%cases IRIS™helped achieve good spatial sensation of the anatomy.There was a high degree of overlap between preoperative and intraoperative questionnaires for the surgical approach,interpreting anatomical details and clinical utility.When comparing plans for selective or off-clamp,the preoperative plan was executed in 90.0%of cases intraoperatively.Conclusion A high degree of overlap between the preoperative surgical approach and intraoperative RAPN execution was found using IRIS™.This is the first study to evaluate the predictive accuracy of IRIS™during RAPN by comparing preoperative plan and intraoperative execution.

Three-Dimensional Analytical Modeling of Axial-Flux Permanent Magnet Drivers

In this paper, the axial-flux permanent magnet driver is modeledand analyzed in a simple and novel way under three-dimensional cylindricalcoordinates. The inherent three-dimensional characteristics of the deviceare comprehensively considered, and the governing equations are solved bysimplifying the boundary conditions. The axial magnetization of the sectorshapedpermanent magnets is accurately described in an algebraic form bythe parameters, which makes the physical meaning more explicit than thepurely mathematical expression in general series forms. The parameters of theBessel function are determined simply and the magnetic field distribution ofpermanent magnets and the air-gap is solved. Furthermore, the field solutionsare completely analytical, which provides convenience and satisfactoryaccuracy for modeling a series of electromagnetic performance parameters,such as the axial electromagnetic force density, axial electromagnetic force,and electromagnetic torque. The correctness and accuracy of the analyticalmodels are fully verified by three-dimensional finite element simulations and a15 kW prototype and the results of calculations, simulations, and experimentsunder three methods are highly consistent. The influence of several designparameters on magnetic field distribution and performance is studied and discussed.The results indicate that the modeling method proposed in this papercan calculate the magnetic field distribution and performance accurately andrapidly, which affords an important reference for the design and optimizationof axial-flux permanent magnet drivers.

Shear behavior of intact granite under thermo-mechanical coupling and three-dimensional morphology of shear-formed fractures

The shear failure of intact rock under thermo-mechanical(TM)coupling conditions is common,such as in enhanced geothermal mining and deep mine construction.Under the effect of a continuous engineering disturbance,shear-formed fractures are prone to secondary instability,posing a severe threat to deep engineering.Although numerous studies regarding three-dimensional(3D)morphologies of fracture surfaces have been conducted,the understanding of shear-formed fractures under TM coupling conditions is limited.In this study,direct shear tests of intact granite under various TM coupling conditions were conducted,followed by 3D laser scanning tests of shear-formed fractures.Test results demonstrated that the peak shear strength of intact granite is positively correlated with the normal stress,whereas it is negatively correlated with the temperature.The internal friction angle and cohesion of intact granite significantly decrease with an increase in the temperature.The anisotropy,roughness value,and height of the asperities on the fracture surfaces are reduced as the normal stress increases,whereas their variation trends are the opposite as the temperature increases.The macroscopic failure mode of intact granite under TM coupling conditions is dominated by mixed tensileeshear and shear failures.As the normal stress increases,intragranular fractures are developed ranging from a local to a global distribution,and the macroscopic failure mode of intact granite changes from mixed tensileeshear to shear failure.Finally,3D morphological characteristics of the asperities on the shear-formed fracture surfaces were analyzed,and a quadrangular pyramid conceptual model representing these asperities was proposed and sufficiently verified.

Study of angiogenesis induced by metastatic and non-metastatic liver cancer by corneal micropocket model in nude mice

AIM To study the angiogenesis induced by liver cancer with different metastatic potentials using corneal micropocket model in nude mice.METHODS Corneal micropockets were created in nude mice. Tumor tissues and liver tissues were implanted into the corneal micropockets. Angiogenesis was observed using a digital camera under slit-lamp biomicroscope, and compared among different grafts and incision alone. Vascular responses were recorded in regard to the range, number and length of new blood vessels toward the grafts or incisions.RESULTS Vascular responses induced by tumor tissues were greater than those by incision alone and liver tissue grafts. LCI-D20 induced more intensive angiogenesis than LCI-D35.CONCLUSION Highly metastatic liver cancer LCI D20 was more angiogenic than low metastatic cancer LCI D35 and liver tissue. Micropocket was a useful model to study dynamic process of angiogenesis in vivo.

Coupled modeling of tumour angiogenesis, tumour growth,and blood perfusion

This paper proposes a more realistic mathematical simulation method to investigate the dynamic process of tumour angio-genesis by fully coupling the vessel growth,tumour growth and associated blood perfusion.The tumour growth and angiogenesis are coupled by the chemical microenvironment and the cell-matrix interaction.The haemodynamic calculation is carried out on the new vasculature,and an estimation of vessel collapse is made according to the wall shear stress criterion.The results are consistent with physiological observations,and further confirm the application of the coupled model feedback mechanism.The model is available to examine the interactions between angiogenesis and tumour growth,to study the change in the dynamic process of chemical environment and the vessel remodeling.

DEVELOPMENT OF A HYBRID MODEL FOR THREE-DIMENSIONAL GIS

This paper presents a hybrid model for three-dimensional Geographical Information Systems which is an integration of surface- and volume-based models. The Triangulated Irregular Network (TIN) and octree models are integrated in this hybrid models. The TIN model works as a surface-based model which mainly serves for surface presentation and visualization. On the other hand, the octree encoding supports volumetric analysis. The designed data structure brings a major advantage in the three-dimensional selective retrieval. This technique increases the efficiency of three-dimensional data operation.

A three-dimensional semi-implicit unstructured grid finite volume ocean model

A new three-dimensional semi-implicit finite-volume ocean model has been developed for simulating the coastal ocean circulation, which is based on the staggered C-unstructured non-orthogonal grid in the hor- izontal direction and z-level grid in the vertical direction. The three-dimensional model is discretized by the semi-implicit finite-volume method, in that the free-surface and the vertical diffusion are semi-implicit, thereby removing stability limitations associated with the surface gravity wave and vertical diffusion terms. The remaining terms in the momentum equations are discretized explicitly by an integral method. The partial cell method is used for resolving topography, which enables the model to better represent irregular topography. The model has been tested against analytical cases for wind and tidal oscillation circulation, and is applied to simulating the tidal flow in the Bohal Sea. The results are in good agreement both with the analytical solutions and measurement results.

Three-dimensional numerical modeling of gravity anomalies based on Poisson equation in spacewavenumber mixed domain

In gravity-anomaly-based prospecting, the computational and memory requirements for practical numerical modeling are potentially enormous. Achieving an efficient and precise inversion for gravity anomaly imaging over large-scale and complex terrain requires additional methods. To this end, we have proposed a new topography-capable By performing a two-dimensional Fourier transform in the horizontal directions, threedimensional partial differential equations in the spatial domain were transformed into a group of independent, one-dimensional differential equations engaged with different wave numbers. These independent differential equations are highly parallel across different wave numbers. differential equations with different wave numbers, and the efficiency of solving fixedbandwidth linear equations was further improved by a chasing method. In a synthetic test, a prism model was used to verify the accuracy and reliability of the proposed algorithm by comparing the numerical solution with the analytical solution. We studied the computational precision and efficiency with and without topography using different Fourier transform methods. The results showed that the Guass-FFT method has higher numerical precision, while the standard FFT method is superior, in terms of computation time, for inversion and quantitative interpretation under complicated terrain.

Platelet-rich plasma enhances adipose-derived stem cell-mediated angiogenesis in a mouse ischemic hindlimb model

AIM To evaluate the angiogenic effect of platelet-rich plasma(PRP)-preconditioned adipose-derived stem cells(ADSCs) both in vitro and in a mouse ischemic hindlimb model.METHODS ADSCs were divided based on culture medium: 2.5% PRP, 5% PRP, 7.5% PRP, and 10% PRP. Cell proliferation rate was analyzed using the MTS assay. The gene expression of CD31, vascular endothelial growth factor, hypoxia-inducible factors, and endothelial cell nitric oxide synthase was analyzed using reverse transcription polymerase chain reaction. Cell markers and structural changes were assessed through immunofluorescence staining and the tube formation assay. Subsequently, we studied the in vivo angiogenic capabilities of ADSCs by a mouse ischemic hindlimb model.RESULTS The proliferation rate of ADSCs was higher in the 2.5%, 5%, and 7.5% PRP groups. The expression of hypoxia-inducible factor, CD31, vascular endothelial growth factor, and endothelial cell nitric oxide synthase in the 5% and 7.5% PRP groups increased. The 5%, 7.5%, and 10% PRP groups showed higher abilities to promote both CD31 and vascular endothelial growth factor production and tubular structure formation in ADSCs. According to laser Doppler perfusion scan, the perfusion ratios of ischemic limb to normal limb were significantly higher in 5% PRP, 7.5% PRP, and human umbilical vein endothelial cells groups compared with the negative control and fetal bovine serum(FBS) groups(0.88 ± 0.08, 0.85 ± 0.07 and 0.81 ± 0.06 for 5%, 7.5% PRP and human umbilical vein endothelial cells compared with 0.42 ± 0.17 and 0.54 ± 0.14 for the negative control and FBS, P < 0.01).CONCLUSION PRP-preconditioned ADSCs presented endothelial cell characteristics in vitro and significantly improved neovascularization in ischemic hindlimbs. The optimal angiogenic effect occurred in 5% PRP-and 7.5% PRPpreconditioned ADSCs.

Three-dimensional cell culture systems as an in vitro platform for cancer and stem cell modeling

Three-dimensional(3D)culture systems are becoming increasingly popular due to their ability to mimic tissue-like structures more effectively than the monolayer cultures.In cancer and stem cell research,the natural cell characteristics and architectures are closely mimicked by the 3D cell models.Thus,the 3D cell cultures are promising and suitable systems for various proposes,ranging from disease modeling to drug target identification as well as potential therapeutic substances that may transform our lives.This review provides a comprehensive compendium of recent advancements in culturing cells,in particular cancer and stem cells,using 3D culture techniques.The major approaches highlighted here include cell spheroids,hydrogel embedding,bioreactors,scaffolds,and bioprinting.In addition,the progress of employing 3D cell culture systems as a platform for cancer and stem cell research was addressed,and the prominent studies of 3D cell culture systems were discussed.

Three-Dimensional Tidal Model and Its Application to Numerical Simulation of Water Quality in Coastal Waters

The turbulence mechanism plays an important part in the mixing process and momentum transfer of turbulence. A three-dimensional Prandtl mixing length tidal model has been developed to simulate tidal flows and water quality. The eddy viscosities and diffusivities are computed from the Prandtl mixing length model. In order to model the water quality of an estuary or coastal area many interdependent processes need to be simulated. These may be conveniently separated into three main groups: transport and mixing processes, biochemical interaction of water quality variables and the utilization and re-cycling of nutrients by living matter. The model simulates full oxygen and nutrient balance, primary productivity and the transport, reaction mechanism and fate of pollutants over tidal time-scales. The model is applied to numerical simulation of tidal flows and water quality in Dalian Bay. The model has been calibrated against a limited data set of historical water quality observations and in general demonstrates excellent agreement with all available data.

Thrombospondin peptide ABT-898 inhibits inflammation and angiogenesis in a colitis model

AIM: To evaluate the efficacy of the improvedthrombospondin mimetic peptide ABT-898 in a murine model of ulcerative colitis. METHODS: The dextran sodium sulfate(DSS) was used for the induction of colitis in both TSP-1 deficient(TSP-1-/-) and wild type(WT) mice during 7 d. While mice were receiving the DSS dissolved in the drinking water, the ABT-898 peptide was dissolved in sterile 5% glucose solution and delivered using mini pumps subcutaneously implanted. Plasma samples were analyzed for interleukin(IL)-6 by ELISA assay and colonic tissues were harvested, fixed and processed for histological evaluation. Immunohistochemistry using antibodies for the detection of CD31 and MECA in endothelial cells was performed. Inflammation was graded in colonic sections and the number of microvessels in each lesion was assessed. Activation of signal transducer and activator of transcription 3(STAT3) in colonic samples was quantified by immunohistochemistry and Western blotting using antibodies against total STAT3 and phosphorylated STAT3(p STAT3)(Ser727).RESULTS: Treatment with ABT-898 considerably diminished the inflammatory response in WT and TSP-1-/- mice(P < 0.0001 in both groups vs control). Identification of blood vessels highlighted by CD31/MECA immunohistochemistry, showed significantly reduced vessel counts in colitic lesions of WT and TSP-1-/- mice treated with ABT898(TSP-1-/- controls/TSP-1-/- treated, P = 0.0002; WT controls/WT treated, P = 0.0005). Consistently, IL-6 was significantly diminished in plasma samples of TSP-1-/- and WT treated with the peptide when compared to the control mice(P = 0.0002 and P = 0.0148, respectively). p STAT3 positive cells were quantified in WT and TSP-1-/- treated with ABT-898. A significant decrease in positive cells for p STAT3 was observed in treated mice(TSP-1-/- controls/TSP-1-/- treated, P = 0.0089; WT/WT treated, P = 0.0110). These results were confirmedby Western blotting analyses showing lower levels of p STAT3 in colitic lesions from mice treated with the peptide ABT-898.CONCLUSION: These findings indicate that the new peptide ABT-898 ameliorates inflammation and angiogenesis and might be a therapeutic alternative in IBD and inflammatory diseases.

Three-dimensional land FD-CSEM forward modeling using edge finite-element method

A modeling tool for simulating three-dimensional land frequency-domain controlled-source electromagnetic surveys,based on a finite-element discretization of the Helmholtz equation for the electric fields,has been developed.The main difference between our modeling method and those previous works is edge finite-element approach applied to solving the three-dimensional land frequency-domain electromagnetic responses generated by horizontal electric dipole source.Firstly,the edge finite-element equation is formulated through the Galerkin method based on Helmholtz equation of the electric fields.Secondly,in order to check the validity of the modeling code,the numerical results are compared with the analytical solutions for a homogeneous half-space model.Finally,other three models are simulated with three-dimensional electromagnetic responses.The results indicate that the method can be applied for solving three-dimensional electromagnetic responses.The algorithm has been demonstrated,which can be effective to modeling the complex geo-electrical structures.This efficient algorithm will help to study the distribution laws of3-D land frequency-domain controlled-source electromagnetic responses and to setup basis for research of three-dimensional inversion.

Modeling time-dependent mechanical behavior of hard rock considering excavation-induced damage and complex 3D stress states

To investigate the long-term stability of deep rocks,a three-dimensional(3D)time-dependent model that accounts for excavation-induced damage and complex stress state is developed.This model comprises three main components:a 3D viscoplastic isotropic constitutive relation that considers excavation damage and complex stress state,a quantitative relationship between critical irreversible deformation and complex stress state,and evolution characteristics of strength parameters.The proposed model is implemented in a self-developed numerical code,i.e.CASRock.The reliability of the model is validated through experiments.It is indicated that the time-dependent fracturing potential index(xTFPI)at a given time during the attenuation creep stage shows a negative correlation with the extent of excavationinduced damage.The time-dependent fracturing process of rock demonstrates a distinct interval effect of the intermediate principal stress,thereby highlighting the 3D stress-dependent characteristic of the model.Finally,the influence of excavation-induced damage and intermediate principal stress on the time-dependent fracturing characteristics of the surrounding rocks around the tunnel is discussed.