Fatigue properties and damage constitutive model of salt rock based on CT scanning

To investigate the macroscopic fatigue properties and the mesoscopic pore evolution characteristics of salt rock under cyclic loading,fatigue tests under different upper-limit stresses were carried out on salt rock,and the mesoscopic pore structures of salt rock before and after fatigue tests and under different cycle numbers were measured using CT scanning instrument.Based on the test results,the effects of the cycle number and the upper-limit stress on the evolution of cracks,pore morphology,pore number,pore volume,pore size,plane porosity,and volume porosity of salt rock were analyzed.The failure path of salt rock specimens under cyclic loading was analyzed using the distribution law of plane porosity.The damage variable of salt rock under cyclic loading was defined on basis of the variation of volume porosity with cycle number.In order to describe the fatigue deformation behavior of salt rock under cyclic loading,the nonlinear Burgers damage constitutive model was further established.The results show that the model established can better reflect the whole development process of fatigue deformation of salt rock under cyclic loading.

A statistical damage-based constitutive model for shearing of rock joints in brittle drop mode

Some rock joints exhibit significant brittleness,characterized by a sharp decrease in shear stress upon reaching the peak strength.However,existing models often fail to accurately represent this behavior and are encumbered by numerous parameters lacking clear mechanical significance.This study presents a new statistical damage constitutive model rooted in both damage mechanics and statistics,containing only three model parameters.The proposed model encompasses all stages of joint shearing,including the compaction stage,linear stage,plastic yielding stage,drop stage,strain softening stage,and residual strength stage.To derive the analytical expression of the constitutive model,three boundary conditions are introduced.Experimental data from both natural and artificial rock joints is utilized to validate the model,resulting in average absolute relative errors ranging from 3%to 8%.Moreover,a comparative analysis with established models illustrates that the proposed model captures stress drop and post-peak strain softening more effectively,with model parameters possessing clearer mechanical interpretations.Furthermore,parameter analysis is conducted to investigate the impacts of model parameters on the curves and unveil the relationship between these parameters and the mechanical properties of rock joints.Importantly,the proposed model is straightforward in form,and all model parameters can be obtained from direct shear tests,thus facilitating the utilization in numerical simulations.

Stability of bedded rock slopes subjected to hydro-fluctuation and associated strength deterioration

Reservoir-induced earthquakes(RIEs)occur frequently in the Three Gorges Reservoir Area(TGRA)and the rock mass strength of the hydro-fluctuation belt(HFB)deteriorates severely due to the reservoirinduced seismic loads.Three models of typical bedded rock slopes(BRSs),i.e.gently(GIS),moderately(MIS),and steeply(SIS)inclined slopes,were proposed according to field investigations.The dynamic response mechanism and stability of the BRSs,affected by the rock mass deterioration of the HFB,were investigated by the shaking table test and the universal distinct element code(UDEC)simulation.Specifically,the amplification coefficient of the peak ground acceleration(PGA)of the slope was gradually attenuated under multiple seismic loads,and the acceleration response showed obvious“surface effect”and“elevation effect”in the horizontal and vertical directions,respectively.The“S-type”cubic function and“steep-rise type”exponential function were used to characterize the cumulative damage evolution of the slope caused by microseismic waves(low seismic waves)and high seismic waves,respectively.According to the dynamic responses of the acceleration,cumulative displacement,rock pressure,pore water pressure,damping ratio,natural frequency,stability coefficient,and sliding velocity of the slope,the typical evolution processes of the dynamic cumulative damage and instability failure of the slope were generalized,and the numerical and experimental results were compared.Considering the dynamic effects of the slope height(SH),slope angle(SA),bedding plane thickness(BPT),dip angle of the bedding plane(DABP),dynamic load amplitude(DLA),dynamic load frequency(DLF),height of water level of the hydro-fluctuation belt(HWLHFB),degradation range of the hydro-fluctuation belt(DRHFB),and degradation shape of the hydro-fluctuation belt(DSHFB),the sensitivity of factors influencing the slope dynamic stability using the orthogonal analysis method(OAM)was DLA>DRHFB>SA>SH>DLF>HWLHFB>DSHFB>DABP>BPT.

Dynamic damage evolution of bank slopes with serrated structural planes considering the deteriorated rock mass and frequent reservoirinduced earthquakes

To investigate the dynamic damage evolution characteristics of bank slopes with serrated structural planes,the shaking table model test and the numerical simulation were utilized.The main findings indicate that under continuous seismic loads,the deformation of the bank slope increased,particularly around the hydro-fluctuation belt,accompanying by the pore water pressure rising.The soil pressure increased and then decreased showed dynamic variation characteristics.As the undulation angle of the serrated structural planes increased(30°, 45°, and 60°),the failure modes were climbing,climbinggnawing,and gnawing respectively.The first-order natural frequency was used to calculate the damage degree(Dd)of the bank slope.During microseisms and small earthquakes,it was discovered that the evolution of Dd followed the“S”shape,which was fitted by a logic function.Additionally,the quadratic function was used to fit the Dd during moderately strong earthquakes.Through the numerical simulation,the variation characteristics of safety factors(Sf)for slopes with serrated structural planes and slopes with straight structural planes were compared.Under continuous seismic loads,the Sf of slopes with straight structural planes reduce stalely,whereas the Sf for slopes with serrated structural planes was greater than the former and the reduction rate was increasing.

Generation of irregular particle packing with prescribed statistical distribution, spatial arrangement, and volume fraction

A method for packing irregular particles with a prescribed volume fraction is proposed.Furthermore,the generated granular material adheres to the prescribed statistical distribution and satisfies the desired complex spatial arrangement.First,the irregular geometries of the realistic particles were obtained from the original particle images.Second,the Minkowski sum was used to check the overlap between irregular particles and place an irregular particle in contact with other particles.Third,the optimised advance front method(OAFM)generated irregular particle packing with the prescribed statistical dis-tribution and volume fraction based on the Minkowski sum.Moreover,the signed distance function was introduced to pack the particles in accordance with the desired spatial arrangement.Finally,seven biaxial tests were performed using the UDEC software,which demonstrated the accuracy and potential usefulness of the proposed method.It can model granular material efficiently and reflect the meso-structural characteristics of complex granular materials.This method has a wide range of applications where discrete modelling of granular media is necessary.

Blockade of neutrophil recruitment to tumor sites based on sialic acid-modified nanoplatforms enhances the efficacy of checkpoint blockade immunotherapy

Checkpoint inhibitors are designed to rejuvenate depleted or suppressed T cells in the tumor microenvironment,relying on the immune system to control and kill tumors.However,accumulating evidence indicates that tumor-infiltrating neutrophils impede the proliferation and activation of T cells and determine the resistance to checkpoint blockade and chemotherapy.In this study,sialic acid ligand-modified colchicine derivative phospholipid complexes specifically targeted tumor-associated neutrophils in the peripheral blood,blocked neutrophil accumulation in tumors,and attenuated the inhibitory effect of infiltrating neutrophils on T cells.Neutrophil blocking therapy enhanced the immunotherapy effect of the PD-L1 antibody in S180 advanced tumors and 4T1 breast cancer.Our study found that PD-L1 antibody monotherapy increased the tumor infiltration of immunosuppressive neutrophils.Combination therapy with neutrophil blocking can greatly reduce tumor-infiltrating neutrophils and increase the proliferation of cytotoxic CD8^(+) T lymphocytes in the tumor.The combination therapy significantly improved the survival rate of mice with advanced S180 tumors and increased the sensitivity of immune checkpoint inhibitors to 4T1 cold tumors.

The Use of Floss in Medical Faculties of Inner Mongolia Medical University in 2017

Purpose: The aim of the present study was to determine the degree of using floss and the demographic characteristics of medical faculties of Inner Mongolia Medical University. Materials and Methods: Participants completed the questionnaire in the classroom. These participants came from the medical faculties of Chinese Medicine and Western Medicine. These participants were interviewed to determine the demographic characteristics. Non-flossors responded according to their reasons for not flossing. Results: A total of 3481 effective data were available for analysis. The floss prevalence was 17.21%, which was lower by 5.72% for students living in rural areas, when compared to students living in urban areas. The largest proportion of non-flossing participants in rural areas answered, “I do not know what a floss is”, while participants in urban answered, “I do not want to use it”. The largest proportion of answered flossing frequency was less than once a month. Conclusion: The present study indicates that the prevalence of using floss in medical faculties in Inner Mongolia Medical University was higher, when compared to that in Sichuan province, China, but lower than that in other countries. Although the students use floss, more than one-third of students use floss less than once a month, which is close to “never”. The prevalence in rural areas is lower than those in urban areas. Male not only comprises the total number of prevalence, but also has a frequency greater than that in females. The emphasis on using floss should be improved in medical students.

Phyto-phospholipid complexes(phytosomes): A novel strategy to improve the bioavailability of active constituents

Although active constituents extracted from plants show robust in vitro pharmacological effects, low in vivo absorption greatly limits the widespread application of these compounds. A strategy of using phyto-phospholipid complexes represents a promising approach to increase the oral bioavailability of active constituents, which is consist of ‘‘label-friendly'phospholipids and active constituents. Hydrogen bond interactions between active constituents and phospholipids enable phospholipid complexes as an integral part. This review provides an update on four important issues related to phyto-phospholipid complexes: active constituents, phospholipids, solvents, and stoichiometric ratios. We also discuss recent progress in research on the preparation, characterization, structural verification, and increased bioavailability of phyto-phospholipid complexes.

Preparation and toxicity evaluation of a novel nattokinase-tauroursodeoxycholate complex

Nattokinase(NK), which has been identified as a potent fibrinolytic protease, has remarkable potential in treatment of thrombolysis, and even has the ability to ameliorate chronic vein thrombosis. To reduce the hemorrhagic risk from an intravenous injection of NK,nattokinase-tauroursodeoxycholate(NK-TUDCA) complex was prepared at different pH values and with different ratios of NK and TUDCA. When assessing survival time, survival state,tail injury, and the body weight of mice, it was found that the NK-TUDCA complex(NK: 10 k IU/ml; TUDCA: 10 mg/ml; pH 5.0) had a lower toxicity when administered at an NK dosage of 130 kIU/kg in the acute toxicity test and 13 kIU/kg in the repeated low-dose challenge. From the results of the in vitro thrombolytic test and characterization of NKTUDCA, we speculated that the delayed release of NK-TUDCA might be the main cause of toxicity reduction by the complex. This study described the preparation of an NK complex with low toxicity following intravenous administration, which could be utilized for further clinical study of NK.

The effect of monosialylganglioside mix modifying the PEGylated liposomal epirubicin on the accelerated blood clearance phenomenon

PEGylated liposomes are potential candidates to improve the pharmacokinetic characteristics of encapsulated drugs, to extend their circulation half-life and facilitate their passive accumulation at tumour sites. However, PEG-modified liposomes can induce accelerated blood clearance(ABC) upon repeated administration, and the extent of ABC phenomenon on the cytotoxic drugs-containing PEGylated liposomes is related to the dose of the cytotoxic drugs.In this study, EPI served as a model cytotoxic drug, a hydrophilic surfactant molecule,monosialylganglioside(GM1) was chosen and modified on the liposomes together with PEG.It was shown that upon mixed modification, when GM1 contents reached 10% or 15% mol,the ABC phenomenon of the PEGylated liposomal EPI significantly reduced. We also found that GM1 played an important role in abrogating the ABC phenomenon in both the induction phase and the effectuation phase. The results suggested that GM1 incorporation unfortunately did not avoid occurrence of ABC phenomenon completely, but GM1 modification on PEGylated liposomes may provide a significant improvement in clinical practice of PEGylated liposomes. Further study must be necessary.

Mechanical behaviours of sandstone containing intersecting fissures under uniaxial compression

Predicting rock cracking is important for assessing the stability of underground engineering.The effects of the intersecting angle a and the distribution orientation angleβof intersecting fissures on the uniaxial compressive strength and the failure characteristics of sandstone containing intersecting fissures are investigated through laboratory experiments and two-dimensional particle flow code(PFC2D).The relationship between the mechanical properties of sandstone and the intersecting angle a and the distribution orientation angleβis analysed.Crack initiation forms and the final failure modes are then categorised and determined via empirical methods.In addition,the cracking processes of intersecting fissures with different a andβvalues are discussed.The results show that variations in the peak stress,peak strain,average modulus,and crack initiation stress of sandstone containing intersecting fissures show a“moth”shape in the space of the a-β-mechanical parameters.Two crack initiation forms are identified:inner tip cracking(usually accompanied by one outer tip cracking)and only outer tips cracking.Two failure modes are observed:(1)the main fracture planes are created at the inner tip and one outer tip,and(2)the main fracture planes are formed at the two outer tips.Two main crack evolution processes of sandstone containing intersecting fissures under uniaxial compression are found.Approaches for quickly determining the crack initiation form and the failure mode are proposed.The combination of the determination equations for the crack initiation form and the failure mode can be used to predict the crack evolution.The approach for determining the crack evolution processes is hence proposed with acceptable precision.

Effects of complement inhibition on the ABC phenomenon in rats

Researchers reported that intravenously injected PEGylated colloidal drug carriers lose their long-circulating characteristic and accumulated extensively in liver when they are administrated twice in the same animal with certain intervals. This phenomenon was referred to as the 'accelerated blood clearance(ABC) phenomenon'. Some former studies had found that complement-mediated phagocytosis, activated by antigen–antibody complex, was responsible for inducing the phenomenon. According to the theory, we have used cobra venom factor to deplete complement in vivo and to investigate the effect of complement inhibition on the ABC phenomenon. Rats were administered by injection of cobra venom factor solution to build up the model of complement exhaustion/inhibition, and the effect of the inhibition of complement on ABC phenomenon was carried out. It seemed that inhibition of complement didn’t affect the pharmacokinetic of the first infection. By contrast, in rats of which complement had been depleted, the second dose of PEGylated nanoemulsions showed enhanced circulation time compared with normal rats in a complement inhibition-independent manner, but the ABC phenomenon was not completely eliminated. It indicated that complement inhibition could certainly weaken the accelerated clearance;meanwhile, there were other factors causing the ABC effect.These findings provide novel insights into the attenuating of ABC phenomenon and lay foundation for further study of immune mechanism.

Effect of Kupffer cells depletion on ABC phenomenon induced by Kupffer cells-targeted liposomes

Accelerated blood clearance(ABC) phenomenon is common in many PEGylated nanocarriers, whose mechanism has not been completely elucidated yet. In this study, the correlation between Kupffer cells(KCs) and ABC phenomenon has been studied by KCs-targeted liposomes inducing ABC phenomenon and KCs depletion. In other words, the 4-aminophenyl-α-D-mannopyranoside(APM) lipid derivative DSPE-PEG 2000-APM(DPM), and 4-aminophenyl-β-L-fucopyranoside(APF) lipid derivative DSPE-PEG 2000-APF(DPF) were conjugated and modified on alendronate sodium(AD) liposomes to specifically target and deplete KCs. The dualligand modified PEGylated liposomes(MFPL) showed stronger ability to damage KCs in vitro and in vivo, which also could indirectly illustrate that dual-ligand modification could better target KCs. Besides, the hepatic biodistribution and pharmacokinetics could directly prove that MFPL had a stronger targeting ability to KCs. In addition, in depletion rats, plasma concentration and splenic biodistribution of MFPL and PEGylated liposomes(PL) were significantly elevated and hepatic biodistribution was significantly reduced, which demonstrated that KCs played an important role on elimination of nanoparticles. What’s more, ABC phenomenon of the secondary injection of PL was stronger in KCs depletion rats than that in normal rats, which indicated that depletion of KCs prolonged the circulation of PL in the first injection repeatedly stimulating B-cells in the marginal region of the spleen and causing it to secrete more IgM antibodies. This could also illustrate that anti-PEG IgM takes up a major station compared with KCs. Most important of all, KCs-targeted liposomes could induce a stronger ABC phenomenon than PL in normal rats, which declared that based on the same IgM concentration, the more the KCs were stimulated, the stronger ABC phenomenon was induced. However, in depletion rats, this difference of ABC phenomenon between PL and MFPL could no more exist, further demonstrating that KCs could participate and play a certain role in the ABC phenomenon.

The accelerated blood clearance phenomenon of PEGylated nanoemulsion upon cross administration with nanoemulsions modified with polyglycerin

For investigating the accelerated blood clearance(ABC) phenomenon of polyglycerin modified nanoemulsions upon cross administration with polyethylene glycol(PEG) covered nanoemulsion, we used the 1,2-distea-royl-sn-glycero-3-phosphoethanolamine-npolyglycerine-610 and the 1,2-distearoyl-n-glycero-3-phosphoethanolamine-n-[methoxy(polyethylene glycol)-2000] as modify materials, the dialkylcarbocyanines as fluorescence indicator. Exhausted macrophages rat model was established and new material containing polycarboxyl structure was synthesized. The microplate reader and the in vivo optical imaging system were applied to measure the concentration of nanoemulsions in tissues.The results show that the first dose of polyglycerin modified nanoemulsion can induce the ABC phenomenon of the second dose of PEGylated nanoemulsion. With the increase in the amount of the surface polyglycerin, the extent of the ABC phenomenon decreases. Liver accumulation has positive relationship with the ABC phenomenon. Furthermore, kupffer cells in liver can get more immune information from polyhydroxy structure than polycarboxyl group in the modify compound. The results of our work imply that the polycarboxyl structure has advantages to eliminate the ABC phenomenon.

Effect of sterilization methods on the flavor of cold brew coffee

This research used ultra-fast E-nose,E-tongue and SCA analysis to explore the effects of different sterilization methods(pasteurization,back pressure sterilization,high temperature short-term sterilization,membrane filtration treatment and high pressure processing)on cold brew coffee.The results showed that non-heat sterilization can better maintain the sensory quality of coffee liquid.Back pressure sterilization could reduce the pH value of coffee liquid to 4.65,and decrease the aroma content significantly by 50.5%(p<0.05),while the sourness and bitterness of coffee samples increased,which lowered the sensory quality of coffee.Among the heat sterilization treatments,high temperature short-term sterilization had relatively little effect on the sensory quality of the coffee beverage,and decreased the bitterness of the coffee.Taking sensory quality,nutrients and cost into consideration,it is suggested that high temperature short time sterilization is a prefered method.Thus,the results of this research provided a theoretical basis for the selection of sterilization method for cold brew coffee.

Physicochemical difference of coffee beans with different species,production areas and roasting degrees

In recent decades,the demand for coffee has seen a continuous increase,and the aroma and flavor of coffee has been widely studied.The current research chose coffee beans of two species(Coffea arabica and C.canephora)from five production areas(Brazil,India,Indonesia,Uganda and Vietnam)with four different roasting degrees(medium light,medium,medium dark and dark),to investigate the difference on physicochemical properties.The results showed that Arabica coffee beans had higher concentrations of fat and organic acids,and total amount of volatile compounds,whereas Robusta beans had higher concentrations of protein.With the increase of roasting degree,the concentrations of protein,fat,organic acids,and the total amount of volatile compounds of coffee beans increased,while the concentrations of chlorogenic acid compounds decreased.The discriminant analysis indicated that the tested coffee beans could be clearly discriminated by species and roasting degrees,but not by production area.The results of this research conclude the physicochemical difference of Arabica and Robusta beans with different roasting degrees.The results can provide a theoretical basis for coffee bean selection for the relevant industries.

Sialic acid-mediated photochemotherapy enhances infiltration of CD8^(+)T cells from tumor-draining lymph nodes into tumors of immunosenescent mice

Immunoscenescence plays a key role in the initiation and development of tumors.Furthermore,immunoscenescence also impacts drug delivery and cancer therapeutic efficacy.To reduce the impact of immunosenescence on anti-tumor therapy,this experimental plan aimed to use neutrophils with tumor tropism properties to deliver sialic acid(SA)-modified liposomes into the tumor,kill tumor cells via SA-mediated photochemotherapy,enhance infiltration of neutrophils into the tumor,induce immunogenic death of tumor cells with chemotherapy,enhance infiltration of CD8^(+)T cells into the tumordraining lymph nodes and tumors of immunosenescent mice,and achieve SA-mediated photochemotherapy.We found that CD8^(+)T cell and neutrophil levels in 16-month-old mice were significantly lower than those in 2-and 8-month-old mice;16-month-old mice exhibited immunosenescence.The anti-tumor efficacy of SA-mediated non-photochemotherapy declined in 16-month-old mice,and tumors recurred after scabbing.SA-mediated photochemotherapy enhanced tumor infiltration by CD8^(+)T cells and neutrophils,induced crusting and regression of tumors in 8-month-old mice,inhibited metastasis and recurrence of tumors and eliminated the immunosenescence-induced decline in antitumor therapeutic efficacy in 16-month-old mice via the light-heat-chemical-immunity conversion.

Study on the pipe friction resistance in long-distance rock pipe jacking engineering

Previous studies on pipe friction resistance are mainly concentrated in the soil layer,whereas the study on that in the rock stratum is limited.To estimate the pipe friction resistance in the rock stratum,the calculation models of pipe friction resistance and their applica-tion conditions were compared first.Then the friction resistance calculation model for pipe jacking in the rock stratum was established and simplified.Lastly,the measured(FM)and the computed(FN)pipe friction resistance was compared to validate the simplified friction resistance calculation model.The following conclusions can be drawn:(1)The existing calculation methods of pipe friction resistance can be well verified in the soil layer but cannot be applied in the rock stratum.(2)Sediment,pipe–rock friction coefficient and mud buoyancy are the main factors affecting the pipe friction resistance in long-distance rock pipe jacking engineering.(3)The simplified calculation model established by Deng et al.can estimate the pipe friction resistance in different rock strata at different jacking stages with satisfac-tory outcomes.Further research on the pipe-rock friction coefficient in different rock strata with different pipe–rock contact conditions merits further investigation to better predict the pipe friction resistance in the rock stratum.The research results have certain practica-bility and can provide a reference for similar projects.

Revealing performance of 78Li_(2)S-22P_(2)S_(5) glass ceramic based solid-state batteries at different operating temperatures

78Li_(2)S-22P_(2)S_(5) are sulfide electrolytes with high lithium-ion conductivity and wide electrochemical windows in the Li_(2)S-P_(2)S_(5) system,making them attractive solid electrolytes for ASSLBs.However,the role and potential of 78Li_(2)S-22P_(2)S_(5) solid electrolytes over a wide temperature range are still not fully understood.Therefore,we constructed solid-state batteries with NCM622 as the positive electrode and 78Li_(2)S-22P_(2)S_(5) glass-ceramics as the electrolyte to investigate in depth the differences in battery performance over a wide temperature range and their intrinsic mechanisms.The in-situ impedance and relaxation time distribution (DRT) demonstrated the electrochemical stability of the electrolyte over a wide temperature range,while the in-situ stacking pressure observed a large volume change during cycling at 60℃,leading to local solid-solid contact failure and poor cycling stability.This study provides insight into the advantages and problems of 78Li_(2)S-22P_(2)S_(5) in the wide temperature range as well as a basis for the construction of ASSLBs with high energy density and long cycle life.

Numerical study of the mechanical process of long-distance replacement of the definitive lining in severely damaged highway tunnels

Mountain road tunnels are prone to water leakage and lining corrosion under the complex geological conditions and corrosive envi-ronments,which will reduce the strength of the lining structure until it loses its load-bearing capacity;eventually,the definitive lining will need to be replaced.In this paper,a highway tunnel in a mountainous area in Southwest China is taken as an example.Field investi-gation found that the tunnel was seriously corroded by sulfate,the strength of the definitive lining decreased,and large-scale cracks and spalling appeared on the surface,so the operator decided to replace the definitive lining by the method of interval replacement.Based on the data obtained from drilling and coring,a numerical model of long-distance replacement of the definitive lining of the damaged tunnel is established.First,the back analysis of the calculation parameters is carried out,and the modified calculation results are com-pared with the field monitoring results for verification.Then,the deformation trend of the tunnel and the development of the plastic zone during the process of long-distance replacement of the definitive lining are studied.Finally,the construction scheme is optimized.Numer-ical analysis results show that the replacement of the definitive lining of the tunnel mainly leads to the settlement of the arch crown and the uplift of the inverted arch.The deformation of the tunnel shows two rapid growth stages and two stable stages during the replace-ment process;after replacement,the deformation of the arch crown and the inverted arch is divided into two buffer zones and one stable zone.In the progress of the replacement of the definitive lining,the plastic zone does not change.Regarding the reinforcement measures,with the increase in the grouting range,the grouting efficiency decreases,and the effect of the temporary steel arch on controlling the overall deformation is not obvious.The length of the replacement of the single section should be determined according to the geological conditions of the replacement section and the monitoring data during construction.The research results can provide a reference for sim-ilar projects for the replacement of the definitive lining.