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.

The Technology and Application of the Tree Planting Baseplate in Bare Rock Area

The ecological greening technology of the bare rock area of the arbor governance be-longs to the field of ecological environment restoration, selection of suitable arbors for vegetation restoration in bare rock area, vegetation recovery is the primary approach to governance the ecological environment of bare rock area. The reconstruction of bare rock area arbor-shrub-grass ecosystems is a global environmental science problem. Paying attention to Geological conditions with rich rock fissures and abundant groundwater in these fissures, following the idea to reconstruct ecosystem from arbor to shrub and grass and the principle one tree in a baseplate, authors develop a baseplate technique for tree planting in bare rock area. The baseplate includes the parent body, the root, and the cover to prevent evaporation. Especially, there are filled in nutritional soil for the parent body and the root, and the composition of nutritional soil are selected by test in laboratory, while optimal mix ratio of the composition is obtained. Then, application method in field is put forward. The technique can guarantee survival at early stage and growth in the later for tree planting in the baseplate. In particular, the root provides a good channel to guide tree roots into fissure rock and absorb groundwater in rock. Test in field shows that the baseplate technique has strong practicality in vegetation recovery of bare rock area. Test in field shows that the baseplate technique has strong practicality in vegetation recovery of bare rock area in the world.

术前预测肝细胞癌微血管侵犯的研究进展

肝细胞癌(hepatocellular carcinoma,HCC)防治是世界范围内的重要公共卫生问题,目前,手术是HCC治疗的主要方式,而复发转移是提高HCC患者生存率的主要障碍。微血管侵犯(microvascular invasion,MVI)是肝血管内微转移的癌细胞栓子,与HCC术后复发转移及不良预后密切相关。目前MVI仅能通过术后病理检查确认,而术前预测MVI有助于HCC患者的精准治疗、提高患者生存率及筛选最佳肝移植受者。本文强调了术前预测MVI对HCC患者精准治疗的重要性,总结了影像学特征、常规血清蛋白标志物、新型分子标志物在预测MVI中的最新进展,以及多指标联合模型对MVI的预测能力,并评估了液体活检在MVI预测方面的巨大潜力。

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.

Advances in nanotechnology-based delivery systems for EGFR tyrosine kinases inhibitors in cancer therapy

Oral tyrosine kinase inhibitors(TKIs) against epidermal growth factor receptor(EGFR) family have been introduced into the clinic to treat human malignancies for decades. Despite superior properties of EGFR-TKIs as small molecule targeted drugs, their applications are still restricted due to their low solubility, capricious oral bioavailability, large requirement of daily dose, high binding tendency to plasma albumin and initial/acquired drug resistance. Nanotechnology is a promising tool to improve efficacy of these drugs. Through non-oral routes. Various nanotechnology-based delivery approaches have been developed for providing efficient delivery of EGFR-TKIs with a better pharmacokinetic profile and tissue-targeting ability. This review aims to indicate the advantage of nanocarriers for EGFR-TKIs delivery.

Thoracic interstitial injection of drug-liposomes in mice for treating atherosclerosis

Intervaginal space injection(ISI)is a novel mode of administration investigated over the last decade.After injecting nanoparticles into the intervaginal space,they can be transported along low flow resistance channels into the interstitial space.This transport has a certain delivery direction,and site-specific injection can work on specific organs or tissues.In this study,the thorax,a new ISI site in the interstitial surrounding the internal thoracic artery named the thoracic interstitial injection(tISI)was investigated.To prove the targeting ability of the tISI,two sizes of gold nanoparticles(AuNPs)(47 and 87 nm)were administered to mice.After 1 h,the biodistribution of AuNPs in the tissues was measured via single particle inductively coupled plasma mass spectrometry(spICP-MS).The results showed that the concentration of AuNPs in the aorta after tISI injection was significantly higher than that after intravenous injection.Moreover,fewer nanoparticles with larger particle sizes were observed to have entered the blood and were better targeted to the aorta.Thereafter,tanshinone IIa sodium sulfonate liposomes were administered for the treatment of aortic atherosclerosis.The proportion of aortic plaques in atherosclerotic Apoe-/-mice administered via tISI was significantly lower than that in other model animals(P<0.001).Furthermore,the proteoglycan content and CD68-positive cell count in the plaques were significantly reduced.The vascular elastic fibers at the plaque site were thickened,and fractures were reduced.tISI was,therefore,determined to be an effective strategy for the treatment of atherosclerotic aortic plaques.

Liposome-coated CaO_(2)nanoblockers for enhanced checkpoint blockade therapy by inhibiting PD-L1 de novo biosynthesis

The blocking of the immune checkpoint pathway with antibodies,especially targeting to programmed death-1/programmed death ligand-1(PD-1/PD-L1)pathway,was currently a widely used treatment strategy in clinical practice.However,the shortcomings of PD-L1 antibodies were constantly exposed with the deepening of its research and their therapeutic effect was limited by the translocation and redistribution of intracellular PD-L1.Herein,we proposed to improve immune checkpoint blockade therapy by using liposomes-coated CaO_(2)(CaO_(2)@Lipo)nanoparticles to inhibit the de novo biosynthesis of PD-L1.CaO_(2)@Lipo would produce oxygen and reduce hypoxia-inducible factor-1α(HIF-1α)level,which then downregulated the expression of PD-L1.Our in vitro and in vivo results have confirmed CaO_(2)@Lipo promoted the degradation of HIF-1αand then downregulated the expression of PD-L1 in cancer cells for avoiding immune escape.Furthermore,to mimicking the clinical protocol of anti-PD-L1 antibodies+chemo-drugs,CaO_(2)@Lipo was combined with doxorubicin(DOX)to investigate the tumor inhibition efficiency.We found CaO_(2)@Lipo enhanced DOX-induced immunogenic cell death(ICD)effect,which then promoted the infiltration of T cells,strengthened the blocking effect,thus provided an effective means to overcome the traditional immune checkpoint blockade treatment.

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.

Economic Optimization Dispatching Strategy of Microgrid for Promoting Photoelectric Consumption Considering Cogeneration and Demand Response

A system combining photovoltaic power generation and cogeneration is proposed to improve the photoelectric absorption capacity. First, a time-of-use price strategy is adopted to guide users to change their electricity consumption habits for participation in the demand response, and a demand response model is established. Then, particle swarm optimization(PSO)is used with the aim of minimizing the operation cost of the microgrid to achieve economic dispatching of the microgrid. This considers power balance equation constraints, unit operation constraints, energy storage constraints, and heat storage constraints. Finally, the simulation results show the improved level of photoelectric consumption using the proposed scheme and the economic benefits of the microgrid.

Cyanobacteria-based near-infrared light-excited self-supplying oxygen system for enhanced photodynamic therapy of hypoxic tumors

Tumor hypoxia has been considered to induce tumor cell resistance to radiotherapy and anticancer chemotherapy,as well as predisposing for increased tumor metastases.Therefore,strategies for the eradication of the hypoxic tumor are highly desirable.Photodynamic therapy(PDT)is a new technique that can be used to treat tumors using laser irradiation to photochemically activate a photosensitizer.Compared to traditional radiotherapy and chemotherapy,photodynamic therapy has many advantages,such as good selectivity,low toxicity,and less trauma and resistance.However,PDT is oxygen-dependent,and the lack of oxygen in hypoxic tumors renders photodynamic therapy ineffective.Cyanobacteria,the earliest photosynthetic oxygen-generating organisms,can utilize water as an electron donor to reduce CO_(2) into organic carbon compounds along with continuously releasing oxygen under sunlight.Inspired by this,herein,cyanobacteria were used as a living carrier of photosensitizer conjugated upconversion nanoparticles(UCNP)to construct a self-supplying oxygen PDT system.Improvement in the PDT efficiency for hypoxic tumors can be achieved as a result of in situ oxygen production by cyanobacteria under near-infrared(NIR)light using UCNP as a light harvesting antenna.A successful demonstration of this concept would be of great significance and could open the door to a new generation of carrier systems in the field of hypoxia-targeted drug transport platforms.

Special interstitial route can transport nanoparticles to the brain bypassing the blood-brain barrier

Nowadays,nanoparticles(NPs)are considered to be ideal tools for bioimaging and drug delivery.Although increasing research has focused on NP biodistribution,transportation in the interstitial architecture has been neglected.The entire body is connected by the interstitial architecture,which can provide a long-range and direct pathway for NP biodistribution in a nonvascular system.In this study,we report that 10-nm gold NPs injected directly into the interstitial architecture of the tarsal tunnel of rats(intervaginal space injection(ISI))were delivered to the brain without crossing the blood-brain barrier.Furthermore,NaGdF4 nanoparticles were used to explore the transportation route by magnetic resonance imaging.The results demonstrated that,after ISI,the NaGdF4 nanoparticles were transported through the perivascular interstitial space of the carotid arteries and brain vessels to the brain.This is a special nonvascular transportation route like a stream based on the interstitial architecture that provides an alternative pathway for NP biodistribution.

Novel directions of precision oncology:circulating microbial DNA emerging in cancer-microbiome areas

Microbiome research has extended into the cancer area in the past decades.Microbes can affect oncogenesis,progression,and treatment response through various mechanisms,including direct regulation and indirect impacts.Microbiota-associated detectionmethods and agents have been developed to facilitate cancer diagnosis and therapy.Additionally,the cancermicrobiome has recently been redefined.The identification of intra-tumoral microbes and cancer-related circulating microbial DNA(cmDNA)has promoted novel research in the cancer–microbiome area.In this review,we define the human system of commensal microbes and the cancer microbiome from a brand-new perspective and emphasize the potential value of cmDNA as a promising biomarker in cancer liquid biopsy.We outline all existing studies on the relationship between cmDNA and cancer and the outlook for potential preclinical and clinical applications of cmDNA in cancer precision medicine,as well as critical problems to be overcome in this burgeoning field.

The damage evolution behavior of polypropylene fiber reinforced concrete subjected to sulfate attack based on acoustic emission

To study the damage evolution behavior of polypropylene fiber reinforced concrete(PFRC)subjected to sulfate attack,a uniaxial compression test was carried out based on acoustic emission(AE).The effect of sulfate attack relative to time and fiber hybridization were analyzed and the compression damage factor was calculated using a mathematical model.The changes to AE ringing counts during the compression could be divided into compaction,elastic,and AE signal hyperactivity stages.In the initial stage of sulfate attack,the concrete micropores and microcracks were compacted gradually under external load and a corrosion products filling effect,and this corresponded with detection of few AE signals and with concrete compression strength enhancement.With increasing sulfate attack time,AE activity decreased.The cumulative AE ringing counts of PFRC at all corrosion ages were much higher than those for plain concrete.PFRC could still produce AE signals after peak load due to drawing effect of polypropylene fiber.After 150 d of sulfate attack,the cumulative AE ringing counts of plain concrete went down by about an order of magnitude,while that for PFRC remained at a high level.The initial damage factor of hybrid PFRC was-0.042 and-0.056 respectively after 150 d of corrosion,indicating that the advantage of hybrid polypropylene fiber was more obvious than plain concrete and single-doped PFRC.Based on a deterioration equation,the corrosion resistance coefficient of hybrid PFRC would be less than 0.75 after 42 drying-wetting sulfate attack cycles,which was 40%longer than that of plain concrete.

Bioinspired Scalable Total Synthesis of Opioids

As one of the largest and most representative families of natural medicines harvested from plants,the mass production of opioids legitimately occupies large,worldwide farmland cultivation of opium poppies,causing severe regulation limitations and supply uncertainty.Due to their complex structures,the chemical synthesis of opioids has been criticized as infeasible for large-scale production in view of lengthy synthetic steps and overall low efficiency.