Nonlinear empirical failure criterion for rocks under triaxial compression

Based on existing triaxial compression experimental data,a new empirical failure criterion with wide applicability was proposed considering hydrostatic pressure,second stress invariance,and maximum shear stress.Four fitting evaluation indicators were used to verify the consistency of the new failure criterion,and the differences with the other 6 failure criteria were discussed.The characteristics of the new failure criteria in the principal stress space were finally analyzed.The results indicate that(1)the new failure criterion exhibits strong predictive ability for triaxial experiments and has good applicability for both intact and jointed rocks;(2)the influence of hydrostatic pressure on the failure surface exhibits a non-linear trend,and different hydrostatic pressure also exhibits different distribution patterns on the deviatoric stress plane,with a distribution characteristic pattern of hexagonal snowflake-regular hexagon.The maximum shear stress has a torsional effect on the new criterion,in the three-dimensional failure surface.The parameters a and b of the rock have an impact on the failure surface morphology of the new criterion function on the offset surface.

Aloe emodin promotes mucosal healing by modifying the differentiation fate of enteroendocrine cells via regulating cellular free fatty acid sensitivity

The proper differentiation and reorganization of the intestinal epithelial cell population is critical to mucosal regeneration post injury.Label retaining cells(LRCs)expressing SRY-box transcription factor 9(SOX9)promote epithelial repair by replenishing LGR5 t intestinal stem cells(ISCs).While,LRCs are also considered precursor cells for enteroendocrine cells(EECs)which exacerbate mucosal damage in inflammatory bowel disease(IBD).The factors that determine LRC-EEC differentiation and the effect of intervening in LRC-EEC differentiation on IBD remain unclear.In this study,we investigated the effects of a natural anthraquinone called aloe emodin(derived from the Chinese herb rhubarb)on mucosal healing in IBD models.Our findings demonstrated that aloe emodin effectively interfered with the differentiation to EECs and preserved a higher number of SOX9t LRCs,thereby promoting mucosal healing.Furthermore,we discovered that aloe emodin acted as an antagonist of free fatty acid receptors(FFAR1),suppressing the FFAR1-mediated Gbg/serine/threonine-protein kinase(AKT)pathway and promoting the translocation of forkhead box protein O1(FOXO1)into the nucleus,ultimately resulting in the intervention of differentiation fate.These findings reveal the effect of free fatty acid accessibility on EEC differentiation and introduce a strategy for promoting mucosal healing in IBD by regulating the FFAR1/AKT/FOXO1 signaling pathway.

Camptothecin multifunctional nanoparticles effectively achieve a balance between the efficacy of breast cancer treatment and the preservation of intestinal homeostasis

Camptothecin(CPT)exhibits potent antitumor activity;however,its clinical application is limited by significant gastrointestinal adverse effects(GAEs).Although the severity of GAEs associated with CPT derivatives has decreased,the incidence rate of these adverse effects has remained high.CPT multifunctional nanoparticles(PCRHNs)have the potential to increase the efficacy of CPT while reducing side effects in major target organs;however,the impact of PCRHNs on the GAEs from CPT remains uncertain.Here,we investigated the therapeutic effects of PCRHNs and different doses of CPT and examined their impacts on the intestinal barrier and the intestinal microbiota.We found that the therapeutic efficacy of PCRHNs+Laser treatment was superior to that of high-dose CPT,and PCRHNs+Laser treatment also provided greater benefits by helping maintain intestinal barrier integrity,intestinal microbiota diversity,and intestinal microbiota abundance.In summary,compared to high-dose CPT treatment,PCRHNs+Laser treatment can effectively balance therapeutic effects and GAEs.A high dose of CPT promotes the enrichment of the pathogenic bacteria Escherichia-Shigella,which may be attributed to diarrhea caused by CPT,thus leading to a reduction in microbial burden;additionally,Escherichia-Shigella rapidly grows and occupies niches previously occupied by other bacteria that are lost due to diarrhea.PCRHNs+Laser treatment increased the abundance of Lactobacillus(probiotics),possibly due to the photothermal effect of the PCRHNs.This effect increased catalase activity,thus facilitating the conversion of hydrogen peroxide into oxygen within tumors and increasing oxygen levels in the body,which is conducive to the growth of facultative anaerobic bacteria.