A generalized nonlinear three-dimensional failure criterion based on fracture mechanics

Based on fracture mechanics theory and wing crack model,a three-dimensional strength criterion for hard rock was developed in detail in this paper.Although the basic expression is derived from initiation and propagation of a single crack,it can be extended to microcrack cluster so as to reflect the macroscopic failure characteristic.Besides,it can be derived as HoekeBrown criterion when the intermediate principal stress σ_(2) is equal to the minimum principal stress σ_(3)(Zuo et al.,2015).In addition,the opening direction of the microcrack cluster decreases with the increase of the intermediate principal stress coefficient,which could be described by an empirical function and verified by 10 kinds of hard rocks.Rock strength is influenced by the coupled effect of stress level and the opening direction of the microcrack clusters related to the stress level.As the effects of these two factors on the strength are opposite,the intermediate principal stress effect is induced.

Experimental investigation on fracturing process of marble under biaxial compression

In this study,servo-controlled biaxial compression tests were conducted on marble specimens to investigate their failure characteristics and fracturing process.The complete stressestrain curves were obtained,and the three-dimensional(3D)features of the failure surfaces were acquired by 3D laser scanning.Acoustic emission(AE)monitoring and moment tensor(MT)analysis were used in combination to better understand the fracturing mechanism of marble under biaxial compression.It was noted that a type of 3D stepwise cracking behaviour occurred on the fracturing surfaces of the examined specimens.The stress dropped multiple times,and a repeated fracturing mode corresponding to the repeated stress drops in the post-peak regime was observed.Three substages,i.e.stress stabilisation,stress decrease and stress increase,were identified for a single fracturing mode.Then quantitative and statistical analyses of the fracturing process at each substage were discussed.Based on the testing results,it was found that at the stress stabilisation substage,the proportion of mixed-mode fractures increased.At the stress decrease substage,the proportion of mixed-mode fractures decreased,and the tensile or shear fractures increased.At the stress increase substage,the proportion of mixed-mode or tensile fractures decreased,and the shear fractures increased.Finally,a conceptual model for the stepwise crack formation was proposed.

Targeted deletion of floral development genes in Arabidopsis with CRISPR/Cas9 using the RNA endoribonuclease Csy4 processing system

The formation of flowers in higher plants is controlled by complex gene regulatory networks.The study of floral development in Arabidopsis is promoted and maintained by transposon-tagged mutant lines.In this study,we report a CRISPR/Cas9 genome-editing system based on RNA endoribonuclease Csy4 processing to induce high-efficiency and inheritable targeted deletion of transcription factors involved in floral development in Arabidopsis.Using AP1,SVP,and TFL1 as the target genes,multisite and multiple-gene mutations were achieved with a tandemly arrayed Csy4-sgRNA architecture to express multiplexed sgRNAs from a single transcript driven by the Pol II promoter in transgenic lines.Targeted deletions of chromosomal fragments between the first exon and second exon in either one or three genes were generated by using a single binary vector.Interestingly,the efficiency of site-targeted deletion was comparable to that of indel mutation with the multiplexed sgRNAs.DNA sequencing analysis of RT-PCR products showed that targeted deletions of AP1 and TFL1 could lead to frameshift mutations and introduce premature stop codons to disrupt the open-reading frames of the target genes.In addition,no RT-PCR amplified product was acquired after SVPtargeted deletion.Furthermore,the targeted deletions resulted in abnormal floral development in the mutant lines compared to that of wild-type plants.AP1 and SVP mutations increased plant branching significantly,while TFL1 mutant plants displayed a change from indeterminate to determinate inflorescences.Thus,our results demonstrate that CRISPR/Cas9 with the RNA endoribonuclease Csy4 processing system is an efficient tool to study floral development and improve floral traits rapidly and simply.

Fusobacterium nucleatum enhances the efficacy of PD-L1 blockade in colorectal cancer

Given that only a subset of patients with colorectal cancer(CRC)benefit from immune checkpoint therapy,efforts are ongoing to identify markers that predict immunotherapeutic response.Increasing evidence suggests that microbes influence the efficacy of cancer therapies.Fusobacterium nucleatum induces different immune responses in CRC with different microsatellite-instability(MSI)statuses.Here,we investigated the effect of F.nucleatum on anti-PD-L1 therapy in CRC.We found that high F.nucleatum levels correlate with improved therapeutic responses to PD-1 blockade in patients with CRC.Additionally,F.nucleatum enhanced the antitumor effects of PD-L1 blockade on CRC in mice and prolonged survival.Combining F.nucleatum supplementation with immunotherapy rescued the therapeutic effects of PD-L1 blockade.Furthermore,F.nucleatum induced PD-L1 expression by activating STING signaling and increased the accumulation of interferon-gamma(IFN-γ)^(+)CD8^(+)tumor-infiltrating lymphocytes(TILs)during treatment with PD-L1 blockade,thereby augmenting tumor sensitivity to PD-L1 blockade.Finally,patient-derived organoid models demonstrated that increased F.nucleatum levels correlated with an improved therapeutic response to PD-L1 blockade.These findings suggest that F.nucleatum may modulate immune checkpoint therapy for CRC.

Correction To: Fusobacterium nucleatum enhances the efficacy of PD-L1 blockade in colorectal cancer

Correction to:Signal Transduction and Targeted Therapy https://doi.org/10.1038/S41392-021-00795-x,published online 19 November 2021 In this article^(1) Qing Wei should have been denoted as a corresponding author along with Huanlong Qin,but was inadvertently removed during the production process.The original article has been corrected.