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The unloading effect by excavation may cause irreversible and severe damage to the surrounding rock masses in underground engineering. In this paper, both conventional triaxial compression (CTC) tests and triaxial unloading confining pressure (TUCP) tests were conducted on fine-grained granite to study its triaxial compression failure processes due to unloading. Based on the crack volumetric strain (CVS) method, the crack axial strain (CAS) method and crack radial area strain (CRAS) method were proposed to identify the failure precursor information (including stress thresholds and axial strain at the initiation point of crack connectivity stage) during the rock failure processes. The results of the CTC tests show that the stable crack development stress σsd, unstable crack development stress σusd, and crack connectivity stress σct identified by the CAS method are 6%, 74%–84%, and 86%–97% of the peak stress, respectively. For the TUCP cases, as the confining pressure increases, the stress thresholds, axial pressure at failure and axial strain at the start of the crack connectivity stage increase, while the time ratio of the crack connectivity stage to the entire unloading stage decreases. This indicates that fine-grained granite is prone to generate more cracks and leads to fail suddenly under high confining pressure. Furthermore, this new method demonstrates that the point at which the derivative of the radial crack area strain transitions from stable to a sudden increase or decrease is defined as the precursor point of rock failure. The results of axial strain at the starting point of the crack connectivity stage are very close to those predicted by the AE method, with β1 no more than 11%.

The monkeypox virus (MPXV) has triggered a current outbreak globally. Genome sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and control. It is a significant challenge but necessary to optimize the strategy and application of rapid full-length genome identification and to track variations of MPXV in clinical specimens with low viral loads, as it is one of the DNA viruses with the largest genome and the most AT-biased, and has a significant number of tandem repeats. Here we evaluated the performance of metagenomic and amplicon sequencing techniques, and three sequencing platforms in MPXV genome sequencing based on multiple clinical specimens of five mpox cases in Chinese mainland. We rapidly identified the full-length genome of MPXV with the assembly of accurate tandem repeats in multiple clinical specimens. Amplicon sequencing enables cost-effective and rapid sequencing of clinical specimens to obtain high-quality MPXV genomes. Third-generation sequencing facilitates the assembly of the terminal tandem repeat regions in the monkeypox virus genome and corrects a common misassembly in published sequences. Besides, several intra-host single nucleotide variations were identified in the first imported mpox case. This study offers an evaluation of various strategies aimed at identifying the complete genome of MPXV in clinical specimens. The findings of this study will significantly enhance the surveillance of MPXV. [ABSTRACT FROM AUTHOR]

Immunotherapy is a promising approach for treating metastatic breast cancer (MBC), offering new possibilities for therapy. While checkpoint inhibitors have shown great progress in the treatment of metastatic breast cancer, their effectiveness in patients with bone metastases has been disappointing. This lack of efficacy seems to be specific to the bone environment, which exhibits immunosuppressive features. In this study, we elucidate the multiple roles of the sialic acid-binding Ig-like lectin (Siglec)-15/sialic acid glyco-immune checkpoint axis in the bone metastatic niche and explore potential therapeutic strategies targeting this glyco-immune checkpoint. Our research reveals that elevated levels of Siglec-15 in the bone metastatic niche can promote tumor-induced osteoclastogenesis as well as suppress antigen-specific T cell responses. Next, we demonstrate that antibody blockade of the Siglec-15/sialic acid glyco-immune checkpoint axis can act as a potential treatment for breast cancer bone metastasis. By targeting this pathway, we not only aim to treat bone metastasis but also inhibit the spread of metastatic cancer cells from bone lesions to other organs. [ABSTRACT FROM AUTHOR]