Experimental study on hydraulic fracture behavior of concrete with wedge-splitting testing

The aim of this paper is to investigate the water pressure effects on hydraulic fracture behavior of concrete with wedge-splitting testing under dynamic loading. Five waterproof strain gauges are stuck along the crack path to observe the fracture process during the experiments. Four silicon water pressure sensors successfully measured the water pressure value on concrete face. The results show that the water pressure on crack faces accelerates the crack propagation of the concrete. The critical values of the splitting force decrease 26.7 and 25.6%, respectively, with the external applied water pressure of 0.2 and 0.4 MPa. Moreover, the hydraulic crack propagation speed increases at the beginning and tends to reach a peak value finally. The peak value of cracking speed is 11.08 m/s, which is high. Under dynamic loading, the water fails to fill the crack and only the trapped water interacts with the crack face. The water pressure is mainly a parabolic curve distribution along the crack path and the peak value decreases with the increase in the crack length

Research on Failure Characteristics and Zoning Control Technology of Thick-Soft Surrounding Rock for Deep Gob-Side Entry Retaining

Controlling the large deformation caused by bed separation failure of thick and soft surrounding rock in gob-side entry retaining is difficult. The deformation and failure modes of thick and soft surrounding rock are summarized and classified based on field research, theoretical analysis, laboratory tests, and actual measurements. Systematic research is conducted on the lithologic characteristics, failure characteristics, and control methods of the surrounding rock. The research findings are as follows: (1) The low strength, softening, and water swelling of thick mudstone, as well as its cataclasis, dilatancy, and long-term creep under strong mining and high stress are the objective reasons for large deformation of the surrounding rock. (2) Due to the weak stability of the surrounding rock-support structure and low collaborative roof side bearing capacity, no complete supporting structure is formed with the supporting system, causing the support body in each area to be crushed one by one, which is the subjective reason for the deformation and failure of the surrounding rock. (3) The deformation and failure characteristics of thick and soft surrounding rock in gob-side entry retaining are primarily divided into eight types: roof bending and sinking type, roof cutting along filling body, rib spalling type, roof fall type, filling body rotation type, filling body crushing type, roof step type, and roof cutting along the coal side. The initial points and key points for a chain reaction of each failure type are determined. (4) The surrounding rock is divided into 10 support zones at four levels, and control technology for “zonal support and overall reinforcement” is put forward. The mechanical effect of the support body in each zone and its role in maintaining the stability of surrounding rock are analyzed. This technology can ensure the integrity of the surrounding rock structure and improve the roof side collaborative bearing capacity

Preclinical and early clinical studies of a novel compound SYHA1813 that efficiently crosses the blood–brain barrier and exhibits potent activity against glioblastoma

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood–brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380)

Molecular signatures of major depression

Adversity, particularly in early life, can cause illness. Clues to the responsible mechanisms may lie with the discovery of molecular signatures of stress, some of which include alterations to an individual's somatic genome. Here, using genome sequences from 11,670 women, we observed a highly significant association between a stress-related disease, major depression, and the amount of mtDNA (p = 9.00 x 10(-42), odds ratio 1.33 [95% confidence interval [CI] = 1.29-1.37]) and telomere length (p = 2.84 x 10(-14), odds ratio 0.85 [95% CI = 0.81-0.89]). While both telomere length and mtDNA amount were associated with adverse life events, conditional regression analyses showed the molecular changes were contingent on the depressed state. We tested this hypothesis with experiments in mice, demonstrating that stress causes both molecular changes, which are partly reversible and can be elicited by the administration of corticosterone. Together, these results demonstrate that changes in the amount of mtDNA and telomere length are consequences of stress and entering a depressed state. These findings identify increased amounts of mtDNA as a molecular marker of MD and have important implications for understanding how stress causes the disease