Laser rock-breaking will produce cracks on the rock, and the cracking of the cracks affects the efficiency of laser rock-breaking. In this paper, the laser rock-breaking experimental platform was set ...up, the morphological characteristics of granite damage and the distribution of temperature field under different laser irradiation times (2∼10 s) were analyzed by SEM and infrared thermal imager. The results show that the temperature of the melting zone under the action of laser is maximum, and the damage manifests itself in the form of step-like pattern fracture. While the damage form of damage zone and thermal affected zone is mainly crack cracking. With the increase of laser irradiation time, the temperature gradient at the same location on the granite surface becomes larger. According to the temperature distribution of granite, innovatively proposed a laser rock breaking simulation model based on the discrete element method, which can reflect the cracking process of rock under the laser. The simulation results show that crack cracking is a dynamic failure process. During the laser irradiation process, the melting zone cracking manifests itself as a tensile failure, while the damage zone and thermal affected zone were dominated by tensile–shear composite damage. The laser rock-breaking efficiency can be improved by controlling the laser damage to the rock in the form of tensile damage. Finally, innovatively established a method for evaluating rock damage under laser action, which can be used to quantitatively evaluate the damage degree of laser rock-breaking and provide a new means for the preferential selection of laser parameters in future drilling processes.
•Reveals the cracking mechanism of rock under the action of laser.•Innovatively proposed a laser rock breaking simulation model based on discrete element method.•Based on fractal theory, a method for evaluating rock damage under laser action is established.
Peptidylarginine deiminase 4 (PAD4), a Ca2+-dependent enzyme, catalyzes the conversion of arginine to citrulline and has been strongly associated with many malignant tumors. However, the molecular ...mechanisms of PAD4 in the development and progression of colorectal cancer (CRC) remain unclearly defined. In our study, PAD4 expression was increased in CRC tissues and cells, and was closely related to tumor size, lymph node metastasis. Moreover, the transcription factor KLF9 directly bound to PADI4 gene promoter, leading to overexpression of PAD4 in CRC cells, which augmented cell growth and migration. We revealed that PAD4 interacted with and citrullinated glycogen synthase kinase-3β (GSK3β) in CRC cells, and GSK3β Arg-344 was the dominating PAD4-citrullination site. Furthermore, IgL2 and catalytic domains of PAD4 directly bound to the kinase domain of GSK3β in CRC cells. Mechanistically, PAD4 promoted the transport of GSK3β from the cytoplasm to the nucleus, thereby increasing the ubiquitin-dependent proteasome degradation of nuclear cyclin-dependent kinase inhibitor 1 (CDKN1A). Our study is the first to reveal the details of a critical PAD4/GSK3β/CDKN1A signaling axis for CRC progression, and provides evidence that PAD4 is a potential diagnosis biomarker and therapeutic target in CRC.
Abstract
IDH1 mutations frequently occur early in human glioma. While IDH1 mutation has been shown to promote gliomagenesis via DNA and histone methylation, little is known regarding its regulation ...in antiviral immunity. Here, we discover that IDH1 mutation inhibits virus-induced interferon (IFN) antiviral responses in glioma cells. Mechanistically, D2HG produced by mutant IDH1 enhances the binding of DNMT1 to
IRF3/7
promoters such that IRF3/7 are downregulated, leading to impaired type I IFN response in glioma cells, which enhances the susceptibility of gliomas to viral infection. Furthermore, we identify DNMT1 as a potential biomarker predicting which IDH1mut gliomas are most likely to respond to oncolytic virus. Finally, both D2HG and ectopic mutant IDH1 can potentiate the replication and oncolytic efficacy of VSVΔ51 in female mouse models. These findings reveal a pivotal role for IDH1 mutation in regulating antiviral response and demonstrate that IDH1 mutation confers sensitivity to oncolytic virotherapy.
•Parents of children with epilepsy have poor sleep quality and a low level of caregiver burden.•Caregiver burden of parents is directly correlated with sleep quality.•Individual resilience is ...indirectly related to sleep quality via caregiver burden.
Parents caring for children with epilepsy have poor sleep quality and experience a certain level of caregiving burden. Individual resilience is a crucial psychological variable that contributes to health during extraordinary challenges. This study aimed to determine the relationships among individual resilience, caregiver burden, and sleep quality.
This was a descriptive cross-sectional study with a convenience sample, following the STROBE guidelines. One hundred and ninety-one parents of children with epilepsy were invited to participate in the study. Of these, 173 participants completed measures of sleep quality, caregiver burden, and individual resilience. Path analysis was performed to probe the indirect relationship between individual resilience and sleep quality via caregiver burden.
Correlation analysis revealed that individual resilience total scores were significantly and marginally negatively correlated with caregiver burden and sleep quality total scores (r = −0.215, P <.01; r = −0.250, P <.01). Moreover, there was a significant moderate positive correlation between the total caregiver burden scores and total sleep quality scores (r = 0.389, P <.001). The path model showed that individual resilience is indirectly associated with sleep quality via caregiver burden.
The higher the level of individual resilience, the less the caregiver burden and the better the sleep quality for parents of children with epilepsy.
The issue of bacterial infectious diseases remains a significant concern worldwide, particularly due to the misuse of antibiotics, which has caused the emergence of antibiotic-resistant strains. ...Fortunately, the rapid development of nanomaterials has propelled significant progress in antimicrobial therapy, offering promising solutions. Among them, the utilization of nanoenzyme-based chemodynamic therapy (CDT) has become a highly hopeful approach to combating bacterial infectious diseases. Nevertheless, the application of CDT appears to be facing certain constraints for its low efficiency in the Fenton reaction at the infected site. In this study, we have successfully synthesized a versatile nanozyme, which was a composite of molybdenum sulfide (MoS2) and iron sulfide (FeS2), through the hydrothermal method. The results showed that iron/molybdenum sulfide nanozymes (Fe/Mo SNZs) with desirable peroxidase (POD) mimic activity can generate cytotoxic reactive oxygen species (ROS) by successfully triggering the Fenton reaction. The presence of MoS2 significantly accelerates the conversion of Fe2+/Fe3+ through a cocatalytic reaction that involves the participation of redox pairs of Mo4+/Mo6+, thereby enhancing the efficiency of CDT. Additionally, based on the excellent photothermal performance of Fe/Mo SNZs, a near-infrared (NIR) laser was used to induce localized temperature elevation for photothermal therapy (PTT) and enhance the POD-like nanoenzymatic activity. Notably, both in vitro and in vivo results demonstrated that Fe/Mo SNZs with good broad-spectrum antibacterial properties can help eradicate Gram-negative bacteria like Escherichia coli and Gram-positive bacteria like Staphylococcus aureus. The most exciting thing is that the synergistic PTT/CDT exhibited astonishing antibacterial ability and can achieve complete elimination of bacteria, which promoted wound healing after infection. Overall, this study presents a synergistic PTT/CDT strategy to address antibiotic resistance, providing avenues and directions for enhancing the efficacy of wound healing treatments and offering promising prospects for further clinical use in the near future.The issue of bacterial infectious diseases remains a significant concern worldwide, particularly due to the misuse of antibiotics, which has caused the emergence of antibiotic-resistant strains. Fortunately, the rapid development of nanomaterials has propelled significant progress in antimicrobial therapy, offering promising solutions. Among them, the utilization of nanoenzyme-based chemodynamic therapy (CDT) has become a highly hopeful approach to combating bacterial infectious diseases. Nevertheless, the application of CDT appears to be facing certain constraints for its low efficiency in the Fenton reaction at the infected site. In this study, we have successfully synthesized a versatile nanozyme, which was a composite of molybdenum sulfide (MoS2) and iron sulfide (FeS2), through the hydrothermal method. The results showed that iron/molybdenum sulfide nanozymes (Fe/Mo SNZs) with desirable peroxidase (POD) mimic activity can generate cytotoxic reactive oxygen species (ROS) by successfully triggering the Fenton reaction. The presence of MoS2 significantly accelerates the conversion of Fe2+/Fe3+ through a cocatalytic reaction that involves the participation of redox pairs of Mo4+/Mo6+, thereby enhancing the efficiency of CDT. Additionally, based on the excellent photothermal performance of Fe/Mo SNZs, a near-infrared (NIR) laser was used to induce localized temperature elevation for photothermal therapy (PTT) and enhance the POD-like nanoenzymatic activity. Notably, both in vitro and in vivo results demonstrated that Fe/Mo SNZs with good broad-spectrum antibacterial properties can help eradicate Gram-negative bacteria like Escherichia coli and Gram-positive bacteria like Staphylococcus aureus. The most exciting thing is that the synergistic PTT/CDT exhibited astonishing antibacterial ability and can achieve complete elimination of bacteria, which promoted wound healing after infection. Overall, this study presents a synergistic PTT/CDT strategy to address antibiotic resistance, providing avenues and directions for enhancing the efficacy of wound healing treatments and offering promising prospects for further clinical use in the near future.
Graphene and its derivatives are the new carbon nanomaterials with the prospect for great applications in electronics, energy storage, biosensors and medicine. However, little is known about the ...toxicity of graphene or its derivatives in the case of occasional or repeated ocular exposure. We performed in vitro and in vivo studies to evaluate the toxicity of graphene oxide (GO) exposure to the eye. Primary human corneal epithelium cells (hCorECs) and human conjunctiva epithelium cells (hConECs) were exposed to GO (12.5-100 μg/mL). Acute GO exposure (2 h) did not induce cytotoxicity to hCorECs. However, short-term GO exposure (24 h) exerted significant cytotoxicity to hCorECs and hConECs with increased intracellular reactive oxygen species (ROS). Glutathione (GSH) reduced the GO-induced cytotoxicity. We further performed acute eye irritation tests in albino rabbits according to the Organization for Economic Cooperation and Development (OECD) guidelines, and the rabbits did not exhibit corneal opacity, conjunctival redness, abnormality of the iris, or chemosis at any time point after the instillation of 100 μg/mL of GO. However, 5-day repeated GO exposure (50 and 100 μg/mL) caused reversible mild corneal opacity, conjunctival redness and corneal epithelium damage to Sprague-Dawley rats, which was also alleviated by GSH. Therefore, our study suggests that GO-induced time- and dose-dependent cytotoxicity to hCorECs and hConECs via oxidative stress. Occasional GO exposure did not cause acute eye irritation; short-term repeated GO exposure generally resulted in reversible damage to the eye via oxidative stress, which may be alleviated by the antioxidant GSH.
•The stiffness threshold and the bending–stretching transitional threshold of buckypapers under arbitrary loads are studied.•The thresholds are revealed to be independent of the load types.•Simple ...expressions are proposed to predict the thresholds.•Simple unified formulas for moduli prediction are established based on the thresholds.•Factors that influence the stiffness and thresholds of buckypapers are investigated.
Buckypaper, a paper-like carbon nanotube (CNT) network, is an important material structure to utilize the micro-scale excellent properties of CNTs into macro-scale materials. Previous study revealed the existence of stiffness threshold and bending–stretching transitional threshold of CNT networks under uniaxial load. However, the load conditions in practical applications are very complicated. Therefore, the stiffness and thresholds of buckypapers under arbitrary loads are studied by both theoretical analysis and finite element simulations. It is revealed that the thresholds for an arbitrary load are exactly same as those for the uniaxial load, indicating that the stiffness threshold and bending–stretching transitional threshold are both independent of load types. Furthermore, the buckypapers with randomly distributed CNTs are revealed to be well isotropic when the CNT concentration is higher than the bending–stretching transitional threshold. Accordingly, a simple unified piecewise analytical expression is summarized to predict the uniaxial, area/bulk and shear moduli of buckypapers. Besides, it is found that the CNT curliness and paper thickness can influence the thresholds, but the curliness effect can be weakened by hydrostatic loading. This study provides a theoretical guidance to the material structural design of buckypapers, and can be extended to other nanotube and/or nanowire constructed networks as well.
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Colorectal cancer (CRC) is a malignant gastrointestinal cancer that seriously threatens human health. Its morbidity and mortality are in the forefront of tumors. Chemotherapy and radiotherapy play an ...important role in the treatment of CRC, which can improve the survival time and quality of life of patients, but the treatment progress is slow, and the treatment effect is not satisfactory. In recent years, immunotherapy has been a new direction in the field of colorectal cancer treatment after radiotherapy, chemotherapy and targeted therapy. Immune checkpoints play a vital role in the immunotherapy of cancer, and take part in the immune escape of cancer, which is closely related to the occurrence and development of cancer. This article reviews the research progress of immune checkpoints and their blockers in the field of CRC, in order to help better use of the immune system to treat cancer.
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