Molecular dynamics simulation of the scratching process of GaAs with different crystal orientations.

CONTEXT: In order to further improve the manufacturing technology of resonator facet of GaAs (gallium arsenide)-based laser, the scratching process of GaAs was simulated by molecular dynamics. Models of GaAs crystals with different orientations, including GaAs [100], GaAs [110], and GaAs [111], were generated, followed by scratch simulations on these models. The surface characteristics of scratches, damage width, subsurface damage, stack height, and the distribution and activity characteristics of dislocations were analyzed based on the simulation results. The results show that there are obvious anisotropy in the deformation of different crystal orientation during the scratching process of GaAs. Surface features, damage width, subsurface damage, and dislocation dynamics during scraping in GaAs crystals strongly depend on crystal orientation. It was also observed that GaAs exhibits distinct characteristics of dislocation activity during the scratching process, depending on its crystal orientation. In addition, GaAs [110] crystal direction has the smallest maximum damage width and subsurface damage depth. The maximum of maximum damage width is in GaAs [100] crystal direction, and the maximum subsurface damage depth is in GaAs [111] crystal direction. In addition, the stacking height is maximum when GaAs [100] is scraped and minimum when GaAs [110] is scraped. METHODS: The engraving quality of GaAs materials was investigated utilizing the LAMMPS software through molecular dynamics simulations, while observations were facilitated using the OVITO software. The MD simulation was conducted employing the NPT ensemble, with the temperature fixed at 300 K. A time step of 2 fs was utilized, and the total duration of the MD simulation spanned 600 ps.

Design and Research of VR Basketball Teaching System Based on Embedded Intelligent Sensor.

Physical education pedagogy serves as a carrier of physical education theory and practical activities and plays an important role in physical education. The reform and development of education are always related closely to the growth of scientific and technological development, and people's physical education training methods are also undergoing subtle changes. The traditional single and formulaic training methods in the past have gradually turned to modern training methods with better interaction and visibility. All of this prompts people to have new requirements on sports training concepts and training modes. On this basis, teachers can conduct virtual teaching in a more interactive, more involved, and orderly manner in the virtual classroom. This paper constructs the implementation framework of VR basketball teaching auxiliary training, divides students into an experimental group and a control group and tests the physical fitness of students before and after the experiment. The students' basic basketball skills were tested by using embedded intelligent sensors to recognize the students' movements. The experimental results showed that after the test, the four basic basketball skills scores of the students in the experimental group were 68.78, 74.02, 73.13, and 72.34, respectively. The virtual reality basketball teaching system designed in this paper can effectively improve the basketball level of students.

Design, Synthesis, and Biological Evaluations of DOT1L Peptide Mimetics Targeting the Protein-Protein Interactions between DOT1L and MLL-AF9/MLL-ENL.

On the basis of a previously identified DOT1L peptide mimetic (compound 3), a series of novel peptide mimetics were designed and synthesized. These compounds can potently bind to AF9 and ENL either in cell-free binding assays or in leukemia cells, and selectively inhibit the growth of leukemia cells containing mixed lineage leukemia (MLL) fusion proteins. The most potent compound 12 exhibited comparable anticancer cellular activities to those of EPZ5676, a clinical stage enzymatic inhibitor of DOT1L in several leukemia cell lines containing MLL fusion proteins. Mechanism studies for compound 12 indicated that it did not affect the global methylation of H3K79 catalyzed by DOT1L but could effectively suppress the methylation of H3K79 at MLL fusion proteins targeted genes and inhibit the expressions of these genes. Our studies thus demonstrated that inhibiting the protein-protein interactions between DOT1L and MLL fusion proteins is a potentially effective strategy for the treatment of MLL rearranged leukemias.

Nephroprotective Effects of Tetramethylpyrazine Nitrone TBN in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal failure, but therapeutic options for nephroprotection are limited. Oxidative stress plays a key role in the pathogenesis of DKD. Our previous studies demonstrated that tetramethylpyrazine nitrone (TBN), a novel nitrone derivative of tetramethylpyrazine with potent free radical-scavenging activity, exerted multifunctional neuroprotection in neurological diseases. However, the effect of TBN on DKD and its underlying mechanisms of action are not yet clear. Herein, we performed streptozotocin-induced rat models of DKD and found that TBN administrated orally twice daily for 6 weeks significantly lowered urinary albumin, N-acetyl-ß-D-glycosaminidase, cystatin C, malonaldehyde, and 8-hydroxy-2'-deoxyguanosine levels. TBN also ameliorated renal histopathological changes. More importantly, in a nonhuman primate model of spontaneous stage III DKD, TBN increased the estimated glomerular filtration rate, decreased serum 3-nitrotyrosine, malonaldehyde and 8-hydroxy-2'-deoxyguanosine levels, and improved metabolic abnormalities. In HK-2 cells, TBN increased glycolytic and mitochondrial functions. The protective mechanism of TBN might involve the activation of AMPK/PGC-1α-mediated downstream signaling pathways, thereby improving mitochondrial function and reducing oxidative stress in the kidneys of DKD rodent models. These results support the clinical development of TBN for the treatment of DKD.

Investigation of echocardiographic characteristics and predictors for persistent defects of patent foramen ovale or patent ductus arteriosus in Chinese newborns.

BACKGROUND: Persistent patent foramen ovale (PFO) and patent ductus arteriosus (PDA) increase the adult risk of cryptogenic embolic stroke and chronic pulmonary hypertension. To understand the characteristics of PFO and PDA in newborns, we investigated the spontaneous closure rate and derived the determinants for residual defects. METHODS: We utilized the database of congenital heart disease (CHD) in Xiamen ChangGung Memorial Hospital from 2015 to 2017 and allocated 2523 eligible newborns into four groups according to PDA, PFO, both or neither at birth. A total of 574, 1229, 202 and 518 newborns were assigned into the group of PFO and PDA, PFO alone, PDA alone and non-PFO/non-PDA, respectively. Regular echocardiographic follow-ups at baseline, 6, 12 and 24 months after birth were performed for evaluating the spontaneous closure rate in the subjects. Regression analysis was carried out to study the risk factors of residual congenital defects. RESULTS: Newborns with PFO alone had the youngest birth age and lowest birth weight among the four groups. About one in four PDA-alone newborns had concomitant small ASD, i.e., <5 mm in diameter. Echocardiographic study showed that 71.3% and 30.8% of CHD newborns had PFO and PDA, respectively, compared to less than 10% of them having ASD or VSD. However, more than 95% of newborns with PFO or PDA closed spontaneously at 6 months, in contrast to about 30% of newborns with ASD or VSD had persistent existence of the intracardiac defects. Complex CHD significantly linked to persistent PFO or PDA at 6 and 12 months, with an adjusted hazard ratio of 9.03 (95% CI 1.97-41.46) and 12.11 (95% CI 2.11-69.72), respectively. CONCLUSIONS: Chinese newborns with PFO or PDA expressed differences in characteristics and concomitant congenital defects. Additionally, persistent PFO or PDA is strongly associated with complex CHD and requires long-term regular monitoring for future associated complications.

Chronic stress-induced immune dysregulation in cancer: implications for initiation, progression, metastasis, and treatment.

Psychological stress is a well-accepted risk factor in cancer initiation and progression. The explosive growth of psychoneuroimmunology research in the past decade has yielded an unprecedented wealth of information about the critical role of chronic stress in the immune dysfunction that influences tumor behaviors, which presents insights to mitigate distress and improve prognosis in cancer patients. Chronic stress exacerbates inflammation and causes a metabolism disorder, making it difficult for the organisms to maintain homeostasis and increasing its susceptibility to cancer. The shifted differentiation and redistribution of the immune system induced by chronic stress fail to combat cancer efficiently. Chronic stress increases the tumor-educated immune suppressive cells and impairs the cytotoxicity of cellular immunity, thereby promoting lymphatic metastasis and hematogenous metastasis. In addition, the efficacy of existing cancer therapies is undermined because chronic stress prevents the immune system from responding properly. Emerging stress-reduction measures have been administered to assist cancer patients to cope with the adverse effects of chronic stress. Here we systematically review the current molecular, cellular, physiological mechanisms about stress-mediated immune responses in the enhancement of tumor initiation and progression, remodeling of tumor microenvironment and impairment of anti-tumor treatment. We also summarize the potential clinically applicable stress-oriented strategies towards cancer and discuss briefly where important knowledge gaps remain.

Systemic Analysis of the Prognosis-Related RNA Alternative Splicing Signals in Melanoma.

BACKGROUND Alternative splicing (AS), the mechanism underlying the occurrence of protein diversity, may result in cancer genesis and development when it becomes out of control, as suggested by a growing number of studies. However, systemically analyze of AS events at the genome-wide level for skin cutaneous melanoma (SKCM) is still in a preliminary phase. This study aimed to systemically analyze the bioinformatics of the AS events at a genome-wide level using The Cancer Genome Atlas (TCGA) SKCM data. MATERIAL AND METHODS The SpliceSeq tool was used to analyze the AS profiles for SKCM clinical specimens from the TCGA database. The association between AS events and overall survival was analyzed by Cox regression analysis. AS event intersections and a gene interaction network were established by UpSet plot. A multivariate survival model was used to establish a feature genes prognosis model. RESULTS A total of 103 SKCM patients with full clinical parameters available were included in this study. We established an AS network that investigated the relationship between AS events and clinical prognosis information. Furthermore, 4 underlying feature genes of SKCM (MCF2L, HARS, TFR2, and RALGPS1) were found in the AS network. We performed function analysis as well as correlation analysis of AS events with gene expression. Using the multivariate survival model, we further confirmed the 4 genes that impacted the classifying SKCM prognosis at the level of AS events as well as gene expression, especially in wild-type SKCM. CONCLUSIONS AS events could be ideal indicators for SKCM prognosis. The key feature gene MCF2L played an important role in wild-type SKCM.

The novel N-methyl-d-aspartate receptor antagonist MN-08 ameliorates lipopolysaccharide-induced acute lung injury in mice.

Acute lung injury (ALI) is a clinically severe respiratory disorder, and effective therapy is urgently needed. MN-08, a novel synthetic N-methyl-d-aspartate receptor (NMDAR) antagonist, was investigated for its effect on lipopolysaccharide (LPS)-induced ALI. In vitro, the protective effect of MN-08 on inflammatory response, oxidative stress, and tight junctions (TJs) structure was explored in LPS-induced RAW 264.7 cells and A549 cells. MN-08 markedly decreased (p < 0.001) the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and reactive oxygen species (ROS), whereas it moderately upregulated (p < 0.05) heme oxygenase (HO)-1 protein expression in LPS-induced RAW 264.7 cells. Moreover, MN-08 significantly inhibited (p < 0.001) cell apoptosis and improved (p < 0.001) protein expression of TJs in LPS-induced A549 cells. In vivo, the therapeutic effect of MN-08 was evaluated in the LPS-induced ALI model through intratracheal instillation in BALB/c mice. MN-08 administration dramatically attenuated (p < 0.001) pulmonary pathological changes and reduced (p < 0.001) the levels of glutamate, myeloperoxidase (MPO), malondialdehyde (MDA), and number of cells in BALF, whereas it increased (p < 0.05) superoxide dismutase (SOD) and glutathione (GSH) activities in ALI mice. Furthermore, MN-08 markedly blocked the mitogen-activated protein kinases (MAPKs)/nuclear translocation of nuclear factor-κB (NF-κB) signaling pathways in RAW 264.7 cells and lung tissues. These results indicate that MN-08 exhibits lung protection in an LPS-induced ALI model via anti-inflammatory and anti-oxidative activities.