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With the complexity and diversification of rocket launch tasks, more stringent requirements are put forward for MEMS electronic equipment, which is closely related to the stability and security of rocket. The key components of the rocket-borne electronic system are composed of discrete components, integrated components and corresponding connected fixed components. The selection, welding and board level connection of each electronic element determine the reliability of the MEMS component. In this paper, the fault tree analysis method is applied to the reliability analysis of the rocket-borne recorder, and the dynamic fault tree analysis method is introduced to compensate the deficiency of the traditional static fault tree analysis method, finally the simulation comparison with Monte-Carlo analysis method is carried out to verify the effectiveness and feasibility of the proposed method. The work of this paper is of great significance for establishing the reliability theory of the system and mastering the experience of quick failure diagnosis.

Sperm-associated antigen 5 (SPAG5) has been identified as a driver in several type of cancers. In this study, we aimed to reveal the role of SPAG5 in melanoma and clarify whether FOXM1 (forkhead box protein M1) /ADAM17 (A disintegrin and metalloproteinase 17) /NOTCH1 signaling was involved. The expression of SPAG5 in malignant melanoma (MM) tissues and matched normal tissues was detected using qRT-PCR, immunohistochemistry and Western blotting. Cell viability was tested using CCK-8 (Cell Count Kit-8), colony formation and EdU staining. Cell migration and epithelial to mesenchymal transition (EMT) were measured using transwell chambers and immunofluorescent staining. Cell cycle distribution and tumorigenesis were assessed by flow cytometry and in vivo tumor-bearing experiments, respectively. The results demonstrated that the expression of SPAG5 was increased in MM tissues and cells. Downregulation of SPAG5 inhibited cell viability, migration, invasion and EMT, and induced a G1-phase arrest. In addition, downregulation of SPAG5 decreased the expression of FOXM1, thereafter inhibiting the expression of ADAM17, NOTCH1 and HES1. Furthermore, deletion of SPAG5 expression decreased the tumorigenesis of MM A375 cells. In conclusion, this study demonstrated that SPAG5 was overexpressed in MM. Downregulation of SPAG5 repressed MM cell growth and EMT, which might be induced by inactivation of the FOXM1/ADAM17/NOTCH1 signaling.

Psoriasis is a systemic inflammatory disease. The autoimmune response plays a role in the pathogenesis of psoriasis. The long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) can regulate the immune response and participate in the pathogenesis of immune-related diseases, however, the role of ANRIL in the pathogenesis of psoriasis requires further clarification.To study the association between ANRIL polymorphisms and psoriasis in the northern Chinese population.We genotyped six SNPs in ANRIL in 270 psoriasis vulgaris patients and 271 healthy controls in the northern Chinese population using an improved multiplexed ligation detection reaction method, in order to identify the role of ANRIL in psoriasis.The C allele of rs3217992 and the T allele of rs2518723 were more prevalent in the case group than in the control group. The haplotypes, CTATAA, CCCCGG, and CTCCGG, were associated with risk of psoriasis, while the TCCCGG, TCATAA and CCATAA haplotypes were protective against psoriasis. Based on subgroup analysis, patients with the CT genotype at the rs3217992 and rs2518723 loci had a higher probability of a family history of psoriasis, and patients with the AA genotype had a higher mean age in the rs1333048 and rs10757278 groups, while those with the TT genotype had a higher mean age in the rs1333045 group.Our study identifies an association between ANRIL genetic variants and risk of psoriasis in northern China.

In this paper, a static load performance testing platform for truck-mounted drilling rigs is constructed, which can directly test the static torque and static lifting force on the truck-mounted drilling rig, and replace current methods of theoretical calculation and construction experience for obtaining the above parameters. This platform detection is intuitive, accurate and efficient, and thus has been successfully applied to static load performance tests and delivery inspections on truck-mounted drilling rigs.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is characterized by deregulated hepatic lipid metabolism; however, the association between MAFLD development and mitochondrial dysfunction has yet to be confirmed. Herein, we employed high-resolution respirometry, blue native polyacrylamide gel electrophoresis-based in-gel activity measurement and immunoblot analysis to assess mitochondrial function in obesity-induced mouse models with varying degrees of MAFLD. Results showed a slight but significant decrease in hepatic mitochondrial respiration in some MAFLD mice compared to mice fed a standard diet. However, the activities and levels of mitochondrial oxidative phosphorylation complexes remained unchanged during obesity-induced MAFLD progression. These results suggest that mitochondrial function, particularly oxidative phosphorylation, was mildly affected during obesity-induced MAFLD development. Moreover, transcriptome profiling of mouse and human liver tissues with varying degrees of MAFLD revealed that the decreased activation of mitochondria-related pathways was only associated with MAFLD of a high histological grade, whereas the major regulators of mitochondrial biogenesis were not altered in mice or humans during MAFLD development. Collectively, our results suggest that impaired hepatic mitochondrial function is not closely associated with obesity-induced MAFLD. Therefore, therapeutic strategies targeting mitochondria for the treatment of MAFLD should be reconsidered.

The phase diagrams of the Mg(NO3)2–Ln(NO3)3 (Ln = Nd, Sm, Eu, Tb)–HNO3–H2O systems in the (∼20%) HNO3 regions at T = 298.15 K were determined by using an isothermal solution saturation method. The Schreinemaker’s wet residues method was used to determine the compositions of solid-phases. Both Mg(NO3)2–Nd(NO3)3–HNO3–H2O and Mg(NO3)2–Sm(NO3)3–HNO3–H2O systems are complicated with three equilibrium solid phases Mg(NO3)2·6H2O, Mg3Ln2(NO3)12·24H2O and Ln(NO3)3·6H2O (Ln = Nd, Sm). But the systems Mg(NO3)2–Eu(NO3)3–HNO3–H2O and Mg(NO3)2–Tb(NO3)3Tb–HNO3–H2O are simple eutonic type. The two new solid-phase compounds Mg3Nd2(NO3)12·24H2O and Mg3Sm2(NO3)12·24H2O are congruently soluble in an average medium of ∼20 mass % HNO3, and they were identified and characterized by the methods of powder X-ray diffraction, X–ray diffraction single crystal structure analysis, and thermogravimetric/differential thermogravimetric. The XRD diffraction patterns for the two new solid-phase compounds are identical due to their isomorphic structure. They belong to hexagonal systems, with space group R3. For Mg3Nd2(NO3)12·24H2O, a = b = (1.0993 ± 0.0005) nm, c = (1.7211 ± 0.0007) nm, V = (1.8012 ± 0.0013) nm3, Dc = (4.2532 ± 0.0024) g·cm−3, Z = 3; for Mg3Sm2(NO3)12·24H2O, (a = b = 1.1198 ± 0.0004) nm, c = (1.7257 ± 0.0006) nm, V = (1.8742 ± 0.0011) nm3, Dc = (4.1201 ± 0.0012) g cm−3, Z = 3. The standard molar enthalpies of solution of the compounds Mg3Nd2(NO3)12·24H2O and Mg3Sm2(NO3)12·24H2O in water (aq) were measured to be (101.26 ± 0.77) kJ mol−1 and (80.27 ± 0.81) kJ mol−1, and their standard molar enthalpies of formation were calculated to be – (12214.13 ± 2.5) kJ mol−1 and – (12183.6 ± 2.5) kJ mol−1, respectively.

Background: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive malignancies, with no effective treatment currently available. The molecular mechanisms of ATC carcinogenesis remain poorly understood. The objective of this study was to investigate the mechanisms and functions of super-enhancer (SE)-driven oncogenic transcriptional addiction in the progression of ATC and identify new drug targets for ATC treatments. Methods: High-throughput chemical screening was performed to identify new drugs inhibiting ATC cell growth. Cell viability assay, colony formation analysis, cell-cycle analysis, and animal study were used to examine the effects of drug treatments on ATC progression. Chromatin immunoprecipitation sequencing was conducted to establish a SE landscape of ATC. Integrative analysis of RNA sequencing, chromatin immunoprecipitation sequencing, and CRISPR/Cas9-mediated gene editing was used to identify THZ1 target genes. Drug combination analysis was performed to assess drug synergy. Patient samples were analyzed to evaluate candidate biomarkers of prognosis in ATC. Results: THZ1, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7), was identified as a potent anti-ATC compound by high-throughput chemical screening. ATC cells, but not papillary thyroid carcinoma cells, are exceptionally sensitive to CDK7 inhibition. An integrative analysis of both gene expression profiles and SE features revealed that the SE-mediated oncogenic transcriptional amplification mediates the vulnerability of ATC cells to THZ1 treatment. Combining this integrative analysis with functional assays led to the discovery of a number of novel cancer genes of ATC, including PPP1R15A, SMG9, and KLF2. Inhibition of PPP1R15A with Guanabenz or Sephin1 greatly suppresses ATC growth. Significantly, the expression level of PPP1R15A is correlated with CDK7 expression in ATC tissue samples. Elevated expression of PPP1R15A and CDK7 are both associated with poor clinical prognosis in ATC patients. Importantly, CDK7 or PPP1R15A inhibition sensitizes ATC cells to conventional chemotherapy. Conclusions: Taken together, these findings demonstrate transcriptional addiction in ATC pathobiology and identify CDK7 and PPP1R15A as potential biomarkers and therapeutic targets for ATC.

Background Genome-wide mapping of transcription factor (TF) binding sites is essential to identify a TF's direct target genes in kidney development and diseases. However, due to the cellular complexity of the kidney and limited numbers of a given cell type, it has been challenging to determine the binding sites of a TF in vivo. cAMP response element-binding protein (CREB) is phosphorylated and hyperactive in autosomal dominant polycystic kidney disease (ADPKD). We focus on CREB as an example to profile genomic loci bound by a TF and to identify its target genes using low numbers of specific kidney cells. Methods Cleavage under targets and release using nuclease (CUT&RUN) assays were performed with Dolichos biflorus agglutinin (DBA)-positive tubular epithelial cells from normal and ADPKD mouse kidneys. Pharmacologic inhibition of CREB with 666-15 and genetic inhibition with A-CREB were undertaken using ADPKD mouse models. Results CUT&RUN to profile genome-wide distribution of phosphorylated CREB (p-CREB) indicated correlation of p-CREB binding with active histone modifications (H3K4me3 and H3K27ac) in cystic epithelial cells. Integrative analysis with CUT&RUN and RNA-sequencing revealed CREB direct targets, including genes involved in ribosome biogenesis and protein synthesis. Pharmacologic and genetic inhibition of CREB suppressed cyst growth in ADPKD mouse models. Conclusions CREB promotes cystogenesis by activating ribosome biogenesis genes. CUT&RUN, coupled with transcriptomic analysis, enables interrogation of TF binding and identification of direct TF targets from a low number of specific kidney cells.

Gastric cancer is a kind of gastric epithelial dysplasia and adenoma. At present, it is recognized that the formation process of gastric cancer is normal gastric mucosa chronic atrophic gastritis (Ag) - intestinal metaplasia (IM) - dysplasia gastric cancer. In addition to genetic factors, environmental factors such as microorganisms, nutrients and drugs in the stomach can affect the formation of dysplasia by changing the stomach. In this paper, the influence of inducing factors on the pathogenicity of dysplastic gastric cancer was discussed.

Melanoma is the main death cause of human skin cancer. Increasing evidences demonstrate that microRNAs act as key roles in mediating tumor occurrence and progression. MiR-508-5p has proved to participate in the development of various types of human malignancies. However, the role of miR-508-5p in melanoma remained unclear. In in vitro study, miR-508-5p level in peripheral blood samples of patients with melanoma and human melanoma A375 cells was downregulated compared to that in normal peripheral blood samples or normal human epidermal melanocytes (MHEM). MiR-508-5p overexpression significantly inhibited the cell proliferation, migration and invasion in A375 cells, and thus inhibiting KIT expression at both gene and protein levels. Furthermore, western blot analysis showed miR-508-5p reduced cell proliferation by targeting KIT to modulate RAS/RAF/MEK/ERK pathway. Taken together, we speculated that miR-508-5p functioned as an important suppressor in human melanoma by targeting KIT, suggesting miR-508-5p might be a promising tumor suppressor gene for further target therapies from bench to clinic.

The standard drill pipe for drilling in coal mine gallery is one of the main drilling tools in underground coal mine drilling. Its reliability directly affects the safety and efficiency of drilling construction. This paper describes the detection method of static torque of standard drill pipe for drilling in coal mine gallery, including detection principle, equipment used, detection method and process, and detection data analysis, which provides basis for the design, testing and inspection of the standard drill pipe for drilling in coal mine gallery, ensures that the standard drill pipe for drilling in coal mine gallery can be used within the torque range it can bear, and provides a safe and reliable guarantee for drilling construction.

Oxidative stress is emerging as a crucial contributor to the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD), but the molecular mechanisms underlying the disturbed redox homeostasis in cystic cells remain elusive. Here, we identified the impaired activity of the NRF2 (nuclear factor erythroid 2-related factor 2) antioxidant pathway as a driver of oxidative damage and ADPKD progression. Using a quantitative proteomic approach, together with biochemical analyses, we found that increased degradation of NRF2 protein suppressed the NRF2 antioxidant pathway in ADPKD mouse kidneys. In a cohort of patients with ADPKD, reactive oxygen species (ROS) frequently accumulated, and their production correlated negatively with NRF2 abundance and positively with disease severity. In an orthologous ADPKD mouse model, genetic deletion of Nrf2 further increased ROS generation and promoted cyst growth, whereas pharmacological induction of NRF2 reduced ROS production and slowed cystogenesis and disease progression. Mechanistically, pharmacological induction of NRF2 remodeled enhancer landscapes and activated NRF2-bound enhancer-associated genes in ADPKD cells. The activation domain of NRF2 formed phase-separated condensates with MEDIATOR complex subunit MED16 in vitro, and optimal Mediator recruitment to genomic loci depended on NRF2 in vivo. Together, these findings indicate that NRF2 remodels enhancer landscapes and activates its target genes through a phase separation mechanism and that activation of NRF2 represents a promising strategy for restoring redox homeostasis and combatting ADPKD.

Functional crosstalk between histone modifications and chromatin remodeling has emerged as a key regulatory mode of transcriptional control during cell fate decisions, but the underlying mechanisms are not fully understood. Here we discover an HRP2–DPF3a–BAF epigenetic pathway that coordinates methylated histone H3 lysine 36 (H3K36me) and ATP-dependent chromatin remodeling to regulate chromatin dynamics and gene transcription during myogenic differentiation. Using siRNA screening targeting epigenetic modifiers, we identify hepatoma-derived growth factor-related protein 2 (HRP2) as a key regulator of myogenesis. Knockout of HRP2 in mice leads to impaired muscle regeneration. Mechanistically, through its HIV integrase binding domain (IBD), HRP2 associates with the BRG1/BRM-associated factor (BAF) chromatin remodeling complex by interacting directly with the BAF45c (DPF3a) subunit. Through its Pro-Trp-Trp-Pro (PWWP) domain, HRP2 preferentially binds to H3K36me2. Consistent with the biochemical studies, ChIP-seq analyses show that HRP2 colocalizes with DPF3a across the genome and that the recruitment of HRP2/DPF3a to chromatin is dependent on H3K36me2. Integrative transcriptomic and cistromic analyses, coupled with ATAC-seq, reveal that HRP2 and DPF3a activate myogenic genes by increasing chromatin accessibility through recruitment of BRG1, the ATPase subunit of the BAF complex. Taken together, these results illuminate a key role for the HRP2-DPF3a-BAF complex in the epigenetic coordination of gene transcription during myogenic differentiation.

We study soliton-modes of optical pulses and their stabilities in a nonlocal nonlinear fused dual-core planar waveguide. Taking the different parameters, we find the symmetric, antisymmetric and asymmetric bright soliton pairs and dipole soliton pairs. During the long-distance propagation, the amplitudes of some solitons adding the white noise exhibit periodic oscillations and the solitons except asymmetric soliton can propagate steadily. We also find that the phases and profiles of solitons in the nonlocal coupler are determined by the propagation constant, the amplitude of the optical field and the region of the fused segment.

Two equilibrium diagrams of the ternary system (CsX + MnX2 + H2O, X = Cl, Br) at 298.15 K are reported in this paper. Each system has two double salts (CsMnX3·2H2O and Cs2MnX4·2H2O X = Cl, Br) in it and the elements of all double salts in phase diagrams are confirmed by Schreinemaker method. Equilibrium phase diagrams show that the chloride double salts are congruently soluble compounds in water, however that the bromide double salts are incongruently soluble compounds in water. All the double salts are characterized by titrimetric analysis, powder X-ray diffraction, thermogravimetric and differential thermalanalysis. The enthalpies of formation of these double salts are first calculated by measuring their enthalpies of dissolution.