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Tumor size is an important prognostic factor without consideration of the necrotic and cystic components within tumor for patients with gastrointestinal stromal tumors (GISTs). We aimed to extract the enhancing viable component from the tumor using computed tomography (CT) post-processing software and evaluate the value of preoperative CT features for predicting the disease-free survival (DFS) after curative resection for patients with primary gastric GISTs.132 Patients with primary gastric GISTs who underwent preoperative contrast-enhanced CT and curative resection were retrospectively analyzed. We used a certain CT attenuation of 30 HU to extract the enhancing tissue component from the tumor. Enhancing tissue volume and other CT features were assessed on venous-phase images. We evaluated the value of preoperative CT features for predicting the DFS after surgery. Univariate and multivariate Cox regression analyses were performed to find the independent risk factor for predicting the DFS.Of the 132 patients, 68 were males and 64 were females, with a mean age of 61 years. The median follow-up duration was 60 months, and 28 patients experienced disease recurrence and distant metastasis during the follow-up period. Serosal invasion (p 0.001; HR = 5.277) and enhancing tissue volume (p = 0.005; HR = 1.447) were the independent risk factors for predicting the DFS after curative resection for patients with primary gastric GISTs.Preoperative contrast-enhanced CT could be useful for predicting the DFS after the surgery of gastric GISTs, and serosal invasion and enhancing tissue volume were the independent risk factors.

Backgroud: Transglutaminases (TGs) are multifunctional enzymes with transglutaminase cross-linking, atypical GTPase/ATPase and kinase activity. Here, an integrated comprehensive analysis shows the genomic, transcriptomic and immunological landscapes of the TGs varies among different cancers. Methods Gene expression pattern and immune cell infiltration in pan-cancer were obtained from The Cancer Genome Atlas (TCGA) databases and Gene Set Enrichment Analysis (GSEA) datasets. Western blotting, immunofluorescence, ELISA, and orthotopic xenograft model were performed to validate our database-derived results. Results The overall expression of TGs (designated as TG score) is significantly upregulated in multiple cancers and related to worse patient survial. The expression of the TG family can be regulated by multiple mechanisms at the genetic, epigenetic and transcriptional levels. Transcriptionfactors crucial for epithelial to mesenchymal transition (EMT) are commonly correlated with TG score in many cancer types. Importantly, TGM2 expression displays a close connection with the chemoresistances of a wide range of chemodrugs. TGM2, F13A1 and overall TG score are positively correlated with the infiltration of immune cells in all cancer types tested. Functional and clinical verification reveals that higher TGM2 expression is linked with worse patient survival, increased IC50 value of gemcitabine, and abundant tumor-infiltrating macrophages in pancreatic cancer. Mechanistically, increased C-C motif chemokine ligand 2 (CCL2) release affored by TGM2 contributes to macrophage infiltration with tumor microenvironment. Conclusions These results reveal the relevances and molecular networks of TG genes in human cancers, highlighting the significance of TGM2 in pancreatic cancer which may provide some promising directions for immunotherapy and dealing with chemoresistance.

Background As a breast cancer suppressor gene, CLDN6 overexpression was found to inhibit breast cancer metastasis in our previous studies, but the specific mechanism remains unclear. This study aimed to clarify the role and mechanism of CLDN6 in inhibiting breast cancer metastasis. Methods Western blot, immunofluorescence and transmission electron microscopy were performed to detect autophagy. Wound healing, transwell assays and lung metastasis mouse models were used to examine breast cancer metastasis. Phalloidin staining and immunofluorescent staining were used to observe actin cytoskeleton. mRNA seq, RT-PCR, western blot, chromatin immunoprecipitation, dual luciferase reporter assay, co-immunoprecipitation and immunofluorescence were performed to define the molecular mechanism. The expression levels and clinical implication of CLDN6, WIP and LC3 in breast cancer tissues were evaluated using immunohistochemistry. Results We demonstrated that CLDN6 inhibited breast cancer metastasis through autophagy in vitro and vivo. We unraveled a novel mechanism that CLDN6 regulated autophagy via WIP-dependent actin cytoskeleton assembly. Through its PDZ-binding motif, overexpressed CLDN6 interacted with JNK and upregulated JNK/c-Jun pathway. C-Jun promoted WIP expression at the transcriptional level. Notably, we observed c-Jun transcriptionally upregulated CLDN6 expression, and there was a positive feedback loop between CLDN6 and JNK/c-Jun. Finally, we found that CLDN6, WIP and LC3 expression correlated with each other, and WIP expression was significantly associated with lymph node metastasis of breast cancer patients. Conclusions The data provide a new insight into the inhibitory effects of CLDN6-mediated autophagy on breast cancer metastasis, and revealed the new mechanism of CLDN6 regulating autophagy through WIP-dependent actin cytoskeleton. Our findings enrich the theoretical basis for CLDN6 as a potential biomarker for breast cancer diagnosis and therapy.

Experimental tests were conducted on a rectangular flume with different grid-type dam grid sizes, channel slopes and debris flow bulk density. We use the Bernoulli equation of energy conservation to deduce a formula to calculate debris-flow discharge. By combining the flume experiments with dimensional analysis methods, we mainly consider the bulk density of the debris flow, grid size of the grid-type dam, and flume slope to establish the discharge-coefficient correction formula and propose a method of calculating debris-flow discharge through a grid-type dam. The practical value of the formulas was illustrated using the Niwan gully, a tributary of Bailong River in Gansu province, China, as an example, which can be used as a reference in further practical engineering applications.

Ultraviolet-B (UV-B) light is an intrinsic part of sunlight that reaches the earth’s surface, and affects plant survival and adaptation. How plants respond to UV-B light is regulated by the wavelength, intensity and duration of UV-B radiation, and is also regulated by photosynthetically active radiation perceived by phytochrome and cryptochrome photoreceptors. Non-damaging UV-B light promotes plant photomorphogenesis and UV-B acclimation which enhances plant tolerance against UV-B stress. However, high-level UV-B radiation induces DNA damage, generates reactive oxygen species (ROS) and impairs photosynthesis. Plants have evolved efficient mechanisms to utilize informational UV-B signal, and protect themselves from UV-B stress. UV RESISTANCE LOCUS8 (UVR8) is a conserved plant-specific UV-B photoreceptor. It interacts with CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1) to initiate UV-B-specific light signaling and regulate UV-B responsive gene expression. A set of transcription factors such as ELONGATED HYPOCOTYL5 (HY5) function downstream of the UVR8-COP1 module to promote seedling de-etiolation for photomorphogenic development and biosynthesis of sunscreen flavonoids for UV-B stress tolerance. In addition to UVR8 signaling pathways, plants subjected to damaging UV-B radiation initiate stress protection and repair mechanisms through UVR8-independent pathways. In this review, we summarize the emerging mechanisms underlying UV-B stress acclimation and protection in plants, primarily revealed in the model plant Arabidopsis thaliana.

Hyperglycemia-induced myelopoiesis and atherosclerotic progression occur in mice with type I diabetes. However, less is known about the effects of metabolites on myelopoesis in type 2 diabetes. Here, we use fluorescence-activated cell sorting to analyze the proliferation of granulocyte/monocyte progenitors (GMP) in db/db mice. Using targeted metabolomics, we identify an increase in inosine monophosphate (IMP) in GMP cells of 24-week-old mice. We show that IMP treatment stimulates cKit expression, ribosomal S6 activation, GMP proliferation, and Gr-1+ granulocyte production in vitro. IMP activates pAkt in non-GMP cells. In vivo, using an established murine acute pancreatitis (AP) model, administration of IMP-treated bone marrow cells enhances the severity of AP. This effect is abolished in the presence of a pAkt inhibitor. Targeted metabolomics show that plasma levels of guanosine monophosphate are significantly higher in diabetic patients with AP. These findings provid a potential therapeutic target for the control of vascular complications in diabetes.

Microglia-mediated neuroinflammation is widely perceived as a contributor to numerous neurological diseases and mental disorders including depression. Discs large homolog 1 (Dlg1), an adaptor protein, regulates cell polarization and the function of K+ channels, which are reported to regulate the activation of microglia. However, little is known about the role of Dlg1 in microglia and the maintenance of central nervous system homeostasis. In this study, we found that Dlg1 knockdown suppressed lipopolysaccharide (LPS)-induced inflammation by down-regulating the activation of nuclear factor-κB signaling and the mitogen-activated protein kinase pathway in microglia. Moreover, using an inducible Dlg1 microglia-specific knockout (Dlg1flox/flox; CX3CR1CreER) mouse line, we found that microglial Dlg1 knockout reduced the activation of microglia and alleviated the LPS-induced depression-like behavior. In summary, our results demonstrated that Dlg1 plays a critical role in microglial activation and thus provides a potential therapeutic target for the clinical treatment of depression.

The existence of the spherical aberration of the thermal lens in the crystal has a certain regulatory effect on the distribution of laser modes. In this paper, using the impact of this aberration on the superposition area of TEM01 and TEM10 modes, we carry out an experimental study of a 1064 nm hollow beam and its nonlinear frequency conversion providing a 532 nm hollow beam. Using a plano-concave cavity structure, under 21.92 W pump power at 808 nm, a 1064 nm hollow beam with an output power of 4.01 W is generated. Based on this result, a 532 nm hollow beam with an output power of 1.08 W is obtained by intracavity frequency doubling with type I phase matching in an LBO crystal. The conversion efficiency is 26.9%.

Hepatic ischemic reperfusion injury (IRI) is a common complication of liver surgery. Although an imbalance between mitochondrial fission and fusion has been identified as the cause of IRI, the detailed mechanism remains unclear. Augmenter of liver regeneration (ALR) was reported to prevent mitochondrial fission by inhibiting dynamin-related protein 1 (Drp1) phosphorylation, contributing partially to its liver protection. Apart from phosphorylation, Drp1 activity is also regulated by small ubiquitin-like modification (SUMOylation), which accelerates mitochondrial fission. This study aimed to investigate whether ALR-mediated protection from hepatic IRI might be associated with an effect on Drp1 SUMOylation. Liver tissues were harvested from both humans and from heterozygous ALR knockout mice, which underwent IRI. The SUMOylation and phosphorylation of Drp1 and their modulation by ALR were investigated. Hepatic Drp1 SUMOylation was significantly increased in human transplanted livers and IRI-livers of mice. ALR-transfection significantly decreased Drp1 SUMOylation, attenuated the IRI-induced mitochondrial fission and preserved mitochondrial stability and function. This study showed that the binding of transcription factor Yin Yang-1 (YY1) to its downstream target gene UBA2, a subunit of SUMO-E1 enzyme heterodimer, was critical to control Drp1 SUMOylation. By interacting with YY1, ALR inhibits its nuclear import and dramatically decreases the transcriptional level of UBA2. Consequently, mitochondrial fission was significantly reduced, and mitochondrial function was maintained. This study showed that the regulation of Drp1 SUMOylation by ALR protects mitochondria from fission, rescuing hepatocytes from IRI-induced apoptosis. These new findings provide a potential target for clinical intervention to reduce the effects of IRI during hepatic surgery.

The limited inter-lamellar bonding in the conventional thermal-sprayed 304SS coating usually leads to much lower corrosion and wear resistance than their bulk counterparts. In this study, Mo-clad stainless steel 304SS-17Mo powders prepared by mechanical alloying were used for plasma spraying to generate ultra-high-tempertature droplets to deposit the coatings with enhanced inter-lamellar bonding. The temperature at the interface between the molten splats and the stainless steel was calculated by numerical simulation, and the surface temperature of in-flight particles was measured by a commercial thermal spray particle diagnostic system. The microstructures of the coatings after etching were characterized to reveal inter-lamellar bonding. The adhesive and cohesive strengthes of the coatings were estimated by tensile and scratch tests. The measurement of the in-flight particle temperature reveals the possibility of creating a self-bonding effect, which is confirmed by microstructure examination, high adhesion over 66 MPa, and cohesion of 221 MPa.

Plasma spraying was employed to deposit an Al coating in order to create a self-metallurgical bonding effect through impact-induced melting with highly overheated molten droplets. Numerical simulation was employed to estimate the interface temperature between the molten Al splat and the Al substrate. The interface bonding was examined from cross sections of the Al splat and the etched coatings. The results show that, with Al droplets higher than 1800°C, impact-induced Al substrate melting occurs. The measurements showed that, during spraying, most Al particles were heated to temperatures theoretically causing an impact-induced melting effect, which subsequently produces a metallurgical self-bonding effect. The observed results confirm the metallurgical bonding in plasma-sprayed Al coating.

A hypereutectic Al–3Fe (wt.%) alloy was subjected by rheo-extrusion, and the effect of sub-rapid cooling and shear deformation on the refinement of Fe-rich phase was investigated. The results showed that both the primary Fe-rich phase and eutectic Fe-rich phase in the solidified Al–Fe alloy were finer than the platelike Fe-rich phase in the as-cast Al–Fe alloy with the same content of Fe. The solidified Al–Fe alloy was subjected to three stages of shear deformation, and both the primary Fe-rich phase and eutectic Fe-rich phase were fractured and the average length was refined to 400 nm, while Fe-rich phase in the as-cast Al–3Fe (wt.%) alloy was platelike and its average length was 40 μm. The tensile strength and elongation of the hypereutectic Al–3Fe (wt.%) alloy containing nanosized Fe-rich phase were 162 MPa and 25.78% while those of the as-cast Al–3Fe (wt.%) alloy containing coarse platelike Fe-rich phase were 102 MPa and 16.84%, respectively. In the refinement of Fe-rich phase in hypereutectic Al–Fe alloy during rheo-extrusion, the three stages of shear deformation contributed more than sub-rapid cooling.

Background Oncostatin M receptor (OSMR), as one of the receptors for oncostatin M (OSM), has previously been shown to mediate the stimulatory role of OSM in osteoclastogenesis and bone resorption. However, it remains to be clarified whether and how OSMR affects the differentiation of osteoblasts. Methods The expression level of OSMR during osteoblast and adipocyte differentiation was examined. The role of OSMR in the differentiation was investigated using in vitro gain-of-function and loss-of-function experiments. The mechanisms by which OSMR regulates bone cell differentiation were explored. Finally, in vivo function of OSMR in cell fate determination and bone homeostasis was studied after transplantation of OSMR-silenced bone marrow stromal cells (BMSCs) to the marrow of ovariectomized mice. Results OSMR was regulated during osteogenic and adipogenic differentiation of marrow stromal progenitor cells and increased in the metaphysis of ovariectomized mice. OSMR suppressed osteogenic differentiation and stimulated adipogenic differentiation of progenitor cells. Mechanistic investigations showed that OSMR inhibited extracellular signal-regulated kinase (ERK) and autophagy signaling. The downregulation of autophagy, which was mediated by ERK inhibition, suppressed osteogenic differentiation of progenitor cells. Additionally, inactivation of ERK/autophagy signaling attenuated the stimulation of osteogenic differentiation induced by Osmr siRNA. Furthermore, transplantation of BMSCs in which OSMR was silenced to the marrow of mice promoted osteoblast differentiation, attenuated fat accumulation and osteoclast differentiation, and thereby relieved the osteopenic phenotype in the ovariectomized mice. Conclusions Our study has for the first time established the direct role of OSMR in regulating osteogenic differentiation of marrow stromal progenitor cells through ERK-mediated autophagy signaling. OSMR thus contributes to bone homeostasis through dual regulation of osteoblasts and osteoclasts. It also suggests that OSMR may be a potential target for the treatment of metabolic disorders such as osteoporosis.

Self-fluxing alloy coatings are usually utilized by spray fusing two-step process for fully dense microstructure and metallurgical bonding to the substrate. The fusing process brings out limitations for coating applications due to the need of high-temperature fusing. In this study, it is found for the first time that metallurgical bonding between NiCrBSi splats can be achieved by deposition of super-hot droplets created by plasma spraying. Thus, a sufficiently dense NiCrBSi coating can be prepared by one-step plasma spraying. NiCrBSi powders with a size range of 30-50 μm were used as typical material for plasma spraying. The particle temperatures were measured by a DPV-2000 thermal spray in-flight particle diagnostic system. The microstructure of coatings was characterized using scanning electron microscopy. Results show that particles can be heated to a significantly high temperature over 2400 °C by the optimal design of the nozzle internal structure, and the plasma-sprayed NiCrBSi coatings are almost fully dense with effective metallurgical interparticle bonding. Based on the numerical simulation result of the interfacial temperature evolution between spreading splat and NiCrBSi substrate, a self-fusing mechanism is proposed for plasma spraying of NiCrBSi. Furthermore, the coating prepared by one-step plasma spraying reveals superior abrasive wear resistance and corrosion resistance as compared with the flame spray and fusing counterpart. It is clearly demonstrated that the new approach to deposit highly dense coatings directly by plasma spraying with self-fusing effect could greatly expand the applications of fluxing alloy coating materials.

North Gulf is China’s important sea route to Asia and Europe, and the seabed is rich in resources. For various reasons, the detection and mapping of submarine terrain are blank. The traditional multi-beam measurement method has high accuracy but uneven spatial distribution. Although the detection line process has high sampling and measurement accuracy, there is a large blank area between adjacent routes, which is difficult to achieve full-scale large area measurement due to environmental, time and budget constraints. On the other hand, the accuracy of the remote sensing inversion depth method is not high, but it can achieve a wide range of coverage, which is characterized by low cost, short cycle and convenient dynamic monitoring. This paper takes North Gulf as the research area, uses remote sensing data to construct the seabed topography, uses multi-beam data for checksum correction and uses distributed computing technology to distribute big data in different computing nodes, and the data are refined and reconstructed in three dimensions to form a 3D seabed topography. The method improves the efficiency and accuracy of multi-beam data processing and can construct a large area, high-resolution submarine DEM and realize database management.