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The fusiform gyrus (FG) subserves a range of visual cognitive functions likely arising from its distinct subregions that present different connectivity profiles. Nevertheless, the molecular basis underlying such connectivity variability across FG subregions is still an open question. Resting-state functional magnetic resonance imaging (fMRI) data were collected from a discovery dataset (361 healthy subjects) and two independent cross-race, cross-scanner validation datasets (103 and 329 healthy subjects). We adopted a newly developed standardized pipeline to process gene expression data from the Allen Human Brain Atlas. Fine-grained FG subregions derived from the Human Brainnetome Atlas were utilized to measure seed-based resting-state functional connectivity (rsFC). Then, transcriptome-neuroimaging spatial association analyses were conducted to identify genes related to rsFC of each FG subregion. Results showed that rsFC of the left A37mv was associated with expression measures of 1063 genes, while there were no expression-rsFC correlations for the other subregions. The 1063 genes were mainly enriched for biological functions and pathways related to synaptic transmission, neurons, and neurotransmitter systems as well as for autism spectrum disorder. Specific expression analyses revealed that these rsFC-related genes were specifically expressed in brain tissue, in cortical neurons and immune cells, and during nearly all developmental periods. In addition, these genes were associated with multiple behavioral domains such as vision, language, and sensation. Finally, protein-protein interaction (PPI) analysis demonstrated that the genes could construct a PPI network with 37 hub genes. These findings may offer unique insights into the molecular basis underlying the functional heterogeneity of the FG.

The identification and treatment of mining-induced ground fissures are of great significance to mine safety and ecological and environmental protection. In this study, a novel method for ground fissure identification and exploration by infrared remote sensing onboard an unmanned aerial vehicle (UAV) was proposed. Using this method, a region of interest (ROI) that includes ground fissures directly above the middle of a long wall face, No. 12401 in the Shangwan coal mine, was monitored continuously during the day and night. Direct field measurements of ground fissure properties were also conducted to provide a calibration dataset for UAV measurements. Using the direct visible image at 5:00 pm as a reference, the average errors of the length and maximum width of Fissure I obtained from infrared images from 9:00 pm to 5:00 am on the next day, were estimated to be 1.8% and 6.5%, respectively. The diurnal variation of the fissure temperature is sinusoidal, and the range of temperature variation in the fissure decreases with the increase in depth. There is an apparent difference between the two common types of fissures depending on whether the fissure has a direct connection to an aquifer or a goaf. In this study, UAV, infrared thermal imager, and visible light camera data were successfully employed to effectively identify mining-induced ground fissures. In addition, the fissure detection error was validated, and the appropriate time for utilizing this method was obtained. Our results show that to identify the two aforementioned types of fissures, monitoring should be conducted between 3:00 am and 5:00 am. This study lays a foundation for the study and application of UAV and infrared thermal imagers for the identification of ground fissures induced by underground mining in large areas.

There is evidence that major depressive disorder (MDD) is related to serum lipid level alterations. However, the neural correlates underlying this association remain poorly understood. Forty-nine patients with MDD and fifty healthy controls (HCs) underwent structural, resting-state functional and diffusion magnetic resonance imaging scans. Voxel-based morphometry, functional connectivity (FC) and tract-based spatial statistics analyses were performed to assess brain structure and function, respectively. Blood samples were collected to measure serum levels of lipid variables including total cholesterol, triglyceride and high density lipoprotein cholesterol (HDL-C). Correlation and mediation analyses were conducted to investigate the associations of serum lipid levels with brain imaging measures in MDD patients and HCs, respectively. We found that the serum HDL-C level in MDD patients was lower than that in HCs. The lower serum HDL-C level was associated with lower gray matter volume (GMV) in ventromedial prefrontal cortex (VMPFC), higher within-network FC of the default mode network, and lower micro-structural integrity in multiple white matter regions in MDD patients. Moreover, the within-default mode network FC mediated the relationship between GMV in VMPFC and serum HDL-C level; white matter integrity in genu of corpus callosum mediated the relationship between serum HDL-C level and depressive symptom severity. However, we did not observe any correlations between serum lipids and brain imaging parameters in HCs. These findings help to identify neural correlates underlying the association between depression and serum HDL-C change, which may provide new insight into intervention, treatment and prevention of depression from the perspective of regulating serum lipids.

Background Sleep disturbance is a common and key symptom that affects most of patients with major depressive disorder (MDD). However, neural substrates underlying sleep disturbance and their clinical relevance in depression remain unclear. Methods Ninety-six MDD patients underwent resting-state functional MRI. Fractional amplitude of low-frequency fluctuation (fALFF) and resting-state functional connectivity (rsFC) were used to measure brain function. Overnight polysomnography was performed to objectively measure sleep efficiency (SE), which was used to classify patients into normal sleep efficiency (NSE) and low sleep efficiency (LSE) groups. Between-group differences in fALFF and rsFC were examined using two-sample t-tests. Moreover, correlation and mediation analyses were conducted to test for potential associations between SE, brain functional changes, and clinical variables. Results LSE group showed decreased fALFF in right cuneus, thalamus, and middle temporal gyrus compared to NSE group. MDD patients with low SE also exhibited lower rsFC of right cuneus to right lateral temporal cortex, which was associated with more severe depression and anxiety symptoms. More importantly, mediation analyses revealed that the relationships between SE and severity of depression and anxiety symptoms were significantly mediated by the altered rsFC. In addition, these low SE-related brain functional alterations were not affected by antidepressant medication and were independent of structural changes. Limitations The lack of healthy controls because of “first-night effect”. Conclusion These findings not only may expand existing knowledge about neuropathology of sleep disturbance in depression, but also may inform real-world clinical practice by improving depression and anxiety symptoms through sleep regulation.

Cardiac hypertrophy is an early milestone of many heart diseases. LncRNAs often play a leading role in this process. However, its mechanism of action in cardiac hypertrophy has not been fully explained. In a previous study, we showed a new mode by which lncRNA-Mhrt inhibited cardiac hypertrophy by inhibiting myocardin. However, the underlying molecular mechanism remains unclear. This study aims to explore potential action modes of Mhrt in regulating the expression of myocardin in the process of cardiac hypertrophy. Here, we find that Mhrt reduces myocardin expression through KLF4 in vivo and in vitro. Meanwhile, Mhrt promotes the expression of KLF4 through direct binding to miR-145a-5p or inhibiting phosphorylation of KLF4 by forming a complex with KLF4 to prevent the binding of ERK and KLF4, thereby inhibiting myocardin expression and the development of myocardial hypertrophy. Taken together, our findings reveal a new pathway, Mhrt-KLF4-myocardin, that regulates cardiac hypertrophy and revealed additional possible action modes of Mhrt in the occurrence and development of cardiac hypertrophy. The new regulatory pathway serves as a potential therapeutic avenue for cardiac hypertrophy.

Since 2010, Tembusu virus (TMUV) has spread widely in China, causing huge economic losses to the poultry industry. Due to the infectious and zoonotic nature of flaviviruses, their potential threat to public health is of great concern. Cellular immune responses usually play a critical role in combating viral infections. To study the molecular basis of cell immunity induced by TMUV, 14 cytotoxic T lymphocyte (CTL) epitope peptides of TMUV antigen E, NS1 and NS3 were predicted by bioinformatics tools. Their abilities to induce cellular immune responses were determined by IFN-γ ELISpot assay, and 4 peptides were found to exhibit highly significant responses upon stimulation. In addition, the cytotoxic activity induced by the epitope peptides was assessed by lactate dehydrogenase (LDH) release assay. Finally, among these peptides, we identified two murine TMUV NS3-derived H-2d-restricted CTL epitopes in BALB/c mice, which could be used to further study of epitope vaccines against TMUV infection.

Thermostable and halotolerant GH11 xylanases are highly desirable in various industrial applications but they were rarely characterized. In this study, we firstly revealed the genetic diversity of GH11 xylanases from the metagenomic DNA of a saline-alkaline soil by constructing a gene fragment library. Twelve distinct xylanase fragment sequences were identified, which shared 62–96% identity to known GH11 xylanases. Among them, Xyn22 with the highest relative abundance was cloned and found to exhibit excellent halotolerance. Xyn22 retained 80 and 58% relative activity in the presence of 3 and 5 M NaCl, respectively, and had no loss of activity after incubation in 3 M NaCl at 37 °C for 1 h. Additionally, the acidic amino acid residues E137 and E139 on the protein's surface were revealed to cooperatively play important roles in its excellent halotolerance and halostabilty. Furthermore, the thermostability of Xyn22 was significantly improved without compromising halotolerance by introducing an aromatic interaction between Y48 and F53. In conclusion, this study not only provides a thermostable and halotolerant GH11 xylanase, but also reveals the key roles of surface-exposed amino acids in its thermostability and halotolerance, which could be used for further molecular modification of other xylanases and similar enzymes.

The emerging graphene foams (GrFs) have received increasing attention in both scientific and engineering fields in recent years. A good elasticity is the prerequisite for its further applications. However, the mechanism and basic characteristics of elasticity of GrFs have not been understood clearly so far. In this paper, we conduct systematic simulations of compression-uncompression and tension-untension to study the characteristics of GrF elasticity using the coarse-grained molecular dynamics (CGMD) method. We find that deformation of GrFs is highly nonuniform at the scale of both flakes and regions, which is qualitatively consistent with the experimental observations. The deformation of GrFs is dominated by the flake bending rather than stretching, which is independent of the loading type, size, shape or thickness of flakes, as well as the density or stiffness of crosslinks. The great asymmetry of elasticity under tension and compression is induced by different mode of bond breaking. Furthermore, by evaluating the elastic energy density, we find that both thicker flakes and more crosslinks are two key factors responsible for good elasticity of GrFs. These results should be useful for understanding GrF elasticity and further design of advanced graphene-based materials.

Heat-injection into coal seam has gained great attention as a supplementary method for the improvement of unconventional gas recovery from deep reservoirs in recent years. However, it involves a lot of ambiguous interactions among the deformation of formation, the transport of gas and the diffusion of heat in the porous coal media, especially the property of gas. In this paper, the seepage behavior of coal seam gas (CSG) that obeys non-Darcy flow law was directly observed in a conducted laboratory experiments. Then, a general Forchheimer equation was confirmed and strictly validated by the experimental data to characterize the non-Darcy seepage phenomenon. Subsequently, a fully coupled thermo-hydro-mechanical model was mathematically established. Based on the finite element approach, a numerical simulation for heat-injection enhanced coal seam gas recovery was then implemented. The susceptibilities of coal permeability and gas production to the gas sorption, heat-mass transfer, and the porosity-seepage characteristics of coal were quantified by a series of numerical scenarios. Final modeling and simulation results reveal that: (1) coal seam gas flow obeys non-Darcy law when the gradient of gas pressure is higher, but trends to be laminar flow that obeys Darcy law when the gradient is lower, and (2) heat-injection to stimulate coal seam could improve the production efficiency, increasing the Langmuir volume sorption parameter, the temperature correction coefficient and the initial values of permeability can improve coal permeability and enhance gas production.

A number of studies microRNAs (miRNA) play an important role in cardiac physiological and pathological processes. In these studies, miRNA regulates gene expression by repressing translation or directing sequence-specific degradation of complementary mRNA. Here, we reveal a new regulatory mechanism in the process of cardiac hypertrophy which miRNA may also regulate the promoter activity of target genes. In the course of the study, we find that miR-466h-5p regulates the occurrence of myocardial hypertrophy via myocardin and it can upregulate the expression of myocardin through directly binding to the promoter region of myocardin. Meanwhile, we also find that myocardin can reverse-activate miR-466h-5p expression through binding to the CarG box. Thus, miR-466h-5p and myocardin form a positive regulation loop in the process of cardiac hypertrophy. These findings reveal a new mode by which miRNAs may regulate gene expression and may play a positive role in revealing the complete mechanisms of cardiac hypertrophy.

Graphite in high grade meta-supracrustal rocks provide an important proxy to characterize biogenic and abiogenic carbon sources. Here we investigate graphite in various associations within the granulite facies metapelites (khondalites) of Kerala in southern India with a view to characterize the textural varieties and their genesis through the application of laser Raman spectroscopy and carbon isotopes. We trace the increasing intensity of metamorphism from the Raman spectra of the different graphite types. The δ13C values of the graphite show two distinct origins; the relatively lighter values in the range of −17.5‰ to −20.7‰ represent a mixture of biogenic and magmatic carbon, whereas the heavier isotopes in the range of −11.7‰ to −13.8‰ are suggested to present graphite precipitation from CO2-rich fluids from sub-crustal magmatic sources. Our study provides insights on the spectral properties of graphite in relation to the intensity of metamorphism and also reveals both biogenic and abiogenic sources of carbon.

The buckling behavior of a single layer MoS2 (SLMoS2) sheet with defects under uniaxial compression is investigated with molecular simulation in the present paper. Five typical defects are introduced to estimate the instability characteristics of defective MoS2 sheet. The buckling responses, including the critical strain and geometric morphology, influenced by defect type, stain rate, defect density and so on, are comprehensively explored. It is found that different type of defects results in reduction of the bending modulus to some different extent. Compared with the other three post-buckling morphologies, the first typical geometric morphology show the biggest difference between the defect-free and defective SLMoS2 sheets. It seems possible to realize our desired morphology in flexible electronics by proper preparing different kinds of defects. The finding in the present paper should be useful for the promising design of flexible optoelectronic devices and soft bioelectronics.

WDR1 is a major cofactor of the actin depolymerizing factor (ADF)/cofilin, accelerating ADF/cofilin-mediated actin disassembly. We had previously showed that WDR1-mediated actin dynamics is required for postnatal myocardial growth and adult myocardial maintenance in mice, in which the detailed phenotypes of adult cardiomyocyte-specific Wdr1 deletion mice had not been analyzed. In this study, we systematically analyzed the role of Wdr1 in adult mouse heart. Adult cardiomyocyte-specific Wdr1 deletion mice (cKO) exhibited cardiac hypertrophy and myocardial fibrosis. Echocardiographic study and electrocardiography revealed impaired contractile function, prolonged QT interval and Tpeak-Tend interval, and abnormal T-wave amplitude in cKO mice. Increased levels of sarcomeric proteins, adherens junction proteins and cofilin, and severe actin filament (F-actin) accumulations were observed in cKO mice heart. Taken together, this finding demonstrates that WDR1 is a critical factor for normal structure and function of adult mouse heart.

Friction exists between two objects contacting with each other in relative motion. Friction generating heat is a common acting form of friction. However, with the increasing understanding of friction generating heat, the researchers realize that the accurate calculation of frictional heat can’t be obtained only from the macroscopic level. Therefore, specifically analyzing of friction generating heat is of great significance for research and development of friction generating heat phenomena from the microscopic level. In this paper, from the microscopic level, a new calculating method of frictional heat based on fractal theory is proposed. The expression of frictional force in the motion system is derived based on the kinematics analysis and contact mechanics analysis of a pair of contact asperities on the micro-contact surface. Frictional heat is affected by the three parameters of this expression. To verify the validity, the method proposed in this paper is applied to the friction generating heat in the process of friction stir welding. Based on the new method, the frictional heat during friction stir welding is simulated by COMSOL Multi-physics software. The effects of area coefficient c, fractal dimension D and scale factor G on frictional heat are obtained. The validity of this new calculating method of frictional heat is verified.

MicroRNAs (miRNAs) are a type of small non-coding RNAs that participate in diverse cellular processes including microbial invasion and immune defense. In a previous study, we identified a large amount of Japanese flounder (Paralichthys olivaceus) miRNAs responsive to megalocytivirus infection. In the present study, we examined the function of one of these miRNAs, pol-miR-194a, in association with the infectivity of Edwardsiella tarda, an intracellular bacterial pathogen to many fish species including flounder. We found that pol-miR-194a was induced in expression to a significant extent in the spleen, liver, and gill of Japanese flounder infected by E. tarda. Transfection of flounder cells with pol-miR-194a mimic significantly enhanced the intracellular replication of E. tarda. pol-miR-194a was able to interact specifically with the 3′UTR of IRF7 in a negative manner, resulting in inhibition of IRF7 expression. Consistently, pol-miR-194a significantly blocked the promoter activity of type Ⅰ interferon. Taken together, these results indicate that pol-miR-194a plays an important role in the regulation of flounder immune response as well as microbial infection, and that pol-miR-194a probably serves as a target for E. tarda to manipulate and escape host immune defense.

The diameter of the ring workpiece is increased all the time in ring rolling. The measured generatrix contour has the dislocation when the ring workpiece is measured directly by the laser scanner. In order to realize the online detection of the generatrix contour for the ring workpiece, a dynamic position compensation method of the online laser detection system is proposed in this paper. Firstly, the data of the ring’s radial cross-section is obtained by laser scanner in ring rolling. Then the data is denoised by Kalman time division multiplexed particle filter. Secondly, the curve fitting is executed on the denoised data. The position deviation of each radial cross-section position coordinate is calculated by fitted curve. Thirdly, the position coordinate of the ring’s radial cross-section is compensated according to the position deviation. The dislocation of the generatrix contour is corrected. Finally, the feasibility of the method proposed is verified by experiments.

Measuring the geometric parameters of ring forgings by laser scanner is an important way to ensure the quality of processing. However, the amount of data obtained by scanner is huge and the noise is complex. The process of data processing is slow. It is impossible to ensure the real-time quality monitoring. Therefore, an improved Quadratic Error Metric (QEM) point cloud data reduction algorithm based on Artificial Immune Algorithm (AIA) is proposed in this study. As for AIA, the choice of antigen and antibody is the critical step. The candidate point cloud is used as the antibody. The antigen is divided into two parts. The first part is the cost function. The cost function is made up of the squares sum of the volumes for two tetrahedra. This is an improved algorithm of QEM. The second part is the optimal solution of the cost function. The antibodies are screened by using the specific reactions between antigens and antibodies, antibodies and antibodies. The point cloud data can be reduced by these specific reactions. Finally, the algorithm is applied to the experiment of measuring the geometric parameters of typical ring forging. The experimental results show that the reduced data can quickly reconstruct the model. The precision of the size parameters for the model can be ensured through the algorithm proposed in the study. Through the comparison experiments, the advantages of the reduced method of the algorithm are further proved. Meanwhile, the real-time performance of the on-line monitoring of the quality for the ring forging can be improved. The measuring method proposed is feasible according to the experimental results.

Lung cancer remains one of the most aggressive human malignancies with a low survival rate. Hyperoside (quercetin-3-O-β- d -galactopyranoside) is a flavonol glycoside with an anti-cancer activity. The microRNA-let-7 was widely regarded as a tumor suppressor in human tumors. Here, we investigated the role of hyperoside and let-7a-5p on the lung cancer cell proliferation, cell cycle and apoptosis in A549 cells in vitro. Our results showed that hyperoside could inhibit the proliferation of A549 cells through inducing apoptosis and G1/S phase arrest. Let-7a-5p could inhibit the proliferation of A549 cells via inhibiting the process of G1/S phase. Additionally, hyperoside and let-7a-5p had a synergetic effect on suppressing the proliferation of A549 cells; microRNA-let-7a-5p directly regulated the expression of CCND1 in A549 cells. Our study illustrated that hyperoside and microRNA-let7a-5p might provide a synergistic effect on anti-cancer, which may provide a new idea for lung cancer treatment.

In this paper, the temperature measurement accuracy of infrared thermal image under different emissivity is studied. Firstly, according to the formula of infrared temperature measurement, the influence of the object surface emissivity on the measurement accuracy of infrared thermal image is analyzed. The factors affecting the emissivity of the object are found. Secondly, the limitation of classical emissivity calculation method in infrared temperature measurement is explained. Thirdly, a model for improving the temperature accuracy of the non-steady state temperature field based on the emissivity of the infrared image is obtained, and the theoretical formula is obtained. Finally, three experiments of cast iron and stainless steel are carried out. The correctness and feasibility of this method is verified by the experimental results.

The failure and design of coal pillars have always been the focus of research in the field of mining engineering, and there are often many water resources in goafs with rich aquifers. Under the influence of mining and long-term water invasion, it is easy to cause gradual failure and instability to coal pillars. Based on this, this paper proposes a numerical simulation method for the coupling of engineering scale mining-water invasion and a quantitative index of the damage ratio of coal pillars. The numerical parameters are calibrated with measurement data from coal-pillar stress. In the simulation process, the evolution of the strength, damage ratio, water pressure, stress, strain, and other parameters in coal pillars under the effect of mining-water invasion is realized, and the progressive failure mechanisms of coal pillars under mining-water immersion are revealed. On this basis, the effects of goaf water-level height and coal-pillar width on coal-pillar stability are quantitatively analyzed, and the critical goaf water-level height corresponding to different coal-pillar widths is obtained. Using the simulation results of this paper, the instability of a coal pillar in a coal mine is effectively solved, and the deformation of the coal-pillar rib and roof of the tailgate is reduced by 39.6% and 30.8%, respectively, which ensures the safe production of the longwall face.

Inflammatory bowel disease (IBD) is a chronic, recurrent, and remitting inflammatory disease resulting from immune dysregulation in the gut. As a clinically frequent disease, it can affect individuals throughout their lives, with multiple complications. Glucagon-like peptide 2 (GLP-2) is a potent epithelium-specific intestinal growth factor. However, native GLP-2 has a relatively short half-life in human circulation because of extensive renal clearance and rapid degradation by the proteolytic enzyme dipeptidyl peptidase-IV (DPP-IV). Previously, We prepared a recombinant GLP-2 variant (GLP-2②), which has increased half-life and activity as compared to the [Gly2]GLP-2 monomer. The aim of the present study was to investigate the protective potential of GLP-2② in IBD models. LPS-induced in vitro model and dextran sulfate sodium (DSS)-induced in vivo model were used to study the anti-inflammatory and therapeutic effect of GLP-2②. We found that treated with GLP-2② showed a significantly reduction in the secretion of inflammatory cytokines. Furthermore, GLP-2② alleviated symptoms of DSS-induced colitis. GLP-2② treated mice displayed an increase in body weight, lower colitis scores, and fewer mucosal damage compared with GLP-2 treated mice. MPO activities, protein expression of NLRP3 and COX2 in the colon tissues were significantly reduced in GLP-2② groups. Importantly, the ameliorative effect of GLP-2② was related to anti-apoptosis effect in colon tissues. These findings demonstrated that GLP-2② may offer a superior therapeutic benefit over [Gly2]GLP-2 monomer for treatment of IBD.

Deposition of type I collage in ECM is an important property of various fibrotic diseases including breast cancer. The excessive expression of type I collagen contributes to the rigidity of cancer tissue and increases the mechanical stresses which facilitate metastasis and proliferation of cancer cells via the activation of TGF-β signaling pathway. The increased mechanical stresses also cause the compression of blood vessels and result in hypoperfusion and impaired drug delivery in cancer tissue. Additionally, type I collage functions as the ligand of α2β1-integrin and DDR1/2 receptors on the membrane of cancer cells to initiate signal transduction leading to metastasis. The expression of type I collage in cancer cells is previously shown to be inducible by TGF-β however the detailed mechanism by which the synthesis of type I collagen is regulated in breast cancer cells remains unclear. Herein, we report that MRTF-A, a co-activator of SRF, is important for the regulation of type I collagen gene COL1A1 in breast cancer cells. MRTF-A physically interacted with the promoter of COL1A1 to facilitate histone acetylation and RNA polymerase II recruitment. The RhoC-ROCK signaling pathway which controls the nuclear localization of MRTF-A regulated the transcription of COL1A1 in human breast cancer cells. TGF-β and Wnt signaling increased the expression of both MRTF-A and COL1A1. Furthermore, depletion of MRTF-A abolished the upregulation of COL1A1 in response to the TGF-β or Wnt signaling, indicating the importance of MRTF-A in the synthesis of type I collagen in breast cancer. Given the crucial roles of type I collagen in the formation of metastasis-prone and hypoperfusion microenvironment, MRTF-A would be a potential target for the development of anti-breast cancer activities.

Background Thymosin beta 4 (Tβ4) is a 43-amino-acid peptide with protective properties in myocardium injury. Previously, we produced a recombinant human dimeric Tβ4 (DTβ4). Here, the cardioprotective effects of DTβ4 and the molecular mechanisms underlying its enhanced activity were investigated. Methods and Results Echocardiography measurements showed that the cardioprotective effect of DTβ4 in myocardial infarction mice was significantly higher than that of wild-type Tβ4. Corresponding in vitro analyses demonstrated that the enhanced cardioprotection provided by DTβ4 was largely due to increased stimulation of angiogenesis. HPLC analysis, western blotting and qRT-PCR indicated that the enhanced pro-angiogenesis activity of DTβ4 was independent of the protein half-life and the known downstream pathways of wild-type Tβ4. Transcriptome deep sequencing (RNA-seq), BrdU incorporation assays, flow cytometry analysis and RNA interference demonstrated that the enhanced angiogenic activity of DTβ4 depended on MALAT1 (metastasis-associated lung adenocarcinoma transcript 1)-induced proliferation of vascular endothelial cells, which has not been reported for wild-type Tβ4. Moreover, transcription factor activation screening, luciferase promoter reporter assay and immunoprecipitation assay demonstrated that DTβ4 enhanced MALAT1 transcription by inhibiting the degradation of prospero-related homeobox 1 (PROX1). Conclusion This study demonstrates the potential applications and the novel bioactivity of the Tβ4 dimer. Moreover, to construct the dimer represents a new method for production of bioactive peptides that may have novel activities.

Immunotherapy is gathering momentum as a kind of important therapy for cancer patients. However, monotherapies have limited efficacy in improving outcomes and benefit only in a small subset of patients. Combination therapies targeting multiple pathways often can augment an immune response to improve survival further. Here, the tumoricidal effects of the dual hPD-L1(human programmed cell death ligand 1) vaccination/HER2(human epidermal growth factor receptor 2) gene vaccination immunotherapy against the established HER2-expressed cancers were observed. Animals treated with combination therapy using hPD-L1 vaccine and HER2 gene vaccine had significantly improved survival in a mammary carcinoma model. We observed an increase in tumor growth inhibition following treatment. The percentage of the tumor-free mice (%) was much higher in the combined PD-L1/HER2 group. Furthermore, under the tumor-burden condition, hPD-L1 vaccine enhanced humoral immunity of HER2 gene vaccine. And the combination treatment increased the IFN-γ-producing effector T cells. Additionally, splenocytes from the combined PD-L1/HER2 group immunized mice possessed higher CTL activity. Notably, vaccination with combination therapy induced a significant decrease in the percentage of CD4+CD25+ Treg cells. Collectively, these data demonstrate that PD-L1/HER2 gene vaccine combination therapy synergistically generates marked tumoricidal effects against established HER2-expressing cancers.

The effect of meteorite impact on basement rocks remains widely debated at Lonar Crater, Central India. We investigate an impact melt-bearing rock from the ejecta layer of Lonar to assess the potential interaction of the projectile with the underlying Archean basement. The investigated sample is a melanocratic, aphanitic melt rock comprising glassy inclusions, and plagioclase and quartz clasts. Plagioclase and quartz show shock-induced features including diaplectic glass and well-developed planar deformation features (PDFs), respectively. The decrease in shock pressure is thus established with the plagioclase of overlying basalt showing shock features like diaplectic glass whereas the quartz from lower Archean basement showing PDF development. Laser Raman spectroscopy reveals the presence of cristobalite. The impact melt-bearing rock shows major element geochemistry similar to that of Deccan basalt with a tholeiitic trend, but the Harker variation plots reveal an independent field for the melt rock between the two end members: Deccan basalt and Archean basement represented by Peninsular gneiss. The REE geochemistry also reveals more fractionation for the melt rock. Zircon U-Pb data indicate an upper intercept age around 3.0 to 3.1 Ga. Chondrite normalized zircon REE data display a positive Eu anomaly indicating a reheating during the impact event. This indicates that the melt rock sample was generated by the incorporation of Archean basement gneiss components, which is compatible with the estimated depth of excavation for an impact structure of this size. This specifies a depth to basement in the range between 522 and 570 m.

This study presents numerical investigations about the role of micro-crack heterogeneity in hydraulic fracture (HF) development and directional hydraulic fracturing (DHF) creation. By comparing the results of heterogeneous models (named DFN models) with the associated homogeneous models, the behavior is categorized into three modes: DFN models, which consume more (A), comparable (B), and much lower (C) energy than the associated homogeneous models. Variation of micro-crack distributions, which determines HFs interaction in the stress shadow zone, contributes to the difference in HF morphologies and injection energy consumption. The connection process, where one HF connects the other, predominates the energy cost in the DHF. Offset-related interactions usually occur between HFs and DFN in case of favorable distribution of micro-cracks, which guides the HFs to propagate through the interaction zone, thus favoring the connection process and improving the DHF efficiency. Adverse distribution of local cracks (even a single crack) with dilation-related interactions near the connection zone can produce extremely high stress due to the opening of the cracks, which significantly deteriorates the connection process and reduces the DHF efficiency. Therefore, a limited variation of crack distribution near the connection zone could cause a pronounced effect on HF connection and the associated energy consumption. Due to the limited sizes and shear slips of the micro-cracks in these simulations, deformation energy and fracture energy dissipation dominate the energy conversion during the injection, while frictional energy consumption plays a secondary role. The two-stage injection strategy can be a promising method to weaken the stress shadow effect, i.e., subsequent HFs extend directly to the previous one by taking advantage of the stress state produced in the first stage. The frictional resistance of micro-cracks also plays a significant role in DHF creation. Weak cracks allow the HFs to go through the interaction zone and avert the strict connection process, consequently improving the DHF efficiency.

Functional stability is a newly developed dynamic functional connectivity approach. The objective of this study was to adopt functional stability to investigate diagnosis-associated abnormalities (patients vs. controls) and status-related changes (acute vs. remitted status) in brain function in major depressive disorder (MDD). 132 MDD patients and 102 healthy controls underwent resting-state functional MRI as well as clinical and cognitive assessment at baseline, with 48 patients completing follow-up examinations at an average of 7 months. Results showed no group differences in baseline functional stability and no longitudinal functional stability changes from acute to remitted status in patients. However, we found that baseline functional stability in the dorsal and ventral anterior cingulate cortex, calcarine sulcus, and middle occipital gyrus could predict improvement in depressive symptoms from acute to remitted status in MDD patients, with longitudinal functional stability changes in these regions related to the degree of symptom improvement. In addition, lower baseline functional stability in the inferior temporal gyrus could predict a greater improvement in sustained attention, which was associated with a greater functional stability increase in this region. Our findings highlight functional stability as a potential prognostic biomarker to predict and track disease progression or stratify MDD patients for optimizing disease management and treatment strategies.

Ring forgings are widely used in industrial fields. It is an important way that the key dimensions of ring forgings are obtained by laser scanning to ensure the processing quality. It is difficult to extract high-precision section line of ring forgings from laser point clouds with a lot of noise. This paper presents a new method for extracting section line from raw point cloud of ring forging. An optimization algorithm is created based on the normal vector and L1-median, which is used to iteratively shrink the sampling points for obtaining the section line of ring forgings. L1-median has the characteristics of noise immunity, adding normal vector can get more detailed features. The extraction of high-precision section line of ring forgings is realized. Taking the second-order ring forging and the third-order ring forging as the experimental object, experiments are carried out to verify the effectiveness of the model.

In this study, the κ-carrageenan supplementation significantly reduced the gains in weight, fat mass, adipocyte size, fasting blood glucose as well as blood lipid in mice with high-fat diet. The investigation of the gene expression levels revealed that κ-carrageenan could improve high-fat diet induced obesity by the AMPK and PPARγ signaling pathway. The level of TNF-α and LPS in the LCGN group was significantly lower than that in the high-fat diet (HFD) group, while there were no significant difference in the HCGN group. The κ-carrageenan treatment was beneficial to the recovery of intestinal homeostasis in mice with high-fat diet, expecially LCGN. The abundance of Firmicutes, Proteobacteria, Lachnospiraceae, and Desulfovibrionaceae were positively correlated with body weight, fasting blood glucose (FBG), serum low density lipoprotein cholesterol (LDL-c), total cholesterol (TC), and triglyceride (TG) levels. By contrast, Bacteroidetes were negatively correlated with LDL-c and TC levels, while positively with FBG.

Fully encapsulated rock bolts are widely used in keeping the stability of underground openings and slopes. However, bonding failure at the bolt/grout (B/G) interface still occurs. Thus, a theoretical solution was proposed to investigate the rock bolting performance. The coupling and decoupling behaviour of the B/G interface is simulated with a bonding-slipping formula. The feasibility of this bonding-slipping formula was confirmed with physical experiments on rock bolts. Then, the rock bolt loading procedures were analysed. The advantage of this theoretical model is that all input parameters can be directly acquired from the experimental pullout scenario. Three physical pullout experiments, including laboratory and field tests, were used to validate this theoretical modelling. After validation, the deduced theoretical model can calculate the rock bolting performance. Then, this model was adopted to perform the parameter analysis. The results reveal that the loading phases of the B/G interface are independent of the encapsulated length. With the increasing encapsulated length, the B/G interface encounters the elastic, elastic-debonding and debonding phases in order. Moreover, with the increasing grouting material modulus, the rock bolt shows more brittle performance.

The spontaneous imbibition in porous medium is of interest for many engineering problems particularly in the reservoir exploitation over several decades. So far, various analytical or numerical models have been proposed to simulate the imbibition, but none of them can fully take into account real microscopic geometry characteristics of pore structure. Therefore, assuming quasi-steady and completely developed laminar flow with no-slip boundary conditions when capillary bundles imbibe an incompressible Newtonian liquid, a generalized spontaneous imbibition model is proposed based on a fractal pore structure consisting of tortuous and nonuniform capillaries with different sizes and noncircular cross-sections. A theoretical analysis and experimental contrast demonstrate that the derived formulas enable the unification of several traditional and newly developed models available from the literature and have the better predicted trend with the relative error controlled within 100% in comparison to them. The obtained model is evaluated against previously reported data of water imbibition measured for various natural porous rocks in multiple directions. The validation results show that the generalized model can be utilized to characterize the imbibition behavior of porous rocks with little clay and even extend to other natural and engineering porous materials, including consolidated and unconsolidated media, and that the interconnected pores cannot always be assumed to be cylindrical or uniform. Moreover, the present model is applied to inversely estimate the pore size as a result of good agreement with experimental measurements. Simultaneously, in accordance with the new theoretical model, the difference in water imbibition is newly revealed for selected rock samples from the literature.

Friction stir welding (FSW) is a solid phase welding method. The weld forming and welding quality are related to the heat production generated by plastic flow during FSW process. Therefore, it is of great importance to measure the viscoplastic heat production during FSW process. In this paper, firstly, taking the welding system during quasi-steady state welding stage as a rotary viscosity measuring meter, the relationship between viscous moment and viscosity is deduced. Secondly, the analysis model for plastic flow around welding pin in FSW process is established by applying the principle of fluid dynamics. The relationship between the temperature gradient on the surface of welding pin, the rotation rate of the FSW machine and viscous torque is obtained. Lastly, a new calculation method for viscoplastic heat production in FSW process is proposed with the help of numerical simulation. To verify the validity of the new calculation method, several groups of friction stir welding experiments are carried on.

Duck enteritis virus (DEV), the causative agent of duck viral enteritis, causes a contagious, lethal viral disease in Anseriformes (waterfowls). In virus infection, host-virus interaction plays a crucial role in virus replication and pathogenesis. In our previous study, mRFP was fused with the C-terminus of DEV glycoprotein C (gC) to construct a fluorescent-tag DEV virus rgCRFP. In the current study, fluorescent fusion protein (gC-mRFP) was used as the proteomic probe. Co-immunoprecipitation and mass spectrometric analysis of proteins from rgCRFP-infected chicken embryo fibroblasts using commercial anti-RFP antibody led to the identification of a total of 21 gC interacting host proteins. Out of these 21 proteins, the interaction of seven host proteins (GNG2, AR1H1, PPP2CA, UBE2I, MCM5, NUBP1, HN1) with DEV gC protein was validated using membrane-bound split-ubiquitin yeast two-hybrid system (MbYTH) and bimolecular fluorescence complementation (BiFC) analyses. It indicated direct interaction between these proteins with DEV gC protein. This study has furthered the current understanding of DEV virus infection and pathogenesis. SIGNIFICANCE: gC is an crucial glycoprotein of duck enteritis virus that plays an important role in the viral life cycle. Uncovering the interaction between virus-host is very important to elucidate the pathogenic mechanism of the virus. In this study, host factors interacting with DEV gC have been discerned. And seven host proteins (GNG2, AR1H1, PPP2CA, UBE2I, MCM5, NUBP1, HN1) have been further validated to interact with DEV gC using MbYTH and BiFC analyses. These outcomes could shed light on how DEV manipulates the cellular machinery, which could further our understanding of DEV pathogenesis.