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Layered rock-like samples containing saw-tooth interfaces of various joint roughness coefficients (JRC) and included angles were conducted uniaxial compression with the loading rate of 0.005 mm/s. The peak stress declines from 38.36–39.90 MPa to 17.35–30.67 MPa for included angle = 15°–60°, and then increases to 24.30–33.83 MPa for 60°–75°, but the peak strain decreases by 22.39%–41.30%. For JRC = 0–19.55, mechanical properties of samples are enhanced, while the anisotropy weakens. When the included angle is small (15°, 30°), the layered samples show a typical tensile splitting failure crossing the weak interlayers. For a large included angle of 45°–75°, failure modes are featured by shear sliding along weak interlayers combined with tensile splitting. As JRC increases, fracturing mechanism transition from shear sliding to mixed tension shear failure then to tensile splitting can be identified. With an increase in JRC or included angles, the global lateral strain of samples in plastic deformation stages changes from “sudden increase” to “progressive increase” to “jump increase”. For included angle = 15°, the layered sample produces dramatic lateral local strain at the weak interlayers due to tensile splitting failure. For included angle = 45°, both axial and lateral local strains at the weak interlayers show an obvious increase at the main shear failure surface. For a large included angle of 75°, the lateral local strain remarkably increases at the weak interlayers along with tensile failure of samples.

A fractal model governing saw-tooth fractures was first introduced to replicate sandstone samples containing an inclined 3D penetrating rough fracture surface with various joint roughness coefficients (JRC). In conventional triaxial compression, the peak strength for fractured samples increased with both confining pressure and JRC. During the unloading confining pressure process, the normal stress of fractures declined but the shear stress increased, resulting in shear sliding of fractures. The shear displacement of fractures exponentially increased, and the positive normal displacement decreased gradually to negative values under coupling effects of shear contraction caused by normal stress and shear dilation due to climbing effects of fractures. Transition from quasi-static to dynamic sliding of the fractures was identified. The sliding resistance duration increased with confining pressure but decreased with JRC. After pre-peak unloading, the fracture surfaces presented a more significant surface wear response and JRC values decreased by 1.70%–59.20% due to more remarkable asperity degradation compared with those after conventional triaxial compression. The theoretical model for shear strength of fractures was established through improving the Ladanyi & Archambault model by introducing the relations between normal stress and surface wear ratios of fractures, which agreed well with the experimental results.

Acute inflammation is the body’s first defense in response to pathogens or injury that is partially governed by a novel genus of endogenous lipid mediators that orchestrate the resolution of inflammation, coined specialized pro-resolving mediators (SPMs). SPMs, derived from omega-3-polyunstaturated fatty acids (PUFAs), include the eicosapentaenoic acid-derived and docosahexaenoic acid-derived Resolvins, Protectins, and Maresins. Herein, we review their biosynthesis, structural characteristics, and therapeutic effectiveness in various diseases such as ischemia, viral infections, periodontitis, neuroinflammatory diseases, cystic fibrosis, lung inflammation, herpes virus, and cancer, especially focusing on therapeutic effectiveness in respiratory inflammation and ischemia-related injuries. Resolvins are sub-nanomolar potent agonists that accelerate the resolution of inflammation by reducing excessive neutrophil infiltration, stimulating macrophage functions including phagocytosis, efferocytosis, and tissue repair. In addition to regulating neutrophils and macrophages, Resolvins control dendritic cell migration and T cell responses, and they also reduce the pro-inflammatory cytokines, proliferation, and metastasis of cancer cells. Importantly, several lines of evidence have demonstrated that Resolvins reduce tumor progression in melanoma, oral squamous cell carcinoma, lung cancer, and liver cancer. In addition, Resolvins enhance tumor cell debris clearance by macrophages in the tumor’s microenvironment. Resolvins, with their unique stereochemical structure, receptors, and biosynthetic pathways, provide a novel therapeutical approach to activating resolution mechanisms during cancer progression.

For either healthy or diseased organisms, lipids are key components for cellular membranes; they play important roles in numerous cellular processes including cell growth, proliferation, differentiation, energy storage and signaling. Exercise and disease development are examples of cellular environment alterations which produce changes in these networks. There are indications that alterations in lipid metabolism contribute to the development and progression of a variety of cancers. Measuring such alterations and understanding the pathways involved is critical to fully understand cellular metabolism. The demands for this information have led to the emergence of lipidomics, which enables the large-scale study of lipids using mass spectrometry (MS) techniques. Mass spectrometry has been widely used in lipidomics and allows us to analyze detailed lipid profiles of cancers. In this article, we discuss emerging strategies for lipidomics by mass spectrometry; targeted, as opposed to global, lipid analysis provides an exciting new alternative method. Additionally, we provide an introduction to lipidomics, lipid categories and their major biological functions, along with lipidomics studies by mass spectrometry in cancer samples. Further, we summarize the importance of lipid metabolism in oncology and tumor microenvironment, some of the challenges for lipodomics, and the potential for targeted approaches for screening pharmaceutical candidates to improve the therapeutic efficacy of treatment in cancer patients.

Currently, the use of robots has altered the way people live and their lifestyles. To realize a human-computer interaction system based on robots’ comprehension of human emotions, this study chooses facial expressions as the research object and constructs a facial expression recognition model based on convolutional neural networks and channel attention. To deploy the recognition model to portable devices, a depth-separable convolution filter pruning algorithm based on principal component analysis is constructed. This model applies principal component analysis to reduce the dimensionality of similar filter matrices obtained by calculating geometric medians to prevent gradient explosion. The proposed algorithm for facial expression recognition in this study achieves a 99% recognition accuracy with an average of 80.39%, while using the least number of parameters among the compared algorithms. The verification experiment results of lightweight network show that when the model depth is 56 and the pruning rate is 40%, the correct rate of facial expression recognition of the network model based on the pruning strategy proposed in the study is 93.24%. When dimension is 0.85, the accuracy of model classification is the highest. The algorithm presented in this study exhibits excellent performance when recognizing facial expressions, demonstrating notable robustness and efficiency. The pruning strategy proposed in this study has a good model acceleration effect. It can not only reduce the memory occupied by about 41% of parameters, but also improve the classification accuracy, running time and calculation cost after pruning to a certain extent. The study applied deep separable convolution and PCA techniques to improve and reduce the dimensionality of the convolutional layer in the ResNet network structure, and improved the comparable filter matrix generated during the filter pruning process.

With the rapid development of computer vision and artificial intelligence, image conversion technology has been widely applied in the fields of digital media and art. Based on the Generative adversarial network, this paper proposes a painting image conversion algorithm for multi class scenes. It performs deep feature extraction in the residual module, divides the encoding and decoding parts of the generator into functional parts, and designs them separately. The mixed attention module is inserted into the decoder and encoder to preserve the texture details of the image. The deep network interpolation is incorporated to achieve smooth and continuous conversion of the painting image. The experiment showed that the loss value of the research method decreases to 0.008 after 400 iterations during the loss value testing. Its maximum peak signal-to-noise ratio is 34.9dB when the bit rate increases to 1000kb/s. In the SAR image conversion dataset, the F1 value increases to 97.4 after 200 iterations. The pixel loss when it reaches 100% conversion in outdoor images is 5.38k. The data indicates that the research method has good performance in painting image conversion and can provide effective technical references for image conversion.

Shear tests on rectangular plate sandstone containing two pre-existing holes were performed to analyze the shear mechanical responses and cracking evolution mechanisms. With generation of the penetrating fracture surfaces, both shear stress and normal displacement show a dramatic drop. Then, during the shear slipping process, the shear stress increases once again due to wear and shear off of the surface asperities, and three different variation trends of the normal deformation including shear dilation, fluctuation, and shear contraction are respectively identified. The role of ligament length and normal stress on several key indices such as peak shear stress, peak normal displacement and residual shear stress was investigated. Violent AE (acoustic emission) responses occur along with penetration of the fracture surfaces, and in the shear slipping process, AE events continue to occur due to wear of surface asperities, while the increase rate of accumulative AE events declines. Cracks coalesced at the rock bridge and running through the rock matrix form the main failure planes of the samples. From the PFC2D simulation results, the crack clusters first initiate from hole-walls and coalesce at the rock bridge for a small ligament length, while first produce the main failure planes at the right/left rock matrix for a large ligament length. The total number of micro cracks shows a “calm → rapid increase → decreasing growth amplitude” variation during shearing, and the induced cracks become more concentrated for a larger normal stress, implying a cumulative damage of the failure surfaces.

Background On the basis of efficacy in mouse tumor models, multiple CD137 (4-1BB) agonist agents are being preclinically and clinically developed. The costimulatory molecule CD137 is inducibly expressed as a transmembrane or as a soluble protein (sCD137). Moreover, the CD137 cytoplasmic signaling domain is a key part in approved chimeric antigen receptors (CARs). Reliable pharmacodynamic biomarkers for CD137 ligation and costimulation of T cells will facilitate clinical development of CD137 agonists in the clinic.Methods We used human and mouse CD8 T cells undergoing activation to measure CD137 transcription and protein expression levels determining both the membrane-bound and soluble forms. In tumor-bearing mice plasma sCD137 concentrations were monitored on treatment with agonist anti-CD137 monoclonal antibodies (mAbs). Human CD137 knock-in mice were treated with clinical-grade agonist anti-human CD137 mAb (Urelumab). Sequential plasma samples were collected from the first patients intratumorally treated with Urelumab in the INTRUST clinical trial. Anti-mesothelin CD137-encompassing CAR-transduced T cells were stimulated with mesothelin coated microbeads. sCD137 was measured by sandwich ELISA and Luminex. Flow cytometry was used to monitor CD137 surface expression.Results CD137 costimulation upregulates transcription and protein expression of CD137 itself including sCD137 in human and mouse CD8 T cells. Immunotherapy with anti-CD137 agonist mAb resulted in increased plasma sCD137 in mice bearing syngeneic tumors. sCD137 induction is also observed in human CD137 knock-in mice treated with Urelumab and in mice transiently humanized with T cells undergoing CD137 costimulation inside subcutaneously implanted Matrigel plugs. The CD137 signaling domain-containing CAR T cells readily released sCD137 and acquired CD137 surface expression on antigen recognition. Patients treated intratumorally with low dose Urelumab showed increased plasma concentrations of sCD137.Conclusion sCD137 in plasma and CD137 surface expression can be used as quantitative parameters dynamically reflecting therapeutic costimulatory activity elicited by agonist CD137-targeted agents.

Primary splenic angiosarcoma (PSA) is a rare malignancy with poor prognosis. At present, little study is available on immunotherapy in PSA. Here, we report a case of a patient with metastatic PSA who was treated with programmed death-1 (PD-1) inhibitors and vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors combined therapy and achieved complete response (CR). The patient was a 57−year−old woman with three liver metastases. She was treated with seven cycles of toripalimab plus anlotinib. Programmed death-ligand 1 (PD-L1) immunohistochemistry and next-generation sequencing was performed, and the PD-L1 tumor proportion score was 75%. Finally, she achieved CR after six cycles of the combined therapy regimen. No serious adverse events were detected. To the best of our knowledge, this is the first clinical evidence that anti-PD-1 plus anti-VEGF therapy might be a promising option for patients with metastatic PSA. However, more clinical trials are needed to verify this conclusion.

[This corrects the article DOI: 10.1371/journal.pone.0168384.].

Mulching management has been used in many places all over the world to improve agricultural sustainability. However, the cycling of carbon in the soil under applications of mulch on sloping arable land is not yet fully understood. A four-year field experiment was carried out in Xiaofuling watershed of Danjiangkou reservoir in China. The object was to evaluate the effects of the application of straw mulch (ST) and grass mulch (GT) on dynamic changes in soil organic carbon and its fractions. Results showed that mulch applied on the soil surface increased the contents of SOC and its active fractions in the soil. Compared to the control without cover (CK), ST and GT treatments increased the contents of SOC, LOC, DOC, POC and EOC by 14.73%, 16.5%, 22.5%, 41.5% and 21%, respectively, in the 0-40 cm soil layer, and by 17%, 14%, 19%, and 30%, respectively, in the 0-100 cm soil layer. The contents of organic carbon and its active fractions decreased with increasing soil depth in all of the treatments. SOC was accumulated in the period of December to the following March. The contents of soil DOC and LOC were high in January to March, while the contents of soil POC and EOC were high in June to September. The relative contents of soil organic carbon fractions were POC > EOC > LOC > DOC over the four years. Straw mulching had no significant effect on the changes in soil organic carbon active fractions during the different periods. Based on this long-term field experiment in Danjiangkou reservoir, we found that straw mulching had a significant effect on soil, increasing SOC content and stock in slopping arable land, and that live grass mulching was more effective than rice straw mulching. We discuss possible optimal periods for the implementation of mulching practices on sloping land.

Endosulfan as a new member of persistent organic pollutants has been shown to induce reproductive dysfunction in various animal models. However, the action mechanism of endosulfan-produced reproductive toxicity remains largely unknown. This study was focused on investigating the reproductive toxicity induced by a-endosulfan and clarifying the role of mitochondria and genotoxic response genes in germ cell apoptosis of Caenorhabditis elegans. Our data showed that endosulfan induced a dose-dependent decrease of life span, fecundity, and hatchability, whereas the germ cell apoptosis was dose-dependently increased. The mitochondria membrane potential was disrupted by endosulfan, leading to a significant increase of germ cell apoptosis in mev-1(kn-1) mutant. However, the apoptotic effects of endosulfan were blocked in mutants of cep-1(w40), egl-1(n487), and hus-1(op241), indicating conserved genotoxic response genes played an essential role in endosulfan-induced germ cell apoptosis. Furthermore, exposure to endosulfan induced the accumulation of HUS-1::GFP foci and the germ cell cycle arrest. These findings provided clear evidence that endosulfan caused significant adverse effects on the reproduction system of C. elegans and increased germ cell apoptosis, which was regulated by mitochondrial dysfunction and DNA damage response genes. This study may help to understand the signal transduction pathways involved in endosulfan-induced reproductive toxicity. [ABSTRACT FROM AUTHOR]

miR-155 (microRNA-155) is an important noncoding RNA in regulating host inflammatory responses. However, its regulatory role in ocular infection remains unclear. Our study first explored the function of miR-155 in Pseudomonas aeruginosa-induced keratitis, one of the most common sight-threatening ocular diseases. We found that miR-155 expression was enhanced in human and mouse corneas after P. aeruginosa infection and was mainly expressed in macrophages but not neutrophils. In vivo studies demonstrated that miR-155 knockout mice displayed more resistance to P. aeruginosa keratitis, with a higher inducible nitric oxide synthase level and a lower bacterial burden. More importantly, in vitro data indicated that miR-155 suppressed the macrophage-mediated bacterial phagocytosis and intracellular killing of P. aeruginosa by targeting Rheb (Ras homolog enriched in brain). To the best of our knowledge, this is the first study to explore the role of miR-155 in bacterial keratitis, which may provide a promising target for clinical treatment of P. aeruginosa keratitis and other infectious diseases. [ABSTRACT FROM AUTHOR]