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Abstract Background Gastric cancer (GC) has a high mortality rate and is one of the most fatal malignant tumours. Male sex has been proven as an independent risk factor for GC. This study aimed to identify immune-related genes (IRGs) associated with the prognosis of male GC. Methods RNA sequencing and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed IRGs between male GC and normal tissues were identified by integrated bioinformatics analysis. Univariate and multivariate Cox regression analyses were applied to screen survival-associated IRGs. Then, GC patients were separated into high- and low-risk groups based on the median risk score. Furthermore, a nomogram was constructed based on the TCGA dataset. The prognostic value of the risk signature model was evaluated by Kaplan-Meier curve, receiver operating characteristic (ROC), Harrell’s concordance index and calibration curves. In addition, the gene expression dataset from the Gene Expression Omnibus (GEO) was also downloaded for external validation. The relative proportions of 22 types of infiltrating immune cells in each male GC sample were evaluated using CIBERSORT. Results A total of 276 differentially expressed IRGs were screened, including 189 up-regulated and 87 down-regulated genes. Subsequently, a seven-IRGs signature (LCN12, CCL21, RNASE2, CGB5, NRG4, AGTR1 and NPR3) was identified to be significantly associated with the overall survival (OS) of male GC patients. Survival analysis indicated that patients in the high-risk group exhibited a poor clinical outcome. The results of multivariate analysis revealed that the risk score was an independent prognostic factor. The established nomogram could be used to evaluate the prognosis of individual male GC patients. Further analysis showed that the prognostic model had excellent predictive performance in both TCGA and validated cohorts. Besides, the results of tumour-infiltrating immune cell analysis indicated that the seven-IRGs signature could reflect the status of the tumour immune microenvironment. Conclusions Our study developed a novel seven-IRGs risk signature for individualized survival prediction of male GC patients.

Abstract In this article, we study the controllability for impulsive fractional integro-differential evolution equation in a Banach space. The discussions are based on the Mönch fixed point theorem as well as the theory of fractional calculus and the ( α , β ) $(\alpha ,\beta )$ -resolvent operator, we concern with the term u ′ ( ⋅ ) $u'(\cdot )$ and finding a control v such that the mild solution satisfies u ( b ) = u b $u(b)=u_{b}$ and u ′ ( b ) = u b ′ $u'(b)=u'_{b}$ . Finally, we present an application to support the validity study.

This paper is concerned with the existence of positive solutions to the fourth-order boundary value problem u(4)(x)=f(x,u(x),u″(x)) on the interval [0, 1] with the boundary condition u(0)=u(1)=u″(0)=u″(1)=0, which models a statically bending elastic beam whose two ends are simply supported. Without assuming that the nonlinearity f(x, u, v) is nonnegative, an existence result of positive solutions is obtained under the inequality conditions that |(u, v)| is small or large enough. The discussion is based on the method of lower and upper solutions.

Abstract Mucosal-associated invariant T (MAIT) cells are an invariant T cell subset, which have been reported to play an antimicrobial role in infectious diseases. However, little is known about it in malignant diseases and tumors, especially in gastric cancer (GC). So in this study, we aim to examine the frequency, phenotype, partial functional capacity and clinical relevance of this cells from GC patients’ peripheral blood by flow cytometry. It was shown that the frequency of peripheral blood MAIT cells was negatively correlated with their increasing age in healthy adults. Importantly, comparing to the healthy controls (HC), the frequency and the absolute number of MAIT cells from GC patients’ peripheral blood with or without chemotherapy were both significantly lower than those. For the phenotype, the proportion of CD4−MAIT cell subset in GC patients without chemotherapy was lower than in HC, but higher than in GC patients with chemotherapy. Whereas, the proportion of CD4−CD8+MAIT cell subset in GC patients without chemotherapy was significantly lower than that in HC. Finally, the level of Granzyme-B (GrB), a molecule associated with MAIT cells was markedly lower in GC patients. But the correlation between the serum levels of GC-associated tumor antigens and the percentages of MAIT cells in GC patients was not observed. In conclusion, our study shows the decreased frequency, changed phenotypes and partial potentially impaired function of MAIT cells in GC patients, suggesting a possible MAIT cell-based immunological surveillance of GC.

Multi-granulation fuzzy probabilistic rough set (MFPRS) model over two universes has various applications in recent years. However, data are typically changing with time in real-life applications. When data changes, people have to spend a lot of unnecessary time to recalculate the approximations in MFPRS over two universes. To address this problem, we design incremental algorithms based on the object-first approach for updating approximations in MFPRS over two universes while the objects are added into or removed from the two universes. Firstly, considering a case where the equivalence class of the object with respect to the fuzzy relation could be empty, we introduce a model of type-empty MFPRS over two universes. Then, based on the matrix, a traditional algorithm is introduced to calculate approximations in MFPRS over two universes. In addition, by optimizing the traditional algorithm, we design the object-first algorithm which could calculate approximations more efficient in MFPRS over two universes. After that, based on the object-first algorithm, four object-first incremental algorithms are designed for updating approximations in MFPRS over two universes while the objects are added into or removed from two universes. Finally, experimental results show that the proposed object-first incremental algorithms for updating approximations in MFPRS over two universes are more efficient in comparison with the non-incremental algorithms and the traditional incremental algorithms.

Choriocarcinoma is a cancer that usually occurs in the uterus during pregnancy. Although choriocarcinoma with renal metastasis and spontaneous renal hemorrhage is very rare, it can occur. We describe a rare case of metastatic choriocarcinoma, wherein the patient presented with acute abdominal pain due to a subcapsular hematoma secondary to a bleeding renal metastasis. We performed a laparoscopic nephron sparing surgery to remove the tumor and control the bleeding. A retrospective analysis revealed that metastasis was detected on 18F-fluorodeoxyglucose PET/CT, but not on CT alone. To our knowledge, a case of choriocarcinoma with such symptoms and treatment has not been described in recent literature. Our case illustrates that acute bleeding from a renal metastasis can be effectively managed by laparoscopic nephron sparing surgery. It also demonstrates the advantage 18F-FDG PET/CT may have in the evaluation of metastatic choriocarcinoma.

The gut microbiota plays vital roles in metabolizing nutrient, maintaining the intestinal epithelial barrier but also in modulating immunity. Host genetics and the pig breed are implicated in shaping gut microbiota. Tibetan pig is a unique native Chinese breed and has evolved to manifest a strong disease resistance. However, the immunity and microbiota of growing Tibetan (TP) pigs were still rarely understood. The jejunal immunity phenotype and microbial composition of TP and Duroc × (Landrace × Yorkshire) (DLY) pigs were explored through immunohistochemistry and 16S rRNA sequencing. Higher scores of clusters of differentiation 4 (CD4+) and Toll-like receptor 9 (TLR9) were observed in TP pigs than those of DLY pigs (p < 0.05), as were Interleukin 10 (IL-10) and zonular occludens 1 (ZO-1) (p < 0.01). Similar levels of bacterial richness and diversity were found in the jejunal microbiota of the TP and DLY pigs. However, the TP pigs showed a significantly different microbiome compared to DLY pigs at the genus level (ANOSIM; p < 0.05). Pseudomonas, Stenotrophomonas, Phenylobacterium, and Sandaracinobacter were enriched in DLY pigs (p < 0.05), while the Lactobacillus and Solibacillus had higher abundances in TP pigs than DLY pigs (p < 0.05). Tibetan pigs have “healthier” intestinal microbial communities than DLY pigs. Close relationships were found between jejunal immune performance and the differential bacteria, Lactobacillus can enhance porcine jejunal immunity, while Stenotrophomonas will have a negative impact on porcine gut immunity.

Opa interacting protein 5 (OIP5), overexpressed in some types of human cancers, has been reported to be associated with the carcinogenesis of human cancer. However, its contribution to cancer immunity remains unknown. Furthermore, the relationship between OIP5 and cancer immunity remains uncertain. In our research, we explored the different expression of OIP5 between 539 ccRCC and 72 normal renal tissues base on TCGA data set. We analyzed the associations between OIP5 expression with ccRCC progression and survival. Next, we compared immune cell profiles in cancer tissues and normal tissues in the Cancer Genome Atlas (TCGA) ccRCC cohort. We found that the level of immune cell infiltration was correlated with the copy number of OIP5 gene in ccRCC. The effect of OIP5 on immune activity was verified by Gene Set Enrichment Analysis of RNA-seq data from 32 ccRCC cell lines in the public database. Moreover, a pathway enrichment analysis of 49 OIP5-associated immunomodulators demonstrated the involvement of the T cell receptor signaling pathway, the JAK-STAT signaling pathway, the NF-kappa B signaling pathway and the primary immunodeficiency pathway. In addition, using OIP5-associated immunomodulators, we constructed multiple-gene risk prediction signatures using the Cox regression model. Our results provided insights into the role of OIP5 in tumor immunity and revealed that OIP5 may be a potential immunotherapeutic target for ccRCC. Designated immune signature is a promising prognostic biomarker in ccRCC.

The presence of strong inter-layer interactions has hindered the synthesis efforts towards large-area and highly crystalline monolayer SnS. Here, the authors report synthesis of large-area monolayer SnS using a liquid metal-based technique, and fabricate piezoelectric nano-generators with average peak output voltage of 150 mV at 0.7% strain.

The Quantougou (QTG) Fauna in central Lanzhou Basin is an important late Mid-Miocene fauna on the northeastern Tibetan Plateau margin, but its numerical age remains a matter of debate. Here, we present a new magnetostratigraphic record for a fluvio-lacustrine section to further constrain the age of the QTG Fauna. Results suggest that the studied section spans from polarity chrons C5Cn.2n to C5n.2n or C5An.1n, with ages of ca. 16.5 Ma to 10 ​Ma or 16.5 Ma to 12 ​Ma. The QTG Fauna is located at the top of polarity chron C5r.3r or C5Ar.2r, which corresponds to an age of 11.7 Ma or 12.8 ​Ma for the fauna. Accordingly, the associated Myocricetodontinae (a subfamily of Gerbillidae, Rodentia) is suggested to have appeared in the Lanzhou Basin at 11.7 ​Ma or 12.8 ​Ma, which is the oldest Myocricetodontinae in East Asia but is still much younger than the ~20 ​Ma appearance of this subfamily in West and South Asia. Our age data support the interpretation that East Asian Myocricetodontinae originated from South Asia. The QTG fauna further suggest a dry and open grassland environment, which is consistent with global cooling after the Mid-Miocene Climatic Optimum.

In this article, we apply the perturbation technique and monotone iterative method in the presence of the lower and the upper solutions to discuss the existence of the minimal and maximal mild solutions to the retarded evolution equations involving nonlocal and impulsive conditions in an ordered Banach space X $$\displaylines{ u'(t)+Au(t)= f(t,u(t),u_t),\quad t\in [0,a],\; t\neq t_k,\cr u(t_k^+)=u(t_k^-)+I_k(u(t_k)),\quad k=1,2,\dots ,m,\cr u(s)=g(u)(s)+\varphi(s),\quad s\in [-r,0], }$$ where $A:D(A)\subset X\to X$ is a closed linear operator and -A generates a strongly continuous semigroup T(t) $(t\geq 0)$ on X, a, r>0 are two constants, $f:[0,a]\times X\times C_0\to X$ is Caratheodory continuous, $0

Abstract This paper deals with the finite-approximate controllability for a class of fractional stochastic evolution equations with nonlocal initial conditions in a Hilbert space. We establish sufficient conditions for the finite-approximate controllability of the control system when the compactness conditions or Lipschitz conditions for the nonlocal term and uniform boundedness conditions for the nonlinear term are not required. The discussion is based on the fixed point theorem, approximation techniques and diagonal argument. In the end, an example is presented to illustrate the abstract theory. Our result improves and extends some relevant results in this area.

Critical thinking is an important part of the quality cultivation of engineering students. At present, many colleges and universities in China have gradually realized it, and mainly strengthen the training of students' critical thinking by offering relevant humanities courses, but there are few researches related to this topic through the penetration of engineering professional courses, and they are not deep enough. This study mainly discusses the efficacy of virtual simulation system teaching method in improving critical thinking of engineering students engaged in NC (Numerical Control) machining. It integrates the types of learning activities in the proposed teaching method with the development elements of critical thinking, and then constructs the context-based teaching design along with a self-developed virtual learning environment for the cultivation of students' critical thinking. We also evaluated students' response towards the research topics to investigate its teaching-learning effectiveness and acceptance by student community. Responses from questionnaires were collected from a convenience sample of 63 junior students majoring in NC machining from the author's university. The subsequent empirical study was conducted to exhibit superior results for mostly the cognitive skills of critical thinking. Students' feedback also revealed that students obtain more satisfaction and self-confidence, and demonstrated high positive attitude towards the proposed teaching method, and showed high perceived usefulness of the context-based teaching design to acquire complete, concrete and confident knowledge of NC machining. The findings of this study are valuable for academic institutions and educators to design the virtual visualized lectures and classrooms to enhance students' performance in critical thinking.

Geosynthetic interlayer systems are effective techniques to control reflective cracking and have better waterproof performance in damaged asphalt pavements. The interlayer bonding performance is critical to its function. This research investigated the interfacial adhesive property and road performance of asphalt overlay with geotextile interlayer. First, shear damage energy characteristics of geotextile interlayer have been investigated by varying tack coat types (SBS-modified asphalt, virgin asphalt, and emulsified asphalt), application rates (0.3 kg/m2–1.2 kg/m2), spraying times (1–2), upper mixture paving temperature (140°C–180°C), service temperature (5°C–45°C), and soaking time (0 h–96 h). In addition, bending fatigue tests, rutting tests, and semicircular bending tests were carried out to evaluate the comprehensive road performance of the asphalt overlay. The results showed that the interface adhesive property of asphalt overlay with geotextile interlayer using SBS-modified asphalt is best when the application rate is 0.8 kg/m2. The higher paving temperature is beneficial for the geotextile interlayer adhesion performance when the SBS-modified asphalt is sprayed at one time, while the paving temperature has almost no effect when the SBS-modified asphalt is sprayed at two times. The geotextile interlayer adhesion performance is less affected by temperature and more affected by water immersion. Compared with the common asphalt overlay types, the asphalt overlay with geotextile interlayer using SBS-modified asphalt shows better overall performance.

Mannan oligosaccharides (MOSs) have been implicated in the animal growth rate, health indices, and lipid oxidative stability. MOSs have been indicated to maintain intestinal health and anti-inflammatory effects via modulation of gut microbiota. Furthermore, the role of MOSs in modulating skeletal muscle function is largely unknown. Here, this study aimed to investigate the effects of MOS supplementation on muscle function and muscle mass in mice. Additionally, the possible underlying mechanisms, including the contributions of gut microbiota and microbial metabolites, were explored. In our study, 3-week-old C57BL/6J male mice (body weight of approximately 10.7 ± 1.1 g) were given pure water or pure water with 1% MOS. To study the effect of MOSs on gut-microbiota-derived metabolites, serum metabolic profiles were analyzed through untargeted metabolomic profiling. Moreover, we detected the downstream signals of differential metabolites, and decanoic acid (DA) was selected as our target spot. Then, DA was used to treat C2C12 cells, and we found that DA promotes C2C12 cell differentiation via the GPR84 and PI3K/AKT signaling pathways. In conclusion, these results showed that MOS supplementation improves muscle function and muscle mass. Additionally, gut microbiome and microbial metabolites were regulated by MOSs, and DA may be one of the most important links between the gut microbiome and skeletal muscle function regulation.

Abstract This paper is concerned with the existence of extremal mild solutions for Hilfer fractional evolution equations with nonlocal conditions in an ordered Banach space E. By employing the method of lower and upper solutions, the measure of noncompactness, and Sadovskii’s fixed point theorem, we obtain the existence of extremal mild solutions for Hilfer fractional evolution equations with noncompact semigroups. Finally, an example is provided to illustrate the feasibility of our main results.

BackgroundThe role of activating transcription factor 4 (ATF4) underlying gastric cancer (GC) remains unclear. The purpose of this study was to investigate the expression levels and biological functions of ATF4 in GC.MethodsExpression of ATF4 was detected by quantitative PCR (qPCR), Western blotting, and immunohistochemistry. Cox regression was used for survival analysis and the construction of the nomogram. Immunofluorescence was used to identify the intracellular localization of ATF4. Knockdown and overexpression of ATF4 in GC cells followed by wound healing and Transwell assays, EdU and Calcein-AM/propidium iodide (PI) staining, and cell cycle detection were performed to examine its function in vitro. Transmission electron microscopy was performed to assess the autophagy levels upon ATF4 silencing. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and gene set enrichment analysis (GSEA) were used to determine gene enrichment. SPSS 22.0 software, GraphPad Prism 7.0, and R version 3.6.1 were used for statistical analysis.ResultsATF4 expression was upregulated in GC cells and tissues compared with corresponding normal tissues. Survival analysis suggested that a high ATF4 expression was strongly associated with worse overall survival (OS) of GC patients (p

Knowledge of paleolake evolution is highly important for understanding the past hydroclimate regime on the Tibetan Plateau and associated forcing mechanisms. However, the hydrological history of paleolakes on the central plateau, the core region of the plateau, remains largely inconclusive. Here we present new biomarker records from lacustrine deposits of the Lunpori section in the Lunpola Basin to reconstruct detailed lake-level fluctuations during the mid-Miocene. A set of n-alkane indexes, including the proportion of aquatic macrophytes (Paq), average chain length and carbon preference index as well as the content of n-alkanes, vary substantially and consistently throughout the studied interval. Our results altogether show relatively low lake level at ∼16.3–15.5 Ma and high lake level before and after the interval, which is in line with the lithological observations in the section. Further comparison with existing regional and global temperature records suggests that lake level fluctuations can be largely linked to global climatic conditions during the mid-Miocene, with lake expansion during relatively warm periods and vice versa. Therefore, we infer that global climatic changes might have controlled the lake-level fluctuations in this region during the mid-Miocene, whereas the tectonic uplift likely played a subordinate role on this timescale.

Appetite is the basis for obtaining food and maintaining normal metabolism. Toll-like receptor 4 (TLR4) is an important receptor expressed in the brain that induces inflammatory signaling after activation. Inflammation is considered to affect the homeostatic and non-homeostatic systems of appetite, which are dominated by hypothalamic and mesolimbic dopamine signaling. Although the pathological features of many types of inflammation are known, their physiological functions in appetite are largely unknown. This review mainly addresses several key issues, including the structures of the homeostatic and non-homeostatic systems. In addition, the mechanism by which TLR4-induced inflammatory signaling contributes to these two systems to regulate appetite is also discussed. This review will provide potential opportunities to develop new therapeutic interventions that control appetite under inflammatory conditions.

This paper deals with the existence of solutions of the elliptic equation with nonlinear gradient term −Δu=f(x,u,∇u) on Ω restricted by the boundary condition u|∂Ω=0, where Ω is a bounded domain in RN with sufficiently smooth boundary ∂Ω, N≥2, and f:Ω¯×R×RN→R is continuous. The existence results of classical solutions and positive solutions are obtained under some inequality conditions on the nonlinearity f(x,ξ,η) when |(ξ,η)| is small or large enough.

Background: Tertiary lymphoid structures (TLSs) are formed by the aggregation of tumour-infiltrating lymphocytes (TILs), which is driven by chemokines or cytokines in the tumour microenvironment. Studies have shown that TLSs are associated with good prognosis in patients with various solid tumours and can improve patient responses to immunotherapy. However, the role of TLSs in hepatocellular carcinoma (HCC) remains controversial, and the underlying molecular mechanism is unclear. Methods: According to haematoxylin-eosin (HE) staining results, HCC patients in Xijing Hospital data and TCGA data were divided into TLS+ and TLS- groups, and Kaplan–Meier (KM) analysis was performed to assess overall survival (OS) and recurrence-free survival (RFS). Immunofluorescence (IF) and immunohistochemistry (IHC) were used to identify TILs in the TLS+ group. Lymphocyte-specific protein tyrosine kinase (LCK), a molecule involved in TLS formation, was explored in LinkedOmics. TILs were divided into two groups by drawing receiver operating characteristic (ROC) curves to calculate cut-off values. Spearman correlation analysis was used to calculate the correlation between LCK and TILs, and the molecular pathways by which LCK regulates immunotherapy were clarified through enrichment analysis. The half-maximal inhibitory concentration (IC50) distribution of sorafenib was observed in groups that varied in LCK expression. Results: According to the HE results, 61 cases in the Xijing Hospital cohort and 195 cases in the TCGA cohort had TLSs, while 89 cases and 136 cases did not. The KM results showed that TLSs had no effect on the OS of HCC patients but significantly affected RFS. The IF/IHC results showed that higher TIL numbers in TLSs were correlated with better prognosis in HCC patients. Spearman correlation analysis showed that LCK expression was positively correlated with TIL numbers. Enrichment analysis showed that upregulation of LCK expression mainly regulated the cytokine signalling pathway, the chemokine signalling pathway and T-cell activation. The IC50 scores of sorafenib in HCC patients with high LCK expression were lower, and the sensitivity was higher. Conclusion: TLSs mainly affected the early RFS of HCC patients but had no effect on OS. The high expression of the TLS formation-related gene LCK can increase the sensitivity of HCC patients to ICIs.

Sapindus delavayi (Franch.) Radlk. (S. delavayi) is an important biological washing material and biomass energy tree species with a peel rich in saponins and a kernel high in oil content. We used the maximum entropy model (MaxEnt) to predict the suitable habitats for S. delavayi in China, screen the dominant environmental factors affecting its distribution, and analyze the changes in its suitable habitats under future climate change. The results provide a scientific basis for its introduction, cultivation, and germplasm resource collection and protection. Twenty-two environmental variables and China distribution data for S. delavayi were used to construct the species distribution model, and the receiver operating characteristic (ROC) curve was used to verify the model’s accuracy. The dominant environmental factors were screened through the jackknife method, then a geographical information system (ArcGIS) was used to determine the level of suitable habitat division and area calculation. The results showed that the MaxEnt model had an excellent predictive effect for which the area under the ROC curve (AUC) value was as high as 0.959. The annual precipitation (Bio18), minimum temperature of the coldest month (Bio6), temperature seasonality (Bio4), and precipitation of the coldest quarter (Bio19) were the dominant environmental factors that affected the distribution of S. delavayi. Under the current climate, the suitable area for S. delavayi is 1,321,308.07 km2, and under the four climate scenarios for the 2050s and 2090s, the suitable area is predicted to change by −3.97%~2.57%. Overall, the centroids of the highly suitable habitats will shift by different degrees to the southwest in the future.

This paper deals with the existence of positive solutions of the fully fourth-order boundary value pqroblem u(4)=f(t,u,u′,u″,u‴) on [0,1] with the boundary condition u(0)=u(1)=u″(0)=u″(1)=0, which models a statically bending elastic beam whose two ends are simply supported, where f:[0,1]×R+×R×R−×R→R+ is continuous. Some precise inequality conditions on f guaranteeing the existence of positive solutions are presented. The inequality conditions allow that f(t,u,v,w,z) may be asymptotically linear, superlinear, or sublinear on u,v,w, and z as |(u,v,w,z)|→0 and |(u,v,w,z)|→∞. Our discussion is based on the fixed point index theory in cones.

BackgroundAbnormal accumulation of macrophages in the colon cancer (CC) contribute to its progression. miR-183-5p has been confirmed as an oncogene in CC and this article explores the effect and mechanism of exosomal miR-183-5p enriched by M2-polarized tumor-associated macrophages (TAM) on CC cells.MethodsThe human macrophage THP1 was induced to M2 polarization through IL-4 and IL-13 treatment. Exosomes in THP1 were isolated through ultracentrifugation, and the miR-183-5p expression in macrophages and exosomes was verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The miR-183-5p inhibitors and mimics were applied to down-regulate and upregulate miR-183-5p in macrophages, respectively. Meanwhile, CC cell lines LoVo and SW480 were treated with the macrophage conditioned medium and exosomes, respectively. CC cells’ proliferation, invasion, and apoptosis were tested by the cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry (FCM), Transwell assay, and xenograft assay, respectively. The profiles of thioesterase superfamily member 4 (THEM4), Akt, and NF-κB were compared by Western blotting (WB).ResultsThe miR-183-5p level in M2-TAM and M2-TAM-derived exosomes was significantly increased. Meanwhile, M2-TAM and M2-TAM-derived exosomes significantly facilitated CC cell proliferation and invasion and dampened apoptosis. Overexpression of miR-183-5p in M2-TAM aggravated M2-TAM-mediated promotive effects on CC cells, with down-regulating miR-183-5p reversed M2-TAM-mediated tumor-promotive effects. Mechanically, miR-183-5p targeted THEM4 and inhibited its mRNA and protein expression. Overexpressing THEM4 abated miR-183-5p-mediated carcinogenic effects and inactivates Akt and NF-κB pathways in CC cells. Overall, this article elaborated that exosomal miR-183-5p shuttled by M2-TAM mediated Akt/NF-κB pathway to accelerate CC progression through targeting THEM4.

Abstract With the increasing demand for vehicle handling comfort in the market, the development of gear shifting performance test systems for automobile transmission has become one of the keys to improving the competitiveness of automobile products. In order to continuously improve the shifting quality of the automobile gearshift control, this research focuses on the study of shifting quality, uses GSA (gear shift analysis) test technology to test and verify the shifting performance of a domestic automobile gearbox, establishes the subjective and objective evaluation criteria for the shifting performance of automobile gearbox, provides a reliable theoretical basis for product optimization design and shifting performance evaluation, and formulates shifting control pertinently. Strategies and optimization measures to ensure that the power, ride, and transmission of the whole vehicle system meet the technical requirements and can shift quickly and smoothly. Not only does this allows to reduce the driver's fatigue strength, but also increases the comfort of the whole shifting process, so as to provide direction to improve the quality of the vehicle's shifting performance and effectively reduce the impact on the driver's health.

Abstract In this paper we discuss the existence of solutions of the fully fourth-order boundary value problem {u(4)=f(t,u,u′,u″,u‴),t∈[0,1],u(0)=u′(0)=u″(1)=u‴(1)=0, $$ \textstyle\begin{cases} u^{(4)}=f(t, u, u', u'', u'''), \quad t\in [0, 1], \\ u(0)=u'(0)=u''(1)=u'''(1)=0 , \end{cases} $$ which models the deformations of an elastic cantilever beam in equilibrium state, where f:[0,1]×R4→R $f:[0, 1]\times {\mathbb{R}}^{4}\to \mathbb{R}$ is continuous. Using the method of lower and upper solutions and the monotone iterative technique, we obtain some existence results under monotonicity assumptions on nonlinearity.

Abstract In this article, we study the existence of mild solutions for damped elastic systems in Banach spaces. The discussion is based on the operator semigroup theory and fixed point theorem. In addition, two examples are given to illustrate our results.

Abstract This paper deals with the existence of solution for the fully fourth-order boundary value problem {u(4)(x)=f(x,u(x),u′(x),u″(1),u‴(x)),x∈[0,1],u(0)=u′(0)=u″(1)=u‴(1)=0, $$ \textstyle\begin{cases} u^{(4)}(x)=f(x, u(x), u'(x), u''(1), u'''(x)),\quad x\in [0, 1], \\ u(0)=u'(0)=u''(1)=u'''(1)=0 , \end{cases} $$ which models a statically elastic beam fixed at the left and freed at the right, and it is called cantilever beam in mechanics, where f:[0,1]×R4→R $f:[0, 1]\times {{\mathbb{R}}}^{4}\to {\mathbb{R}}$ is continuous. Some inequality conditions on f guaranteeing the existence and uniqueness of solutions are presented. The inequality conditions allow f(x,y0,y1,y2,y3) $f(x, y_{0}, y_{1}, y_{2}, y_{3})$ to grow superlinearly on y0 $y_{0}$, y1 $y_{1}$, y2 $y_{2}$, and y3 $y_{3}$.

This study evaluated the effect of a plateau environment on the heart and liver oxidation state of Tibetan pigs (TPs) and DLY pigs through analyzing AMPK, p38 MAPK, and Nrf2 signaling pathways. Twelve 120-day-old TPs and twelve 120-day-old DLY pigs were randomly divided into two groups in a plateau environment for three weeks. Exposed to a plateau environment, TPs exhibited a lower (p < 0.05) malondialdehyde level but higher (p < 0.05) glutathione, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) activities in the liver and heart than those observed in DLY pigs. TPs also showed higher (p < 0.05) mRNA levels of SOD and GSH-Px in the liver and heart compared with those of DLY pigs. The TPs showed higher (p < 0.05) mRNA and protein levels of AMPK and Nrf2 in the liver and heart compared with those of DLY pigs. Furthermore, TPs showed higher (p < 0.05) mRNA and protein levels of p38 MAPK in the heart and higher mRNA levels of p38 MAPK in the liver compared with those of DLY pigs under a plateau environment. In summary, TPs possess a stronger antioxidant capacity in the heart and liver than that of DLY pigs in a plateau environment through AMPK/p38 MAPK/Nrf2-ARE signaling pathways.

Abstract Objective To evaluate the intraoperative and short-term postoperative outcomes of a novel robotic intracorporeal π-shaped esophagojejunostomy (EJS) after D2 total gastrectomy (TG) using the Da Vinci robotic surgical system for intracorporeal anastomosis after TG. Background Intracorporeal π-shaped EJS, using a linear stapler, was recently reported for laparoscopic total gastrectomy in patients with gastric cancer. However, robotic intracorporeal π-shaped EJS using a linear stapler has not been reported. This report aimed to describe the use of a novel technique for π-shaped EJS using the Da Vinci robotic system. Methods Robotic intracorporeal π-shaped esophagojejunostomy after total gastrectomy was performed in 11 consecutive patients diagnosed with early gastric cancer, and their perioperative outcomes were analyzed. Results All the operations were successful without conversion to open or laparoscopic surgery and postoperative complications. The total number of patients was 11 (7 males and 4 females). The mean age of the patients was 63.36 ± 10.56 years old. Seven patients were diagnosed with cardia cancer, 3 patients were diagnosed with gastric body cancer, and 1 patient was diagnosed with gastric antrum cancer. The patients’ mean proximal resection margin was 3.18 ± 1.17 cm, the distal resection margin was 6.18 ± 1.40 cm, the mean length of the incision was 4.55 ± 0.69 cm, the mean operative time was 287.27 ± 30.69 min, the mean day of first flatus was 3.27 ± 0.79 days, the mean day of the start of diet was 2.91 ± 0.94 days, the mean postoperative hospital stay was 11.45 ± 5.13 days, and the mean operative blood loss was 47.27 ± 31.33 ml. No complications were observed during anastomosis, and the median anastomosis time was 19.5 min. The mean number of lymph node dissections was 17.91 ± 4.59, the mean number of positive lymph nodes was 0.45 ± 0.69, all patients were diagnosed with stage I–II gastric cancer, and the mean maximum diameter of the tumor was 2.67 ± 1.30 cm. All the patients had a smooth hospital discharge. Conclusion A novel robotic gastrectomy with intracorporeal π-shaped EJS for esophagojejunal anastomosis described and shows acceptable resulted. This technique has the potential to offer better short-term surgical outcomes and overcomes the drawbacks of laparoscopy with a decreased risk of complications during and after surgery.

Objective To explore the relationship between the omentin-1 gene rs2274907 A>T polymorphism and colorectal cancer (CRC) in the Chinese Han population. Methods rs2274907 A>T was assessed by PCR–restriction fragment length polymorphism analysis. Plasma omentin-1 expression from 358 patients with CRC and 286 healthy controls was analyzed by enzyme-linked immunosorbent assay. CRC and control groups were divided into subgroups according to the body mass index (BMI) threshold of 25 kg/m 2 . Results No significant differences were observed between CRC and control groups in terms of genotype or allele frequencies of rs2274907 A>T. Compared with individuals with BMI T polymorphism does not seem to play a critical role in the development of CRC in the Chinese Han population, but an interaction between the rs2274907 A allele and BMI may increase the CRC risk. The rs2274907 AA genotype is a potential biomarker for CRC stage progression.

Recently, 3D-printed polyether-ether-ketone (PEEK) components have been shown to offer many applications in state-of-the-art electronics, 5G wireless communications, medical implantations, and aerospace components. Nevertheless, a critical barrier that limits the application of 3D printed PEEK components is their weak interfacial bonding strength. Herein, we propose a novel method to improve this unsatisfied situation via the interface plasticizing effect of benzene derivatives obtained from the thermal pyrolysis of trisilanolphenyl polyhedral oligomeric silsequioxane (POSS). Based on this method, the bonding strength of the filaments and interlayers of 3D-printed POSS/PEEK components can reach 82.9 MPa and 59.8 MPa, respectively. Moreover, the enhancing mechanism of the pyrolysis products derived from the POSS is characterized using pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS), Fourier transform infrared spectroscopy (FTIR), and X-ray computed tomography (X-CT). Our proposed strategy broadens the novel design space for developing additional 3D-printed materials with satisfactory interfacial bonding strength.

In order to obtain the accurate contact parameters in the simulation process of powder screw conveying, this paper took wheat flour as an example, based on the discrete element JKR (Johnson-Kendall-Roberts) contact model, and directly calibrated the simulation contact parameters in the process of screw conveying in response to the mass flow rate of wheat flour. Firstly, the simulation density of wheat flour particles was calibrated, and the simulation density of wheat flour particles was 1320 kg/m. Then, Plackett-Burman experiment was used to screen out the parameters that had significant influence on the mass flow rate: surface energy JKR, coefficient of static friction between wheat flour and wheat flour, and the coefficient of static friction between wheat flour and stainless steel. The second-order regression model of mass flow rate and significance parameters was established and optimized based on Box-Behnken experiment, and the optimal combination of significance parameters: JKR was obtained to be 0.364; the static friction coefficient of wheat flour to wheat flour was 0.437; and the static friction coefficient of wheat flour to stainless steel was 0.609. Finally, the calibration parameters were used for simulation. By comparing the mass flow rate of simulation and experiment, the relative error of the two was 1.37%. The simulation and experiment flow rate values at different rotating speeds (60 r/min, 80 r/min, 100 r/min, 120 r/min, and 140 r/min) were further compared, and the errors were all within 3%. The method of directly calibrating the simulation contact parameters through the screw conveying process can improve the accuracy of screw conveying simulation, and providing a method and basis for powder contact parameters calibration and screw conveying simulation of wheat flour.

In the present work, heat transfer and fluid flow and their effects on entropy generation in a realistic catalytic converter of a Lada Niva 21214 vehicle are studied using large eddy simulation. At first, the pressure drop over the catalytic converter is measured for dry air at constant temperature (T=298 K), different volumetric flow rates, and extrapolated to large volumetric flow rates for dry air (T=298 K) and for the exhaust gas under realistic engine conditions (T=900 K) using the Darcy–Forchheimer relation. Then, coupled heat and fluid flow phenomena inside the catalytic converter are analyzed for nonreacting isothermal conditions and nonreacting conditions with conjugate heat transfer by using the large-eddy simulation. The predicted pressure drop agrees well with the measured and extrapolated data. Based on the obtained numerical results, the characteristic flow features are identified, namely: the impinging flow with stagnation, recirculation, flow separation and laminarization within the fine ducts of the monolith, which depends on the heat transfer through temperature-dependent thermophysical properties of exhaust gas. Moreover, due to high-velocity gradients at the wall of the narrow ducts in the monolith, entropy production by viscous dissipation is observed predominantly in the monolith region. In contrast, entropy production due to heat transport is relatively small in the monolith region, while it overwhelms viscous dissipation effects in the pipe regions.

Tassel branch number (TBN) is one of the important agronomic traits that contribute to the efficiency of seed production and has been selected strongly during the modern maize breeding process. However, the genetic mechanisms of TBN in maize are not entirely clear. In this study, we used a B73 × CML247 recombination inbred lines (RILs) population to detect quantitative trait loci (QTLs) for TBN. A total of four QTLs (qTBN2a, qTBN2b, qTBN4, and qTBN6) and six candidate genes were identified through expression analysis. Further, one of the candidates (GRMZM2G010011, ZmPAT7) encoding an S-acyltransferase was selected to validate its function by CRISPR-Cas9 technology, and its loss-of-function lines showed a significant increase in TBN. A key SNP(−101) variation in the promoter of ZmPAT7 was significantly associated with TBN. A total of 17 distant eQTLs associated with the expression of ZmPAT7 were identified in expression quantitative trait loci (eQTL) analysis, and ZmNAC3 may be a major factor involved in regulating ZmPAT7. These findings of the present study promote our understanding of the genetic basis of tassel architecture and provide new gene resources for maize breeding improvement.

Safety assessment of genetically modified (GM) crops is crucial at the product-development phase before GM crops are placed on the market. Determining characteristics of sequences flanking exogenous insertion sequences is essential for the safety assessment and marketing of transgenic crops. In this study, we used genome walking and whole-genome sequencing (WGS) to identify the flanking sequence characteristics of the SbSNAC1 transgenic drought-tolerant maize line "SbSNAC1-382", but both of the two methods failed. Then, we constructed a genomic fosmid library of the transgenic maize line, which contained 4.18×105 clones with an average insertion fragment of 35 kb, covering 5.85 times the maize genome. Subsequently, three positive clones were screened by pairs of specific primers, and one of the three positive clones was sequenced by using single-molecule real-time (SMRT) sequencing technology. More than 1.95 Gb sequence data (~105× coverage) for the sequenced clone were generated. The junction reads mapped to the boundaries of T-DNA, and the flanking sequences in the transgenic line were identified by comparing all sequencing reads with the maize reference genome and the sequence of the transgenic vector. Furthermore, the putative insertion loci and flanking sequences were confirmed by PCR amplification and Sanger sequencing. The results indicated that two copies of the exogenous T-DNA fragments were inserted at the same genomic site, and the exogenous T-DNA fragments were integrated at the position of Chromosome 5 from 177155650 to 177155696 in the transgenic line 382. In this study, we demonstrated the successful application of the SMRT technology for the characterization of genomic insertion and flanking sequences.

Abstract In this paper, we use a monotone iterative technique in the presence of lower and upper solutions to discuss the existence and uniqueness of periodic solutions for a class of fractional differential equations in an ordered Banach space E. Under some monotonicity conditions and noncompactness measure conditions of nonlinearity, we obtain the existence of extremal solutions and a unique solution between lower and upper solutions.

Abstract In this paper we consider the existence of positive solutions of nth-order Sturm–Liouville boundary value problems with fully nonlinear terms, in which the nonlinear term f involves all of the derivatives u′,…,u(n−1) $u',\ldots, u^{(n-1)}$ of the unknown function u. Such cases are seldom investigated in the literature. We present some inequality conditions guaranteeing the existence of positive solutions. Our inequality conditions allow that f(t,x0,x1,…,xn−1) $f(t, x_{0}, x_{1},\ldots, x_{n-1})$ is superlinear or sublinear growth on x0,x1,…,xn−1 $x_{0}, x_{1},\ldots, x_{n-1}$. Our discussion is based on the fixed point index theory in cones.

This paper deals with the existence of positive $ømega$-periodic solutions for the neutral functional differential equation with multiple delays (u(t)-cu(t-\delta))'+a(t) u(t)=f(t, u(t-\tau_1), \cdots, u(t-\tau_n)). The essential inequality conditions on the existence of positive periodic solutions are obtained. These inequality conditions concern with the relations of $c$ and the coefficient function $a(t)$, and the nonlinearity $f(t, x_1,\cdots, x_n)$. Our discussion is based on the perturbation method of positive operator and fixed point index theory in cones.

In this paper, advanced wall-modeled large eddy simulation (LES) techniques are used to predict conjugate heat transfer processes in turbulent channel flow. Thereby, the thermal energy transfer process involves an interaction of conduction within a solid body and convection from the solid surface by fluid motion. The approaches comprise a two-layer RANS–LES approach (zonal LES), a hybrid RANS–LES representative, the so-called improved delayed detached eddy simulation method (IDDES) and a non-equilibrium wall function model (WFLES), respectively. The results obtained are evaluated in comparison with direct numerical simulation (DNS) data and wall-resolved LES including thermal cases of large Reynolds numbers where DNS data are not available in the literature. It turns out that zonal LES, IDDES and WFLES are able to predict heat and fluid flow statistics along with wall shear stresses and Nusselt numbers accurately and that are physically consistent. Furthermore, it is found that IDDES, WFLES and zonal LES exhibit significantly lower computational costs than wall-resolved LES. Since IDDES and especially zonal LES require considerable extra work to generate numerical grids, this study indicates in particular that WFLES offers a promising near-wall modeling strategy for LES of conjugated heat transfer problems. Finally, an entropy generation analysis using the various models showed that the viscous entropy production is zero inside the solid region, peaks at the solid–fluid interface and decreases rapidly with increasing wall distance within the fluid region. Except inside the solid region, where steep temperature gradients lead to high (thermal) entropy generation rates, a similar behavior is monitored for the entropy generation by heat transfer process.

Abstract Background The aberrant expression of microRNA-140-5p (miR-140-5p) has been described in gastric cancer (GC). However, the role of miR-140-5p in GC remains unclear. In this study, the prognostic relevance of miR-140-5p in GC was investigated and YES1 was identified as a novel target of miR-140-5p in regulating tumor progression. Methods miR-140-5p level was determined in 20 paired frozen specimens through quantitative real-time PCR, and analyzed in tissue microarrays through in situ hybridization. The target of miR-140-5p was verified through a dual luciferase reporter assay, and the effects of miR-140-5p on phenotypic changes in GC cells were investigated in vitro and in vivo. Results Compared with that in adjacent normal tissues, miR-140-5p expression decreased in cancerous tissues. The downregulated miR-140-5p in 144 patients with GC was significantly correlated with the reduced overall survival of these patients. miR-140-5p could inhibit GC cell proliferation, migration and invasion by directly targeting 3′–untranlated region of YES1. miR-140-5p could also remarkably reduce the tumor size in GC xenograft mice. Conclusions miR-140-5p serves as a potential prognostic factor in patients with GC, and miR-140-5p mediated YES1 inhibition is a novel mechanism behind the suppressive effects of miR-140-5p in GC.

Abstract Introduction Ginseng polysaccharide (GPS, same as Panax polysaccharide) is a kind of polysaccharide extracted from ginseng. It has been reported that GPS has the ability to activate innate immunity, regulates blood sugar balance, and improves antioxidant capacity, but the effect on feeding behavior and its mechanism remains unclear. Method To investigate the possible effect of GPS on feeding behavior of animals, mice were supplied with GPS in water, and food intake, hedonic feeding behavior, anxiety‐like behavior, expression of appetite‐regulation peptides in the central nervous system and glucose‐related hormone levels in the serum of mice were measured. Results Ginseng polysaccharide significantly increased the average daily food intake in mice and promoted hedonic eating behavior. Meanwhile, the levels of serum glucose and glucagon were significantly reduced by GPS, and GPS promoted hypothalamic neuropeptide Y expression, inhibited proopiomelanocortin (POMC) expression, and reduced dopamine D1 receptor (DRD1) levels in the midbrain. We also found that the anxiety level of mice was significantly lower after GPS intake. In conclusion, oral supplementation with GPS promoted food intake in mice, most likely through the regulation of circulating glucose levels.

Drought has become one of the most serious abiotic stresses influencing crop production worldwide. Understanding the molecular regulatory networks underlying drought adaption and tolerance in crops is of great importance for future breeding. microRNAs (miRNAs), as important components of post-transcriptional regulation, play crucial roles in drought response and adaptation in plants. Here, we report a miRNome analysis of two maize inbred lines with contrasting levels of drought tolerance under soil drought in the field. Differential expression analysis showed 11 and 34 miRNAs were uniquely responded to drought in H082183 (drought tolerant) and Lv28 (drought sensitive), respectively, in leaves. In roots, 19 and 23 miRNAs uniquely responded to drought in H082183 and Lv28, respectively. Expression analysis of these drought-responsive miRNA-mRNA modules revealed miR164-MYB, miR164-NAC, miR159-MYB, miR156-SPL and miR160-ARF showed a negative regulatory relationship. Further analysis showed that the miR164-MYB and miR164-NAC modules in the tolerant line modulated the stress response in an ABA (abscisic acid)-dependent manner, while the miR156-SPL and miR160-ARF modules in the sensitive line participated in the inhibition of metabolism in drought-exposed leaves. Together, our results provide new insight into not only drought-tolerance-related miRNA regulation networks in maize but also key miRNAs for further characterization and improvement of maize drought tolerance.

This paper deals with the existence of ω-periodic solutions for nth-order ordinary differential equation involving fixed delay in Banach space E. Lnu(t)=f(t,u(t),u(t−τ)),t∈R, where Lnu(t):=u(n)(t)+∑i=0n−1aiu(i)(t), ai∈R, i=0,1,⋯,n−1, are constants, f(t,x,y):R×E×E⟶E is continuous and ω-periodic with respect to t, τ>0. By applying the approach of upper and lower solutions and the monotone iterative technique, some existence and uniqueness theorems are proved under essential conditions.

We consider the existence of a mild solution of supdiffusion equations and obtain some results under some growth and noncompactness conditions of nonlinearity without coefficient restriction; and some new results for Ulam-Hyers-Rassias stability are obtained.

In this article, we study the existence of piecewise-continuous mild solutions for the initial value problems for a class of semilinear evolution equations. These equations have non-instantaneous impulses in Banach spaces and the corresponding solution semigroup is noncompact. We assume that the nonlinear term satisfies certain local growth condition and a noncompactness measure condition. Also we assume the non-instantaneous impulsive functions satisfy some Lipschitz conditions. An example is given to illustrate our results.

We consider the existence and uniqueness of the saturated classical solutions and the positive classical solutions to initial boundary value problems of semi-linear sub-diffusion with gradient terms. Applying this to the fractional power of the sectorial operator theory and the imbedding theory in the interpolation spaces, where the nonlinear term satisfies more general conditions, we obtain the existence and uniqueness of the saturated classical solutions. The results obtained generalize the recent conclusions on this topic. Finally, an example is given to illustrate the feasibility of our main results.

In this paper, we compare the capabilities of two open source near-wall-modeled large eddy simulation (NWM-LES) approaches regarding prediction accuracy, computational costs and ease of use to predict complex turbulent flows relevant to internal combustion (IC) engines. The applied open source tools are the commonly used OpenFOAM, based on the finite volume method (FVM), and OpenLB, an implementation of the lattice Boltzmann method (LBM). The near-wall region is modeled by the Musker equation coupled to a van Driest damped Smagorinsky-Lilly sub-grid scale model to decrease the required mesh resolution. The results of both frameworks are compared to a stationary engine flow bench experiment by means of particle image velocimetry (PIV). The validation covers a detailed error analysis using time-averaged and root mean square (RMS) velocity fields. Grid studies are performed to examine the performance of the two solvers. In addition, the differences in the processes of grid generation are highlighted. The performance results show that the OpenLB approach is on average 32 times faster than the OpenFOAM implementation for the tested configurations. This indicates the potential of LBM for the simulation of IC engine-relevant complex turbulent flows using NWM-LES with computationally economic costs.