Triple positive solutions for semipositone fractional differential equations m-point boundary value problems with singularities and p–q-order derivatives

In this paper, by means of Leggett–Williams and Guo–Krasnosel'skii fixed point theorems, together with height functions of the nonlinearity on different bounded sets, triple positive solutions are obtained for some fractional differential equations with p–q-order derivatives involved in multi-point boundary value conditions. The nonlinearity may not only take negative infinity but also may permit singularities on both the time and the space variables

Single-cell RNA sequencing reveals cell subpopulations in the tumor microenvironment contributing to hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is among the deadliest cancers worldwide, and advanced HCC is difficult to treat. Identifying specific cell subpopulations in the tumor microenvironment and exploring interactions between the cells and their environment are crucial for understanding the development, prognosis, and treatment of tumors.Methods: In this study, we constructed a tumor ecological landscape of 14 patients with HCC from 43 tumor tissue samples and 14 adjacent control samples. We used bioinformatics analysis to reveal cell subpopulations with potentially specific functions in the tumor microenvironment and to explore the interactions between tumor cells and the tumor microenvironment.Results: Immune cell infiltration was evident in the tumor tissues, and BTG1+RGS1+ central memory T cells (Tcms) interact with tumor cells through CCL5-SDC4/1 axis. HSPA1B may be associated with remodeling of the tumor ecological niche in HCC. Cancer-associated fibroblasts (CAFs) and macrophages (TAMs) were closely associated with tumor cells. APOC1+SPP1+ TAM secretes SPP1, which binds to ITGF1 secreted by CAFs to remodel the tumor microenvironment. More interestingly, FAP+ CAF interacts with naïve T cells via the CXCL12–CXCR4 axis, which may lead to resistance to immune checkpoint inhibitor therapy.Conclusion: Our study suggests the presence of tumor cells with drug-resistant potential in the HCC microenvironment. Among non-tumor cells, high NDUFA4L2 expression in fibroblasts may promote tumor progression, while high HSPA1B expression in central memory T cells may exert anti-tumor effects. In addition, the CCL5–SDC4/1 interaction between BTG1+RGS1+ Tcms and tumor cells may promote tumor progression. Focusing on the roles of CAFs and TAMs, which are closely related to tumor cells, in tumors would be beneficial to the progress of systemic therapy research

Identification of a novel microRNA-mRNA regulatory biomodule in human prostate cancer

Our recent study identified a list of differentially expressed microRNAs (miRNAs) in human prostate cancer (PCa) tissues compared to adjacent benign prostate tissues. In the current study, to identify the crucial miRNA–mRNA regulatory biomodule involved into prostate carcinogenesis based on the previous miRNA expression profile in PCa, we proposed an integrated systematic approach which combined miRNA-mediated gene expression regulatory network analysis, experimental validations in vitro and in vivo, as well as clinical significance evaluation. As a result, the CCND1-RNASEL-CDKN1A-TP73-MDM2-UBE2I axis was identified as a bottleneck in the miRNA-mediated gene expression regulatory network of PCa according to network topological analysis. The direct binding relationship between TP73 and PCa downregulated miR-193a-5p, and the direct binding relationship between UBE2I and PCa upregulated miR-188-5p were both experimentally validated. In addition, miR-193a-5p had a more significant regulatory effect on the tumor promoter isoform of TP73-deltaNp73 than on the tumor suppressive isoform of TP73-TAp73. Importantly, the deregulation of either the miR-193a-5p-TP73 or miR-188-5p-UBE2I axes was significantly associated with aggressive progression and poor prognosis in PCa patients. Gain- and loss-of-function experiments showed that miR-193a-5p efficiently inhibited in vitro PCa cell proliferation, migration, and invasion, and in vivo tumor growth, and markedly induced PCa cell apoptosis via regulating TP73 with a corresponding suppression of the CCND1-RNASEL-CDKN1A-MDM2 axis. In contrast, miR-188-5p exerted its tumor promoter roles through targeting UBE2I with a subsequent activation of the CCND1-RNASEL-CDKN1A-MDM2 axis. Taken together, this integrated analysis revealed the potential roles of the miR-193a-5p/TP73 and miR-188-5p/UBE2i negative regulation pairs in PCa. In addition to the significant clinical relevance, miR-193a-5p- and miR-188-5p-regulated CCND1-RNASEL-CDKN1A-TP73-MDM2-UBE2I signaling may be a novel regulatory biomodule in prostate carcinogenesis

A novel planarization method based on photoinduced confined chemical etching

National Science Foundation of China [91023043, 21021002, 91023006]A photoinduced confined chemical etching system based on TiO2 nanotube arrays is developed for the planarization of the copper surface, which is proved to be a prospective stress-free chemical planarization method for metals and semiconductors

TP53-related signature for predicting prognosis and tumor microenvironment characteristics in bladder cancer: A multi-omics study

Background: The tumor suppressor gene TP53 is frequently mutated or inactivated in bladder cancer (BLCA), which is implicated in the pathogenesis of tumor. However, the cellular mechanisms of TP53 mutations are complicated, yet well-defined, but their clinical prognostic value in the management of BLCA remains controversial. This study aimed to explore the role of TP53 mutation in regulating the tumor microenvironment (TME), elucidate the effects of TP53 activity on BLCA prognosis and immunotherapy response.Methods: A TP53-related signature based on TP53-induced and TP53-repressed genes was used to construct a TP53 activity-related score and classifier. The abundance of different immune cell types was determined using CIBERSORT to estimate immune cell infiltration. Moreover, the heterogeneity of the tumor immune microenvironment between the high and low TP53 score groups was further evaluated using single-cell mass cytometry (CyTOF) and imaging mass cytometry (IMC). Moreover, pathway enrichment analysis was performed to explore the differential biological functions between tumor epithelial cells with high and low TP53 activity scores. Finally, the receptor–ligand interactions between immune cells and tumor epithelial cells harboring distinct TP53 activity were analyzed by single-cell RNA-sequencing.Results: The TP53 activity-related gene signature differentiated well between TP53 functional retention and inactivation in BLCA. BLCA patients with low TP53 scores had worse survival prognosis, more TP53 mutations, higher grade, and stronger lymph node metastasis than those with high TP53 scores. Additionally, CyTOF and IMC analyses revealed that BLCA patients with low TP53 scores exhibited a potent immunosuppressive TME. Consistently, single-cell sequencing results showed that tumor epithelial cells with low TP53 scores were significantly associated with high cell proliferation and stemness abilities and strongly interacted with immunosuppressive receptor–ligand pairs.Conclusion: BLCA patients with low TP53 scores have a worse prognosis and a more immunosuppressive TME. This TP53 activity-related signature can serve as a potential prognostic signature for predicting the immune response, which may facilitate the development of new strategies for immunotherapy in BLCA

Multiple positive solutions to some second-order integral boundary value problems with singularity on space variable

Abstract This article deals with integral boundary value problems of the second-order differential equations { u ″ ( t ) + a ( t ) u ′ ( t ) + b ( t ) u ( t ) + f ( t , u ( t ) ) = 0 , t ∈ J + , u ( 0 ) = ∫ 0 1 g ( s ) u ( s ) d s , u ( 1 ) = ∫ 0 1 h ( s ) u ( s ) d s , $$\left \{ \textstyle\begin{array}{lcl} u''(t)+a(t)u'(t)+b(t)u(t)+f(t,u(t))=0,\quad t\in J_{+},\\ u(0)= \int_{0}^{1}g(s)u(s)\,\text{d}s,\qquad u(1)=\int _{0}^{1}h(s)u(s)\,\text{d}s, \end{array}\displaystyle \right .$$ where a ∈ C ( J ) $a\in C(J)$ , b ∈ C ( J , R − ) $b\in C(J, R_{-})$ , f ∈ C ( J + × R + , R + ) $f\in C(J_{+}\times R_{+}, R^{+})$ and g , h ∈ L 1 ( J ) $g, h\in L^{1}(J)$ are nonnegative. The result of the existence of two positive solutions is established by virtue of fixed point index theory on cones. Especially, the nonlinearity f permits the singularity on the space variable

Multiple positive solutions for singular higher-order semipositone fractional differential equations with p-Laplacian

In this article, together with Leggett–Williams and Guo–Krasnosel’skii fixed point theorems, height functions on special bounded sets are constructed to obtain the existence of at least three positive solutions for some higher-order fractional differential equations with p-Laplacian. The nonlinearity permits singularities both on the time and the space variables, and it also may change its sign

Analysing Drivers and Barriers of Accommodation Sharing in Dubai Using the Grey-DEMATEL Approach

The continuous growth of the sharing economy has the potential to transform the competition in the accommodation sector. At present, research on accommodation sharing is scarce. This paper identifies drivers and barriers to accommodation sharing in Dubai. Taking into account different viewpoints of accommodation sharing professionals in Dubai and the grey-based Decision-Making Trial and Evaluation Laboratory (DEMATEL) method, this study singles out the essential drivers and barriers and examines the cause and effect connections between them. The process starts with a review of the existing accommodation sharing literature and the feedback from the industry experts to identify the drivers and barriers. Then, the elaboration of the questionnaire, data collection from five experts, data analysis with grey-based DEMATEL, and the sensitivity analysis follow. The lower costs, higher value, ease of use, wealth of available information, and contributions to the development of the local economy and residents are the most influential drivers of accommodation sharing in Dubai. The difficulties related to learning and using new technology along with insufficient or underdeveloped accommodation sharing legislation are the most critical barriers. The paper ends with implications for the stakeholders, limitations, and future directions for research on accommodation sharing