Cancer-associated fibroblasts (CAFs) are considered one of the most critical stromal cells that interact with pancreatic ductal adenocarcinoma (PDAC) and promote tumor growth, metastasis, and treatment resistance. Previous studies illustrated macroautophagy/autophagy contributes to CAF activation during tumor progression. Here in our study, we found that autophagy deficiency in CAFs impedes CAF activation by inhibiting proline biosynthesis and collagen production. Furthermore, we uncovered that autophagy promotes proline biosynthesis through mitophagy-mediated regulation of NADK2 (NAD kinase 2,...

The growth of the manufacturing industry is the engine of rapid economic growth in developing regions. Characterizing the geographical distribution of manufacturing firms is critically important for scientists and policymakers. However, data on the manufacturing industry used in previous studies either have a low spatial resolution (or fuzzy classification) or high-resolution information is lacking. Here, we propose a map point-of-interest classification method based on machine learning technology and build a dataset of the distribution of...

The evolution of the Tethys is one of the key issues in revealing the global ocean-continent transition tectonic process. The East Kunlun Orogenic Belt (E-KOB) in the northern Tibetan Plateau witnessed the subduction-accretion process of the Proto- and Palaeo-Tethyan Oceans formed a trench-arc-back arc basin system. Thus, this back arc basin is a window for exploring the tectonic evolution of the Tethys. In this study, the Adatan garnet amphibolites and the host paragneiss were investigated...

Collaborative geographic analysis can lead to better outcomes but requires complicated interactions among participants, support resources and analytic tools. A process expression with explicit structure and content can help coordinate and guide these interactions. For different geographic problems, the structure and content of collaborative geographic analysis are generally distinct. Since the process structure embodies the pathway of problem-solving and the process content contains the information flow and internal interactions, both the structure and the content...

Purpose: The aim of the present study was to investigate the injuries of spleen and intestinal immune system induced by 2 Gy 60Co γ ray in mice. Materials and methods: A total of 120 Balb/c mice were randomly divided into two groups: blank control (Ctrl) and model (IR). The IR mice were exposed to a single dose of total body irradiation (2 Gy, dose rate: 1 Gy/min) and sacrificed on 1st, 3rd, 7th, 14th and...

Increasing uranium (U) content in soils due to anthropogenic U contamination causes accumulation of U in plants, which greatly increases human health risks. This review identified the diverse sources of soil U contamination and their significant spatial variations in surface soils globally based on 789 soil sampling sites collected from 76 studies. The relationships between U biogeochemical transformation and its bioavailability in soil are significantly affected by soil redox potential, pH, metal (hydr)oxides, organic matter,...

PCGEM1 facilitates prostate cancer (PCa) progression. This study aimed to elucidate the mechanism of action of PCGEM1 in PCa. The expression of PCGEM1, microRNA miR-129-5p, chromatin licensing, and DNA replication factor 1 (CDT1) was detected by quantitative reverse transcription-PCR (qRT-PCR). A series of function experiments including cell counting kit-8 (CCK-8), caspase-3 activity, and cell cycle assays were performed to evaluate the influence of PCGEM1, miR-129-5p, and CDT1 on the biological processes of PCa cells. CyclinD1,...

The late Paleozoic tectonic evolution of the Lhasa terrane and subduction of Sumdo Paleo-Tethys ocean remains controversial due to limited data and variable Permian magmatism in central and southern Lhasa. We report new zircon U–Pb ages and Hf-isotope ratios as well as whole-rock major element, trace element, and Sr–Nd isotope data from middle Permian (266 ~ 257 Ma) arc-related magmatism, including high-Mg quartz diorite and trondhjemite in the Tangjia-Sumdo area. The quartz diorite has high...

Ischemia–reperfusion injury (IRI) is one of the major causes of acute kidney injury (AKI). tRNA derived fragments (tRFs/tiRNAs) are groups of small noncoding RNAs derived from tRNAs. To date, the role of tRFs/tiRNAs in renal IRI has not been reported. Herein, we aimed to investigate the involvement of tRFs/tiRNAs in the occurrence and development of ischemia–reperfusion-induced AKI. Moderate/severe renal IRI mouse models were established by bilateral renal pedicle clamping. The tRF/tiRNA profiles of healthy controls...

Ischemia–reperfusion injury (IRI) is one of the major causes of acute kidney injury (AKI). tRNA derived fragments (tRFs/tiRNAs) are groups of small noncoding RNAs derived from tRNAs. To date, the role of tRFs/tiRNAs in renal IRI has not been reported. Herein, we aimed to investigate the involvement of tRFs/tiRNAs in the occurrence and development of ischemia–reperfusion-induced AKI. Moderate/severe renal IRI mouse models were established by bilateral renal pedicle clamping. The tRF/tiRNA profiles of healthy controls...

Recent research unveiled that LINC00857 plays a regulatory role in multiple human cancers, such as lung adenocarcinoma and gastric cancer. Nevertheless, the function of LINC00857 in pancreatic adenocarcinoma (PAAD) remains unclear. This study concentrates on LINC00857 to discuss the relevant molecular mechanism of this gene in PAAD. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot were implemented for measuring the expressions of RNAs and proteins. Wound healing and Transwell assays were used to...

We introduce a pair of Shiny web applications that allow users to visualize random forest prediction intervals alongside those produced by linear regression models. The apps are designed to help undergraduate students deepen their understanding of the role that assumptions play in statistical modeling by comparing and contrasting intervals produced by regression models with those produced by more flexible algorithmic techniques. We describe the mechanics of each approach, illustrate the features of the apps, provide...

We introduce a pair of Shiny web applications that allow users to visualize random forest prediction intervals alongside those produced by linear regression models. The apps are designed to help undergraduate students deepen their understanding of the role that assumptions play in statistical modeling by comparing and contrasting intervals produced by regression models with those produced by more flexible algorithmic techniques. We describe the mechanics of each approach, illustrate the features of the apps, provide...

Modeling and inference for heterogeneous data have gained great interest recently due to rapid developments in personalized marketing. Most existing regression approaches are based on the conditional mean and may require additional cluster information to accommodate data heterogeneity. In this article, we propose a novel nonparametric resolution-wise regression procedure to provide an estimated distribution of the response instead of one single value. We achieve this by decomposing the information of the response and the predictors...

High-grade serous ovarian cancer (HGSOC) is the most common and malignant type of ovarian cancer, accounting for 70%–80% of mortality. However, the treatment of HGSOC has improved little in the past few decades. Metformin is the first-line medication for the treatment of type 2 diabetes and has now gained more attention in cancer treatment. In this study, we sought to identify potential hub genes that metformin could target in the treatment of HGSOC. We downloaded...

Additional file 10. A excel file that includes the values of data points in all figures

Combining individual p-values to perform an overall test is often encountered in statistical applications. The Cauchy combination test (CCT) (Journal of the American Statistical Association, 2020, 115, 393–402) is a powerful and computationally efficient approach to integrate individual p-values under arbitrary dependence structures for sparse signals. We revisit this test to additionally show that (i) the tail probability of the CCT can be approximated just as well when more relaxed assumptions are imposed on individual...

Objectives: Spinal cord injury (SCI) is a most debilitating traumatic injury, and cytotherapy is a promising alternative treatment strategy. Here we investigated the effect and mechanism of adipose-derived stem/stromal cells (ASCs) with overexpressing brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) (BDNF-NT3) in combination with silk fibroin/chitosan scaffold (SFCS) in SCI. Methods: Female Sprague-Dawley rats were used as an SCI model. SFCS,SFCS and ASCs, or ASCs overexpressing NT3, BDNF, and BDNF-NT3 were implanted into SCI rats....

Additional file 2: Supplementary Table 1. The results of the GSEA.

Additional file 2: Supplementary Table 1. The results of the GSEA.

Additional file 4: Table S8. Associations between genetically inferred ancestry and phecodes within ATLAS while adjusting for SIRE.

Additional file 8: Table S12. Effective sample sizes and effect sizes of correlated phenotypes for chronic nonalcoholic liver disease. Table S13. Role of phecode occurrences for defining cases. Table S14. Summary of methods. Table S15. Comparison of GIA clusters when restricting to unrelated individuals. Table S16. Comparison of genetic ancestry proportions within SIREs when using unrelated individuals.

Acinetobacter baumannii has become a major healthcare threat that causes nosocomial infections, especially in critically ill patients. The spread of carbapenem-resistant A. baumannii (CRAB) strains has long been a clinical concern. It is important to study the epidemiology and virulence characteristics of different CRAB isolates in order to tailor infection prevention and antibiotic prescribing. In this study, a total of 71 CRAB isolates were collected in the hospital, and clinical characteristics of infections were analyzed....

Vascular aging has been closely associated with various cardiovascular disorders; however, its molecular mechanism remains poorly understood. In our study, RNA sequencing was utilized to explore the expression profiles of long non-coding RNAs (lncRNAs) and mRNAs in the thoracic aortas of young (3 weeks) and old (16 weeks) rats. Functional categorization of differentially expressed mRNAs was evaluated using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases, and lncRNA–microRNA–mRNA networks was constructed using...

Excessive activation of signal transducer and activator of transcription 3 (STAT3) is implicated in breast cancer (BC) chemoresistance, but its underlying mechanism is not fully understood. There are STAT3 binding sites in fat mass and obesity-associated protein (FTO) promoter region, thus STAT3 may regulate the transcription of FTO. This study aimed to investigate the correlation between FTO and STAT3 in BC chemoresistance. Herein, FTO and STAT3 were highly expressed in doxorubicin-resistant BC (BC-DoxR) cells. CHIP...