Chronic pancreatitis (CP) is a chronic inflammatory disease of the pancreas. This study aimed to compare the natural course of alcoholic chronic pancreatitis (ACP) and idiopathic chronic pancreatitis ...(ICP).
CP patients admitted to our center from January 2000 to December 2013 were enrolled. Characteristics were compared between ACP and ICP patients. Cumulative rates of diabetes mellitus (DM), steatorrhea, pancreatic stone, pancreatic pseudocyst, biliary stricture, and pancreatic cancer after the onset and the diagnosis of CP were calculated, respectively. The cumulative rates of DM and steatorrhea after diagnosis of pancreatic stone were also calculated.
A total of 2,037 patients were enrolled. Among them, 19.8% (404/2,037) were ACP and 80.2% (1,633/2,037) were ICP patients. ACP and ICP differs in many aspects, especially in gender, age, smoking, complications, morphology of pancreatic duct, and type of pain. The development of DM, steatorrhea, PPC, pancreatic stone, and biliary stricture were significantly earlier and more common in ACP patients. No significant difference was observed for pancreatic cancer development. There was a rather close correlation between exocrine/endocrine insufficiency and pancreatic stone in ACP patients, which was much less correlated in ICP patients.
The long-term profile of ACP and ICP differs in some important aspects. ACP patients usually have a more severe course of CP. These differences should be recognized in the diagnosis and treatment of CP.
Chronic pancreatitis (CP) is characterized by persistent inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement ...with fibrotic tissue. Currently, the clinical therapeutic scheme of CP is mainly symptomatic treatment including pancreatic enzyme replacement, glycaemic control and nutritional support therapy, lacking of specific therapeutic drugs for prevention and suppression of inflammation and fibrosis aggravating in CP. Here, we investigated the effect of isoliquiritigenin (ILG), a chalcone‐type dietary compound derived from licorice, on pancreatic fibrosis and inflammation in a model of caerulein‐induced murine CP, and the results indicated that ILG notably alleviated pancreatic fibrosis and infiltration of macrophages. Further in vitro studies in human pancreatic stellate cells (hPSCs) showed that ILG exerted significant inhibition on the proliferation and activation of hPSCs, which may be due to negative regulation of the ERK1/2 and JNK1/2 activities. Moreover, ILG significantly restrained the M1 polarization of macrophages (RAW 264.7) via attenuation of the NF‐κB signalling pathway, whereas the M2 polarization was hardly affected. These findings indicated that ILG might be a potential anti‐inflammatory and anti‐fibrotic therapeutic agent for CP.
Perovskite solar cells (PSCs) may offer huge potential in photovoltaic conversion, yet their practical applications face one major obstacle: their low stability, or quick degradation of their initial ...efficiencies. Here, a new design scheme is presented to enhance the PSC stability by using low‐temperature hydrothermally grown hierarchical nano‐SnO2 electron transport layers (ETLs). The ETL contains a thin compact SnO2 layer underneath a mesoporous layer of SnO2 nanosheets. The mesoporous layer plays multiple roles of enhancing photon collection, preventing moisture penetration and improving the long‐term stability. Through such simple approaches, PSCs with power conversion efficiencies of ≈13% can be readily obtained, with the highest efficiency to be 16.17%. A prototypical PSC preserves 90% of its initial efficiency even after storage in air at room temperature for 130 d without encapsulation. This study demonstrates that hierarchical SnO2 is a potential ETL for fabricating low‐cost and efficient PSCs with long‐term stability.
Low‐temperature hydrothermally grown hierarchical SnO2
, a mesoporous layer of nanosheet arrays on a compact nanoparticle layer, is used as the electron transporting layer to enhance the long‐term stability of perovskite solar cells. A mesoporous device preserves 90% of its initial efficiency, even after storage in air for 130 d without encapsulation.
Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in ...PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways. A subsequent study confirmed that CHD1 deletion significantly upregulated hypoxia-inducible factor 1α (HIF1α) expression. Mechanistic investigation revealed that CHD1 deletion upregulated HIF1α by transcriptionally downregulating prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase catalyzing the hydroxylation of HIF1α and thus promoting its degradation by the E3 ligase von Hippel-Lindau tumor suppressor (VHL). Functional analysis showed that CHD1 deletion promoted angiogenesis and glycolysis, possibly through HIF1α target genes. Taken together, these findings indicate that CHD1 deletion enhances HIF1α expression through PHD2 downregulation and therefore promotes angiogenesis and metabolic reprogramming in PCa.
Strengthening concrete structures with ultra-high performance concrete (UHPC) can both improve the bearing capacity of the original normal concrete (NC) structure and prolong the service life of the ...structure due to the high strength and durability of UHPC. The key to the synergistic work of the UHPC-strengthened layer and the original NC structures lies in the reliable bonding of their interfaces. In this research study, the shear performance of the UHPC-NC interface was investigated by the direct shear (push-out test) test method. The effects of different interface preparation methods (smoothing, chiseling, and planting straight and hooked rebars) and different aspect ratios of planted rebars on the failure mode and shear performance of the pushed-out specimens were studied. Seven groups of push-out specimens were tested. The results show that the interface preparation method can significantly affect the failure mode of the UHPC-NC interface, which is specifically divided into interface failure, planted rebar pull-out, and NC shear failure. The critical aspect ratio for the pull-out or anchorage of planted rebars in UHPC is around 2. The interface shear strength of straight-planted rebar interface preparation is significantly improved compared with that of the chiseled and smoothened interfaces, and as the embedding length of the planted rebar becomes longer, it first increases greatly and then tends to be stable when the rebar planted in UHPC is fully anchored. The shear stiffness of UHPC-NC increases with the increase of the aspect ratio of planted rebars. A design recommendation based on the experimental results is proposed. This research study supplements the theoretical basis of the interface design of UHPC-strengthened NC structures.
This study identifies implications of dark tourism and describes how tourists and destinations, which are principal collateral cores, define what constitutes “dark” travel. The study also examines ...the dimensions of dark tourism motivation and experience and finds that the former partly affects the latter. The exploratory factor analysis and confirmatory factor analysis aimed to examine why tourists approach and engage with disaster sites and how such experiences may affect tourists motivation and emotional reaction. It is the first paper that applies structural equation modelling to dark tourism research. We focus on the causal relationships between dimensions of motivation and experience, and the relationship that the emotional reactions effect on tourist experiences. We find that the curious visitors are likely to engage cognitively by learning about the incident or related issues and tourists' emotional reaction to the “dark” space influence more heavily emotional tourist experiences than cognitive experiences do.
•Our study focuses on the motivation–experience relationship and the regulatory function of emotional reaction.•Implications of dark tourism are identified.•Tourists' emotional reactions influence more heavily emotional tourist experiences than cognitive experiences do.•The curious visitors are likely to engage cognitively by learning about the incident or related issues.•Not all tourists visit the dark tourism destination for dark tourism.
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Chronic pancreatitis (CP) is characterized by persistent inflammation and fibrosis of the pancreas. To date, no clinical therapy is available to reverse the inflammatory damage or ...pancreatic fibrosis associated with CP. This study systematically investigated the effect of Dasatinib, a multiple tyrosine kinases (TKs) inhibitor, on pancreatic fibrosis and inflammation in vivo and in vitro. We found that Dasatinib notably ameliorated pancreatic fibrosis and infiltration of macrophages in a model of caerulein-induced murine CP. Further RNA-seq and phosphoproteomic analysis and in vitro validation assays indicated that Dasatinib exerted a marked inhibition on the proliferation and activation of PSCs, which may be resulted from increased GSK3β-mediated β-catenin cytosol retention by inhibiting upstream multiple TKs (such as PDGFR and Src) and MAPK cascades (including ERK1/2 and p38 MAPK). In addition, Dasatinib significantly restrained both the M1 and M2 polarization of macrophages, and impeded its recruitment and crosstalk with PSCs. Our findings indicated that Dasatinib is a potential anti-inflammatory and anti-fibrotic therapeutic strategy for CP.
Modern tropical rainforests have the highest biodiversity of terrestrial biomes and are restricted to three low-latitude areas. However, the actual timeframe during which tropical rainforests began ...to appear on a global scale has been intensely disputed. Here, we used the moonseed family (Menispermaceae), an important physiognomic and structural component of tropical rainforests on a worldwide basis, to obtain new insights into the diversification of this biome.
We integrated phylogenetic, biogeographic and molecular dating methods to analyse temporal and spatial patterns of global diversification in Menispermaceae.
Importantly, a burst of moonseed diversification occurred in a narrow window of time, which coincides with the Cretaceous–Paleogene (K–Pg) boundary. Our data also suggest multiple independent migrations from a putative ancestral area of Indo-Malay into other tropical regions.
Our data for Menispermaceae suggest that modern tropical rainforests may have appeared almost synchronously throughout the three major tropical land areas close to, or immediately following, the K–Pg mass extinction.
Developing nonspecific, fast, and strong adhesives that can glue hydrogels and biotissues substantially promotes the application of hydrogels as biomaterials. Inspired by the ubiquitous adhesiveness ...of bacteria, it is reported that neutral polyampholyte hydrogels, through their self‐adjustable surface, can show rapid, strong, and reversible adhesion to charged hydrogels and biological tissues through the Coulombic interaction.
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•Pirfenidone alleviated pancreatic fibrosis and inflammation in a murine model.•Pirfenidone suppressed ECM production in PSCs via TGF-β/Smad pathway.•Pirfenidone inhibited PSCs ...activation and proliferation via Wnt/β-catenin pathway.•Pirfenidone reduced pro-inflammatory cytokine expression via JAK1/STAT3 pathway.•Pirfenidone restrained the M1 polarization of macrophages via STAT3-related pathway.
In the realm of fibroinflammatory conditions, chronic pancreatitis (CP) stands out as a particularly challenging ailment, lacking a dedicated, approved treatment. The potential of Pirfenidone (PFD), a drug originally used for treating idiopathic pulmonary fibrosis (IPF), in addressing CP's fibrotic aspects has sparked new interest. This investigation focused on the role of PFD in diminishing fibrosis and immune response in CP, using a mouse model induced by caerulein. The research extended to in vitro studies examining the influence of PFD on pancreatic stellate cells' (PSCs) behavior and the polarization of macrophages into M1 and M2 types. Advanced techniques like RNA sequencing and comprehensive data analyses were employed to decode the molecular interactions of PFD with PSCs. Supplementary experiments using techniques such as quantitative real-time PCR, western blotting, and immunofluorescence were also implemented. Results showed a notable reduction in pancreatic damage in PFD-treated mice, manifested through decreased acinar cell atrophy, lower collagen deposition, and a reduction in macrophage presence. Further investigation revealed PFD's capacity to hinder PSCs' migration, growth, and activation, alongside a reduction in the production and secretion of extracellular matrix proteins. This effect is primarily achieved by interfering with signaling pathways such as TGF-β/Smad, Wnt/β-catenin, and JAK/STAT. Additionally, PFD selectively hampers M1 macrophage polarization through the STAT3 pathway, without impacting M2 polarization. These outcomes highlight PFD's dual mechanism in moderating PSC activity and M1 macrophage polarization, positioning it as a promising candidate for CP therapy.
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