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Pancreatic cancer remains one of the most lethal malignant diseases. Gemcitabine‐based chemotherapy is still one of the first‐line systemic treatments, but chemoresistance occurs in the majority of patients. Recently, accumulated evidence has demonstrated the role of the tumour microenvironment in promoting chemoresistance. In the tumour microenvironment, pancreatic stellate cells (PSCs) are among the main cellular components, and extracellular vesicles (EVs) are common mediators of cell‒cell communication. In this study, we showed that SP1‐transcribed miR‐31‐5p not only targeted LATS2 in pancreatic cancer cells but also regulated the Hippo pathway in PSCs through EV transfer. Consequently, PSCs synthesized and secreted protein acidic and rich in cysteins (SPARC), which was preferentially expressed in stromal cells, stimulating Extracellular Signal regulated kinase (ERK) signalling in pancreatic cancer cells. Therefore, pancreatic cancer cell survival and chemoresistance were improved due to both the intrinsic Hippo pathway regulated by miR‐31‐5p and external SPARC‐induced ERK signalling. In mouse models, miR‐31‐5p overexpression in pancreatic cancer cells promoted the chemoresistance of coinjected xenografts. In a tissue microarray, pancreatic cancer patients with higher miR‐31‐5p expression had shorter overall survival. Therefore, miR‐31‐5p regulates the Hippo pathway in multiple cell types within the tumour microenvironment via EVs, ultimately contributing to the chemoresistance of pancreatic cancer cells. [ABSTRACT FROM AUTHOR]

Amino acid metabolism plays a pivotal role in tumor microenvironment, influencing various aspects of cancer progression. The metabolic reprogramming of amino acids in tumor cells is intricately linked to protein synthesis, nucleotide synthesis, modulation of signaling pathways, regulation of tumor cell metabolism, maintenance of oxidative stress homeostasis, and epigenetic modifications. Furthermore, the dysregulation of amino acid metabolism also impacts tumor microenvironment and tumor immunity. Amino acids can act as signaling molecules that modulate immune cell function and immune tolerance within the tumor microenvironment, reshaping the anti-tumor immune response and promoting immune evasion by cancer cells. Moreover, amino acid metabolism can influence the behavior of stromal cells, such as cancer-associated fibroblasts, regulate ECM remodeling and promote angiogenesis, thereby facilitating tumor growth and metastasis. Understanding the intricate interplay between amino acid metabolism and the tumor microenvironment is of crucial significance. Expanding our knowledge of the multifaceted roles of amino acid metabolism in tumor microenvironment holds significant promise for the development of more effective cancer therapies aimed at disrupting the metabolic dependencies of cancer cells and modulating the tumor microenvironment to enhance anti-tumor immune responses and inhibit tumor progression. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a poor prognosis and limited therapeutic options. Research on the tumor microenvironment (TME) of PDAC has propelled the development of immunotherapeutic and targeted therapeutic strategies with a promising future. The emergence of single-cell sequencing and mass spectrometry technologies, coupled with spatial omics, has collectively revealed the heterogeneity of the TME from a multiomics perspective, outlined the development trajectories of cell lineages, and revealed important functions of previously underrated myeloid cells and tumor stroma cells. Concurrently, these findings necessitated more refined annotations of biological functions at the cell cluster or single-cell level. Precise identification of all cell clusters is urgently needed to determine whether they have been investigated adequately and to identify target cell clusters with antitumor potential, design compatible treatment strategies, and determine treatment resistance. Here, we summarize recent research on the PDAC TME at the single-cell multiomics level, with an unbiased focus on the functions and potential classification bases of every cellular component within the TME, and look forward to the prospects of integrating single-cell multiomics data and retrospectively reusing bulk sequencing data, hoping to provide new insights into the PDAC TME. [ABSTRACT FROM AUTHOR]

To improve the solubility, a series of novel pharmaceutical salts prepared by ciprofloxacin as the active pharmaceutical ingredient (API) and phthalic acid and its isomers or substituted benzene carboxylic acids as the coformers were synthesized and structurally characterized. The solubility of these pharmaceutical salts is enhanced compared to the parent APIs. The solubility values of three benzene dicarboxylates of ciprofloxacin in phosphate buffer (pH = 6.8) are 20.5 times, 21.8 times, and 2.0 times that of ciprofloxacin, respectively. In particular, the solubility of ciprofloxacin salicylate hydrate has been dramatically improved (up to 349 times) in both neutral (1.45 and 1.32 mg mL−1 at pH 6.4 and 6.8, respectively) and acidic (13.96 mg mL−1 at pH 1.2) environments. Computational chemistry was employed to analyze the solubility of ciprofloxacin salts and elucidate the mechanisms underlying their enhanced solubility. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant neoplasm characterized by a poor prognosis and limited therapeutic strategy. The PDAC tumor microenvironment presents a complex heterogeneity, where neutrophils emerge as the predominant constituents of the innate immune cell population. Leveraging the power of single-cell RNA-seq, spatial RNA-seq, and multi-omics approaches, we included both published datasets and our in-house patient cohorts, elucidating the inherent heterogeneity in the formation of neutrophil extracellular traps (NETs) and revealed the correlation between NETs and immune suppression. Meanwhile, we constructed a multi-omics prognostic model that suggested the patients exhibiting downregulated expression of NETs may have an unfavorable outcome. We also confirmed TLR2 as a potent prognosis factor and patients with low TLR2 expression had more effective T cells and an overall survival extension for 6 months. Targeting TLR2 might be a promising strategy to reverse immunosuppression and control tumor progression for an improved prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Intraductal papillary mucinous neoplasm (IPMN) is an important precursor lesion of pancreatic cancer. Systemic inflammatory parameters are widely used in the prognosis prediction of cancer; however, their prognostic implications in IPMN with associated invasive carcinoma (IPMN-INV) are unclear. This study aims to explore the prognostic value of systemic inflammatory parameters in patients with IPMN-INV. Methods: From 2015 to 2021, patients with pathologically confirmed IPMN who underwent surgical resection at Peking Union Medical College Hospital were enrolled. The clinical, radiological, and pathological data of the enrolled patients were collected and analyzed. Preoperative systemic inflammatory parameters were calculated as previously reported. Results: Eighty-six patients with IPMN-INV met the inclusion criteria. The lymphocyte-to-monocyte ratio (LMR) was the only systemic inflammatory parameter independently associated with the cancer-specific survival (CSS). An LMR higher than 3.5 was significantly associated with a favorable CSS in univariate (hazard ratio [HR] 0.305, p = 0.003) and multivariate analyses (HR 0.221, p = 0.001). Other independently prognostic factors included the presence of clinical symptoms, cyst size, N stage, and tumor differentiation. Additionally, a model including LMR was established for the prognosis prediction of IPMN-INV and had a C-index of 0.809. Conclusions: Preoperative LMR could serve as a feasible prognostic biomarker for IPMN-INV. A decreased LMR (cutoff value of 3.5) was an independent predictor of poor survival for IPMN-INV. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with high probability of recurrence and distant metastasis. Liver metastasis is the predominant metastatic mode developed in most pancreatic cancer cases, which seriously affects the overall survival rate of patients. Abnormally activated endoplasmic reticulum stress and lipid metabolism reprogramming are closely related to tumor growth and metastasis. This study aims to construct a prognostic model based on endoplasmic reticulum stress and lipid metabolism for pancreatic cancer, and further explore its correlation with tumor immunity and the possibility of immunotherapy. Methods: Transcriptomic and clinical data are acquired from TCGA, ICGC, and GEO databases. Potential prognostic genes were screened by consistent clustering and WGCNA methods, and the whole cohort was randomly divided into training and testing groups. The prognostic model was constructed by machine learning method in the training cohort and verified in the test, TCGA and ICGC cohorts. The clinical application of this model and its relationship with tumor immunity were analyzed, and the relationship between endoplasmic reticulum stress and intercellular communication was further explored. Results: A total of 92 characteristic genes related to endoplasmic reticulum stress, lipid metabolism and liver metastasis were identified in pancreatic cancer. We established and validated a prognostic model for pancreatic cancer with 7 signatures, including ADH1C, APOE, RAP1GAP, NPC1L1, P4HB, SOD2, and TNFSF10. This model is considered to be an independent prognosticator and is a more accurate predictor of overall survival than age, gender, and stage. TIDE score was increased in high-risk group, while the infiltration levels of CD8+ T cells and M1 macrophages were decreased. The number and intensity of intercellular communication were increased in the high ER stress group. Conclusions: We constructed and validated a novel prognostic model for pancreatic cancer, which can also be used as an instrumental variable to predict the prognosis and immune microenvironment. In addition, this study revealed the effect of ER stress on cell–cell communication in the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Live streaming is an essential means through which spectators view and engage with esports. In this study, an extended model is proposed and tested based on the expectation confirmation theory to examine esports fans' live streaming experience and the factors contributing to their intention to continue using particular live streaming platforms. Survey data (N = 1004) were collected from King Pro League fans in China and analyzed using structural equation modeling. The results demonstrate that effort and enjoyment expectancies are important factors driving fans' confirmation of expectations regarding live streaming services. The findings also confirm that both spatial presence and co-presence positively relate to viewers' satisfaction with a live streaming platform and their continued intention to use it. This study provides new insights into esports fans' viewing practices and the experiences they find most engaging via live streaming platforms. [ABSTRACT FROM AUTHOR]

Epigenetic modifications are defined as heritable changes in gene activity that do not involve changes in the underlying DNA sequence. The oncogenic process is driven by the accumulation of alterations that impact genome's structure and function. Genetic mutations, which directly disrupt the DNA sequence, are complemented by epigenetic modifications that modulate gene expression, thereby facilitating the acquisition of malignant characteristics. Principals among these epigenetic changes are shifts in DNA methylation and histone mark patterns, which promote tumor development and metastasis. Notably, the reversible nature of epigenetic alterations, as opposed to the permanence of genetic changes, positions the epigenetic machinery as a prime target in the discovery of novel therapeutics. Our review delves into the complexities of epigenetic regulation, exploring its profound effects on tumor initiation, metastatic behavior, metabolic pathways, and the tumor microenvironment. We place a particular emphasis on the dysregulation at each level of epigenetic modulation, including but not limited to, the aberrations in enzymes responsible for DNA methylation and histone modification, subunit loss or fusions in chromatin remodeling complexes, and the disturbances in higher‐order chromatin structure. Finally, we also evaluate therapeutic approaches that leverage the growing understanding of chromatin dysregulation, offering new avenues for cancer treatment. [ABSTRACT FROM AUTHOR]

Purpose: Patients with pancreatic cancer (PC) can be classified into various molecular subtypes and benefit from some precise therapy. Nevertheless, the interaction between metabolic and immune subtypes in the tumor microenvironment (TME) remains unknown. We hope to identify molecular subtypes related to metabolism and immunity in pancreatic cancer Methods: Unsupervised consensus clustering and ssGSEA analysis were utilized to construct molecular subtypes related to metabolism and immunity. Diverse metabolic and immune subtypes were characterized by distinct prognoses and TME. Afterward, we filtrated the overlapped genes based on the differentially expressed genes (DEGs) between the metabolic and immune subtypes by lasso regression and Cox regression, and used them to build risk score signature which led to PC patients was categorized into high- and low-risk groups. Nomogram were built to predict the survival rates of each PC patient. RT-PCR, in vitro cell proliferation assay, PC organoid, immunohistochemistry staining were used to identify key oncogenes related to PC Results: High-risk patients have a better response for various chemotherapeutic drugs in the Genomics of Drug Sensitivity in Cancer (GDSC) database. We built a nomogram with the risk group, age, and the number of positive lymph nodes to predict the survival rates of each PC patient with average 1-year, 2-year, and 3-year areas under the curve (AUCs) equal to 0.792, 0.752, and 0.751. FAM83A, KLF5, LIPH, MYEOV were up-regulated in the PC cell line and PC tissues. Knockdown of FAM83A, KLF5, LIPH, MYEOV could reduce the proliferation in the PC cell line and PC organoids Conclusion: The risk score signature based on the metabolism and immune molecular subtypes can accurately predict the prognosis and guide treatments of PC, meanwhile, the metabolism-immune biomarkers may provide novel target therapy for PC [ABSTRACT FROM AUTHOR]

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Magnetic Cu‐BTC@Fe3O4 materials were synthesized as core‐shell nanocomposites through a secondary growth technique by the combination of magnetic Fe3O4 and Cu‐BTC, which effectively improved the thermal stability of the materials. The interaction energy of Cu‐BTC and Cu‐BTC@Fe3O4 with the xylene isomers, o‐xylene (OX), m‐xylene (MX) and p‐xylene (PX), was calculated by DFT method, which were consistent with the results of the experimental adsorption separation results. In order to study the adsorption performance of xylene isomers on Cu‐BTC@Fe3O4 composite materials, the thermodynamics and kinetics were systematically studied. The adsorption equilibrium curves were obtained by collecting the gas phase adsorption equilibrium data at different temperatures (298, 318 and 338 K) and being fitted with Langmuir and Freundlich isothermal models, respectively, in which the Langmuir isotherm equation was fitted well. Further thermodynamic calculations indicated that the affinity of xylene on Cu‐BTC@Fe3O4 is spontaneous physical adsorption combining exothermic process, while kinetic studies showed the adsorption of xylene isomers on Cu‐BTC@Fe3O4 a pseudo‐second‐order kinetic model. In breakthrough experiments, Cu‐BTC@Fe3O4 has a high adsorption capacity and selectivity (3.3 for OX/MX) at 453 K, 1.0 MPa. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a high mortality rate and a poor prognosis. The human microbiota has been confirmed to participate in oncogenesis and may influence the treatment response to both chemotherapy and immunotherapy. Evidence for the association of the microbiota with PDAC risk, tumorigenesis, treatment response, and survival period is rapidly emerging. The oral microbiota and gut microbiota have the potential to be used in early diagnosis and risk stratification. Intratumor microbiota-targeted intervention strategies may be used as adjuvants to current treatments to improve therapeutic efficacy and overall survival. Here, we summarize the effect and association of the oral, gut and intratumor microbiota on the oncogenesis, progression and treatment of PDAC, as well as the potential of the microbiota to serve as a biomarker for the diagnosis and prognosis of PDAC, as well as a therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) tends to undergo distant metastasis, especially liver metastasis, leading to a poor prognosis. Metabolic remodelling and epigenetic reprogramming are two important hallmarks of malignant tumours and participate in regulating PDAC tumorigenesis and metastasis. However, the interaction between these two processes during PDAC metastasis has not been fully elucidated. Methods: We performed metabolomics analysis to identify the critical metabolites associated with PDAC liver metastasis and focused on guanidinoacetic acid (GAA). Intracellular GAA content was significantly increased in liver metastatic PDAC cells compared to primary cancer cells in mouse xenograft tumour models. The effects of GAA supplementation and glycine amidinotransferase (GATM) knockdown on PDAC metastasis were assessed by analysing cell migration, filopodia formation, epithelial-mesenchymal transition (EMT), and in vivo metastasis in different cell and animal models. Next, ChIP‒qPCR, 3C‒qPCR, and CRISPRi/dCas9-KRAB experiments were used to validate the "epigenome-metabolome" mechanism. Finally, the results of in vitro approaches, including RNA-seq, CUT&RUN, RT‒qPCR, and western blot analyses, as well as luciferase reporter gene assay and transwell assay, revealed the GAA-c-Myc-HMGA axis and transcription-activating histone modifications reprogramming. Results: A high level of intracellular GAA was associated with PDAC liver metastasis. GAA could promote the migration, EMT, and liver metastasis of pancreatic cancer cells in vitro and in vivo. Next, we explored the role of GATM-mediated de novo GAA synthesis in pancreatic cancer metastasis. High expression of GATM was positively correlated with advanced N stage in PDAC. Knockdown of GATM significantly reduced the intracellular level of GAA, suppressed EMT, and inhibited PDAC liver metastasis, and these effects were attenuated by GAA supplementation. Mechanistically, we identified the active enhancers looped to the Gatm gene locus that promoted GATM expression and PDAC liver metastasis. Furthermore, we found that GAA promoted cell migration and EMT by regulating c-Myc-mediated high mobility group AT-hook protein expression. Moreover, GAA increased the H3K4me3 modification level by upregulating histone methyltransferases, which induced the transcription of metastasis-related genes, including Myc. Conclusions: These findings revealed the critical role of the epigenome-metabolome interaction in regulating PDAC liver metastasis and suggested potential therapeutic strategies targeting GAA metabolism and epigenetic regulatory mechanisms. [ABSTRACT FROM AUTHOR]

Herein, we have developed a sequential visible-light-promoted Wolff rearrangement of 1-diazonaphthalen-2(1H)-ones, followed by capturing the in situ generated ketene intermediates with various alcohols, producing diverse 1H-indene-3-carboxylates in moderate to good yields under mild reaction conditions. The broad substrate scope, high functional group tolerance, and robust conditions make the resulting derivative a versatile platform for the synthesis of plenty of bioactive molecules. [ABSTRACT FROM AUTHOR]

With the increasing utilization of clean energy, the development and utilization of hydrogen energy has become a research topic of great significance. Cobalt selenide (CS) is an electrocatalyst with great potential for oxygen evolution reaction (OER). In this paper, a nitrogen-doped biomass carbon (1NC@3)-based composite cobalt selenide (CS) heterojunction was prepared via a solvothermal method using kelp as the raw material. Structural, morphological, and electrochemical analyses were conducted to evaluate its performance. The electrochemical test results demonstrate that the overpotential of the CS/1NC@3 catalyst in the OER process was 292 mV, with a Tafel slope of 98.71 mV·dec−1 at a current density of 10 mA·cm−2. The electrochemical performance of the CS/1NC@3 catalyst was further confirmed by theoretical calculations, which revealed that the presence of the biomass carbon substrate enhanced the charge transport speed of the OER process and promoted the OER process. This study provides a promising strategy for the development of efficient electrocatalysts for OER applications. [ABSTRACT FROM AUTHOR]

The field of electronic sports (eSports) is thriving worldwide but has received limited attention as a cultural and creative industry (CCI). This study is the first to employ three layers (productivity, robustness, and niche creation) of the business ecosystem (BE) to systematically examine the flourishing eSports sector and its development as a CCI-BE. It also maps out the dynamic and emerging stakeholders that have contributed to the eSports ecosystem. We conducted content analysis combined with observations, fifty interviews with elite stakeholders, and analysis of financial and investment data. We found that the development of eSports as a CCI-BE reflects great potential and precarity. First, the business agenda of the media conglomerate Tencent aligns with the 'cultural confidence' slogan proposed by the government, thus ensuring the robustness and stability of the eSports ecosystem. Second, municipal governments, local real estate developers, and eSports tournaments are increasingly interconnected and their contemporary business models and innovation activities in the eSports industry have co-evolved. Third, the role of real estate developers remains nascent without the ability to coordinate and co-evolve with the eSports value chain. eSports may provide a novel converging territory for contemporary cultural and creative industries/traits in the Chinese digital society. [ABSTRACT FROM AUTHOR]

Football in China is undergoing an unprecedented expansion, the result of targeted industrial policy, private sector investment, and the increased popularity of the world's most popular game in the world's most populous nation. Yet, as China's own football infrastructure matures and foreign clubs seek to establish new fanbases there, little is known about Chinese football fans themselves, the ways in which they express their fandom, or the methods by which they consume football. This study aims to take a first step in identifying and exploring football fandom in the People's Republic of China, with a view to critically understanding the context out of which it has emerged, and its likely trajectory of development in the short-to-medium term. Adopting an inductive approach to survey research to explore the attitudes, behaviours and activities of Chinese football fans, an online survey resulting in 710 usable responses was conducted on a Chinese online survey platform Wenjuanxing (问卷星) for three weeks in March 2018. Our research identifies similarities with fandom found elsewhere in the world, yet with key differences generally characteristic of Chinese football fans resulting from the geography, distance and league structures of China's domestic football infrastructure. A tendency to support more than one club, often one domestic and one foreign club, is also noted, with distinct methods of consumption which eschew traditional forms such as match attendance. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer (PC) is a highly malignant tumor featured with high intra-tumoral heterogeneity and poor prognosis. Cell-in-cell (CIC) structures have been reported in multiple cancers, and their presence is associated with disease progression. Nonetheless, the prognostic values and biological functions of CIC-related genes in PC remain poorly understood.Methods: The sequencing data, as well as corresponding clinicopathological information of PC were collected from public databases. Random forest screening, least absolute shrinkage, and selection operator (LASSO) regression and multivariate Cox regression analysis were performed to construct a prognostic model. The effectiveness and robustness of the model were evaluated using receiver operating characteristic (ROC) curves, survival analysis and establishing the nomogram model. Functional enrichment analyses were conducted to annotate the biological functions. The immune infiltration levels were evaluated by ESTIMATE and CIBERSORT algorithms. The expression of KRT7 (Keratin 7) was validated by quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry (IHC) staining. The CIC formation, cell clusters, cell proliferation, migration and invasion assays were applied to investigate the effects of silencing the expression of KRT7.Results: A prognostic model based on four CIC-related genes was constructed to stratify the patients into the low- and high-risk subgroups. The high-risk group had a poorer prognosis, higher tumor mutation burden and lower immune cell infiltration than the low-risk group. Functional enrichment analyses showed that numerous terms and pathways associated with invasion and metastasis were enriched in the high-risk group. KRT7, as the most paramount risk gene in the prognostic model, was significantly associated with a worse prognosis of PC in TCGA dataset and our own cohort. High expression of KRT7 might be responsible for the immunosuppression in the PC microenvironment. KRT7 knockdown was significantly suppressed the abilities of CIC formation, cell cluster, cell proliferation, migration, and invasion in PC cell lines.Conclusions: Our prognostic model based on four CIC-related genes has a significant potential in predicting the prognosis and immune microenvironment of PC, which indicates that targeting CIC processes could be a therapeutic option with great interests. Further studies are needed to reveal the underlying molecular mechanisms and biological implications of CIC phenomenon and related genes in PC progression. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) is a highly lethal and aggressive disease with its incidence and mortality quite discouraging. A robust prognostic signature and novel biomarkers are urgently needed for accurate stratification of the patients and optimization of clinical decision-making. Since the critical role of immune microenvironment in the progression of PC, a prognostic signature based on seven immune-related genes was established, which was validated in The Cancer Genome Atlas (TCGA) training set, TCGA testing set, TCGA entire set and GSE71729 set. Furthermore, S100A14 (S100 Calcium Binding Protein A14) was identified as the gene occupying the most paramount position in risk signature. According to the GSEA, CIBERSORT and ESTIMATE algorithm, S100A14 was mainly associated with lower proportion of CD8 + T cells and higher proportion of M0 macrophages in PC tissue. Meanwhile, analysis of single-cell dataset CRA001160 revealed a significant negative correlation between S100A14 expression in PC cells and CD8 + T cell infiltration, which was further confirmed by tissue microenvironment landscape imaging and machine learning-based analysis in our own PUMCH cohort. Additionally, analysis of a pan-pancreatic cancer cell line illustrated that S100A14 might inhibit CD8 + T cell activation via the upregulation of PD-L1 expression in PC cells, which was also verified by the immunohistochemical results of PUMCH cohort. Finally, tumor mutation burden analysis and immunophenoscore algorithm revealed that patients with high S100A14 expression had a higher probability of responding to immunotherapy. In conclusion, our study established an efficient immune-related prediction model and identified the potential role of S100A14 in regulating the immune microenvironment and serving as a biomarker for immunotherapy efficacy prediction. [ABSTRACT FROM AUTHOR]

Simple Summary: Hyperglycemia has been reported to increase the risk of pancreatic cancer, while the association between temporal glycemic changes and the risk of pancreatic cancer remains uncertain. This study used data from a prospective cohort and found a U-shaped association between annual change in fasting blood glucose and risk of pancreatic cancer in males. A higher coefficient of variance and a greater range of fasting blood glucose were also associated with the increased risk of pancreatic cancer. These findings may help identify individuals at high risk for pancreatic cancer; thus, appropriate measures can be taken to prevent pancreatic cancer. Hyperglycemia has been reported to increase the risk of pancreatic cancer (PC), while the association between glycemic change and PC risk has rarely been explored. Using data from a prospective cohort study conducted in China since 2006, 138,870 males with available fasting blood glucose (FBG) levels, including 106,632 males with at least two FBG measurements, were analyzed. The associations between FBG (level, change, and stability) and PC incidence were evaluated using Cox proportional hazard regression and restricted cubic splines. Baseline (p = 0.109) and recent (p = 0.070) FBG levels and incident PC were not significantly associated. U-shaped associations were observed between the annual FBG change and PC risk. Compared with stable FBG, participants with annual FBG change rates <−0.05 mmol/L or >0.15 mmol/L had about four-fold (HR, 4.010; 95% CI: 1.920–8.375) and six-fold (HR, 5.897; 95% CI: 2.935–11.848) higher PC risks, respectively. The PC risk increased by 2.5% (HRlinear = 1.025, 95% CI:1.009–1.042) for every 1% increase in the coefficient of variation for FBG. A subgroup analysis of males without diabetes at baseline showed stronger associations. Temporal FBG changes may be an important factor for identifying populations with high PC risks. [ABSTRACT FROM AUTHOR]

Purpose: To determine the optimal imaging tool for clinical evaluation of pancreatic neoplasm by comparing the performance of 18F-FDG PET/MRI and PET/CT.Procedures: Patients with suspected pancreatic neoplasms underwent PET/MRI and PET/CT in the same day prior to resection or endoscopic ultrasound-guided fine-needle aspiration. Histology served as the golden standard of lesion classification. Visual assessment on lesion type and lesion malignancy via PET/MRI and PET/CT images was compared. Standard uptake values (SUVs) of PET images from the two scanners were measured and their correlations were further evaluated.Results: Thirty-nine patients were included for the final analysis. In visual assessment, we found MRI achieved better performance than CT in differentiating solid and cystic neoplasms, with accuracy of 100% vs. 87%, respectively. In visual malignancy diagnosis, the accuracy of PET/CT was 92.3% for overall lesions and 90.9% for cysts, while the accuracy of PET/MRI was 92.3% and 86.4%, respectively. Besides, semi-quantitative analysis achieved better specificity than visual assessment for both hybrid modalities (100% vs. 87.5% for PET/CT; 100% vs. 81.5% for PET/MR). Furthermore, strong correlation of SUV was found between PET/CT and PET/MRI, with Pearson's correlation coefficients > 0.82.Conclusions: In this study, we found PET/MRI and PET/CT, both using 18F-FDG as tracer, had comparable overall performance in identification of pancreatic neoplasms. Interestingly, for patients who had suspected pancreatic neoplasm but invisible FDG uptake, PET/MRI had shown exceptionally better performance, probably because MR images could detect tiny abnormal structures to improve diagnosis. [ABSTRACT FROM AUTHOR]

Hip-hop culture has evolved into a global phenomenon, attracting extensive academic research on its adaptation and localization in different societies. However, most studies have either neglected the influence of political economic power on hybridization or have overestimated the rationality of the artists in hip-hop culture. This study adopted critical transculturalism theory to shed light on the agency and power relations involved in the localization and mainstream emergence of Chinese hip-hop music from both longitudinal and comparative perspectives. The findings, which are based on qualitative content analysis and critical discourse analysis of news articles published in the three golden years (2008, 2010, and 2017) of the development of Chinese hip-hop music, suggest that whereas cultural and political factors were influential on both the localization and mainstream emergence processes, economic factors played a greater role in mainstream emergence. The enhancement of literacy in professional knowledge aroused public interest, and the use of symbolic hybridity created a role model for underground rappers and attracted social attention. Both these factors helped Chinese hip-hop music enter the mainstream industry. The idea of symbolic hybridity proposed in this study, which provides a mesolevel perspective, is worth further research. [ABSTRACT FROM AUTHOR]

Background: The consensus guidelines for branch-duct intraductal papillary mucinous neoplasm (BD-IPMN) of the pancreas are mostly based on imaging features. This study aimed to determine imaging features and their diagnostic accuracy for predicting high-grade dysplasia (HGD)/malignancy in BD-IPMN, including mixed type. Methods: The PubMed, Embase, and Cochrane databases were searched, and data were extracted from relevant studies. As the main diagnostic accuracy index, diagnostic odds ratios (DORs) of imaging features for diagnosing HGD/malignancy in BD-IPMNs were pooled using the random-effects model. A bivariate random-effects approach was used to construct summary receiver operating characteristic curves for sensitivity and specificity estimation. Results: The pooled DOR was the highest for the enhanced solid component/mural nodule (MN) (DOR, 12.21; 95 % confidence interval [CI], 6.14–24.27), followed by a main pancreatic duct (MPD) diameter of 10 mm or greater (DOR, 7.93; 95 % CI, 3.02–20.83), solid component (DOR, 4.85; 95 % CI, 2.49–9.42), lymphadenopathy (DOR, 4.84; 95 % CI, 1.11–21.06), MN (DOR, 4.48; 95 % CI, 3.15–6.39), an MPD diameter of 5 mm or greater (DOR, 3.69; 95 % CI, 2.62–5.19), abrupt change in MPD caliber with distal pancreatic atrophy (DOR, 2.65; 95 % CI, 1.66–4.24), thickened/enhancing walls (DOR, 2.38; 95 % CI, 1.57–3.60), and cyst size of 3 cm or larger (DOR, 1.98; 95 % CI, 1.48–2.64). The largest area under the curve (0.89 and 0.95, respectively) and high specificity (0.95 and 0.98, respectively) also were found for enhanced solid component/MN and an MPD diameter of 10 mm or greater, albeit with low sensitivity (0.38 and 0.14, respectively). Conclusions: The aforementioned imaging features could aid in predicting HGD/malignancy of BD-IPMN. Furthermore, enhanced solid component/MN and an MPD diameter of 10 mm or greater were the most important predictors of HGD/malignancy in BD-IPMN and should be considered as indications for surgery. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) is a highly fatal and aggressive disease with its incidence and mortality quite discouraging. It is of great significance to construct an effective prognostic signature of PC and find the novel biomarker for the optimization of the clinical decision-making. Due to the crucial role of immunity in tumor development, a prognostic model based on nine immune-related genes was constructed, which was proved to be effective in The Cancer Genome Atlas (TCGA) training set, TCGA testing set, TCGA entire set, GSE78229 set, and GSE62452 set. Furthermore, S100A2 (S100 Calcium Binding Protein A2) was identified as the gene occupying the most paramount position in risk model. Gene set enrichment analysis (GSEA), ESTIMATE and CIBERSORT algorithm revealed that S100A2 was closely associated with the immune status in PC microenvironment, mainly related to lower proportion of CD8+T cells and activated NK cells and higher proportion of M0 macrophages. Meanwhile, patients with high S100A2 expression might get more benefit from immunotherapy according to immunophenoscore algorithm. Afterwards, our independent cohort was also used to demonstrate S100A2 was an unfavorable marker of PC, as well as its remarkably positive correlation with the expression of PD-L1. In conclusion, our results demonstrate S100A2 might be responsible for the preservation of immune-suppressive status in PC microenvironment, which was identified with significant potentiality in predicting prognosis and immunotherapy response in PC patients. [ABSTRACT FROM AUTHOR]

Micro-liquid dispensing technology is widely used in the field of in vitro diagnostics. To study the influence of the system factors on the liquid dispensing process, a micro-liquid dispensing system based on a syringe pump is designed in this paper, and a Fluent simulation model is established to simulate the dispensing process. Taking into account the existence of the air column in the simulation model, the simulation and analysis of the influence of the system parameters is carried under different air volume conditions, and the reliability of the simulation results are verified through experiments. The experimental and simulation results show that ideal dispensing can be achieved when the surface tension of reagent is large and its viscosity is small. Moreover, breakages, satellite droplets, and bubbles will appear successively with an increase in the outlet diameter when the inlet velocity is large, while adhesion will occur when the inlet velocity is small. These results will be used to guide the design and control of this system. [ABSTRACT FROM AUTHOR]

Background: Prophylactic somatostatin to reduce the incidence of clinically relevant postoperative pancreatic fistula after pancreaticoduodenectomy remains controversial. We assessed the preventive efficacy of somatostatin on clinically relevant postoperative pancreatic fistula in intermediate-risk patients who underwent pancreaticoduodenectomy at pancreatic centres in China. Methods: In this multicentre, prospective, randomised controlled trial, we used the updated postoperative pancreatic fistula classification criteria and cases were confirmed by an independent data monitoring committee to improve comparability between centres. The primary endpoint was the rate of clinically relevant postoperative pancreatic fistula within 30 days after pancreaticoduodenectomy. Results: Eligible patients (randomised, n = 205; final analysis, n = 199) were randomised to receive postoperative intravenous somatostatin (250 μg/h over 120 h; n = 99) or conventional therapy (n = 100). The primary endpoint was significantly lower in the somatostatin vs control group (n = 13 vs n = 25; 13% vs 25%, P = 0.032). There were no significant differences for biochemical leak (P = 0.289), biliary fistula (P = 0.986), abdominal infection (P = 0.829), chylous fistula (P = 0.748), late postoperative haemorrhage (P = 0.237), mean length of hospital stay (P = 0.512), medical costs (P = 0.917), reoperation rate (P > 0.99), or 30 days' readmission rate (P = 0.361). The somatostatin group had a higher rate of delayed gastric emptying vs control (n = 33 vs n = 21; 33% vs 21%, P = 0.050). Conclusions: Prophylactic somatostatin treatment reduced clinically relevant postoperative pancreatic fistula in intermediate-risk patients after pancreaticoduodenectomy. Trial registration: NCT03349424. [ABSTRACT FROM AUTHOR]

Previous studies on eSports have essentially focused on its "sportiness" without giving attention to aspects such as media, information, and technology. By assessing the emerging research field of eSports through the lens of Actor-Network Theory, this study regards the Chinese eSports industry as an assemblage of heterogeneous elements. Accordingly, this study disassembles and unpacks eSports to understand how it is assembled, disassembled, and reassembled. Using research methods such as participant observation and in-depth interviews, this study evaluates the material actors and relational networks of the Chinese eSports industry to trace how the actors come to be assembled, how they associate and exercise force, and how they persist or decline each other's effects. Thus, it suggests that material actors and relational networks with an agency are not simply mediating, but also structuring eSports, indicating the explicit and implicit dynamics of power within the actor-network. [ABSTRACT FROM AUTHOR]

Enucleation is an effective surgical method to treat pancreatic insulinoma, however, the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) is high. We aim to investigate the risk factors for CR-POPF which have not been well characterized and develop effective methods to prevent CR-POPF after enucleation. This retrospective cohort study included 161 patients diagnosed with insulinoma from June 2016 to July 2020 in Peking Union Medical College Hospital. The risk factors for CR-POPF were evaluated and the role of prophylactic pre-operative pancreatic stent to prevent the occurrence of CR-POPF after enucleation of pancreatic insulinoma were explored. A cohort of 161 insulinoma cases were reviewed. The CT or MRI imaging reports could be tracked in 108 cases. A total of 96 patients underwent surgery, while 81 experienced pancreatic enucleation. Univariate and multivariate analyses showed that the distance from insulinoma to the main pancreatic duct (MPD) ≤2 mm was an independent risk factor for CR-POPF (p = 0.003, OR = 6.011, 95% Cl 1.852–19.512). The pre-operative pancreatic stent substantially reduced the incidence of CR-POPF in patients with tumor located in proximity to (distance ≤2 mm) the MPD (CR-POPF of the stented group vs the non-stented group: 37.5% vs 71.4%, p = 0.028). The distance from insulinoma to MPD ≤2 mm is a predictive factor for CR-POPF after enucleation. Pancreatic duct stenting may benefit patients with insulinoma in proximity to the MPD by enabling a lower CR-POPF rate, so it should be considered before the enucleation of the insulinoma in proximity to the MPD (distance ≤2 mm). [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer's poor prognosis is caused by distal metastasis, which is associated with epigenetic changes. However, the role of the 3D epigenome in pancreatic cancer biology, especially its metastasis, remains unclear. Methods: Here, we developed high-resolution 3D epigenomic maps of cells derived from normal pancreatic epithelium, primary and metastatic pancreatic cancer by in situ Hi-C, ChIP-seq, ATAC-seq, and RNA-seq to identify key genes involved in pancreatic cancer metastasis Results: We found that A/B compartments, contact domains, and chromatin loops changed significantly in metastatic pancreatic cancer cells, which are associated with epigenetic state alterations. Moreover, we found that upregulated genes, which were located in switched compartments, changed contact domains, and metastasis-specific enhancer-promoter loops, were related to cancer metastasis and poor prognosis of patients with pancreatic cancer. We also found that transcription factors in specific enhancer-promoter loop formation were also associated with metastasis. Finally we demonstrated that LIPC, looped to metastasis-specific enhancers, could promote pancreatic cancer metastasis. Conclusions: These results highlight the multiscale 3D epigenome reprogramming during pancreatic cancer metastasis and expand our knowledge of mechanisms of gene regulation during pancreatic cancer metastasis. [ABSTRACT FROM AUTHOR]

Through our analysis of the performances and corpus of lyrics produced on the Reality TV show The Rap of China, we investigate how discrete Chinese inflections refract globally resonant hip-hop themes such as representations of masculinity and loyalty. We identify how rappers use classical Chinese cultural templates, invoking the knights-errant who populate the physical and ideational realm of Jianghu that underpins China's long tradition of folk tales, martial arts literature, and film. The article explores how Chinese rappers invoke such templates to navigate the twin demands of authenticity and the political imperative of positive energy. [ABSTRACT FROM AUTHOR]

Introduction: Radical antegrade modular pancreatosplenectomy (RAMPS) was proposed a decade ago with the aim to achieve higher R0 tangential margin and radical N1 lymph node resection for left-sided pancreatic adenocarcinoma (PDAC), which has been widely accepted worldwide at present. Laparoscopic RAMPS (Lap-RAMPS) has been attempted for PDAC during last several years, however, no outcomes evaluation by comparison between laparoscopic vs open RAMPS has been reported yet. Materials and methods: From August, 2012 to March, 2018, patients undergoing open or lap-RAMPS for the diagnosis of left-sided PDAC were reviewed from a prospective database. Patients excluded if they were related with combined organs or vessels resection, systematic metastasis as well as conversion from open RAMPS to lap RAMPS. The surgical and oncologic outcomes were compared. Results: A total of 48 PDAC patients were enrolled (25 underwent lap-RAMPS and 23 underwent open-RAMPS). There were no significant differences in demographic or perioperative morbidity. In the lap-RAMPS group, R0 transection margin and retroperitoneal margin were both achieved in 23 of 25 patients (92%). In the open RAMPS group, R0 transection margin was achieved in 21 of 23 patients (91.3%), R0 retroperitoneal margin was 22 of 23 patients (95.65%). There were no differences in pathological examinations. The number of lymph node (LN) retrieved between lap-RAMPS and open- RAMPS group was not significant difference (15.84 vs 18.22; P = 0.268). Median disease-free survival (DFS) was analogous in two groups (18.11 m vs 20.00 m, P = 0.999). Median overall survival (OS) was 24.53 m in lap-RAMPS group and 28.73 m in the open-RAMPS group (P = 0.633). Conclusions: Lap-RAMPS is technically feasible, and has comparable long-term oncological outcome with open-RMAPS. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer (PC) is a highly fatal and aggressive disease with its incidence and mortality quite discouraging. An effective prediction model is urgently needed for the accurate assessment of patients' prognosis to assist clinical decision-making. Methods: Gene expression data and clinicopathological data of the samples were acquired from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases. Differential expressed genes (DEGs) analysis, univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression analysis, random forest screening and multivariate Cox regression analysis were applied to construct the risk signature. The effectiveness and independence of the model were validated by time-dependent receiver operating characteristic (ROC) curve, Kaplan–Meier (KM) survival analysis and survival point graph in training set, test set, TCGA entire set and GSE57495 set. The validity of the core gene was verified by immunohistochemistry and our own independent cohort. Meanwhile, functional enrichment analysis of DEGs between the high and low risk groups revealed the potential biological pathways. Finally, CMap database and drug sensitivity assay were utilized to identify potential small molecular drugs as the risk model-related treatments for PC patients. Results: Four histone modification-related genes were identified to establish the risk signature, including CBX8, CENPT, DPY30 and PADI1. The predictive performance of risk signature was validated in training set, test set, TCGA entire set and GSE57495 set, with the areas under ROC curve (AUCs) for 3-year survival were 0.773, 0.729, 0.775 and 0.770 respectively. Furthermore, KM survival analysis, univariate and multivariate Cox regression analysis proved it as an independent prognostic factor. Mechanically, functional enrichment analysis showed that the poor prognosis of high-risk population was related to the metabolic disorders caused by inadequate insulin secretion, which was fueled by neuroendocrine aberration. Lastly, a cluster of small molecule drugs were identified with significant potentiality in treating PC patients. Conclusions: Based on a histone modification-related gene signature, our model can serve as a reliable prognosis assessment tool and help to optimize the treatment for PC patients. Meanwhile, a cluster of small molecule drugs were also identified with significant potentiality in treating PC patients. [ABSTRACT FROM AUTHOR]

Objective: Postoperative intra-abdominal infection is one of the most serious complications after pancreatic resection. In this article, we investigated the relationship between serum lactate level and postoperative infection, to suggest a new predictor of potential infection risk after pancreatectomy. Methods: A retrospective analysis of 156 patients who underwent pancreatic surgery and admitted in the intensive care unit for recovery after surgery between August 2017 and August 2019 was performed. Results: The basic characteristics, preoperative information, pathological diagnoses, surgical methods, and intraoperative situations of patients in the postoperative intra-abdominal infection group (n = 52) and non-infection group (n = 104) showed no significant differences. With the same postoperative treatments and results of fluid balance, blood pressure maintenance, and laboratory tests, postoperative serum lactate level increased much higher in the infection group than non-infection group (P < 0.001), while the base excess level declined much lower (P = 0.002). Patients in the infection group needed more time to elute lactate (P < 0.001), and stayed longer in the intensive care unit after surgery (P = 0.007). The overall postoperative complications were certainly more in the infection group (P < 0.001), resulting in a longer hospitalization time (P < 0.001). Conclusions: When patients recovered smoothly from anesthesia with a stable hemodynamics situation and normal results of laboratory tests, abnormally high serum lactate level could be a predictor of postoperative intra-abdominal infection after pancreatic resection. [ABSTRACT FROM AUTHOR]

Meerwein-Ponndorf-Verley (MPV) reduction has gained much attention due to is mid reaction conditions, and this reaction can be performed without the presence of reductive atmosphere and the reaction conditions of high temperature and high pressure. Solid bases with abundant strong basic sites can be synthesized with metal-organic frameworks (MOFs) as precursors. These MOFs are immobilized with alkane metal nitrides, followed by calcination to produce the desired basic metal oxides. The basic zirconia shows highly efficient catalytic performance in MPV reduction of substrates with the carbonyl group, and benzaldehyde can be completely reduced in 6 hours with a mild reaction temperature (160 °C) in the absence of hydrogen gas. The catalytic efficiency is determined by the amounts of strong basic sites, but not the total amounts of basic sites, and this phenomenon is proved by the contrast experiments with the catalytic test of weak solid bases. Furthermore, the cooperative action between basic and acid sites can also enhance the catalytic performance in MPV reactions. With MOFs as precursors, metal oxide catalysts can be synthesized with well dispersed active sites. [ABSTRACT FROM AUTHOR]

Valve-controlled pneumatic jetting technology, which is characterized by high accuracy, fast dispensing speed, and strong adaptability, has been widely applied in the field of life sciences. This paper examines the formation and separation of droplets by reporting the comprehensive influence of system parameters on the morphological changes of droplets, which was simulated by using several dimensionless numbers, including the Weber number, Reynolds number, and Ohnesorge number. In the next step, the simulation results are verified through experimental results, and the rules of the regular ejection of droplets are summarized. The simulation and experimental results indicate that if We is higher than the upper critical value or lower than the lower critical value, jetting failure situations, such as adhesion, satellite droplets, sputtering, and flow-stream will occur. Similarly, jetting failures such as adhesion or flow-stream will appear with oversize or undersize Reynolds number. Through Oh, only when the system parameters should be adjusted to keep the values of We and Re within the proposed range can normal droplets be jetted. The research also provides the recommended ranges of system parameters for ensuring successful droplet ejection, which has important reference significance for guiding the design and control of valve-controlled pneumatic jetting systems. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) is a highly malignant tumor in the digestive system. Both long noncoding RNAs (lncRNAs) and autophagy play vital roles in the development and progress of PC. Here, we constructed a prognostic risk score system based on the expression profile of autophagy-associated lncRNAs for prognostic prediction in PC patients. Firstly, we extracted the expression profile of lncRNA and clinical information from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The autophagy-associated genes were from The Human Autophagy Database. Through Cox regression and survival analysis, we screened out seven autophagy-associated lncRNAs and built the risk score system in which the patients with PC were distinguished into high- and low-risk groups in both training and validation datasets. PCA plot displayed distinct discrimination, and risk score system displayed independently predictive value for PC patient survival time by multivariate Cox regression. Then, we built a lncRNA and mRNA co-expression network via Cytoscape and Sankey diagram. Finally, we analyzed the function of lncRNAs in high- and low-risk groups by gene set enrichment analysis (GSEA). The results showed that autophagy and metabolism might make significant effects on PC patients of low-risk groups. Taken together, our study provides a new insight to understand the role of autophagy-associated lncRNAs and finds novel therapeutic and prognostic targets in PC. [ABSTRACT FROM AUTHOR]

In China, the expanding eSports culture has produced a vast cohort of video-game players whose peak age ranges between 16 and 22 years. This study explores the dynamic identity transformation and mental wellbeing development processes of eSports professionals in a risk-prone society. It comprises in-depth interviews with players, coaches, managers, and commentators working in 15 top eSports clubs in the Chinese cities of Shanghai, Guangzhou, Suzhou, and Chengdu. We find eSports is perceived as non-secure, casual, and irregular by the Chinese public and that the mental changes experienced by eSports professionals throughout their careers have been significantly influenced by a more sophisticated form of state power and social norms, including cultural cognitive beliefs, economic stimulation, and authority attributions. [ABSTRACT FROM AUTHOR]