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Introduction Severe acute pancreatitis (SAP) is a crucial gastrointestinal disease characterized by systemic inflammatory responses and persistent multiple organ failure. The role of bile acids (BAs) in diverse inflammatory diseases is increasingly recognized as crucial, but the underlying role of BA conjugation remains elusive. Objectives Our study aim to investigate the potential role of conjugated bile acids in SAP and reveal the molecular mechanisms underlying its regulatory effects. We hypothesized that taurochenodeoxycholic acid (TCDCA) and glycochenodeoxycholic acid (GCDCA) could protect SAP through inhibiting the activation of NLRP3 inflammasomes via the TGR5 pathway in macrophages. Methods To test our hypothesis, we used BA-CoA: amino acid N-acyltransferase knockout ( Baat −/− ) mice and established SAP mouse models using caerulein- and sodium taurocholate- induced. We utilized a range of methods, including pathology sections, qRT-PCR, immunofluorescence, Western blotting, and ELISA, to identify the mechanisms of regulation. Results BA-CoA: Amino acid N-acyltransferase knockout ( Baat −/− ) mice significantly exacerbated pancreatitis by increasing pancreatic and systemic inflammatory responses and pancreatic damage in SAP mouse models. Moreover, the serum TCDCA levels in Baat −/− mice were lower than those in wild-type (WT) mice with or without SAP, and GCDCA and TCDCA showed stronger anti-inflammatory effects than chenodeoxycholic acid (CDCA) in vitro. TCDCA treatment alleviated SAP in a Takeda G protein-coupled receptor 5 and NOD-like receptor family, pyrin domain containing 3 —dependent manner in vivo. Reinforcing our conclusions from the mouse study, clinical SAP patients exhibited decreased serum content of conjugated BAs, especially GCDCA, which was inversely correlated with the severity of systemic inflammatory responses. Conclusion Conjugated bile acids significantly inhibit NLRP3 inflammasome activation by activating TGR5 pathway, thereby alleviating pancreatic immunopathology. The results provide new insights into the variability of clinical outcomes and paves the way for developing more effective therapeutic interventions for AP.

Extracting local variable is a well-known and widely used refactoring technique designed to enhance code readability by replacing complex expressions with simpler variable references. Although most integrated development environments (IDEs) provide tool support for such refactoring, these tools often result in semantic errors due to a lack of in-depth analysis. To overcome these limitations, we present ValExtractor, a novel and reliable approach for reliable automated variable extraction. The key challenge involves accurately and efficiently identifying the side effects of extracted expressions and their potential interactions with the surrounding context, without resorting to time-consuming dynamic execution. ValExtractor employs lightweight static source code analysis to validate the side effects of selected expressions and determine which instances of the expressions can be extracted together without altering program semantics or introducing new potential exceptions. Our evaluation demonstrates that mainstream refactoring engines, such as those in Eclipse and IntelliJ IDEA, frequently generate incorrect variable extractions, whereas ValExtractor successfully avoids these errors. The algorithm and its implementation have been integrated into Eclipse, serving over three million global Eclipse users.

Twenty-four-month-old male C57BU6 mice with low serum testosterone levels were used as a late-onset hypogonadism （LOH） animal model for examining the effects of velvet antler polypeptide （VAP） on sexual function and testosterone synthesis. These mice received VAP for 5 consecutive weeks by daily gavage at doses of 100, 200, or 300 mg kg-1 body weight per day （n = 10 mice per dose）. Control animals （n = 10） received the same weight-based volume of vehicle. Sexual behavior and testosterone levels in serum and interstitial tissue of testis were measured after the last administration of VAP. Furthermore, to investigate the mechanisms of how VAP affects sexual behavior and testosterone synthesis in vivo, the expression of steroidogenic acute regulatory protein （STAR）, cytochrome P450 cholesterol side-chain cleavage enzyme （P450scc）, and 3β-hydroxysteroid dehydrogenase （3βHSD） in Leydig cells was also measured by immunofluorescence staining and quantitative real-time PCR. As a result, VAP produced a significant improvement in the sexual function of these aging male mice. Serum testosterone level and intratesticular testosterone （ITT） concentration also increased in the VAP-treated groups. The expression of STAR, P450scc, and 3β-HSD was also found to be enhanced in the VAP-treated groups compared with the control group. Our results suggested that VAP was effective in improving sexual function in aging male mice. The effect of velvet antler on sexual function was due to the increased expression of several rate-limiting enzymes of testosterone synthesis （STAR, P450scc, and 3β-HSD） and the following promotion of testosterone syothesis in vivo.

With the increasing use of field-programmable gate arrays （FPGAs） in embedded systems and many embedded applications, the failure to protect FPGA-based embedded systems from cloning attacks has brought serious losses to system developers. This paper proposes a novel combinational logic binding technique to specially protect FPGA-based embedded systems from cloning attacks and provides a pay-per-device licensing model for the FPGA market. Security analysis shows that the proposed binding scheme is robust against various types of malicious attacks. Experimental evaluations demonstrate the low overhead of the proposed technique.

A series of sulfonated polyimides (SPIs) containing pyridine groups were prepared by direct polycondensation from 1,4,5,8-naphthalenetetracarboxylic dianhydride (NTDA), 4,4′-diaminodiphenyl ether-2,2′-disulfonic acid (ODADS) and 4-(4-methoxy)phenyl-2,6-bis(4-aminophenyl)pyridine (DAM). The resulting copolymers displayed good solubility in common organic solvents. Flexible, transparent, tough membranes were obtained via solution casting. All the films showed high thermal stability with desulfonation temperature over 300°C. They exhibited prominent mechanical properties with Young’s modulus around 2.0 GPa. High proton conductivity (0.23 S/cm at 100% RH) was also observed. More importantly, the new materials exhibited low water uptake (30 wt%–75 wt% at 80°C) and improved water stability, which were attributed to the acid-base interaction between sulfonic acid and pyridine functional groups.

Multi-agent simulation could make a contribution to a better understanding of social and economic systems. To some extent, multi-agent simulation can be seen as experimental technique for hypothesis testing and scenario analysis, which can be used complementary and in combination with experiments in social and economic systems. The multi-agent model represent a broad class of models which have been introduced to describe the economic dynamics in a more realistic way. Their building blocks are: the agents are heterogeneous with respect to their various properties like strategies, wealth, time scale,etc; the interaction between them is a fundamental element and, of course, it can have many different characteristics; price dynamics depends on the balance between offer and demand but the specific implementation can be different. In the framework of applied-information technology of microscopic simulation, a multi-agent model of the stock exchange is developed for the case of one type of shares.

Physical unclonable function （PUF） makes use of the uncontrollable process variations during the production of IC to generate a unique signature for each IC. It has a wide application in security such as FPGA intellectual property （IP） protection, key generation and digital rights management. Ring oscillator （RO） PUF and Arbiter PUF are the most popular PUFs, but they are not specially designed for FPGA. RO PUF incurs high resource overhead while obtaining less challenge-response pairs, and requires ＂hard macros＂ to implement on FPGAs. The arbiter PUF brings low resource overhead, but its structure has big bias when it is mapped on FPGAs. Anderson PUF can address these weaknesses of current Arbiter and RO PUFs implemented on FPGAs. However, it cannot be directly implemented on the new generation 28 nm FPGAs. In order to address these problems, this paper designs and implements a delay-based PUF that uses two LUTs in an SLICEM to implement two 16-bit shift registers of the PUF, 2-to-1 multiplexers in the carry chain to implement the multiplexers of the PUF, and any one of the 8 flip-flops to latch 1-bit PUF signatures. The proposed delay-based PUF is completely realized on 28 nm commercial FPGAs, and the experimental results show its high uniqueness, reliability and reconfigurability. Moreover, we test the impact of aging on it, and the results show that the effect of aging on the proposed PUF is insignificant, with only 6% bit-flips. Finally, the prospects of the proposed PUF in the FPGA binding and volatile key generation are discussed.

Background： Decoy receptor 3 （DcR3） is a protein with anti-apoptotic effect that belongs to the tumor necrosis factor receptor superfamily. DcR3 is highly expressed in a variety of malignant tumors including cholangiocarcinoma and its expression was found to be related to the clinical stage, the invasion, and tile metastasis of the tumor. This in vitro study aimed to investigate the effect ofdownregulated expression of DcR3 on cell viability, cell apoptosis, and cell cycle in cholangiocarcinoma cell line TFK-1. Methods： Three different cell lines were cultured： human cholangiocarcinoma TFK-I, human biliary epithelial carcinoma HuCCT-1, and human cholangiocarcinoma RBE. The cholangiocarcinoma cell line with the highest expression of DcR3 was selected for further investigation. The expression of DcR3 was silenced/knocked down by transfection with DcR3-siRNA in the selected cell line. Various biological phenotype parameters such as cell viability, apoptosis, and cell cycle were observed. Results： The mRNA and protein levels of DcR3 were measured in the three cell lines, and TFK-1 was selected. After the treatment with DcR3-siRNA for 48 h, DcR3 mRNA and protein expression in the treatment group were 38.45% （P 〈 0.01 ） and 48.03% （P 〈 0.05） of that of＇the control, respectively. It was found that the cell viability decreased to 61.87% of the control group （P 〈 0.01 ） after the downregulation of DcR3 in cholangiocarcinoma cell line TFK- 1 by transfection with DcR3-siRNA, while tile percentage ofapoptotic cells was 2.98 times as compared with the control group （P 〈 0.05）. Compared with the control group the ratio of G0/G1 increased, and the ratio of G2/M dccreased in the treatment group. However, the differences were not statistically significant. Conclusions： The effect of DcR3 on the growth and apoptosis ofcholangiocarcinoma has been demonstrated. DcR3 is not only a predictive marker for malignant tumor but it is also likely to be a potential target for cancer gene therapy. Further studies should focus on exploring the binding ligand of DcR3, the signaling pathway involved, and the molecular mechanism for the regulation of DcR3 expression in cholangiocarcinoma.

Chinese men should have a higher prostate-specific antigen （PSA） ＂gray zone＂ than the traditional value of 2.5-10.0 ng ml-1 since the incidence of prostate cancer （PCa） in Chinese men is relative low. We hypothesized that PSA density （PSAD） could improve the rate of PCa detection in Chinese men with a PSA higher than the traditional PSA ＂gray zone.＂ A total of 461 men with a PSA between 2.5 and 20.0 ng ml-1, who had undergone prostatic biopsy at two Chinese centers were included in the analysis. The men were then further divided into groups with a PSA between 2.5-10.0 ng ml-1 and 10.1-20.0 ng ml-1. Receiver operating characteristic （ROC） curve was used to evaluate the efficacy of PSA and PSAD for the diagnosis of PCa. In men with a PSA of 2.5-10.0 ng ml-1 or 10.1-20.0 ng ml-z, the areas under the ROC curve were higher for PSAD than for PSA. This was consistent across both centers and the cohort overall. When the entire cohort was considered, the optimal PSAD cut-off for predicting PCa in men with a PSA of 2.5-10.0 ng m1-1 was 0.15 ng ml-2 ml-2, with a sensitivity of 64.4% and specificity of 64.6%. The optimal cut-off for PSAD in men with a PSA of 10.1-20.0 ng m1-1 was 0.33 ng ml-1 ml-1, with a sensitivity of 60.3% and specificity of 82.7%. PSAD can improve the effectiveness for PCa detection in Chinese men with a PSA of 2.5-10.0 ng ml-1 （traditional Western PSA ＂gray zone＂） and 10.1-20.0 ng ml-2 （Chinese PSA ＂gray zone＂）.

The poor stability of Ru-based acidic oxygen evolution (OER) electrocatalysts has greatly hampered their application in polymer electrolyte membrane electrolyzers (PEMWEs). Traditional understanding of performance degradation centered on influence of bias fails in describing the stability trend, calling for deep dive into the essential origin of inactivation. Here we uncover the decisive role of reaction route (including catalytic mechanism and intermediates binding strength) on operational stability of Ru-based catalysts. Using MRuO x (M = Ce 4+ , Sn 4+ , Ru 4+ , Cr 4+ ) solid solution as structure model, we find the reaction route, thereby stability, can be customized by controlling the Ru charge. The screened SnRuO x thus exhibits orders of magnitude lifespan extension. A scalable PEMWE single cell using SnRuO x anode conveys an ever-smallest degradation rate of 53 μV h −1 during a 1300 h operation at 1 A cm −2 . The poor stability of ruthenium-based catalysts has greatly hampered their application in polymer electrolyte membrane water electrolysis. Here, the authors uncover the decisive role of reaction route on catalytic performance, which enables the screening of efficient ruthenium-based water oxidation catalysts.