Inflammatory bowel disease (IBD) is a chronic, relapsing disease that severely affects patients’ quality of life. The exact cause of IBD is uncertain, but current studies suggest that abnormal ...activation of the immune system, genetic susceptibility, and altered intestinal flora due to mucosal barrier defects may play an essential role in the pathogenesis of IBD. Unfortunately, IBD is currently difficult to be wholly cured. Thus, more treatment options are needed for different patients. Stem cell therapy, mainly including hematopoietic stem cell therapy and mesenchymal stem cell therapy, has shown the potential to improve the clinical disease activity of patients when conventional treatments are not effective. Stem cell therapy, an emerging therapy for IBD, can alleviate mucosal inflammation through mechanisms such as immunomodulation and colonization repair. Clinical studies have confirmed the effectiveness of stem cell transplantation in refractory IBD and the ability to maintain long-term remission in some patients. However, stem cell therapy is still in the research stage, and its safety and long-term efficacy remain to be further evaluated. This article reviews the upcoming stem cell transplantation methods for clinical application and the results of ongoing clinical trials to provide ideas for the clinical use of stem cell transplantation as a potential treatment for IBD.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background and Purpose
Interleukin‐36 is induced by proinflammatory cytokines and promotes inflammatory responses, creating an IL‐36‐based inflammation loop. Although hepatocytes, produce IL‐36 ...responses to drug‐induced liver injury, little is known about the mechanistic role of IL‐36 signalling during the progression of alcoholic steatohepatitis (ASH). Regarding IL‐36/IL‐36R and P2X7R coregulating the inflammatory response, we elucidated that modulation of IL‐36R‐P2X7R‐TLR axis affected hepatocyte steatosis as well as the IL‐36‐based inflammatory feedback loop that accompanies the onset of ASH.
Experimental Approach
C57BL/6J mice were subjected to either chronic‐plus‐binge ethanol feeding or acute gavage with multiple doses of ethanol to establish ASH, followed by pharmacological inhibition or genetic silencing of IL‐36R and P2X7R. AML12 cells or mouse primary hepatocytes were stimulated with alcohol, LPS plus ATP or Poly(I:C) plus ATP, followed by silencing of IL‐36γ, IL‐36R or P2X7R.
Key Results
P2X7R and IL‐36R deficiency blocked the inflammatory loop, specifically initiated by IL‐36 cytokines, in hepatocytes of mice suffering from ASH. Pharmacological inhibition to P2X7R or IL‐36R alleviated lipid accumulation and inflammatory response in ASH. IL‐36R was indispensable for P2X7R modulated NLRP3 inflammasome activation in ASH, and IL‐36 led to a vicious cycle of P2X7R‐driven inflammation in alcohol‐treated hepatocytes. TLR ligands promoted IL‐36γ production in hepatocytes, based on synergism with P2X7R.
Conclusions and Implications
Blockade of IL‐36 based inflammatory feedback loop, via IL‐36R‐P2X7R‐TLRs‐modulated NLRP3 inflammasome activation, circumvented steatosis and inflammation that accompanies the onset of ASH, suggesting that targeting IL‐36 can serve as a novel therapeutic approach to combat ASH.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Wuhan Leishenshan/Leishenshan (“Leishenshan” for short) hospital is a makeshift emergency hospital for treating patients diagnosed with the novel coronavirus-infected pneumonia (NCIP). Engineering ...construction uses modular composite building finished products to the greatest extent, which reduces the workload of field operations and saves a lot of time. The building information model (BIM) technology assists in design and construction work to meet rapid construction requirements. Besides, based on the unmanned aerial vehicles (UAVs) data analysis and application platform, digitization and intelligence in engineering construction are improved. Simultaneously, on-site construction and overall hoisting were carried out to achieve maximum efficiency. This article aims to take the construction of Leishenshan Hospital as an example to illustrate how to adopt BIM technology and other high-tech technology such as big data, artificial intelligence, drones, and 5G for the fast construction of the fabricated steel structure systems in emergency engineering projects.
•Assembled design, clean and dirty partition, total impermeability;•Modular sealing and anti-diffusion air pressure management unit;•Optimal architecture, development, logistics and process alignment;•BIM, 5G, AI, IoT, among other IT applications;•Cloud supervisors and civic engagement
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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Purinergic receptor P2x7 (P2x7R) is a key modulator of liver inflammation and fibrosis. The present study aimed to investigate the role of P2x7R in hepatic stellate cells activation. ...Lipopolysaccharide (LPS) or the conditioned medium (CM) from LPS-stimulated RAW 264.7 mouse macrophages was supplemented to human hepatic stellate cells, LX-2 for 24h and P2x7R selective antagonist A438079 (10μM) was supplemented to LX-2 cells 1h before LPS or CM stimulation. In addition LX-2 cells were primed with LPS for 4h and subsequently stimulated for 30min with 3mM of adenosine 5′-triphosphate (ATP). A438079 was supplemented to LX-2 cells 10min prior to ATP. Directly treated with LPS on LX-2 cells, mRNA expressions of interleukin (IL)-1β, IL-18 and IL-6 were increased, as well as mRNA expressions of P2x7R, caspase-1, apoptosis-associated speck-like protein containing CARD (ASC) and NOD-like receptor family, pyrin domain containing 3 (NLRP3) mRNA. LPS also increased α-smooth muscle actin (α-SMA) and type I collagen mRNA expressions, as well as collagen deposition. Interestingly treatment of LX-2 cells with LPS-activated CM exhibited the greater increase of above factors than those in LX-2 cells directly treated with LPS. Pretreatment of A438079 on LX-2 cells stimulated by LPS or LPS-activated CM both suppressed IL-1β mRNA expression. LPS combined with ATP dramatically increased protein synthesis and cleavage of IL-1β and its mRNA level than those in HSC treated with LPS or ATP alone. Additionally LX-2 cells primed with LPS and subsequently stimulated for 30min with ATP greatly increased mRNA and protein expression of caspase-1, NLRP3 and P2x7R, as well as liver fibrosis markers, α-SMA and type I collagen. These events were remarkably suppressed by A438079 pretreatment. siRNA against P2x7R reduced protein expression of NLRP3 and α-SMA, and suppressed deposition and secretion of type I collagen. The involvement of P2X7R-mediated NLRP3 inflammasome activation in IL-1β production of HSC might contribute to ECM deposition and suggests that blockade of the P2x7R-NLRP3 inflammasome axis represents a potential therapeutic target to liver fibrosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The microstructure of polymer chains plays a critical role in determining the performance of polymeric materials. Various studies have demonstrated that aside from the overall copolymer composition, ...the distribution of monomers along the polymer chains is a crucial microstructural factor in controlling the morphologies of the polymer chains. Gradient copolymers, which possess a gradual change in composition along the chain backbone, can exhibit diverse monomer sequence distributions due to variations in compositions. In this study, we conducted a computational investigation using coarse-grained models to systematically assess the effect of the monomer sequence distribution on the microphase separation morphologies and mechanical properties of the as-formed materials. Our findings indicated that systems with different monomer sequence distributions display distinct microphase separation morphologies characterized by effective Flory parameter χeff and microphase separation domain sizes. Additionally, we found that it is possible to modify the monomer sequence distributions to adjust the glass transition temperature (T g) and the divergence of T g. Moreover, our research revealed that the unique arrangement of gradient copolymers results in a hierarchical response during tensile deformation process. Specifically, under small strains, the soft segments with a low T g respond initially, while the hard domains with a high T g come into play under larger strains. The systematic understanding of the relationship between copolymer composition, structure, and properties will facilitate the design of application-oriented polymer materials, enabling the synthesis of more tailored materials for specific applications.
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IJS, KILJ, NUK, PNG, UL, UM
The current study focused on the regulatory effects of parthenolide (PNL), a bioactive component derived from Chrysanthemum parthenium L., against hepatic fibrosis via regulating the crosstalk of ...toll‐like receptor 4 (TLR4) and signal transducer and activator of transcription 3 (STAT3) in activated hepatic stellate cells (HSCs). HSCs or Raw 264.7 macrophages were activated by TGF‐β or LPS for 1 hr, respectively, and then treated with PNL, CLI‐095 (TLR4 inhibitor), or Niclosamide (STAT3 inhibitor) for the indicated time to detect the crosstalk of TLR4 and STAT3. PNL significantly decreased the expressions of α‐SMA, collagen I, and the ratio of TIMP1 and MMP13 in TGF‐β‐activated HSCs. PNL significantly reduced the releases of pro‐inflammatory cytokines, including IL‐6, IL‐1β, IL‐1α, IL‐18, and regulated signaling P2X7r/NLRP3 axis activation. PNL obviously induced the apoptosis of activated HSCs by regulating bcl‐2 and caspases family. PNL significantly inhibited the expressions of TLR4 and STAT3, including their downstream signaling. PNL could regulate the crosstalk of TLR4 and STAT3, which were verified by their inhibitors in activated HSCs or Raw 264.7 cell macrophages. Thus, PNL could decrease the expressions of fibrosis markers, reduce the releases of inflammatory cytokines, and also induce the apoptosis of activated HSCs. In conclusion, PNL could bi‐directionally inhibit TLR4 and STAT3 signaling pathway, suggesting that blocking the crosstalk of TLR4 and STAT3 might be the potential mechanism of PNL against hepatic fibrosis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The leakage current degradation, single-event burnout (SEB), and single-event gate rupture (SEGR) behaviors induced by the heavy-ion irradiation in p-Channel and n-Channel power U-shaped ...metal-oxide-semiconductor field-effect transistors (UMOSFETs) are comparatively investigated in this article via experiments and simulations. The SEB and SEGR performances of a commercially available −100-V-rated p-Channel UMOSFET are tested under heavy-ion irradiation. The experimental results show that the sample devices can be prevented from the drain leakage current or gate leakage current degradation under the bias conditions of <inline-formula> <tex-math notation="LaTeX">V_{\mathrm {GS}} = -100 </tex-math></inline-formula> V and <inline-formula> <tex-math notation="LaTeX">V_{\mathrm {GS}} = 0 </tex-math></inline-formula>. However, a severe gate leakage current degradation can occur at <inline-formula> <tex-math notation="LaTeX">V_{\mathrm {DS}} = -100 </tex-math></inline-formula> V when <inline-formula> <tex-math notation="LaTeX">V_{\mathrm {GS}} \ge 5 </tex-math></inline-formula> V. In addition, the SEB and SEGR characteristics of a 100-V-rated n-Channel UMOSFET are obtained by simulations. The simulation results indicate that a p-Channel UMOSFET can achieve much better robustness against heavy ions compared with an n-Channel UMOSFET. Further, the leakage current degradation and failure mechanisms induced by heavy-ion irradiation are investigated via simulations. Finally, an effective method, which enlarges the width and depth of the source contact trench, is introduced to enhance the SEB tolerance of an n-Channel UMOSFET. The simulation result shows that the SEB threshold voltage can represent an increase of 23.1% with the hardening method.
As the largest genus of Gentianaceae family, the Gentiana genus harbors over 400 species, widely distributed in the alpine areas of temperate regions worldwide. Plants from Gentiana genus are ...traditionally used to treat a wide variety of diseases including easing pain dispelling rheumatism, and treating liver jaundice, chronic pharyngitis and arthritis in China since ancient times. In this review, a systematic and constructive overview of the traditional uses, phytochemistry, molecular mechanisms, toxicology and pharmacological activities of the researched species of genus Gentiana is provided.
The used information in this review is based on various databases (PubMed, Science Direct, Wiley online library, Wanfang Data, Web of Science) through a search using the keyword “Gentiana” in the period of 1981–2019. Besides, other ethnopharmacological information was acquired from Chinese herbal classic books and Chinese pharmacopoeia 2015 edition.
The plants from Gentiana genus have a long tradition of various medicinal uses in Europe and Asia. Phytochemical studies showed that the main bioactive components isolated from this genus includes iridoids xanthones and flavonoids. These compounds and extracts isolated from this genus show a wide range of protective activities including hepatic protection, gastrointestinal protection, cardiovascular protection, immunomodulation, joint protection, pulmonary protection, bone protection and reproductive protection. Molecular mechanism studies also indicated several potential therapeutic targets in the treatment of certain diseases by plants from this genus. Besides, natural products from this plant show no significant animal toxicity, cytotoxicity or genotoxicity.
This review summarized the traditional medicinal uses, phytochemistry, pharmacology, toxicology and molecular mechanism of genus Gentiana, providing references and research tendency for plant-based drug development and further clinical studies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The aim of this study was to investigate the relationship between serum level of hemoglobin and neurological outcomes following cardiac arrest. Relevant studies were identified by searching ...electronic databases including PubMed, Web of Science, Cochrane Library, and Embase from June 2012 through April 2023. Articles were rigorously reviewed for their study inclusion and exclusion criteria. Pooled effect date was determined using the standardized mean difference (SMD) and 95% confidence intervals (CI). The Newcastle-Ottawa Scale was used to evaluate study quality. Subgroup analyses were conducted to determine confounding factors affecting patient outcomes. Study heterogeneity, sensitivity, and publication bias were also determined.This meta-analysis included 11 studies involving 2519 patients. Our results suggest that high serum level of hemoglobin may improve neurological prognosis(SMD = 0.60, 95%CI = 0.49-0.71, I
= 10.85). The findings of this study indicate that serum level of hemoglobin may be associated with better neurological prognosis, perhaps an appropriate increase in serum haemoglobin levels can improve the neurological prognosis of patients in cardiac arrest.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A new atmospheric pressure ionization method, plasmaspray ionization, termed as PSI, was developed to be an alternative ambient ion source for mass spectrometry. It comprises a plasma jet device and ...a sample spray part. While the nonthermal plasma jet strikes the surface of stainless steel tube out of the spray capillary, the sprayed sample will be ionized with the assistant of auxiliary gas. Although PSI is a little bit more complex than electrospray ionization (ESI) in instrument, it shows both better linearity and higher sensitivity for organic compounds. For protein samples, it presents wider distributions of multiply charged ions and higher mass resolution without sacrificing any sensitivity. For the mechanism of PSI, the charge build‐up process on the tip of capillary should play a key role for the ion formation, and the stimulated pulsed voltage on the flow tube will promote the ion aggregation speed until the charge density is high enough. PSI source contains the features of plasma ionization and ESI and can be considered as a novel combo bridging these techniques. These results reflect that this method of PSI can be applied and further developed as a versatile new ion source for a wild range of organic and biological samples.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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