IR Models Research Articles

Mild hypothermia pretreatment improves hepatic ischemia-reperfusion injury: A systematic review and meta-analysis of animal experiments.

Mild hypothermia in hepatic ischemia-reperfusion injury is increasingly being studied. This study aimed to conduct a systematic evaluation of the effectiveness of mild hypothermia in improving hepatic ischemia-reperfusion injury. We systematically searched CNKI, WanFang Data, PubMed, Embase, and Web of Science for original studies that used animal experiments to determine how mild hypothermia(32-34°C) pretreatment improves hepatic ischemia-reperfusion injury(in situ 70% liver IR model). The search period ranged from the inception of the databases to May 5, 2023. Two researchers independently filtered the literature, extracted the data, and assessed the risk of bias incorporated into the study. The meta-analysis was performed using RevMan 5.4.1 and Stata 15 software. Eight randomized controlled trials (RCTs) involving a total of 117 rats/mice were included. The results showed that the ALT levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [Standardized Mean Difference (SMD) = -5.94, 95% CI(-8.09, -3.78), P<0.001], and AST levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [SMD = -4.45, 95% CI (-6.10, -2.78), P<0.001]. The hepatocyte apoptosis rate in the mild hypothermia pretreatment group was significantly lower than that in the normothermic control group [SMD = -6.86, 95% CI (-10.38, -3.33), P<0.001]. Hepatocyte pathology score in the mild hypothermia pretreatment group was significantly lower than that in the normothermic control group [SMD = -4.36, 95% CI (-5.78, -2.95), P<0.001]. There was no significant difference in MPO levels between the mild hypothermia preconditioning group and the normothermic control group [SMD = -4.83, 95% CI (-11.26, 1.60), P = 0.14]. SOD levels in the mild hypothermia preconditioning group were significantly higher than those in the normothermic control group [SMD = 3.21, 95% CI (1.27, 5.14), P = 0.001]. MDA levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [SMD = -4.06, 95% CI (-7.06, -1.07) P = 0.008]. Mild hypothermia can attenuate hepatic ischemia-reperfusion injury, effectively reduce oxidative stress and inflammatory response, prevent hepatocyte apoptosis, and protect liver function.

Liver Fatty Acid-binding Protein Is a More Reliable Biomarker for Liver Injury in Nonalcoholic Steatohepatitis than Other Etiologies of Hepatitis.

Liver fatty acid-binding protein (LFABP) controls hepatocyte lipid metabolism and can be a biomarker in liver diseases. We compared the correlation of LFABP levels with liver histology in viral hepatitis and nonalcoholic fatty liver disease (NAFLD) and investigated the utility of serum LFABP as a biomarker for liver damage. We included 142 patients (60 chronic viral hepatitis B [CHB], 35 chronic viral hepatitis C [CHC], 47 NAFLD) and 40 healthy controls. LFABP levels were determined in all participants, and a liver biopsy was performed on patients. The nonalcoholic steatohepatitis (NASH) activity score (NAS), hepatosteatosis, liver inflammation, and fibrosis were evaluated for NAFLD patients. Ishak's histological scores were used for viral hepatitis. The correlation between LFABP levels and histologic scores was assessed in each group. Serum LFABP levels in CHB, CHC, NAFLD, and control groups were 2.2, 3.5, 7.6, and 2.1 ng/mL, respectively. LFABP levels were significantly higher in the NAFLD group compared to the control, CHC, and CHB groups. LFABP was significantly higher in the NASH group than in nonalcoholic steatohepatitis, 8 ng/mL and 5.4 ng/mL, respectively (P = .001). In the NAFLD group, LFABP levels showed a moderate positive correlation with NAS score (r = 0.58, P <.001), ballooning degeneration (r = 0.67, P <.001), and lobular inflammation (r = 0.62, P <.001). A logistic regression study showed that the level of LFABP was predictive of NASH independent of age, gender, homeostasis model of IR, body mass index, aspartate aminotransferase, and alanine aminotransferase (OR = 1.869, P = .01). LFABP specifically correlates with liver histology in NAFLD compared to viral hepatitis. Additionally, it can distinguish NASH from simple steatosis. LFABP may be a valuable biomarker for hepatocyte injury in NASH.

Reliability analysis of multiple repairable systems under imperfect repair and unobserved heterogeneity

AbstractImperfect repairs (IRs) are widely applicable in reliability engineering since most equipment is not completely replaced after failure. In this sense, it is necessary to develop methodologies that can describe failure processes and predict the reliability of systems under this type of repair. One of the challenges in this context is to establish reliability models for multiple repairable systems considering unobserved heterogeneity associated with systems failure times and their failure intensity after performing IRs. Thus, in this work, frailty models are proposed to identify unobserved heterogeneity in these failure processes. In this context, we consider the arithmetic reduction of age (ARA) and arithmetic reduction of intensity (ARI) classes of IR models, with constant repair efficiency and a power‐law process distribution to model failure times and a univariate Gamma distributed frailty by all systems failure times. Classical inferential methods are used to estimate the parameters and reliability predictors of systems under IRs. An extensive simulation study is carried out under different scenarios to investigate the suitability of the models and the asymptotic consistency and efficiency properties of the maximum likelihood estimators. Finally, we illustrate the practical relevance of the proposed models on two real data sets.

Revisiting Bag of Words Document Representations for Efficient Ranking with Transformers

Modern transformer-based information retrieval models achieve state-of-the-art performance across various benchmarks. The self-attention of the transformer models is a powerful mechanism to contextualize terms over the whole input but quickly becomes prohibitively expensive for long input as required in document retrieval. Instead of focusing on the model itself to improve efficiency, this paper explores different bag of words document representations that encode full documents by only a fraction of their characteristic terms, allowing us to control and reduce the input length. We experiment with various models for document retrieval on MS MARCO data, as well as zero-shot document retrieval on Robust04, and show large gains in efficiency while retaining reasonable effectiveness. Inference time efficiency gains are both lowering the time and memory complexity in a controllable way, allowing for further trading off memory footprint and query latency. More generally, this line of research connects traditional IR models with neural “NLP” models and offers novel ways to explore the space between (efficient, but less effective) traditional rankers and (effective, but less efficient) neural rankers elegantly.

Bioinspired Herbicides-Ionic Liquids or Liquid Cocrystals?

This research provides information about combinations of several amino acids, including l-proline (Pro), l-arginine (Arg), and l-histidine (His), with phenoxyacetic acid herbicides (MCPA and 2,4-D). Five amino acid ionic liquids (AAILs), one amino acid higher-melting salt (AAHMS), and two amino acid liquid cocrystals (AALCs) were obtained in high yields (>90%). The ionization of the six new structures was confirmed by NMR, IR, and molecular modeling. X-ray crystallography was used to definitively confirm the binding location of the mobile hydrogen. Furthermore, we propose a computational method for estimating the energy of specific hydrogen bond(s) in AAIL crystals based on the NBO and QTAIM hydrogen bond parameters obtained by model calculations. An in-depth analysis of the structures allowed to answer the question posed in the title, ionic liquids or liquid cocrystals? AAILs based on arginine and histidine were obtained. In contrast, combining proline with MCPA and 2,4-D led to AALCs. Finally, the compounds were analyzed to measure their herbicidal activity. These studies proved that the novel form of MCPA or 2,4-D improved its ability to control weeds compared to commercial formulations containing the same active ingredients.

Improving Performance of Neural IR Models by Using a Keyword-Extraction-Based Weak-Supervision Method

Improving Performance of Neural IR Models by Using a Keyword-Extraction-Based Weak-Supervision Method

Ulinastatin protects against myocardial ischemia/reperfusion injury in rats via Rho/ROCK signaling pathway.

We aimed to study the influences of ulinastatin on diseased myocardial tissues, cardiomyocyte apoptosis and inflammatory reaction in rats with myocardial ischemia/reperfusion injury (IRI) via the Ras homolog (Rho)/Rho-associated kinase (ROCK) signaling pathway and its mechanism. The rats were randomly divided into three groups: control group (C group), IR model group (IR group) and IR model + ulinastatin treatment group (UR group). The pathological changes in myocardial tissues were detected via HE staining, the markers of myocardial injury were examined using kits, and apoptosis was determined through TUNEL assay. Moreover, ELISA was applied to measure the expressions of TNF-α, interleukin-6 (IL-6) and IL-8 in cardiac tissues, and Western blotting was performed to detect the protein expression levels of RhoA, ROCK2 and MLCP. The myocardial infarction area in the IR group was markedly larger than that in the C group (P<0.01) but was significantly reduced after ulinastatin treatment (P<0.05), and the IR group had higher levels of AST, cTnI, CK-MB and LDH than C group, but the levels of those indexes were significantly reduced after ulinastatin treatment.The cardiomyocyte apoptosis was increased in the IR group compared with that in the C group, while it was decreased in the UR group in comparison with that in the IR group. Besides, the UR group exhibited lowered expression levels of the Rho/ROCK signaling pathway-related proteins compared with the IR group. Ulinastatin may ameliorate the prognosis of rats with myocardial IRI via the Rho/ROCK signaling pathway.

Molecular mechanism of Gan-song Yin inhibiting the proliferation of renal tubular epithelial cells by regulating miR-21-5p in adipocyte exosomes

Ethnopharmacological relevanceGan-song Yin is derived from the classic ancient prescription " Gan-song pill " for the treatment of wasting-thirst in Ningxia combined with the characteristic “fragrant medicine”. It is clinically used for the treatment of early renal fibrosis caused by diabetic nephropathy. Previous studies have shown that it has a good effect and great potential in the prevention and treatment of diabetic nephropathy, but its mechanism research is still limited. Aim of the studyTo investigate the mechanism of GSY to improve DN by interfering with miR-21-5p and glycolipid metabolism in adipocyte exosomes using 3T3-L1 and TCMK-1 co-culture system. Materials and methodsThe co-culture system of 3T3-L3 and TCMK-1 was established, the IR model was established, and the stability, lipid drop change, glucose consumption, triglyceride content, cell viability, cell cycle and apoptosis level, protein content and mRNA expression of the IR model were detected. ResultsGSY inhibited 3T3-L1 activity, increased glucose consumption and decreased TG content. Decreased TCMK-1 cell viability, inhibited apoptosis, cell cycle arrest occurred in G0/G1 phase and S phase. Adipocyte IR model and co-culture system were stable within 48 h. After GSY intervention, lipid droplet decomposition and glucose consumption increased. The TG content of adipocytes increased, while the TG content of co-culture system decreased. GSY can regulate the expression of TGF-β1/SMAD signaling pathway protein in IR state. After GSY intervention, the expression of miR-21-5p was increased in 3T3-L1 and Exo cells, and decreased in TCMK-1 cells. ConclusionsGSY can regulate TGF-β1/SMAD signaling pathway through the secretion of miR-21-5p from adipocytes, protect IR TCMK-1, regulate the protein and mRNA expression levels of PPARγ, GLUT4, FABP4, and improve glucose and lipid metabolism.

NIR-Prompt: A Multi-task Generalized Neural Information Retrieval Training Framework

Information retrieval aims to find information that meets users’ needs from the corpus. Different needs correspond to different IR tasks such as document retrieval, open-domain question answering, retrieval-based dialogue, and so on, while they share the same schema to estimate the relationship between texts. It indicates that a good IR model can generalize to different tasks and domains. However, previous studies indicate that state-of-the-art neural information retrieval (NIR) models, e.g., pre-trained language models (PLMs) are hard to generalize. It is mainly because the end-to-end fine-tuning paradigm makes the model overemphasize task-specific signals and domain biases but loses the ability to capture generalized essential signals. To address this problem, we propose a novel NIR training framework named NIR-Prompt for retrieval and reranking stages based on the idea of decoupling signal capturing and combination. NIR-Prompt exploits Essential Matching Module (EMM) to capture the essential matching signals and gets the description of tasks by Matching Description Module (MDM). The description is used as task-adaptation information to combine the essential matching signals to adapt to different tasks. Experiments under in-domain multi-task, out-of-domain multi-task, and new task adaptation settings show that NIR-Prompt can improve the generalization of PLMs in NIR for both retrieval and reranking stages compared with baselines.

Introducing high concentration of hexafluorosilicate anions into an ultra-microporous MOF for highly efficient C2H2/CO2 and C2H2/C2H4 separation

Tremendous effort has been endeavored to improve the C2H2 separation performance of porous solid materials from CO2 and C2H4, aiming to gain high purity of C2H2 for producing various downstream commodities. Herein, an ultra-microporous interpenetrated MOF, SIFSIX-DPA-Cu-i, featuring multiple functional hexafluorosilicate anions, has been constructed for efficient C2H2 separation from C2H2/CO2 and C2H2/C2H4 gases mixture. Significantly, SIFSIX-DPA-Cu-i presents good C2H2/CO2 and C2H2/C2H4 separation performance, especially for C2H2/CO2, with the value of 9.34 at 298 K and 1 bar due to the introduction of a high concentration of hexafluorosilicate anions capable of preferentially capturing C2H2 through forming a strong C2H2 nano-trap arising from the strong C-H∙∙∙F and C≡C∙∙∙H interactions confirmed by in situ IR and molecular modeling. Moreover, the consecutive transient-breakthrough experiments further demonstrate the outstanding potential of SIFSIX-DPA-Cu-i for practical C2H2/CO2 and C2H2/C2H4 separation applications.

MedCPT: Contrastive Pre-trained Transformers with large-scale PubMed search logs for zero-shot biomedical information retrieval.

Information retrieval (IR) is essential in biomedical knowledge acquisition and clinical decision support. While recent progress has shown that language model encoders perform better semantic retrieval, training such models requires abundant query-article annotations that are difficult to obtain in biomedicine. As a result, most biomedical IR systems only conduct lexical matching. In response, we introduce MedCPT, a first-of-its-kind Contrastively Pre-trained Transformer model for zero-shot semantic IR in biomedicine. To train MedCPT, we collected an unprecedented scale of 255 million user click logs from PubMed. With such data, we use contrastive learning to train a pair of closely integrated retriever and re-ranker. Experimental results show that MedCPT sets new state-of-the-art performance on six biomedical IR tasks, outperforming various baselines including much larger models, such as GPT-3-sized cpt-text-XL. In addition, MedCPT also generates better biomedical article and sentence representations for semantic evaluations. As such, MedCPT can be readily applied to various real-world biomedical IR tasks. The MedCPT code and model are available at https://github.com/ncbi/MedCPT.

Ischemia‒Reperfusion accelerates neointimal hyperplasia via IL-1β-mediated pyroptosis after balloon injury in the rat carotid artery

BackgroundIschemia‒reperfusion (IR) is a pathological process that causes secondary damage to blood vessels. However, whether IR can further worsen neointima formation after balloon injury and the detailed mechanism are unclear. MethodsAn in vivo model of balloon injury to the rat carotid artery was established to study the effect of IR following balloon injury on neointima formation. Smooth muscle cells (SMCs) were isolated from rat aortas and exposed to hypoxia-reoxygenation to mimic the IR process in vitro. The in vitro cell model was used to investigate the mechanism of IR-mediated neointima formation after balloon injury, which was further confirmed in an in vivo rat model. ResultsIR aggravated neointima formation in the rat carotid artery 2 weeks after balloon injury compared with that observed in the absence of balloon injury (P < 0.001). Compared with that of normal SMCs in the rat carotid artery, the expression of IL-1β, a key proinflammatory cytokine associated with pyroptosis, was increased more than 3-fold in the IR-induced neointima (P < 0.0001) and contributed to the proliferation and migration of rat primary aortic SMCs (P < 0.0001). This process was alleviated by the antioxidant acetylcysteine (NAC), suggesting its partial dependence on intracellular ROS. In the rat model of IR following balloon injury in the carotid artery, the carotid artery that was locally transfected with AAV carrying sh-IL-1β or sh-caspase-1, which alleviated neointima formation, as indicated by a reduction in intima-media thickness in the rat carotid artery (P < 0.0001). ConclusionOur results suggested that IR could promote IL-1β production in SMCs in the carotid artery after balloon injury and aggravate neointimal hyperplasia, which was alleviated by silencing caspase-1/IL-1β signaling in SMCs in the carotid artery. These results suggest that IL-1β may be an effective target to combat IR-related neointima formation.

Purinergic P2Y2 receptor-induced activation of endothelial TRPV4 channels mediates lung ischemia-reperfusion injury.

Lung ischemia-reperfusion injury (IRI), characterized by inflammation, vascular permeability, and lung edema, is the major cause of primary graft dysfunction after lung transplantation. Here, we investigated the cellular mechanisms underlying lung IR-induced activation of endothelial TRPV4 channels, which play a central role in lung edema and dysfunction after IR. In a left lung hilar-ligation model of IRI in mice, we found that lung IRI increased the efflux of ATP through pannexin 1 (Panx1) channels at the endothelial cell (EC) membrane. Elevated extracellular ATP activated Ca2+ influx through endothelial TRPV4 channels downstream of purinergic P2Y2 receptor (P2Y2R) signaling. P2Y2R-dependent activation of TRPV4 channels was also observed in human and mouse pulmonary microvascular endothelium in ex vivo and in vitro models of IR. Endothelium-specific deletion of P2Y2R, TRPV4, or Panx1 in mice substantially prevented lung IRI-induced activation of endothelial TRPV4 channels and lung edema, inflammation, and dysfunction. These results identify endothelial P2Y2R as a mediator of the pathological sequelae of IRI in the lung and show that disruption of the endothelial Panx1-P2Y2R-TRPV4 signaling pathway could be a promising therapeutic strategy for preventing lung IRI after transplantation.

Cross Language Information Retrieval based on Automatic Query Translation for Marathi Documents

Abstract: The current research article explores the realm of Cross Language Information Retrieval (CLIR) and its significance in the digital age. It addresses the challenges faced in CLIR, including lexical and semantic disparities, the scarcity of parallel corpora, cultural nuances, and more. The article discusses innovative solutions encompassing Machine Translation, Query Expansion, Cross-Lingual Word Embeddings, and Multilingual Information Retrieval Models to enhance CLIR's effectiveness. Furthermore, it sheds light on Information Retrieval Models, such as the Boolean Model, Vector Space Model (VSM), and Probabilistic Models, explaining their principles and applications. The study also presents experimental results highlighting the limitations of monolingual IR models and the effectiveness of crosslingual techniques, such as translation and query expansion, in improving CLIR, making it a valuable tool for accessing information across languages.

Gracilaria chorda subcritical-water extracts as ameliorant of insulin resistance induced by high-glucose in zebrafish and dexamethasone in L6 myotubes

Background and aimInsulin resistance (IR) is a pathological condition in which cells fail to respond normally to insulin. Loss of insulin sensitivity disrupts glucose homeostasis and elevates the risk of developing the metabolic syndrome that includes Type 2 diabetes. This study assesses the effect on subcritical-water extract of Gracilaria chorda (GC) at 210 °C (GCSW210) in IR induction models of high glucose (HG)-induced zebrafish larvae and dexamethasone (DEX)-induced L6 myotubes. Experimental procedureThe dose of HG and DEX for IR induction in zebrafish larvae and L6 myotubes was 130 mM or 0.5 μM. The capacity of glucose uptake was quantified by fluorescence staining or intensity. In addition, the activation of protein and mRNA expressions for insulin signaling (insulin-dependent or independent pathways) was measured. Results and conclusionExposure of zebrafish larvae to HG significantly reduced the intracellular glucose uptake with dose-dependnet manner compared to control. However, the group treated with GCSW210 significantly averted HG levels like the insulin-treated group, and significantly up- or down-regulated the mRNA expressions related to insulin production (insα) and insulin signaling pathways. Moreover, the treatment with GCSW210 effectively regulated the protein expression of PI3K/AKT, AMPK, and GLUT4 involved in the action of insulin in IR models of L6 myotubes compared to DEX-treated control. Our data indicate that GCSW210 stimulates activation of PI3K/AKT and AMPK pathways to attenuate the development of IR induced by HG in zebrafish and DEX in L6 myotubes. In conclusion, GCSW210 is a potential agent for alleviating various diseases associated with the insulin resistance.

Studies on transition metals (Rh, Ir, Co) doped silicon carbide nanotubes (SiCNT) for the detection and adsorption of acrolein: Insight from DFT approach

The remarkable ability for gas sensors to detect pollutants makes the development of sensors an interesting one. Employing the density functional theory at the DFT/ωB97XD/def2-SVP (d,p) level of computation, the potential for SiC (Nanotube) and Rh, Ir and Co doped models to effectively adsorbed acrolein is investigated. The electronic properties of the nanotubes show, the significance of doping as observed energy gap of doped surfaces was considerably reduced compared to the native SiCNT, while the sensitivity, and adsorption properties of the Rh, Ir, and Co doped systems are enhanced and confirms suitability for the adsorption of acrolein. Similarly, the doped systems showed strong intermolecular interaction owing to high values for perturbation energies with major contributions from the donor lone pair (LP) orbital – antibonding (π*) acceptor orbital. Also, the density of state (DOS) plot revealed the presence of antibonding MOs in the studied systems. From the topology analysis, the non-covalent nature of the interaction between the adsorbate and adsorbent is dominant for all systems which implies excellent adsorptive behavior. Furthermore, our estimates for adsorption energies reveal that SiCNT adsorbs acrolein more strongly than doped systems, with an Eads of −4.54 eV, while Ir@SiCNT exhibits less adsorption than other systems, with an Eads of −4.10 eV, markedly suggesting it as a potential acrolein sensing material, profoundly supported by the enthalpy change and free Gibbs energy thermodynamic properties results in conjunction Furthermore, our estimates for adsorption energies reveal that SiCNT adsorbs acrolein more strongly than doped systems, with an Eads of −4.54 eV, while Ir@SiCNT exhibits less adsorption than other systems, with an Eads of −4.10 eV, markedly suggesting it as a potential acrolein sensing material, profoundly supported by the enthalpy change and free Gibbs energy thermodynamic properties results in conjunction with the systems’ electrical conductivity (σ), charge transfer (Qt), Fermi level (EFL), recovery time, and sensor response mechanism of detection. SiCNT_AC from the ab initio molecular dyanamic simulation showed a stable configuration with an initial total energy of 794.730 and a decrease final energy of 794.048 which gave rise to an average and standard deviation of 793.748 ± 0.357 compared to other studied systems. Our findings demonstrate the efficacy of the studied metallic SiCNT materials to effectively adsorb acrolein gas molecules, which provides for sensitivity, repeatability, reproducibility of acrolein sensing experimental work.

MODELING OF FARMER EXCHANGE RATE IN ACEH PROVINCE USING LONGITUDINAL DATA ANALYSIS

Farmer's Exchange Rate (FER) is one indicator to see the level of farmers' welfare. From 2014 to 2020, Aceh Province's FER was below 100 which indicates that farmers have not yet reached the level of welfare. This happens because of various factors including the price received by farmers (IR) is smaller than the price paid by farmers (IP). To find out the factors that influence the FER, it is necessary to do an analysis by forming a model. In this study, modeling of the FER data will be carried out, and see the factors that influence the index number with the longitudinal data regression approach. There are three estimation models, i.e. Common Effect Model, Fixed Effect Model, and Random Effect Model. Model selection of the best model is by using the Chow, Hausman, and Lagrange Multiplier tests. Furthermore, test the significance of the parameters using the simultaneous and partial tests and also see the value of the coefficient of determination (R2). The results obtained indicate that the appropriate model for the IR and IP data is the Random Effect Model where the R2for the IR and IP models are 67.06% and 85.42 respectively.

Quercitrin alleviates lipid metabolism disorder in polycystic ovary syndrome-insulin resistance by upregulating PM20D1 in the PI3K/Akt pathway

BackgroundAbnormal endocrine metabolism caused by polycystic ovary syndrome combined with insulin resistance (PCOS-IR) poses a serious risk to reproductive health in females. Quercitrin is a flavonoid that can efficiently improve both endocrine and metabolic abnormalities. However, it remains unclear if this agent can exert therapeutic effect on PCOS-IR. MethodsThe present study used a combination of metabolomic and bioinformatic methods to screen key molecules and pathways involved in PCOS-IR. A rat model of PCOS-IR and an adipocyte IR model were generated to investigate the role of quercitrin in regulating reproductive endocrine and lipid metabolism processes in PCOS-IR. ResultsPeptidase M20 domain containing 1 (PM20D1) was screened using bioinformatics to evaluate its participation in PCOS-IR. PCOS-IR regulation via the PI3K/Akt signaling pathway was also investigated. Experimental analysis showed that PM20D1 levels were reduced in insulin-resistant 3T3-L1 cells and a letrozole PCOS-IR rat model. Reproductive function was inhibited, and endocrine metabolism was abnormal. The loss of adipocyte PM20D1 aggravated IR. In addition, PM20D1 and PI3K interacted with each other in the PCOS-IR model. Furthermore, the PI3K/Akt signaling pathway was shown to participate in lipid metabolism disorders and PCOS-IR regulation. Quercitrin reversed these reproductive and metabolic disorders. ConclusionPM20D1 and PI3K/Akt were required for lipolysis and endocrine regulation in PCOS-IR to restore ovarian function and maintain normal endocrine metabolism. By upregulating the expression of PM20D1, quercitrin activated the PI3K/Akt signaling pathway, improved adipocyte catabolism, corrected reproductive and metabolic abnormalities, and had a therapeutic effect on PCOS-IR.

Propofol inhibits myocardial injury induced by microvesicles derived from hypoxia-reoxygenated endothelial cells via lncCCT4-2/CCT4 signaling

BackgroundIschemia-reperfusion (IR) induces increased release of extracellular vesicles in the heart and exacerbates myocardial IR injury. We have previously shown that propofol attenuates hypoxia/reoxygenation (HR)-induced injury in human umbilical vein endothelial cells (HUVECs) and that microvesicles derived from propofol-treated HUVECs inhibit oxidative stress in endothelial cells. However, the role of microvesicles derived from propofol post-treated HUVECs ((HR + P)-EMVs) in IR-injured cardiomyocytes is unclear. In this study, we aimed to investigate the role of (HR + P)-EMVs in cardiac IR injury compared to microvesicles derived from hypoxic/reoxygenated HUVECs (HR-EMVs) and to elucidate the underlying mechanisms.MethodsHypoxia/reoxygenation (HR) models of HUVECs and AC16 cells and a mouse cardiac IR model were established. Microvesicles from HR-injured HUVECs, DMSO post-treated HUVECs and propofol post-treated HUVECs were extracted by ultra-high speed centrifugation, respectively. The above EMVs were co-cultured with HR-injured AC16 cells or injected intracardially into IR mice. Flow cytometry and immunofluorescence were used to determine the levels of oxidative stress and apoptosis in cardiomyocytes. Apoptosis related proteins were detected by Western blot. Echocardiography for cardiac function and Evans blue-TTC staining for myocardial infarct size. Expression of lncCCT4-2 in EMVs and AC16 cells was analysed by whole transcriptome sequencing of EMVs and RT-qPCR. The molecular mechanism of inhibition of myocardial injury by (HR + P)-EMVs was elucidated by lentiviral knockdown of lncCCT4-2, plasmid overexpression or knockdown of CCT4, and actinomycin D assay.ResultsIn vitro and in vivo experiments confirmed that HR-EMVs exacerbated oxidative stress and apoptosis in IR-injured cardiomyocytes, leading to increased infarct size and worsened cardiac function. Notably, (HR + P)-EMVs induced significantly less oxidative stress and apoptosis in IR-injured cardiomyocytes compared to HR-EMVs. Mechanistically, RNA sequencing of EMVs and RT-qPCR showed that lncCCT4-2 was significantly upregulated in (HR + P)-EMVs and cardiomyocytes co-cultured with (HR + P)-EMVs. Reduction of lncCCT4-2 in (HR + P)-EMVs enhanced oxidative stress and apoptosis in IR-injured cardiomyocytes. Furthermore, the anti-apoptotic activity of lncCCT4-2 from (HR + P)-EMVs was achieved by increasing the stability of CCT4 mRNA and promoting the expression of CCT4 protein in cardiomyocytes.ConclusionsOur study showed that (HR + P)-EMVs uptake by IR-injured cardiomyocytes upregulated lncCCT4-2 in cardiomyocytes and promoted CCT4 expression, thereby inhibiting HR-EMVs induced oxidative stress and apoptosis.

A target-cell limited model can reproduce influenza infection dynamics in hosts with differing immune responses

We consider a hierarchy of ordinary differential equation models that describe the within-host viral kinetics of influenza infections: the IR model explicitly accounts for an immune response to the virus, while the simpler, target-cell limited TEIV and TV models do not. We show that when the IR model is fitted to pooled experimental murine data of the viral load, fraction of dead cells, and immune response levels, its parameters values can be determined. However, if, as is common, only viral load data are available, we can estimate parameters of the TEIV and TV models but not the IR model. These results are substantiated by a structural and practical identifiability analysis. We then use the IR model to generate synthetic data representing infections in hosts whose immune responses differ. We fit the TV model to these synthetic datasets and show that it can reproduce the characteristic exponential increase and decay of viral load generated by the IR model. Furthermore, the values of the fitted parameters of the TV model can be mapped from the immune response parameters in the IR model. We conclude that, if only viral load data are available, a simple target-cell limited model can reproduce influenza infection dynamics and distinguish between hosts with differing immune responses.