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Abstract We have conducted a model independent analysis of the $$K^+ \bar{K}^0$$ K + K ¯ 0 pair correlation function obtained from ultra high energy pp collisions, with the aim of extracting the information encoded in it related to the $$K\bar{K}$$ K K ¯ interaction and the coupled channel $$\pi ^+ \eta $$ π + η . With the present large errors at small relative $$K^+\bar{K}^0$$ K + K ¯ 0 momenta, we find that the information obtained about the scattering matrix suffers from large uncertainties. Even then, we are able to show that the data imply the existence of the $$a_0$$ a 0 resonance, $$a_0(980)$$ a 0 ( 980 ) , showing as a strong cusp close to the $$K\bar{K}$$ K K ¯ threshold. We also mention that the measurement of the $$\pi ^+ \eta $$ π + η correlation function will be essential in order to constrain more the information on $$K\bar{K}$$ K K ¯ dynamics that can be obtained from correlation functions.

A reasonable heat treatment process for TC4 ELI titanium alloy is crucial to tune microstructures to improve its explosion resistance. However, there is limited investigation on tuning microstructures of TC4 ELI to improve explosion resistance. Moreover, the current challenge is quantifying microstructural changes’ effects on explosion resistance and incorporating microstructural changes into finite element models. This work aims to tune microstructures to improve explosion resistance and elucidate their anti-explosion mechanism, and find a suitable method to incorporate microstructural changes into finite element models. In this work, we systematically study the deformation and failure characteristics of TC4 ELI plates with varying microstructures using an air explosion test and LS-DYNA finite element modeling. The Johnson‒Cook (JC) constitutive parameters are used to quantify the effects of microstructural changes on explosion resistance and incorporate microstructural changes into finite element models. Because of the heat treatment, one plate has equiaxed microstructure and the other has bimodal microstructure. The convex of the plate after the explosion has a quadratic relationship with the charge mass, and the simulation results demonstrate high reliability, with the error less than 17.5%. Therefore, it is feasible to obtain corresponding JC constitutive parameters based on the differences in microstructures and mechanical properties and characterize the effects of microstructural changes on explosion resistance. The bimodal target exhibits excellent deformation resistance. The response of bimodal microstructure to the shock wave may be more intense under explosive loading. The well-coordinated structure of the bimodal target enhances its resistance to deformation.

Abstract Activation of the mechanistic target of rapamycin (mTOR) is a key metabolic checkpoint of pro-inflammatory T-cell development that contributes to the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE), however, the underlying mechanisms remain poorly understood. Here, we identify a functional role for Rab4A-directed endosome traffic in CD98 receptor recycling, mTOR activation, and accumulation of mitochondria that connect metabolic pathways with immune cell lineage development and lupus pathogenesis. Based on integrated analyses of gene expression, receptor traffic, and stable isotope tracing of metabolic pathways, constitutively active Rab4AQ72L exerts cell type-specific control over metabolic networks, dominantly impacting CD98-dependent kynurenine production, mTOR activation, mitochondrial electron transport and flux through the tricarboxylic acid cycle and thus expands CD4+ and CD3+CD4−CD8− double-negative T cells over CD8+ T cells, enhancing B cell activation, plasma cell development, antinuclear and antiphospholipid autoantibody production, and glomerulonephritis in lupus-prone mice. Rab4A deletion in T cells and pharmacological mTOR blockade restrain CD98 expression, mitochondrial metabolism and lineage skewing and attenuate glomerulonephritis. This study identifies Rab4A-directed endosome traffic as a multilevel regulator of T cell lineage specification during lupus pathogenesis.

Abstract Background Postoperative hyper-inflammation is a frequent event in patients with acute Stanford type A aortic dissection (ATAAD) after surgical repair. This study's objective was to determine which inflammatory biomarkers could be used to make a better formula for identifying postoperative hyper-inflammation, and which risk factors were associated with hyper-inflammation. Methods A total of 405 patients were enrolled in this study from October 1, 2020 to April 1, 2023. Of these patients, 124 exhibited poor outcomes. In order to investigate the optimal cut-off values for poor outcomes, logistic and receiver operating characteristic analyses were performed on the following parameters on the first postoperative day: procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), and systemic immune-inflammation index (SII). These cut-off points were used to separate the patients into hyper-inflammatory (n = 52) and control (n = 353) groups. Finally, the logistic were used to find the risk factors of hyper-inflammatory. Results PCT, CRP, IL-6, and SII were independent risk factors of poor outcomes in the multivariate logistic model. Cut-off points of these biomarkers were 2.18 ng/ml, 49.76 mg/L, 301.88 pg/ml, 2509.96 × 109/L respectively. These points were used to define postoperative hyper-inflammation (OR 2.97, 95% CI 1.35–6.53, P 180 min, and deep hypothermia circulatory arrest (DHCA) > 40 min were the independent risk factors for hyper-inflammation. Conclusions PCT > 2.18, CRP > 49.76, IL-6 > 301.88, and SII 180 min and DHCA > 40 min were separate risk factors for postoperative hyper-inflammation.

Abstract Liver injury is a core pathological process in the majority of liver diseases, yet the genetic factors predisposing individuals to its initiation and progression remain poorly understood. Here we show that asialoglycoprotein receptor 1 (ASGR1), a lectin specifically expressed in the liver, is downregulated in patients with liver fibrosis or cirrhosis and male mice with liver injury. ASGR1 deficiency exacerbates while its overexpression mitigates acetaminophen-induced acute and CCl4-induced chronic liver injuries in male mice. Mechanistically, ASGR1 binds to an endoplasmic reticulum stress mediator GP73 and facilitates its lysosomal degradation. ASGR1 depletion increases circulating GP73 levels and promotes the interaction between GP73 and BIP to activate endoplasmic reticulum stress, leading to liver injury. Neutralization of GP73 not only attenuates ASGR1 deficiency-induced liver injuries but also improves survival in mice received a lethal dose of acetaminophen. Collectively, these findings identify ASGR1 as a potential genetic determinant of susceptibility to liver injury and propose it as a therapeutic target for the treatment of liver injury.

Abstract Tumor organoids, especially patient-derived organoids (PDOs) exhibit marked similarities in histopathological morphology, genomic alterations, and specific marker expression profiles to those of primary tumour tissues. They are applied in various fields including drug screening, gene editing, and identification of oncogenes. However, CAR-T therapy in the treatment of solid tumours is still at an exploratory stage. Tumour organoids offer unique advantages over other preclinical models commonly used for CAR-T therapy research, which the preservation of the biological characteristics of primary tumour tissue is critical for the study of early-stage solid tumour CAR-T therapies. Although some investigators have used this co-culture model to validate newly targeted CAR-T cells, optimise existing CAR-T cells and explore combination therapy strategies, there is still untapped potential in the co-culture models used today. This review introduces the current status of the application of tumour organoid and CAR-T cell co-culture models in recent years and commented on the limitations of the current co-cultivation model. Meanwhile, we compared the tumour organoid model with two pre-clinical models commonly used in CAR-T therapy research. Eventually, combined with the new progress of organoid technologies, optimization suggestions were proposed for the co-culture model from five perspectives: preserving or reconstructing the tumor microenvironment, systematization, vascularization, standardized culture procedures, and expanding the tumor organoids resource library, aimed at assisting related researchers to better utilize co-culture models.

Abstract We study under which conditions a first-order phase transition in a composite dark sector can yield an observable stochastic gravitational-wave signal. To this end, we employ the Linear-Sigma model featuring N f = 3, 4, 5 flavours and perform a Cornwall-Jackiw-Tomboulis computation also accounting for the effects of the Polyakov loop. The model allows us to investigate the chiral phase transition in regimes that can mimic QCD-like theories incorporating in addition composite dynamics associated with the effects of confinement-deconfinement phase transition. A further benefit of this approach is that it allows to study the limit in which the effective interactions are weak. We show that strong first-order phase transitions occur for weak effective couplings of the composite sector leading to gravitational-wave signals potentially detectable at future experimental facilities.