Influence of Acetaldehyde Induction on Monomeric and Polymeric Polyphenols in Wine using the Polyphenol/Protein-binding Model

Polyphenols make a substantial contribution to the sensory properties of wine, and their evolution is affected by the acetaldehyde present during fermentation and ageing. In this work, five typical monomeric phenolic standards and three different polymeric flavanol fractions separated from wine were tested for polyphenol/protein binding by means of circular dichroism measurement and fluorescence spectrum assay in the presence or absence of acetaldehyde, and the formation of new oligomeric compounds linked by ethyl bridges was observed through HPLC-MS analyses. The results show that the protein-binding ability of these monomers was in the order of gallic acid > caffeic acid > quercetin > (+)-catechin > (-)-epicatechin, while acetaldehyde exerted a stronger effect on (+)-catechin and (-)-epicatechin monomers. Moreover, different wine fractions had different responses when reacted with proteins with the participation of acetaldehyde, while the polymeric proanthocyanidins produced the largest value (84.67%) of the salivary protein precipitation index and the strongest fluorescence-quenching effect

Automated identification and quantification of myocardial inflammatory infiltration in digital histological images to diagnose myocarditis

This study aims to develop a new computational pathology approach that automates the identification and quantification of myocardial inflammatory infiltration in digital HE-stained images to provide a quantitative histological diagnosis of myocarditis.898 HE-stained whole slide images (WSIs) of myocardium from 154 heart transplant patients diagnosed with myocarditis or dilated cardiomyopathy (DCM) were included in this study. An automated DL-based computational pathology approach was developed to identify nuclei and detect myocardial inflammatory infiltration, enabling the quantification of the lymphocyte nuclear density (LND) on myocardial WSIs. A cutoff value based on the quantification of LND was proposed to determine if the myocardial inflammatory infiltration was present. The performance of our approach was evaluated with a five-fold cross-validation experiment, tested with an internal test set from the myocarditis group, and confirmed by an external test from a double-blind trial group. An LND of 1.02/mm2 could distinguish WSIs with myocarditis from those without. The accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) in the five-fold cross-validation experiment were 0.899 plus or minus 0.035, 0.971 plus or minus 0.017, 0.728 plus or minus 0.073 and 0.849 plus or minus 0.044, respectively. For the internal test set, the accuracy, sensitivity, specificity, and AUC were 0.887, 0.971, 0.737, and 0.854, respectively. The accuracy, sensitivity, specificity, and AUC for the external test set reached 0.853, 0.846, 0.858, and 0.852, respectively. Our new approach provides accurate and reliable quantification of the LND of myocardial WSIs, facilitating automated quantitative diagnosis of myocarditis with HE-stained images.Comment: 21 pages,5 figures,6 Tables, 25 reference

Cosmic test of sTGC detector prototype made in China for ATLAS experiment upgrade

Following the Higgs particle discovery, the Large Hadron Collider complex will be upgraded in several phases allowing the luminosity to increase to $7 \times 10^{34}cm^{-2}s^{-1}$. In order to adapt the ATLAS detector to the higher luminosity environment after the upgrade, part of the ATLAS muon end-cap system, the Small Wheel, will be replaced by the New Small Wheel. The New Small Wheel includes two kinds of detectors: small-strip Thin Gap Chambers and Micromegas. Shandong University, part of the ATLAS collaboration, participates in the construction of the ATLAS New Small Wheel by developing, producing and testing the performance of part of the small-strip Thin Gap Chambers. This paper describes the construction and cosmic-ray testing of small-strip Thin Gap Chambers in Shandong University

Molecular mechanisms of pruritus in prurigo nodularis

Pruritus is the most common symptom of dermatological disorders, and prurigo nodularis (PN) is notorious for intractable and severe itching. Conventional treatments often yield disappointing outcomes, significantly affecting patients’ quality of life and psychological well-being. The pathogenesis of PN is associated with a self-sustained “itch-scratch” vicious cycle. Recent investigations of PN-related itch have partially revealed the intricate interactions within the cutaneous neuroimmune network; however, the underlying mechanism remains undetermined. Itch mediators play a key role in pruritus amplification in PN and understanding their action mechanism will undoubtedly lead to the development of novel targeted antipruritic agents. In this review, we describe a series of pruritogens and receptors involved in mediating itching in PN, including cytokines, neuropeptides, extracellular matrix proteins, vasculogenic substances, ion channels, and intracellular signaling pathways. Moreover, we provide a prospective outlook on potential therapies based on existing findings

A pyroptosis-related gene signature for prognosis prediction in hepatocellular carcinoma

IntroductionHepatocellular carcinoma (HCC) is one of the most invasive cancers with a low 5-year survival rate. Pyroptosis, a specialized form of cell death, has shown its association with cancer progression. However, its role in the prognosis of HCC has not been fully understood.MethodsIn our study, clinical information and mRNA expression for 1076 patients with HCC were obtained from the five public cohorts. Pyroptotic clusters were generated by unsupervised clustering based on 40 pyroptosis-related genes (PRGs) in the TCGA and ICGC cohort. A pyroptosis-related signature was constructed using least absolute shrinkage and selection operator (LASSO) regression according to differentially expressed genes (DEGs) of pyroptotic clusters. The signature was then tested in the validation cohorts (GES10142 and GSE14520) and subsequently validated in the CPTAC cohort (n=159) at both mRNA and protein levels. Response to sorafenib was explored in GSE109211.ResultsThree clusters were identified based on the 40 PRGs in the TCGA cohort. A total of 24 genes were selected based on DEGs of the above three pyroptotic clusters to construct the pyroptotic risk score. Patients with the high-risk score showed shorter overall survival (OS) compared to those with the low-risk score in the training set (P<0.001; HR, 3.06; 95% CI, 2.22-4.24) and the test set (P=0.008; HR, 1.61; 95% CI, 1.13-2.28). The predictive ability of the risk score was further confirmed in the CPTAC cohort at both mRNAs (P<0.001; HR, 2.99; 95% CI, 1.67-5.36) and protein levels (P<0.001; HR, 2.97; 95% CI 1.66-5.31). The expression of the model genes was correlated with immune cell infiltration, angiogenesis-related genes, and sensitivity to antiangiogenic therapy (P<0.05).DiscussionIn conclusion, we established a prognostic signature of 24 genes based on pyroptosis clusters for HCC patients, providing insight into the risk stratification of HCC

Aspect of Clusters Correlation at Light Nuclei Excited State

The correlation of $\alpha\alpha$ was probed via measuring the transverse momentum $p_{T}$ and width $\delta p_{T}$ of one $\alpha$, for the first time, which represents the spatial and dynamical essentialities of the initial coupling state in $^{8}$Be nucleus. The weighted interaction vertex of 3$\alpha$ reflected by the magnitudes of their relative momentums and relative emission angles proves the isosceles triangle configuration for 3$\alpha$ at the high excited energy analogous Hoyle states.Comment: 8 pages, 9 figure

Variation of Tensor Force due to Nuclear Medium Effect

The enhancement of $J^{\pi}(T)$=3$^{+}$(0) state with isospin $T=0$ excited by the tensor force in the free $^{6}$Li nucleus has been observed, for the first time, relative to a shrinkable excitation in the $^{6}$Li cluster component inside its host nucleus. Comparatively, the excitation of $J^{\pi}(T)$=0$^{+}$(1) state with isospin $T=1$ for these two $^{6}$Li formations take on an approximately equal excitation strength. The mechanism of such tensor force effect was proposed due to the intensive nuclear medium role on isospin $T$=0 state.Comment: 6 pages, 4 figure

Opposing transcriptional programs of KLF5 and AR emerge during therapy for advanced prostate cancer.

Endocrine therapies for prostate cancer inhibit the androgen receptor (AR) transcription factor. In most cases, AR activity resumes during therapy and drives progression to castration-resistant prostate cancer (CRPC). However, therapy can also promote lineage plasticity and select for AR-independent phenotypes that are uniformly lethal. Here, we demonstrate the stem cell transcription factor Krüppel-like factor 5 (KLF5) is low or absent in prostate cancers prior to endocrine therapy, but induced in a subset of CRPC, including CRPC displaying lineage plasticity. KLF5 and AR physically interact on chromatin and drive opposing transcriptional programs, with KLF5 promoting cellular migration, anchorage-independent growth, and basal epithelial cell phenotypes. We identify ERBB2 as a point of transcriptional convergence displaying activation by KLF5 and repression by AR. ERBB2 inhibitors preferentially block KLF5-driven oncogenic phenotypes. These findings implicate KLF5 as an oncogene that can be upregulated in CRPC to oppose AR activities and promote lineage plasticity