Efficacy and safety of intracoronary pro-urokinase combined with low-pressure balloon pre-dilatation during percutaneous coronary intervention in patients with anterior ST-segment elevation myocardial infarction.

BACKGROUND: The efficacy and safety of low-pressure balloon pre-dilatation before intracoronary pro-urokinase (pro-UK) in preventing no-reflow during percutaneous coronary intervention (PCI) remains unknown. This study aimed to evaluate the clinical outcomes of intracoronary pro-UK combined with low-pressure balloon pre-dilatation in patients with anterior ST-segment-elevation myocardial infarction (STEMI). METHODS: This was a randomized, single-blind, investigator-initiated trial that included 179 patients diagnosed with acute anterior STEMI. All patients were eligible for PCI and were randomized into two groups: intracoronary pro-UK combined with (ICPpD group, n = 90) or without (ICP group, n = 89) low-pressure balloon pre-dilatation. The main efficacy endpoint was complete epicardial and myocardial reperfusion. The safety endpoints were major adverse cardiovascular events (MACEs), which were analyzed at 12 months follow-up. RESULTS: Patients in the ICPpD group presented significantly higher TIMI myocardial perfusion grade 3 (TMPG3) compared to those in the ICP group (77.78% versus 68.54%, P = 0.013), and STR ≥ 70% after PCI 30 min (34.44% versus 26.97%, P = 0.047) or after PCI 90 min (40.0% versus 31.46%, P = 0.044). MACEs occurred in 23 patients (25.56%) in the ICPpD group and in 32 patients (35.96%) in the ICP group. There was no difference in hemorrhagic complications during hospitalization between the groups. CONCLUSION: Patients with acute anterior STEMI presented more complete epicardial and myocardial reperfusion with adjunctive low-pressure balloon pre-dilatation before intracoronary pro-UK during PCI. TRIAL REGISTRATION: 2019xkj213.

Streptococcus salivarius ameliorates the destructive effect on the epithelial barrier by inhibiting the growth of Prevotella melaninogenica via metabolic acid production.

BACKGROUND: Oral lichen planus (OLP) is one of the most common oral mucosal diseases, exhibiting a higher prevalence in women than men, but its pathogenesis is still unclear. Current research suggests that microbial dysbiosis may play an important role in the pathogenesis of OLP. Our previous research has found that the increase of Prevotella melaninogenica and decrease of Streptococcus salivarius have been identified as a potential pathogenic factor in OLP. Consequently, the objective of this study is to examine whether S. salivarius can counteract the detrimental effects of P. melaninogenica on the integrity of the epithelial barrier function. MATERIALS AND METHODS: Epithelial barrier disruption was induced by P. melaninogenica in human keratinocytes (HaCaT cells). HaCaT cells were pretreated with S. salivarius(MOI = 20) or cell-free supernatant for 3 h, followed by treatment with P. melaninogenica (MOI = 5) for 3 h. The epithelial barrier integrity of HaCaT cells was detected by FD4 permeability. The mRNA level of tight junction protein was detected by quantitative real-time polymerase chain reaction (PCR). Immunofluorescence and Western Blot were used to detect the protein expression of zonula occludin-1 (ZO-1). The serial dilution-spotting assay was applied to monitor the viability of P. melaninogenica at the end of 8 and 24 h incubation. RESULTS: Challenge by P. melaninogenica decreased the levels of tight junction proteins, including occludin, ZO-1, and claudin in HaCaT cells. S. salivarius or its cell-free supernatant inhibited the down-regulation of ZO-1 mRNA and protein expression levels induced by P. melaninogenica and thus improved the epithelial barrier function. The inhibitory effect of the cell-free supernatant of S. salivarius on the growth of P. melaninogenica is associated with metabolic acid production rather than with bacteriocins and hydrogen peroxide. CONCLUSIONS: These results suggest that live S. salivarius or its cell-free supernatant significantly ameliorated the disruption of epithelial tight junctions induced by P. melaninogenica, likely through the inhibition of P. melaninogenica growth mediated by metabolic acid production.

[Toxic effect and mechanism of Tripterygium glycosides on ovarian germline stem cells of mice in vitro by Notch signaling pathway].

The ovarian germline stem cells(OGSCs) cultured in the optimized culture system were used as the research object to observe the effect of Tripterygium glycosides(TG) on OGSCs and explore the mechanism of reproductive toxicity by the Notch signaling pathway. Cell counting kit-8(CCK-8) was used to observe the viability level of OGSCs in mice cultured in vitro by TG of 3.75, 7.5, and 15 µg·mL~(-1). Immunofluorescence technology and reverse transcription-polymerase chain reaction(RT-PCR) were used to detect the protein and gene expression level of OGSCs marker mouse vasa homologue(MVH) and octamer-binding transcription factor 4(Oct4) by TG of 3.75 µg·mL~(-1). RT-PCR detected the gene expression of neurogenic locus Notch homolog protein 1(Notch1), Hes family BHLH transcription factor 1(Hes1), and jagged canonical Notch ligand 1(Jagged1). The RNA was extracted for transcriptome analysis to analyze the mechanism of action of TG intervention on OGSCs. 3.75 µg·mL~(-1) of TG was combined with 40 ng·mL~(-1) Notch signaling pathway γ-secretagocin agonist jagged canonical notch ligand(Jagged) for administration. CCK-8 was used to detect the viability level of OGSCs. Double immunofluorescence technology was used to detect the protein co-expression of MVH with Hes1, Notch1, and Jagged1. The results showed that compared with the blank group, the TG administration group significantly inhibited the activity of OGSCs(P<0.01 or P<0.001). It could reduce the protein and gene expression of OGSC markers, namely MVH and Oct4(P<0.05, P<0.01, or P<0.001). It could significantly inhibit the gene expression of Notch1, Hes1, and Jagged1(P<0.001). Transcriptomic analysis showed that TG affected the growth and proliferation of OGSCs by intervening Jagged1, a ligand associated with the Notch signaling pathway. The experimental results showed that the combination of Notch signaling pathway γ-secretagorein agonist Jagged could significantly alleviate the decrease in OGSC viability induced by TG(P<0.001) and significantly increased the OGSC viability compared with the TG group(P<0.001). It also could significantly increase the co-expression of MVH/Jagged1, MVH/Hes1, and MVH/Notch1 proteins(P<0.01 or P<0.001). It suggested that TG play the role of γ-secretagorease inhibitors by downregulating the OGSC markers including MVH and Oct4 and Notch signaling pathway molecules such as Notch1, Hes1, and Jagged1, participate in the OGSC pathway, and mediate reproductive toxicity caused by the Notch signaling pathway.

Exploring the Role of Traditional Chopstick Culture and Interpersonal Communication in Health Campaign-Targeted Behavior.

Traditional chopstick culture is widely recognized as a vital factor associated with health behavior. After the outbreak of COVID-19 in China, the Gongkuai campaign aims to change long-held traditions of communal eating habits. Little is known about the effect of individuals' perception of traditional chopstick culture and other factors on Gongkuai campaign-targeted goal. This study investigates how social-environmental and cognitive factors motivate individuals to use serving chopsticks (the Chinese Gongkuai campaign-targeted goal) and how such effects are moderated by traditional chopstick culture. Data was collected using a nationwide online survey and analyzed using structural equation modeling. The findings revealed that campaign-generated interpersonal communication positively affects individual cognitive factors. Furthermore, cognitive factors promote behavioral intentions to use serving chopsticks. While traditional chopstick culture does not directly influence an intention to use serving chopsticks, it plays a different role in the relationships between three cognitive factors and serving chopsticks use intention. Based on the results, policy implications about how to motivate individuals to use serving chopsticks are discussed.

Association of glycogen synthase kinase-3ß with cognitive impairment in type 2 diabetes patients: a six-year follow-up study.

Background: Our previous multicenter case-control study showed that aging, up-regulation of platelet glycogen synthase kinase-3ß (GSK-3ß), impaired olfactory function, and ApoE ϵ4 genotype were associated with cognitive decline in type 2 diabetes mellitus (T2DM) patients. However, the causal relationship between these biomarkers and the development of cognitive decline in T2DM patients remains unclear. Methods: To further investigate this potential relationship, we designed a 6-year follow-up study in 273 T2DM patients with normal cognitive in our previous study. Baseline characteristics of the study population were compared between T2DM patients with and without incident mild cognitive impairment (MCI). We utilized Cox proportional hazard regression models to assess the risk of cognitive impairment associated with various baseline biomarkers. Receiver operating characteristic curves (ROC) were performed to evaluate the diagnostic accuracy of these biomarkers in predicting cognitive impairment. Results: During a median follow-up time of 6 years (with a range of 4 to 9 years), 40 patients (16.13%) with T2DM developed MCI. Participants who developed incident MCI were more likely to be older, have a lower education level, have more diabetic complications, a higher percentage of ApoE ϵ4 allele and a higher level of platelet GSK-3ß activity (rGSK-3ß) at baseline (P<0.05). In the longitudinal follow-up, individuals with higher levels of rGSK-3ß were more likely to develop incident MCI, with an adjusted hazard ratio (HR) of 1.60 (95% confidence interval [CI] 1.05, 2.46), even after controlling for potential confounders. The AUC of the combination of age, rGSK-3ß and ApoEϵ4 allele predicted for incident MCI was 0.71. Conclusion: Platelet GSK-3ß activity could be a useful biomarker to predict cognitive decline, suggesting the feasibility of identifying vulnerable population and implementing early prevention for dementia.

Association between the cumulative triglyceride-glucose index and the recurrence of atrial fibrillation after radiofrequency catheter ablation.

BACKGROUND: Triglyceride-glucose (TyG) index values are a new surrogate marker for insulin resistance. This study aimed to explore the relationship between cumulative TyG index values and atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA). METHODS: A total of 576 patients with AF who underwent RFCA at the Second Affiliated Hospital of Xi'an Jiaotong University were included in this study. The participants were grouped based on cumulative TyG index values tertiles within 3 months after ablation. Cox regression and restricted cubic spline analyses were used to determine the relationship between cumulative TyG index values and AF recurrence. The predictive value of all risk factors was assessed by receiver operating curve analysis. RESULTS: There were 375 patients completed the study (age: 63.23 ± 10.73 years, 64.27% male). The risk of AF recurrence increased with increasing cumulative TyG index values tertiles. After adjusting for potential confounders, patients in the medium cumulative TyG index group [hazard ratio (HR) = 4.949, 95% CI: 1.778-13.778, P = 0.002] and the high cumulative TyG index group (HR = 8.716, 95% CI: 3.371-22.536, P < 0.001) had a higher risk of AF recurrence than those in the low cumulative TyG index group. The restricted cubic spline regression model also showed an increased risk of AF recurrence with increasing cumulative TyG index values. When considering cumulative TyG index values, left atrial diameter, and lactate dehydrogenase levels as a comprehensive factor, the model could effectively predict AF recurrence after RFCA [area under the curve (AUC) = 0.847, 95% CI: 0.797-0.897, P < 0.001]. CONCLUSIONS: Cumulative TyG index values were a risk factor for AF recurrence after RFCA. Monitoring longitudinal TyG index values may assist with optimized for risk stratification and outcome prediction for AF recurrence.

Ultrasound-based Radiomics Predicts Short-term Outcomes in Hepatitis B Virus-related Acute-on-chronic Liver Failure.

BACKGROUND: The prognosis in hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) is challenging due to heterogeneity. Radiomics may enable noninvasive outcome prediction. OBJECTIVE: This study aimed to evaluate ultrasound-based radiomics for predicting outcomes in HBV-ACLF. METHODS: We enrolled 264 HBV-ACLF patients, dividing them into a training cohort (n=184) and a validation cohort (n=80). From hepatic ultrasound images, 455 radiomic features were extracted. Radiomics-based phenotypes were identified through unsupervised hierarchical clustering. A radiomic signature was developed using a Cox-LASSO algorithm to predict 30-day mortality. Furthermore, we integrated the signature with independent clinical predictors via multivariate Cox regression to construct a combined clinical-radiomic nomogram (CCR-nomogram). Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) assessed performance improvements achieved by adding radiomic features to clinical data. RESULTS: Both clustering and radiomic signature identified two distinct subgroups with significant differences in clinical characteristics and 30-day prognosis. In the training cohort, the signature achieved a C-index of 0.746, replicated in validation with a C-index of 0.747. The CCR-nomogram achieved C-indices of 0.834 and 0.819 for the training and validation cohorts. Incorporating radiomic features significantly improved the CCRnomogram over the signature and clinical-only models, evidenced by IDI of 0.108-0.264 and NRI of 0.292-0.540 in both cohorts (all p0.05). CONCLUSION: Ultrasound-based radiomics offered prognostic information complementary to clinical data and demonstrated potential to enhance outcome prediction in HBV-ACLF.

Prognostic nomogram in patients with gastrointestinal stromal tumors: a SEER-based study.

Background: Gastrointestinal stromal tumor (GIST) is a common mesenchymal tumor of the gastrointestinal system. They originate from the interstitial cells of Cajal located within the muscle layer and are characterized by over-expression of the tyrosine kinase receptor KIT. Methods: Data from the Surveillance Epidemiology, and End Results (SEER) database of 1,213 patients diagnosed with GIST between 2010 and 2019 were dichotomized into a modeling set and a validation set at a 2:1 ratio. For the modeling set, both univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. A nomogram was then constructed based on these determinants. Model efficacy was tested using receiver operating characteristic (ROC) curves, calibration curves, clinical decision curves, and risk stratification analysis in both subsets. Results: Identified prognostic determinants included age, sex, pathological differentiation level, tumor-node-metastasis (TNM) stage, surgical intervention, radiotherapy, and marital status. The constructed nomogram showed area under the ROC curve (AUC) values of 0.822, 0.793, and 0.779 for 1-, 3-, and 5-year overall survival (OS) in the modeling set, respectively, while in the validation set, the values were 0.796, 0.823, and 0.806, respectively. Calibration plots from both sets confirmed the concordance between predicted and observed survival. Decision curve analysis (DCA) indicated significant clinical utility for the nomogram. Risk stratification of the patient data revealed distinct survival differences between high-risk and low-risk cohorts in both sets (P<0.001). Conclusions: A novel and potent nomogram for the prognosis of GIST has been introduced. This model's precision offers crucial insights for clinical decisions, yet further external validation remains essential.

Reproductive outcomes following copper­containing intrauterine device after hysteroscopic lysis for intrauterine adhesions.

The present study aimed to investigate the reproductive outcomes of copper-containing intrauterine devices (IUDs) after hysteroscopic lysis in patients with mild to severe intrauterine adhesions (IUAs), according to the American Fertility Society (AFS) classification. Therefore, a prospective randomized controlled study was conducted at the Affiliated Jinhua Hospital of Wenzhou Medical University (Jinhua, China). A total of 173 women with IUAs were initially recruited between January 2020 and June 2021 and were then randomized to the copper-containing IUD group or the no barrier device group. Following hysteroscopic procedure, the fertility and obstetric outcomes were analyzed. Among the 173 patients enrolled, a total of 109 participants completed the study protocol. The results showed that AFS scores were not significantly different between the two groups prior to hysteroscopy. In addition, no statistically significant differences were recorded in pregnancy and live birth rates between the copper-containing IUD and no barrier device groups. Overall, the results of the current study indicated that the copper-containing IUDs had no positive effect on pregnancy and live birth rates in patients with mild to severe IUAs after hysteroscopic adhesiolysis. The present trial was retrospectively registered in the Chinese Clinical Trial Registry on 28th December 2023 (registration no. ChiCTR2300079233).

Overexpression of P5CDH from Cleistogenes songorica improves alfalfa growth performance under field drought conditions.

Water stress affects the metabolic regulation and delays the growth and development of alfalfa, causing a reduction in biomass. New alfalfa germplasm was created with improved drought tolerance in greenhouse conditions by introducing the key gene P5CDH1 from C. songorica, a xerophytic grass. However, the field adaptability and response mechanism of new drought-tolerant alfalfa germplasms under water stress are still unclear. In the present study, the yield and quality traits of transgenic CsP5CDH1 alfalfa lines under water stress and normal irrigation conditions were measured and analyzed for two years. The genetic variance components of the tested traits were calculated from the data fitted by the mixed linear model. The plant height of all lines showed significant genotypic variation (σ2g) (P < 0.05), and the stem diameter, stem number, and dry weight of all lines had a significant genotype × environment interaction (σ2ge) (P < 0.05). The heritability (H) of plant height, stem diameter, stem number, dry weight and leaf-to-stem ratio of alfalfa lines were 0.87, 0.52, 0.59, 0.52 and 0.50, respectively. There were significant genotype × environment interactions (σ2ge) (P < 0.05) for the quality traits of all lines. The heritabilities (H) of acid detergent fiber and neutral detergent fiber were 0.65 and 0.64, respectively. The results of transcriptional expression analysis with RNA-seq showed that the genes MsProDH1, MsProDH4, MsProDH5, MsP5CDH1, MsP5CS5, MsP5CS9, and MsP5CR1, which are involved in the proline metabolism pathway, played an important role in the drought tolerance of innovative alfalfa germplasm. Under water stress, with the regulation of key genes in the proline metabolism pathway, the proline content of all alfalfa lines increased to varying degrees. Among them, the proline content in the shoots and roots of transgenic line L6 was 7.29 times and 12.22 times that under normal irrigation conditions, respectively. The present study helped to clarify that the new germplasm of alfalfa transformed with the CsP5CDH gene synthesized a large amount of proline under water stress, and effectively slowed leaf water loss, thus improving the drought resistance of alfalfa.

Inhibition of SIRT7 overcomes sorafenib acquired resistance by suppressing ERK1/2 phosphorylation via the DDX3X-mediated NLRP3 inflammasome in hepatocellular carcinoma.

AIMS: Sirtuin 7 (SIRT7) plays an important role in tumor development, and has been characterized as a potent regulator of cellular stress. However, the effect of SIRT7 on sorafenib acquired resistance remains unclear and a possible anti-tumor mechanism beyond this process in HCC has not been clarified. We examined the therapeutic potential of SIRT7 and determined whether it functions synergistically with sorafenib to overcome chemoresistance. METHODS: Cancer Genome Atlas-liver HCC data and unbiased gene set enrichment analyses were used to identify SIRT7 as a potential effector molecule in sorafenib acquired resistance. Two types of SIRT7 chemical inhibitors were developed to evaluate its therapeutic properties when synergized with sorafenib. Mass spectrometry was performed to discover a direct target of SIRT7, DDX3X, and DDX3X deacetylation levels and protein stability were explored. Moreover, an in vivo xenograft model was used to confirm anti-tumor effect of SIRT7 and DDX3X chemical inhibitors combined with sorafenib. RESULTS: SIRT7 inhibition mediated DDX3X depletion can re-sensitize acquired sorafenib resistance by disrupting NLRP3 inflammasome assembly, finally suppressing hyperactive ERK1/2 signaling in response to NLRP3 inflammasome-mediated IL-1ß inhibition. CONCLUSIONS: SIRT7 is responsible for sorafenib acquired resistance, and its inhibition would be beneficial when combined with sorafenib by suppressing hyperactive pro-cell survival ERK1/2 signaling.

A dicarbonate solvent electrolyte for high performance 5 V-Class Lithium-based batteries.

Rechargeable lithium batteries using 5 V positive electrode materials can deliver considerably higher energy density as compared to state-of-the-art lithium-ion batteries. However, their development remains plagued by the lack of electrolytes with concurrent anodic stability and Li metal compatibility. Here we report a new electrolyte based on dimethyl 2,5-dioxahexanedioate solvent for 5 V-class batteries. Benefiting from the particular chemical structure, weak interaction with lithium cation and resultant peculiar solvation structure, the resulting electrolyte not only enables stable, dendrite-free lithium plating-stripping, but also displays anodic stability up to 5.2 V (vs. Li/Li+), in additive or co-solvent-free formulation, and at low salt concentration of 1 M. Consequently, the Li | |LiNi0.5Mn1.5O4 cells using the 1 M LiPF6 in 2,5-dioxahexanedioate based electrolyte retain >97% of the initial capacity after 250 cycles, outperforming the conventional carbonate-based electrolyte formulations, making this, and potentially other dicarbonate solvents promising for future Lithium-based battery practical explorations.

Genome-wide detection of structural variation in some sheep breeds using whole-genome long-read sequencing data.

Genomic structural variants (SVs) constitute a significant proportion of genetic variation in the genome. The rapid development of long-reads sequencing has facilitated the detection of long-fragment SVs. There is no published study to detect SVs using long-read data from sheep. We applied a long-read mapping approach to detect SVs and characterized a total of 30,771 insertions, deletions, inversions and translocations. We identified 716, 916, 842 and 303 specific SVs in Southdown sheep, Alpine merino sheep, Qilian White Tibetan sheep and Oula sheep, respectively. We annotated these SVs and found that these SV-related genes were primarily enriched in the well-established pathways involved in the regulation of the immune system, growth and development and environmental adaptability. We detected and annotated SVs based on NGS resequencing data to validate the accuracy based on third-generation detection. Moreover, five candidate SVs were verified using the PCR method in 50 sheep. Our study is the first to use a long-reads sequencing approach to construct a novel structural variation map in sheep. We have completed a preliminary exploration of the potential effects of SVs on sheep.

From Liquid to Solid-State Batteries: Li-Rich Mn-Based Layered Oxides as Emerging Cathodes with High Energy Density.

Li-rich Mn-based (LRMO) cathode materials have attracted widespread attention due to their high specific capacity, energy density, and cost-effectiveness. However, challenges such as poor cycling stability, voltage deca,y and oxygen escape limit their commercial application in liquid Li-ion batteries. Consequently, there is a growing interest in the development of safe and resilient all-solid-state batteries (ASSBs), driven by their remarkable safety features and superior energy density. ASSBs based on LRMO cathodes offer distinct advantages over conventional liquid Li-ion batteries, including long-term cycle stability, thermal and wider electrochemical windows stability, as well as the prevention of transition metal dissolution. This review aims to recapitulate the challenges and fundamental understanding associated with the application of LRMO cathodes in ASSBs. Additionally, it proposes the mechanisms of interfacial mechanical and chemical instability, introduces noteworthy strategies to enhance oxygen redox reversibility, enhances high-voltage interfacial stability, and optimizes Li+ transfer kinetics. Furthermore, it suggests potential research approaches to facilitate the large-scale implementation of LRMO cathodes in ASSBs.

On-Demand Dynamic Terahertz Polarization Manipulation Based on Pneumatically Actuated Metamaterial.

In this paper, a new tuning strategy is proposed by incorporating a pneumatically actuated metamaterial to achieve on-demand polarization manipulation at THz frequencies. Through controlling the actuation pressure, the device function can be flexibly switched among three types of polarization conversion capabilities within the same operation frequency band, from 1.3 THz to 1.5 THz, in which the mutual conversion between linear polarization and circular polarization, such as a quarter-wave plate, and handedness inversion between circular polarizations as a helicity inverter as well as a helicity keeper, have been successfully achieved between the incidence and reflection. Moreover, the intrinsic tuning mechanism for the polarization manipulation is also discussed.

PhyGCN: Pre-trained Hypergraph Convolutional Neural Networks with Self-supervised Learning.

Hypergraphs are powerful tools for modeling complex interactions across various domains, including biomedicine. However, learning meaningful node representations from hypergraphs remains a challenge. Existing supervised methods often lack generalizability, thereby limiting their real-world applications. We propose a new method, Pre-trained Hypergraph Convolutional Neural Networks with Self-supervised Learning (PhyGCN), which leverages hypergraph structure for self-supervision to enhance node representations. PhyGCN introduces a unique training strategy that integrates variable hyperedge sizes with self-supervised learning, enabling improved generalization to unseen data. Applications on multi-way chromatin interactions and polypharmacy side-effects demonstrate the effectiveness of PhyGCN. As a generic framework for high-order interaction datasets with abundant unlabeled data, PhyGCN holds strong potential for enhancing hypergraph node representations across various domains.

Shear wave elastography-based deep learning model for prognosis of patients with acutely decompensated cirrhosis.

PURPOSE: This study aimed to develop and validate a deep learning model based on two-dimensional (2D) shear wave elastography (SWE) for predicting prognosis in patients with acutely decompensated cirrhosis. METHODS: We prospectively enrolled 288 acutely decompensated cirrhosis patients with a minimum 1-year follow-up, divided into a training cohort (202 patients, 1010 2D SWE images) and a test cohort (86 patients, 430 2D SWE images). Using transfer learning by Resnet-50 to analyze 2D SWE images, a SWE-based deep learning signature (DLswe) was developed for 1-year mortality prediction. A combined nomogram was established by incorporating deep learning SWE information and laboratory data through a multivariate Cox regression analysis. The performance of the nomogram was evaluated with respect to predictive discrimination, calibration, and clinical usefulness in the training and test cohorts. RESULTS: The C-index for DLswe was 0.748 (95% CI 0.666-0.829) and 0.744 (95% CI 0.623-0.864) in the training and test cohorts, respectively. The combined nomogram significantly improved the C-index, accuracy, sensitivity, and specificity of DLswe to 0.823 (95% CI 0.763-0.883), 86%, 75%, and 89% in the training cohort, and 0.808 (95% CI 0.707-0.909), 83%, 74%, and 85% in the test cohort (both p < 0.05). Calibration curves demonstrated good calibration of the combined nomogram. Decision curve analysis indicated that the nomogram was clinically valuable. CONCLUSIONS: The 2D SWE-based deep learning model holds promise as a noninvasive tool to capture valuable prognostic information, thereby improving outcome prediction in patients with acutely decompensated cirrhosis.

Potential selection for lipid kinase activity and spermatogenesis in Henan native pig breeds and growth shaping by introgression of European genes.

BACKGROUND: China has one third of the worldwide indigenous pig breeds. The Henan province is one of the earliest pig domestication centers of China (about 8000 years ago). However, the precise genetic characteristics of the Henan local pig breeds are still obscure. To understand the origin and the effects of selection on these breeds, we performed various analyses on lineage composition, genetic structure, and detection of selection sweeps and introgression in three of these breeds (Queshan, Nanyang and Huainan) using genotyping data on 125 Queshan, 75 Nanyang, 16 Huainan pigs and 878 individuals from 43 Eurasian pig breeds. RESULTS: We found no clear evidence of ancestral domestic pig DNA lineage in the Henan local breeds, which have an extremely complicated genetic background. Not only do they share genes with some northern Chinese pig breeds, such as Erhualian, Hetaodaer, and Laiwu, but they also have a high admixture of genes from foreign pig breeds (33-40%). Two striking selection sweeps in small regions of chromosomes 2 and 14 common to the Queshan and Nanyang breeds were identified. The most significant enrichment was for lipid kinase activity (GO:0043550) with the genes FII, AMBRA1, and PIK3IP1. Another interesting 636.35-kb region on chromosome 14 contained a cluster of spermatogenesis genes (OSBP2, GAL3ST1, PLA2G3, LIMK2, and PATZ1), a bisexual sterility gene MORC2, and a fat deposition gene SELENOM. Reproduction and growth genes LRP4, FII, and ARHGAP1 were present in a 238.05-kb region on SSC2 under selection. We also identified five loci associated with body length (P = 0.004) on chromosomes 1 and 12 that were introgressed from foreign pig breeds into the Henan breeds. In addition, the Chinese indigenous pig breeds fell into four main types instead of the previously reported six, among which the Eastern type could be divided into two subgroups. CONCLUSIONS: Admixture of North China, East China and foreign pigs contributed to high genetic diversity of Henan local pigs. Ontology terms associated with lipid kinase activity and spermatogenesis and growth shaping by introgression of European genes in Henan pigs were identified through selective sweep analyses.

Structure-Activity Relationships of Alanine Scan Mutants αO-Conotoxins GeXIVA[1,2] and GeXIVA[1,4].

αO-Conotoxin GeXIVA is a selective α9α10 nicotinic acetylcholine receptor (nAChR) inhibitor displaying two disulfide bonds that can form three isomers. The bead (GeXIVA[1,2]) and ribbon (GeXIVA[1,4]) isomers possess the highest activity on rat and human α9α10 nAChRs. However, the molecular mechanism by which they inhibit the α9α10 nAChR is unknown. Here, an alanine scan of GeXIVA was used to elucidate key interactions between the peptides and the α9α10 nAChR. The majority of GeXIVA[1,2] analogues preserved affinity at α9α10 nAChR, but [R17A]GeXIVA[1,2] enhanced selectivity on the α9α10 nAChR. The I23A replacement of GeXIVA[1,4] increased activity at both rat and human α9α10 nAChRs by 10-fold. Surprisingly, these results do not support the molecular model of an interaction in the orthosteric binding site proposed previously, but rather may involve allosteric coupling with the voltage-sensitive domain of the α9α10 nAChR. These results could help to guide further development of GeXIVA analogues as analgesics.

Regulating SEI Components of Sodium Anode via Capturing Organic-Molecule Intermediates in Ester-Based Electrolyte.

Highly reversible sodium metal anodes are still regarded as a stubborn hurdle in ester-based electrolytes due to the issue of uncontrollable dendrites and incredibly unstable interphase. Evidently, a strong protective film on sodium is decisive, while the quality of the protective film is mainly determined by its components. However, it is challenging to actively adjust the expected components. This work can regulate the solid electrolyte interphase (SEI) components by introducing a functional electrolyte additive (2-chloro-1,3-dimethylimidazoline hexafluorophosphate (CDIH, namely CDI+ +PF6 - )) into FEC/PC ester-based electrolyte. Specifically, the chloride element in the CDI+ can easily react to form a NaF/NaCl-rich SEI together with the decomposition products of FEC; then the CDI+ without chlorine as a gripper to capture the organic-molecule intermediates generated during FEC decomposition to greatly reduce the content of unstable organic components in SEI, which can be confirmed by molecular dynamic simulation and experiment. Eventually, a highly reversible Na deposition behavior can be delivered. As expected, under the action of CDIH additives, the Na||Na symmetrical cell performs an excellent long-term cycling (>800 h, 0.5 mA cm-2 -0.5 mAh cm-2 ) and rate performance (0.5-4 mA cm-2 ). Furthermore, the Na||PB full cell exhibits the outstanding electrochemical performance with small polarization.