Stratifying risk of failure to achieve textbook outcomes among patients undergoing hepatectomy for hepatocellular carcinoma: A multicenter score validation study.

BACKGROUND AND AIMS: The concept of textbook outcomes (TOs) has gained increased attention as a critical metric to assess the quality and success of outcomes following complex surgery. A simple yet effective scoring system was developed and validated to predict risk of not achieving textbook outcomes (non-TOs) following hepatectomy for hepatocellular carcinoma (HCC). METHODS: Using a multicenter prospectively collected database, risk factors associated with non-TO among patients who underwent hepatectomy for HCC were identified. A predictive scoring system based on factors identified from multivariate regression analysis was used to risk stratify patients relative to non-TO. The score was developed using 70 % of the overall cohort and validated in the remaining 30 %. RESULTS: Among 3681 patients, 1458 (39.6 %) failied to experience a TO. Based on the derivation cohort, obesity, American Society of Anaesthesiologists score(ASA score), Child-Pugh grade, tumor size, and extent of hepatectomy were identified as independent predictors of non-TO. The scoring system ranged from 0 to 10 points. Patients were categorized into low (0-3 points), intermediate (4-6 points), and high risk (7-10 points) of non-TO. In the validation cohort, the predicted risk of developing non-TOs was 39.0 %, which closely matched the observed risk of 39.9 %. There were no differences among the predicted and observed risks within the different risk categories. CONCLUSIONS: A novel scoring system was able to predict risk of non-TO accurately following hepatectomy for HCC. The score may enable early identification of individuals at risk of adverse outcomes and inform surgical decision-making, and quality improvement initiatives.

Linearly Arranged Multi-π-Stacked Structure for Efficient Through-Space Charge-Transfer Emitters.

Noncovalent spatial interaction has become an intriguing and important tool for constructing optoelectronic molecules. In this study, we linearly attached three conjugated units in a multi π-stacked manner by using just one trident bridge based on indeno[2,1-b]fluorene. To achieve this structure, we improved the synthetic approach through double C-H activation, significantly simplifying the preparation process. Due to the proximity of the C10, C11, and C12 sites in indeno[2,1-b]fluorene, we derived two novel donor|acceptor|donor (D|A|D) type molecules, 2DMB and 2DMFB, which exhibited closely packed intramolecular stacking, enabling efficient through-space charge transfer. This molecular construction is particularly suitable for developing high-performance thermally activated delayed fluorescence materials. With donor(s) and acceptor(s) constrained and separated within this spatially rigid structure, elevated radiative transition rates, and high photoluminescence quantum yields were achieved. Organic light-emitting diodes incorporating 2DMB and 2DMFB demonstrated superior efficiency, achieving maximum external quantum efficiencies of 28.6% and 16.2%, respectively.

Varied immune responses of HBV-specific B cells in patients undergoing pegylated interferon-alpha treatment for chronic hepatitis B.

BACKGROUND & AIMS: The changes of HBV-specific B-cells in chronic hepatitis B (CHB) patients underwent pegylated interferon-alfa (PEG-IFNα) treatment and achieved functional cure remain unclear. We aimed to evaluate the alterations in HBV-specific B-cells during treatment and therefore explored the mechanism of functional recovery of HBsAg-specific B-cells. METHODS: We included 39 nucleos(t)ide analogues-treated CHB patients who received sequential combination therapy with PEG-IFNα and 8 treatment-naive CHB patients. HBV-specific B-cells were characterized ex vivo using fluorescent labeled HBsAg and HBcAg. The frequency, phenotype, and subsets of HBV-specific B-cells and follicular helper T cells (Tfh-cells) were detected using flow cytometry. The functionality of HBV-specific B-cells was quantified through ELISpot assays. RESULTS: During treatment, the fraction of activated memory B-cells (MBCs) among HBsAg-specific B-cells and the expression of IgG, CXCR3, and CD38 increased. Antibody-secretion capacity of HBsAg-specific B-cell was restored after treatment only in patients with a functional cure and it showed a positive correlation with serum hepatitis B surface antibody levels. The phenotype and function of HBsAg-specific B-cells differed between patients with and without functional cure. Patients with functional cure exhibited IgG+ classical MBCs and plasmablasts in HBsAg-specific B-cells. HBcAg-specific B-cells displayed both attenuated antibody secretion with reduced IgG expression and an IgM+ atypical type of MBCs after treatment, irrespective of with and without functional cure. The number of CD40L+ Tfh-cells increased after PEG-IFNα treatment and positively correlated with HBsAg-specific B-cell activation. CONCLUSIONS: After PEG-IFNα treatment, HBsAg- and HBcAg-specific B-cells exhibit various changes in antibody secretion. Their functional differences are reflected in the alterations in phenotypes and subtypes. The presence of CD40L+ Tfh-cells is associated with the active recovery of HBsAg-specific B-cells. IMPACT AND IMPLICATIONS: HBV-related complications and hepatocellular carcinoma remain the leading causes of mortality from chronic liver disease worldwide, and a cure is rarely achieved with antiviral therapies. Elucidating the immunological mechanisms underlying the functional cure of CHB patients offers a promising therapeutic strategy for viral clearance, such as therapeutic vaccine. We analyzed the alterations in HBV-specific B-cells in patients treated with PEG-IFNα and identified novel pathways for immunotherapeutic boosting of B cell immunity.

Neuroprotective and vasoprotective effects of herb pair of Zhiqiao-Danggui in ischemic stroke uncovered by LC-MS/MS-based metabolomics approach.

Ischemic stroke is the most important cause of disability and death worldwide, but current treatments remain limited. Traditional Chinese medicine (TCM) including the herb pair of Zhiqiao-Danggui (ZD) offers a multifaceted treatment approach through promoting blood circulation, yet its specific anti-ischemic mechanism remains unclear. This study used the photochemically induced thrombosis (PIT) mouse model and the oxygen glucose deprivation/reoxygenation (OGD/R) cell model to explore the therapeutic effect of ZD on ischemic stroke. Mice were treated with high and low doses of ZD extract or positive control. Behavior was assessed using the grid test. The brain tissue was then subjected to infarct volume assessment, histopathology, oxidative stress marker detection, LC/MS metabolomic analysis and qRT-PCR validation. The therapeutic effect of ZD-medicated serum on OGD/R model was tested on cells. Experimental results show that ZD can improve motor function, reduce infarct size, neuronal damage and apoptosis as well as alleviate oxidative stress in mice. ZD-medicated serum promotes endothelial cell proliferation, improves cell survival against OGD/R-induced injury, reduces oxidative damage and protects mitochondrial function. Metabolomics reveals ZD regulation of metabolites in energy metabolism, amino acid metabolism, TCA cycle, and angiogenesis signaling pathways. qRT-PCR results also showed that ZD could attenuate abnormal conduction of angiogenic signals and enhance vessel stability. This study confirmed the neuroprotective and vasoprotective effects of ZD, highlighted its potential in treating ischemic stroke, and provided a scientific basis for the traditional use of ZD.

Development and validation of a HPLC method for the determination of chemical and radiochemical purity of O-(2-[18F]fluoroethyl-l-tyrosine ([18F]FET)), a PET radiotracer for the imaging of brain tumor.

A novel HPLC method was developed and validated to determine radiochemical identity, radiochemical purity and chemical purity for the analysis of O-(2-[18F]fluoroethyl-l-tyrosine ([18F]FET). In this method, an analytical Phenomenex Gemini C18 column was used with an isocratic eluent of 7 % ethanol and 93 % 50 mM potassium phosphate buffer (pH = 6.9). The flow rate was 1.0 mL/min and the injection volume was 10 µL. A photo-diode array detector set at 220 nm was used for UV mass detection and a single channel, high sensitivity radiation detector was used. The method validation assays including specificity, linearity, precision, accuracy, and robustness were evaluated. Results show that the method was suitable for qualitative and quantitative determination of radiochemical and chemical purity of [18F]FET. This system has been routinely used for the analysis of more than 120 batches of [18F]FET with radiochemical yield 23.7 ± 6 % (no decay corrected) and molar activity 593 ± 284 GBq/µmole in our facility to support human use.

HRAS Induces Ferroptosis through Upregulating HSPB1 in Hepatocellular Carcinoma.

BACKGROUND: The aim of this study is to explore the mechanism of HRAS and HSPB1 in ferroptosis. Primary liver cancer is the third leading cause of tumor death worldwide. Hepatocellular carcinoma (HCC) constitutes 75%-85% of cases of primary liver cancer. HRAS and HSPB1 co-express in multiple cells and participate in tumor progression regulation. However, their expression regulation and role in HCC have not been reported. METHODS: We investigated the effects of HRAS and HSPB1 on ferroptosis in in vitro experiments. Here, the role and mechanism of HRAS and HSPB1 on ferroptosis were investigated by transfecting the specific siRNA or overexpressing plasmids in HCC cells. RESULTS: Bioinformatics analysis proved that HRAS and HSPB1 were highly expressed in HCC tissues and associated with poor prognosis of patients with HCC. In vitro, HRAS overexpression reduced the level of intracellular iron, ROS, and MDA production in HCC cells. Mechanistically, HRAS increased GPX4 expression and decreased the levels of ACSL4 and P53. HRAS also increased HSPB1 expression, and HRAS knockdown downregulated HSPB1 levels in HCC cells. Importantly, overexpression of HSPB1 reversed HRAS-increased concentration of iron, MDA, and ROS and eliminated HRAS-induced ferroptosis. Moreover, HRAS enhanced the proliferation and invasion by targeting HSPB1. CONCLUSION: The regulation of HSPB1 by HRAS enhanced the resistance of HCC cells to ferroptosis. HRAS promoted proliferation and invasion by upregulating HSPB1. This research provides a new potential strategy for HCC treatment.

In Silico Screening of Bioactive Peptides in Stout Beer and Analysis of ACE Inhibitory Activity.

Stout beer was selected as the research object to screen angiotensin-converting enzyme (ACE) inhibitory peptides. The peptide sequences of stout beer were identified using ultra-performance liquid chromatography-quadrupole-Orbitrap mass spectrometry with de novo, and 41 peptides were identified with high confidence. Peptide Ranker was used to score the biological activity and six peptides with a score ≥ 0.5 were screened to predict their potential ACE inhibitory (ACEI) activity. The toxicity, hydrophilicity, absorption, and excretion of these peptides were predicted. In addition, molecular docking between the peptides and ACE revealed a significant property of the peptide DLGGFFGFQR. Furthermore, molecular docking conformation and molecular dynamics simulation revealed that DLGGFFGFQR could be tightly bound to ACE through hydrogen bonding and hydrophobic interaction. Lastly, the ACEI activity of DLGGFFGFQR was confirmed using in vitro evaluation and the IC50 value was determined to be 24.45 µM.

The Efficacy of Probiotics, Prebiotics, Synbiotics, and Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with gut microbiota imbalance playing a significant role. There are increasing numbers of research studies exploring treatment options involving probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT), but it is still uncertain which treatment option is superior. The research was conducted on various databases and unpublished trial data (up to February 2023). Randomized controlled trials (RCTs) were screened for adult patients with IBS comparing interventions with placebo. Probiotics, prebiotics, synbiotics, and FMT were assessed for their impact using mean difference and Bayesian network meta-analysis. Out of 6528 articles, 54 were included for probiotics, 7 for prebiotics/synbiotics, and 6 for FMT. Probiotics showed improvement in IBS symptoms, particularly with Bifidobacterium and Lactobacillus strains. Prebiotics and synbiotics did not show significant improvement. Network meta-analysis indicated the favorable effects of probiotics (OR = 0.53, 95% CI, 0.48 to 0.59) and FMT (OR = 0.46, 95% CI, 0.33 to 0.64) on IBS, with no serious adverse events reported. In short, probiotics and FMT are effective for managing IBS, with Bifidobacterium and Lactobacillus being dominant strains. However, the most effective probiotic combination or strain remains unclear, while prebiotics and synbiotics did not show significant improvement.

Analytical model for the mitigation of VOC vapor with horizontal permeable reactive barrier in the contaminated site considering non-uniform source.

Volatile organic compounds (VOCs) contamination at the groundwater may cause vapor intrusion and pose significant threats to human health. As a novel low-carbon mitigation technology, a horizontal permeable reactive barrier (HPRB) is proposed to remove the VOC vapor in the vadose zone and mitigate the vapor intrusion risk. To estimate the performance of HPRB in the contaminated site with a non-uniform source, a transient two-dimensional analytical model is developed in this study to simulate the VOC vapor migration and oxidation processes in the layered soil. The analytical model is verified against the experimental results and numerical simulation first and the parameter study is then conducted. The HPRB has good performance for the contaminated sites involving factors including deep source and local soil with low effective diffusivity. To consider the vertical heterogeneity of the local soil, the traditional equivalent homogeneity method has limitations in considering the horizontal migration of VOC vapor and is not suitable for the two-dimensional model. On the contrary, the artificial layered method based on the proposed analytical model has better accuracy and is recommended to be adopted in practice. Leading to the exponential decrease in the VOC vapor concentration at the ground surface, increasing the thickness of HPRB is an effective measure to enhance the performance of HPRB. The fitting exponential function can be applied to determine the minimum design value of the thickness of HPRB in practice.

Detection of minimal hepatic encephalopathy in patients with cirrhosis based on the Stroop-CN model (NCRCID-CHESS 2106): a prospective multicenter study.

Minimal hepatic encephalopathy (MHE) has a substantial impact on the clinical outcomes and quality of life (QOL) of patients with cirrhosis. However, timely diagnosis and intervention are challenging due to sophisticated diagnostic methods. In this study, 673 healthy controls and 905 patients with cirrhosis were screened, and 660 healthy controls and 757 patients with cirrhosis, divided into the test (292 patients) and validation (465 patients) cohort, were analyzed after screening. A diagnostic model of the Stroop test (Stroop-CN) was constructed by multivariate linear regression based on the results of healthy controls. The prevalence of MHE and the comparison results with psychometric hepatic encephalopathy score through the Stroop-CN model were stable in the test and validation cohorts. Moreover, the prevalence of MHE remained significantly higher in patients with worse disease conditions marked as high Child-Pugh grades and the Model for End-stage Liver Disease and Sodium (MELD-Na) scores in the test and validation cohort. The EuroQol 5-D questionnaire revealed that patients with MHE had a worse QOL than those without MHE both in the test and validation cohort. In conclusion, an easy and practical Stroop-CN model for MHE diagnosis based on the EncephalApp is established. It is found that a considerable number of Chinese patients with cirrhosis experience MHE, which significantly impacts their QOL.

Electrophysiological correlation of auditory selective spatial attention in the "cocktail party" situation.

The auditory system can selectively attend to the target source in complex environments, the phenomenon known as the "cocktail party" effect. However, the spatiotemporal dynamics of electrophysiological activity associated with auditory selective spatial attention (ASSA) remain largely unexplored. In this study, single-source and multiple-source paradigms were designed to simulate different auditory environments, and microstate analysis was introduced to reveal the electrophysiological correlates of ASSA. Furthermore, cortical source analysis was employed to reveal the neural activity regions of these microstates. The results showed that five microstates could explain the spatiotemporal dynamics of ASSA, ranging from MS1 to MS5. Notably, MS2 and MS3 showed significantly lower partial properties in multiple-source situations than in single-source situations, whereas MS4 had shorter durations and MS5 longer durations in multiple-source situations than in single-source situations. MS1 had insignificant differences between the two situations. Cortical source analysis showed that the activation regions of these microstates initially transferred from the right temporal cortex to the temporal-parietal cortex, and subsequently to the dorsofrontal cortex. Moreover, the neural activity of the single-source situations was greater than that of the multiple-source situations in MS2 and MS3, correlating with the N1 and P2 components, with the greatest differences observed in the superior temporal gyrus and inferior parietal lobule. These findings suggest that these specific microstates and their associated activation regions may serve as promising substrates for decoding ASSA in complex environments.

Synergistically active Fe3O4 magnetic and EDTA modified cellulose cotton fabric using chemical method and their effective pollutants removal ability from wastewater.

A unique combination of cotton fabric (CF) with a mixture of EDTA and APTES Fe3O4 magnetic particles was developed and utilized for the first time as an adsorbent for removing pollutants from wastewater. Initially, Fe3O4 was synthesized using the co-precipitation method. Further, the surface of Fe3O4 was modified by introducing amino functional groups through a reaction with APTES, resulting in Fe3O4-NH2. Following this, the surface of carbon fiber (CF) was altered using ethylenediaminetetraacetic acid (EDTA) to create CF@EDTA. Through the use of EDC-HCl and NHS, Fe3O4-NH2 was attached to the surface of CF@EDTA, resulting in the final product CF@EDTA/Fe3O4. Subsequently, the prepared CF@EDTA/Fe3O4 was utilized to adsorb metal pollutants from wastewater, with a thorough analysis conducted using various characterization techniques including FTIR, SEM, EDX, XRD, VSM, and XPS to study the materials. The study specifically aimed to assess the adsorption performance of our cotton-based material towards As(III) and Cr3+ metal ions. The pH study was also performed. Results indicated that the material exhibited an adsorption capacity of approximately 714 mg/g for As(III) ions and 708 mg/g for Cr3+ ions. The Langmuir and Freundlich models, as well as pseudo-first and second-order models were also analyzed. The Langmuir and pseudo-second-order models were found to best fit the data. In terms of regeneration and reusability, the materials showed straightforward regeneration and recyclability for up to 15 cycles. The remarkable adsorption capacity, combined with the unique blend of cotton and Fe3O4 magnet, along with its recyclability, positions our material CF@EDTA/Fe3O4 as a promising contender for wastewater treatment and other significant areas in water research.

Prognostic Function and Immunologic Landscape of a Predictive Model Based on Five Senescence-Related Genes in IPF Bronchoalveolar Lavage Fluid.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a type of interstitial lung disease characterized by unknown causes and a poor prognosis. Recent research indicates that age-related mechanisms, such as cellular senescence, may play a role in the development of this condition. However, the relationship between cellular senescence and clinical outcomes in IPF remains uncertain. METHODS: Data from the GSE70867 database were meticulously analyzed in this study. The research employed differential expression analysis, as well as univariate and multivariate Cox regression analysis, to pinpoint senescence-related genes (SRGs) linked to prognosis and construct a prognostic risk model. The model's clinical relevance and its connection to potential biological processes were systematically assessed in training and testing datasets. Additionally, the expression location of prognosis-related SRGs was identified through immunohistochemical staining, and the correlation between SRGs and immune cell infiltration was deduced using the GSE28221 dataset. RESULT: The prognostic risk model was constructed based on five SRGs (cellular communication network factor 1, CYR61, stratifin, SFN, megakaryocyte-associated tyrosine kinase, MATK, C-X-C motif chemokine ligand 1, CXCL1, LIM domain, and actin binding 1, LIMA1). Both Kaplan-Meier (KM) curves (p = 0.005) and time-dependent receiver operating characteristic (ROC) analysis affirmed the predictive accuracy of this model in testing datasets, with respective areas under the ROC curve at 1-, 2-, and 3-years being 0.721, 0.802, and 0.739. Furthermore, qRT-RCR analysis and immunohistochemical staining verify the differential expression of SRGs in IPF samples and controls. Moreover, patients in the high-risk group contained higher infiltration levels of neutrophils, eosinophils, and M1 macrophages in BALF, which appeared to be independent indicators of poor prognosis in IPF patients. CONCLUSION: Our research reveals the effectiveness of the 5 SRGs model in BALF for risk stratification and prognosis prediction in IPF patients, providing new insights into the immune infiltration of IPF progression.

Atomic dynamics of electrified solid-liquid interfaces in liquid-cell TEM.

Electrified solid-liquid interfaces (ESLIs) play a key role in various electrochemical processes relevant to energy1-5, biology6 and geochemistry7. The electron and mass transport at the electrified interfaces may result in structural modifications that markedly influence the reaction pathways. For example, electrocatalyst surface restructuring during reactions can substantially affect the catalysis mechanisms and reaction products1-3. Despite its importance, direct probing the atomic dynamics of solid-liquid interfaces under electric biasing is challenging owing to the nature of being buried in liquid electrolytes and the limited spatial resolution of current techniques for in situ imaging through liquids. Here, with our development of advanced polymer electrochemical liquid cells for transmission electron microscopy (TEM), we are able to directly monitor the atomic dynamics of ESLIs during copper (Cu)-catalysed CO2 electroreduction reactions (CO2ERs). Our observation reveals a fluctuating liquid-like amorphous interphase. It undergoes reversible crystalline-amorphous structural transformations and flows along the electrified Cu surface, thus mediating the crystalline Cu surface restructuring and mass loss through the interphase layer. The combination of real-time observation and theoretical calculations unveils an amorphization-mediated restructuring mechanism resulting from charge-activated surface reactions with the electrolyte. Our results open many opportunities to explore the atomic dynamics and its impact in broad systems involving ESLIs by taking advantage of the in situ imaging capability.

[Pollution Characteristics and Multilevel Risk Assessments of Antibiotics in the Urban Rivers of Beijing, China].

To comprehensively assess the pollution characteristics and ecological risks of antibiotics in the rivers in Beijing, the concentrations of 35 common antibiotics belonging to four categories were quantified by using solid phase extraction combined with high-performance liquid chromatography-tandem mass spectrometry. The ecological risks of antibiotics were evaluated using the methods of risk quotient (RQ) and joint probability curves (JPCs). The results showed that a total of 33 antibiotics were detected in the surface water of ten rivers in Beijing, and the total concentrations of antibiotics ranged from N.D. to 1 573.57 ng·L-1. Sulfamethoxazole showed the highest concentration (N.D.-160.04 ng·L-1), followed by sulfadiazine (0.09-147.90 ng·L-1) and ofloxacin (0.28-94.72 ng·L-1). There were 16 antibiotics with a detection frequency greater than 50.0 %. The RQ method showed that there were 12 antibiotics with potential ecological risks. Tetracycline, clarithromycin, and trimethoprim showed the highest risks, with RQs of 3.99, 1.86, and 1.01, respectively. The risks of antibiotics at the outlets of wastewater treatment plants were higher than those in mainstream rivers. The PNEC exceedance rates of tetracycline, clarithromycin, and trimethoprim were above 2.3 %. Based on JPCs, the maximum risk product of clarithromycin was 1.66 %, and it showed low risks to 0.3 %-7.0 % of species. The risks of other antibiotics could be ignored. The detection frequency, distribution of concentrations, most sensitive species, and species sensitivity distribution of antibiotics had important impacts on the ecological risk assessment. Using the multilevel ecological risk assessment strategy can effectively avoid inadequate protection and overprotection and is also conducive to the hierarchical and zoning management of antibiotics throughout the region.

Musical experience enhances time discrimination: Evidence from cortical responses.

Time discrimination, a critical aspect of auditory perception, is influenced by numerous factors. Previous research has suggested that musical experience can restructure the brain, thereby enhancing time discrimination. However, this phenomenon remains underexplored. In this study, we seek to elucidate the enhancing effect of musical experience on time discrimination, utilizing both behavioral and electroencephalogram methodologies. Additionally, we aim to explore, through brain connectivity analysis, the role of increased connectivity in brain regions associated with auditory perception as a potential contributory factor to time discrimination induced by musical experience. The results show that the music-experienced group demonstrated higher behavioral accuracy, shorter reaction time, and shorter P3 and mismatch response latencies as compared to the control group. Furthermore, the music-experienced group had higher connectivity in the left temporal lobe. In summary, our research underscores the positive impact of musical experience on time discrimination and suggests that enhanced connectivity in brain regions linked to auditory perception may be responsible for this enhancement.

Machine Learning-Based Models for Advanced Fibrosis and Cirrhosis Diagnosis in Chronic Hepatitis B Patients With Hepatic Steatosis.

BACKGROUND AND AIMS: The global rise of chronic hepatitis B (CHB) superimposed on hepatic steatosis (HS) warrants noninvasive, precise tools for assessing fibrosis progression. This study leveraged machine learning (ML) to develop diagnostic models for advanced fibrosis and cirrhosis in this patient population. METHODS: Treatment-naive CHB patients with concurrent HS who underwent liver biopsy in 10 medical centers were enrolled as a training cohort and an independent external validation cohort (NCT05766449). Six ML models were implemented to predict advanced fibrosis and cirrhosis. The final models, derived from SHAP (Shapley Additive exPlanations), were compared with Fibrosis-4 Index, nonalcoholic fatty liver disease Fibrosis Score, and aspartate aminotransferase-to-platelet ratio index using the area under receiver-operating characteristic curve (AUROC) and decision curve analysis (DCA). RESULTS: Of 1,198 eligible patients, the random forest model achieved AUROCs of 0.778 (95% confidence interval [CI], 0.749-0.807) for diagnosing advanced fibrosis (random forest advanced fibrosis model) and 0.777 (95% CI, 0.748-0.806) for diagnosing cirrhosis (random forest cirrhosis model) in the training cohort, and maintained high AUROCs in the validation cohort. In the training cohort, the random forest advanced fibrosis model obtained an AUROC of 0.825 (95% CI, 0.787-0.862) in patients with hepatitis B virus DNA ≥105 IU/mL, and the random forest cirrhosis model had an AUROC of 0.828 (95% CI, 0.774-0.883) in female patients. The 2 models outperformed Fibrosis-4 Index, nonalcoholic fatty liver disease Fibrosis Score, and aspartate aminotransferase-to-platelet ratio index in the training cohort, and also performed well in the validation cohort. CONCLUSIONS: The random forest models provide reliable, noninvasive tools for identifying advanced fibrosis and cirrhosis in CHB patients with concurrent HS, offering a significant advancement in the comanagement of the 2 diseases. CLINICALTRIALS: gov, Number: NCT05766449.

Unveiling Highly Sensitive Active Site in Atomically Dispersed Gold Catalysts for Enhanced Ethanol Dehydrogenation.

Developing a desirable ethanol dehydrogenation process necessitates a highly efficient and selective catalyst with low cost. Herein, we show that the "complex active site" consisting of atomically dispersed Au atoms with the neighboring oxygen vacancies (Vo) and undercoordinated cation on oxide supports can be prepared and display unique catalytic properties for ethanol dehydrogenation. The "complex active site" Au-Vo-Zr3+ on Au1/ZrO2 exhibits the highest H2 production rate, with above 37,964 mol H2 per mol Au per hour (385 g H2 g Au - 1 ${{\rm{g}}_{{\rm{Au}}}^{ - 1} }$ h-1) at 350 °C, which is 3.32, 2.94 and 15.0 times higher than Au1/CeO2, Au1/TiO2, and Au1/Al2O3, respectively. Combining experimental and theoretical studies, we demonstrate the structural sensitivity of these complex sites by assessing their selectivity and activity in ethanol dehydrogenation. Our study sheds new light on the design and development of cost-effective and highly efficient catalysts for ethanol dehydrogenation. Fundamentally, atomic-level catalyst design by colocalizing catalytically active metal atoms forming a structure-sensitive "complex site", is a crucial way to advance from heterogeneous catalysis to molecular catalysis. Our study advanced the understanding of the structure sensitivity of the active site in atomically dispersed catalysts.

Sirtuin-6 knockout causes exacerbated stalled healing of diabetic ulcers in mice.

BACKGROUND: Diabetic ulcers (DUs) are characterized by chronic inflammation and delayed re-epithelialization, with a high incidence and weighty economic burden. The primary therapeutic strategies for refractory wounds include surgery, non-invasive wound therapy, and drugs, while the optimum regimen remains controversial. Sirtuin-6 (SIRT6) is a histone deacetylase and a key epigenetic factor that exerts anti-inflammatory and pro-proliferatory effects in wound healing. However, the exact function of SIRT6 in DUs remains unclear. METHODS: We generated tamoxifen-inducible SIRT6 knockout mice by crossing SIRT6flox/flox homozygous mice with UBC-creERT2+ transgenic mice. Systemic SIRT6 null mice, under either normal or diabetic conditions, were utilized to assess the effects of SIRT6 in DUs treatment. Gene and protein expressions of SIRT6 and inflammatory cytokines were measured by Western blotting and RT-qPCR. Histopathological examination confirmed the altered re-epithelialization (PCNA), inflammation (NF-κB p50 and F4/80), and angiogenesis (CD31) markers during DUs restoration. RESULTS: Knockout of SIRT6 inhibited the healing ability of DUs, presenting attenuated re-epithelialization (PCNA), exacerbated inflammation responses (NF-κB p50, F4/80, Il-1ß, Tnf-α, Il-6, Il-10, and Il-4), and hyperplasia vascular (CD31) compared with control mice. CONCLUSIONS: SIRT6 could boost impaired wound healing through improving epidermal proliferation, inflammation, and angiogenesis. Our study highlighted the therapeutic potential of the SIRT6 agonist for DUs treatment.

The potent potential of MFAP2 in prognosis and immunotherapy of triple-negative breast cancer.

BACKGROUNDS: Microfibril-associated protein 2 (MFAP2) is a protein presenting in the extracellular matrix that governs the activity of microfibrils through its interaction with fibrillin. While the involvement of MFAP2 in metabolic disorders has been documented, its expression and prognostic significance in triple-negative breast cancer (TNBC) remain unexplored. METHODS: We acquired datasets pertaining to breast cancer (BC) from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Next, a Venn diagram was used to identify the differentially expressed genes (DEGs). The DEGs were used to perform Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI), immune and survival analysis. The expressions of MFAP2, PD-1 and PD-L1 were examined by immunohistochemistry and western blot and their relationship with clinical pathological parameters were analyzed by clinical specimen samples from patients with TNBC. Tumor Immune Estimation Resource (TIMER, https://cistrome.shinyapps.io/timer/ ) was adopted to calculate the immune infiltration level of TNBC. The link between gene expression and tumor mutational burden (TMB) was described using Spearman's correlation analysis. RESULTS: We identified 66 differentially expressed genes (DEGs) that were up-regulated. Among these DEGs, MFAP2 was found to be overexpressed in TNBC and was associated with a lower probability of survival. This finding was confirmed through the use of immunohistochemistry and western blot techniques. Additionally, MFAP2 was found to be related to various pathological parameters in TNBC patients. Mechanistically, gene set enrichment analysis (GSEA) revealed that MFAP2 primarily influenced cellular biological behavior in terms of epithelial mesenchymal transition, glycolysis, and apical junction. Notably, MFAP2 expression was positively correlated with the abundance of macrophages, while a negative correlation was observed with the abundance of B cells, CD4 + T cells, CD8 + T cells, neutrophils and dendritic cells through immune analysis. Furthermore, it was observed that MFAP2 displayed a negative correlation not only with tumor mutational burden (TMB), a recognized biomarker for PD-1/PD-L1 immunotherapy, but also with PD-L1 in samples of TNBC. CONCLUSION: MFAP2 may be an important prognostic biomarker for TNBC, as well as a viable target for immunotherapy in this disease.