Development and validation of a prognostic model for 90-day survival in patients with alcohol-associated cirrhosis and acute decompensation.

BACKGROUND/PURPOSE: Patients with alcohol-associated cirrhosis and acute decompensation are considered critically ill and have a higher risk of short-term mortality. This study aimed to establish a nomogram to evaluate their 90-day survival and identify factors that affect disease progression. METHODS: We included patients from September 2008 to December 2016 (n = 387 in the derivation group) and from January 2017 to August 2020 (n = 157 in the validation group). LASSO regression and Cox multivariate risk regression were used to analyze the influencing factors of the 90-day mortality risk, and a nomogram was constructed. The performance of a model was analyzed based on the C-index, area under the receiver operating curve, calibration curve, and decision curve analysis. RESULTS: Total bilirubin >10 upper limit of normal, high-density lipoprotein cholesterol, lymphocyte and monocyte ratios ≤2.33, white blood cells, and hemoglobin were identified as independent risk factors affecting the 90-day mortality risk of patients and the nomogram was developed. A nomogram demonstrated excellent model predictive accuracy in both the derivation and validation cohorts (C-index: 0.976 and 0.945), which was better than other commonly used liver scoring models (p < 0.05). The nomogram also performed good calibration ability and more clinical net benefit. According to the nomogram score, patients were divided into high- and low-risk groups. Mortality was significantly higher in the high-risk group than in the low-risk group (p < 0.0001). CONCLUSION: The nomogram could accurately predict the 90-day mortality risk in patients with alcohol-associated cirrhosis and acute decompensation, helping to identify high-risk patients and personalize treatment at their first admission.

Metabolic biomarkers significantly enhance the prediction of HBV-related ACLF occurrence and outcomes.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a clinical syndrome associated with high short-term mortality in patients with chronic liver disease. Chronic hepatitis B is the main cause of ACLF (HBV-ACLF) in China and other Asian countries. To improve disease management and survival for patients with ACLF, we aimed to discover novel biomarkers to enhance HBV-ACLF diagnosis and prognostication. METHODS: We performed a metabolomics profiling of 1,024 plasma samples collected from patients with HBV-related chronic liver disease with acute exacerbation at hospital admission in a multi-year and multi-center prospective study (367 ACLF and 657 non-ACLF). The samples were randomly separated into equal halves as a discovery set and a validation set. We identified metabolites associated with 90-day mortality in the ACLF group and the progression to ACLF within 28 days in the non-ACLF group (pre-ACLF) using statistical analysis and machine learning. We developed diagnostic algorithms in the discovery set and used these to assess the findings in the validation set. RESULTS: ACLF significantly altered the plasma metabolome, particularly in membrane lipid metabolism, steroid hormones, oxidative stress pathways, and energy metabolism. Numerous metabolites were significantly associated with 90-day mortality in the ACLF group and/or pre-ACLF in the non-ACLF group. We developed algorithms for the prediction of 90-day mortality in patients with ACLF (area under the curve 0.87 and 0.83 for the discovery set and validation set, respectively) and the diagnosis of pre-ACLF (area under the curve 0.94 and 0.88 for the discovery set and validation set, respectively). To translate our discoveries into practical clinical tests, we developed targeted assays using liquid chromatography-mass spectrometry. CONCLUSIONS: Based on novel metabolite biomarkers, we established tests for HBV-related ACLF with higher accuracy than existing methods. CLINICAL TRIAL NUMBER: NCT02457637 and NCT03641872. IMPACT AND IMPLICATIONS: Acute-on-chronic liver failure (ACLF) is a clinical syndrome associated with high short-term mortality affecting 25% of patients hospitalized with cirrhosis. Chronic hepatitis B is the main etiology of ACLF in China and other Asian counties. There is currently no effective therapy. Early diagnosis and accurate prognostication are critical for improving clinical outcomes in patients with ACLF. Based on novel metabolite biomarkers, we developed liquid chromatography-mass spectrometry tests with improved accuracy for the early diagnosis and prognostication of HBV-related ACLF. The liquid chromatography-mass spectrometry tests can be implemented in clinical labs and used by physicians to triage patients with HBV-related ACLF to ensure optimized clinical management.

Portal vein thrombosis compromises the performance of MELD and MELD-Na scores in patients with cirrhosis.

BACKGROUND AND AIMS: The accuracy of model for end-stage liver disease (MELD) and MELD with sodium (MELD-Na) scores in reflecting the clinical outcomes of patients with cirrhosis and portal vein thrombosis (PVT) remains unclear. This study aimed to evaluate the performance of scores in predicting 90-day mortality in patients with cirrhosis and PVT. METHODS: Post hoc analysis was performed in two prospective cohorts (NCT02457637 and NCT03641872). The correlation between the MELD/MELD-Na score and 90-day liver transplantation (LT)-free mortality was investigated in patients with cirrhosis with and without PVT. RESULTS: In this study, 2826 patients with cirrhosis were included, and 255 (9.02%) had PVT. The cumulative incidence of 90-day LT-free mortality did not significantly differ between patients with and without PVT (log-rank P = 0.0854). MELD [area under the receiver operating curve (AUROC), 0.649 vs. 0.842; P = 0.0036] and MELD-Na scores (AUROC, 0.691 vs. 0.851; P = 0.0108) were compared in patients with and without PVT, regarding the prediction of 90-day LT-free mortality. In MELD < 15 and MELD-Na < 20 subgroups, patients with PVT had a higher 90-day LT-free mortality than those without PVT (7.91% vs. 2.64%, log-rank P = 0.0011; 7.14% vs. 3.43%, log-rank P = 0.0223), whereas in MELD ≥ 15 and MELD-Na ≥ 20 subgroups, no significant difference was observed between patients with and without PVT. CONCLUSIONS: The performance of MELD and MELD-Na scores in predicting 90-day LT-free mortality of patients with cirrhosis was compromised by PVT. MELD < 15 or MELD-Na < 20 may underestimate the 90-day LT-free mortality in patients with PVT.

Severe anemia is associated with increased short-term and long-term mortality in patients hospitalized with cirrhosis.

INTRODUCTION AND OBJECTIVES: The relationship between anemia and the outcome of patients with cirrhosis is not completely clear. Therefore, we performed this large-scale epidemiological study to investigate the prevalence and severity of anemia in patients with cirrhosis and acute decompensation or liver injury and how anemia impacts short-term and long-term outcomes. PATIENTS AND METHODS: Patients with cirrhosis and acute decompensation (AD) or acute liver injury (ALI) were enrolled in the Chinese AcuTe on CHronic LIver FailurE (CATCH-LIFE) studies, which consisted of two large, multicenter, prospective, observational cohorts between January 2015 and December 2016 and July 2018 and January 2019. We conducted data analysis on the prevalence of anemia and determined the relationship between anemia and prognosis. RESULTS: Among 1979 patients, 1389 (70.2%) had anemia, among whom 599 (41.3%) had mild anemia, 595 (15.8%) had moderate anemia and 195 (2.4%) had severe anemia. A linear association between hemoglobin level and 90-day or 1-year LT-free mortality was shown, and a 10 g/L decrease in hemoglobin level was associated with a 6.8% extra risk of 90-day death and a 5.7% extra risk of 1-year death. Severe anemia was an independent risk factor for 90-day [HR=1.649 (1.100, 2.473), p=0.016] and 1-year LT-free mortality [HR=1.610 (1.159, 2.238), p=0.005]. Multinomial logistic regression analysis further identified that severe anemia was significantly associated with post-28-day mortality but not within-28-day mortality. CONCLUSIONS: Anemia is common in patients with cirrhosis admitted for acute events. Severe anemia was associated with poor 90-day and 1-year prognoses in these patients.

3D Porous Structure in MXene/PANI Foam for a High-Performance Flexible Pressure Sensor.

The fields of electronic skin, man-machine interaction, and health monitoring require flexible pressure sensors with great sensitivity. However, most microstructure designs utilized to fabricate high-performance pressure sensors require complex preparation processes. Here, MXene/polyaniline (PANI) foam with 3D porous structure is achieved by using a steam-induced foaming method. Based on the structure, a flexible piezoresistive sensor is fabricated. It exhibits high sensitivity (690.91 kPa-1 ), rapid response, and recovery times (106/95 ms) and outstanding fatigue resistance properties (10 000 cycles). The MXene/PANI foam-based pressure sensor can swiftly detect minor pressure and be further used for human activity and health monitoring.

Overexpression of LPCAT1 enhances endometrial cancer stemness and metastasis by changing lipid components and activating the TGF/ß-Smad2/3 signaling pathway.

The incidence of endometrial cancer (EC) increases annually and tends to occur in younger women. A particularly important relationship exists between EC and metabolic disorders. As one of the most important components of lipid metabolism, phospholipids play an indispensable role in metabolic balance. LPCAT1 is a key enzyme regulating phospholipid metabolism. In this study, we perform further investigations to seek mechanistic insight of LPCAT1 in EC. Our results demonstrate that silencing of LPCAT1 inhibits the growth of endometrial cancer, while overexpression of LPCAT1 results in enhanced stemness and metastasis in endometrial cancer cell lines. Meanwhile, the contents of various phospholipids including phosphatidylethanolamine (PE), phosphatidylcholine (PC), and triglyceride (TG) change significantly after overexpression of LPCAT1. In addition, through RNA-sequencing and western blot analysis, we observe that the TGF-ß/Smad2/3 signaling pathway is of great importance in the tumor-promoting function of LPCAT1. LPCAT1 promotes the expressions of stem cell-related transcription factors and epithelial-mesenchymal transition (EMT) related proteins through the TGF-ß/Smad2/3 signaling pathway. Moreover, we find that TSI-01, which can inhibit the activity of LPCAT1, is able to restrain the proliferation of EC cell lines and promote cell apoptosis. Collectively, we demonstrate that LPCAT1 enhances the stemness and metastasis of EC by activating the TGF-ß/Smad2/3 signaling pathway and that TSI-01 may have potential use for the treatment of EC.

Elevated expression of LPCAT1 predicts a poor prognosis and is correlated with the tumour microenvironment in endometrial cancer.

BACKGROUND: Endometrial cancer (EC) is one of the three malignant reproductive tumours that threaten women's lives and health. Glycerophospholipids (GPLs) are important bioactive lipids involved in various physiological and pathological processes, including cancer. Immune infiltration of the tumour microenvironment (TME) is positively associated with the overall survival in EC. Exploring GPL-related factors associated with the TME in endometrial cancer can aid in the prognosis of patients and provide new therapeutic targets. METHODS: Differentially expressed GPL-related genes were identified from TCGA-UCEC datasets and the Molecular Signatures Database (MSigDB). Univariate Cox regression analysis was used to select GPL-related genes with prognostic value. The Random forest algorithm, LASSO algorithm and PPI network were used to identify critical genes. ESTIMATEScore was calculated to identify genes associated with the TME. Then, differentiation analysis and survival analysis of LPCAT1 were performed based on TCGA datasets. GSE17025 and immunohistochemistry (IHC) verified the results of the differentiation analysis. An MTT assay was then conducted to determine the proliferation of EC cells. GO and KEGG enrichment analyses were performed to explore the underlying mechanism of LPCAT1. In addition, we used the ssGSEA algorithm to explore the correlation between LPCAT1 and cancer immune infiltrates. RESULTS: Twenty-three differentially expressed GPL-related genes were identified, and eleven prognostic genes were selected by univariate Cox regression analysis. Four significant genes were identified by two different algorithms and the PPI network. Only LPCAT1 was significantly correlated with the tumour microenvironment. Then, we found that LPCAT1 was highly expressed in tumour samples compared with that in normal tissues, and lower survival rates were observed in the groups with high LPCAT1 expression. Silencing of LPCAT1 inhibited the proliferation of EC cells. Moreover, the expression of LPCAT1 was positively correlated with the histologic grades and types. The ROC curve indicated that LPCAT1 had good prognostic accuracy. Receptor ligand activity, pattern specification process, regionalization, anterior/posterior pattern specification and salivary secretion pathways were enriched as potential targets of LPCAT1. By using the ssGSEA algorithm, fifteen kinds of tumor-infiltrating cells (TICs) were found to be correlated with LPCAT1 expression. CONCLUSION: These findings suggested that LPCAT1 may act as a valuable prognostic biomarker and be correlated with immune infiltrates in endometrial cancer, which may provide novel therapy options for and improved treatment of EC.

Prevalence and Clinical Significance of Portal Vein Thrombosis in Patients With Cirrhosis and Acute Decompensation.

BACKGROUND & AIMS: Portal vein thrombosis (PVT) is a common and serious complication in patients with cirrhosis. However, little is known about PVT in patients with cirrhosis and acute decompensation (AD). We investigated the prevalence and clinical significance of PVT in nonmalignant patients with cirrhosis and AD. METHODS: We performed a retrospective study of 2 cohorts of patients with acute exacerbation of chronic liver disease who participated in the Chinese AcuTe on CHronic LIver FailurE study, established by the Chinese Chronic Liver Failure Consortium, from January 2015 through December 2016 (n = 2600 patients) and July 2018 through January 2019 (n = 1370 patients). We analyzed data on the prevalence, clinical manifestations, and risk factors of PVT from 2826 patients with cirrhosis, with and without AD. RESULTS: The prevalence of PVT in patients with cirrhosis and AD was 9.36%, which was significantly higher than in patients with cirrhosis without AD (5.24%) (P = .04). Among patients with cirrhosis and AD, 63.37% developed PVT recently (the first detected PVT with no indication of chronic PVT). Compared with patients without PVT, a significantly higher proportion of patients with PVT had variceal bleeding (47.33% vs 19.63%; P < .001) and patients with PVT had a significantly higher median serum level of D-dimer (2.07 vs 1.25; P < .001). Splenectomy and endoscopic sclerotherapy were independent risk factors for PVT in patients with cirrhosis and AD. The 1-year mortality rate did not differ significantly between patients with vs without PVT. CONCLUSIONS: In an analysis of data from 2826 patients with cirrhosis, a significantly higher proportion of those with AD had PVT than those without AD. PVT was associated with increased variceal bleeding, which would increase the risk for AD. Strategies are needed to prevent PVT in patients with cirrhosis, through regular screening, to reduce portal hypertension. ClinicalTrials.gov no: NCT02457637 and NCT03641872.

Artificial neural network-based models used for predicting 28- and 90-day mortality of patients with hepatitis B-associated acute-on-chronic liver failure.

BACKGROUND: This study aimed to develop prognostic models for predicting 28- and 90-day mortality rates of hepatitis B virus (HBV)-associated acute-on-chronic liver failure (HBV-ACLF) through artificial neural network (ANN) systems. METHODS: Six hundred and eight-four cases of consecutive HBV-ACLF patients were retrospectively reviewed. Four hundred and twenty-three cases were used for training and constructing ANN models, and the remaining 261 cases were for validating the established models. Predictors associated with mortality were determined by univariate analysis and were then included in ANN models for predicting prognosis of mortality. The receiver operating characteristic curve analysis was used to evaluate the predictive performance of the ANN models in comparison with various current prognostic models. RESULTS: Variables with statistically significant difference or important clinical characteristics were input in the ANN training process, and eight independent risk factors, including age, hepatic encephalopathy, serum sodium, prothrombin activity, γ-glutamyltransferase, hepatitis B e antigen, alkaline phosphatase and total bilirubin, were eventually used to establish ANN models. For 28-day mortality in the training cohort, the model's predictive accuracy (AUR 0.948, 95% CI 0.925-0.970) was significantly higher than that of the Model for End-stage Liver Disease (MELD), MELD-sodium (MELD-Na), Chronic Liver Failure-ACLF (CLIF-ACLF), and Child-Turcotte-Pugh (CTP) (all p < 0.001). In the validation cohorts the predictive accuracy of ANN model (AUR 0.748, 95% CI: 0.673-0.822) was significantly higher than that of MELD (p = 0.0099) and insignificantly higher than that of MELD-Na, CTP and CLIF-ACLF (p > 0.05). For 90-day mortality in the training cohort, the model's predictive accuracy (AUR 0.913, 95% CI 0.887-0.938) was significantly higher than that of MELD, MELD-Na, CTP and CLIF-ACLF (all p < 0.001). In the validation cohorts, the prediction accuracy of the ANN model (AUR 0.754, 95% CI: 0.697-0.812 was significantly higher than that of MELD (p = 0.019) and insignificantly higher than MELD-Na, CTP and CLIF-ACLF (p > 0.05). CONCLUSIONS: The established ANN models can more accurately predict short-term mortality risk in patients with HBV- ACLF. The main content has been postered as an abstract at the AASLD Hepatology Conference (https://doi.org/10.1002/hep.30257).

Protective Effect of Probiotics against Esophagogastric Variceal Rebleeding in Patients with Liver Cirrhosis after Endoscopic Therapy.

BACKGROUND Probiotic therapy has been shown to be beneficial against some liver diseases. However, there is still uncertainty regarding the clinical efficacy of probiotics for the treatment of variceal rebleeding. This research explored the efficacy of probiotics in variceal rebleeding. MATERIAL AND METHODS This was a retrospective study of 704 consecutive patients with liver cirrhosis who recovered from esophagogastric variceal bleeding after endoscopic treatment. Patients were subdivided into a probiotics cohort (n=214) and a non-probiotics cohort (n=490) based on the cumulative defined daily dose (cDDD) of probiotics received during follow-up. Propensity score matching was utilized to obtain a relatively balanced cohort of 200 patients per group for the analysis. Patients were monitored for rebleeding during the one-year follow-up. RESULTS Multivariate Cox regression analysis revealed that probiotic therapy (≥28cDDD) was an independent protector against rebleeding (AHR=0.623; 95% CI=0.488-0.795; P<0.001). After propensity score matching, Kaplan-Meier analysis revealed that the rebleeding rate was higher in the non-probiotics cohort (n=200) than in the probiotics cohort (n=200) (56.0% vs. 44.0%, P=0.002). The incidence of rebleeding decreased with increased probiotic dosage (56.0%, 48.5%, 43.3%, and 38.1% in <28 cDDD, 28-60 cDDD, 61-90 cDDD, and >90 cDDD groups, respectively; P=0.011). The median rebleeding interval in the probiotics cohort (n=95) was significantly longer than that in the non-probiotics cohort (n=261) (147.0 vs. 91.0 days; P<0.001). CONCLUSIONS Adjuvant probiotic therapy significantly reduced the incidence of variceal rebleeding and delayed rebleeding after endotherapy in patients with cirrhosis.

Land-use intensification exerts a greater influence on soil microbial communities than seasonal variations in the Taihu Lake region, China.

The Taihu Lake region has undergone intensive land-use conversions from natural wetlands (NW) to conventional rice-wheat rotation fields (RW) and further to greenhouse vegetable fields (GH). Nevertheless, the effects of these conversions on soil microbes, particularly in wetland ecosystem, are not well explicit. To explore the impact of land-use intensification on soil microbial communities, monthly soil samples were obtained from replicate plots representing three land-use types (NW, RW, and GH) in subtropical wetlands and then subjected to amplicon sequencing. Land-use intensification had direct effects on bacterial and fungal community composition, with a more pronounced impact on bacteria than on fungi. These changes in bacterial communities were closely correlated with variations in soil environmental variables, such as NO3--N, pH, and electrical conductivity. Land-use intensification led to a decrease in bacterial deterministic processes, with an opposing trend observed in the fungal community. In addition, arable lands (RW and GH), which are affected by anthropogenic activities, exhibited more complex networks. Potential metabolic functional groups in GH had higher absolute abundance. Seasonal variations significantly influenced microbial diversity, composition, and potential metabolic functional groups within each land-use type, particularly in summer, although the magnitude of this impact was much smaller than the impact of land-use intensification. Our findings emphasize the importance of comprehending the ecological consequences of land-use intensification in wetlands for sustainable resource management and biodiversity conservation.

The effect of STAT1, miR-99b, and MAP2K1 in alcoholic liver disease (ALD) mouse model and hepatocyte.

Alcoholic liver disease (ALD) serves as the leading cause of chronic liver diseases-related morbidity and mortality, which threatens the life of millions of patients in the world. However, the molecular mechanisms underlying ALD progression remain unclear. Here, we applied microarray analysis and experimental approaches to identify miRNAs and related regulatory signaling that associated with ALD. Microarray analysis identified that the expression of miR-99b was elevated in the ALD mouse model. The AML-12 cells were treated with EtOH and the expression of miR-99b was enhanced in the cells. The expression of miR-99b was positively correlated with ALT levels in the ALD mice. The microarray analysis identified the abnormally expressed mRNAs in ALD mice and the overlap analysis was performed with based on the differently expressed mRNAs and the transcriptional factors of miR-99b, in which STAT1 was identified. The elevated expression of STAT1 was validated in ALD mice. Meanwhile, the treatment of EtOH induced the expression of STAT1 in the AML-12 cells. The expression of STAT1 was positively correlated with ALT levels in the ALD mice. The positive correlation of STAT1 and miR-99b expression was identified in bioinformatics analysis and ALD mice. The expression of miR-99b and pri-miR-99b was promoted by the overexpression of STAT1 in AML-12 cells. ChIP analysis confirmed the enrichment of STAT1 on miR-99b promoter in AML-12 cells. Next, we found that the expression of mitogen-activated protein kinase kinase 1 (MAP2K1) was negatively associated with miR-99b. The expression of MAP2K1 was downregulated in ALD mice. Consistently, the expression of MAP2K1 was reduced by the treatment of EtOH in AML-12 cells. The expression of MAP2K1 was negative correlated with ALT levels in the ALD mice. We identified the binding site of MAP2K1 and miR-99b. Meanwhile, the treatment of miR-99b mimic repressed the luciferase activity of MAP2K1 in AML-12 cells. The expression of MAP2K1 was suppressed by miR-99b in the cells. We observed that the expression of MAP2K1 was inhibited by the overexpression of STAT1 in AML-12 cells. Meanwhile, the apoptosis of AML-12 cells was induced by the treatment of EtOH, while miR-99b mimic promoted but the overexpression of MAP2K1 attenuated the effect of EtOH in the cells. In conclusion, we identified the correlation and effect of STAT1, miR-99b, and MAP2K1 in ALD mouse model and hepatocyte. STAT1, miR-99b, and MAP2K1 may serve as potential therapeutic target of ALD.

Stabilization of NCM811 cathode interface through macromolecular compound protective film formed by 2,5-bis(2,2,2-trifluoroethoxy)-benzoic acid additive in lithium metal batteries.

Lithium metal batteries (LMBs) offer substantial promise for next-generation energy storage owing to lithium metal's low reduction potential (-3.045 V vs. the standard hydrogen electrode) and its high specific capacity of 3860 mA h g-1. Among various cathode materials in LMBs, LiNi0.8Co0.1Mn0.1O2 (NCM811) is extensively employed because of its notably high specific capacity (over 200 mA h g-1) and comparatively lower cost. However, structural stress, nickel ions migration, and uneven Li+ deposition in NCM811 particles lead to cracking, irreversible decomposition of active substances, and the growth of mossy Li dendrites, causing severe capacity decline and low Coulomb efficiency in LMBs. In this study, we introduce an effective ethoxyl additive, 2,5-bis(2,2,2-trifluoroethoxy)-benzoic acid (2,5BTBA), directly into the carbonate electrolyte. This additive forms a dense and conductive macromolecular protective film on the NCM811 cathode and lithium metal anode during initial cycles, preventing electrode contact with the electrolyte. Consequently, it safeguards the cathode's structural integrity and enables dense lithium deposition. Adding 3 wt% 2,5BTBA, the Li/NCM811 battery retains a high capacity of 150.60 mA h g-1 and 89.41% retention after 700 cycles at 0.5C, maintaining an average Coulomb efficiency of 99.13%. This study presents an efficient and straightforward strategy to enhance the capacity retention of LMBs.

Age dependent path integration deficit in 5xFAD mice.

Alzheimer's disease (AD) is a severe neurodegenerative disorder and the most common form of dementia in elderly individuals, characterized by memory deficits, cognitive decline, and neuropathology. The identification of preclinical markers for AD remains elusive. We employed an ultrasound-evoked spatial memory assay to investigate path integration (PI) in wild type C57BL/6 J and 5xFAD mice. We observed significant recruitment of the mammillary bodies (MB) and subiculum (Sub) - core regions of the Papez circuit during PI, as indicated by increased expression of the immediate early gene c-Fos in C57BL/6 J mice. In 5xFAD mice, amyloid-beta (Aß) vulnerability in the MB and Sub was evident at 3-months of age, preceding widespread pathology at 5-months of age. In parallel, we detected significant behavioral deficits in PI in the 5XFAD mice at 5- but not 3-months of age. Sex based analysis revealed a more profound deficit in males compared to females at 5-months of age. Our data suggest PI may be as an early indicator of AD, potentially associated with dysfunction within the Papez circuit.

Soil pH amendment alters the abundance, diversity, and composition of microbial communities in two contrasting agricultural soils.

Soil microorganisms are the most active participants in terrestrial ecosystems, and have key roles in biogeochemical cycles and ecosystem functions. Despite the extensive research on soil pH as a key predictor of microbial community and composition, a limitation of these studies lies in determining whether bacterial and/or fungal communities are directly or indirectly influenced by pH. We conducted a controlled laboratory experiment to investigate the effects of soil pH amendment (+/- 1-2 units) with six levels on soil microbial communities in two contrasting Chinese agricultural soils (pH 8.43 in Dezhou, located in the North China Plain, Shandong vs pH 6.17 in Wuxi, located in the Taihu Lake region, Jiangsu, east China). Results showed that the fungal diversity and composition were related to soil pH, but the effects were much lower than the effects of soil pH on bacterial community in two soils. The diversity and composition of bacterial communities were more closely associated with soil pH in Wuxi soils compared to Dezhou soils. The alpha diversity of bacterial communities peaked near in situ pH levels in both soils, displaying a quadratic fitting pattern. Redundancy analysis and variation partition analysis indicated that soil pH affected bacterial community and composition by directly imposing a physiological constraint on soil bacteria and indirectly altering soil characteristics (e.g., nutrient availability). The study also examined complete curves of taxa relative abundances at the phylum and family levels in response to soil pH, with most relationships conforming to a quadratic fitting pattern, indicating soil pH is a reliable predictor. Furthermore, soil pH amendment affected the transformation of nitrogen and the abundances of functional genes involved in the nitrogen cycle, and methane production and consumption. Overall, results from this study would enhance our comprehension of how soil microorganisms in contrasting farmlands will respond to soil pH changes, and would contribute to more effective soil management and conservation strategies. IMPORTANCE: This study delves into the impact of soil pH on microbial communities, investigating whether pH directly or indirectly influences bacterial and fungal communities. The research involved two contrasting soils subjected to a 1-2 pH unit amendment. Results indicate bacterial community composition was shaped by soil pH through physiological constraints and nutrient limitations. We found that most taxa relative abundances at the phylum and family levels responded to pH with a quadratic fitting pattern, indicating that soil pH is a reliable predictor. Additionally, soil pH was found to significantly influence the predicted abundance of functional genes involved in the nitrogen cycle as well as in methane production and consumption processes. These insights can contribute to develop more effective soil management and conservation strategies.

Functional versatility of Zur in metal homeostasis, motility, biofilm formation, and stress resistance in Yersinia pseudotuberculosis.

Zur (zinc uptake regulator) is a significant member of the Fur (ferric uptake regulator) superfamily, which is widely distributed in bacteria. Zur plays crucial roles in zinc homeostasis and influences cell development and environmental adaptation in various species. Yersinia pseudotuberculosis is a Gram-negative enteric that pathogen usually serves as a model organism in pathogenicity studies. The regulatory effects of Zur on the zinc transporter ZnuABC and the protein secretion system T6SS have been documented in Y. pseudotuberculosis. In this study, a comparative transcriptomics analysis between a ∆zur mutant and the wild-type (WT) strain of Y. pseudotuberculosis was conducted using RNA-seq. This analysis revealed global regulation by Zur across multiple functional categories, including membrane transport, cell motility, and molecular and energy metabolism. Additionally, Zur mediates the homeostasis not only of zinc but also ferric and magnesium in vivo. There was a notable decrease in 35 flagellar biosynthesis and assembly-related genes, leading to reduced swimming motility in the ∆zur mutant strain. Furthermore, Zur upregulated multiple simple sugar and oligopeptide transport system genes by directly binding to their promoters. The absence of Zur inhibited biofilm formation as well as reduced resistance to chloramphenicol and acidic stress. This study illustrates the comprehensive regulatory functions of Zur, emphasizing its importance in stress resistance and pathogenicity in Y. pseudotuberculosis. IMPORTANCE: Bacteria encounter diverse stresses in the environment and possess essential regulators to modulate the expression of genes in responding to the stresses for better fitness and survival. Zur (zinc uptake regulator) plays a vital role in zinc homeostasis. Studies of Zur from multiple species reviewed that it influences cell development, stress resistance, and virulence of bacteria. Y. pseudotuberculosis is an enteric pathogen that serves a model organism in the study of pathogenicity, virulence factors, and mechanism of environmental adaptation. In this study, transcriptomics analysis of Zur's regulons was conducted in Y. pseudotuberculosis. The functions of Zur as a global regulator in metal homeostasis, motility, nutrient acquisition, glycan metabolism, and nucleotide metabolism, in turn, increasing the biofilm formation, stress resistance, and virulence were reviewed. The importance of Zur in environmental adaptation and pathogenicity of Y. pseudotuberculosis was emphasized.

Development and Validation of a Machine Learning-Based Model Used for Predicting Hepatocellular Carcinoma Risk in Patients with Hepatitis B-Related Cirrhosis: A Retrospective Study.

Object: Our objective was to estimate the 5-year cumulative risk of HCC in patients with HBC by utilizing an artificial neural network (ANN). Methods: We conducted this study with 1589 patients hospitalized at Beijing Ditan Hospital of Capital Medical University and People's Liberation Army Fifth Medical Center. The training cohort consisted of 913 subjects from Beijing Ditan Hospital of Capital Medical University, while the validation cohort comprised 676 subjects from People's Liberation Army Fifth Medical Center. Through univariate analysis, we identified factors that independently influenced the occurrence of HCC, which were then used to develop the ANN model. To evaluate the ANN model, we assessed its predictive accuracy, discriminative ability, and clinical net benefit using metrics such as the area under the receiver operating characteristic curve (AUC), concordance index (C-index), calibration curves. Results: In total, we included nine independent risk factors in the development of the ANN model. Remarkably, the AUC of the ANN model was 0.880, significantly outperforming the AUC values of other existing models including mPAGE-B (0.719) (95% CI 0.670-0.768), PAGE-B (0. 710) (95% CI 0.660-0.759), FIB-4 (0.693) (95% CI 0.640-0.745), and Toronto hepatoma risk index (THRI) (0.705) (95% CI 0.654-0.756) (p<0.001 for all). The ANN model effectively stratified patients into low, medium, and high-risk groups based on their 5-year In the training cohort, the positive predictive value (PPV) for low-risk patients was 26.2% (95% CI 25.0-27.4), and the negative predictive value (NPV) was 98.7% (95% CI 95.2-99.7). For high-risk patients, the PPV was 54.7% (95% CI 48.6-60.7), and the NPV was 91.6% (95% CI 89.4-93.4). These findings were validated in the independent validation cohort. Conclusion: The ANNs model has good individualized prediction performance and may be helpful to evaluate the probability of the 5-year risk of HCC in patients with HBC.

MXene-Integrated Perylene Anode with Ultra-Stable and Fast Ammonium-Ion Storage for Aqueous Micro Batteries.

The aqueous micro batteries (AMBs) are expected to be one of the most promising micro energy storage devices for its safe operation and cost-effectiveness. However, the performance of the AMBs is not satisfactory, which is attributed to strong interaction between metal ions and the electrode materials. Here, the first AMBs are developed with NH4 + as charge carrier. More importantly, to solve the low conductivity and the dissolution during the NH4 + intercalation/extraction problem of perylene material represented by perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA), the Ti3 C2 Tx MXene with high conductivity and polar surface terminals is introduced as a conductive skeleton (PTCDA/Ti3 C2 Tx MXene). Benefitting from this, the PTCDA/Ti3 C2 Tx MXene electrodes exhibit ultra-high cycle life and rate capability (74.31% after 10 000 galvanostatic chargedischarge (GCD) cycles, and 91.67 mAh g-1 at 15.0 A g-1 , i.e., capacity retention of 45.2% for a 30-fold increase in current density). More significantly, the AMBs with NH4 + as charge carrier and PTCDA/Ti3 C2 Tx MXene anode provide excellent energy density and power density, cycle life, and flexibility. This work will provide strategy for the development of NH4 + storage materials and the design of AMBs.

The clinical courses of HBV-related acute-on-chronic liver failure and a multi-state model to predict disease evolution.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a highly dynamic syndrome. The objective of this study was to delineate the clinical course of patients with HBV-ACLF and to develop a model to estimate the temporal evolution of disease severity. METHODS: We enrolled eligible patients from 2 large, multicenter prospective cohorts. The ACLF grade, organ failures, and outcomes were assessed at multiple time points (days 1/4/7/14/21/28). Probabilities for ACLF transitions between these disease states and to death within 28 days were calculated using a multi-state model that used baseline information and updated ACLF status. The model was validated in independent patients. RESULTS: Among all the 445 patients with HBV-ACLF, 76 represented disease progression, 195 had a stable or fluctuating course, 8 with improvement, and the remaining 166 with resolution within 28-day follow-up. New coagulation (63.64%) or renal failure (45.45%) was frequently observed during early progression. Patients with disease progression had a higher incidence of new episodes of ascites [10 (13.16%) vs. 22 (5.96%), p = 0.027] and HE [13(17.11%) vs. 21 (5.69%), p = 0.001], and a significant increase in white blood cell count. The multi-state model represented dynamic areas under the receiver operating characteristic curves ranging from 0.71 to 0.84 for predicting all ACLF states and death at 4, 7, 14, 21, and 28 days post-enrollment and from 0.73 to 0.94 for predicting death alone, performing better than traditional prognostic scores. CONCLUSIONS: HBV-ACLF is a highly dynamic syndrome with reversibility. The multi-state model is a tool to estimate the temporal evolution of disease severity, which may inform clinical decisions on treatment.

Characterization of acute-on-chronic liver diseases: A multicenter prospective cohort study.

BACKGROUND: Acute-on-chronic liver disease (AoCLD) accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases. AIM: To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD. METHODS: Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (ACLF) study cohort were included in this study. The clinical characteristics and outcomes, and the 90-d survival rate associated with each clinical type of AoCLD were analyzed, using the Kaplan-Meier method and the log-rank test. RESULTS: A total of 3375 patients with AoCLD were enrolled, including 1679 (49.7%) patients with liver cirrhosis acute decompensation (LC-AD), 850 (25.2%) patients with ACLF, 577 (17.1%) patients with chronic hepatitis acute exacerbation (CHAE), and 269 (8.0%) patients with liver cirrhosis active phase (LC-A). The most common cause of chronic liver disease (CLD) was HBV infection (71.4%). The most common precipitants of AoCLD was bacterial infection (22.8%). The 90-d mortality rates of each clinical subtype of AoCLD were 43.4% (232/535) for type-C ACLF, 36.0% (36/100) for type-B ACLF, 27.0% (58/215) for type-A ACLF, 9.0% (151/1679) for LC-AD, 3.0% (8/269) for LC-A, and 1.2% (7/577) for CHAE. CONCLUSION: HBV infection is the main cause of CLD, and bacterial infection is the main precipitant of AoCLD. The most common clinical type of AoCLD is LC-AD. Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.