Angiogenesis unveiled: Insights into its role and mechanisms in cartilage injury.

Osteoarthritis (OA) commonly results in compromised mobility and disability, thereby imposing a significant burden on healthcare systems. Cartilage injury is a prevalent pathological manifestation in OA and constitutes a central focus for the development of treatment strategies. Despite the considerable number of studies aimed at delaying this degenerative process, their outcomes remain unvalidated in preclinical settings. Recently, therapeutic strategies focused on angiogenesis have attracted the growing interest from researchers. Thus, we conducted a comprehensive literature review to elucidate the current progress in research and pinpoint research gaps in this domain. Additionally, it provides theoretical guidance for future research endeavors and the development of treatment strategies.

Development and Validation of a Stromal-Immune Signature to Predict Prognosis in Intrahepatic Cholangiocarcinoma.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. Patients and methods: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. Results: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. Conclusion: We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.

OsUVR8b, rather than OsUVR8a, plays a predominant role in rice UVR8-mediated UV-B response.

UV RESISTANCE LOCUS 8 (UVR8) has been identified in Arabidopsis thaliana as the receptor mediating responses to UV-B radiation. However, UVR8-mediated UV-B signaling pathways in rice, which possesses two proteins (UVR8a and UVR8b) with high identities to AtUVR8, remain largely unknown. Here, UVR8a/b were found to be predominantly expressed in rice leaves and leaf sheaths, while the levels of UVR8b transcript and UVR8b protein were both higher than those of UVR8a. Compared to wild-type (WT) plants, uvr8b and uvr8a uvr8b rice mutants exposed to UV-B showed reduced UV-B-induced growth inhibition and upregulation of CHS and HY5 transcripts alongside UV-B acclimation. However, uvr8a mutant was similar to WT plants and exhibited changes comparable with WT. Overexpressing OsUVR8a/b enhanced UV-B-induced growth inhibition and acclimation to UV-B. UV-B was able to enhance the interaction between E3 ubiquitin ligase OsCOP1 and OsUVR8a/b, whereas the interaction of the homologous protein of Arabidopsis REPRESSOR OF UV-B PHOTOMORPHOGENESIS2 (AtRUP2) in rice with OsUVR8a/b was independent of UV-B. Additionally, OsUVR8a/b proteins were also found in the nucleus and cytoplasm even in the absence of UV-B. The abundance of OsUVR8 monomer showed an invisible change in the leaves of rice seedlings transferred from white light to that supplemented with UV-B, even though UV-B was able to weaken the interactions between OsUVR8a and OsUVR8b homo and heterodimers. Therefore, both OsUVR8a and OsUVR8b, which have different localization and response patterns compared with AtUVR8, function in the response of rice to UV-B radiation, whereas OsUVR8b plays a predominant role in this process.

Dapagliflozin restores autophagy and attenuates apoptosis via the AMPK/mTOR pathway in diabetic nephropathy rats and high glucose-induced HK-2 cells.

PURPOSE: Diabetic nephropathy (DN) is a serious microvascular complication of diabetes mellitus. Significantly reduced levels of autophagy in diabetic kidneys play an important role in the development of DN. The present study investigated the effects of dapagliflozin (DAP) on renal autophagy and AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway in vivo and in vitro. METHODS: We explored the effect of DAP in streptozotocin (STZ)-induced DN rats. The anti-DN effect of DAP was assessed by body weight, kidney weight/body weight ratio, blood and urine biochemical parameters, and pathological changes of kidney tissue. Number of autophagosomes in the kidney was investigated through Transmission electron microscopy. Besides, cell viability and apoptosis of DAP alone or combined with Compound C (CC, a selective AMPK inhibitor)-treated high glucose (HG)-induced HK-2 cells were detected by Cell Counting Kit-8 (CCK-8) and flow cytometry assays. Immunohistochemistry, Western blot, Enzyme-linked immunosorbent assay (ELISA), and immunofluorescence were employed to detect the expression levels of extracellular matrix (ECM) deposition, autophagy, apoptosis, and AMPK/mTOR pathway-associated targets in vivo and in vitro. RESULTS: The results showed that DAP ameliorated the body weight and decreased kidney weight, fasting blood glucose, and serum/urine biochemical parameters of renal damage, as well as renal pathological changes. Moreover, DAP significantly ameliorated HG-induced cell apoptosis and ECM deposition in HK-2 cells. However, these favorable effects of DAP could be abolished by co-treatment with CC in HG-induced HK-2 cells. Mechanistically, DAP can enhance autophagy in DN including increased LC3-II/I ratio, Beclin-1, p-AMPK protein levels, and decreased p62 and p-mTOR protein expressions, as well as inhibited renal fibrosis and apoptosis. CONCLUSION: In summary, DAP alleviated fibrosis, apoptosis, and autophagy in DN rats and HG-induced HK-2 cells by regulating the AMPK/mTOR pathway.

Inequities in Alcohol Screening of Primary Care Patients with Chronic Conditions.

INTRODUCTION: Routine alcohol screening of people with chronic health conditions that are exacerbated by alcohol can help to prevent morbidity and mortality. The U.S. Affordable Care Act and other recent health reforms expanded insurance coverage and supported alcohol screening in primary care. This study assessed increases in alcohol screening following health reform, and insurance-related and racial and ethnic disparities in screening. METHODS: Data are from the 2013-2019 National Surveys on Drug Use and Health for adults with alcohol-related chronic conditions who received primary care in the past year (N=46,014). The outcome was receipt of alcohol screening (yes/no) in which a health care provider inquired whether, how often, or how much the respondent drank, or about having alcohol-related problems. Multivariable logistic regression models assessed temporal changes in screening overall and by insurance type and race/ethnicity, adjusting for demographics, health conditions, and primary care utilization. Statistical analysis was performed in 2023. RESULTS: Alcohol screening prevalence rose from 69% to 77% from 2013 through 2019, with a notable increase in 2014-15 for both Medicaid-insured and privately-insured patients. Black and Asian American patients were generally less likely to be screened than White patients. Importantly, racial disparities in screening were found among privately-insured patients, patients with hypertension, patients with heart disease, and patients with diabetes who drink alcohol. CONCLUSIONS: Alcohol screening of primary care patients with chronic conditions increased following health reform, but persistent disparities among patients with private insurance and specific chronic conditions underscore the need to address drivers of unequal preventive care.

Exploring research hotspots and emerging trends in neuroimaging of vascular cognitive impairment: a bibliometric and visualized analysis.

Background: Vascular cognitive impairment (VCI) manifests in memory impairment, mental slowness, executive dysfunction, behavioral changes, and visuospatial abnormalities, significantly compromising the quality of daily life for patients and causing inconvenience to caregivers. Neuroimaging serves as a crucial approach to evaluating the extent, location, and type of vascular lesions in patients suspected of VCI. Nevertheless, there is still a lack of comprehensive bibliometric analysis to discern the research status and emerging trends concerning VCI neuroimaging. Objective: This study endeavors to explore the collaboration relationships of authors, countries, and institutions, as well as the research hotspots and frontiers of VCI neuroimaging by conducting a bibliometric analysis. Methods: We performed a comprehensive retrieval within the Core Collection of Web of Science, spanning from 2000 to 2023. After screening the included literature, CiteSpace and VOSviewer were utilized for a visualized analysis aimed at identifying the most prolific author, institution, and journal, as well as extracting valuable information from the analysis of references. Results: A total of 1,024 publications were included in this study, comprising 919 articles and 105 reviews. Through the analysis of keywords and references, the research hotspots involve the relationship between neuroimaging of cerebral small vessel disease (CSVD) and VCI, the diagnosis of VCI, and neuroimaging methods pertinent to VCI. Moreover, potential future research directions encompass CSVD, functional and structural connectivity, neuroimaging biomarkers, and lacunar stroke. Conclusion: The research in VCI neuroimaging is constantly developing, and we hope to provide insights and references for future studies by delving into the research hotspots and frontiers within this field.

[Material basis of kidney Yang deficiency rats before and after salt processing of Dipsacus asper based on spectrum-effect relationship].

This paper aims to study the spectrum-effect relationship between the fingerprints before and after salt processing of Dipsacus asper and the efficacy of warming and tonifying kidney Yang and find the main active components against kidney Yang deficiency before and after salt processing of D. asper, so as to provide the basis for clarifying the effect of salt processing on kidney Yang deficiency. The HPLC fingerprint before and after salt processing of D. asper was established by the HPLC-DAD. 15 common peaks were obtained, and 11 components were identified. The content changes of various components in rat serum were detected, and the difference in efficacy before and after salt processing was compared. The results of pharmacological experiments showed that salt processing of D. asper could enhance the kidney index. At the same dose, there was a significant difference between the raw D. asper and D. asper after salt processing groups. Compared with the model group, the contents of ACTH, cAMP, CORT, E_2, GH, Na~+-K~+-ATPase, T, and T4 in the serum of rats in the administration group increased to a certain extent, and the contents of cGMP and TNF-α decreased to a certain extent. Among them, there were significant differences in the above indexes in the serum of rats in the high-dose group of raw D. asper, middle-dose group of D. asper after salt processing, high-dose group of D. asper after salt processing, and the positive drug group. The overall results showed that D. asper after salt processing was more effective than raw D. asper in preventing kidney yang deficiency. The efficacy of D. asper was evaluated by grey correlation analysis, entropy method, and Pearson correlation analysis, and the components of D. asper after salt processing against kidney yang deficiency were screened out. According to the results of correlation degree ranking, the components with increased ranking before and after salt processing of D. asper were loganin, chlorogenic acid, dipsacoside A, asperosaponin Ⅵ, caffeic acid, and isochlorogenic acid B. It was preliminarily speculated that these compounds may be the potential pharmacodynamic components for the treatment of kidney yang deficiency before and after salt processing of D. asper. The changing components before and after the salt processing of D. asper were determined, which proved that D. asper after salt processing was superior to D. asper in the treatment of kidney yang deficiency. The spectrum-effect relationship between the efficacy of D. asper before and after salt processing and the treatment of kidney yang deficiency was established, which laid a foundation for the subsequent study on the pharmacodynamic components and molecular mechanism of salt processing of D. asper.

Clinical prediction of insufficient vaults after implantable collamer lens implantation.

AIM: To determine the factors related to preoperative ocular characters that are predictive of insufficient vault (<250 µm) after implantable collamer lens (ICL V4c; STAAR Surgical) implantation. METHODS: The participants underwent ICL surgery and were divided into the low (<250 µm) and normal (250-1000 µm) vault groups based on the postoperative vault at 3mo. The preoperative biometric parameters and clinical outcomes were compared between the two groups. The relationship between the 3-month vault values and preoperative ocular parameters were evaluated by Generalized estimating equations. RESULTS: Sixteen (23 eyes) and 36 patients (63 eyes) were in the low and normal vault groups, respectively. All implantation procedures were uneventful with no cataract formation in the early postoperative period. The sulcus-to-sulcus lens rise (STSL) and iris ciliary angle (ICA) were correlated with vault at 3mo after surgery. Every 0.1 mm increase in STSL was associated with 38.9 µm decrease in the postoperative 3-month vault. A rise of 1 degree in ICA is associated with a reduction of 4 µm in vault. CONCLUSION: Eyes with a narrow ciliary sulcus are associated with a higher rate of low vault after ICL implantation, suggesting a need for adjustments to the ICL size in these patients. Evaluating the characteristics of the ciliary sulcus contributes valuable information to predict low vault after surgery.

Patient-Specific Factors Predicting Renal Denervation Response in Patients With Hypertension: A Systematic Review and Meta-Analysis.

BACKGROUND: The accurate selection of patients likely to respond to renal denervation (RDN) is crucial for optimizing treatment outcomes in patients with hypertension. This systematic review was designed to evaluate patient-specific factors predicting the RDN response. METHODS AND RESULTS: We focused on individuals with hypertension who underwent RDN. Patients were categorized based on their baseline characteristics. The primary outcome was blood pressure (BP) reduction after RDN. Both randomized controlled trials and nonrandomized studies were included. We assessed the risk of bias using corresponding tools and further employed the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the overall quality of evidence. A total of 50 studies were ultimately included in this systematic review, among which 17 studies were for meta-analysis. Higher baseline heart rate and lower pulse wave velocity were shown to be associated with significant antihypertensive efficacy of RDN on 24-hour systolic BP reduction (weighted mean difference, -4.05 [95% CI, -7.33 to -0.77]; weighted mean difference, -7.20 [95% CI, -9.79 to -4.62], respectively). In addition, based on qualitative analysis, higher baseline BP, orthostatic hypertension, impaired baroreflex sensitivity, and several biomarkers are also reported to be associated with significant BP reduction after RDN. CONCLUSIONS: In patients with hypertension treated with the RDN, higher heart rate, and lower pulse wave velocity were associated with significant BP reduction after RDN. Other factors, including higher baseline BP, hypertensive patients with orthostatic hypertension, BP variability, impaired cardiac baroreflex sensitivity, and some biomarkers are also reported to be associated with a better BP response to RDN.

Construction of a new prognostic model for colorectal cancer based on bulk RNA-seq combined with The Cancer Genome Atlas data.

Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths, and improving the prognosis of CRC patients is an urgent concern. The aim of this study was to explore new immunotherapy targets to improve survival in CRC patients. Methods: We analyzed CRC-related single-cell data GSE201348 from the Gene Expression Omnibus (GEO) database, and identified differentially expressed genes (DEGs). Subsequently, we performed differential analysis on the rectum adenocarcinoma (READ) and colon adenocarcinoma (COAD) transcriptome sequencing data [The Cancer Genome Atlas (TCGA)-CRC queue] and clinical data downloaded from TCGA database. Subgroup analysis was performed using CIBERSORTx and cluster analysis. Finally, biomarkers were identified by one-way cox regression as well as least absolute shrinkage and selection operator (LASSO) analysis. Results: In this study, we analyzed CRC-related single-cell data GSE201348, and identified 5,210 DEGs. Subsequently, we performed differential analysis on the TCGA-CRC queue database, and obtained 4,408 DEGs. Then, we categorized the cancer samples in the sequencing data into three groups (k1, k2, and k3), with significant differences observed between the k1 and k2 groups via survival analysis. Further differential analysis on the samples in the k1 and k2 groups identified 1,899 DEGs. A total of 77 DEGs were selected among those DEGs obtained from three differential analyses. Through subsequent Cox univariate analysis and LASSO analysis, seven biomarkers (RETNLB, CLCA4, UGT2A3, SULT1B1, CCL24, BMP5, and ATOH1) were identified and selected to establish a risk score (RS). Conclusions: To sum up, this study demonstrates the potential of the seven-gene prognostic risk model as instrumental variables for predicting the prognosis of CRC.

[Identification of the binding proteins of organic acid metabolites by matrix thermal shift assay].

Organic acid metabolites exhibit acidic properties. These metabolites serve as intermediates in major carbon metabolic pathways and are involved in several biochemical pathways, including the tricarboxylic acid (TCA) cycle and glycolysis. They also regulate cellular activity and play crucial roles in epigenetics, tumorigenesis, and cellular signal transduction. Knowledge of the binding proteins of organic acid metabolites is crucial for understanding their biological functions. However, identifying the binding proteins of these metabolites has long been a challenging task owing to the transient and weak nature of their interactions. Moreover, traditional methods are unsuitable for the structural modification of the ligands of organic acid metabolites because these metabolites have simple and similar structures. Even minor structural modifications can significantly affect protein interactions. Thermal proteome profiling (TPP) provides a promising avenue for identifying binding proteins without the need for structural modifications. This approach has been successfully applied to the identification of the binding proteins of several metabolites. In this study, we investigated the binding proteins of two TCA cycle intermediates, i.e., succinate and fumarate, and lactate, an end-product of glycolysis, using the matrix thermal shift assay (mTSA) technique. This technique involves combining single-temperature (52 ℃) TPP and dose-response curve analysis to identify ligand-binding proteins with high levels of confidence and determine the binding affinity between ligands and proteins. To this end, HeLa cells were lysed, followed by protein desalting to remove endogenous metabolites from the cell lysates. The desalted cell lysates were treated with fumarate or succinate at final concentrations of 0.004, 0.04, 0.4, and 2 mmol/L in the experimental groups or 2 mmol/L sodium chloride in the control group. Considering that the cellular concentration of lactate can be as high as 2-30 mmol/L, we then applied lactate at final concentrations of 0.2, 1, 5, 10, and 25 mmol/L in the experimental groups or 25 mmol/L sodium chloride in the control group. Using high-sensitivity mass spectrometry coupled with data-independent acquisition (DIA) quantification, we quantified 5870, 5744, and 5816 proteins in succinate, fumarate, and lactate mTSA experiments, respectively. By setting stringent cut-off values (i.e., significance of changes in protein thermal stability (p-value)<0.001 and quality of the dose-response curve fitting (square of Pearson's correlation coefficient, R2)>0.95), multiple binding proteins for these organic acid metabolites from background proteins were confidently determined. Several known binding proteins were identified, notably fumarate hydratase (FH) as a binding protein for fumarate, and α-ketoglutarate-dependent dioxygenase (FTO) as a binding protein for both fumarate and succinate. Additionally, the affinity data for the interactions between these metabolites and their binding proteins were obtained, which closely matched those reported in the literature. Interestingly, ornithine aminotransferase (OAT), which is involved in amino acid biosynthesis, and 3-mercaptopyruvate sulfurtransferase (MPST), which acts as an antioxidant in cells, were identified as lactate-binding proteins. Subsequently, an orthogonal assay technique developed in our laboratory, the solvent-induced precipitation (SIP) technique, was used to validate the mTSA results. SIP identified OAT as the top target candidate, validating the mTSA-based finding that OAT is a novel lactate-binding protein. Although MPST was not identified as a lactate-binding protein by SIP, statistical analysis of MPST in the mTSA experiments with 10 or 25 mmol/L lactate revealed that MPST is a lactate-binding protein with a high level of confidence. Peptide-level empirical Bayes t-tests combined with Fisher's exact test also supported the conclusion that MPST is a lactate-binding protein. Lactate is structurally similar to pyruvate, the known binding protein of MPST. Therefore, assuming that lactate could potentially occupy the binding site of pyruvate on MPST. Overall, the novel binding proteins identified for lactate suggest their potential involvement in amino acid synthesis and redox balance regulation.

Optimizing the Microenvironment in Solid Polymer Electrolytes by Anion Vacancy Coupled with Carbon Dots.

The practical application of solid polymer electrolyte is hindered by the small transference number of Li+, low ionic conductivity and poor interfacial stability, which are seriously determined by the microenvironment in polymer electrolyte. The introduction of functional fillers is an effective solution to these problems. In this work, based on density functional theory (DFT) calculations, it is demonstrated that the anion vacancy of filler can anchor anions of lithium salt, thereby significantly increasing the transference number of Li+ in the electrolyte. Therefore, flower-like SnS2-based filler with abundant sulfur vacancies is prepared under the regulation of functionalized carbon dots (CDs). It is worth mentioning that the CDs dotted on the surface of SnS2 have rich organic functional groups, which can serve as the bridging agent to enhance the compatibility of filler and polymer, leading to superior mechanical performance and fast ion transport pathway. Additionally, the in-situ formed Li2S/Li3N at the interface of Li metal and electrolyte facilitate the fast Li+ diffusion and uniform Li deposition, effectively mitigating the growth of lithium dendrites. As a result, the assembled lithium metal batteries exhibit excellent cycling stability, reflecting the superiority of the carbon dots derived vacancy-rich inorganic filler modification strategy.

FXR activation remodels hepatic and intestinal transcriptional landscapes in metabolic dysfunction-associated steatohepatitis.

The escalating obesity epidemic and aging population have propelled metabolic dysfunction-associated steatohepatitis (MASH) to the forefront of public health concerns. The activation of FXR shows promise to combat MASH and its detrimental consequences. However, the specific alterations within the MASH-related transcriptional network remain elusive, hindering the development of more precise and effective therapeutic strategies. Through a comprehensive analysis of liver RNA-seq data from human and mouse MASH samples, we identified central perturbations within the MASH-associated transcriptional network, including disrupted cellular metabolism and mitochondrial function, decreased tissue repair capability, and increased inflammation and fibrosis. By employing integrated transcriptome profiling of diverse FXR agonists-treated mice, FXR liver-specific knockout mice, and open-source human datasets, we determined that hepatic FXR activation effectively ameliorated MASH by reversing the dysregulated metabolic and inflammatory networks implicated in MASH pathogenesis. This mitigation encompassed resolving fibrosis and reducing immune infiltration. By understanding the core regulatory network of FXR, which is directly correlated with disease severity and treatment response, we identified approximately one-third of the patients who could potentially benefit from FXR agonist therapy. A similar analysis involving intestinal RNA-seq data from FXR agonists-treated mice and FXR intestine-specific knockout mice revealed that intestinal FXR activation attenuates intestinal inflammation, and has promise in attenuating hepatic inflammation and fibrosis. Collectively, our study uncovers the intricate pathophysiological features of MASH at a transcriptional level and highlights the complex interplay between FXR activation and both MASH progression and regression. These findings contribute to precise drug development, utilization, and efficacy evaluation, ultimately aiming to improve patient outcomes.

Simplified liver imaging reporting and data system for the diagnosis of hepatocellular carcinoma on gadoxetic acid-enhanced magnetic resonance imaging.

BACKGROUND: The liver imaging reporting and data system (LI-RADS) diagnostic table has 15 cells and is too complex. The diagnostic performance of LI-RADS for hepatocellular carcinoma (HCC) is not satisfactory on gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI). AIM: To evaluate the ability of the simplified LI-RADS (sLI-RADS) to diagnose HCC on EOB-MRI. METHODS: A total of 331 patients with 356 hepatic observations were retrospectively analysed. The diagnostic performance of sLI-RADS A-D using a single threshold was evaluated and compared with LI-RADS v2018 to determine the optimal sLI-RADS. The algorithms of sLI-RADS A-D are as follows: The single threshold for sLI-RADS A and B was 10 mm, that is, classified observations ≥ 10mm using an algorithm of 10-19 mm observations (sLI-RADS A) and ≥ 20 mm observations (sLI-RADS B) in the diagnosis table of LI-RADS v2018, respectively, while the classification algorithm remained unchanged for observations < 10 mm; the single threshold for sLI-RADS C and D was 20 mm, that is, for < 20 mm observations, the algorithms for < 10 mm observations (sLI-RADS C)and 10-19 mm observations (sLI-RADS D) were used, respectively, while the algorithm remained unchanged for observations ≥ 20 mm. With hepatobiliary phase (HBP) hypointensity as a major feature (MF), the final sLI-RADS (F-sLI-RADS) was formed according to the optimal sLI-RADS, and its diagnostic performance was evaluated. The times needed to classify the observations according to F-sLI-RADS and LI-RADS v2018 were compared. RESULTS: The optimal sLI-RADS was sLI-RADS D (with a single threshold of 20 mm), because its sensitivity was greater than that of LI-RADS v2018 (89.8% vs 87.0%, P = 0.031), and its specificity was not lower (89.4% vs 90.1%, P > 0.999). With HBP hypointensity as an MF, the sensitivity of F-sLI-RADS was greater than that of LI-RADS v2018 (93.0% vs 87.0%, P < 0.001) and sLI-RADS D (93.0% vs 89.8%, P = 0.016), without a lower specificity (86.5% vs 90.1%, P = 0.062; 86.5% vs 89.4%, P = 0.125). Compared with that of LI-RADS v2018, the time to classify lesions according to F-sLI-RADS was shorter (51 ± 21 s vs 73 ± 24 s, P < 0.001). CONCLUSION: The use of sLI-RADS with HBP hypointensity as an MF may improve the sensitivity of HCC diagnosis and reduce lesion classification time.

High-Voltage Long-Cycling All-Solid-State Lithium Batteries with High-Valent-Element-Doped Halide Electrolytes.

All-solid-state batteries (ASSBs) have garnered considerable attention as promising candidates for next-generation energy storage systems due to their potentially simultaneously enhanced safety capacities and improved energy densities. However, the solid future still calls for materials with high ionic conductivity, electrochemical stability, and favorable interfacial compatibility. In this study, we present a series of halide solid-state electrolytes (SSEs) utilizing a doping strategy with highly valent elements, demonstrating an outstanding combination of enhanced ionic conductivity and oxidation stability. Among these, Li2.6In0.8Ta0.2Cl6 emerges as the standout performer, displaying a superionic conductivity of up to 4.47 mS cm-1 at 30 °C, along with a low activation energy barrier of 0.321 eV for Li+ migration. Additionally, it showcases an extensive oxidation onset of up to 5.13 V (vs Li+/Li), enabling high-voltage ASSBs with promising cycling performance. Particularly noteworthy are the ASSBs employing LiCoO2 cathode materials, which exhibit an extended cyclability of over 1400 cycles, with 70% capacity retention under 4.6 V (vs Li+/Li), and a capacity of up to 135 mA h g-1 at a 4 C rate, with the loading of active materials at 7.52 mg cm-2. This study demonstrates a feasible approach to designing desirable SSEs for energy-dense, highly stable ASSBs.

Metformin-Induced Invertase Unfolding: Enzyme Kinetics and Activity Regulation.

The effects of metformin on invertase activity and its inhibition on sucrose digestion were studied. The rapid unfolding kinetics of invertases, followed a two-state model with an inactive intermediate formation. The dynamic interaction between metformin and invertase caused the secondary structure of the enzyme to become less ß-sheet, more α-helix, and random coiling oriented, which weakened the binding force between enzyme and its substrate. Metformin acted as a chaotrope and disrupted the hydrogen bonds of water, which facilitated the unfolding of invertase. However, some sugar alcohols, which promoted the H-bond formation of water, could repair the secondary structure of metformin-denatured invertase and therefore regulate the enzyme activity. This research enriches our understanding of the mechanism of enzyme unfolding induced by guanidine compounds. Moreover, because metformin and sugar substitutes are of concern to diabetes, this research also provides useful information for understanding the activity of the digestive enzyme that coexists with metformin and sugar alcohols.

Heterogeneous body compositions and all-cause mortality in acute coronary syndrome patients: a ten-year retrospective cohort study.

BACKGROUND: The association of different body components, including lean mass and body fat, with the risk of death in acute coronary syndrome (ACS) patients are unclear. METHODS: We enrolled adults diagnosed with ACS at our center between January 2011 and December 2012 and obtained follow-up outcomes via telephone questionnaires. We used restricted cubic splines (RCS) with the Cox proportional hazards model to analyze the associations between body mass index (BMI), predicted lean mass index (LMI), predicted body fat percentage (BF), and the value of LMI/BF with 10-year mortality. We also examined the secondary outcome of death during hospitalization. RESULTS: During the maximum 10-year follow-up of 1398 patients, 331 deaths (23.6%) occurred, and a U-shaped relationship was found between BMI and death risk (P nonlinearity = 0.03). After adjusting for age and history of diabetes, the overweight group (24 ≤ BMI < 28 kg/m2) had the lowest mortality (HR = 0.53, 95% CI: 0.29-0.99). Predicted LMI and LMI/BF had an inverse linear relationship with a 10-year death risk (P nonlinearity = 0.24 and P nonlinearity = 0.38, respectively), while an increase in BF was associated with increased mortality (P nonlinearity = 0.64). During hospitalization, 31 deaths (2.2%) were recorded, and the associations of the indicators with in-hospital mortality were consistent with the long-term outcome analyses. CONCLUSION: Our study provides new insight into the "obesity paradox" in ACS patients, highlighting the importance of considering body composition heterogeneity. Predicted LMI and BF may serve as useful tools for assessing nutritional status and predicting the prognosis of ACS, based on their linear associations with all-cause mortality.

Elongatibacter sediminis gen. nov., sp. nov., isolated from intertidal sediment, and genomic comparison with all genera in the family Wenzhouxiangellaceae.

A novel slightly halophilic, aerobic, and Gram-stain-negative strain, designated as CH-27T, was isolated during a bacterial resource investigation of intertidal sediment collected from Xiaoshi Island in Weihai, PR China. Cells of strain CH-27T were rod-shaped with widths of 0.3-0.6 µm and lengths of 2.0-11.0 µm. Strain CH-27T grew optimally at 37 °C, pH 7.0 and with 2.0 % (w/v) NaCl. Catalase activity was weakly positive and oxidase activity was positive. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CH-27T was most related to Marinihelvus fidelis KCTC 92639T (93.6 %), followed by Wenzhouxiangella marina MCCC 1K00261T (92.0 %). Based on genome comparisons between strain CH-27T and M. fidelis KCTC 92639T, the average amino acid identity was 63.6 % and the percentage of conserved proteins was 48.3 %. The major cellular fatty acid of strain CH-27T (≥10 %) was iso-C15 : 0 and the sole respiratory quinone was quinone-8. The polar lipids were phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, and aminophospholipid. The DNA G+C content was 62.7 mol%. Based on comprehensive analysis of its phylogenetic, physiological, biochemical, and chemotaxonomic characteristics, strain CH-27T represents a novel species in a novel genus, for which the name Elongatibacter sediminis gen. nov., sp.nov. is proposed. The type strain is CH-27T (=MCCC 1H00480T=KCTC 8011T).

Construction of Conjugated Organic Polymers for Efficient Photocatalytic Hydrogen Peroxide Generation with Adequate Utilization of Water Oxidation.

The visible-light-driven photocatalytic production of hydrogen peroxide (H2O2) is currently an emerging approach for transforming solar energy into chemical energy. In general, the photocatalytic process for producing H2O2 includes two pathways: the water oxidation reaction (WOR) and the oxygen reduction reaction (ORR). However, the utilization efficiency of ORR surpasses that of WOR, leading to a discrepancy with the low oxygen levels in natural water and thereby impeding their practical application. Herein, we report a novel donor-bridge-acceptor (D-B-A) organic polymer conjugated by the Sonogashira-Hagihara coupling reaction with tetraphenylethene (TPE) units as the electron donors, acetylene (A) as the connectors and pyrene (P) moieties as the electron acceptors. Notably, the resulting TPE-A-P exhibits a remarkable solar-to-chemical conversion of 1.65% and a high BET-specific surface area (1132 m2·g-1). Furthermore, even under anaerobic conditions, it demonstrates an impressive H2O2 photosynthetic efficiency of 1770 µmol g-1 h-1, exceeding the vast majority of previously reported photosynthetic systems of H2O2. The outstanding performance is attributed to the effective separation of electrons and holes, along with the presence of sufficient reaction sites facilitated by the incorporation of alkynyl electronic bridges. This protocol presents a successful method for generating H2O2 via a water oxidation reaction, signifying a significant advancement towards practical applications in the natural environment.