Infection­associated bile acid disturbance contributes to macrophage activation in patients with cirrhosis.

Cirrhosis impairs macrophage function and disrupts bile acid homeostasis. Although bile acids affect macrophage function in patients with sepsis, whether and how the bile acid profile is changed by infection in patients with cirrhosis to modulate macrophage function remains unclear. The present study aimed to investigate the changes in the bile acid profile of patients with cirrhosis and infection and their effects on macrophage function. Serum was collected from 20 healthy subjects, 18 patients with cirrhosis and 39 patients with cirrhosis and infection. Bile acid profiles were detected using high­performance liquid chromatography­triple time­of­flight mass spectrometer. The association between bile acid changes and infection was analysed using receiver operating characteristic (ROC) curves. Infection­altered bile acids were used in combination with lipopolysaccharides (LPS) to stimulate RAW264.7/THP­1 cells in vitro. The migratory capacity was evaluated using wound healing and Transwell migration assays. The expression of Arg­1, iNOS, IκBα, phosphorylated (p­)IκBα and p65 was examined with western blotting and immunofluorescence, Tnfα, Il1b and Il6 mRNA was examined with RT­qPCR, and CD86, CD163 and phagocytosis was measured with flow cytometry. The ROC curves showed that decreased hyodeoxycholic acid (HDCA) and deoxycholic acid (DCA) levels were associated with infection. HDCA or DCA combined with LPS enhanced the phagocytic and migratory ability of macrophages, accompanied by upregulation of iNOS and CD86 protein expression as well as Tnfα, Il1b, and Il6 mRNA expression. However, neither HDCA nor DCA alone showed an effect on these phenotypes. In addition, DCA and HDCA acted synergistically with LPS to increase the expression of p­IκBα and the intranuclear migration of p65. Infection changed the bile acid profile in patients with cirrhosis, among which the reduction of DCA and HDCA associated most strongly with infection. HDCA and DCA enhanced the sensitivity of macrophage function loss to LPS stimulation. These findings suggested a potential role for monitoring the bile acid profile that could help manage patients with cirrhosis and infection.

The value of D-dimer and platelet-lymphocyte ratio combined with CT signs for predicting intestinal ischemia in patients with bowel obstruction.

OBJECTIVE: To investigate the diagnostic value of D-dimer, platelet-lymphocyte rate (PLR) and CT signs for intestinal ischemia in patients with bowel obstruction. METHODS: We retrospectively analyzed the clinical and imaging data of 105 patients diagnosed with bowel obstruction, and performed univariate and multivariate analyses to determine the independent risk factors for intestinal ischemia in patients with bowel obstruction. Moreover, the receiver operating characteristic curve (ROC) was plotted to examine the diagnostic value of D-dimer, PLR and CT signs in patients with bowel obstruction. Besides, Kappa tests were used to assess inter-observer agreement. RESULTS: We included 56 men (53%) and 49 women (47%) with mean age of 66.05 ± 16 years. Univariate and multivariate analyses showed that D-dimer, PLR and two significant CT signs (i.e., increased unenhanced bowel-wall attenuation and mesenteric haziness) were independent risk factors for intestinal ischemia in patients with bowel obstruction. ROC analysis showed that the combined use of D-dimer, PLR and the said two CT signs had better performance than single indicators in predicting intestinal ischemia in patients with bowel obstruction. The area under the curve (AUC) of the joint model III was 0.925 [95%CI: 0.876-0.975], with a sensitivity of 79.2% [95CI%: 67.2-91.1] and a specificity of 91.2% [95%CI: 83.7-98.9]. CONCLUSION: The combined use of D-dimer, PLR and CT signs has high diagnostic value for intestinal ischemia in patients with bowel obstruction and will prompt surgical exploration to evaluate intestinal blood flow.

Iron-Based Catalysts Derived from Iron-Containing Sludge for Enhanced Catalytic Performance of H2S Selective Catalytic Oxidation.

In this work, iron-containing sludge is used to prepare iron-based catalysts for efficient H2S selective catalytic oxidation. First, the effect of calcination temperatures on the catalytic activities of H2S selective oxidation is carried out and it can be found that S-500 calcined at 500 °C performs excellent catalytic activity. Then, the catalytic performance of the S-500 catalyst is further optimized using alkaline treatment with different concentrations of NaOH solution. The results indicate that S-500(2.0) treated with 2 M NaOH solution has the highest catalytic activity of H2S selective oxidation. Next, various characterization methods are used to analyze the structure and physical-chemical of the sludge-based catalysts. N2-Brunauer-Emmett-Teller (N2-BET) and X-ray photoelectron spectroscopy analyses show that the S-500(2.0) catalyst has the smallest average particle (11.17 nm), the biggest ratio of S ext/S micro(17.98) with bigger external specific surface area (49.09 m2·g-1), a higher proportion of Fe3+ species (50.88%), and surface adsorbed oxygen species (48.07%). Meanwhile, O2-TPD and CO2-TPD analysis indicates that the S-500(2.0) catalyst has a bigger value of the Oads/OTotal ratio (50.56%) and (CO2)(weak+moderate) /(CO2)Total ratio of (31.41%), indicating that there are much more oxygen vacancies and weak alkaline sites. As a result, the excellent catalytic performance of H2S selective oxidation can be attributed to its outstanding physical-chemical properties.

Coumestrol facilitates apoptosis in colorectal cancer cells by interacting with ZIP8 protein via the ferroptosis pathway.

Objective: So far, there have been no reports of coumestrol inhibiting colorectal cancer (CRC) through the ferroptosis pathway. This study is to investigate the mechanism of the traditional Chinese medicine monomer coumestrol in the treatment of CRC. Methods: Data on CRC transcriptome sequencing was obtained from the GEO database and TCGA database. Bioinformatics analyses were conducted to screen for CRC prognostic-related key genes and their potential binding monomers in traditional Chinese medicine. The inhibitory effect of coumestrol on CRC cell lines (COLO 205 & HCT 116) was determined using the CCK-8 assay, and cell apoptosis was assessed by flow cytometry. The content of ferrous ions was measured using the Ferrous Ion Content Assay Kit. The expression of ferroptosis pathway-related genes SLC39A8, NCOA4, VDAC2, and NOX2 before and after small interference RNA (siRNA) was examined through real-time PCR and Western blotting. Results: SLC39A8 was found to be associated with CRC clinical progression staging, and its encoded protein ZIP8 may bind to coumestrol. KEGG enrichment analysis suggested that ZIP8 plays a role in iron transmembrane transport and may affect the expression of ferroptosis pathway-related genes NCOA4, VDAC2, and NOX2. Coumestrol was found to induce apoptosis in CRC cell lines by upregulating the expression of ferroptosis pathway-related genes SLC39A8, NCOA4, VDAC2, and NOX2. However, coumestrol was unable to upregulate the expression of ferroptosis pathway-related genes in CRC cell lines after SLC39A8 interference. Conclusion: Coumestrol facilitates apoptosis in CRC cells by interacting with ZIP8 protein via the ferroptosis pathway.

A CRISPR activation screen identifies FBXO22 supporting targeted protein degradation.

Targeted protein degradation (TPD) represents a potent chemical biology paradigm that leverages the cellular degradation machinery to pharmacologically eliminate specific proteins of interest. Although multiple E3 ligases have been discovered to facilitate TPD, there exists a compelling requirement to diversify the pool of E3 ligases available for such applications. Here we describe a clustered regularly interspaced short palindromic repeats (CRISPR)-based transcriptional activation screen focused on human E3 ligases, with the goal of identifying E3 ligases that can facilitate heterobifunctional compound-mediated target degradation. Through this approach, we identified a candidate proteolysis-targeting chimera (PROTAC), 22-SLF, that induces the degradation of FK506-binding protein 12 when the transcription of FBXO22 gene is activated. Subsequent mechanistic investigations revealed that 22-SLF interacts with C227 and/or C228 in F-box protein 22 (FBXO22) to achieve target degradation. Lastly, we demonstrated the versatility of FBXO22-based PROTACs by effectively degrading additional endogenous proteins, including bromodomain-containing protein 4 and the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion protein.

IL-1ra loaded chondroitin sulfate-functionalized microspheres for minimally invasive treatment of intervertebral disc degeneration.

Presently, the clinical treatment of intervertebral disc degeneration (IVDD) remains challenging, but the strategy of simultaneously overcoming the overactive inflammation and restoring the anabolic/catabolic balance of the extracellular matrix (ECM) in the nucleus pulposus (NP) has become an effective way to alleviate IVDD. IL-1ra, a natural antagonist against IL-1ß, can mitigate inflammation and promote regeneration in IVDD. Chondroitin sulfate (CS), an important component of the NP, can promote ECM synthesis and delay IVDD. Thus, these were chosen and integrated into functionalized microspheres to achieve their synergistic effects. First, CS-functionalized microspheres (GelMA-CS) with porous microstructure, good monodispersion, and about 200 µm diameter were efficiently and productively fabricated using microfluidic technology. After lyophilization, the microspheres with good local injection and tissue retention served as the loading platform for IL-1ra and achieved sustained release. In in vitro experiments, the IL-1ra-loaded microspheres exhibited good cytocompatibility and efficacy in inhibiting the inflammatory response of NP cells induced by lipopolysaccharide (LPS) and promoting the secretion of ECM. In in vivo experiments, the microspheres showed good histocompatibility, and local, minimally invasive injection of the IL-1ra-loaded microspheres could reduce inflammation, maintain the height of the intervertebral disc (IVD) and the water content of NP close to about 70 % in the sham group, and retain the integrated IVD structure. In summary, the GelMA-CS microspheres served as an effective loading platform for IL-1ra, eliminated inflammation through the controlled release of IL-1ra, and promoted ECM synthesis via CS to delay IVDD, thereby providing a promising intervention strategy for IVDD. STATEMENT OF SIGNIFICANCE: The strategy of simultaneously overcoming the overactive inflammation and restoring the anabolic/catabolic balance of the extracellular matrix (ECM) in nucleus pulposus (NP) has shown great potential prospects for alleviating intervertebral disc degeneration (IVDD). From the perspective of clinical translation, this study developed chondroitin sulfate functionalized microspheres to act as the effective delivery platform of IL-1ra, a natural antagonist of interleukin-1ß. The IL-1ra loading microspheres (GelMA-CS-IL-1ra) showed good biocompatibility, good injection with tissue retention, and synergistic effects of inhibiting the inflammatory response induced by lipopolysaccharide and promoting the secretion of ECM in NPCs. In vivo, they also showed the beneficial effect of reducing the inflammatory response, maintaining the height of the intervertebral disc and the water content of the NP, and preserving the integrity of the intervertebral disc structure after only one injection. All demonstrated that the GelMA-CS-IL-1ra microspheres would have great promise for the minimally invasive treatment of IVDD.

The Asian Fabry Cardiomyopathy High-Risk Screening Study 2 (ASIAN-FAME-2): Prevalence of Fabry Disease in Patients with Left Ventricular Hypertrophy.

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder that commonly manifests cardiovascular complications. We aimed to assess the prevalence of FD in a Chinese population with left ventricular hypertrophy (LVH) whilst implementing a gender-specific screening approach. Methods: Patients with LVH, defined as a maximum thickness of the left ventricular septal/posterior wall ≥ 13 mm, were considered eligible. All patients with hypertrophic cardiomyopathy (HCM) were excluded. Plasma α-galactosidase (α-GLA) enzyme activity was assessed using a dried blood spot test. Males with low enzyme activity underwent genetic testing to confirm a diagnosis of FD whereas females were screened for both α-GLA and globotriaosylsphingosine concentration and underwent genetic analysis of the GLA gene only if testing positive for ≥1 parameter. Results: 426 unrelated patients (age = 64.6 ± 13.0 years; female: male = 113:313) were evaluated. FD was diagnosed in 3 unrelated patients (age = 69.0 ± 3.5 years, female: male = 1:2) and 1 related female subject (age = 43 years). Genetic analyses confirmed the late-onset cardiac variant GLA c.640-801G>A (n = 3) and the missense variant c.869T>C associated with classic FD (n = 1). Cardiac complications were the only significant findings associated with the late-onset c.640-801G>A mutation, manifesting as mild or severe concentric LVH. In contrast, the classic c.869T>C mutation FD exhibited multisystemic manifestations in addition to severe concentric LVH. Conclusions: The prevalence of FD is lower in Chinese patients with LVH when HCM is excluded. The pathological variant c.640-801G>A remains the most common cause of late-onset FD, while the detection of FD in females can be improved by utilizing a gender-specific screening method.

A portable europium complex-loaded fluorescent test paper combined with smartphone analysis for the on-site and visual detection of mancozeb in food samples.

The on-site detection of mancozeb in food samples holds immense value for food safety. A red-fluorescent europium complex (Eu-PYDC-Phen) has been prepared and employed as a fluorescence probe for mancozeb detection. The optimized probe suspension exhibits excellent detection performances, including a wide linear range (0-0.24 mM), low detection limit (65 nM), rapid response (2 mins) and high selectivity. Moreover, a portable detection platform was carefully designed, integrating the Eu-PYDC-Phen-based fluorescent test strips with smartphone color recognition software. This innovative platform enables visual and on-site detection of mancozeb in tomato, apple, and lettuce, achieving satisfactory recovery rates (90.34 to 106.50%). Furthermore, the integration of machine learning techniques based on hierarchical clustering algorithm has the potential to further improve the prediction and decision-making efficiency in mancozeb detection. This work provides an economical, convenient, and reliable strategy for on-site detection of pesticide in agricultural products, thereby making a meaningful contribution to food safety.

WT1 gene mutations impact post-transplant relapse in myelodysplastic syndrome with excess blasts 2 patients.

Wilms tumor 1 (WT1) gene mutations are infrequent in myelodysplastic syndrome (MDS), but MDS with WT1 mutations (WT1mut) is considered high risk for acute myeloid leukemia (AML) transformation. The influence of WT1 mutations in patients with MDS after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unclear. We performed a retrospective analysis of 136 MDS with excess blasts 2 (MDS-EB2) patients with available WT1 status who underwent their first allo-HSCT between 2017 and 2022 in our center. There were 20 (20/136, 15%) cases in the WT1mut group and 116 (116/136, 85%) cases in the WT1 wild-type (WT1wt) group. WT1mut patients had a higher 2-year cumulative incidence of relapse (CIR) than WT1wt cases (26.2% vs. 9.4%, p = 0.037) after allo-HSCT. Multivariate analysis of relapse showed that WT1 mutations (HR, 6.0; p = 0.002), TP53 mutations (HR, 4.2; p = 0.021), and ≥ 5% blasts in bone marrow (BM) at transplantation (HR, 6.6; p = 0.004) were independent risk factors for relapse. Patients were stratified into three groups according to the risk factors. Two-year CIR differed significantly in high-, intermediate-, and low-risk groups (31.8%, 11.6%, and 0%, respectively). Hence, WT1 mutations may be related to post-transplant relapse in patients with MDS-EB2, which warrants further study.

Hydroxyproline Concentration and Associated Factors of Preserved Small Incision Lenticule Extraction-Derived Corneal Stromal Lenticules.

PURPOSE: To evaluate changes of hydroxyproline concentration and its influencing factors of small incision lenticule extraction (SMILE)-derived corneal stromal lenticules with different preservation methods. METHODS: A total of 390 corneal stromal lenticules of 195 patients were derived from SMILE surgeries. Thirty of the lenticules were classified as the fresh (control) group, and the rest were randomly and evenly divided and stored in anhydrous glycerol, silicone oil, Optisol, and cryopreservation for 1 day, 1 week, or 1 month. A hydroxyproline assay kit (ab222941, Abcam) was used to measure the hydroxyproline concentration in each preservation method. Concentrations of MMP-2, TIMP-2, TNFα, TGFß2, and reactive oxygen species were also evaluated. RESULTS: In the anhydrous glycerol group, the concentration of hydroxyproline decreased within 1 week (fresh: 1 dΔ = 0.229, P < 0.001*; 1 d - 1 wΔ = 0.055, P < 0.001*) while that in the silicone oil group remained stable in 1 week (1 d - 1 wΔ = -0.005, P = 0.929) and decreased significantly in 1 m (1 m - 1 wΔ = -0.041, P = 0.003*). The sequence of hydroxyproline concentration in the Optisol group was 1 m > 1 day > 1 week. Hydroxyproline concentration in the cryopreservation group decreased within 1 m. Hydroxyproline concentration was highest in the Optisol group and lowest in the anhydrous glycerol group under the same preservation time. Hydroxyproline concentration was negatively correlated with MMP-2 (r = -0.16, P = 0.421) and TIMP-2 (r = -0.56, P = 0.002*) while MMP-2 and TNFα (r = 0.17, P = 0.242), TIMP-2 and TGFß2 (r = 0.21, P = 0.207), and TNFα and reactive oxygen species (r = 0.52, P = 0.007*) were positively correlated. CONCLUSIONS: More collagen was retained in SMILE lenticules preserved in Optisol under the same preservation time. The mechanism of the changes of collagen in preserved SMILE-derived lenticules and oxidative stress requires additional investigation.

Recombinant collagen coating 3D printed PEGDA hydrogel tube loading with differentiable BMSCs to repair bile duct injury.

Bile duct injury presents a significant clinical challenge following hepatobiliary surgery, necessitating advancements in the repair of damaged bile ducts is a persistent issue in biliary surgery. 3D printed tubular scaffolds have emerged as a promising approach for the repair of ductal tissues, yet the development of scaffolds that balance exceptional mechanical properties with biocompatibility remains an ongoing challenge. This study introduces a novel, bio-fabricated bilayer bile duct scaffold using a 3D printing technique. The scaffold comprises an inner layer of polyethylene glycol diacrylate (PEGDA) to provide high mechanical strength, and an outer layer of biocompatible, methacryloylated recombinant collagen type III (rColMA) loaded with basic fibroblast growth factor (bFGF)-encapsulated liposomes (bFGF@Lip). This design enables the controlled release of bFGF, creating an optimal environment for the growth and differentiation of bone marrow mesenchymal stem cells (BMSCs) into cholangiocyte-like cells. These cells are instrumental in the regeneration of bile duct tissues, evidenced by the pronounced expression of cholangiocyte differentiation markers CK19 and CFTR. The PEGDA//rColMA/bFGF@Lip bilayer bile duct scaffold can well simulate the bile duct structure, and the outer rColMA/bFGF@Lip hydrogel can well promote the growth and differentiation of BMSCs into bile duct epithelial cells. In vivo experiments showed that the scaffold did not cause cholestasis in the body. This new in vitro pre-differentiated active 3D printed scaffold provides new ideas for the study of bile duct tissue replacement.

Tagging large CNV blocks in wheat boosts digitalization of germplasm resources by ultra-low-coverage sequencing.

BACKGROUND: The massive structural variations and frequent introgression highly contribute to the genetic diversity of wheat, while the huge and complex genome of polyploid wheat hinders efficient genotyping of abundant varieties towards accurate identification, management, and exploitation of germplasm resources. RESULTS: We develop a novel workflow that identifies 1240 high-quality large copy number variation blocks (CNVb) in wheat at the pan-genome level, demonstrating that CNVb can serve as an ideal DNA fingerprinting marker for discriminating massive varieties, with the accuracy validated by PCR assay. We then construct a digitalized genotyping CNVb map across 1599 global wheat accessions. Key CNVb markers are linked with trait-associated introgressions, such as the 1RS·1BL translocation and 2NvS translocation, and the beneficial alleles, such as the end-use quality allele Glu-D1d (Dx5 + Dy10) and the semi-dwarf r-e-z allele. Furthermore, we demonstrate that these tagged CNVb markers promote a stable and cost-effective strategy for evaluating wheat germplasm resources with ultra-low-coverage sequencing data, competing with SNP array for applications such as evaluating new varieties, efficient management of collections in gene banks, and describing wheat germplasm resources in a digitalized manner. We also develop a user-friendly interactive platform, WheatCNVb ( http://wheat.cau.edu.cn/WheatCNVb/ ), for exploring the CNVb profiles over ever-increasing wheat accessions, and also propose a QR-code-like representation of individual digital CNVb fingerprint. This platform also allows uploading new CNVb profiles for comparison with stored varieties. CONCLUSIONS: The CNVb-based approach provides a low-cost and high-throughput genotyping strategy for enabling digitalized wheat germplasm management and modern breeding with precise and practical decision-making.

Synthesis of Sulfonated Phenylsilsesquioxanes Guided by Machine Learning.

Sulfonated octaphenylsilsesquioxane (SPOSS) has garnered significant interest due to its unique structural properties of containing the -SO3H group and its wide range of applications. This study introduces a novel approach to the synthesis of SPOSS, leveraging machine learning algorithms to explore new recipes and achieve higher -SO3H functionality. The focus was on synthesizing SPOSS with 2, 4, 6, and 8-SO3H functional groups on the phenyl group, marked as SPOSS-2, SPOSS-4, SPOSS-6, and SPOSS-8, respectively. The successful synthesis of SPOSS-8 was achieved by 5 training outputs based on the recipes of 21 sets of low-functionality (<4) SPOSS. The structure of SPOSS was confirmed using Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and time-of-flight mass spectrometry (MALDI-TOF MS). Machine learning analysis revealed that K2SO4 is an important additive to improve the functionality of SPOSS. A synthetic mechanism was proposed and validated that K2SO4 participated in the reaction to generate sulfur trioxide (SO3), a sulfonating agent with high reactivity. SPOSS shows thermal stability superior to octaphenylsilsesquioxane (OPS) according to thermogravimetric analysis (TGA) and TG-FTIR.

MiR398b Targets Superoxide Dismutase Genes in Soybean in Defense Against Heterodera glycines via Modulating ROS Homeostasis.

MicroRNAs (miRNAs) play crucial roles in plant defense responses. However, the underlying mechanism by which miR398b contributes to soybean responses to soybean cyst nematode (SCN, Heterodera glycines) remains elusive. In this study, by using Agrobacterium rhizogenes-mediated transformation of soybean hairy roots, we observed that miR398b and target genes GmCCS and GmCSD1b played vital functions in soybean-H. glycines interaction. The study revealed that the abundance of miR398b was down-regulated by H. glycines infection, and overexpression miR398b enhanced susceptibility of soybean to H. glycines. Conversely, silencing of miR398b improved soybean resistance to H. glycines. Detection assays revealed that miR398b rapidly senses stress-induced ROS, leading to the repression of target genes GmCCS and GmCSD1b, and regulating the accumulation of plant defense genes against nematodes infection. Moreover, exogenous synthetic ds-miR398b enhanced soybean sensitivity to H. glycines by modulating H2O2 and O2- levels. Functional analysis demonstrated that overexpression GmCCS and GmCSD1b in soybean enhanced resistance to H. glycines. RNA interference (RNAi)-mediated repression of GmCCS and GmCSD1b in soybean increased susceptibility to H. glycines. RNA-sequencing revealed that a majority of differentially expressed genes (DEGs) in overexpression GmCCS were associated with oxidative stress. Overall, the results indicate that miR398b targets superoxide dismutase genes, which negatively regulate soybean resistance to H. glycines via modulating ROS levels and defense signal.

Risk factors for thrombotic events in systemic lupus erythematosus patients with antiphospholipid antibodies: insights from morphometric measurements of carotid arteries.

Objective: To identify the correlation between thrombosis and atherosclerosis in systemic lupus erythematosus (SLE) patients with antiphospholipid antibodies (aPLs) (SLE/aPLs) through high-resolution magnetic resonance imaging (HR-MRI) of the carotid artery. Methods: A single-center, cross-sectional study was conducted. We collected consecutive patients with SLE/aPLs and healthy controls who underwent carotid HR-MRI examinations. The morphometric characteristics of the common carotid artery (CCA), internal carotid artery (ICA), external carotid artery (ECA), and carotid bulb (Sinus) were measured, and the differences in morphometric parameters between different groups were analyzed. Results: A total of 144 carotid arteries were analyzed. Compared with the control group, the wall area, wall thickness (WT and WTmax), and normalized wall index of CCA, ICA, ECA, and Sinus were increased in patients with SLE/aPLs, and the total vascular area (TVA) of CCA, ICA, and Sinus, and the bifurcation angle (BIFA) of ICA-ECA were also increased. A negative lupus anticoagulant (LAC) (with or without positive anticardiolipin antibody (aCL) or anti-ß2glycoprotein antibody (aß2GPI)) contributed to illustrating lower increased TVA and thickened vessel walls of CCA and ICA in SLE/aPLs patients without thrombotic events. Logistic regression analysis showed that WTmaxSinus and WTmaxGlobal were independent risk factors for thrombotic events in SLE/aPLs patients. The receiver operator characteristic curve showed that the cut-off value of WTmaxSinus was 2.855 mm, and WTmaxGlobal was 3.370 mm. Conclusion: HR-MRI ensures the complete and accurate measurement of carotid morphometric parameters. Compared with the control group, the carotid artery in patients with SLE/aPLs is mainly characterized by diffusely thickened vessel walls, and the patients with thrombotic events showed additional higher vascular area of CCA and ICA, and BIFA of ICA-ECA without significant change in lumen area. The carotid arteries of SLE/aPLs patients with thrombotic events exhibited significant vessel wall thickening in all segments except ECA compared to those without thrombotic events. LAC-negative and non-thrombotic events distinguish relatively early atherosclerosis in the carotid arteries in patients with SLE/aPLs. Patients with SLE/aPLs that possess circumscribed thickened carotid vessel walls (>3.370 mm), particularly thickened at the Sinus (>2.855 mm), may require management strategies for the risk of thrombotic events.

Plasma von Willebrand factor levels in patients with cancer: A meta­analysis.

von Willebrand Factor (VWF) is well recognized for being dysregulated in various malignancies and has emerged as a potential biomarker for cancer detection. The present meta-analysis aimed to elucidate the association between plasma VWF and the incidence and metastasis of cancer. For this purpose, a comprehensive search was conducted across multiple databases from their inception until March 3, 2023. This culminated in the selection of 15 original studies on various types of cancer, including a collective sample of 1,403 individuals. The standardized mean difference (SMD) and 95% confidence intervals (CIs) were employed as statistical parameters to determine the association between plasma VWF and the incidence and metastasis of cancer. These were estimated using a random-effects model. The pooled data revealed that the plasma VWF levels of patients with cancer were significantly elevated compared with those of healthy controls (SMD, 0.98; 95% CI, 0.59-1.36), and a significant association was observed between plasma VWF levels and cancer metastasis (SMD, 0.69; 95% CI, 0.33-1.06). The symmetry of the Begg's funnel plots indicated that no significant bias was present in the analyses of VWF in cancer and its metastasis. In summary, the results of the present meta-analysis support the hypothesis that increased plasma VWF levels may serve as a biomarker for cancer and metastatic progression.

Urinary enterolignans and enterolignan-predicting microbial species are favourably associated with liver fat and other obesity markers.

Aims: Plant-derived lignans may protect against obesity, while their bioactivity needs gut microbial conversion to enterolignans. We used repeated measures to identify enterolignan-predicting microbial species and investigate whether enterolignans and enterolignan-predicting microbial species are associated with obesity. Methods: Urinary enterolignans, fecal microbiota, body weight, height, and circumferences of the waist (WC) and hips (HC) were repeatedly measured at the baseline and after 1 year in 305 community-dwelling adults in Huoshan, China. Body composition and liver fat [indicated by the controlled attenuation parameter (CAP)] were measured after 1 year. Multivariate-adjusted linear models and linear mixed-effects models were used to analyze single and repeated measurements, respectively. Results: Enterolactone and enterodiol levels were both inversely associated with the waist-to-hip ratio, body fat mass (BFM), visceral fat level (VFL), and liver fat accumulation (all P < 0.05). Enterolactone levels were also associated with lower WC (ß = -0.0035 and P = 0.013) and HC (ß = -0.0028 and P = 0.044). We identified multiple bacterial genera whose relative abundance was positively associated with the levels of enterolactone (26 genera) and enterodiol (22 genera, all P false discovery rate < 0.05), and constructed the enterolactone-predicting microbial score and enterodiol-predicting microbial score to reflect the overall enterolignan-producing potential of the host gut microbiota. Both these scores were associated with lower body weight and CAP (all P < 0.05). The enterolactone-predicting microbial score was also inversely associated with the BFM (ß = -0.1128 and P = 0.027) and VFL (ß = -0.1265 and P = 0.044). Conclusion: Our findings support that modulating the host gut microbiome could be a potential strategy to prevent obesity by enhancing the production of enterolignans.

Learning and depicting lobe-based radiomics feature for COPD Severity staging in low-dose CT images.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a prevalent and debilitating respiratory condition that imposes a significant healthcare burden worldwide. Accurate staging of COPD severity is crucial for patient management and treatment planning. METHODS: The retrospective study included 530 hospital patients. A lobe-based radiomics method was proposed to classify COPD severity using computed tomography (CT) images. First, we segmented the lung lobes with a convolutional neural network model. Secondly, the radiomic features of each lung lobe are extracted from CT images, the features of the five lung lobes are merged, and the selection of features is accomplished through the utilization of a variance threshold, t-Test, least absolute shrinkage and selection operator (LASSO). Finally, the COPD severity was classified by a support vector machine (SVM) classifier. RESULTS: 104 features were selected for staging COPD according to the Global initiative for chronic Obstructive Lung Disease (GOLD). The SVM classifier showed remarkable performance with an accuracy of 0.63. Moreover, an additional set of 132 features were selected to distinguish between milder (GOLD I + GOLD II) and more severe instances (GOLD III + GOLD IV) of COPD. The accuracy for SVM stood at 0.87. CONCLUSIONS: The proposed method proved that the novel lobe-based radiomics method can significantly contribute to the refinement of COPD severity staging. By combining radiomic features from each lung lobe, it can obtain a more comprehensive and rich set of features and better capture the CT radiomic features of the lung than simply observing the lung as a whole.

Scutellarein Suppresses the Production of ROS and Inflammatory Mediators of LPS-Activated Bronchial Epithelial Cells and Attenuates Acute Lung Injury in Mice.

Scutellarein is a key active constituent present in many plants, especially in Scutellaria baicalensis Georgi and Erigeron breviscapus (vant.) Hand-Mazz which possesses both anti-inflammatory and anti-oxidative activities. It also is the metabolite of scutellarin, with the ability to relieve LPS-induced acute lung injury (ALI), strongly suggesting that scutellarein could suppress respiratory inflammation. The present study aimed to investigate the effects of scutellarein on lung inflammation by using LPS-activated BEAS-2B cells (a human bronchial epithelial cell line) and LPS-induced ALI mice. The results showed that scutellarein could reduce intracellular reactive oxygen species (ROS) accumulation through inhibiting the activation of NADPH oxidases, markedly downregulating the transcription and translation of pro-inflammatory cytokines, including interleukin-6 (IL-6), C-C motif chemokine ligand 2 (CCL2), and C-X-C motif chemokine ligand (CXCL) 8 in LPS-activated BEAS-2B cells. The mechanism study revealed that it suppressed the phosphorylation and degradation of IκBα, consequently hindering the translocation of p65 from the cytoplasm to the nucleus and its subsequent binding to DNA, thereby decreasing NF-κB-regulated gene transcription. Notably, scutellarein had no impact on the activation of AP-1 signaling. In LPS-induced ALI mice, scutellarein significantly decreased IL-6, CCL2, and tumor necrosis factor-α (TNF-α) levels in the bronchoalveolar lavage fluid, attenuated lung injury, and inhibited neutrophil infiltration. Our findings suggest that scutellarein may be a beneficial agent for the treatment of infectious pneumonia by virtue of its anti-oxidative and anti-inflammatory activities.

Genetic association of glycemic traits and antihyperglycemic agent target genes with the risk of lung cancer: A Mendelian randomization study.

AIMS: To evaluate the potential causal effect of glycemic traits on lung cancer and investigate the impact of antihyperglycemic agent-target genes on lung cancer risk. METHODS: Genetic variants associated with glycemic traits, antihyperglycemic agent-target genes, and lung cancer were extracted from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), expression quantitative trait loci (eQTLs), protein quantitative trait loci (pQTLs), and the International Lung Cancer Consortium (ILCCO), respectively. Mendelian randomization (MR) analyses were performed to examine the associations of glycemic traits and antihyperglycemic agent-target genes with lung cancer. Mediation analysis was conducted to explore whether overweight operated as a mediator between antihyperglycemic agents and lung cancer outcomes. RESULTS: Genetically determined glycated hemoglobin A1c levels were associated with squamous cell lung cancer (OR = 1.78; 95 % CI, 1.08-2.92; p = 0.023). The PRKAB1 gene (the target of metformin) was associated with a lower risk of developing lung adenocarcinoma (OR = 0.85; 95 % CI, 0.76-0.96; p = 0.006). Further mediation analyses did not support overweight as a mediator between PRKAB1 activation and lung adenocarcinoma. CONCLUSION: Our analyses suggest an association of genetically determined abnormal glycemic traits with squamous cell lung cancer. The potential association between PRKAB1 activation and a reduced risk of developing lung adenocarcinoma appears to be independent of the anti-obesity effects of metformin, suggesting that PRKAB1 activation may have a direct protective effect on lung adenocarcinoma development.