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1.
J Immunol ; 212(7): 1075-1080, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38363205

ABSTRACT

B cell trafficking involves the coordinated activity of multiple adhesive and cytokine-receptor interactions, and the players in this process are not fully understood. In this study, we identified the tetraspanin CD53 as a critical regulator of both normal and malignant B cell trafficking. CXCL12 is a key chemokine in B cell homing to the bone marrow and secondary lymphoid organs, and both normal and malignant B cells from Cd53-/- mice have reduced migration toward CXCL12 in vitro, as well as impaired marrow homing in vivo. Using proximity ligation studies, we identified the CXCL12 receptor, CXCR4, as a novel, to our knowledge, CD53 binding partner. This interaction promotes receptor function, because Cd53-/- B cells display reduced signaling and internalization of CXCR4 in response to CXCL12. Together, our data suggest that CD53 interacts with CXCR4 on both normal and malignant B cells to promote CXCL12 signaling, receptor internalization, and marrow homing.


Subject(s)
B-Lymphocytes , Bone Marrow , Animals , Mice , Bone Marrow/metabolism , B-Lymphocytes/metabolism , Chemokine CXCL12/metabolism , Signal Transduction , Tetraspanins/metabolism , Carrier Proteins/metabolism , Receptors, CXCR4/metabolism , Cell Movement/physiology , Bone Marrow Cells/metabolism
2.
Proc Natl Acad Sci U S A ; 120(29): e2215744120, 2023 07 18.
Article in English | MEDLINE | ID: mdl-37428911

ABSTRACT

Hepatocellular carcinoma (HCC) takes the predominant malignancy of hepatocytes with bleak outcomes owing to high heterogeneity among patients. Personalized treatments based on molecular profiles will better improve patients' prognosis. Lysozyme (LYZ), a secretory protein with antibacterial function generally expressed in monocytes/macrophages, has been observed for the prognostic implications in different types of tumors. However, studies about the explicit applicative scenarios and mechanisms for tumor progression are still quite limited, especially for HCC. Here, based on the proteomic molecular classification data of early-stage HCC, we revealed that the LYZ level was elevated significantly in the most malignant HCC subtype and could serve as an independent prognostic predictor for HCC patients. Molecular profiles of LYZ-high HCCs were typical of those for the most malignant HCC subtype, with impaired metabolism, along with promoted proliferation and metastasis characteristics. Further studies demonstrated that LYZ tended to be aberrantly expressed in poorly differentiated HCC cells, which was regulated by STAT3 activation. LYZ promoted HCC proliferation and migration in both autocrine and paracrine manners independent of the muramidase activity through the activation of downstream protumoral signaling pathways via cell surface GRP78. Subcutaneous and orthotopic xenograft tumor models indicated that targeting LYZ inhibited HCC growth markedly in NOD/SCID mice. These results propose LYZ as a prognostic biomarker and therapeutic target for the subclass of HCC with an aggressive phenotype.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Animals , Mice , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Muramidase/metabolism , Proteomics , Cell Line, Tumor , Mice, Inbred NOD , Mice, SCID , Prognosis , Neoplastic Processes , Biomarkers, Tumor/genetics , Cell Proliferation , Gene Expression Regulation, Neoplastic
3.
Blood ; 141(10): 1180-1193, 2023 03 09.
Article in English | MEDLINE | ID: mdl-36542833

ABSTRACT

The hematopoietic stem cell (HSC) cycle responds to inflammatory and other proliferative stressors; however, these cells must quickly return to quiescence to avoid exhaustion and maintain their functional integrity. The mechanisms that regulate this return to quiescence are not well understood. Here, we show that tetraspanin CD53 is markedly upregulated in HSCs in response to a variety of inflammatory and proliferative stimuli and that the loss of CD53 is associated with prolonged cycling and reduced HSC function in the context of inflammatory stress. Mechanistically, CD53 promotes the activity of the dimerization partner, RB-like, E2F, and multi-vulva class B (DREAM) transcriptional repressor complex, which downregulates genes associated with cycling and division. Proximity labeling and confocal fluorescence microscopy studies showed that CD53 interacts with DREAM-associated proteins, specifically promoting the interaction between Rbl2/p130 and its phosphatase protein phosphatase 2A (PP2A), effectively stabilizing p130 protein availability for DREAM binding. Together, these data identified a novel mechanism by which stressed HSCs resist cycling.


Subject(s)
Hematopoietic Stem Cells , Tetraspanin 25 , Female , Humans , Cell Division , Hematopoietic Stem Cells/metabolism , Mice , Tetraspanin 25/metabolism , Animals
4.
EMBO Rep ; 24(6): e55837, 2023 06 05.
Article in English | MEDLINE | ID: mdl-37039033

ABSTRACT

Dedifferentiation is the reversion of mature cells to a stem cell-like fate, whereby gene expression programs are altered and genes associated with multipotency are (re)expressed. Misexpression of multipotency factors and pathways causes the formation of ectopic neural stem cells (NSCs). Whether dedifferentiated NSCs faithfully produce the correct number and types of progeny, or undergo timely terminal differentiation, has not been assessed. Here, we show that ectopic NSCs induced via bHLH transcription factor Deadpan (Dpn) expression fail to undergo appropriate temporal progression by constantly expressing mid-temporal transcription factor(tTF), Sloppy-paired 1/2 (Slp). Consequently, this resulted in impaired terminal differenation and generated an excess of Twin of eyeless (Toy)-positive neurons at the expense of Reversed polarity (Repo)-positive glial cells. Preference for a mid-temporal fate in these ectopic NSCs is concordant with an enriched binding of Dpn at mid-tTF loci and a depletion of Dpn binding at early- and late-tTF loci. Retriggering the temporal series via manipulation of the temporal series or cell cycle is sufficient to reinstate neuronal diversity and timely termination.


Subject(s)
Drosophila Proteins , Neural Stem Cells , Drosophila Proteins/genetics , Neural Stem Cells/metabolism , Transcription Factors/metabolism , Neurons/metabolism , Neuroglia , Cell Differentiation/genetics , Gene Expression Regulation, Developmental
5.
J Biol Chem ; 299(2): 102835, 2023 02.
Article in English | MEDLINE | ID: mdl-36581203

ABSTRACT

Tetraspanins are transmembrane signaling and proinflammatory proteins. Prior work demonstrates that the tetraspanin, CD53/TSPAN25/MOX44, mediates B-cell development and lymphocyte migration to lymph nodes and is implicated in various inflammatory diseases. However, CD53 is also expressed in highly metabolic tissues, including adipose and liver; yet its function outside the lymphoid compartment is not defined. Here, we show that CD53 demarcates the nutritional and inflammatory status of hepatocytes. High-fat exposure and inflammatory stimuli induced CD53 in vivo in liver and isolated primary hepatocytes. In contrast, restricting hepatocyte glucose flux through hepatocyte glucose transporter 8 deletion or through trehalose treatment blocked CD53 induction in fat- and fructose-exposed contexts. Furthermore, germline CD53 deletion in vivo blocked Western diet-induced dyslipidemia and hepatic inflammatory transcriptomic activation. Surprisingly, metabolic protection in CD53 KO mice was more pronounced in the presence of an inciting inflammatory event. CD53 deletion attenuated tumor necrosis factor alpha-induced and fatty acid + lipopolysaccharide-induced cytokine gene expression and hepatocyte triglyceride accumulation in isolated murine hepatocytes. In vivo, CD53 deletion in nonalcoholic steatohepatitis diet-fed mice blocked peripheral adipose accumulation and adipose inflammation, insulin tolerance, and liver lipid accumulation. We then defined a stabilized and trehalase-resistant trehalose polymer that blocks hepatocyte CD53 expression in basal and over-fed contexts. The data suggest that CD53 integrates inflammatory and metabolic signals in response to hepatocyte nutritional status and that CD53 blockade may provide a means by which to attenuate pathophysiology in diseases that integrate overnutrition and inflammation, such as nonalcoholic steatohepatitis and type 2 diabetes.


Subject(s)
Hepatocytes , Non-alcoholic Fatty Liver Disease , Tetraspanin 25 , Animals , Mice , Diet, High-Fat , Hepatocytes/metabolism , Inflammation/genetics , Inflammation/metabolism , Liver/metabolism , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/metabolism , Obesity/metabolism , Tetraspanin 25/metabolism , Tetraspanins/genetics , Tetraspanins/metabolism , Trehalose/metabolism
6.
EMBO J ; 39(21): e106564, 2020 11 02.
Article in English | MEDLINE | ID: mdl-33021741

ABSTRACT

Glycolysis is a major metabolic process which ensures the break down of glucose into pyruvate via multiple enzymatic steps, but if and how this catabolism can impact on developmental patterning is unclear. In this issue, Spannl et al (2020) demonstrate a novel link between energy metabolism and tissue formation in the fly imaginal discs. They show that ATPs generated via glycolysis maintain active transport of a smoothened inhibitor, which keeps Hh signalling in check to preserve the correct shape and proportion of the developing wing.


Subject(s)
Drosophila Proteins , Hedgehog Proteins , Adenosine Triphosphate/metabolism , Animals , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Glycolysis , Hedgehog Proteins/metabolism , Membrane Potentials , Plasma/metabolism , Wings, Animal/metabolism
7.
Anal Chem ; 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38329031

ABSTRACT

We present UniSpec, an attention-driven deep neural network designed to predict comprehensive collision-induced fragmentation spectra, thereby improving peptide identification in shotgun proteomics. Utilizing a training data set of 1.8 million unique high-quality tandem mass spectra (MS2) from 0.8 million unique peptide ions, UniSpec learned with a peptide fragmentation dictionary encompassing 7919 fragment peaks. Among these, 5712 are neutral loss peaks, with 2310 corresponding to modification-specific neutral losses. Remarkably, UniSpec can predict 73%-77% of fragment intensities based on our NIST reference library spectra, a significant leap from the 35%-45% coverage of only b and y ions. Comparative studies with Prosit elucidate that while both models are strong at predicting their respective fragment ion series, UniSpec particularly shines in generating more complex MS2 spectra with diverse ion annotations. The integration of UniSpec's predictions into shotgun proteomics data analysis boosts the identification rate of tryptic peptides by 48% at a 1% false discovery rate (FDR) and 60% at a more confident 0.1% FDR. Using UniSpec's predicted in-silico spectral library, the search results closely matched those from search engines and experimental spectral libraries used in peptide identification, highlighting its potential as a stand-alone identification tool. The source code and Python scripts are available on GitHub (https://github.com/usnistgov/UniSpec) and Zenodo (https://zenodo.org/records/10452792), and all data sets and analysis results generated in this work were deposited in Zenodo (https://zenodo.org/records/10052268).

8.
Anal Chem ; 96(22): 9051-9059, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38776068

ABSTRACT

Surface-enhanced Raman spectroscopy (SERS) tags have the advantages of unique fingerprint vibration spectrum, ultranarrow spectral line widths, and weak photobleaching effect, showing great potential for bioimaging. However, SERS imaging is still hindered for further application due to its weak spontaneous Raman scattering, biomolecular signal interference, and long acquisition times. Here, we develop a novel SERS tag of the core (Au)-shell (N-doped graphene) structure (Au@NGs) with ultrastrong and stable Raman signal (2180 cm-1) in the cellular Raman-silent region (1800-2800 cm-1) through base-promoted oxidative decarboxylation of amino acids. Exploring the factors (metal salts, amino acids, catalysts, temperature, etc.) to obtain Au@NGs with the strongest Raman signal commonly requires more than 100,000 separate experiments, while that using an orthogonal array testing strategy is reduced to 56. The existence of deep charge transfer between the Au surface and C≡N-graphene is proved by theoretical calculations, which means the ultrastrong signal of Au@NGs is the joint effect of electromagnetic and chemical enhancement. The Au@NGs have a detection sensitivity down to a single-nanoparticle level, and high-speed and high-resolution cellular imaging (4453 pixels) is obtained within 10 s by global Raman imaging. The combination of Au@NGs-based tags with ultrastrong intrinsic Raman imaging capability and global imaging technology holds great promise for high-speed Raman imaging.


Subject(s)
Gold , Graphite , Spectrum Analysis, Raman , Spectrum Analysis, Raman/methods , Gold/chemistry , Graphite/chemistry , Humans , Metal Nanoparticles/chemistry , Surface Properties , Amino Acids/analysis , Amino Acids/chemistry
9.
Small ; 20(14): e2306155, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37991257

ABSTRACT

Helicobacter pylori (H. pylori) is the major etiological factor of a variety of gastric diseases. However, the treatment of H. pylori is challenged by the destruction of targeted drugs by gastric acid and pepsin. Herein, a dual-targeted cascade catalytic nanozyme PtCo@Graphene@Hemin-2(L-arginine) (PtCo@G@H2A) is designed for the treatment of H. pylori. The dual-targeting ability of PtCo@G@H2A is derived from directly targeting the receptor protein of H. pylori through hemin and responding to the acidic environment to cause charge reversal (protonation of L-arginine) to capture H. pylori, achieving efficient targeting effect. Compared with the single-targeting strategy relying on hemin, the dual-targeting strategy can greatly improve the targeting rate, achieving an increase of 850% targeting rate. At the concentration of NaHCO3 in intestinal fluid, the surface potential of PtCo@G@H2A can be quickly restored to avoid side effects. Meanwhile, PtCo@G@H2A has pH-responsive oxidase-like activity, which can generate nitric oxide (NO) through a cascade catalytic process that first generates reactive oxygen species (ROS) with oxygen, and further oxidizes L-arginine through ROS, realizing a superior acid-selective bactericidal effect. Overall, it proposes a promising strategy for the treatment of H. pylori that maintains high targeting and therapeutic effects in the environment of gastric acid and pepsin.


Subject(s)
Graphite , Helicobacter pylori , Helicobacter pylori/metabolism , Pepsin A/pharmacology , Reactive Oxygen Species , Graphite/pharmacology , Hemin , Arginine/metabolism , Arginine/pharmacology
10.
Eur J Clin Invest ; 54(6): e14179, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38363025

ABSTRACT

BACKGROUND: Emerging data suggested that lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease. Previous studies indicated fibrinogen (Fib) had synergetic effect on Lp(a)-induced events. However, combined impact of Fib and Lp(a) on ischemic stroke has not been elucidated. METHODS: In this prospective study, we consecutively enrolled 8263 patients with stable coronary artery diseases (CAD) from 2011 to 2017. Patients were categorized into three groups according to tertiles of Lp(a) levels [Lp(a)-low, Lp(a)-medium, and Lp(a)-high] and further divided into nine groups by Lp(a) and Fib levels. All subjects were followed up for the occurrence of ischemic stroke. RESULTS: During a median follow-up of 37.7 months, 157 (1.9%) ischemic strokes occurred. Stroke incidence increased by Lp(a) (1.1 vs. 2.1 vs. 2.5%, Cochran-Armitage p < .001) and Fib (1.1 vs. 2.0 vs. 2.6%, Cochran-Armitage p < .001) categories. When further classified into nine groups by Lp(a) and Fib levels, the incidence of ischemic stroke in group 9 [Lp(a)-high and Fib-high] was significantly higher than that in group 1 [Lp(a)-low and Fib-low] (3.1 vs. 6%, p < .001). The group 9 was associated with a highest risk for ischemic stroke (adjusted HR 4.907, 95% CI: 2.154-11.18, p < .001), compared with individuals in the Lp(a)-high (adjusted HR 2.290, 95% CI: 1.483-3.537, p < .001) or Fib-high (adjusted HR 1.184, 95% CI: 1.399-3.410, p = .001). Furthermore, combining Lp(a) with Fib increased C-statistics by .045 (p = .004). CONCLUSIONS: Current study first demonstrated that elevated Lp(a) combining with Fib evaluation enhanced the risk of ischemic stroke in patients with CAD beyond Lp(a) or Fib alone.


Subject(s)
Coronary Artery Disease , Fibrinogen , Ischemic Stroke , Lipoprotein(a) , Humans , Lipoprotein(a)/blood , Lipoprotein(a)/metabolism , Fibrinogen/metabolism , Male , Female , Coronary Artery Disease/epidemiology , Middle Aged , Aged , Prospective Studies , Ischemic Stroke/epidemiology , Stroke/epidemiology , Incidence , Risk Factors
11.
Adv Appl Microbiol ; 127: 45-142, 2024.
Article in English | MEDLINE | ID: mdl-38763529

ABSTRACT

Edible fungi, commonly known as mushrooms, are precious medicinal and edible homologous gifts from nature to us. Edible fungal polysaccharides (EFPs) are a variety of bioactive macromolecular which isolated from fruiting bodies, mycelia or fermentation broths of edible or medicinal fungus. Increasing researches have confirmed that EFPs possess multiple biological activities both in vitro and in vivo settings, including antioxidant, antiviral, anti-inflammatory, immunomodulatory, anti-tumor, hypoglycemic, hypolipidemic, and regulating intestinal flora activities. As a result, they have emerged as a prominent focus in the healthcare, pharmaceutical, and cosmetic industries. Fungal EFPs have safe, non-toxic, biodegradable, and biocompatible properties with low immunogenicity, bioadhesion ability, and antibacterial activities, presenting diverse potential applications in the food industries, cosmetic, biomedical, packaging, and new materials. Moreover, varying raw materials, extraction, purification, chemical modification methods, and culture conditions can result in variances in the structure and biological activities of EFPs. The purpose of this review is to provide comprehensively and systematically organized information on the structure, modification, biological activities, and potential applications of EFPs to support their therapeutic effects and health functions. This review provides new insights and a theoretical basis for prospective investigations and advancements in EFPs in fields such as medicine, food, and new materials.


Subject(s)
Fungal Polysaccharides , Fungal Polysaccharides/chemistry , Humans , Animals , Agaricales/chemistry , Agaricales/metabolism , Antioxidants/chemistry , Antioxidants/pharmacology , Immunologic Factors/chemistry , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology
12.
World J Urol ; 42(1): 274, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38689003

ABSTRACT

BACKGROUND: Kidney stones exhibit a robust correlation with cardiovascular disease (CVD). The objective of this research is to investigate the correlation between kidney stones and Life's Essential 8 (LE8), a newly updated assessment of cardiovascular health (CVH), among adults in the United States. METHODS: In this study, which analyzed data from the 2007-2018 National Health and Nutrition Examination Survey, we employed LE8 scores (ranging from 0 to 100) as the independent variable, classifying them into low, moderate, and high CVH categories. The research examined the relationship between LE8 scores and kidney stones by using multivariate logistic regression and restricted cubic spline models, with kidney stones as the dependent variable. RESULTS: Out of the 14,117 participants in this research, the weighted mean LE8 score was 69.70 ± 0.27. After accounting for confounding factors, there was an inverse association between higher LE8 scores and the likelihood of developing kidney stones (OR of 0.81 per 10-point increase, with a 95% confidence interval of 0.77-0.85), demonstrating a non-linear dose-response pattern. Similar patterns were observed for health behaviors, health factor scores, and kidney stones. Stratified analyses demonstrated a stable negative correlation between LE8 scores and kidney stones across different subgroups. CONCLUSION: LE8 and its subscale scores exhibited a robust and inverse correlation with the occurrence of kidney stones. Encouraging adherence to optimal CVH levels has the potential to serve as an effective strategy in preventing and minimizing the occurrence of kidney stones.


Subject(s)
Kidney Calculi , Humans , Kidney Calculi/epidemiology , Male , Female , Middle Aged , Adult , Nutrition Surveys , United States/epidemiology , Aged , Cardiovascular Diseases/epidemiology , Cross-Sectional Studies
13.
Article in English | MEDLINE | ID: mdl-38695864

ABSTRACT

A novel actinobacterium, designated strain CWNU-1T, was isolated from the rhizospheric soil of Fritillaria cirrhosa D. Don and examined using a polyphasic taxonomic approach. The organism developed pale blue aerial mycelia that was simply branched and terminated in open or closed coils of three or more volutions on International Streptomyces Project 3 agar. Spores were ellipsoidal to cylindrical with wrinkled surfaces. The strain showed high 16S rRNA gene sequence similarity to Streptomyces kurssanovii NBRC 13192T (98.8 %), Streptomyces xantholiticus NBRC 13354T (98.7 %) and Streptomyces peucetius JCM 9920T (98.6 %). The phylogenetic result based on 16S rRNA gene and genome sequences clearly demonstrated that strain CWNU-1T formed an independent phylogenetic lineage. On the basis of orthologous average nucleotide identity, CWNU-1T was most closely related to Streptomyces inusitatus NBRC 13601T with 79.3 % identity. The results of the digital DNA-DNA hybridization analysis also indicated low levels of relatedness with other species, as the highest value was observed with S. inusitatus NBRC 13601T (25.3 %). With reference to phenotypic characteristics, phylogenetic data, orthologous average nucleotide identity and digital DNA-DNA hybridization results, strain CWNU-1T was readily distinguished from its most closely related strains and classified as representing a novel species, for which the name Streptomyces albipurpureus sp. nov. is proposed. The type strain is CWNU-1T (=CGMCC 4.7758T=MCCC 1K07402T=JCM 35391T).


Subject(s)
Bacterial Typing Techniques , Base Composition , DNA, Bacterial , Fatty Acids , Fritillaria , Nucleic Acid Hybridization , Phylogeny , RNA, Ribosomal, 16S , Rhizosphere , Sequence Analysis, DNA , Soil Microbiology , Streptomyces , Streptomyces/genetics , Streptomyces/classification , Streptomyces/isolation & purification , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , Fatty Acids/analysis , Fritillaria/microbiology , Vitamin K 2/analogs & derivatives
14.
Eur Radiol ; 34(8): 4852-4863, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38216755

ABSTRACT

OBJECTIVES: To evaluate the value of CT-based whole lung radiomics nomogram for identifying the risk of cardiovascular disease (CVD) in patients with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: A total of 974 patients with COPD were divided into a training cohort (n = 402), an internal validation cohort (n = 172), and an external validation cohort (n = 400) from three hospitals. Clinical data and CT findings were analyzed. Radiomics features of whole lung were extracted from the non-contrast chest CT images. A radiomics signature was constructed with algorithms. Combined with the radiomics score and independent clinical factors, multivariate logistic regression analysis was used to establish a radiomics nomogram. ROC curve was used to analyze the prediction performance of the model. RESULTS: Age, weight, and GOLD were the independent clinical factors. A total of 1218 features were extracted and reduced to 15 features to build the radiomics signature. In the training cohort, the combined model (area under the curve [AUC], 0.731) showed better discrimination capability (p < 0.001) than the clinical factors model (AUC, 0.605). In the internal validation cohort, the combined model (AUC, 0.727) performed better (p = 0.032) than the clinical factors model (AUC, 0.629). In the external validation cohort, the combined model (AUC, 0.725) performed better (p < 0.001) than the clinical factors model (AUC, 0.690). Decision curve analysis demonstrated the radiomics nomogram outperformed the clinical factors model. CONCLUSION: The CT-based whole lung radiomics nomogram has the potential to identify the risk of CVD in patients with COPD. CLINICAL RELEVANCE STATEMENT: This study helps to identify cardiovascular disease risk in patients with chronic obstructive pulmonary disease on chest CT scans. KEY POINTS: • To investigate the value of CT-based whole lung radiomics features in identifying the risk of cardiovascular disease in chronic obstructive pulmonary disease patients. • The radiomics nomogram showed better performance than the clinical factors model to identify the risk of cardiovascular disease in patients with chronic obstructive pulmonary disease. • The radiomics nomogram demonstrated excellent performance in the training, internal validation, and external validation cohort (AUC, 0.731; AUC, 0.727; AUC, 0.725).


Subject(s)
Cardiovascular Diseases , Nomograms , Pulmonary Disease, Chronic Obstructive , Tomography, X-Ray Computed , Humans , Pulmonary Disease, Chronic Obstructive/diagnostic imaging , Pulmonary Disease, Chronic Obstructive/complications , Male , Female , Tomography, X-Ray Computed/methods , Cardiovascular Diseases/diagnostic imaging , Middle Aged , Aged , Risk Assessment/methods , Lung/diagnostic imaging , Risk Factors , Retrospective Studies , Radiomics
15.
Inorg Chem ; 63(21): 10011-10021, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38752554

ABSTRACT

The combination of piezoelectric catalysis and photocatalysis could effectively enhance the carrier separation efficiency and further improve the hydrogen production activity. However, piezoelectric polarization always suffers from a low polarization strength, which severely restricts its actual applications. In this study, we successfully synthesized a novel sulfur vacancy-rich Bi2S3/ZnSn (OH)6 (BS-12/ZSH) piezo-photocatalyst for hydrogen evolution through water splitting. Notably, the piezo-photocatalytic hydrogen generation rate of the 8% BS-12/ZSH catalyst (336.21 µmol/g/h) was superior to that of pristine ZSH (29.71 µmol/g/h) and BS-12 (21.66 µmol/g/h). In addition, the hydrogen generation for 8% BS-12/ZSH (336.21 µmol/g/h) under ultrasonic coupling illumination was significantly higher than that under single illumination (52.09 µmol/g/h) and ultrasound (121.90 µmol/g/h), owing to the cooperative interaction of the sulfur vacancy and piezoelectric field. Various characterization analyses confirmed that (1) the introduction of sulfur vacancies in BS-12 provided more active sites, (2) BS-12 with sulfur vacancies acted as a co-catalyst to accelerate the hydrogen production rate, and (3) the piezoelectric field eliminated the electrostatic shielding and offered an additional driving force, which effectively promoted the separation of electron-hole pairs. This research clearly reveals the synergistic effect between piezocatalysis and photocatalysis as well as offers a promising sight for the rational design of high-efficiency piezo-photocatalysts.

16.
Eur J Clin Pharmacol ; 80(7): 1069-1078, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38546841

ABSTRACT

PURPOSE: Adefovir (as dipivoxil) was selected as a probe drug in a previous transporter cocktail phenotyping study to assess renal organic anion transporter 1 (OAT1), with renal clearance (CLR) as the primary parameter describing renal elimination. An approximately 20% higher systemic exposure of adefovir was observed when combined with other cocktail components (metformin, sitagliptin, pitavastatin, and digoxin) compared to sole administration. The present evaluation applied a population pharmacokinetic (popPK) modeling approach to describe adefovir pharmacokinetics as a cocktail component in more detail. METHODS: Data from 24 healthy subjects were reanalyzed. After establishing a base model, covariate effects, including the impact of co-administered drugs, were assessed using forward inclusion then backward elimination. RESULTS: A one-compartment model with first-order absorption (including lag time) and a combination of nonlinear renal and linear nonrenal elimination best described the data. A significantly higher apparent bioavailability (73.6% vs. 59.0%) and a lower apparent absorption rate constant (2.29 h-1 vs. 5.18 h-1) were identified in the combined period compared to the sole administration period, while no difference was seen in renal elimination. The population estimate for the Michaelis-Menten constant (Km) of the nonlinear renal elimination was 170 nmol/L, exceeding the observed range of adefovir plasma maximum concentration, while the maximum rate (Vmax) of nonlinear renal elimination was 2.40 µmol/h at the median absolute estimated glomerular filtration rate of 105 mL/min. CONCLUSION: The popPK modeling approach indicated that the co-administration primarily affected the apparent absorption and/or prodrug conversion of adefovir dipivoxil, resulting in the minor drug-drug interaction observed for adefovir as a victim. However, renal elimination remained unaffected. The high Km value suggests that assessing renal OAT1 activity by CLR has no relevant misspecification error with the cocktail doses used.


Subject(s)
Adenine , Models, Biological , Organophosphonates , Humans , Organophosphonates/pharmacokinetics , Organophosphonates/blood , Organophosphonates/administration & dosage , Adenine/analogs & derivatives , Adenine/pharmacokinetics , Adenine/administration & dosage , Male , Adult , Female , Organic Anion Transport Protein 1/metabolism , Organic Anion Transport Protein 1/genetics , Drug Interactions , Phenotype , Middle Aged , Young Adult , Digoxin/pharmacokinetics , Digoxin/blood , Digoxin/administration & dosage , Metformin/pharmacokinetics , Metformin/administration & dosage , Metformin/blood , Sitagliptin Phosphate/pharmacokinetics , Biological Availability
17.
Jpn J Clin Oncol ; 54(1): 23-30, 2024 Jan 07.
Article in English | MEDLINE | ID: mdl-37850297

ABSTRACT

BACKGROUND: Sarcopenia, overweight and obesity are all dynamic changes in body composition, which may have a negative effect on the prognosis for patients with colorectal cancer. The aim of this study was to investigate the predictive role of sarcopenia on overweight or obese patients with colorectal cancer. METHODS: We conducted an observative study on the population of overweight or obese patients with colorectal cancer who underwent curative surgeries in two centers between 2015 and 2021. They were grouped by the presence of sarcopenia. Propensity score match analysis was used to balance the baseline of clinicopathologic characteristics of the two groups. Then, the postoperative outcomes between the two groups were compared. Independent risk factors were evaluated for complications using univariate and multivariate analysis. RESULTS: Of 827 patients enrolled, 126 patients were matched for analysis. Patients with sarcopenia had a higher incidence of total complication and medical complications, a higher rate of laparoscopic surgery performed and higher hospitalization costs. Old age (≥65 years, P = 0.012), ASA grade (III, P = 0.008) and sarcopenia (P = 0.036) were independent risk factors for total complications. ASA grade (III, P = 0.002) and sarcopenia (P = 0.017) were independent risk factors for medical complications. CONCLUSIONS: Sarcopenia was prevalent among overweight or obese patients with colorectal cancer and was associated with negative postoperative outcomes. Early recognition of changes in body composition could help surgeons be well prepared for surgical treatment for overweight or obese patients.


Subject(s)
Colorectal Neoplasms , Sarcopenia , Humans , Aged , Sarcopenia/complications , Sarcopenia/epidemiology , Overweight/complications , Colorectal Neoplasms/complications , Colorectal Neoplasms/surgery , Obesity/complications , Prognosis , Risk Factors , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies
18.
Lipids Health Dis ; 23(1): 158, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802797

ABSTRACT

BACKGROUND: Recent interest in the Non-High Density to High Density Lipoprotein Cholesterol ratio (NHHR) has emerged due to its potential role in metabolic disorders. However, the connection between NHHR and the development of kidney stones still lacks clarity. The primary goal of this research is to explore how NHHR correlates with kidney stone incidence. METHODS: An analysis was conducted on the data collected by the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018, focusing on adults over 20 years diagnosed with kidney stones and those with available NHHR values. Employing weighted logistic regression and Restricted Cubic Spline (RCS) models, NHHR levels' correlation with kidney stone risk was examined. Extensive subgroup analyses were conducted for enhanced reliability of the findings. RESULTS: The findings indicate a heightened kidney stone risk for those at the highest NHHR levels relative to those at the lowest (reference group). A notable non-linear correlation of NHHR with kidney stone incidence has been observed, with a significant P-value (< 0.001), consistent across various subgroups. CONCLUSION: A clear link exists between high NHHR levels and increased kidney stone risk in the American adult population. This study highlights NHHR's significance as a potential indicator in kidney stone formation.


Subject(s)
Kidney Calculi , Nutrition Surveys , Humans , Kidney Calculi/blood , Kidney Calculi/epidemiology , Adult , Male , Female , Middle Aged , Cross-Sectional Studies , Risk Factors , Cholesterol, HDL/blood , United States/epidemiology , Incidence , Aged , Logistic Models
19.
BMC Pediatr ; 24(1): 243, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38580968

ABSTRACT

Cholangiocarcinoma in patients with Choledochal cysts is rare in childhood; however, it seriously affects the prognosis of the disease. The key to addressing this situation lies in completely removing the extrahepatic cyst. We herein present a case report of a 3-year-old boy with cholangiocarcinoma associated with a choledochal cyst (CDC). Preoperative 3D simulation, based on CT data, played an important role in the treatment of this patient.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Choledochal Cyst , Male , Humans , Child, Preschool , Choledochal Cyst/complications , Choledochal Cyst/diagnostic imaging , Choledochal Cyst/surgery , Cholangiocarcinoma/complications , Cholangiocarcinoma/diagnostic imaging , Cholangiocarcinoma/pathology , Bile Ducts, Intrahepatic/diagnostic imaging , Bile Ducts, Intrahepatic/pathology , Bile Duct Neoplasms/complications , Bile Duct Neoplasms/diagnostic imaging , Bile Duct Neoplasms/pathology
20.
Surg Radiol Anat ; 46(2): 117-124, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38189912

ABSTRACT

PURPOSE: This study aimed to investigate the effectiveness of the Hisense computer-assisted surgery system (CAS) in teaching pediatric liver surgical anatomy. METHODS: The research subjects were residents who underwent standardized training at the Department of Pediatric Surgery at Yijishan Hospital of Wannan Medical College from May 2022 to May 2023. RESULTS: The study recruited a total of 62 students, with 31 students assigned to the Hisense CAS group (12 males and 19 females) and the remaining 31 students serving as controls (Control group, 15 males and 16 females). There were no significant differences in baseline characteristics observed between the two groups. This study found that the average scores of the Hisense CAS teaching group in the liver surgery evaluations were higher than those of the control group. Specifically, the Hisense CAS group had an average score of 84.25 ± 5.70 points in the liver surgery knowledge test, 77.10 ± 8.12 points in the image reading test, and 70.58 ± 8.79 points in the surgical simulation test, while the traditional teaching group had average scores of 73.45 ± 6.12 points, 69.81 ± 6.05 points, and 66.42 ± 6.61 points, respectively; the differences between the two groups were statistically significant (P < 0.05). Furthermore, this study also found that the Hisense CAS teaching model resulted in significantly better teaching satisfaction on the part of the residents in terms of standardized teaching for physicians in pediatric liver surgical anatomy. CONCLUSION: In conclusion, this study demonstrated greater satisfaction of the residents with the use of 3D reconstruction added to traditional teaching sessions and better performance during the posttraining evaluation.


Subject(s)
Anatomy , Computer-Assisted Instruction , Surgery, Computer-Assisted , Male , Female , Humans , Child , Liver/surgery , Computer Simulation , Surgery, Computer-Assisted/methods , Teaching , Anatomy/education
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