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1.
J Hazard Mater ; 476: 135124, 2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38981237

ABSTRACT

Exposure to mycotoxins is unavoidable in daily life through ingestion, dermal, and inhalation routes. Toxicological studies found that exposure to mycotoxins might affect male reproductive function. However, there is still a lack of population evidence. We aimed to assess the association of individual and joint exposure to spectrum of mycotoxins with semen quality. The present study included 192 participants in Beijing, China. We measured conventional semen parameters and assessed semen quality. Sixty-seven traditional or emerging mycotoxins were determined to describe the spectrum of mycotoxins. The participants were widely exposed to multiple mycotoxins, and nearly half were simultaneously exposed to more than six mycotoxins. After adjusting potential confounders, logistic regression indicated that the number and concentration of plasma mycotoxin were correlated to the risk of low semen quality. Plasma beauvericin and citrinin concentrations were associated with lower semen quality. The least absolute shrinkage and selection operator regression showed similar results to logistic regression. Quantile-based g-computation and Bayesian kernel machine regression models found that the mixture of mycotoxins was harmful to semen quality, especially in sperm motility. In conclusion, both individual and mixture of mycotoxin exposure were correlated with lower semen quality. More regulations and measures should be taken to reduce mycotoxin contamination.

2.
Food Chem ; 459: 140357, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-39003851

ABSTRACT

In-depth research into the precise evaluation of enzymatic digestion efficiency and the selection of a suitable deuterium-labelled internal standard remains a gap in the accurate determination of ß2-agonists in animal-derived food by isotope dilution-liquid chromatography/tandem mass spectrometry (ID-LC-MS/MS). In this study, the enzymatic digestion conditions were optimized by monitoring the presence of ß2-agonist conjugates in positive samples, which proved to be reliable for ensuring complete enzymatic digestion. Comparative analysis of deuterium-labelled internal standards for salbutamol (SAL), ractopamine (RAC), and clenbuterol (CLB) revealed that CLB-D6 and SAL-D9 were less effective in compensating for matrix effects due to hydrogen­deuterium exchange during MS fragment formation. Consequently, SAL-D3, RAC-D3 and CLB-D9 were chosen for the implementation of ID-LC-MS/MS. The developed method demonstrates high accuracy and precision, with the average recoveries ranging from 93.8% to 107.3% with RSD <6.1%, which can provide higher-order measurement results for ß2-agonists in pork.

3.
Clinics (Sao Paulo) ; 79: 100446, 2024.
Article in English | MEDLINE | ID: mdl-39003926

ABSTRACT

OBJECTIVE: The study aimed at analyzing the serum expression of Immature Granulocyte percentage (IG %) and D-Dimer (D-D) in patients with severe pancreatitis and exploring their clinical diagnostic value. METHODS: Eighty-four cases with severe pancreatitis received in Shengjing Hospital, China Medical University from July 2020 to July 2023 were regarded as the study group and conducted for retrospective analysis. They were divided into a survival group (n = 62) and a death group (n = 22) based on the prognosis. Another 80 patients diagnosed with mild and moderate pancreatitis were selected as the control group. Serum IG % and D-D levels of all subjects were analyzed and the value of IG % and D-D in the evaluation of severe pancreatitis and its prognosis was conducted by Receiver Operating Characteristic (ROC) curve. RESULTS: The IG % and D-D levels in the study group were markedly higher than the control group (p < 0.05). The IG % and D-D level in the death group were observably higher than the survival group (p < 0.05). The Area Under the Curve (AUC) of IG % and D-D combined assessment for severe pancreatitis was 0.963, and the sensitivity and specificity were 98.75 %, 82.14 %, respectively. The AUC of IG % and D-D combined assessment for prognosis of severe pancreatitis was 0.814 with a sensitivity of 79.03 % and a specificity of 77.27 %. The efficiency of joint evaluation of the two indicators is superior to the individual evaluation. CONCLUSION: Serum IG % and D-D are highly expressed in patients with severe pancreatitis, which has important clinical value for the evaluation of severe pancreatitis and its prognosis.


Subject(s)
Fibrin Fibrinogen Degradation Products , Granulocytes , Pancreatitis , ROC Curve , Severity of Illness Index , Humans , Fibrin Fibrinogen Degradation Products/analysis , Female , Male , Middle Aged , Prognosis , Retrospective Studies , Pancreatitis/blood , Pancreatitis/mortality , Pancreatitis/diagnosis , Adult , Sensitivity and Specificity , Aged , Biomarkers/blood , Leukocyte Count , Case-Control Studies
4.
Sci Total Environ ; : 174624, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38986704

ABSTRACT

Current-use pesticides (CUPs), including insecticides, fungicides, and herbicides, are extensively employed in agriculture to manage pests, diseases, and weeds. Nonetheless, their widespread application raises significant concerns regarding potential impacts on human health, particularly with reproductive health. This study focuses on exploring the landscape of CUP exposure among pre-pregnancy women. Based on a cohort study comprising 354 pre-pregnancy women of reproductive age in Beijing, China, we measured the concentrations of 94 CUPs in serum and conducted an in-depth analysis of exposure profiles, health risks, and contributing factors. The results revealed that the serum of pre-pregnancy women was contaminated with CUPs, of which the median concentrations ranged from 0.114 (fenamiphos-sulfone) to 61.2 ng/L (mefenacet). Among the 94 CUPs, 54 exhibited detection rates higher than 50 %, including 26 insecticides, 14 fungicides, and 14 herbicides. The exposure concentration profile highlighted that the insecticides contributed 56 % to the total CUP concentration percentages, with organophosphate insecticides being the primary contributors within this category (63.0 %). The average daily intake (ADI) of CUPs ranged from 2.23 to 16,432.28 ng/kg, while diflubenzuron had the highest ADI. Health risk assessments showed that exposure to a combination of total insecticides or herbicides poses a moderate risk for 15.8 % and 30.2 % of women, with mefenacet being the most significant, which showed moderate hazard in 29.4 % of participants. The overlap analysis showed that methiocarb-sulfone, diflubenzuron, and mefenacet were the dominant pesticides. In addition, maternal age, annual income level, smoking, and vitamin B12 supplementation were associated with serum CUP concentrations. Our study contributes a novel and comprehensive exposure profile of CUPs in pre-pregnancy women in northern China, providing valuable insights for evaluating the potential consequences of pre-pregnancy exposure on reproductive health. SYNOPSIS: We provided a comprehensive exposure landscape, health effects, and influential factors of 94 current-use pesticides among pre-pregnancy women in China.

5.
World J Diabetes ; 15(6): 1111-1121, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38983817

ABSTRACT

Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease. Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes. With the development of immunological technology, many studies have shown that diabetic nephropathy is an immune complex disease, and that most patients have immune dysfunction. However, the immune response associated with diabetic nephropathy and autoimmune kidney disease, or caused by ischemia or infection with acute renal injury, is different, and has a com-plicated pathological mechanism. In this review, we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism, to provide guidance and advice for early intervention and treatment of diabetic nephropathy.

6.
Chem Sci ; 15(27): 10499-10507, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38994430

ABSTRACT

Chirality plays an indispensable role in various biological processes, and interactions between chiral enantiomers and biomolecular targets provide new perspectives in precision drug development. While ferroptosis has received increasing attention as a novel pathway to reverse drug resistance, work on the design of precise ferroptosis-targeting molecules through chiral programming was limited. In this work, we designed and synthesized a pair of chirality-dependent ferroptosis-inducing Ir(iii)-phenylquinazolinone complexes (Δ-IrPPQ and Λ-IrPPQ) by inhibiting ferroptosis suppressor protein-1 (FSP1), while the pair of IrPPQ complexes induced extremely different ferroptosis effects as well as distinct photodynamic therapy (PDT) responses toward pancreatic cancer cells. Interestingly, this chirality-dependent biological mechanism through proteomic analysis and molecular simulation revealed that the specific binding and inhibition of metallothionein-1 (MT1) by Λ-IrPPQ sensitized cancer cells to ferroptosis, inducing a burst of reactive oxygen species, lipid peroxidation, glutathione depletion, and inactivation of FSP1. While in comparison, Δ-IrPPQ induced mild ferroptotic cell death. Through simple chiral resolution, the obtained Λ-IrPPQ achieved precise regulation of ferroptosis in pancreatic cancer cells. This work provides new insights into the design of chiral ferroptosis-inducing metallodrugs for future pancreatic cancer therapy.

7.
Cureus ; 16(6): e62301, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39006611

ABSTRACT

RASopathies are a group that encompasses a spectrum of related disorders caused by mutations linked to the RAS/mitogen-activated protein kinase (RAS/MAPK) pathway, including neurofibromatosis type 1 (NF1), Noonan syndrome (NS), neurofibromatosis-Noonan syndrome (NFNS), Noonan syndrome with multiple lentigines (NSML). Neurofibromas, as a hallmark of NF1, are extremely rare in patients with other RASopathies. Here we present a case of a 39-year-old Chinese male displaying orbital neurofibromas and lumbosacral plexiform neurofibromas. Histopathology of a CT-guided biopsy of the mass revealed it to be a neurofibroma. The targeted sequencing analysis did not find any pathogenic sequence alteration in the NF1 or NF2 causative genes in blood lymphocytes and hypertrophic nerve tissue, and no additional signs of NF1 were detected, thereby not meeting the diagnostic criteria for NF1. However, we identified a heterozygous mutation (c.836A>G, p.Y279C) in the PTPN11 gene, which is one of the key components of the RAS-MAPK signaling pathway and is associated with NS, NFNS, and NSML. Nonetheless, a thorough examination did not reveal any signs of these syndromes in the patient. Consequently, it was inferred that this patient likely falls within the spectrum of the RASopathies. This represents a unique case manifesting as orbital and lumbosacral plexiform neurofibromas carrying a PTPN11 gene mutation, thereby broadening the phenotype spectrum of PTPN11 mutations. Our results also highlight the overlap between RASopathies. Neurofibromas should be considered indicative of a broader spectrum of disorders resulting from mutations in RASopathies other than NF1.

8.
Commun Biol ; 7(1): 860, 2024 Jul 13.
Article in English | MEDLINE | ID: mdl-39003419

ABSTRACT

Alternative polyadenylation (APA) plays a crucial role in cancer biology. Here, we used data from the 3'aQTL-atlas, GTEx, and the China Nanjing Lung Cancer GWAS database to explore the association between apaQTL/eQTL-SNPs and the risk of lung adenocarcinoma (LUAD). The variant T allele of rs277646 in NIT2 is associated with an increased risk of LUAD (OR = 1.12, P = 0.015), lower PDUI values, and higher NIT2 expression. The 3'RACE experiment showed multiple poly (A) sites in NIT2, with the rs277646-T allele causing preferential use of the proximal poly (A) site, resulting in a shorter 3'UTR transcript. This leads to the loss of the hsa-miR-650 binding site, thereby affecting LUAD malignant phenotypes by regulating the expression level of NIT2. Our findings may provide new insights into understanding and exploring APA events in LUAD carcinogenesis.


Subject(s)
Adenocarcinoma of Lung , Genetic Predisposition to Disease , Lung Neoplasms , Quantitative Trait Loci , Humans , Adenocarcinoma of Lung/genetics , China/epidemiology , East Asian People/genetics , Gene Expression Regulation, Neoplastic , Genome-Wide Association Study , Lung Neoplasms/genetics , Polyadenylation , Polymorphism, Single Nucleotide
9.
Article in English | MEDLINE | ID: mdl-38968001

ABSTRACT

There is an urgent need to develop phototherapeutic agents with imaging capabilities to assess the treatment process and efficacy in real-time during cancer phototherapy for precision cancer therapy. The safe near-infrared (NIR) fluorescent dyes have garnered significant attention and are desirable for theranostics agents. However, until now, achieving excellent photostability and fluorescence (FL) imaging capability in aggregation-caused quenching (ACQ) dyes remains a big challenge. Here, for the only FDA-approved NIR dye, indocyanine green (ICG), we developed a dual-ferrocene (Fc) chimeric nanonetwork ICG@HFFC based on the rigid-flexible strategy through one-step self-assembly, which uses rigid Fc-modified hyaluronic acid (HA) copolymer (HA-Fc) and flexible octadecylamine (ODA) bonded Fc (Fc-C18) as the delivery system. HA-Fc reserved the ability of HA to target the CD44 receptor of the tumor cell surface, and the dual-Fc region provided a rigid space for securely binding ICG through metal-ligand interaction and π-π conjugation, ensuring excellent photostability. Additionally, the alkyl chain provided flexible confinement for the remaining ICG through hydrophobic forces, preserving its FL. Thereby, a balance is achieved between outstanding photostability and FL imaging capability. In vitro studies showed improved photobleaching resistance, enhanced FL stability, and increased singlet oxygen (1O2) production efficiency in ICG@HFFC. Further in vivo results display that ICG@HFFC had good tumor tracing ability and significant tumor inhibition which also exhibited good biocompatibility.. Therefore, ICG@HFFC provides an encouraging strategy to realize simultaneous enhanced tumor tracing and photothermal/photodynamic therapy (PTT/PDT) and offers a novel approach to address the limitations of ACQ dyes.

10.
Commun Biol ; 7(1): 797, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956406

ABSTRACT

The nonconventional yeast Kluyveromyces marxianus has potential for industrial production, but the lack of advanced synthetic biology tools for precise engineering hinders its rapid development. Here, we introduce a CRISPR-Cas9-mediated multilocus integration method for assembling multiple exogenous genes. Using SlugCas9-HF, a high-fidelity Cas9 nuclease, we enhance gene editing precision. Specific genomic loci predisposed to efficient integration and expression of heterologous genes are identified and combined with a set of paired CRISPR-Cas9 expression plasmids and donor plasmids to establish a CRISPR-based biosynthesis toolkit. This toolkit enables genome integration of large gene modules over 12 kb and achieves simultaneous quadruple-locus integration in a single step with 20% efficiency. As a proof-of-concept, we apply the toolkit to screen for gene combinations that promote heme production, revealing the importance of HEM4Km and HEM12Sc. This CRISPR-based toolkit simplifies the reconstruction of complex pathways in K. marxianus, broadening its application in synthetic biology.


Subject(s)
CRISPR-Cas Systems , Gene Editing , Kluyveromyces , Kluyveromyces/genetics , Gene Editing/methods , Plasmids/genetics , Synthetic Biology/methods , Heme/metabolism , Heme/genetics , Heme/biosynthesis
11.
J Proteomics ; 305: 105247, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38950696

ABSTRACT

The aim of this study was to explore potential novel plasma protein biomarkers for lung adenocarcinoma (LUAD). A plasma proteomics analysis was carried out and candidate protein biomarkers were validated in 102 LUAD cases and 102 matched healthy controls. The same LUAD tumor tissues were detected to explore the correlation between the expression of candidate proteins in tissues and plasma and vascular normalization. A LUAD active metastasis mice model was constructed to explore the role of candidate proteins for lung metastasis. GPI and PGD were verified to be upregulated in plasma from LUAD patients, and the expression of GPI in tumor tissue was positively correlated with the expression of GPI in plasma and negatively correlated with the normalization of tumor blood vessels. Meanwhile, a negative correlation between the expression of GPI and PGD in plasma and tumor vascular normalization was discovered. In the LUAD active metastasis model, the lowest levels of vascular normalization and the highest expression of GPI and PGD were found in mice with lung metastases. This study found that GPI and PGD may be potential plasma biomarkers for LUAD, and monitoring those may infer the risk of metastasis and malignancy of the tumor. SIGNIFICANT: We identified GPI and PGD as potential novel diagnostic and prognostic biomarkers for LUAD. PGD and GPI can be used as diagnostic biomarkers in combination with other available strategies to assist in the screening and diagnosis of LUAD, and as prognostic biomarkers aid in predict the risk of tumor metastasis and malignancy in patients with LUAD.

12.
J Psychiatr Res ; 177: 59-65, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38972266

ABSTRACT

Abnormal functional connectivity (FC) within the fear network model (FNM) has been identified in panic disorder (PD) patients, but the specific local structural and functional properties, as well as effective connectivity (EC), remain poorly understood in PD. The purpose of this study was to investigate the structural and functional patterns of the FNM in PD. Magnetic resonance imaging data were collected from 33 PD patients and 35 healthy controls (HCs). Gray matter volume (GMV), degree centrality (DC), regional homogeneity (ReHo), and amplitude of low-frequency fluctuation (ALFF) were used to identify the structural and functional characteristics of brain regions within the FNM in PD. Subsequently, FC and EC of abnormal regions, based on local structural and functional features, and their correlation with clinical features were further examined. PD patients exhibited preserved GMV, ReHo, and ALFF in the brain regions of the FNM compared with HCs. However, increased DC in the bilateral amygdala was observed in PD patients. The amygdala and its subnuclei exhibited altered EC with rolandic operculum, insula, medial superior frontal gyrus, supramarginal gyrus, opercular part of inferior frontal gyrus, and superior temporal gyrus. Additionally, Hamilton Anxiety Scale score was positively correlated with EC from left lateral nuclei (dorsal portion) of amygdala to right rolandic operculum and left superior temporal gyrus. Our findings revealed a reorganized functional network in PD involving brain regions regulating exteroceptive-interoceptive signals, mood, and somatic symptoms. These results enhance our understanding of the neurobiological underpinnings of PD, suggesting potential biomarkers for diagnosis and targets for therapeutic intervention.

13.
Nat Commun ; 15(1): 5680, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38971819

ABSTRACT

Obesity shapes anti-tumor immunity through lipid metabolism; however, the mechanisms underlying how colorectal cancer (CRC) cells utilize lipids to suppress anti-tumor immunity remain unclear. Here, we show that tumor cell-intrinsic ATP6V0A1 drives exogenous cholesterol-induced immunosuppression in CRC. ATP6V0A1 facilitates cholesterol absorption in CRC cells through RAB guanine nucleotide exchange factor 1 (RABGEF1)-dependent endosome maturation, leading to cholesterol accumulation within the endoplasmic reticulum and elevated production of 24-hydroxycholesterol (24-OHC). ATP6V0A1-induced 24-OHC upregulates TGF-ß1 by activating the liver X receptor (LXR) signaling. Subsequently, the release of TGF-ß1 into the tumor microenvironment by CRC cells activates the SMAD3 pathway in memory CD8+ T cells, ultimately suppressing their anti-tumor activities. Moreover, we identify daclatasvir, a clinically used anti-hepatitis C virus (HCV) drug, as an ATP6V0A1 inhibitor that can effectively enhance the memory CD8+ T cell activity and suppress tumor growth in CRC. These findings shed light on the potential for ATP6V0A1-targeted immunotherapy in CRC.


Subject(s)
CD8-Positive T-Lymphocytes , Cholesterol , Colorectal Neoplasms , Signal Transduction , Transforming Growth Factor beta1 , Colorectal Neoplasms/immunology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Humans , Animals , Cholesterol/metabolism , Mice , Cell Line, Tumor , Transforming Growth Factor beta1/metabolism , Immunologic Memory , Vacuolar Proton-Translocating ATPases/metabolism , Tumor Microenvironment/immunology , Liver X Receptors/metabolism , Hydroxycholesterols/metabolism , Hydroxycholesterols/pharmacology , Pyrrolidines/pharmacology , Smad3 Protein/metabolism , Mice, Inbred C57BL , Carbamates/pharmacology
14.
Heliyon ; 10(12): e32932, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38975066

ABSTRACT

This study investigates the simultaneous influence of the digital economy, environmental technologies, business activity, and institutional quality on both the environment and economic growth in G7 economies from 1996 to 2020. The study provides an in-depth analysis to investigate the influence of institutional quality, particularly the regulatory environment, on business activity. Employing a rigorous methodology encompassing correlation analysis, long-term examination using Driscoll and regression estimators, and the utilization of various digital economy indicators such as internet usage and cell subscriptions, we uncover significant insights. The findings underscore the substantial impact of digital economies in mitigating carbon emissions and driving economic growth at an accelerated rate. Moreover, the study reveals that certain regulatory constraints on corporate operations can paradoxically facilitate carbon emission management while also fostering economic expansion. The study validates the presence of an inverted U-shaped Environmental Kuznets Curve (EKC) in G7 economies. This suggests that there is a specific point at which economic activities start to contribute more to carbon emissions. Moreover, the study highlights the importance of achieving a balance between economic growth driven by foreign direct investment and the goals of environmental sustainability. Environmental technology is becoming increasingly important in the regulation of emissions. Significantly, the study highlights the need to enhance the quality of implementing institutional regulations. It suggests that G7 economies can improve both environmental quality and economic growth by adopting superior regulatory methods. These findings are relevant for governments seeking economic growth and environmental protection. They suggest the need for specific policy actions to accomplish sustainable development goals.

15.
Food Chem ; 458: 140204, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38964092

ABSTRACT

The bacterial derived osmolyte ectoine has been shown to stabilize cell structure and function, a property that may help to extend the shelf life of broccoli. The impact of ectoine on broccoli stored for 4 d at 20 °C and 90% relative humidity was investigated. Results indicated that 0.20% ectoine treatment maintained the quality of broccoli, by reducing rate of respiration and ethylene generation, while increasing the levels of total phenolics, flavonoids, TSS, soluble protein, and vitamin C, relative to control. Headspace-gas chromatography-mass spectrometry, transcriptomic and metabolomic analyses revealed that ectoine stabilized aroma components in broccoli by maintaining level of volatile compounds and altered the expression of genes and metabolites associated with sulfur metabolism, as well as fatty acid and amino acid biosynthesis pathways. These findings provide a greater insight into how ectoine preserves the flavor and nutritional quality of broccoli, thus, extending its shelf life.

16.
Behav Brain Funct ; 20(1): 18, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38965529

ABSTRACT

BACKGROUND: Anxiety disorders are one of the most common mental disorders. Ghrelin is a critical orexigenic brain-gut peptide that regulates food intake and metabolism. Recently, the ghrelin system has attracted more attention for its crucial roles in psychiatric disorders, including depression and anxiety. However, the underlying neural mechanisms involved have not been fully investigated. METHODS: In the present study, the effect and underlying mechanism of ghrelin signaling in the nucleus accumbens (NAc) core on anxiety-like behaviors were examined in normal and acute stress rats, by using immunofluorescence, qRT-PCR, neuropharmacology, molecular manipulation and behavioral tests. RESULTS: We reported that injection of ghrelin into the NAc core caused significant anxiolytic effects. Ghrelin receptor growth hormone secretagogue receptor (GHSR) is highly localized and expressed in the NAc core neurons. Antagonism of GHSR blocked the ghrelin-induced anxiolytic effects. Moreover, molecular knockdown of GHSR induced anxiogenic effects. Furthermore, injection of ghrelin or overexpression of GHSR in the NAc core reduced acute restraint stress-induced anxiogenic effects. CONCLUSIONS: This study demonstrates that ghrelin and its receptor GHSR in the NAc core are actively involved in modulating anxiety induced by acute stress, and raises an opportunity to treat anxiety disorders by targeting ghrelin signaling system.


Subject(s)
Anxiety , Ghrelin , Nucleus Accumbens , Rats, Sprague-Dawley , Receptors, Ghrelin , Signal Transduction , Stress, Psychological , Animals , Ghrelin/metabolism , Nucleus Accumbens/metabolism , Nucleus Accumbens/drug effects , Male , Anxiety/metabolism , Anxiety/psychology , Receptors, Ghrelin/metabolism , Receptors, Ghrelin/genetics , Rats , Stress, Psychological/metabolism , Stress, Psychological/psychology , Signal Transduction/drug effects , Signal Transduction/physiology , Behavior, Animal/drug effects
17.
Article in English | MEDLINE | ID: mdl-38980946

ABSTRACT

BACKGROUND: Various prognostic factors are expected to refine the American Thyroid Association (ATA) recurrence risk stratification for patients with papillary thyroid cancer (PTC). However, it remains unclear to what extent integrating these factors improves patient treatment decision-making. METHODS: We developed two predictive models for structural incomplete response (SIR) at the one-year follow-up visit, based on comprehensive clinical data from a retrospective cohort of 2539 patients. Model 1 included the recurrence risk stratification and lymph node features (i.e., number and ratio of metastatic lymph nodes, N stage). Model 2 further incorporated preablation stimulated thyroglobulin (s-Tg). An independent cohort of 746 patients was used for validation analysis. We assessed the models' predictive performance compared to the recurrence risk stratification using the integrated discrimination improvement (IDI) and the continuous net reclassification improvement (NRI). The clinical utility of the models was evaluated using decision curve analysis. RESULTS: Both Model 1 and Model 2 outperformed the recurrence risk stratification in predicting SIR, with improved correct classification rates (Model 1: IDI=0.02, event NRI=42.31%; Model 2: IDI=0.07, event NRI=53.54%). The decision curves indicated that both models provided greater benefits over the risk stratification system in clinical decision-making. In the validation set, Model 2 maintained similar performance while Model 1 did not significantly improve correct reclassification. CONCLUSION: The inclusion of lymph node features and s-Tg showed potential to enhance the predictive accuracy and clinical utility of the existing risk stratification system for PTC patients.

18.
Anal Chem ; 96(25): 10116-10120, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38858219

ABSTRACT

In this letter, a sensitive microfluidic immunosensor chip was developed using tetrakis(4-aminophenyl)ethene (TPE)-derived covalent organic frameworks (T-COF) as aggregation-induced electrochemiluminescence (AIECL) emitters and nanobodies as efficient immune recognition units for the detection of thymic stromal lymphopoietin (TSLP), a novel target of asthma. The internal rotation and vibration of TPE molecules were constrained within the framework structure, forcing nonradiative relaxation to convert into pronounced radiative transitions. A camel-derived nanobody exhibited superior specificity, higher residual activity and epitope recognition postcuring compared to monoclonal antibodies. Benefiting from the affinity between silver ions (Ag+) and cytosine (C), a double-stranded DNA (dsDNA) embedded with Ag+ was modified onto the surface of TSLP. A positive correlation was obtained between the TSLP concentration (1.00 pg/mL to 4.00 ng/mL) and ECL intensity, as Ag+ was confirmed to be an excellent accelerator of the generation of free radical species. We propose that utilizing COF to constrain luminescent molecules and trigger the AIECL phenomenon is another promising method for preparing signal tags to detect low-abundance disease-related markers.


Subject(s)
Cytokines , Electrochemical Techniques , Luminescent Measurements , Stilbenes , Thymic Stromal Lymphopoietin , Cytokines/analysis , Cytokines/metabolism , Stilbenes/chemistry , Humans , Metal-Organic Frameworks/chemistry , Biosensing Techniques , Immunoassay/methods , Single-Domain Antibodies/chemistry , Single-Domain Antibodies/immunology , Microfluidic Analytical Techniques/instrumentation
19.
Children (Basel) ; 11(6)2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38929267

ABSTRACT

Through a thematic analysis of firsthand posts from 258 abuse survivors in online forums from 2016 to 2023, this research examines the barriers that Chinese children encounter when disclosing sexual abuse. The anonymous narratives shed light on the motives behind survivors' reluctance to reveal abuse, the outcomes following disclosure, and the wider implications for survivors and their families under culture. The findings underscore the need for early intervention upon disclosure, aiming to safeguard children from further harm and foster the development of an effective child protection framework.

20.
J Colloid Interface Sci ; 673: 934-942, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38909492

ABSTRACT

Exploring the intrinsic relationship between the network structure and the performance of catalyst layer (CL) by rational design its structure is of paramount importance for proton exchange membrane (PEM) electrolyzers. This study reveals the relative effect of polymeric dispersion evolution on oxygen evolution reaction (OER) performance and cell voltage loss and linked to CL network structure. The results show that although the dispersed particle size of the ionomer and ink increases with increasing the solubility parameter (δ) difference between the mixed solvent and the ionomer, MeOH-cat (ink from MeOH aqueous solution) has the largest ionomer and ink particle size resulting in the poorest stability, but has comparable OER overpotential to that of IPA-cat (249 mV@10 mA cm-2), which has the smallest dispersed size. While at 100 mA cm-2, the overpotential of the ink rises as the particle size increases, suggesting that the electrode structure becomes more influential as the current density increases. Quantitatively analyzed the electrolyzers' voltage losses and determined that the CL from MeOH-cat has the lowest kinetic overpotential. However, its performance is the worst because of the insufficient network structure of CL, resulting in an output of 1.96 V at 1.5 A cm-2. Comparatively, the CL from IPA-cat has the highest kinetic overpotential yet can achieve the greatest performance of 1.76 V at 2 A cm-2 due to its homogeneous network structure and optimal mass transport. Furthermore, the performance variation becomes more pronounced as current density rises. Hence, this study highlights the significant impact of CL structure on electrolyzer's performance. To improve performance in PEM water electrolysis technology, especially for large work current density, it is crucial to enhance the CL's network structure.

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