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1.
Clin Otolaryngol ; 2024 Oct 02.
Article in English | MEDLINE | ID: mdl-39358666

ABSTRACT

OBJECTIVE: To assess the prevalence of depression, anxiety, insomnia and somatic symptom disorder (SSD) in chronic rhinosinusitis (CRS) patients who were waiting for surgery and to predict these psychiatric disorders using the 22-item Sinonasal Outcome Test (SNOT-22). DESIGN: A prospective cross-sectional study. SETTING: The rhinology ward at our institution, a tertiary hospital. PARTICIPANTS: Adult patients (> 18 years) diagnosed with CRS who were admitted to the rhinology ward for endoscopic sinus surgery and were able to understand and complete the study questionnaires. MAIN OUTCOME MEASURES: Patient Health Questionnaire-9 (PHQ-9), Generalised Anxiety Disorder-7 (GAD-7), Insomnia Severity Index (ISI), Patient Health Questionnaire-15 (PHQ-15) and SNOT-22. RESULTS: Of the 159 participants recruited, 58 were at risk of depression (defined by PHQ-9 > 4, while 25 with PHQ-9 > 9), 49 were at risk of anxiety (defined by GAD-7 > 4, while 25 with GAD-7 > 9), 81 were at risk of insomnia (defined by ISI > 7, while 51 with ISI > 14) and 69 were at risk of SSD (defined by PHQ-15 > 4, while 24 with PHQ-15 > 9). The SNOT-22 score was closely correlated with the scores of psychometric tests and was an independent predictor of these psychiatric disorders. Patients with a high SNOT-22 score (> 30) are likely to be affected by comorbid psychiatric disorders and should be further evaluated by otolaryngologists. CONCLUSION: Depression, anxiety, insomnia and SSD are prevalent in CRS patients. Otolaryngologists should have a low threshold to ask the patient about psychiatric symptoms, especially for patients with an SNOT-22 score > 30.

2.
Eur J Med Chem ; 280: 116905, 2024 Sep 28.
Article in English | MEDLINE | ID: mdl-39368263

ABSTRACT

Antibiotic resistance has become a serious threat to public health, thus novel antibiotics are urgently needed to combat drug-resistant bacteria including methicillin-resistant Staphylococcus aureus (MRSA). The 1,4-dicarbonylthiosemicarbazide is an interesting chemotype that could exhibit antibacterial activity. However, the currently available compounds are not as potent as clinical antibiotics. Herein, we adopted the computer-aided drug design strategy, substructure search, to retrieve antibacterial 1,4-dicarbonylthiosemicarbazide derivatives, and identified compound B5 (Specs ID: AG-690/15432331) from the Specs chemical library that exhibited moderate activity (minimum inhibitory concentration (MIC): 6.25 µg/mL) against Staphylococcus aureus ATCC 29213. Based on that compound, we further designed and synthesized 45 derivatives, and evaluated their antibacterial activity. Eight derivatives were more potent than or equivalent to vancomycin (MIC: 1.56 µg/mL). We compared the three most potent ones for their cytotoxicity to HepG2 and HUVEC cells and selected compound 1b as our lead compound for comprehensive biological evaluation. As a result, compound 1b exhibited a bacteriostatic mode, and was active against a panel of Gram-positive bacteria strains, metabolically stable, and effective to protect the mice from MRSA infection. More importantly, we applied 2D similarity calculation and reverse docking to predict potential targets of compound 1b. Through experimental validation and molecular dynamics simulation, we were able to confirm that compound 1b inhibited Staphylococcus aureus DNA gyrase (IC50: 1.81 µM) and DNA supercoiling, potentially by binding to the ATPase domain, where ASP81, GLU58 and GLN91 formed key hydrogen bonds. Taken together, we have discovered a new class of DNA gyrase inhibitors represented by compound 1b for the treatment of MRSA infection, through the design, synthesis, and biological evaluation of novel 1,4-dicarbonylthiosemicarbazides.

3.
Clin Exp Med ; 24(1): 238, 2024 Oct 09.
Article in English | MEDLINE | ID: mdl-39382711

ABSTRACT

This study aimed to evaluate how the timing of transarterial chemoembolization (TACE) relative to systemic therapy (tyrosine-kinase inhibitors [TKIs] and immune checkpoint inhibitors [ICIs]) influences oncological outcomes in patients with hepatocellular carcinoma (HCC). A retrospective analysis was conducted on HCC patients treated with TACE plus TKIs and ICIs from January 2018 to February 2023. We compared objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) between patients receiving TACE before versus after systemic therapies. Multivariate Cox regression analyses identified potential prognostic factors. Of the 194 patients enrolled, 111 received TACE before systemic therapies, and 83 after. The median age at diagnosis was 52.8 years. There were no significant differences in ORR (40.72% vs. 30.41%, p = 0.989) or DCR (48.45% vs. 35.57%, p = 0.770) between the groups. Likewise, OS (18.73 vs. 18.20 months, p = 0.091) and PFS (11.53 vs. 10.05 months, p = 0.336) were similar regardless of treatment sequence. In the result of Cox analysis, a 20% decrease in AFP from baseline at one month was associated with improved OS (HR = 0.35, 95% CI 0.17-0.70, p = 0.003) and PFS (HR = 0.69, 95% CI 0.49-0.96, p = 0.028). Large tumor size (≥ 10 cm) was a poor prognostic factor for OS (HR = 2.12, 95% CI 1.07-4.21, p = 0.032), and the presence of portal vein tumor thrombus adversely affected PFS (HR = 2.31, 95% CI 1.47-3.62, p < 0.001). The sequencing of TACE and systemic therapies does not significantly impact the prognosis of advanced HCC. A 20% reduction in AFP within one month of treatment commencement emerges as a protective prognostic factor for HCC.


Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/mortality , Liver Neoplasms/therapy , Liver Neoplasms/pathology , Liver Neoplasms/mortality , Middle Aged , Male , Female , Retrospective Studies , Adult , Treatment Outcome , Aged , Immune Checkpoint Inhibitors/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Prognosis , Survival Analysis
4.
Genomics ; : 110948, 2024 Oct 07.
Article in English | MEDLINE | ID: mdl-39384163

ABSTRACT

Rhubarb is a traditional medicinal plant in China, whose pharmacological effects derive mainly from its anthraquinones. However, the regulatory mechanism affecting anthraquinone biosynthesis in R. officinale remains poorly understood. We assembled a high-quality, full-length transcriptome using single-molecule real-time (SMRT) sequencing. 274 unigenes potentially involved in the biosynthesis of anthraquinones, including those in the shikimate, polyketide, MVA and MEP pathways, were identified based on full-length transcriptome. Differentially expressed genes (DEGs) induced by MeJA treatment and DEGs between different tissues were identified through next-generation sequencing (NGS), revealing the genes that may be involved in the biosynthesis of anthraquinones. The basic leucine zipper (bZIP) transcription factors of R. officinale were systematically identified. Key genes such as RobZIP50 and RobZIP53 were systematically identified and found to be associated with anthraquinone biosynthesis in R. officinale through differential expression, co-expression and protein interaction analyses. RobZIP50 and RobZIP53 were highly expressed in roots and rhizomes, and significantly increased after 12 h of MeJA treatment. Additionally, both RobZIP50 and RobZIP53 were localized exclusively in the nucleus, with RobZIP53 showing significant transcriptional activity. Taken together, our results suggest that RobZIP53 may play a role in regulating anthraquinone biosynthesis in R. officinale.

5.
Front Pharmacol ; 15: 1463864, 2024.
Article in English | MEDLINE | ID: mdl-39380909

ABSTRACT

Introduction: Due to its remarkable anti-inflammatory pharmacological activity, Farfarae Flos has gained extensive usage in the treatment of various inflammatory diseases such as bronchitis, pneumonia, prostatitis and colitis. And Farfarae Flos come in two color types depending on the color of the flowers: yellowish-white (YW), and purplish-red (PR). However, the difference in anti-inflammatory activity and metabolic profiles between the two flower colors remains unexplored. Methods: This study aims to explore the difference in the anti-inflammatory potential between YW and PR variants of Farfarae Flos and unravel the mechanisms responsible for the observed differences in anti-inflammatory activity through an integrated approach encompassing untargeted metabolomics and in vivo/vitro experimental studies. Initially, we verified the contrasting effects of YW and PR on the inhibition of the inflammatory factors interleukin-6 (IL-6) and nitric oxide (NO) by utilizing an in vitro RAW 264.7 cell inflammation model. Subsequently, a comprehensive evaluation of the systemic inhibitory capacity of YW and PR on IL-6, Interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) was conducted using a validated whole-body mouse model, followed by the analysis of inflammatory factors and histological examination of collected serum, liver, and spleen after 7 days. Furthermore, non-targeted metabolomics profiling was employed to analyze the metabolite profiles of Farfarae Flos with different colors, and quantitative analysis was conducted to identify differential metabolites between YW and PR. The correlation between the anti-inflammatory activities of differentially accumulated metabolites (DAMs) and Farfarae Flos was investigated, resulting in the identification of 48 compounds exhibiting significant anti-inflammatory activity. Additionally, KEGG pathway enrichment analysis was performed to elucidate the underlying mechanisms. Results: Our findings demonstrate that both YW and PR possess anti-inflammatory abilities, with PR exhibiting significantly superior efficacy. The integration of in vivo/vitro experiments and non-targeted metabolomics confirmed the exceptional anti-inflammatory potential of PR and solidified its classification as the "purplish-red better" of Farfarae Flos. Discussion: This study provides valuable insights into the breeding and medical transformation of Farfarae Flos varieties, along with a scientific basis for the establishment of quality standards and the development of new drugs utilizing Farfarae Flos.

6.
Kaohsiung J Med Sci ; 2024 Oct 12.
Article in English | MEDLINE | ID: mdl-39394911

ABSTRACT

This study investigated the impact of LNP023 on the AMPK/mTOR signaling pathway in lupus nephritis (LN) and its effects on autophagy and oxidative stress. A mouse model of LN was established, and renal injury was confirmed by assessing various LN markers, including antinuclear antibody, ds-DNA, anti-Sm antibody, and others. Mice were treated with LNP023, the AMPK activator AICAR, or the AMPK inhibitor dorsomorphin. Renal injury and fibrosis were evaluated using HE and Masson staining. Expression levels of AMPK, mTOR, LC3, Beclin1, and p62 were assessed by immunohistochemistry and Western blot. Oxidative stress and inflammatory markers were measured by polymerase chain reaction and enzyme-linked immunosorbent assay. LN mice exhibited low AMPK/p-AMPK and high mTOR/p-mTOR levels, alongside significant renal injury, fibrosis, reduced autophagy, and elevated oxidative stress. LNP023 treatment improved these parameters, with enhanced effects when combined with AICAR. Conversely, dorsomorphin reversed LNP023's therapeutic benefits. The complement factor B inhibitor LNP023 promotes kidney health in LN mice by mediating the AMPK/mTOR pathway, promoting autophagy, and attenuating oxidative stress.

7.
Article in English | MEDLINE | ID: mdl-39361608

ABSTRACT

The emergent reconfigurable metasurfaces (RMs) have attracted a lot of attention due to their potential in broad applications. As a general platform, RMs are able to control the reflection (or refraction) of incident waves with predefined functionalities. Nevertheless, the operation of RMs is highly dependent on the arrival direction of incidence. The self-adaptive design of an RM, so that it can respond to varied incident waves automatically, is highly requested in practical implementation, which is actually challenging. This study reports the realization of an intelligent RM (IRM) system, which can detect the arrival direction of impinging waves and respond to the incidence with a predefined functionality accordingly. This IRM system is constructed by integrating a direction of the arrival estimation module, a frontend by the varactor-based metasurface, and a central control unit. In experiments, an IRM system designed for TM polarization is demonstrated to perform various functions, i.e., retroreflection, directional reflection, and fixed-point energy focusing, which are highly requested by edge communication and sensing. The measured results imply that this IRM system responds quite well within a wide incident range from -60° to 60° in a frequency range from 9 to 9.5 GHz. The proposed IRM can be a good candidate for boosting 5G communication and Internet of Things applications, including beam shaping/steering, RCS manipulation, object imaging, and sensor recharging.

8.
Stem Cell Res Ther ; 15(1): 344, 2024 Oct 08.
Article in English | MEDLINE | ID: mdl-39380037

ABSTRACT

BACKGROUND: Lung injury and pulmonary fibrosis (PF), frequently arising as sequelae of severe and acute lung disease, currently face a dearth of effective therapeutic potions. Mesenchymal stem cells (MSCs) with immunomodulatory and tissue repair functions have immense potential to treat lung injury and PF. However, the optimal route of administration, timing, and frequency of dosing remain elusive. Human embryonic stem cell-derived immunity-and-matrix-regulatory cells (IMRCs) have shown therapeutic potential for lung injury and PF. METHODS: To ascertain the optimal therapeutic regimen for IMRCs in PF, we conducted an experimental study. Utilizing a mouse model of PF induced by bleomycin (BLM), IMRCs were administered via either a single or double intravenous (IV) or intratracheal (IT) injection on the first and seventh days post-BLM induction. RESULTS: Our findings revealed that IV infusion of IMRCs surpassed IT infusion in enhancing survival rates, facilitating body weight recovery, and optimizing Ashcroft and Szapiel scores among the model mice. Notably, IV administration exhibited a more profound ability to mitigate lung inflammation and fibrosis. Moreover, earlier and more frequent administrations of IMRCs were found to be advantageous in enhancing their therapeutic effects. Specifically, early administration with two IV infusions significantly improved body weight, lung organ coefficient, pulmonary ventilation and diffusion functions, and PF. This was accompanied by an increase in alveolar type I and II epithelial cells and a suppression of macrophage infiltration via CD24. CONCLUSION: Collectively, these results suggested that IMRCs infusion ameliorated lung injury by promoting lung regeneration and inhibiting macrophage infiltration in a route, time, and frequency-dependent manner.


Subject(s)
Bleomycin , Human Embryonic Stem Cells , Lung Injury , Pulmonary Fibrosis , Animals , Mice , Humans , Human Embryonic Stem Cells/cytology , Pulmonary Fibrosis/therapy , Pulmonary Fibrosis/pathology , Pulmonary Fibrosis/chemically induced , Lung Injury/therapy , Lung Injury/pathology , Disease Models, Animal , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Mice, Inbred C57BL
9.
Adv Sci (Weinh) ; : e2408686, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-39387324

ABSTRACT

Distinct types of luminescence that are activated by various stimuli in a single material offer exciting developmental opportunities for functional materials. A versatile sensing platform that exhibits photoluminescence (PL), persistent luminescence (PersL), and mechanoluminescence (ML) is introduced, which enables the sensitive detection of temperature, pressure, and force/stress. The developed Sr2MgSi2O7:Eu2+/Dy3+ material exhibits a linear relationship between ML intensity and force and can be used as an ML stress sensor. Additionally, the bandwidth of the PL emission band and the PL lifetime of this material are remarkably sensitive to temperature, with values of ≈0.05 nm K-1 and 1.29%/K, respectively. This study demonstrates PersL pressure sensing for the first time, using long-lasting (seconds) lifetime as a manometric parameter. The developed material functions as an exceptionally sensitive triple-mode visual pressure sensor; specifically, it exhibits: i) a sensitivity of ≈-297.4 cm GPa-1 (8.11 nm GPa-1) in bandshift mode, ii) a sensitivity of ≈272.7 cm-1/GPa (14.8 nm GPa-1) in bandwidth mode, and iii) a sensitivity of 42%GPa-1 in PL-lifetime mode, which is the highest value reported to date. Notably, anti-counterfeiting, night-vision safety-sign, 8-bit optical-coding, and QR-code applications that exhibit intense PersL are demonstrated by 3D-printing the studied material in combination with a polymer.

10.
Microbiol Spectr ; : e0425423, 2024 Oct 10.
Article in English | MEDLINE | ID: mdl-39387591

ABSTRACT

The emergence of multidrug-resistant Citrobacter freundii poses a significant threat to public health. C. freundii isolates were collected from clinical patients in a Chinese hospital during 2020-2022. An unusual strain, GMU8049, was not susceptible to any of the antibiotics tested, including the novel ß-lactam/ß-lactamase inhibitor combination ceftazidime-avibactam. Whole-genome sequencing (WGS) revealed that GMU8049 harbors a circular chromosome belonging to the rare ST257 and an IncX3 resistance plasmid. Genomic analysis revealed the coexistence of two ß-lactamase genes, including plasmid-mediated blaNDM-1 and chromosomal blaCMY encoding a novel CMY variant, combined with an outer membrane porin deficiency, which may account for the extreme resistance to ß-lactams. Conjugation experiment confirmed that the blaNDM-1 resistance gene located on pGMU8049 could be successfully transferred to Escherichia coli EC600. The novel CMY variant had an amino acid substitution at position 106 (N106S) compared to the closely related CMY-51. Additionally, a GMU8049-specific truncation in an OmpK37 variant that produces a premature stop codon. Moreover, a variety of chromosome-located efflux pump coding genes and virulence-related genes were also identified. Analysis of strain GMU8049 in the context of other C. freundii strains reveals an open pan-genome and the presence of mobile genetic elements that can mediate horizontal gene transfer of antimicrobial resistance and virulence genes. Our work provides comprehensive insights into the genetic mechanisms of highly resistant C. freundii, highlighting the importance of genomic surveillance of this opportunistic pathogen as a high-risk population for emerging resistance and pathogenicity.IMPORTANCEEmerging pathogens exhibiting multi-, extremely, and pan-drug resistance are a major concern for hospitalized patients and the healthcare community due to limited antimicrobial treatment options and the potential for spread. Genomic technologies have enabled clinical surveillance of emerging pathogens and modeling of the evolution and transmission of antimicrobial resistance and virulence. Here, we report the genomic characterization of an extremely drug-resistant ST257 Citrobacter freundii clinical isolate. Genomic analysis of GMU8049 with a rare ST type and unusual phenotypes can provide information on how this extremely resistant clinical isolate has evolved, including the acquisition of blaNDM-1 via the IncX3 plasmid and accumulation through chromosomal mutations leading to a novel CMY variant and deficiency of the outer membrane porin OmpK37. Our work highlights that the emergence of extremely resistant C. freundii poses a significant challenge to the treatment of clinical infections. Therefore, great efforts must be made to specifically monitor this opportunistic pathogen.

12.
Int J Mol Med ; 54(5)2024 Nov.
Article in English | MEDLINE | ID: mdl-39301658

ABSTRACT

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end­stage renal disease, and is characterized by persistent proteinuria and decreased glomerular filtration rate. Despite extensive efforts, the increasing incidence highlights the urgent need for more effective treatments. Histone methylation is a crucial epigenetic modification, and its alteration can destabilize chromatin structure, thereby regulating the transcriptional activity of specific genes. Histone methylation serves a substantial role in the onset and progression of various diseases. In patients with DKD, changes in histone methylation are pivotal in mediating the interactions between genetic and environmental factors. Targeting these modifications shows promise in ameliorating renal histological manifestations, tissue fibrosis and proteinuria, and represents a novel therapeutic frontier with the potential to halt DKD progression. The present review focuses on the alterations in histone methylation during the development of DKD, systematically summarizes its impact on various renal parenchymal cells and underscores the potential of targeted histone methylation modifications in improving DKD outcomes.


Subject(s)
Diabetic Nephropathies , Epigenesis, Genetic , Histones , Humans , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/genetics , Diabetic Nephropathies/therapy , Diabetic Nephropathies/drug therapy , Histones/metabolism , Animals , Methylation , Protein Processing, Post-Translational , Histone Code
13.
Front Cell Dev Biol ; 12: 1431173, 2024.
Article in English | MEDLINE | ID: mdl-39224435

ABSTRACT

During the metamorphosis of anuran amphibians, the tail resorption process is a necessary and crucial change. One subject that has received relatively little or no attention is the expression patterns of proteins and metabolites in the different tail portions during metamorphosis, especially in highland amphibians. The mechanisms of tail resorption in three portions (the tip, middle and root) of the tail were investigated in N. pleskei G43 tadpole based on two omics (proteomic and metabolomic). Integrin αVß3 was found to be high expressed in the distal portion of the tail, which could improve the sensitiveness to thyroid hormones in the distal portion of the tail. Muscle regression displayed a spatial pattern with stronger regression in distal and weaker one in proximal portion. Probably, this stronger regression was mainly performed by the proteases of proteasome from the active translation by ribosomes. The suicide model and murder model coexisted in the tail resorption. Meanwhile, fatty acids, amino acids, pyrimidine, and purine which derived from the breakdown of tissues can be used as building blocks or energy source for successful metamorphosis. Our data improved a better comprehension of the tail resorption mechanisms underlying the metamorphism of N. pleskei tadpole through identifying important participating proteins and metabolites.

15.
World J Gastroenterol ; 30(31): 3689-3704, 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39193000

ABSTRACT

BACKGROUND: Inflammatory bowel disease, particularly Crohn's disease (CD), has been associated with alterations in mesenteric adipose tissue (MAT) and the phenomenon termed "creeping fat". Histopathological evaluations showed that MAT and intestinal tissues were significantly altered in patients with CD, with these tissues characterized by inflammation and fibrosis. AIM: To evaluate the complex interplay among MAT, creeping fat, inflammation, and gut microbiota in CD. METHODS: Intestinal tissue and MAT were collected from 12 patients with CD. Histological manifestations and protein expression levels were analyzed to determine lesion characteristics. Fecal samples were collected from five recently treated CD patients and five control subjects and transplanted into mice. The intestinal and mesenteric lesions in these mice, as well as their systemic inflammatory status, were assessed and compared in mice transplanted with fecal samples from CD patients and control subjects. RESULTS: Pathological examination of MAT showed significant differences between CD-affected and unaffected colons, including significant differences in gut microbiota structure. Fetal microbiota transplantation (FMT) from clinically healthy donors into mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD ameliorated CD symptoms, whereas FMT from CD patients into these mice exacerbated CD symptoms. Notably, FMT influenced intestinal permeability, barrier function, and levels of proinflammatory factors and adipokines. Furthermore, FMT from CD patients intensified fibrotic changes in the colon tissues of mice with TNBS-induced CD. CONCLUSION: Gut microbiota play a critical role in the histopathology of CD. Targeting MAT and creeping fat may therefore have potential in the treatment of patients with CD.


Subject(s)
Crohn Disease , Disease Models, Animal , Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Crohn Disease/microbiology , Crohn Disease/therapy , Crohn Disease/pathology , Crohn Disease/metabolism , Animals , Humans , Mice , Female , Male , Adult , Feces/microbiology , Trinitrobenzenesulfonic Acid , Colon/microbiology , Colon/pathology , Colon/immunology , Fibrosis , Mesentery , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Middle Aged , Mice, Inbred C57BL , Case-Control Studies , Young Adult , Permeability , Adipose Tissue , Adipokines/metabolism
16.
Sci Rep ; 14(1): 18697, 2024 08 12.
Article in English | MEDLINE | ID: mdl-39134694

ABSTRACT

Neuroblastoma, the deadliest solid tumor in children, exhibits alarming mortality rates, particularly among high-risk cases. To enhance survival rates, a more precise risk stratification for patients is imperative. Utilizing proteomic data from 34 cases with or without N-Myc amplification, we identified 28 differentially expressed ubiquitination-related proteins (URGs). From these, a prognostic signature comprising 6 URGs was constructed. A nomogram incorporating clinical-pathological parameters yielded impressive AUC values of 0.88, 0.93, and 0.95 at 1, 3, and 5 years, respectively. Functional experiments targeting the E3 ubiquitin ligase FBXO42, a component of the prognostic signature, revealed its TP53-dependent promotion of neuroblastoma cell proliferation. In conclusion, our ubiquitination-related prognostic model robustly predicts patient outcomes, guiding clinical decisions. Additionally, the newfound pro-proliferative role of FBXO42 offers a novel foundation for understanding the molecular mechanisms of neuroblastoma.


Subject(s)
Cell Proliferation , Neuroblastoma , Humans , Neuroblastoma/metabolism , Neuroblastoma/genetics , Neuroblastoma/pathology , Prognosis , Male , Ubiquitination , Cell Line, Tumor , Female , Proteomics/methods , Gene Expression Regulation, Neoplastic , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , F-Box Proteins/metabolism , F-Box Proteins/genetics , Child, Preschool , Infant , Child
17.
Heliyon ; 10(12): e32695, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-39183826

ABSTRACT

This paper uses panel data of 260 prefecture-level cities from 2000 to 2019 to explore spatial characteristics such as spatiotemporal divergence and dynamic convergence based on measuring the level of human capital misallocation in Chinese cities and empirically tests the green development effect of human capital misallocation. The study finds that: ① the human capital misallocation levels of the country and the eight major urban agglomerations show a fluctuating downward trend. ② Divergences in human capital misallocation continue to narrow across the country and urban agglomerations, and the difference between inter-urban agglomerations is the primary source of regional difference. ③ The YRD, PRD, MYR, HC, and CP have significant σ-convergence characteristics of human capital misallocation. Meanwhile, the country and each urban agglomeration show significant spatial absolute ß-convergence and conditional ß-convergence trends. ④ Human capital misallocation significantly negatively affects green economic efficiency, inhibiting green economy efficiency. Therefore, in the future, it is necessary to improve the match between regional industrial structure and human capital allocation through a combination of targeted policy guidance and market mechanisms tailored to local conditions to enhance the efficiency of the green economy. The significance of the study lies in accelerating the accumulation of human capital while realizing the appropriate matching of human capital, releasing the human capital dividend to the maximum extent, and boosting the structural reform of the labor market to realize the transformation of the green economy.

18.
Front Med (Lausanne) ; 11: 1419058, 2024.
Article in English | MEDLINE | ID: mdl-39086938

ABSTRACT

Objective: This study aimed to investigate the use of radiomics features and clinical information by four machine learning algorithms for predicting the prognosis of patients with hepatocellular carcinoma (HCC) who have been treated with transarterial chemoembolization (TACE). Methods: A total of 105 patients with HCC treated with TACE from 2002 to 2012 were enrolled retrospectively and randomly divided into two cohorts for training (n = 74) and validation (n = 31) according to a ratio of 7:3. The Spearman rank, random forest, and univariate Cox regression were used to select the optimal radiomics features. Univariate Cox regression was used to select clinical features. Four machine learning algorithms were used to develop the models: random survival forest, eXtreme gradient boosting (XGBoost), gradient boosting, and the Cox proportional hazard regression model. The area under the curve (AUC) and C-index were devoted to assessing the performance of the models in predicting HCC prognosis. Results: A total of 1,834 radiomics features were extracted from the computed tomography images of each patient. The clinical risk factors for HCC prognosis were age at diagnosis, TNM stage, and metastasis, which were analyzed using univariate Cox regression. In various models, the efficacy of the combined models generally surpassed that of the radiomics and clinical models. Among four machine learning algorithms, XGBoost exhibited the best performance in combined models, achieving an AUC of 0.979 in the training set and 0.750 in the testing set, demonstrating its strong prognostic prediction capability. Conclusion: The superior performance of the XGBoost-based combined model underscores its potential as a powerful tool for enhancing the precision of prognostic assessments for patients with HCC.

19.
Nat Commun ; 15(1): 6704, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39112454

ABSTRACT

Body heat, a clean and ubiquitous energy source, is promising as a renewable resource to supply wearable electronics. Emerging tough thermogalvanic device could be a sustainable platform to convert body heat energy into electricity for powering wearable electronics if its Carnot-relative efficiency (ηr) reaches ~5%. However, maximizing both the ηr and mechanical strength of the device are mutually exclusive. Here, we develop a rational strategy to construct a flexible thermogalvanic armor (FTGA) with a ηr over 8% near room temperature, yet preserving mechanical robustness. The key to our design lies in simultaneously realizing the thermosensitive-crystallization and salting-out effect in the elaborately designed ion-transport highway to boost ηr and improve mechanical strength. The FTGA achieves an ultrahigh ηr of 8.53%, coupling with impressive mechanical toughness of 70.65 MJ m-3 and substantial elongation (~900%) together. Our strategy holds sustainable potential for harvesting body heat and powering wearable electronics without recharging.

20.
Genet Res (Camb) ; 2024: 3577395, 2024.
Article in English | MEDLINE | ID: mdl-39139739

ABSTRACT

Esophageal cancer is a major global health challenge with a poor prognosis. Recent studies underscore the extracellular matrix (ECM) role in cancer progression, but the full impact of ECM-related genes on patient outcomes remains unclear. Our study utilized next-generation sequencing and clinical data from esophageal cancer patients provided by The Cancer Genome Atlas, employing the R package in RStudio for computational analysis. This analysis identified significant associations between patient survival and various ECM-related genes, including IBSP, LINGO4, COL26A1, MMP12, KLK4, RTBDN, TENM1, GDF15, and RUNX1. Consequently, we developed a prognostic model to predict patient outcomes, which demonstrated clear survival differences between high-risk and low-risk patient groups. Our comprehensive review encompassed clinical correlations, biological pathways, and variations in immune response among these risk categories. We also constructed a nomogram integrating clinical information with risk assessment. Focusing on the TENM1 gene, we found it significantly impacts immune response, showing a positive correlation with T helper cells, NK cells, and CD8+ T cells, but a negative correlation with neutrophils and Th17 cells. Gene Set Enrichment Analysis revealed enhanced pathways related to pancreatic beta cells, spermatogenesis, apical junctions, and muscle formation in patients with high TENM1 expression. This research provides new insights into the role of ECM genes in esophageal cancer and informs future research directions.


Subject(s)
Esophageal Neoplasms , Extracellular Matrix , Tumor Microenvironment , Humans , Esophageal Neoplasms/genetics , Tumor Microenvironment/genetics , Extracellular Matrix/genetics , Extracellular Matrix/metabolism , Prognosis , Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic , Male , Nomograms
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