A radiomics-based interpretable model to predict the pathological grade of pancreatic neuroendocrine tumors.

OBJECTIVES: To develop a computed tomography (CT) radiomics-based interpretable machine learning (ML) model to predict the pathological grade of pancreatic neuroendocrine tumors (pNETs) in a non-invasive manner. METHODS: Patients with pNETs who underwent contrast-enhanced abdominal CT between 2010 and 2022 were included in this retrospective study. Radiomics features were extracted, and five radiomics-based ML models, namely logistic regression (LR), random forest (RF), support vector machine (SVM), XGBoost, and GaussianNB, were developed. The performance of these models was evaluated using a time-independent testing set, and metrics such as sensitivity, specificity, accuracy, and the area under the receiver operating characteristic curve (AUC) were calculated. The accuracy of the radiomics model was compared to that of needle biopsy. The Shapley Additive Explanation (SHAP) tool and the correlation between radiomics and biological features were employed to explore the interpretability of the model. RESULTS: A total of 122 patients (mean age: 50 ± 14 years; 53 male) were included in the training set, whereas 100 patients (mean age: 48 ± 13 years; 50 male) were included in the testing set. The AUCs for LR, SVM, RF, XGBoost, and GaussianNB were 0.758, 0.742, 0.779, 0.744, and 0.745, respectively, with corresponding accuracies of 73.0%, 70.0%, 77.0%, 71.9%, and 72.9%. The SHAP tool identified two features of the venous phase as the most significant, which showed significant differences among the Ki-67 index or mitotic count subgroups (p < 0.001). CONCLUSIONS: An interpretable radiomics-based RF model can effectively differentiate between G1 and G2/3 of pNETs, demonstrating favorable interpretability. CLINICAL RELEVANCE STATEMENT: The radiomics-based interpretable model developed in this study has significant clinical relevance as it offers a non-invasive method for assessing the pathological grade of pancreatic neuroendocrine tumors and holds promise as an important complementary tool to traditional tissue biopsy. KEY POINTS: • A radiomics-based interpretable model was developed to predict the pathological grade of pNETs and compared with preoperative needle biopsy in terms of accuracy. • The model, based on CT radiomics, demonstrated favorable interpretability. • The radiomics model holds potential as a valuable complementary technique to preoperative needle biopsy; however, it should not be considered a replacement for biopsy.

Long-term ozone exposure is negatively associated with estimated glomerular filtration rate in Chinese middle-aged and elderly adults.

Chronic kidney disease (CKD) is an inflammatory disease characterized by the deterioration of renal function, which imposes a significant burden on the healthcare system. In the recent decades, the ageing of the population and the increase of ozone pollution have accelerated. However, epidemiological associations between long-term ozone exposure and renal function in susceptible populations are understudied. In this study, we aimed to investigate the association of 1 y ozone exposure with renal function among the older adults in Xiamen City, China. We recruited 6024 eligible participants with a median age of 65.00 years, estimated their ozone exposure data, and collected questionnaires on demographic status and lifestyle factors as well as information on healthcare access. A generalized linear model was used to assess the association. An increase of 10 µg/m3 of 1 y ozone exposure was negatively associated with the estimated glomerular filtration rate (eGFR) [-3.12 (95% CI: -4.76, -1.48)]. The associations were stronger in men, non-smokers, and those with hypertension or T2DM. Clinical indicators of high-density lipoprotein, low-density lipoprotein, triglycerides, and total cholesterol were the main mediators to regulate the ozone-renal function association. Our results suggested that long-term ozone exposure is a potential risk factor for renal function in Chinese middle-aged and elderly adults.

Enhancing sorption of layered double hydroxide-based magnetic biochar for arsenic and cadmium through optimized preparation protocols.

The impact of multiple preparation protocols on properties and performance of modified biochar remains unclear. This study prepared layered double hydroxide (LDH)-based magnetic biochars (LMBCs) with different LDH loading rates (LLR), pyrolysis temperatures, and biomass sources to explore their performance-characterization relationships toward As(III) and Cd(II). Higher LLR and pyrolysis temperature enhanced LMBCs᾿ adsorption capacities by increasing specific surface area (SSA) and metal/O-containing groups. Hence, LMBC produced at 2:1 LLR (LDH: magnetic biochar) and 800 ℃ pyrolysis exhibited maximum adsorption over 2 times that of LMBC with 0.5:1 LLR and 400 ℃ pyrolysis. Bamboo-sourced LMBC demonstrated superior adsorption than sewage sludge and garlic-sourced LMBCs due to its increased SSA, enabling a higher loading of nano-LDH. Adsorption of As(III) and Cd(II) onto LMBCs was governed by metal-mineral and metal-containing group through co-precipitation and complexation. This study provides a reference for adjusting the preparation protocols to improve sorption performance of modified biochar toward multiple heavy metals.

Perilipin 5 deficiency aggravates cardiac hypertrophy by stimulating lactate production in leptin-deficient mice.

BACKGROUND: Perilipin 5 (Plin5) is well known to maintain the stability of intracellular lipid droplets (LDs) and regulate fatty acid metabolism in oxidative tissues. It is highly expressed in the heart, but its roles have yet to be fully elucidated. METHODS: Plin5-deficient mice and Plin5/leptin-double-knockout mice were produced, and their histological structures and myocardial functions were observed. Critical proteins related to fatty acid and glucose metabolism were measured in heart tissues, neonatal mouse cardiomyocytes and Plin5-overexpressing H9C2 cells. 2-NBDG was employed to detect glucose uptake. The mitochondria and lipid contents were observed by MitoTracker and BODIPY 493/503 staining in neonatal mouse cardiomyocytes. RESULTS: Plin5 deficiency impaired glucose utilization and caused insulin resistance in mouse cardiomyocytes, particularly in the presence of fatty acids (FAs). Additionally, Plin5 deficiency increased the NADH content and elevated the expression of lactate dehydrogenase (LDHA) in cardiomyocytes, which resulted in increased lactate production. Moreover, when fatty acid oxidation was blocked by etomoxir or LDHA was inhibited by GSK2837808A in Plin5-deficient cardiomyocytes, glucose utilization was improved. Leptin-deficient mice exhibited myocardial hypertrophy, insulin resistance and altered substrate utilization, and Plin5 deficiency exacerbated myocardial hypertrophy in leptin-deficient mice. CONCLUSION: Our results demonstrated that Plin5 plays a critical role in coordinating fatty acid and glucose oxidation in cardiomyocytes, providing a potential target for the treatment of metabolic disorders in the heart.

Understanding consumers' intentions to purchase smart clothing using PLS-SEM and fsQCA.

With the advancement of artificial intelligence (AI) and the Internet of Things (IoT), smart clothing, which has enormous growth potential, has developed to suit consumers' individualized demands in various areas. This paper aims to construct a model that integrates that technology acceptance model (TAM) and functionality-expressiveness-aesthetics (FEA) model to explore the key factors influencing consumers' smart clothing purchase intentions (PIs). Partial least squares structural equation modeling (PLS-SEM) was employed to analyze the data, complemented by fuzzy-set qualitative comparative analysis (fsQCA). The PLS-SEM results identified that the characteristics of functionality (FUN), expressiveness (EXP), and aesthetics (AES) positively and significantly affect perceived ease of use (PEOU), and only EXP affects perceived usefulness (PU). PU and PEOU positively impact consumers' attitudes (ATTs). Subsequently, PU and consumers' ATTs positively influence PIs. fsQCA revealed the nonlinear and complex interaction effects of the factors influencing consumers' smart clothing purchase behaviors and uncovered five necessary and six sufficient conditions for consumers' PIs. This paper furthers theoretical understanding by integrating the FEA model into the TAM. Additionally, on a practical level, it provides significant insights into consumers' intentions to purchase smart clothing. These findings serve as valuable tools for corporations and designers in strategizing the design and promotion of smart clothing. The results validate theoretical conceptions about smart clothing PIs and provide useful insights and marketing suggestions for smart clothing implementation and development. Moreover, this study is the first to explain smart clothing PIs using symmetric (PLS-SEM) and asymmetric (fsQCA) methods.

ALKBH5 promotes hypopharyngeal squamous cell carcinoma apoptosis by targeting TLR2 in a YTHDF1/IGF2BP2-mediated manner.

Hypopharyngeal squamous cell carcinoma (HPSCC) is one of the most aggressive cancers and is notorious for its extremely poor prognosis. However, very few molecular biological studies have been performed. As a novel method of epigenetic gene modulation, N6-methyladenosine (m6A) RNA modification occurs in HPSCC. The expression of the m6A demethylase AlkB homolog 5 (ALKBH5) is frequently downregulated in human HPSCC. Furthermore, we found that ALKBH5 impaired cell proliferation by regulating human Toll-like receptor 2 (TLR2) in an m6A-dependent manner in HPSCC cells. ALKBH5 decreased TLR2 m6A modification, which could be recognized by the m6A readers IGF2BP2 and YTHDF1. IGF2BP2 facilitates TLR2 mRNA stability, whereas YTHDF1 promotes TLR2 mRNA translation. The current work uncovered a critical function of ALKBH5 in TLR2 regulation and provides a novel role for m6A demethylation of mRNA in HPSCC. The inhibition of m6A modification of ALKBH5 in HPSCC deserves further clinical investigation.

Regional homogeneity alterations of resting-state functional magnetic resonance imaging of chronic rhinosinusitis with olfactory dysfunction.

Objectives: The aim of this study was to assess the brain functional changes of patients with chronic rhinosinusitis with olfactory dysfunction (CRSwOD) using regional homogeneity (ReHo) of resting-state functional magnetic resonance imaging (MRI) scans, and to better explain the occurrence and development of olfactory decline in patients with chronic sinusitis provides a new idea for the study of more advanced olfactory therapy modalities. Methods: A total of 28 CRSwOD patients, 24 patients with CRS without olfactory dysfunction (CRSsOD), and 25 healthy controls (HCs) were recruited. All subjects underwent olfactory testing, clinical and brief psychological assessments, and MRI scans. A two-sided two-sample t test with AlphaSim correction (voxel-p < 0.001, cluster size >54 voxels) was used to detect differences between CRSwOD, CRSsOD, and HC groups. Results: Compared with HCs, the ReHo values in traditional olfactory regions (e.g., parahippocampal gyrus (PHG), hippocampal, olfactory cortex) were increased, and ReHo values in the frontal gyrus, middle temporal gyrus, precuneus, and posterior cingulate gyrus were decreased in CRSwOD patients. The ReHo values in the precuneus and posterior cingulate gyrus of CRSwOD patients were negatively correlated with Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) scores. Compared with CRSsOD patients, the ReHo values in cerebellar regions were increased and those in the inferior temporal gyrus, precuneus, postcentral, and paracentral gyrus were decreased in CRSwOD patients. The receiver operating characteristic (ROC) curve showed that the mean ReHo values significantly differed between the CRSwOD and CRSsOD groups. Conclusion: Synchronization of regional brain activity in the regions of the secondary olfactory cortex orbitofrontal cortex (OFC), temporal gyrus, precuneus, and cerebellum may be closely related to the development of olfactory dysfunction. Precuneus and posterior cingulate gyrus may be critical brain areas of action for emotional dysfunction in CRSwOD patients.

Calculated plasma volume status is associated with poor outcomes in acute ischemic stroke treated with endovascular treatment.

Background and purpose: The impact of calculated plasma volume status (PVS) on the prognosis of acute ischemic stroke treated with endovascular treatment (EVT) remains undetermined. This study aimed to investigate the association between PVS and 90 days functional outcomes after EVT. Methods: We enrolled patients treated with EVT in the anterior circulation from a prospective registry. The endpoint was a modified Rankin scale score of ≥3 points at 90 days after EVT. We used multivariable logistic regression models to investigate the association between PVS and poor outcomes. We used the restricted cubic spline to present the linearity between PVS and poor outcomes. Results: Among the 187 enrolled patients (median age, 65 years; 35.8% women), a total of 81 patients (43.3%) experienced poor outcomes at 90 days. In multivariable analyses, PVS was associated with poor outcomes despite increasing confounding factors (odds ratio, 3.157; 95% confidence interval, 1.942-5.534; P < 0.001). The restricted cubic spline revealed a positive correlation between PVS and the risk of poor outcomes after EVT (P for nonlinearity = 0.021). Conclusion: Our study found that an elevated PVS value was associated with poor outcomes after EVT. Further prospective cohorts were warranted to evaluate the utility of PVS in AIS treated with EVT.

Whole Genomic Analysis Revealed High Genetic Diversity and Drug-Resistant Characteristics of Mycobacterium tuberculosis in Guangxi, China.

Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a major public health issue in China. Nevertheless, the prevalence and drug resistance characteristics of isolates vary in different regions and provinces. In this study, we investigated the population structure, transmission dynamics and drug-resistant profiles of Mtb in Guangxi, located on the border of China. Methods: From February 2016 to April 2017, 462 clinical M. tuberculosis isolates were selected from 5 locations in Guangxi. Drug-susceptibility testing was performed using 6 common anti-tuberculosis drugs. The genotypic drug resistance and transmission dynamics were analyzed by the whole genome sequence. Results: Our data showed that the Mtb in Guangxi has high genetic diversity including Lineage 1 to Lineage 4, and mostly belong to Lineage 2 and Lineage 4. Novelty, 9.6% of Lineage 2 isolates were proto-Beijing genotype (L2.1), which is rare in China. About 12.6% of isolates were phylogenetically clustered and formed into 28 transmission clusters. We observed that the isolates with the high resistant rate of isoniazid (INH, 21.2%), followed by rifampicin (RIF, 13.2%), and 6.7%, 12.1%, 6.7% and 1.9% isolates were resistant to ethambutol (EMB), streptomycin (SM), ofloxacin (OFL) and kanamycin (KAN), respectively. Among these, 6.5% and 3.3% of isolates belong to MDR-TB and Pre-XDR, respectively, with a high drug-resistant burden. Genetic analysis identified the most frequently encountered mutations of INH, RIF, EMB, SM, OFL and KAN were katG_Ser315Thr (62.2%), rpoB_Ser450Leu (42.6%), embB_Met306Vol (45.2%), rpsL_Lys43Arg (53.6%), gyrA_Asp94Gly (29.0%) and rrs_A1401G (66.7%), respectively. Additionally, we discovered that isolates from border cities are more likely to be drug-resistant than isolates from non-border cities. Conclusion: Our findings provide a deep analysis of the genomic population characteristics and drug-resistant of M. tuberculosis in Guangxi, which could contribute to developing effective TB prevention and control strategies.

Surgery for fibrosing mediastinitis with severe pulmonary hypertension due to pulmonary venous stenosis.

A 21-year-old woman with severe pulmonary hypertension and circulatory collapse was referred to our hospital for possible lung transplantation with extracorporeal membrane oxygenation support. Computed tomography revealed severe stenosis of all four pulmonary veins, and fibrosing mediastinitis was suspected. Surgical reconstruction of the pulmonary veins was performed, and extracorporeal membrane oxygenation support was weaned off. After surgery, pulmonary vascular resistance normalized. This successful case demonstrates that surgical pulmonary venous reconstruction is an important treatment for fibrosing mediastinitis induced by pulmonary venous stenosis and pulmonary hypertension.

Genome-wide identification and analysis of a cotton secretome reveals its role in resistance against Verticillium dahliae.

BACKGROUND: The extracellular space between the cell wall and plasma membrane is a battlefield in plant-pathogen interactions. Within this space, the pathogen employs its secretome to attack the host in a variety of ways, including immunity manipulation. However, the role of the plant secretome is rarely studied for its role in disease resistance. RESULTS: Here, we examined the secretome of Verticillium wilt-resistant Gossypium hirsutum cultivar Zhongzhimian No.2 (ZZM2, encoding 95,327 predicted coding sequences) to determine its role in disease resistance against the wilt causal agent, Verticillium dahliae. Bioinformatics-driven analyses showed that the ZZM2 genome encodes 2085 secreted proteins and that these display disequilibrium in their distribution among the chromosomes. The cotton secretome displayed differences in the abundance of certain amino acid residues as compared to the remaining encoded proteins due to the localization of these putative proteins in the extracellular space. The secretome analysis revealed conservation for an allotetraploid genome, which nevertheless exhibited variation among orthologs and comparable unique genes between the two sub-genomes. Secretome annotation strongly suggested its involvement in extracellular stress responses (hydrolase activity, oxidoreductase activity, and extracellular region, etc.), thus contributing to resistance against the V. dahliae infection. Furthermore, the defense response genes (immunity marker NbHIN1, salicylic acid marker NbPR1, and jasmonic acid marker NbLOX4) were activated to varying degrees when Nicotina benthamiana leaves were agro-infiltrated with 28 randomly selected members, suggesting that the secretome plays an important role in the immunity response. Finally, gene silencing assays of 11 members from 13 selected candidates in ZZM2 displayed higher susceptibility to V. dahliae, suggesting that the secretome members confer the Verticillium wilt resistance in cotton. CONCLUSIONS: Our data demonstrate that the cotton secretome plays an important role in Verticillium wilt resistance, facilitating the development of the resistance gene markers and increasing the understanding of the mechanisms regulating disease resistance.

Identification of Immune-Linked Hub Genes and Diagnostic Model Construction in Schizophrenia.

Schizophrenia (SCZ) is a prevalent, severe, and persistent mental disorder with an unknown etiology. Growing evidence indicates that immunological dysfunction is vital in the development of SCZ. Our study aims to uncover potential immune-linked hub genes and immune infiltration characteristics of SCZ, as well as to develop a diagnostic model based on immune-linked central genes. GSE38484 and GSE54913 chip expression data for patients with SCZ and healthy controls were retrieved. Weighted gene co-expression network analysis (WGCNA) was performed to identify major module genes and critical immune-linked genes. Functional enrichment analysis was conducted to elucidate the involvement of key genes in the immunological response to SCZ, along with the examination of their protein interactions. Moreover, 202 peripheral blood samples were examined using the single-sample gene set enrichment analysis (ssGSEA) method to detect distinct immune cell types. Hub immune-linked genes in SCZ were identified using the minimal absolute contraction and selection operator analysis. Receptor profiles of central immune-linked genes were analyzed to distinguish the two groups. Finally, the association between immune-linked hub genes and various types of immune cells was assessed. Our findings revealed ten immune cell types and nine key genes involved in SCZ, including effector memory CD4+ T cells, activated CD8+ T cells, mast cells, naive CD8+ T cells, PBMC, type 17 helper cells (Th17), central memory CD8+ T cells, CD56 bright NK cells, memory B cells, and regulatory T cells. Diagnostic models constructed using LASSO regression exhibited an average area under the curve (AUC) of 0.866. Our results indicate immunological dysfunction as a factor in the development of SCZ. ASGR2, ADRM1, AHANK, S100A8, FUCA1, AKNA, GATA3, AHCYL2, and PTRH2 are the key regulatory genes of immune cells, highlighting their potential as novel therapeutic targets for SCZ.

Regulation and role of extracellular polymeric substances in the defensive responses of Dictyosphaerium sp. to enrofloxacin stress.

Algae are susceptible to enrofloxacin (ENR), an antibiotic frequently detected in aquatic environments. However, algal responses, especially the secretion and roles of extracellular polymeric substances (EPS), under ENR exposure remain unknown. This study is the first to elucidate the variation in algal EPS triggered by ENR at both the physiological and molecular levels. The results showed that EPS were significantly (P < 0.05) overproduced along with increased polysaccharide and protein contents in algae exposed to 0.05, 0.5, and 5 mg/L ENR. Secretion of aromatic proteins, especially tryptophan-like substances with more functional groups or aromatic rings, was specifically stimulated. Furthermore, the genes with upregulated expression related to carbon fixation, aromatic protein biosynthesis, and carbohydrate metabolism are direct causes of enhanced EPS secretion. Improved EPS levels increased the cell surface hydrophobicity and provided more adsorption sites for ENR, which strengthened the van der Waals interaction and reduced ENR internalization. The hormesis effects of ENR were alleviated, as illustrated by the less affected cell density, chlorophyll a/b, and carotenoids biosynthesis in algae with EPS. These findings demonstrate the involvement of EPS in algal ENR resistance and promote a deeper understanding of the ecological effects of ENR in aquatic environments.

Dissolved organic matter promotes photocatalytic degradation of refractory organic pollutants in water by forming hydrogen bonding with photocatalyst.

Removing refractory organic pollutants in real water using photocatalysis is a great challenge because coexisting dissolved organic matter (DOM) can quench photogenerated holes and thus prevent generation of reactive oxygen species (ROS). Herein, for the first time, we develop a hydrogen bonding strategy to avoid the scavenging of photoexcited holes, by which DOM even promotes photocatalytic degradation of refractory organic pollutants. Theoretical calculations combined with experimental studies reveal the formation of hydrogen bonding between DOM and a hydroxylated S-scheme heterojunction photocatalyst (Mo-Se/OHNT) consisting of hydroxylated nitrogen doped TiO2 (OHNT) and molybdenum doped selenium (Mo-Se). The hydrogen bonding is demonstrated to change the interaction between DOM and Mo-Se/OHNT from DOM-Ti (IV) to a hydrogen bonded complexation through the hydroxyl/amine groups of DOM and the OHNT in Mo-Se/OHNT. The formed hydrogen network can stabilize excited-state of DOM and inject its electron to the conduction band rather than the valence band of the OHNT upon light irradiation, realizing the key to preventing hole quenching. The electron-hole separation in Mo-Se/OHNT is consequently improved for generating more ROS to be involved in removing refractory organic pollutants. Moreover, this hydrogen bonding strategy is generalized to nitrogen doped zinc oxide and graphitic carbon nitride and applies to real water. Our findings provide a new insight into handling the DOM problem for photocatalytic technology towards water and wastewater treatment.

Characterizing Conformational Change of a Thermoresponsive Polymeric Nanoparticle with Raman Spectroscopy.

Molecular conformational changes in the collapsing and reswelling processes occurring during the phase transition at the lower critical solution temperature (LCST) of the polymer are not well understood. In this study, we characterized the conformational change of Poly(oligo(Ethylene Glycol) Methyl Ether Methacrylate)-144 (POEGMA-144) synthesized on silica nanoparticles using Raman spectroscopy and zeta potential measurements. Changes in distinct Raman peaks associated with the oligo(Ethylene Glycol) (OEG) side chains (1023, 1320, and 1499 cm-1) with respect to the methyl methacrylate (MMA) backbone (1608 cm-1) were observed and investigated under increasing and decreasing temperature profiles (34 °C to 50 °C) to evaluate the polymer collapse and reswelling around its LCST (42 °C). In contrast to the zeta potential measurements that monitor the change in surface charges as a whole during the phase transition, Raman spectroscopy provided more detailed information on vibrational modes of individual molecular moieties of the polymer in responding to the conformational change.

Exosome-derived circKIF20B suppresses gefitinib resistance and cell proliferation in non-small cell lung cancer.

BACKGROUND: The gefitinib resistance mechanism in non-small cell lung cancer (NSCLC) remains unclear, albeit exosomal circular RNA (circRNA) is known to possibly play a vital role in it. METHODS: We employed high-throughput sequencing techniques to detect the expressions of exosomal circRNA both in gefitinib-resistant and gefitinib-sensitive cells in this study. The circKIF20B expression was determined in serum exosomes and tissues of patients by qRT-PCR. The structure, stability, and intracellular localization of circKIF20B were verified by Sanger sequencing, Ribonuclease R (RNase R)/actinomycin D (ACTD) treatments, and Fluorescence in situ hybridization (FISH). The functions of circKIF20B were investigated by 5-Ethynyl-20-deoxyuridine (EdU), flow cytometry, Cell Counting Kit-8 (CCK-8), oxygen consumption rate (OCR), and xenograft model. Co-culture experiments were performed to explore the potential ability of exosomal circKIF20B in treating gefitinib resistance. The downstream targets of circKIF20B were determined by luciferase assay, RNA pulldown, and RNA immunoprecipitation (RIP). RESULTS: We found that circKIF20B was poorly expressed in the serum exosomes of gefitinib-resistant patients (n = 24) and the tumor tissues of patients with NSCLC (n = 85). CircKIF20B was negatively correlated with tumor size and tumor stage. Decreasing circKIF20B was found to promote gefitinib resistance by accelerating the cell cycle, inhibiting apoptosis, and enhancing mitochondrial oxidative phosphorylation (OXPHOS), whereas increasing circKIF20B was found to restore gefitinib sensitivity. Mechanistically, circKIF20B is bound to miR-615-3p for regulating the MEF2A and then altering the cell cycle, apoptosis, and mitochondrial OXPHOS. Overexpressing circKIF20B parental cells can restore sensitivity to gefitinib in the recipient cells by upregulating the exosomal circKIF20B expression. CONCLUSIONS: This study revealed a novel mechanism of circKIF20B/miR-615-3p/MEF2A signaling axis involving progression of gefitinib resistance in NSCLC. Exosomal circKIF20B is expected to be an easily accessible and alternative liquid biopsy candidate and potential therapeutic target in gefitinib-resistant NSCLC. The schematic diagram of mechanism in this study. Exosomal circKIF20B inhibits gefitinib resistance and cell proliferation by arresting the cell cycle, promoting apoptosis, and reducing OXPHOS via circKIF20B/miR-615-3p/MEF2A axis in NSCLC.

Microplastics in the soil environment: Focusing on the sources, its transformation and change in morphology.

Microplastics (MPs) are small plastic pieces less than 5 mm in size. Previous studies have focused on the sources, transports, and fates of MPs in marine or sediment environments. However, limited attention has been given to the role of land as the primary source of MPs, and how plastic polymers are transformed into MPs through biological or abiotic effects during the transport process remains unclear. Here, we focus on the exploration of the main sources of MPs in the soil, highlighting that MP generation is not solely a byproduct of plastic production but can also result from the impact of biological and abiotic factors during the process of MPs transport. This review presents a new perspective on understanding the degradation of MPs in soil, considering soil as a distinct fluid and suggesting that the main transformation and change mediated by abiotic factors occur on the soil surface, while the main biodegradation occurs in the soil interior. This viewpoint is suggested because the role of some abiotic factors becomes less obvious in the soil interior, and MPs, whose surface is expected to colonize microorganisms, are gradually considered a carbon source independent of photosynthesis and net primary production. This review emphasizes the need to understand basic MPs information in soil for a rational evaluation of its environmental toxicity. Such understanding enables better control of MPs pollution in affected areas and prevents contamination in unaffected regions. Finally, knowledge gaps and future research directions necessary for advancements in this field are provided.

An imaging-based machine learning model outperforms clinical risk scores for prognosis of cirrhotic variceal bleeding.

OBJECTIVES: To develop and validate a machine learning model based on contrast-enhanced CT to predict the risk of occurrence of the composite clinical endpoint (hospital-based intervention or death) in cirrhotic patients with acute variceal bleeding (AVB). METHODS: This retrospective study enrolled 330 cirrhotic patients with AVB between January 2017 and December 2020 from three clinical centers. Contrast-enhanced CT and clinical data were collected. Centers A and B were divided 7:3 into a training set and an internal test set, and center C served as a separate external test set. A well-trained deep learning model was applied to segment the liver and spleen. Then, we extracted 106 original features of the liver and spleen separately based on the Image Biomarker Standardization Initiative (IBSI). We constructed the Liver-Spleen (LS) model based on the selected radiomics features. The performance of LS model was evaluated by receiver operating characteristics and calibration curves. The clinical utility of models was analyzed using decision curve analyses (DCA). RESULTS: The LS model demonstrated the best diagnostic performance in predicting the composite clinical endpoint of AVB in patients with cirrhosis, with an AUC of 0.782 (95% CI 0.650-0.882) and 0.789 (95% CI 0.674-0.878) in the internal test and external test groups, respectively. Calibration curves and DCA indicated the LS model had better performance than traditional clinical scores. CONCLUSION: A novel machine learning model outperforms previously known clinical risk scores in assessing the prognosis of cirrhotic patients with AVB CLINICAL RELEVANCE STATEMENT: The Liver-Spleen model based on contrast-enhanced CT has proven to be a promising tool to predict the prognosis of cirrhotic patients with acute variceal bleeding, which can facilitate decision-making and personalized therapy in clinical practice. KEY POINTS: • The Liver-Spleen machine learning model (LS model) showed good performance in assessing the clinical composite endpoint of cirrhotic patients with AVB (AUC ≥ 0.782, sensitivity ≥ 80%). • The LS model outperformed the clinical scores (AUC ≤ 0.730, sensitivity ≤ 70%) in both internal and external test cohorts.

Diffusion-weighted and diffusion kurtosis imaging analysis of microstructural differences in clear cell renal cell carcinoma: a comparative study.

OBJECTIVE: To quantitatively compare the diagnostic values of conventional diffusion-weighted imaging (DWI) and diffusion kurtosis imaging (DKI) analysis of microstructural differences for clear cell renal cell carcinoma (CRCC). METHODS: A total of 108 patients with pathologically confirmed CRCC, including 38 Grade I, 37 Grade II, 18 Grade III and 15 Grade IV, were enrolled and divided into groups according to tumor grade [low grade (Ⅰ+Ⅱ, n = 75) and high grade (Ⅲ+Ⅳ, n = 33)]. Apparent diffusion coefficient (ADC), mean diffusivity (MD), mean kurtosis (MK), kurtosis anisotropy (KA) and radial kurtosis (RK) were performed. RESULTS: Both the ADC (r = -0.803) and MD (-0.867) values showed a negative correlation with tumor grading (p < 0.05) and MK (r = 0.812), KA (0.816) and RK (0.853) values a positive correlation with tumor grading (p < 0.05). Mean FA values showed no significant differences among CRCC grades (p > 0.05). ROC curve analyses showed that MD values had the highest diagnostic efficacy in differentiating low/high and Ⅱ/Ⅲ tumor grading. MD values gave AUC: 0.937 (0.896); sensitivity: 92.0% (86.5%); specificity: 78.8% (77.8%) and accuracy: 90.7% (87.3%). ADC performed worse than MD, MK, KA or RK (all p < 0.05) during pair-wise comparisons of ROC curves to show diagnostic efficacy. CONCLUSION: DKI analysis performs better than ADC in differentiating CRCC grading. ADVANCES IN KNOWLEDGE: Both the ADC and MD values correlated negatively with CRCC grading.The MK, KA and RK values correlated positively with CRCC grading.MD values had the highest diagnostic efficacy in differentiating low/high and Ⅱ/Ⅲ CRCC grading.

H3K27me3 of Rnf19a promotes neuroinflammatory response during Japanese encephalitis virus infection.

Histone methylation is an important epigenetic modification that affects various biological processes, including the inflammatory response. In this study, we found that infection with Japanese encephalitis virus (JEV) leads to an increase in H3K27me3 in BV2 microglial cell line, primary mouse microglia and mouse brain. Inhibition of H3K27me3 modification through EZH2 knockdown and treatment with EZH2 inhibitor significantly reduces the production of pro-inflammatory cytokines during JEV infection, which suggests that H3K27me3 modification plays a crucial role in the neuroinflammatory response caused by JEV infection. The chromatin immunoprecipitation-sequencing (ChIP-sequencing) assay revealed an increase in H3K27me3 modification of E3 ubiquitin ligases Rnf19a following JEV infection, which leads to downregulation of Rnf19a expression. Furthermore, the results showed that Rnf19a negatively regulates the neuroinflammatory response induced by JEV. This is achieved through the degradation of RIG-I by mediating its ubiquitination. In conclusion, our findings reveal a novel mechanism by which JEV triggers extensive neuroinflammation from an epigenetic perspective.