Decontamination promotes the release of incorporated organic contaminants in hair: Novel insights into non-invasive biomonitoring.

Human hair is increasingly employed as a non-invasive biomonitoring matrix for exposure to organic contaminants (OCs). Decontamination procedures are generally needed to remove external contamination from hair prior to analysis of OCs. Despite various existing decontamination protocols, their impacts on internally incorporated (endogenous) OCs in hair remain poorly understood. This study aims to quantitatively assess the impact of decontamination procedures on endogenous OCs in hair, and investigate optimal decontamination processes and factors influencing the removal of endogenous OCs. In this study, guinea pig was exposed to 6 OCs (triphenyl phosphate (TPHP), tris(1,3-dichloro-2-propyl) phosphate (TDCPP), and tri-n-butyl phosphate (TNBP), bisphenol A (BPA), perfluorooctanoic acid (PFOA), and phenanthrene (PHE)), and 6 decontamination procedures with different solvents (methanol, n-hexane, acetone, ultrapure water, Triton X-100, and sodium dodecyl sulfate) were used to rinse exposed guinea pig hair. All OCs and three metabolites (diphenyl phosphate (DPHP), dibutyl phosphate (DBP), and bis(1,3-dichloro-2-propyl) phosphate (BDCPP)) were detected in the majority of washing solutions. The decontamination procedures apparently resulted in the release of endogenous OCs from hair. The percentages of residual OCs in hair exhibited a linear or exponential decrease with more washing cycles. Furthermore, the residuals of OCs in hair washed with organic and aqueous solvents showed negative correlations with molecular weight, polarizability, and their initial concentrations. Although these findings need to be validated with a broader range of OCs, the results obtained in this study provide compelling evidence that current hair decontamination procedures have significant impacts on the analysis of endogenous OCs in hair. Therefore, it is important to interpret quantitative data on hair OC concentrations with caution and to thoroughly consider each decontamination procedure during analysis.

Probing the capacity of a spatiotemporal deep learning model for short-term PM2.5 forecasts in a coastal urban area.

Accurate forecast of fine particulate matter (PM2.5) is crucial for city air pollution control, yet remains challenging due to the complex urban atmospheric chemical and physical processes. Recently deep learning has been routinely applied for better urban PM2.5 forecasts. However, their capacity to represent the spatiotemporal urban atmospheric processes remains underexplored, especially compared with traditional approaches such as chemistry-transport models (CTMs) and shallow statistical methods other than deep learning. Here we probe such urban-scale representation capacity of a spatiotemporal deep learning (STDL) model for 24-hour short-term PM2.5 forecasts at six urban stations in Rizhao, a coastal city in China. Compared with two operational CTMs and three statistical models, the STDL model shows its superiority with improvements in all five evaluation metrics, notably in root mean square error (RMSE) for forecasts at lead times within 12 h with reductions of 49.8 % and 47.8 % respectively. This demonstrates the STDL model's capacity to represent nonlinear small-scale phenomena such as street-level emissions and urban meteorology that are in general not well represented in either CTMs or shallow statistical models. This gain of small-scale representation in forecast performance decreases at increasing lead times, leading to similar RMSEs to the statistical methods (linear shallow representations) at about 12 h and to the CTMs (mesoscale representations) at 24 h. The STDL model performs especially well in winter, when complex urban physical and chemical processes dominate the frequent severe air pollution, and in moisture conditions fostering hygroscopic growth of particles. The DL-based PM2.5 forecasts align with observed trends under various humidity and wind conditions. Such investigation into the potential and limitations of deep learning representation for urban PM2.5 forecasting could hopefully inspire further fusion of distinct representations from CTMs and deep networks to break the conventional limits of short-term PM2.5 forecasts.

Characterization of Cancer Stem Cells in Laryngeal Squamous Cell Carcinoma by Single-cell RNA Sequencing.

Cancer stem cells (CSCs) constitute a pivotal element within the tumor microenvironment (TME), driving the initiation and progression of cancer. However, the identification of CSCs and their underlying molecular mechanisms in laryngeal squamous cell carcinoma (LSCC) remains a formidable challenge. We employed single-cell RNA sequencing of matched primary tumor tissues, paracancerous tissues, and local lymph nodes from three LSCC patients. Two distinct clusters of stem cells originating from epithelial populations were delineated and verified as CSCs and normal stem cells (NSCs), respectively. CSCs were abundant in the paracancerous tissues compared to the tumor tissues. CSCs showed high expression of stem cell marker genes such as PROM1, ALDH1A1, and SOX4, and increased the activity of tumor-related hypoxia, Wnt/ß-catenin, and Notch signaling pathways. We then explored the intricate crosstalk between CSCs and the TME cells and identified targets within the TME that related with CSCs. We also found eight marker genes of CSCs that correlated significantly with the prognosis of LSCC patients. Furthermore, bioinformatics analyses showed that drugs such as erlotinib, OSI-027, and ibrutinib selectively targeted the CSC-specifically expressed genes. In conclusion, our results represent the first comprehensive characterization of CSCs properties in LSCC at the single-cell level.

Synthesis and resolution of multi-chiral carbonyl-N embedded hetero[7]helicenes for efficient circularly polarized luminescence.

Novel carbonyl-N embedded hetero[7]helicene diastereomers incorporating axially chiral binaphthyl were facilely synthesized and separated. The separated homochiral hetero[7]helicenes exhibit intense green photoluminescence and circularly polarized luminescence (CPL) with luminescence dissymmetry factors (glum) of 1.4 × 10-3 due to the intrinsic helical multiple-resonance skeleton.

Molecular response to the influences of Cu(II) and Fe(III) on forming biogenic manganese oxides by Pseudomonas putida MnB1.

The biogeochemical cycle of biogenic manganese oxides (BioMnOx) is closely associated with the environmental behavior and fate of various pollutants. It is significantly interfered by many metals, such as Cu and Fe. However, the bacterial molecular responses are not clear. Here, the effects of Cu(II) and Fe(III) on oxidation of manganese by Pseudomonas putida MnB1 and the bacterial molecular response mechanisms have been studied. The bacterial oxidation of manganese were promoted by both Fe(III) and Cu(II) and the final manganese oxidation rate of the Cu(II) group exceeded 16 % that of the Fe(III) group. The results of transcriptome indicated that Cu(II) promoted manganese oxidation by up-regulating the expression levels of multicopper oxidase (MCO) and peroxidase(POD), and by stimulating electron transfer, while Fe(III) promoted this process by accelerating the electron transfer and nitrogen cycling, and activating POD. The protein-protein interaction (PPI) network indicated that the MCO genes (mnxG and mcoA) were directly linked to the copper homeostasis proteins (cusA, cusB, czcC and cusF). Cytochrome c was closely related to the genes related to nitrogen cycling (glnA, glnL, and putA) and electrons transfer (cycO, cycD, nuoA, nuoK, and nuoL), which also promoted manganese oxidation. This study provides a molecular level insight into the oxidation of Mn(II) by Pseudomonas putida MnB1 with Cu(II) and/or Fe(III) ions.

Simultaneously inhibit cadmium and arsenic uptake in rice (Oryza sativa L.) by Selenium enhanced iron plaque: Performance and mechanism.

Selenium (Se) fortification is witnessed to simultaneously inhibit absorbing Cadmium (Cd) and Arsenic (As) by rice plants, but the mechanism is unclear. Here, the effects of Se on the root morphology, iron plaque (IP) content, soil Fe2+ content, radial oxygen loss (ROL), and enzyme activities of the rice plants in the soil contaminated by Cd and As were intensively investigated through the hydroponic and soil experiments. Se effectively alleviated the toxic effects of Cd and As on the plants and the dry weight, root length, and root width were increased by 203.18%, 33.41%, and 52.81%, respectively. It also elucidated that ROL was one of the key factors to elevate IP formation by Se and the specific pathways of Se enhancing ROL were identified. ROL of the plants in the experiment group treated by Se was increased 36.76%, and correspondingly IP was magnified 50.37%, compared to the groups with Cd and As. It was owing to Se significantly increased the root porosity (62.11%), facilitating O2 transport to the roots. Additionally, Se enhanced the activities of catalase (CAT) and superoxide dismutase (SOD) to promote the catalytic degradation of ROS induced by Cd and As stress. It indirectly increased O2 release in the rhizosphere, which benefit to form more robust IP serve as stronger barrier to Cd and As. The results of our study provide a novel molecular level insight for Se promoting root IP to block Cd and As uptake by the rice plants.

Transformation of As and Cd associated with Fe-Mn-modified biochar during simultaneous remediation on the contaminated soil.

Here, Fe- and Mn-modified biochar (BC-Fe-Mn) was applied to simultaneously stabilize As and Cd in the contaminated soil. The removal efficiencies for NaHCO3-extractable As and DTPA-extractable Cd by BC-Fe-Mn were 60.8% and 49.6%, respectively. The speciation analyses showed that the transformation to low-crystallinity Fe-bound (F3) As, Fe-Mn oxide-bound (OX) of Cd, and residual As and Cd was primarily attributed to stabilizing the two metal(loid)s. Moreover, the correlation analyses showed that the increase of As in F3 fraction was significantly and positively associated with the increase of OX fraction Mn (r = 0.64). Similarly, OX fraction Cd was increased notably with increasing OX fraction Fe (r = 0.91) and OX fraction Mn (r = 0.76). In addition, a novel dialysis experiment was performed to separate the reacted BC-Fe-Mn from the soil for intensively investigating the stabilization mechanisms for As and Cd by BC-Fe-Mn. The characteristic crystalline compounds of (Fe0.67Mn0.33)OOH and Fe2O3 on the surface of BC-Fe-Mn were revealed by SEM-EDS and XRD. And FTIR analyses showed that α-FeOOH, R-COOFe/Mn+, and O-H on BC-Fe-Mn potentially served as the reaction sites for As and Cd. A crystalline compound of MnAsO4 was found in the soil treated by BC-Fe-Mn in the dialysis experiment. Thus, our results are beneficial to deeper understand the mechanisms of simultaneous stabilization of As and Cd by BC-Fe-Mn in soil and support the application of the materials on a large scale.

Synthesis and biological evaluation of chrysin derivatives containing α-lipoic acid for the treatment of inflammatory bowel disease.

This study introduces newly discovered chrysin derivatives that show potential as candidate molecules for treating inflammatory bowel disease (IBD). Compound 4b, among the synthesized compounds, displayed significant inhibitory effects on monocyte adhesion to colon epithelium induced by TNF-α, with an IC50 value of 4.71 µM. Further mechanistic studies demonstrated that 4b inhibits the production of reactive oxygen species (ROS) and downregulates the expression of ICAM-1 and MCP-1, key molecules involved in monocyte-epithelial adhesion, as well as the transcriptional activity of NF-κB. In vivo experiments have shown that compound 4b exhibits a dose-dependent inhibition of 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats, thereby validating its effectiveness as a colitis inhibitor in animal models. These results indicate that 4b shows considerable promise as a therapeutic agent for managing IBD.

Functional metabolomics characterizes the contribution of farnesoid X receptor in pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome.

Consumption of herbal products containing pyrrolizidine alkaloids (PAs) is one of the major causes for hepatic sinusoidal obstruction syndrome (HSOS), a deadly liver disease. However, the crucial metabolic variation and biomarkers which can reflect these changes remain amphibious and thus to result in a lack of effective prevention, diagnosis and treatments against this disease. The aim of the study was to determine the impact of HSOS caused by PA exposure, and to translate metabolomics-derived biomarkers to the mechanism. In present study, cholic acid species (namely, cholic acid, taurine conjugated-cholic acid, and glycine conjugated-cholic acid) were identified as the candidate biomarkers (area under the ROC curve 0.968 [95% CI 0.908-0.994], sensitivity 83.87%, specificity 96.55%) for PA-HSOS using two independent cohorts of patients with PA-HSOS. The increased primary bile acid biosynthesis and decreased liver expression of farnesoid X receptor (FXR, which is known to inhibit bile acid biosynthesis in hepatocytes) were highlighted in PA-HSOS patients. Furtherly, a murine PA-HSOS model induced by senecionine (50 mg/kg, p.o.), a hepatotoxic PA, showed increased biosynthesis of cholic acid species via inhibition of hepatic FXR-SHP singling and treatment with the FXR agonist obeticholic acid restored the cholic acid species to the normal levels and protected mice from senecionine-induced HSOS. This work elucidates that increased levels of cholic acid species can serve as diagnostic biomarkers in PA-HSOS and targeting FXR may represent a therapeutic strategy for treating PA-HSOS in clinics.

Multimodal neuroimaging network associated with executive function in adolescent major depressive disorder patients via cognition-guided magnetic resonance imaging fusion.

Adolescents are high-risk population for major depressive disorder. Executive dysfunction emerges as a common feature of depression and exerts a significant influence on the social functionality of adolescents. This study aimed to identify the multimodal co-varying brain network related to executive function in adolescent with major depressive disorder. A total of 24 adolescent major depressive disorder patients and 43 healthy controls were included and completed the Intra-Extra Dimensional Set Shift Task. Multimodal neuroimaging data, including the amplitude of low-frequency fluctuations from resting-state functional magnetic resonance imaging and gray matter volume from structural magnetic resonance imaging, were combined with executive function using a supervised fusion method named multimodal canonical correlation analysis with reference plus joint independent component analysis. The major depressive disorder showed more total errors than the healthy controls in the Intra-Extra Dimensional Set Shift task. Their performance on the Intra-Extra Dimensional Set Shift Task was negatively related to the 14-item Hamilton Rating Scale for Anxiety score. We discovered an executive function-related multimodal fronto-occipito-temporal network with lower amplitude of low-frequency fluctuation and gray matter volume loadings in major depressive disorder. The gray matter component of the identified network was negatively related to errors made in Intra-Extra Dimensional Set Shift while positively related to stages completed. These findings may help to deepen our understanding of the pathophysiological mechanisms of cognitive dysfunction in adolescent depression.

Development and application of machine learning models for prediction of soil available cadmium based on soil properties and climate features.

Identifying the key influencing factors in soil available cadmium (Cd) is crucial for preventing the Cd accumulation in the food chain. However, current experimental methods and traditional prediction models for assessing available Cd are time-consuming and ineffective. In this study, machine learning (ML) models were developed to investigate the intricate interactions among soil properties, climate features, and available Cd, aiming to identify the key influencing factors. The optimal model was obtained through a combination of stratified sampling, Bayesian optimization, and 10-fold cross-validation. It was further explained through the utilization of permutation feature importance, 2D partial dependence plot, and 3D interaction plot. The findings revealed that pH, surface pressure, sensible heat net flux and organic matter content significantly influenced the Cd accumulation in the soil. By utilizing historical soil surveys and climate change data from China, this study predicted the spatial distribution trend of available Cd in the Chinese region, highlighting the primary areas with heightened Cd activity. These areas were primarily located in the eastern, southern, central, and northeastern China. This study introduces a novel methodology for comprehending the process of available Cd accumulation in soil. Furthermore, it provides recommendations and directions for the remediation and control of soil Cd pollution.

First Insight into Fetal Exposure to Legacy and Emerging Plasticizers Revealed by Infant Hair and Meconium: Occurrence, Biotransformation, and Accumulation.

Epidemiological studies have demonstrated the embryonic and developmental toxicity of plasticizers. Thus, understanding the in utero biotransformation and accumulation of plasticizers is essential to assessing their fate and potential toxicity in early life. In the present study, 311 infant hair samples and 271 paired meconium samples were collected at birth in Guangzhou, China, to characterize fetal exposure to legacy and emerging plasticizers and their metabolites. Results showed that most of the target plasticizers were detected in infant hair, with medians of 9.30, 27.6, and 0.145 ng/g for phthalate esters (PAEs), organic phosphate ester (OPEs), and alternative plasticizers (APs), and 1.44, 0.313, and 0.066 ng/g for the metabolites of PAEs, OPEs, and APs, respectively. Positive correlations between plasticizers and their corresponding primary metabolites, as well as correlations among the oxidative metabolites of bis(2-ethylhexyl) phthalate (DEHP) and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), were observed, indicating that infant hair retained the major phase-I metabolism of the target plasticizers. While no positive correlations were found in parent compounds or their primary metabolites between paired infant hair and meconium, significant positive correlations were observed among secondary oxidative metabolites of DEHP and DINCH in hair and meconium, suggesting that the primary metabolites in meconium come from hydrolysis of plasticizers in the fetus but most of the oxidative metabolites come from maternal-fetal transmission. The parent compound/metabolite ratios in infant hair showed a decreasing trend across pregnancy, suggesting in utero accumulation and deposition of plasticizers. To the best of our knowledge, this study is the first to report in utero exposure to both parent compounds and metabolites of plasticizers by using paired infant hair and meconium as noninvasive biomonitoring matrices and provides novel insights into the fetal biotransformation and accumulation of plasticizers across pregnancy.

HMGA2 alleviates ferroptosis by promoting GPX4 expression in pancreatic cancer cells.

Pancreatic cancer is one of the most malignant tumor types and is characterized by high metastasis ability and a low survival rate. As a chromatin-binding protein, HMGA2 is widely overexpressed and considered an oncogene with various undefined regulatory mechanisms. Herein, we demonstrated that HMGA2 is highly expressed in pancreatic cancer tissues, mainly distributed in epithelial cells, and represents a subtype of high epithelial-mesenchymal transition. Deletion of HMGA2 inhibits tumor malignancy through cell proliferation, metastasis, and xenograft tumor growth in vivo. Moreover, HMGA2 enhanced the cellular redox status by inhibiting reactive oxygen species and promoting glutathione production. Importantly, ferroptotic cell death was significantly ameliorated in cells overexpressing HMGA2. Conversely, HMGA2 deletion exacerbated ferroptosis. Mechanistically, HMGA2 activated GPX4 expression through transcriptional and translational regulation. HMGA2 binds and promotes cis-element modification in the promoter region of the GPX4 gene by enhancing enhancer activity through increased H3K4 methylation and H3K27 acetylation. Furthermore, HMGA2 stimulated GPX4 protein synthesis via the mTORC1-4EBP1 and -S6K signaling axes. The overexpression of HMGA2 alleviated the decrease in GPX4 protein levels resulting from the pharmacologic inhibition of mTORC1. Conversely, compared with the control, HMGA2 deletion more strongly reduced the phosphorylation of 4EBP1 and S6K. A strong positive correlation between HMGA2 and GPX4 expression was confirmed using immunohistochemical staining. We also demonstrated that HMGA2 mitigated the sensitivity of cancer cells to combination treatment with a ferroptosis inducer and mTORC1 inhibition or gemcitabine. In summary, our results revealed a regulatory mechanism by which HMGA2 coordinates GPX4 expression and underscores the potential value of targeting HMGA2 in cancer treatment.

Adsorption behavior of lead, cadmium, and arsenic on manganese-modified biochar: competition and promotion.

Biochar adsorption of heavy metals has been a research hotspot, yet there has been limited reports on the effect of heavy metal interactions on adsorption efficiency in complex systems. In this study, the adsorbent was prepared by pyrolysis of rice straw loaded with manganese (BC-Mn). The interactions of Pb, Cd and As adsorption on BC-Mn were systematically studied. The results of the adsorption isotherms for the binary metal system revealed a competitive adsorption between Pb and Cd, resulting in decreased Pb (from 214.38 mg/g to 148.20 mg/g) and Cd (from 165.73 mg/g to 92.11 mg/g). A notable promotion occurred between As and Cd, showing an increase from 234.93 mg/g to 305.00 mg/g for As and 165.73 mg/g to 313.94 mg/g for Cd. In the ternary metal system, Pb inhibition did not counteract the promotion of Cd and As. Furthermore, the Langmuir isotherm effectively described BC-Mn's adsorption process in monometallic, binary, and ternary metal systems (R2 > 0.9294). Zeta and FTIR analyses revealed simultaneous competition between Pb and Cd for adsorption on BC-Mn's -OH sites. XPS analysis revealed that As adsorption by BC-Mn facilitated the conversion of MnO2 and MnO to MnOOH, resulting in increased hydroxyl radical production on BC-Mn's surface. Simultaneously, Cd combined with the adsorbed As to form ternary Cd-As-Mn complexes, which expedited the removal of Cd. These results help to provide theoretical support as well as technical support for the treatment of Pb-Cd-As contaminated wastewater.

Extra-Cavity Image Registration via the Aortic Root During Left Ventricular Mapping and Ablation.

BACKGROUND: Computed tomography (CT) image integration is of limited use in left ventricular (LV) ablation due to inadequate accuracy of registration. The current study aimed to investigate the accuracy and feasibility of extra-cavity LV image registration via the coronary cusp. METHODS: Consecutive patients were enrolled as the validation group (n = 41) and feasibility group (n = 48). After extra-cavity registration via the aortic root, the LV anatomy derived from CT image was activated and moved into real space. Accuracy of LV anatomy via this registration method was verified by intracardiac echocardiography reconstruction in the validation group and tested further in the feasibility group via measuring the location differences (<3 mm) and volume difference (<8 mL). RESULTS: In validation group, the LV volume of CT image and ICE map were comparable (113.6 ± 15.5 mL vs. 109.0 ± 15.3 mL, P =.27), and the location difference was 3.1 ± 1.1 mm at LV summit, 1.8 ± 0.9 mm at the free wall, and 1.8 ± 0.7 mm at the LV apex. There was a mean of 2.9 ± 1.2 mm and 3.0 ± 1.0 mm length difference in anterior PM and posterior PM, the position difference of the PM's base was 2.8 ± 0.9 mm for anterior PM and 2.2 ± 0.9 mm for posterior PM. In feasibility group, the distance differences of LV summit, LV septum, LV apex, and LV free averaged 1.8 ± 0.8 mm, 1.5 ± 0.7 mm, 1.4 ± 0.6 mm, 1.3 ± 0.7 mm, respectively. Compared with validation group, acute success (100% vs. 96.5%, P =.51), complications rate (4.9% vs. 2.0%, P = 0.59) and fluoroscopic time (1.6 ± 1.1 vs. 1.9 ± 1.6 minutes, P =.30) exhibited no significant difference, but was significantly reduced with procedure time (74.5 ± 8.1 vs. 61.2 ± 9.5 minutes, P <.001) with CT image registration only. CONCLUSION: LV mapping and ablation could be successfully achieved by extra-cavity registration via coronary cusp without needing positions within LV beforehand.

LncRNA RPARP-AS1 promotes the progression of osteosarcoma cells through regulating lipid metabolism.

Osteosarcoma (OS) is a highly malignant tumor, and its dysregulated lipid metabolism is associated with tumorigenesis and unfavorable prognosis. Interestingly, long noncoding RNAs (lncRNAs) have emerged as pivotal regulators of lipid metabolism, exerting notable impacts on tumor proliferation. Nevertheless, the involvement of RPARP-AS1, a novel lipid metabolism-associated lncRNA, remains unexplored in the context of OS. This study aims to identify functionally relevant lncRNAs impacting OS proliferation and lipid metabolism and seeks to shed light on the upstream regulatory mechanisms governing lipogenic enzyme activity. Based on comprehensive bioinformatic analysis and the establishment of a risk model, we identified seven lncRNAs significantly associated with clinical characteristics and lipid metabolism-related genes in patients with OS. Among these, RPARP-AS1 was selected for in-depth investigation regarding its roles in OS proliferation and lipid metabolism. Experimental techniques including RT-qPCR, Western blot, cell viability assay, assessment, and quantification of free fatty acids (FFAs) and triglycerides (TGs) were utilized to elucidate the functional significance of RPARP-AS1 in OS cells and validate its effects on lipid metabolism. Manipulation of RPARP-AS1 expression via ectopic expression or siRNA-mediated knockdown led to alterations in epithelial-mesenchymal transition (EMT) and expression of apoptosis-associated proteins, thereby influencing OS cell proliferation and apoptosis. Mechanistically, RPARP-AS1 was found to augment the expression of key lipogenic enzymes (FABP4, MAGL, and SCD1) and potentially modulate the Akt/mTOR pathway, thereby contributing to lipid metabolism (involving alterations in FFA and TG levels) in OS cells. Collectively, our findings establish RPARP-AS1 as a novel oncogene in OS cells and suggest its role in fostering tumor growth through the enhancement of lipid metabolism.

Changes of structural functional connectivity coupling and its correlations with cognitive function in patients with major depressive disorder.

BACKGROUND: Previous neuroimaging studies have reported structural and functional brain abnormalities in major depressive disorder (MDD). This study aimed to explore whether the coherence of structural-functional networks was affected by disease and investigate its correlation with clinical manifestations. METHODS: The severity of symptoms and cognitive function of 121 MDD patients and 139 healthy controls (HC) were assessed, and imaging data, including diffusion tensor imaging, T1 structural magnetic resonance imaging (MRI) and resting-state functional MRI, were collected. Spearman correlation coefficients of Kullback-Leibler similarity (KLS), fiber number (FN), fractional anisotropy (FA) and functional connectivity (FC) were calculated as coupling coefficients. Double-weight median correlation analysis was conducted to investigate the correlations between differences in brain networks and clinical assessments. RESULTS: The percentage of total correct response of delayed matching to sample and the percentage of delayed correct response of pattern recognition memory was lower in MDD. Compared with the HC, KLS-FC coupling between the parietal lobe and subcortical area, FA-FC coupling between the temporal and parietal lobe, and FN-FC coupling in the frontal lobe was lower in MDD. Several correlations between structural-functional connectivity and clinical manifestations were identified. LIMITATIONS: First, our study lacks longitudinal follow-up data. Second, the sample size was relatively small. Moreover, we only used the Anatomical Automatic Labeling template to construct the brain network. Finally, the validation of the causal relationship of neuroimaging-behavior factors was still insufficient. CONCLUSIONS: The alternation in structural-functional coupling were related to clinical characterization and might be involved in the neuropathology of depression.

scQTLbase: an integrated human single-cell eQTL database.

Genome-wide association studies (GWAS) have identified numerous genetic variants associated with diseases and traits. However, the functional interpretation of these variants remains challenging. Expression quantitative trait loci (eQTLs) have been widely used to identify mutations linked to disease, yet they explain only 20-50% of disease-related variants. Single-cell eQTLs (sc-eQTLs) studies provide an immense opportunity to identify new disease risk genes with expanded eQTL scales and transcriptional regulation at a much finer resolution. However, there is no comprehensive database dedicated to single-cell eQTLs that users can use to search, analyse and visualize them. Therefore, we developed the scQTLbase (http://bioinfo.szbl.ac.cn/scQTLbase), the first integrated human sc-eQTLs portal, featuring 304 datasets spanning 57 cell types and 95 cell states. It contains ∼16 million SNPs significantly associated with cell-type/state gene expression and ∼0.69 million disease-associated sc-eQTLs from 3 333 traits/diseases. In addition, scQTLbase offers sc-eQTL search, gene expression visualization in UMAP plots, a genome browser, and colocalization visualization based on the GWAS dataset of interest. scQTLbase provides a one-stop portal for sc-eQTLs that will significantly advance the discovery of disease susceptibility genes.

Identification of hypoxia-related gene signatures based on multi-omics analysis in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common type of lung cancer and one of the malignancies with the highest incidence rate and mortality worldwide. Hypoxia is a typical feature of tumour microenvironment (TME), which affects the progression of LUAD from multiple molecular levels. However, the underlying molecular mechanisms behind LUAD hypoxia are not fully understood. In this study, we estimated the level of hypoxia by calculating a score based on 15 hypoxia genes. The hypoxia scores were relatively high in LUAD patients with poor prognosis and were bound up with tumour node metastasis (TNM) stage, tumour size, lymph node, age and gender. By comparison of high hypoxia score group and low hypoxia score group, 1820 differentially expressed genes were identified, among which up-regulated genes were mainly about cell division and proliferation while down-regulated genes were primarily involved in cilium-related biological processes. Besides, LUAD patients with high hypoxia scores had higher frequencies of gene mutations, among which TP53, TTN and MUC16 had the highest mutation rates. As for DNA methylation, 1015 differentially methylated probes-related genes were found and may play potential roles in tumour-related neurobiological processes and cell signal transduction. Finally, a prognostic model with 25 multi-omics features was constructed and showed good predictive performance. The area under curve (AUC) values of 1-, 3- and 5-year survival reached 0.863, 0.826 and 0.846, respectively. Above all, our findings are helpful in understanding the impact and molecular mechanisms of hypoxia in LUAD.

Lusianthridin ameliorates high fat diet-induced metabolic dysfunction-associated fatty liver disease via activation of FXR signaling pathway.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common chronic liver disease, but there are few specific medications for it. Lusianthridin, a major phenanthrene component that originates from Dendrobium Sonia, has various in vitro biological functions. In this study, we aimed to evaluate the therapeutic effects of lusianthridin on high-fat diet (HFD)-induced MAFLD as well as to examine the mechanism of its effects. We fed male mice high-fat-diet for 12 weeks to induce MAFLD and then continued to feed them, either with or without lusianthridin, for another six weeks. We found that lusianthridin decreased serum triacylglycerol, hepatic triacylglycerol, and serum low density lipoprotein cholesterol. It also reduced hepatic lipid accumulation based on the results of morphology analysis. Besides, it improved hepatic inflammation as well, including a decrease in serum alanine aminotransferase and a reduction in macrophage and neutrophil infiltration. Mechanistically, surface plasmon resonance, cell thermal shift assay and dual-luciferase report system results suggested that lusianthridin combined with farnesoid X receptor (FXR) ligand binding region and activated its transcriptional activity. Lusianthridin also decreased de no lipogenesis though inhibiting Srebp1c and downstream Scd-1, Lpin1 and Dgat2 expression in a FXR-dependent manner in oleic acid treated L02 cells. Correspondingly, lusianthridin inhibited Srebp1c and downstream lipogenesis in MAFLD liver tissues of mice at both of genetic and protein levels. Finally, the protective effects of lusianthridin on hepatic steaotosis were abolished in Fxr-/- mice. Taken together, our results suggested that lusianthridin attenuated high-fat-diet induced MAFLD via activation the FXR signaling pathway.