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BACKGROUND: Motor impairments and sensory processing abnormalities are prevalent in autism spectrum disorder (ASD), closely related to the core functions of the primary motor cortex (M1) and the primary somatosensory cortex (S1). Currently, there is limited knowledge about potential therapeutic targets in the subregions of M1 and S1 in ASD patients. This study aims to map clinically significant functional subregions of M1 and S1. METHODS: Resting-state functional magnetic resonance imaging data (NTDâ¯=â¯266) from Autism Brain Imaging Data Exchange (ABIDE) were used for subregion modeling. We proposed a distance-weighted sparse representation algorithm to construct brain functional networks. Functional subregions of M1 and S1 were identified through consensus clustering at the group level. Differences in the characteristics of functional subregions were analyzed, along with their correlation with clinical scores. RESULTS: We observed symmetrical and continuous subregion organization from dorsal to ventral aspects in M1 and S1, with M1 subregions conforming to the functional pattern of the motor homunculus. Significant intergroup differences and clinical correlations were found in the dorsal and ventral aspects of M1 (pâ¯<â¯0.05/3, Bonferroni correction) and the ventromedial BA3 of S1 (pâ¯<â¯0.05/5). These functional characteristics were positively correlated with autism severity. All subregions showed significant results in the ROI-to-ROI intergroup differential analysis (pâ¯<â¯0.05/80). LIMITATIONS: The generalizability of the segmentation model requires further evaluation. CONCLUSIONS: This study highlights the significance of M1 and S1 in ASD treatment and may provide new insights into brain parcellation and the identification of therapeutic targets for ASD.
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The low efficiency of charge carrier separation is a major limitation hindering the application of photocatalytic technology. Constructing S-scheme heterojunction photocatalysts not only effectively promotes the separation of charge carriers, but also maximizes the oxidative and reductive capabilities of the two monomers. In this study S-scheme heterogeneous InVO4/Bi5O7I photocatalyst was synthesized by hydrothermal method combined with calcination. The optimal sample 20 % InVO4/Bi5O7I can completely deactivate Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) in 30 min, remove 20 mg/L TC 76.0 % in 60 min and 20 mg/L BPA 93.0 % in 90 min. Intermediate products of TC and BPA degradation were detected using LC-MS, and possible degradation pathways were proposed. The photocurrent and electrochemical impedance spectroscopy (EIS) tests confirm that InVO4/Bi5O7I exhibits excellent photocurrent intensity and photocarrier migration ability, which are crucial reasons for the enhancement of the photocatalytic performance of the InVO4/Bi5O7I composite. Capture experiments indicate that OH, O2-, h+ and e-are reactive species. EPR further confirms the generation of OH and O2-. Combined with Kelvin probe force microscopy (KPFM) and band structure analysis, it is proposed that InVO4/Bi5O7I has an S-scheme charge transfer mechanism.
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Background: LIN9, a gene associated with various cancers, is considered a tumor suppressor. However, the role of LIN9 in lung adenocarcinoma (LUAD) remains unknown. In this study, we aimed to assess the role of LIN9 in the occurrence and prognosis of LUAD. Methods: Using three-tier HTSeq count RNA sequencing data from The Cancer Genome Atlas, we assessed LIN9 expression for the LUAD dataset using the DESeq2 R package and RT-qPCR experiments. Biological functions were assessed using gene set enrichment analysis (clusterProfiler and GOplot). The expression of LIN9 and the infiltration of immune cells were assessed by Single-sample gene set enrichment analysis. We conducted correlation study using clinical characteristics and receiver operating characteristic curve analysis. The predictive value of LIN9 was determined using univariate and multivariate Cox regression as well as Kaplan-Meier analysis. Additionally, functional studies were conducted to validate its role in the progression of LUAD. Results: Expression of LIN9 was significantly elevated in LUAD, primarily influencing cell cycle, division, and signaling pathways. High LIN9 expression correlated positively with the infiltration of Th2 cells and inversely with that of plasmacytoid dendritic cells. Furthermore, LIN9 was associated with older age and advanced clinical stages, posing risks to overall, progression-free, and disease-specific survival. LIN9 served as a good diagnostic marker, particularly in females, patients aged over 65, and those with clinical N1-3 and M1 stages. Elevated LIN9 expression enhanced proliferation, migration, and invasion of LUAD cells. Conclusion: High LIN9 expression potentially contributes to LUAD occurrence through cell cycle regulation and chromosomal modification. It promotes the malignant characteristics of LUAD cells and holds prognostic value for affected patients.
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BACKGROUND: FMX101 4%, as a topical foam formulation of minocycline, has been approved by US Food and Drug Administration for the treatment of moderate-to-severe acne vulgaris (AV). OBJECTIVE: To evaluate the efficacy and safety of FMX101 4% in treating Chinese subjects with moderate-to-severe facial AV. METHODS: This was a multi-centre, randomized, double-blind, vehicle-controlled phase 3 study in Chinese subjects with moderate-to-severe AV. Eligible subjects were randomized 2:1 to receive either FMX101 4% or vehicle foam treatment for 12 weeks. The primary efficacy endpoint was the change in inflammation lesion count (ILC) from baseline at week 12. The key secondary endpoint was the treatment success rate according to Investigator's Global Assessment (IGA) at week 12. RESULTS: In total, 372 subjects were randomized into two groups (FMX101 4% group, n = 248; vehicle group, n = 124). After 12 weeks treatment, the reduction in ILC from baseline was statistically significant in favour of FMX101 4%, compared with vehicle foam (-21.0 [0.08] vs. -12.3 [1.14]; LSM [SE] difference, -8.7 [1.34]; 95% CI [-11.3, -6.0]; p < 0.001). FMX101 4% treatment yielded significantly higher IGA treatment success rate at week 12 as compared to the control treatment (8.06% vs. 0%). Applying FMX101 4% also resulted in significant reduction in noninflammatory lesion count (nILC) versus vehicle foam at week 12 (-19.4 [1.03] vs. -14.9 [1.47]; LSM [SE] difference, -4.5 [1.74]; 95% CI [-8.0, -1.1]; p = 0.009). Most treatment-emergent adverse events (TEAEs) were mild-to-moderate in severity, and no treatment-related treatment-emergent serious adverse event (TESAE) occurred. Thus, FMX101 4% was considered to be a safe and well-tolerated product during the 12-week treatment period. CONCLUSION: FMX101 4% treatment for 12 weeks could lead to significantly reduced ILC and nILC, and improved IGA treatment success rate in Chinese subjects with moderate-to-severe facial AV. It also showed a well acceptable safe and tolerability profile.
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Missingness in intensive longitudinal data triggered by latent factors constitute one type of nonignorable missingness that can generate simultaneous missingness across multiple items on each measurement occasion. To address this issue, we propose a multiple imputation (MI) strategy called MI-FS, which incorporates factor scores, lag/lead variables, and missing data indicators into the imputation model. In the context of process factor analysis (PFA), we conducted a Monte Carlo simulation study to compare the performance of MI-FS to listwise deletion (LD), MI with manifest variables (MI-MV, which implements MI on both dependent variables and covariates), and partial MI with MVs (PMI-MV, which implements MI on covariates and handles missing dependent variables via full-information maximum likelihood) under different conditions. Across conditions, we found MI-based methods overall outperformed the LD; the MI-FS approach yielded lower root mean square errors (RMSEs) and higher coverage rates for auto-regression (AR) parameters compared to MI-MV; and the PMI-MV and MI-MV approaches yielded higher coverage rates for most parameters except AR parameters compared to MI-FS. These approaches were also compared using an empirical example investigating the relationships between negative affect and perceived stress over time. Recommendations on when and how to incorporate factor scores into MI processes were discussed.
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As the development of aluminum-ion batteries is still in its infancy, researchers are still dedicated to exploring suitable host materials and investigating their aluminum intercalation behaviours. Here, a series of cyanido-bridged chain compounds with the formula {[FeIII(Tp)(CN)3]2[MII(H2O)2]}n (M = Ni, Co, Mn, Zn, Cu) are studied as cathode electrodes for aluminum-ion batteries with [EMIm]Cl-AlCl3 (1-ethyl-3-methylimidazolium chloride-AlCl3) ionic liquid as the electrolyte. The electrochemical properties suggested Fe3+/Fe2+ to be the redox-active couple during the aluminum intercalation and deintercalation processes of these compounds, and the observed maximum specific capacity obtained by the Fe-Co compound is 200 mA h g-1 despite the rapid specific capacity fading. To gain a deeper understanding of the capacity decay suffered by these compounds, further investigation was conducted to explore the evolution of compounds during the electrochemical measurements. It has been attributed to the following reasons: 1. thermodynamic instability results in the transformation/damage of two of the chain structures (for the Fe-Ni and Fe-Co compounds) during heat treatment on electrodes, a crucial step in electrode preparation; 2. the acidic nature of the electrolyte triggers the destruction of the chain structure, with the appearance of partial reduction of Fe3+ to Fe2+, and a new interaction of the cyano group with aluminum; 3. the high charge density of inserted Al ions makes the chain structure suffer from structural damage during both the charging and discharging processes. The progressive accumulation of trapped intercalated ions hampers their involvement in the reaction, consequently decreasing electrochemical reversibility.
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MicroRNAs (miRNAs) have been demonstrated to act as crucial modulators with considerable impacts on the immune system. Cottonseed meal is often used as a protein source in aqua feed, cottonseed meal contains gossypol, which is harmful to animals. However, there is a lack of research on the role of miRNAs in fish exposed to gossypol stress. To determine the regulatory effects of miRNAs on gossypol toxicity, Cyprinus carpio were given to oral administration of 20 mg/kg gossypol for 7 days, and the gossypol concentration in the tissues was tested. Then, we detected spleen index, histology, immune enzyme activities of fish induced by gossypol. The results of miRNA sequencing revealed 8 differentially expressed miRNAs in gossypol group, and miR-214_L-1R+4 was found involved in immune response induced by gossypol. The potential targets of miR-214_L-1R+4 were predicted, and found a putative miR-214_L-1R+4 binding site in the 3'UTR of MyD88a. Furthermore, dual-luciferase reporter assays displayed miR-214_L-1R+4 decreased MyD88a expression through binding to the 3'UTR of MyD88a. Moreover, miR-214_L-1R+4 antagomir were intraperitoneally administered to C. carpio, down-regulated miR-214_L-1R+4 could increase MyD88a expression, as well as inflammatory cytokines and anti-inflammatory cytokines expression. These findings revealed that miR-214_L-1R+4 via the MyD88-dependent signaling pathway modulate the immune response to gossypol in C. carpio spleen.
Subject(s)
Carps , Fish Proteins , Gossypol , MicroRNAs , Myeloid Differentiation Factor 88 , Signal Transduction , Animals , Carps/immunology , Carps/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Gossypol/pharmacology , Gossypol/administration & dosage , Signal Transduction/drug effects , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/metabolism , Fish Proteins/genetics , Fish Proteins/immunology , Fish Proteins/metabolism , Immunity, Innate/drug effects , Immunity, Innate/geneticsABSTRACT
Fungi as heterotrophs are key participants in the decomposition of organic materials and the transformation of nutrients in agroecosystems. Ditch-buried straw return as a novel conservation management strategy can improve soil fertility and alter hydrothermal processes. However, how ditch-buried straw return strategies affect the soil fungal community is still unclear. Herein, a 7-year field trial was conducted to test the influences of burial depth (0, 10, 20, 30, and 40 cm) and the amount of ditch-buried straw (half, full, double) on the diversity, composition, and predicted functions of a soil fungal community, as well as the activities of carbon-degraded enzymes. Under the full amount of straw burial, the abundance of phylum Ascomycota was 7.5% higher as compared to other burial amount treatments. This further increased the activity of cellobiohydrolase by 32%, as revealed by the positive correlation between Ascomycota and cellobiohydrolase. With deeper straw burial, however, the abundance of Ascomycota and ß-D-glucopyranoside activity decreased. Moreover, genus Alternaria and Fusarium increased while Mortierella decreased with straw burial amount and depth. FUNgild prediction showed that plant fungal pathogens were 1- to 2-fold higher, whilst arbuscular mycorrhizal fungi were 64% lower under straw buried with double the amount and at a depth of 40 cm. Collectively, these findings suggest that ditch-buried straw return with a full amount and buried at a depth less than 30 cm could improve soil nutrient cycles and health and may be beneficial to subsequent crop production.
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BACKGROUND: Neoadjuvant treatment has been developed as a systematic approach for patients with early breast cancer and has resulted in improved breast-conserving rate and survival. However, identifying treatment-sensitive patients at the early phase of therapy remains a problem, hampering disease management and raising the possibility of disease progression during treatment. METHODS: In this retrospective analysis, we collected 2-deoxy-2-[F-18] fluoro-d-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) images of primary tumor sites and axillary areas and reciprocal clinical pathological data from 121 patients who underwent neoadjuvant treatment and surgery in our center. The univariate and multivariate logistic regression analyses were performed to investigate features associated with pathological complete response (pCR). An 18F-FDG PET/CT-based prediction model was trained, and the performance was evaluated by receiver operating characteristic curves (ROC). RESULTS: The maximum standard uptake values (SUVmax) of 18F-FDG PET/CT were a powerful indicator of tumor status. The SUVmax values of axillary areas were closely related to metastatic lymph node counts (Râ =â 0.62). Moreover, the early SUVmax reduction rates (between baseline and second cycle of neoadjuvant treatment) were statistically different between pCR and non-pCR patients. The early SUVmax reduction rates-based model showed great ability to predict pCR (AUCâ =â 0.89), with all molecular subtypes (HR+HER2-, HR+HER2+, HR-HER2+, and HR-HER2-) considered. CONCLUSION: Our research proved that the SUVmax reduction rate of 18F-FDG PET/CT contributed to the early prediction of pCR, providing rationales for utilizing PET/CT in NAT in the future.
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Nandina domestica: Thunb. is a traditional Chinese herbal drug that has long been used in China and Japan for the treatment of colds, fevers, asthma, chronic bronchitis, conjunctivitis, whooping cough, pharyngeal tumors, etc. Published data have reported at least 366 constituents from N. domestica, including alkaloids, flavonoids, lignans, terpenoids, phenolic acids and their derivatives, fatty acids, and others. Of these, the isoquinoline alkaloids are considered characteristic markers for N. domestica. These alkaloids also showed the most promising bioactivities. The crude extracts or semi-purified constituents of N. domestica exhibit a variety of activities, including antitumor, dermatological, anti-inflammatory, antioxidant, antimicrobial, and detoxification activities, as well as effects on respiratory system, etc. The fruit is considered poisonous when eaten raw, with nausea, vomiting, diarrhea, and abdominal pain as side effects after ingestion. Most traditional uses are supported by biological activities demonstrated in modern experimental studies, suggesting a potential medicinal value of N. domestica. However, more information is needed on its mechanisms of activity, pharmacokinetic profile of the constituents, and its safety and efficacy profile in humans.
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Background: Qiguiyin decoction (QGYD) is a traditional Chinese medicine (TCM) and its combined application with levofloxacin (LVFX) has been confirmed effective in the clinical treatment of multidrug-resistant Pseudomonas aeruginosa (MDR PA) infection. This study investigated the therapeutic effect and possible mechanism of QGYD in sensitizing LVFX against MDR PA infection. Materials and Methods: Pulmonary infections were induced in rats by MDR PA. The changes in pharmacokinetics-pharmacodynamics (PK-PD) parameters of LVFX after combined with QGYD were investigated in MDR PA-induced rats. Subsequently, the correlation between PK and PD was analyzed and PK-PD models were established to elucidate the relationship between QGYD-induced alterations in LVFX metabolism and its sensitization to LVFX. Antibody chip technology was used to detect the levels of inflammatory factors, suggesting the relationship between the beneficial effect of immune regulation and the sensitization of QGYD. Results: QGYD significantly enhanced the therapeutic efficacy of LVFX against MDR PA infection. The combination of QGYD changed the PK parameters of LVFX such as Tmax, t1/2, MRT, Vd/F, CL/F and PD parameters such as MIC, AUC0-24h/MIC. Predicted results from PK-PD models demonstrated that the antibacterial effect of LVFX was significantly enhanced with the combination of QGYD, consistent with experimental findings. Antibody chip results revealed that the combination of QGYD made IL-1 ß, IL-6, TNF- α, IL-10, and MCP-1 levels more akin to those of the blank group. Conclusion: These findings indicated that QGYD could change the PK-PD behaviors of LVFX and help the body restore immune balance faster. This implied that a potential drug interaction might occur between QGYD and LVFX, leading to improved clinical efficacy when combined.
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Climate warming poses a serious threat to soil biodiversity and crop yield. Application of organic fertilizer has been extensively practiced to improve soil health and crop productivity. However, information is limited about the effects of organic fertilizer on microbial communities and diversity (richness) under warming. Thus, to investigate the interactive effects of temperature (ambient temperature and warming) and fertilizer (chemical fertilizer and partial substitution of chemical fertilizer with organic fertilizer) on microbial properties and wheat yield, a two-factorial pot experiment was conducted using soils with high and low fertility The results showed that warming and organic fertilizer had minor effects on bacterial Shannon and Simpson indexes. Due to concomitant reductions in soil moisture, warming decreased the average Chao index by 5.4 % and Ace index by 3.8 % for soils with high and low fertility (P < 0.05). High-throughput sequence presented that dominated genus was Bacillus with spore-forming ability. Under warming and drying conditions, microbes with adaptive traits (spore-forming ability) would outcompete the other microbes, and decrease microbial Chao and Ace index (richness). However, organic fertilizer counteracted the adverse effects of warming on microbial richness attributed to positive interaction between temperature and fertilizer on soil nutrients and organic carbon. The strong relationships between bacterial richness and wheat yield, as well as soil nutrients, highlighted the importance of soil biodiversity in improving soil nutrients and crop productivity. Partial substitution of chemical fertilizer with organic fertilizer significantly increased wheat yield by 27.1 % and 14.9 % under ambient temperature and by 28.0 % and 19.6 % under warming for soils with high and low fertility, respectively. Overall, this study provided the possibility to increase bacterial richness related to nutrient turnover and crop production by organic fertilizer application with reduced chemical fertilizer, especially under climate warming.
Subject(s)
Fertilizers , Soil Microbiology , Soil , Triticum , Triticum/microbiology , Soil/chemistry , Biodiversity , Global Warming , Microbiota , Bacteria , Agriculture/methodsABSTRACT
Phase measuring deflectometry (PMD) is a key measurement technology for specular surfaces form measurement. Compared with conventional PMD techniques, the near optical coaxial PMD (NCPMD) can achieve compact configuration, light weight and reducing measurement error caused by shadows of the surface structures through utilizing a plate beamsplitter. However, the introduction of the plate beamsplitter will affect the measurement accuracy of the NCPMD system. The refraction of the plate beamsplitter needs to be considered. In this work, a virtual system of NCPMD was established, and an error model of the NCPMD system by considering the refraction influence of the plate beamsplitter was presented to analyze the shape reconstruction error caused by the plate beamsplitter. Moreover, the calibration method of the beamsplitter and the ray tracing algorithm to achieve error compensation of the beamsplitter were proposed. The proposed error compensation method can effectively improve the measurement accuracy of NCPMD system which has been confirmed by surface measurement experiments.
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Intracerebral hemorrhage (ICH) can induce intensive oxidative stress, neuroinflammation, and brain cell apoptosis. However, conventional methods for ICH treatment have many disadvantages. There is an urgent need for alternative, effective therapies with minimal side effects. Pharmacodynamics experiment, molecular docking, network pharmacology, and metabolomics were adopted to investigate the treatment and its mechanism of Jingfang Granules (JFG) in ICH. In this study, we investigated the therapeutic effects of JFG on ICH using behavioral, brain water content and Magnetic resonance imaging experiments. However, the key active component and targets of JFG remain unknown. Here we verified that JFG was beneficial to improve brain injury after ICH. A network pharmacology analysis revealed that the anti-inflammatory effect of JFG is predominantly mediated by its activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway through Luteolin, (+)-Anomalin and Phaseol and their targeting of AKT1, tumor necrosis factorα (TNF-α), and interleukin-1ß (IL-1ß). Molecular docking analyses revealed an average affinity of -8.633 kcal/mol, indicating a binding strength of less than -5 kcal/mol. Metabolomic analysis showed that JFG exerted its therapeutic effect on ICH by regulating metabolic pathways, such as the metabolism of taurine and hypotaurine, biosynthesis of valine, leucine, and isoleucine. In conclusion, we demonstrated that JFG attenuated neuroinflammation and BBB injury subsequent to ICH by activating the PI3K/Akt signaling pathway.
Subject(s)
Blood-Brain Barrier , Cerebral Hemorrhage , Drugs, Chinese Herbal , Molecular Docking Simulation , Cerebral Hemorrhage/drug therapy , Cerebral Hemorrhage/metabolism , Animals , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Drugs, Chinese Herbal/pharmacology , Male , Neuroinflammatory Diseases/drug therapy , Neuroinflammatory Diseases/metabolism , Neuroprotective Agents/pharmacology , Signal Transduction/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Mice , Rats , Anti-Inflammatory Agents/pharmacology , Network Pharmacology , Disease Models, AnimalABSTRACT
OBJECTIVE: Patients undergoing oral and maxillofacial flap reconstruction often need blood transfusions due to massive blood loss. With the increasing limitations of allogeneic blood transfusion (ABT), doctors are considering acute normovolemic hemodilution (ANH) because of its advantages. By comparing the differences in the (Δ) blood indices and postoperative complications of patients receiving ABT or ANH during the reconstruction and repair of oral and maxillofacial tumor flaps, this study's purpose was to provide a reference for the clinical application of ANH. METHODS: The clinical data of 276 patients who underwent oral and maxillofacial flap reconstruction from September 25, 2017, to October 11, 2021, in the Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, were retrospectively analyzed. According to the intraoperative blood transfusion mode, the patients were divided into two groups: ABT and ANH. The differences in the (Δ) blood indices and the incidence of postoperative complications between the groups were analyzed. RESULTS: Among the 276 patients who had ANH (124/276) and ABT (152/276), there were no differences in (Δ) Hb, (Δ) PT, or (Δ) FIB (P > 0.05), while (Δ) WBC, (Δ) PLT, (Δ) APTT and (Δ) D-dimer were significantly different (P < 0.05). The blood transfusion method was not an independent factor for flap crisis (P > 0.05). The wound infection probability in patients with high post-PTs was 1.953 times greater than that in patients with low post-PTs (OR = 1.953, 95% CI: 1.232 â¼ 3.095, P = 0.004). A normal or overweight BMI was a protective factor for pulmonary infection, and the incidence of pulmonary infection in these patients was only 0.089 times that of patients with a low BMI (OR = 0.089, 95% CI: 0.017 â¼ 0.462). Moreover, a high ASA grade promoted the occurrence of pulmonary infection (OR = 6.373, 95% CI: 1.681 â¼ 24.163). The blood transfusion mode (B = 0.310, ß = 0.360, P < 0.001; ANH: ln hospital stay = 2.20 ± 0.37; ABT: ln hospital stay = 2.54 ± 0.42) improved the length of hospital stay. CONCLUSION: Preoperative and postoperative blood transfusion (Δ) Hb, (Δ) PT, and (Δ) FIB did not differ; (Δ) WBC, (Δ) PLT, (Δ) APTT, and (Δ) D-dimer did differ. There was no difference in the effects of the two blood transfusion methods on flap crisis, incision infection or lung infection after flap reconstruction, but ANH resulted in a 3.65 day shorter average hospital stay than did ABT.
Subject(s)
Blood Transfusion , Hemodilution , Plastic Surgery Procedures , Postoperative Complications , Surgical Flaps , Humans , Retrospective Studies , Male , Female , Middle Aged , Postoperative Complications/etiology , Plastic Surgery Procedures/methods , Plastic Surgery Procedures/adverse effects , Blood Transfusion/statistics & numerical data , Hemodilution/methods , Adult , Aged , Oral Surgical Procedures/adverse effects , Oral Surgical Procedures/methods , Blood Loss, SurgicalABSTRACT
BACKGROUND AND HYPOTHESIS: Schizophrenia (SZ) is a prevalent mental disorder that imposes significant health burdens. Diagnostic accuracy remains challenging due to clinical subjectivity. To address this issue, we explore magnetic resonance imaging (MRI) as a tool to enhance SZ diagnosis and provide objective references and biomarkers. Using deep learning with graph convolution, we represent MRI data as graphs, aligning with brain structure, and improving feature extraction, and classification. Integration of multiple modalities is expected to enhance classification. STUDY DESIGN: Our study enrolled 683 SZ patients and 606 healthy controls from 7 hospitals, collecting structural MRI and functional MRI data. Both data types were represented as graphs, processed by 2 graph attention networks, and fused for classification. Grad-CAM with graph convolution ensured interpretability, and partial least squares analyzed gene expression in brain regions. STUDY RESULTS: Our method excelled in the classification task, achieving 83.32% accuracy, 83.41% sensitivity, and 83.20% specificity in 10-fold cross-validation, surpassing traditional methods. And our multimodal approach outperformed unimodal methods. Grad-CAM identified potential brain biomarkers consistent with gene analysis and prior research. CONCLUSIONS: Our study demonstrates the effectiveness of deep learning with graph attention networks, surpassing previous SZ diagnostic methods. Multimodal MRI's superiority over unimodal MRI confirms our initial hypothesis. Identifying potential brain biomarkers alongside gene biomarkers holds promise for advancing objective SZ diagnosis and research in SZ.
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To identify protein biomarkers capable of early prediction regarding the distinguishing malignant pleural effusion (MPE) from benign pleural effusion (BPE) in patients with lung disease. A four-dimensional data independent acquisition (4D-DIA) proteomic was performed to determine the differentially expressed proteins in samples from 20 lung adenocarcinoma MPE and 30 BPE. The significantly differential expressed proteins were selected for Gene Ontology (GO) enrichment and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. Protein biomarkers with high capability to discriminate MPE from BPE patients were identified by Random Forest (RF) algorithm prediction model, whose diagnostic and prognostic efficacy in primary tumors were further explored in public datasets, and were validated by ELISA experiment. 50 important proteins (30 up-regulated and 20 down-regulated) were selected out as potential markers to distinguish the MPE from BPE group. GO analysis revealed that those proteins involving the most important cell component is extracellular space. KEGG analysis identified the involvement of cellular adhesion molecules pathway. Furthermore, the Area Under Curve (AUC) of these proteins were ranged from 0.717 to 1.000ï¼with excellent diagnostic properties to distinguish the MPE. Finally, significant survival and gene and protein expression analysis demonstrated BPIFB1, DPP4, HPRT1 and ABI3BP had high discriminating values. SIGNIFICANCE: We performed a 4D-DIA proteomics to determine the differentially expressed proteins in pleural effusion samples from MPE and BPE. Some potential protein biomarkers were identified to distinguish the MPE from BPE patients., which may provide helpful diagnostic and therapeutic insights for lung cancer. This is significant because the median survival time of patients with MPE is usually 4-12 months, thus, it is particularly important to diagnose MPE early to start treatments promptly. The most common causes of MPE are lung cancers, while pneumonia and tuberculosis are the main causes of BPE. If more diagnostic markers could be identified periodically, there would be an important significance to clinical diagnose and treatment with drugs in lung cancer patients.
Subject(s)
Biomarkers, Tumor , Lung Neoplasms , Pleural Effusion, Malignant , Pleural Effusion , Proteomics , Humans , Pleural Effusion, Malignant/metabolism , Pleural Effusion, Malignant/diagnosis , Biomarkers, Tumor/analysis , Biomarkers, Tumor/metabolism , Proteomics/methods , Female , Male , Lung Neoplasms/metabolism , Lung Neoplasms/diagnosis , Pleural Effusion/metabolism , Pleural Effusion/diagnosis , Diagnosis, Differential , Middle Aged , Neoplasm Proteins/metabolism , Aged , Adenocarcinoma of Lung/metabolism , Adenocarcinoma of Lung/diagnosisABSTRACT
BACKGROUND: Estrogen receptor (ER) positive human epidermal growth factor receptor 2 (HER2) negative breast cancer (ER+/HER2-BC) and triple-negative breast cancer (TNBC) are two distinct breast cancer molecular subtypes, especially in tumor immune microenvironment (TIME). The TIME of TNBC is considered to be more inflammatory than that of ER+/HER2-BC. Natural killer (NK) cells are innate lymphocytes that play an important role of tumor eradication in TME. However, studies focusing on the different cell states of NK cells in breast cancer subtypes are still inadequate. METHODS: In this study, single-cell mRNA sequencing (scRNA-seq) and bulk mRNA sequencing data from ER+/HER2-BC and TNBC were analyzed. Key regulator of NK cell suppression in ER+/HER2-BC, S100A9, was quantified by qPCR and ELISA in MCF-7, T47D, MDA-MB-468 and MDA-MB-231 cell lines. The prognosis predictability of S100A9 and NK activation markers was evaluated by Kaplan-Meier analyses using TCGA-BRAC data. The phenotype changes of NK cells in ER+/HER2-BC after overexpressing S100A9 in cancer cells were evaluated by the production levels of IFN-gamma, perforin and granzyme B and cytotoxicity assay. RESULTS: By analyzing scRNA-seq data, we found that multiple genes involved in cellular stress response were upregulated in ER+/HER2-BC compared with TNBC. Moreover, TLR regulation pathway was significantly enriched using differentially expressed genes (DEGs) from comparing the transcriptome data of ER+/HER2-BC and TNBC cancer cells, and NK cell infiltration high/low groups. Among the DEGs, S100A9 was identified as a key regulator. Patients with higher expression levels of S100A9 and NK cell activation markers had better overall survival. Furthermore, we proved that overexpression of S100A9 in ER+/HER2-cells could improve cocultured NK cell function. CONCLUSION: In conclusion, the study we presented demonstrated that NK cells in ER+/HER2-BC were hypofunctional, and S100A9 was an important regulator of NK cell function in ER+BC. Our work contributes to elucidate the regulatory networks between cancer cells and NK cells and may provide theoretical basis for novel drug development.
Subject(s)
Breast Neoplasms , Calgranulin B , Killer Cells, Natural , Receptors, Estrogen , Humans , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Female , Calgranulin B/genetics , Calgranulin B/metabolism , Receptors, Estrogen/metabolism , Breast Neoplasms/immunology , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Tumor Microenvironment/immunology , Triple Negative Breast Neoplasms/immunology , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathology , Prognosis , Cell Line, Tumor , Gene Expression Regulation, NeoplasticABSTRACT
Excessive cadmium (Cd) concentration in wheat grain is becoming a widespread concern in China. Considering the complexity of Cd transfer in the soil-wheat system, how the Cd risk in wheat grain be accurately predicted from the limited details available is of great significance for the risk management of Cd. Bayes' theory could leverage existing data by combining prior information and observational data, providing a promising strategy with which to calculate a more robust posterior probability of a grain sample exceeding the food safety standard (FSS) for Cd (0.1 mg kg-1). In the current study, a risk prediction model, based on Bayes' theory, was established to achieve a more accurate prediction of the wheat grain Cd risk from a limited number of soil parameters. The risk prediction model could predict the risk probability of wheat grain with a Cd concentration exceeding the FSS under a given soil concentration of either total Cd or diethylenetriaminepentaacetic acid (DTPA)-extractable Cd. Soil total Cd concentration proved to be a better variable for the model with greater predictive accuracy. The model predicted that fewer than 5% of the wheat grain would have a Cd concentration exceeding the FSS when grown in soil with a total Cd concentration of less than 0.299 mg kg-1. The risk probability rose significantly to 50% when the soil total Cd reached 0.778 mg kg-1. The accuracy of the model was greater than the widely applied multiple linear regression model, whereas previously published data from similar soil conditions also confirmed that the Bayesian model could predict wheat Cd risk with minimal error. The proposed model provides an accurate, accessible and cost-effective methodology for predicting Cd risk in wheat grown in alkaline soils before harvest. The wider application to other soil conditions, crops or contaminants using the Bayesian model is also promising for risk management authorities.
Subject(s)
Bayes Theorem , Cadmium , Soil Pollutants , Soil , Triticum , Cadmium/analysis , Triticum/chemistry , Triticum/growth & development , Soil Pollutants/analysis , Soil/chemistry , China , Risk Assessment , Edible Grain/chemistry , Food Contamination/analysis , Models, TheoreticalABSTRACT
The electrical manipulation of the magnetic transition and spin-polarized states has attracted extensive attention in the field of spintronics. In this work, we perform a detailed study on the electronic and magnetic properties of the carrier-doped monolayer CrCTe3by using first-principles calculation. It is found that, the magnetic transition from Néel-antiferomagnetic (nAFM) to ferromagnetic (FM) is observed in the case of the electron doping, while for hole doping a magnetic transition sequence of nAFMâzigzag-AFMâFM is observed in the monolayer CrCTe3. Interestingly, the carrier doping induced FM ground state always exhibits half-metallicity with full spin polarization. Moreover, the spin polarity of the half-metallic electronic states is opposite for electron and hole doping, meaning that the spin polarization direction can be tuned by manipulating a gate voltage. The Monte Carlo calculations show that the magnetic transition temperature of the doped FM CrCTe3is rapidly increased with the increasing doping concentration and is extremely expected to achieve room temperature at a suitable doping concentration. These findings demonstrate that the monolayer AFM system possesses a potential application in spintronic devices with electrically tunable spin polarization.