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Abstract Objective This study aims to investigate the effect of CD206 on the progression of hepatocellular carcinoma (HCC) and the regulation of the tumour immune microenvironment. Methods A subcutaneous mouse model of HCC was established and treated with CD206-overexpressing adenovirus by tail vein injection or CD206 antibody C068C2 by intratumoral injection. The hepatocarcinoma-bearing mice were divided into four groups (IgG+ tail vein adenovirus group, IgG group, C068C2+ tail vein adenovirus group and C068C2 group) to observe the changes in tumour weight and volume with different expression levels of CD206. The proportion of M2-type tumour-associated macrophages (TAMs) was detected by flow cytometry and immunofluorescence. The apoptosis of tumour cells was detected using terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining, and inflammatory factors in serum and tissues were detected using the ENZYME-LINKED IMMUNOSORBENT ASSAY. Results Compared with the mice with low CD206 expression, the hepatocarcinoma-bearing mice with high CD206 expression in HCC exhibited faster tumour growth and more aggressive progression. Flow cytometry and immunofluorescence staining revealed that the expression level of CD206-positive M2-type TAMs was highest in the IgG + adenovirus group and lowest in the C068C2 group (p

Abstract Background Non-suicidal self-injury (NSSI) is a significant public health concern among adolescents with major depressive disorders (MDD). Although previous research has linked child maltreatment (CM) to NSSI, the precise mechanisms remain unclear. This study aims to investigate the association between CM, cognitive reappraisal (CR), negative coping styles (NC) and NSSI in adolescents with MDD, from the perspectives of both Latent Variable Theory and the Network Theory of Mental Disorder. Methods A sample of 651 adolescents with MDD was recruited from January to December 2023. Data on CM, CR, NC, and NSSI were collected through paper-based self-reported questionnaires. Data analysis primarily involved structural equation modeling and network analysis. Results The reporting rate of NSSI among adolescents with MDD was 48.2%. CM showed a significant positive correlation with NSSI. NSSI was affected by CM through three paths: the mediating role of CR, the mediating role of NC, and the chain mediating role of both CR and NC. Emotional abuse (EA) was the central node, while NSSI, EA, and “The urge to cry quietly when faced with troubles“(NC10) were the key bridge nodes. Conclusions This study is the first to use both structural equation modeling and network analysis to explore the explore the relationship between CM, CR, NC, and NSSI in adolescents with MDD, providing a theoretical basis for future early prevention and targeted interventions for adolescents with MDD.

With the rapid development of the civil aviation industry, flight delays caused by convective weather are becoming increasingly severe. In terminal airspace with complex traffic environments, these delays can propagate to subsequent arrivals and departures, thereby affecting the operational efficiency of the terminal airspace and potentially disrupting the entire air traffic system. Accurate short-term forecasting of convective weather can help reduce flight delays, improve airspace utilization, and decrease the workload of air traffic controllers. This study, grounded in supervised deep learning, addresses civil aviation operational requirements by developing a short-term forecasting model for convective weather based on a Convolutional Neural Network-Transformer (CNN-Transformer). The model leverages eight types of weather products from civil aviation weather radar and ERA5, including basic reflectance, echo top, vertically integrated liquid, relative humidity, temperature, U-component of wind, V-component of wind, and vertical velocity. The training was conducted using 241 datasets, totaling 23,881 samples. To evaluate the model’s validity, ablation studies were performed on each parameter, and its performance was compared with the Centroid Method, Optical Flow, CNN-CNN, and CNN-Long Short-Term Memory (CNN-LSTM). According to six evaluation indicators, traditional radar echo extrapolation showed better forecast accuracy within 1 hour, while the CNN-Transformer-based short-term forecasting model for convective weather demonstrated superior performance for 2-6 hour forecasts.

Cyclobalanopsis gilva, a valuable timber species in China, holds significant importance for understanding the constraints imposed by climate change on the dynamic geographic distribution of tree species. This study utilized the MaxEnt maximum entropy model to reconstruct the migratory dynamics of C. gilva geographical distribution since the Last Glacial Maximum. The objective was to comprehend the restrictive mechanisms of environmental factors on its potential geographical distribution, aiming to provide insights for mid-to-long-term afforestation planning of C. gilva. The optimized MaxEnt model exhibited a significantly high predictive accuracy, with an average AUC value of 0.949 ± 0.004 for the modern suitable habitat model of C. gilva. The total suitable habitat area for C. gilva in contemporary times was 143.05 × 104 km2, with a highly suitable habitat area of 3.14 × 104 km2. The contemporary suitable habitat was primarily located in the southeastern regions of China, while the highly suitable habitat was concentrated in eastern Fujian and central-eastern Taiwan. Bioclimatic variables such as mean diurnal range (Bio2), min temperature of coldest month (Bio6), precipitation of driest quarter (Bio17), and precipitation of driest month (Bio14) predominantly influenced the modern geographic distribution pattern of C. gilva, with temperature factors playing a leading role. With global climate warming, there is a risk of fragmentation or even loss of suitable habitat for C. gilva by 2050 and 2090. Therefore, the findings of this study can significantly contribute to initiating a habitat conservation campaign for this species.

The polysaccharides in honeysuckle leaves (PHL) were separated and characterized for the first time. The nano-emulsion stabilized by PHL and whey protein isolate (WPI) were also fabricated based on the ultrasonic method. The results indicated that PHL was mainly composed of glucose (47.40 mol%), galactose (19.21 mol%) and arabinose (20.21 mol%) with the weight-average molecular weight of 137.97 ± 4.31 kDa. The emulsifier concentration, WPI-to-PHL ratio, ultrasound power and ultrasound time had significant influence on the droplet size of PHL-WPI nano-emulsion. The optimal preparation conditions were determined as following: emulsifier concentration, 1.7%; WPI/PHL ratio, 3:1; ultrasonic power, 700 W; ultrasonic time, 7 min. Under the above conditions, the median diameter of the obtained nano-emulsion was 317.70 ± 5.26 nm, close to the predicted value of 320.20 nm. The protective effect of PHL-WPI emulsion on β-carotene against UV irradiation was superior to that of WPI emulsion. Our results can provide reference for the development of honeysuckle leaves.

Exacum affine Balf.f. ex Regel is a traditional medicinal plant in Yemen and also a popular potted plant. In this study, we sequenced the complete chloroplast genome of E. affine on the Illumina HiSeq Platform. The plastome sequence is 153,311 bp in length with a typical quadripartite structure, containing a pair of inverted repeated (IR) regions of 26,079 bp that are separated by a large single copy (LSC) region of 83,724 bp, and a small single copy (SSC) region of 17,509 bp. The GC content of the whole cp genome was 43.14%. A total of 132 functional genes were annotated, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The complete plastome sequence of E. affine will provide genetic and genomic information to promote its horticulture, officinal utilisation and systematics research of Gentianaceae (especially the tribe Exaceae).

Background • Hepatocellular carcinoma (HCC) is a highly malignant tumor, which is difficult to treat and has a poor prognosis. Immunotherapy has been a hot topic in liver cancer treatment in recent years, and macrophages play an important role in liver cancer immunotherapy. In this paper, we will use bioinformatics to analyze the significance of macrophage-associated genes (Mags) in hepatocellular carcinoma. Our goal is to determine the impact of macrophage-related genes on the immunotherapy, prognosis, and tumor microenvironment of HCC patients. Methods • 343 HCC patients with complete survival data were selected from RNA sequencing data from the Cancer Genome Atlas Hepatocellular carcinoma (TCGA-LIHC) database. Using univariate Cox regression analysis and Lasso regression analysis to identify macrophage-related genetic markers for prognostic HCC and constructed risk scores. Kaplan-Meier survival analysis helped to determine the relationship between genetic markers and overall survival (OS). Kaplan-Meier analysis was used to compare OS in stratified high-risk and low-risk groups. Risk scores and other clinical features were included to develop a prognostic profile of HCC. The accuracy of the model was evaluated by the receiver operating curve and calibration curve, respectively. Results • A prognostic risk model consisting of 7 Mags was constructed to accurately predict OS in the TCGA cohort. In univariate and multivariate Cox regression analyses, risk scores were prognostic factors independent of other clinical factors. The prognostic histogram showed that risk score had a good prognostic effect on survival risk stratification. The expression of immunotherapy markers such as CTLA4 and TNFRSF9 was upregulated in high-risk patients, indicating an underlying immunotherapy response in these patients. Conclusion • Our study constructs a macrophageassociated genetic marker for predicting OS in HCC patients, which may help guide clinical immunotherapy. [ABSTRACT FROM AUTHOR]

Abstract The epigenetic regulation of N6-methyladenosine (m6A) has attracted considerable interest in tumor research, but the potential roles of m6A regulator-related genes, remain largely unknown within the context of gastric cancer (GC) and tumor microenvironment (TME). Here, a comprehensive strategy of data mining and computational biology utilizing multiple datasets based on 28 m6A regulators (including novel anti-readers) was employed to identify m6A regulator-related genes and patterns and elucidate their underlying mechanisms in GC. Subsequently, a scoring system was constructed to evaluate individual prognosis and immunotherapy response. Three distinct m6A regulator-related patterns were identified through the unsupervised clustering of 56 m6A regulator-related genes (all significantly associated with GC prognosis). TME characterization revealed that these patterns highly corresponded to immune-inflamed, immune-excluded, and immune-desert phenotypes, and their TME characteristics were highly consistent with different clinical outcomes and biological processes. Additionally, an m6A-related scoring system was developed to quantify the m6A modification pattern of individual samples. Low scores indicated high survival rates and high levels of immune activation, whereas high scores indicated stromal activation and tumor malignancy. Furthermore, the m6A-related scores were correlated with tumor mutation loads and various clinical traits, including molecular or histological subtypes and clinical stage or grade, and the score had predictive values across all digestive system tumors and even in all tumor types. Notably, a low score was linked to improved responses to anti-PD-1/L1 and anti-CTLA4 immunotherapy in three independent cohorts. This study has expanded the important role of m6A regulator-related genes in shaping TME diversity and clinical/biological traits of GC. The developed scoring system could help develop more effective immunotherapy strategies and personalized treatment guidance.

AbstractThe oxidation of unsaturated lipids, facilitated by the enzyme Arachidonic acid 15-lipoxygenase (ALOX15), is an essential element in the development of ferroptosis. This study combined a dual-score exclusion strategy with high-throughput virtual screening, naive Bayesian and recursive partitioning machine learning models, the already established ALOX15 inhibitor i472, and a docking-based fragment substitution optimisation approach to identify potential ALOX15 inhibitors, ultimately leading to the discovery of three FDA-approved drugs that demonstrate optimal inhibitory potential against ALOX15. Through fragment substitution-based optimisation, seven new inhibitor structures have been developed. To evaluate their practicality, ADMET predictions and molecular dynamics simulations were performed. In conclusion, the compounds found in this study provide a novel approach to combat conditions related to ferroptosis-related injury by inhibiting ALOX15.

In this study, taking the Jurassic Lianggaoshan Formation (J1l) tight sandstones in the eastern Sichuan Basin as an example, the types and well-logging responses of main sedimentological and diagenetic facies in the lacustrine delta-front are investigated based on summarizing the sedimentary characteristics and reservoir properties. Subsequently, further validation and application are conducted in the study area through machine learning. Research results show that the J1l lacustrine delta-front in the eastern Sichuan Basin mainly develops subaqueous distributary channels and mouth bar sand bodies, exhibiting typical densification reservoirs, with porosity and permeability distributed between 0.48% and 11.24% (av. 3.87%) and 0.0003–0.653 × 10−3 μm2 (av. 0.026 × 10−3 μm2), respectively. Strong compaction and strong cementation are the primary factors leading to densification, whereas chlorite coatings and weak dissolution play constructive roles in preserving some primary pores, creating a small amount of dissolution pores, and enhancing permeability. In terms of manifestation, the pore-throat content with a radius greater than 0.006 μm governs the reservoir quality. Furthermore, five types of diagenetic facies are identified in the J1l subaqueous distributary channels and mouth bars: strong compaction facies (Type I), strong cementation facies (Type II), chlorite-coating and intergranular pore facies (Type III), weak dissolution and intragranular pore facies (Type IV), and medium compaction and cementation facies (Type V). Overall, the thick and coarse-grained subaqueous distributary channels can be considered as the preferred exploration targets for tight oil and gas, with type III and type IV diagenetic facies being the most favorable reservoirs, characterized by well-logging responses of high AC and low GR, DEN, and RT. Based on the fine division of sedimentological and diagenetic facies, establishing well-logging interpretation models and then employing machine learning to achieve sweet spot reservoir prediction can provide valuable insights for tight oil and gas exploration in regions lacking core data.

Various phthalic acid esters (PAEs) such as dibutyl phthalate (DBP) and butyl benzyl phthalate (BBP) co-exist with nanopollutants in aquatic environment. In this study, Daphnia magna was exposed to nano-CuO and DBP or BBP at environmental relevant concentrations for 21-days to investigate these combined toxic effects. Acute EC50 values (48 h) of nano-CuO, DBP, and BBP were 12.572 mg/L, 8.978 mg/L, and 4.785 mg/L, respectively. Results showed that co-exposure with nano-CuO (500 μg/L) for 21 days significantly enhanced the toxicity of DBP (100 μg/L) and BBP (100 μg/L) to Daphnia magna by 18.37% and 18.11%, respectively. The activities of superoxide dismutase, catalase, and glutathione S-transferase were enhanced by 10.95% and 14.07%, 25.63% and 25.91%, and 39.93% and 35.01% in nano-CuO+DBP and nano-CuO+BBP treatments as compared to the individual exposure groups, verifying that antioxidative defense responses were activated. Furthermore, the co-exposure of nano-CuO and PAEs decreased the population richness and diversity microbiota, and changed the microbial community composition in Daphnia magna. Metabolomic analysis elucidated that nano-CuO + PAEs exposure induced stronger disturbance on metabolic network and molecular function, including amino acid, nucleotides, and lipid metabolism-related metabolic pathways, as comparison to PAEs single exposure treatments. In summary, the integration of physiological, microflora, and untargeted metabolomics analysis offers a fresh perspective into the potential ecological risk associated with nanopollutants and phthalate pollution in aquatic ecosystems.

Abstract Objective The purpose of this study was to investigate the predictive value of mean platelet volume (MPV) and platelet count (PC) in branch atheromatous disease (BAD). Methods This retrospective study included 216 patients with BAD‐stroke within 48 h of symptom onset. These patients were divided into good and poor prognosis groups according to their 3‐month modified Rankin scale scores after discharge. Multiple logistic regression analysis was used to evaluate independent predictors of poor prognosis in BAD‐stroke patients. Receiver‐operating characteristic (ROC) analysis was used to estimate the predictive value of MPV and PC on BAD‐stroke. Results Our research showed that a higher MPV (aOR, 2.926; 95% CI, 2.040–4.196; p

Oil content and the movability of shale oil are important indicators for the evaluation of continental shale oil. In recent years, the sandwiched shale oil in the fourth member of the Shahejie Formation in the Liaohe Western Depression area of the Bohai Bay Basin has shown great exploration potential, while the understanding of shale oil content and the movability of shale oil is weak. In this study, through a combination of core observations and experiments, we clarified the shale lithofacies types in the fourth member of the Shahejie Formation in the Liaohe Western Depression and explored the influencing factors of the characteristics in the oil-bearing and movability of shales in different lithofacies. The results of the study show that the organic matter content of the shale is high (TOC = 2.2–4.3%), but the maturity of thermal evolution is low (Ro = 0.38–0.55%), and the mineral component is dominated by clay minerals (30.3–72.7%), with quartz, feldspar, and other feldspar minerals developing secondarily. According to the content of organic matter, the mineral component, and the sedimentary structure, five types of lithofacies can be classified: organic-rich laminated clay-bearing felsic shale lithofacies (LS1), organic-rich laminated clay felsic mixed shale lithofacies (LS2), organic-rich layered clay felsic mixed shale lithofacies (LS3), organic-containing massive felsic-bearing clay shale lithofacies (LS4), and organic-containing massive clay felsic mixed shale lithofacies (LS5). The oil content of shale is mainly affected by the organic matter. The rate of increase in oil content of shale is fastest when the organic matter content is between 2 and 4%. The movability of shale oil is mainly controlled by the sedimentary structure, mineral component, and microscopic pore structure; the more the shale laminae is developed, the lower the clay content is, and the more the pore space is developed, the better the movability of shale oil is. Combined with the results of the shale oil content and mobility analysis in the study area, LS2 and LS3 are the dominant lithofacies in the fourth member of the Shahejie Formation in the study area, followed by LS1 >LS5 >LS4, so shale oil exploration should focus on the development of LS2 and LS3.

Abstract Insufficient immune cell infiltration into the tumor microenvironment (TME) greatly compromises the clinical application of immune‐checkpoint inhibitors (ICIs)‐based immunotherapy. Recent findings have shown that activation of the cyclic GMP‐AMP synthase‐stimulator of interferon genes (cGAS‐STING) pathway can enhance natural immunity and increase lymphocyte infiltration into the TME, which presents a promising strategy for cancer immunotherapy. In this study, we constructed hydroxyapatite nanoparticles co‐loaded with curcumin and L‐oxaliplatin (Cur/L‐OHP@HAP NPs). We analyzed the particle‐size distribution, zeta potential, spectral characteristics (Fourier‐transform infrared spectroscopy, X‐ray photoelectron spectroscopy, ultraviolet–visible spectroscopy), and drug‐release properties of the Cur/L‐OHP@HAP NPs. The cellular uptake of the Cur/L‐OHP@HAP NPs detected by flow cytometry and confocal laser‐scanning microscopy. We comprehensively evaluated the anti‐tumor properties and immune‐activating effects of the NPs, both in vitro and in vivo. Physicochemical characterizations demonstrated that the Cur/L‐OHP@HAP NPs were successfully synthesized and were capable of pH‐dependent drug release. Notably, the Cur/L‐OHP@HAP NPs efficiently entered cancer cells, after which the released L‐OHP induced nuclear DNA (nDNA) damage to some extent. HAP promoted the release of intracellular Ca2+ stores in cancer cells, and curcumin inhibited Ca2+ efflux, resulting in intracellular Ca2+ overload and the release of mitochondrial DNA (mtDNA). Damage to both nDNA and mtDNA greatly stimulated the cGAS‐STING pathway, thereby activating natural immunity, accompanied by immune cell recruitment to the TME. In summary, the Cur/L‐OHP@HAP NPs show good prospects for improving cancer immunotherapy.

The application of constructal networks to cool a heat‐generating volume has been the subject of many research studies in the past decade. However, the current volume‐point constructs mainly include rectangular, triangular, and parabolic‐shaped constructs, and none of them are similar to the constructs of common plant leaves in nature. A bionic quadrilateral volume based on the shape of common leaf veins is proposed, and the heat‐conductive model of the quadrilateral volume is established. The analysis results show that the minimal peak temperature difference can be as low as 1.3k when the porosity α1 of the quadrilateral volume is equal to 0.15; the recommended value of interval number n of central link is 30, the optimal value of exponent m1 of the width of central link is about 0.9; and the optimal value of the aspect ratio H1/L1 remains nearly constant at 0.7. When the quadrilateral volume obtains highest heat conductivity, the branching cooling links should be perpendicular to the central link. [ABSTRACT FROM AUTHOR]

Current models emphasize that membrane voltage (Vm) depolarization-induced Ca2+ influx triggers the fusion of vesicles to the plasma membrane. In sympathetic adrenal chromaffin cells, activation of a variety of G protein coupled receptors (GPCRs) can inhibit quantal size (QS) through the direct interaction of G protein Giβγ subunits with exocytosis fusion proteins. Here we report that, independently from Ca2+, Vm (action potential) per se regulates the amount of catecholamine released from each vesicle, the QS. The Vm regulation of QS was through ATP-activated GPCR-P2Y12 receptors. D76 and D127 in P2Y12 were the voltage-sensing sites. Finally, we revealed the relevance of the Vm dependence of QS for tuning autoinhibition and target cell functions. Together, membrane voltage per se increases the quantal size of dense-core vesicle release of catecholamine via Vm → P2Y12(D76/D127) → Giβγ → QS → myocyte contractility, offering a universal Vm-GPCR signaling pathway for its functions in the nervous system and other systems containing GPCRs. [ABSTRACT FROM AUTHOR]

In this paper, a new excitation control of variable speed pumped storage unit (VSPS) for electromechanical transient modeling is presented. Compared with the traditional VSPS excitation control based on current source, the inner loop control of rotor current is retained. The new VSPS excitation control model considers the rotor flux dynamics and represents it as a second-order system. The effectiveness of the proposed excitation control model is verified by the comparison between electromagnetic transient simulation and electromechanical transient simulation. The electromechanical transient simulation of VSPS based on current source and VSPS based on voltage source is compared to verify the necessity of considering rotor flux dynamics. The proposed VSPS excitation control model reflects the characteristics of controllable voltage source and can provide more accurate reactive power and voltage simulation results in transient stability analysis.