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Abstract Lung cancer is a malignant tumor with highly heterogeneous characteristics. A classic Chinese medicine, Pinellia ternata (PT), was shown to exert therapeutic effects on lung cancer cells. However, its chemical and pharmacological profiles are not yet understood. In the present study, we aimed to reveal the mechanism of PT in treating lung cancer cells through metabolomics and network pharmacology. Metabolomic analysis of two strains of lung cancer cells treated with Pinellia ternata extracts (PTE) was used to identify differentially abundant metabolites, and the metabolic pathways associated with the DEGs were identified by MetaboAnalyst. Then, network pharmacology was applied to identify potential targets against PTE-induced lung cancer cells. The integrated network of metabolomics and network pharmacology was constructed based on Cytoscape. PTE obviously inhibited the proliferation, migration and invasion of A549 and NCI-H460 cells. The results of the cellular metabolomics analysis showed that 30 metabolites were differentially expressed in the lung cancer cells of the experimental and control groups. Through pathway enrichment analysis, 5 metabolites were found to be involved in purine metabolism, riboflavin metabolism and the pentose phosphate pathway, including D-ribose 5-phosphate, xanthosine, 5-amino-4-imidazolecarboxyamide, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Combined with network pharmacology, 11 bioactive compounds were found in PT, and networks of bioactive compound–target gene–metabolic enzyme–metabolite interactions were constructed. In conclusion, this study revealed the complicated mechanisms of PT against lung cancer. Our work provides a novel paradigm for identifying the potential mechanisms underlying the pharmacological effects of natural compounds.

Abstract Intrahepatic cholestasis of pregnancy (ICP) can lead to many adverse pregnancy outcomes, and the influencing factors remain unclear at present. This study retrospectively analyzed clinical data from 1815 pregnant women with ICP and evaluated the relationship between ICP subtypes, gestational age at onset, and pregnancy outcomes. The results of this study show that during pregnancy, the levels of biochemical indicators (TBA, DBIL and ALT) in the serum of pregnant women initially diagnosed with subtypes of ICP were noted to constantly change, and the subtype of ICP and its severity also changed. The incidence of adverse pregnancy outcomes [meconium-stained amniotic fluid (MSAF), NICU transfer, Apgar score ≤ 7 at 1 min, and preterm birth] in patients with ICP1 (icteric type) was significantly higher than for patients with ICP2, ICP3 or ICP4. The preterm birth rate of early-onset ICP was higher than that of late-onset ICP in ICP1 and ICP3 subtypes. In conclusion, the outcome of pregnancy in women with ICP is closely related to the serum TBA level and ICP subtype, which should be recognized in the clinic.

Abstract Glioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by invasive behavior and a compromised immune response, presenting treatment challenges. Surgical debulking of GBM fails to address its highly infiltrative nature, leaving neoplastic satellites in an environment characterized by impaired immune surveillance, ultimately paving the way for tumor recurrence. Tracking and eradicating residual GBM cells by boosting antitumor immunity is critical for preventing postoperative relapse, but effective immunotherapeutic strategies remain elusive. Here, we report a cavity-injectable bacterium-hydrogel superstructure that targets GBM satellites around the cavity, triggers GBM pyroptosis, and initiates innate and adaptive immune responses, which prevent postoperative GBM relapse in male mice. The immunostimulatory Salmonella delivery vehicles (SDVs) engineered from attenuated Salmonella typhimurium (VNP20009) seek and attack GBM cells. Salmonella lysis-inducing nanocapsules (SLINs), designed to trigger autolysis, are tethered to the SDVs, eliciting antitumor immune response through the intracellular release of bacterial components. Furthermore, SDVs and SLINs administration via intracavitary injection of the ATP-responsive hydrogel can recruit phagocytes and promote antigen presentation, initiating an adaptive immune response. Therefore, our work offers a local bacteriotherapy for stimulating anti-GBM immunity, with potential applicability for patients facing malignancies at a high risk of recurrence.

BackgroundLong-term heat stress (HS) severely restricts the growth performance of beef cattle and causes various health problems. The gut microbiota plays a crucial role in HS-associated inflammation and immune stress involving lymphocyte function. This study investigated the effects of dietary tea polysaccharide (TPS), a natural acidic glycoprotein, on HS-induced anorexia, inflammation, and gut microbiota dysbiosis in Simmental beef cattle.MethodsThe cattle were divided into two groups, receiving either normal chow or normal chow plus TPS (8 g/kg, 0.8%). Transcriptome sequencing analysis was used to analysis the differential signaling pathway of liver tissue. 16S rDNA sequencing was performed to analysis gut microbiota of beef cattle. Serum metabolite components were detected by untargeted metabolomics analysis.ResultsHepatic transcriptomics analysis revealed that differentially expressed genes in TPS-fed cattle were primarily enriched in immune processes and lymphocyte activation. TPS administration significantly reduced the expression of the TLR4/NF-κB inflammatory signaling pathway, alleviating HS-induced hepatic inflammation. Gut microbiota analysis revealed that TPS improved intestinal homeostasis in HS-affected cattle by increasing bacterial diversity and increasing the relative abundances of Akkermansia and Alistipes while decreasing the Firmicutes-to-Bacteroidetes ratio and the abundance of Agathobacter. Liquid chromatography-tandem mass spectrometry (LC‒MS/MS) analysis indicated that TPS significantly increased the levels of long-chain fatty acids, including stearic acid, linolenic acid, arachidonic acid, and adrenic acid, in the serum of cattle.ConclusionThese findings suggest that long-term consumption of tea polysaccharides can ameliorate heat stress-induced hepatic inflammation and gut microbiota dysbiosis in beef cattle, suggesting a possible liver-gut axis mechanism to mitigate heat stress.

Recent studies show that cellular neighborhoods play an important role in evolving biological events such as cancer and diabetes. Therefore, it is critical to accurately and efficiently identify cellular neighborhoods from spatially-resolved single-cell transcriptomic data or single-cell resolution tissue imaging data. In this work, we develop CNTools, a computational toolbox for end-to-end cellular neighborhood analysis on annotated cell images, comprising both the identification and analysis steps. It includes state-of-the-art cellular neighborhood identification methods and post-identification smoothing techniques, with our newly proposed Cellular Neighbor Embedding (CNE) method and Naive Smoothing technique, as well as several established downstream analysis approaches. We applied CNTools on three real-world CODEX datasets and evaluated identification methods with smoothing techniques quantitatively and qualitatively. It shows that CNE with Naive Smoothing overall outperformed other methods and revealed more convincing biological insights. We also provided suggestions on how to choose proper identification methods and smoothing techniques according to input data.

Abstract Electrocatalytic nitrate reduction is a promising approach to remove harmful nitrate and produce ammonia in aqueous media. Here, we demonstrate how 3D printed polymer electrodes can be electroless plated with a bimetallic NiCu alloy film suitable for sustained nitrate‐to‐ammonia reduction. Characterization by powder X‐ray diffraction, X‐ray photoelectron spectroscopy, scanning/transmission electron microscopy and energy‐dispersive X‐ray spectroscopy indicate that the electrode has a two‐layer structure consisting of polymer/ coating layer of metal alloys. The composite electrode shows high‐performance in the nitrate‐to‐ammonia electroreduction, giving NH3 Faradaic efficiencies of up to 83 % and NH3 yield rates up to 860 μg/(h cm2) at −0.38 V vs. RHE. We show that the electrode can easily be integrated into a Zn‐nitrate battery, giving a power density of 3.8 mW cm−2 with continuous NH3 production. The system combines three productive outputs, that is removal of nitrate pollutants, synthesis of valuable ammonia and generation of “green” electricity.

Although particular attention has been paid to responses of hydrocarbon storage and percolation capacity to the devitrification concerning lacustrine tuffaceous shale reservoirs in recent years, there is still a lack of systematical and comparative investigation on differential patterns and potential triggering mechanisms concerning development of the pore-microfracture systems and characteristics of surface wettability between the fresh-water and saline lacustrine settings, which is of considerable importance in fully understanding of genesis and spatial distribution of dessert reservoir intervals of tuffaceous shale reservoirs, and to provide further conceptual basis for deciphering shale-oil movability of saline lacustrine fine-grained mixed sedimentary sequences. In this study, tuffaceous shales from both the Upper Triassic Yanchang Formation in the Ordos Basin and Middle Permian Jingjingzigou Formation in the Junggar Basin are targeted to unravel the differential behavior of tuff devitrification and potential impacts on reservoir wettability and pore connectivity concerning fresh-water and saline lacustrine settings, and we present new results here from integrated analyses and combined interpretation of FE-SEM, Image Pro Plus (IPP) software image processing, contact angle and spontaneous imbibition experiments. In view of comparative analysis from representative samples, the tuffaceous shales from saline lacustrine environments are characterized by well-developed intergranular-intercrystalline and dissolution pores, and inorganic microfractures, generally yield a higher plane porosity of representative pore-fracture spaces and spontaneous imbibition slopes, a relatively lower average of n-decane contact angles and corresponding wettability parameters. The saline lacustrine tuffaceous shales are thus suspected to have undergone more intense devitrification resulting in a higher amount of devitrification and associated dissolution pores, and a relatively better connectivity between isolated micropore systems with adjacent microfractures. This would significantly facilitate the interface wettability reversal and occurrence of movable hydrocarbon fluid in microscopic reservoir spaces. Finally, a comprehensive and conceptual model is established illustrating the effects of differential devitrification on reservoir-forming patterns concerning tuffaceous shales developed in the fresh-water and saline lacustrine settings, respectively. These findings are of great theoretical and practical significance to enrich theory of high-quality reservoir formation and shale-oil accumulation in saline lacustrine tuffaceous shale reservoirs, and lay the foundation for guiding efficient exploration of continental fine-grained mixed sedimentary sequences.

Summary: Despite the success of programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibition in tumor therapy, many patients do not benefit. This failure may be attributed to the intrinsic functions of PD-L1. We perform a genome-wide CRISPR synthetic lethality screen to systematically explore the intrinsic functions of PD-L1 in head and neck squamous cell carcinoma (HNSCC) cells, identifying ferroptosis-related genes as essential for the viability of PD-L1-deficient cells. Genetic and pharmacological induction of ferroptosis accelerates cell death in PD-L1 knockout cells, which are also more susceptible to immunogenic ferroptosis. Mechanistically, nuclear PD-L1 transcriptionally activates SOD2 to maintain redox homeostasis. Lower reactive oxygen species (ROS) and ferroptosis are observed in patients with HNSCC who have higher PD-L1 expression. Our study illustrates that PD-L1 confers ferroptosis resistance in HNSCC cells by activating the SOD2-mediated antioxidant pathway, suggesting that targeting the intrinsic functions of PD-L1 could enhance therapeutic efficacy.

Abstract Background Temperature control plays a pivotal role in patients with heat stroke (HS), but little work has been done sufficiently on the use of temperature control to reflect disease progression. Here, we defined and analyzed the concrete role of controlling time for core temperature to physiological level (CTTP), in order to explore a potential index to guide the treatment of HS. Method This is a retrospective cohort study. From three hospitals located in Sichuan province, China, we collected a total of 179 HS cases with clinical diagnosis and treatment records. We defined CTTP as the time interval of HS onset to stabilization of core temperature (rectal temperature) below 37.7°C and analyzed the correlation between CTTP and inpatient death of HS patients. Results Of all the cases, 64.80% were male and 53.07% were exertional heat stroke (EHS). The median (IQR) age was 59 (23.5–73) years old, and the median (IQR) onset temperature was 42 (40.4–42)°C. Multivariable analysis demonstrated significantly high inpatient death in the highest CTTP tertile (>18 h) (hazard ratio: 18.75; 99% confidence interval: 4.06–86.59; p = .0002). In addition, compared with patients in lowest CTTP tertile, patients in highest CTTP tertile were at significantly higher risk of organ damage: 3.48‐fold for respiratory failure (95% CI: 1.41–8.59, p = .0069); 3.18‐fold for shock (95% CI: 1.37–7.39, p = .0071); 4.09‐fold for rhabdomyolysis (95% CI: 1.73–9.64, p = .0013); 4.64‐fold for renal damage (95% CI: 2.12–10.14, p = .0001). Conclusion Long of CTTP predicts inpatient death of HS patients with a CTTP tertile >18 h associated with the highest rate of inpatient death.

Abstract The lattice reduction-aided algorithm has received broad attention from researchers since it operates as a maximum likelihood receiver with better system performance for multiple-input multiple-output orthogonal frequency division multiplexing systems and contains a full diversity. A novel iterative detection algorithm canceling parallel iterations that employ the lattice reduction-aided approach is proposed. Soft information is exchanged through the detector itself. Its iteration occurs inside the detector, which reduces much of the exchange cost between the multiple-input multiple-output orthogonal frequency division multiplexing detector and the turbo decoder. Since the parallel interference cancellation algorithm is constrained by the accuracy of the initial value of the detection, it is easy to form error propagation after several iterations. Due to the lattice reduction-aided algorithm, its performance is approximated with the maximum likelihood algorithm. Therefore, the lattice reduction-aided algorithm is introduced into the parallel interference cancellation algorithm to make its detection algorithm more accurate and overcome the effect of error propagation in the manuscript. Simulation results indicate that the proposed algorithm leads to an improvement of 0.8–2 dB when the bit error rate is set to 10–4 when compared to other algorithms.

Abstract Metallofullerenes are an important type of metallic nanomaterial with promising applications in several medical fields. Thermal ablation, including radiofrequency ablation (RFA) and microwave ablation (MWA), is an important treatment strategy for advanced hepatocellular carcinoma (HCC). The thermal expansion of fullerenes makes them good adjuncts to thermal ablation treatment of HCC. In this study, we used an innovative method of emulsification and cross-linking to produce CS-C60-Fe3O4 (Chitosan-C60-Fe3O4) nanoparticles, which have the advantages of uniform particle size and high bioavailability, as a kind of novel nano-pharmaceutical. The CS-C60-Fe3O4 nanoparticles were prepared by the cross-linking reaction from chitosan–acetic acid solution, Fe3O4 nanoparticles by Fe2SO4·7H2O and FeCl3·6H2O, and C60. The average particle size of CS-C60-Fe3O4 was 194.3 nm. Because CS-C60-Fe3O4 is magnetic, it can achieve specific and tissue aggregation in HCC tumor tissues. Moreover, compared with normal soluble C60 (EL35-C60), CS-C60-Fe3O4 prolonged the retention time of C60 in the blood of mice. CS-C60-Fe3O4 alone is not cytotoxic to cultured cells or tumor tissues, but when combined with thermal ablation strategies (RFA and MWA), it significantly upregulates the antitumor effects of thermal ablation on HCC tissues, that is, it acts as a sensitiser to thermal ablation. In the presence of thermal ablation, CS-C60-Fe3O4 interfered with iron metabolism in HCC cells and induced ferroptosis of HCC cells in the tumor tissues. These results not only expand our understanding of metallofullerenes but also provide additional options for the treatment of advanced HCC.

BackgroundFor Rheumatoid Arthritis (RA), a long-term chronic illness, it is essential to identify and describe patient subtypes with comparable goal status and molecular biomarkers. This study aims to develop and validate a new subtyping scheme that integrates genome-scale transcriptomic profiles of RA peripheral blood genes, providing a fresh perspective for stratified treatments.MethodsWe utilized independent microarray datasets of RA peripheral blood mononuclear cells (PBMCs). Up-regulated differentially expressed genes (DEGs) were subjected to functional enrichment analysis. Unsupervised cluster analysis was then employed to identify RA peripheral blood gene expression-driven subtypes. We defined three distinct clustering subtypes based on the identified 404 up-regulated DEGs.ResultsSubtype A, named NE-driving, was enriched in pathways related to neutrophil activation and responses to bacteria. Subtype B, termed interferon-driving (IFN-driving), exhibited abundant B cells and showed increased expression of transcripts involved in IFN signaling and defense responses to viruses. In Subtype C, an enrichment of CD8+ T-cells was found, ultimately defining it as CD8+ T-cells-driving. The RA subtyping scheme was validated using the XGBoost machine learning algorithm. We also evaluated the therapeutic outcomes of biological disease-modifying anti-rheumatic drugs. ConclusionsThe findings provide valuable insights for deep stratification, enabling the design of molecular diagnosis and serving as a reference for stratified therapy in RA patients in the future.

Background: Esophageal cancer (EC) is a prevalent malignancy with heterogeneous outcomes. This study explores the significance of anoikis-related long non-coding RNAs (lncRNAs) in EC, aiming to unravel their molecular roles and clinical implications. Methods: Transcriptome and clinical data were obtained from TCGA database for EC samples. We identified anoikis-related genes and lncRNAs by Pearson correlation analysis. The risk score model hinged on prognostic lncRNAs filtered from multiple steps. Risk scores were calculated using the derived formula, and categorized patients into low- and high-risk groups. Model robustness was assessed through Kaplan-Meier (KM) survival analysis and Receiver Operating Characteristic (ROC) curve, with clinical utility achieved via a constructed nomogram. We also explored the interplay between the risk score and immune cell infiltration, and investigated drug sensitivity. Results: We identified 2365 anoikis-related lncRNAs through co-expression analysis, including 1415 significant lncRNAs differentially expressed between normal and tumor samples. A risk score model was constructed from ten prognostic lncRNAs. The risk score model effectively stratified patients based on the median score, and its predictive capacity was validated through KM survival, ROC curve analyses, and the external GSE53622 dataset. The nomogram provided a practical tool for individualized prognosis evaluation. We unveiled significant correlations between specific immune cell subsets and the risk score. Eosinophils and common lymphoid progenitors exhibited positive associations, while endothelial cells and myeloid dendritic cells showed negative correlations. Drug sensitivity analysis revealed potential sensitive drugs for EC treatment that aligned with the risk subgroups. Conclusion: This study established an anoikis-related lncRNAs risk score model that may predict the prognosis, immune infiltration, and drug sensitivity in EC, in hope of facilitating tailored patient management.

Abstract Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), and alpha-fetoprotein (AFP) are widely used tumor markers for colorectal cancer (CRC), but their clinical significance is unknown when the levels of these tumor markers were within the normal range. This retrospective study included 2145 CRC patients. The entire cohort was randomly divided into training and validation datasets. The optimal cut-off values of tumor markers were calculated using X-tile software, and univariate and multivariate analyses were performed to assess its association with overall survival (OS). The nomogram model was constructed and validated. The entire cohort was randomly divided into a training dataset (1502 cases, 70%) and a validation dataset (643 cases,30%). Calculated from the training dataset, the optimal cut-off value was 2.9 ng/mL for CEA, 10.1 ng/mL for CA19-9, 13.4 U/mL for CA125, and 1.8 ng/mL for AFP, respectively. Multivariate analysis revealed that age, tumor location, T stage, N stage, preoperative CA19-9, and CA125 levels were independent prognostic predictors. Even within the normal range, CRC patients with relatively high levels of CA19-9 or CA125 worse OS compared to those with relatively low levels. Then, based on the independent prognostic predictors from multivariate analysis, two models with/without (model I/II) CA19-9 and CA125 were built, model I showed better prediction and reliability than model II. Within the normal range, relatively high levels of preoperative CA19-9 and CA125 were significantly associated with poor OS in CRC patients. The nomogram based on CA19-9 and CA125 levels showed improved predictive accuracy ability for CRC.

Abstract The role of mast cells (MCs) in colorectal cancer (CRC) remains unclear, and a comprehensive single-cell study on CRC MCs has not been conducted. This study used a multi-omics approach, integrating single-cell sequencing, spatial transcriptomics, and bulk tissue sequencing data to investigate the heterogeneity and impact of MCs in CRC. Five MC signature genes (TPSAB1, TPSB2, CPA3, HPGDS, and MS4A2) were identified, and their average expression was used as a marker of MCs. The MC density was found to be lower in CRC compared to normal tissue, but MCs in CRC demonstrated distinct activation features. Activated MCs were defined by high expression of receptors and MC mediators, while resting MCs had low expression. Most genes, including the five MC signature genes, were expressed at higher levels in activated MCs. The MC signature was linked to a better prognosis in both CRC and pan-cancer patient cohorts. Elevated KITLG expression was observed in fibroblasts and endothelial cells in CRC samples compared to normal tissue, and co-localization of MCs with these cell types was revealed by spatial transcriptome analysis. In conclusion, this study finds decreased MC density in CRC compared to normal tissue, but highlights a shift in MC phenotype from CMA1 high resting cells to activated TPSAB1 high, CPA3 high, and KIT high cells. The elevated KITLG expression in the tumor microenvironment’s fibroblasts and endothelial cells may activate MCs through the KITLG-KIT axis, potentially suppressing tumor progression.

Abstract The clinical benefit of tyrosine kinase inhibitors (TKIs)-based systemic therapy for advanced hepatocellular carcinoma (HCC) is limited due to drug resistance. Here, we uncover that lipid metabolism reprogramming mediated by unconventional prefoldin RPB5 interactor (URI) endows HCC with resistance to TKIs-induced ferroptosis. Mechanistically, URI directly interacts with TRIM28 and promotes p53 ubiquitination and degradation in a TRIM28-MDM2 dependent manner. Importantly, p53 binds to the promoter of stearoyl-CoA desaturase 1 (SCD1) and represses its transcription. High expression of URI is correlated with high level of SCD1 and their synergetic expression predicts poor prognosis and TKIs resistance in HCC. The combination of SCD1 inhibitor aramchol and deuterated sorafenib derivative donafenib displays promising anti-tumor effects in p53-wild type HCC patient-derived organoids and xenografted tumors. This combination therapy has potential clinical benefits for the patients with advanced HCC who have wild-type p53 and high levels of URI/SCD1.

The use of ferronickel slag powder (FNSP) as a cementitious additional material has been supported by numerous reports. FNSP concrete has the same shortcomings as ordinary concrete, including low hardness. In this study, in order to make FNSP concrete more durable, end-hooked type steel fibers were incorporated. To understand how various elements affect the mechanical properties of steel fibers, an experiment was carried out on the mechanical properties of steel FNSP concrete (SFNSPC). FNSP’s principal ingredients, with a particle size distribution ranging from 0.5 to 100 μm and a sheet-like powder shape, are CaO, SiO2, Al2O3, MgO, and others, according to tests conducted on the material’s microstructure and composition. Then, eighteen mix proportions were developed, comprising six distinct FNSP replacement rate types and three distinct steel fiber content types. Crucial metrics were evaluated and analyzed, including the relationship among the toughness, tensile strength, and compressive strength as well as slump, splitting tensile strength, compressive strength, and uniaxial compressive stress–strain curve of SFNSPC. The results showed that the slump of SFNSPC under different FNSP replacement rates decreased with increasing steel fiber volume. Steel fibers have a small but positive effect on SFNSPC’s compressive strength; nonetheless, as FNSP replacement rates increased, SFNSPC’s slump gradually decreased, though not by much. These results show that FNSP is a viable alternative cementitious material in terms of strength. Specifically, the splitting tensile strength of SFNSPC improves with an increase in steel fiber content, and the pace at which SFNSPC strength drops with an increase in the FNSP replacement rate. With varying mix proportions, the stress–strain curve trend of SFNSPC remains mostly constant, and steel fibers improve the compressive toughness of SFNSPC. After adding 0.5% and 1.0% steel fibers, the toughness index of concrete with different FNSP replacement rates increased by 8–30% and 12–43%, respectively.

Data aggregation plays a critical role in sensor networks for efficient data collection. However, the assumption of uniform initial energy levels among sensors in existing algorithms is unrealistic in practical production applications. This discrepancy in initial energy levels significantly impacts data aggregation in sensor networks. To address this issue, we propose Data Aggregation with Different Initial Energy (DADIE), a novel algorithm that aims to enhance energy-saving, privacy-preserving efficiency, and reduce node death rates in sensor networks with varying initial energy nodes. DADIE considers the transmission distance between nodes and their initial energy levels when forming the network topology, while also limiting the number of child nodes. Furthermore, DADIE reconstructs the aggregation tree before each round of data transmission. This allows nodes closer to the receiving end with higher initial energy to undertake more data aggregation and transmission tasks while limiting energy consumption. As a result, DADIE effectively reduces the node death rate and improves the efficiency of data transmission throughout the network. To enhance network security, DADIE establishes secure transmission channels between transmission nodes prior to data transmission, and it employs slice-and-mix technology within the network. Our experimental simulations demonstrate that the proposed DADIE algorithm effectively resolves the data aggregation challenges in sensor networks with varying initial energy nodes. It achieves 5–20% lower communication overhead and energy consumption, 10–20% higher security, and 10–30% lower node mortality than existing algorithms.

Tungsten (W) stands out as a highly promising plasma-facing materials (PFMs) for future nuclear fusion reactors due to its advantages of excellent high temperature strength, low tritium retention and high recrystallization temperature (RCT). Notably, the potassium-doped tungsten-rhenium (W-Re-K) alloy exhibits exceptional performance when compared to other potential W-based alloys. Nevertheless, even a small amount of Re addition can reduce the thermal conductivity of W, which falls short of the requirement for PFMs. In this study, W-Re-K alloys with Re addition from 0.1 wt% to 0.5 wt% and minor K doping (40 ∼ 50 ppm) were manufactured via powder metallurgy and thermo-mechanical processes. The results revealed that the presence of Re had a grain-refining effect, which became more obvious as its content increased. The incorporation of a small amount of Re (W-0.5 wt% Re-K) exhibited favorable characteristics. Featuring an average grain size of 20.25 µm, and displayed a room temperature thermal conductivity of 163 W/(m⋅K), and an elevated RCT of approximately 1588 °C.

This research aims to evaluate various traditional or deep machine learning algorithms for the prediction of groundwater level (GWL) using three key input variables specific to Izeh City in the Khuzestan province of Iran: groundwater extraction rate (E), rainfall rate (R), and river flow rate (P) (with 3 km distance). Various traditional and deep machine learning (DML) algorithms, including convolutional neural network (CNN), recurrent neural network (RNN), support vector machine (SVM), decision tree (DT), random forest (RF), and generative adversarial network (GAN), were evaluated. The convolutional neural network (CNN) algorithm demonstrated superior performance among all the algorithms evaluated in this study. The CNN model exhibited robustness against noise and variability, scalability for handling large datasets with multiple input variables, and parallelization capabilities for fast processing. Moreover, it autonomously learned and identified data patterns, resulting in fewer outlier predictions. The CNN model achieved the highest accuracy in GWL prediction, with an RMSE of 0.0558 and an R2 of 0.9948. It also showed no outlier data predictions, indicating its reliability. Spearman and Pearson correlation analyses revealed that P and E were the dataset’s most influential variables on GWL. This research has significant implications for water resource management in Izeh City and the Khuzestan province of Iran, aiding in conservation efforts and increasing local crop productivity. The approach can also be applied to predicting GWL in various global regions facing water scarcity due to population growth. Future researchers are encouraged to consider these factors for more accurate GWL predictions. Additionally, the CNN algorithm’s performance can be further enhanced by incorporating additional input variables.

Abstract Clinical evidence shows that the mechanical stimulation obtained from occlusion could enhance periodontal ligament (PDL) remodeling. Mechano‐growth factor (MGF) is a growth factor produced specifically following mechanical stimulus Here, we aim to investigate the mechanical enhancement potential and mechanism of the MGF in PDL regeneration. In vivo study found that MGF produced from the PDL under occlusion force could strongly enhance PDL remodeling. In vitro experiments and mathematical modeling further confirmed the mechanical enhancement effect of MGF for PDLSC differentiation toward fibroblasts. A mechanochemical coupling effect of MGF mediated the enhancement of mechanical effect, which was modulated by Fyn‐FAK kinases signaling and subsequent MAPK pathway. Finally, enhanced PDL regeneration under the mechanochemical coupling of MGF and occlusal force was verified in vivo. There exists an additive mechanical effect of MGF mediated by Fyn‐FAK crosstalk and subsequent ERK1/2 and p38 phosphorylation, which could be developed as an MGF‐centered adjuvant treatment to optimize PDL remodeling, especially for patients with weakened bite force or destroyed periodontium.

Beijing Plain is an important region for ecological planning and management. In the past decade, human activities have dramatically changed the spatial and landscape patterns of greenspaces in Beijing Plains. However, very few studies have assessed the main causative factors of these changes. Herein, we analyzed the spatial patterns of greenspaces in the Beijing Plains between 2015 and 2020 using multi-source remote sensing data, geographical information system, and the landscape pattern index. Additionally, we utilized gray correlation analysis to quantitatively analyze the main factors contributing to dynamic changes in the greenspace landscape patterns. We found that the greenspaces in Beijing showed a gradual increase annually from 2015 to 2020. Further, the conversion of greenspace types throughout the study period mainly included the interconversion of woodland and cropland, water, and impervious surfaces. The transfer out of woodlands has been decreasing annually while the transfer in has been increasing. Grassland and shrubs were almost entirely converted into woodlands and other land use types. The fragmentation of the overall greenspace reduced, aggregation increased, and landscape patches tended to be fully distributed, connected, simpler, concentrated, and regular. The advantages of woodland landscapes were gradually becoming more evident. Population urbanization, rapid economic growth, and policies were important factors affecting changes in greenspace landscape patterns. The study findings provide a scientific reference to adjust the greenspace structure, transform and upgrade the existing greenspaces, and ensure sustainable development of cities.

The Well Tashen 5 (TS5), drilled and completed at a vertical depth of 9017 m in the Tabei Uplift of the Tarim Basin, NW China, is the deepest well in Asia. It has been producing both oil and gas from the Sinian at a depth of 8780–8840 m, also the deepest in Asia in terms of oil discovery. In this paper, the geochemical characteristics of Sinian oil and gas from the well were investigated and compared with those of Cambrian oil and gas discovered in the same basin. The oil samples, with Pr/Ph ratio of 0.78 and a whole oil carbon isotopic value of −31.6‰, have geochemical characteristics similar to those of Ordovician oils from the No. 1 fault in the North Shuntuoguole area (also named Shunbei area) and the Middle Cambrian oil from wells Zhongshen 1 (ZS1) and Zhongshen 5 (ZS5) of Tazhong Uplift. The maturity of light hydrocarbons, diamondoids and aromatic fractions all suggest an approximate maturity of 1.5%–1.7% Ro for the samples. The (4-+3-) methyldiamantane concentration of the samples is 113.5 μg/g, indicating intense cracking with a cracking degree of about 80%, which is consistent with the high bottom hole temperature (179 °C). The Sinian gas samples are dry with a dryness coefficient of 0.97. The gas is a mixture of kerogen-cracking gas and oil-cracking gas and has Ro values ranging between 1.5% and 1.7%, and methane carbon isotopic values of −41.6‰. Based on the equivalent vitrinite reflectance (Reqv = 1.51%–1.61%) and the thermal evolution of source rocks from the Cambrian Yu'ertusi Formation of the same well, it is proposed that the Sinian oil and gas be mainly sourced from the Cambrian Yu'ertusi Formation during the Himalayan period but probably also be joined by hydrocarbon of higher maturity that migrated from other source rocks in deeper formations. The discovery of Sinian oil and gas from Well TS5 suggests that the ancient ultra-deep strata in the northern Tarim Basin have the potential for finding volatile oil or condensate reservoirs.

Abstract Osteoarthritis is a prevalent age-related disease characterized by dysregulation of extracellular matrix metabolism, lipid metabolism, and upregulation of senescence-associated secretory phenotypes. Herein, we clarify that CircRREB1 is highly expressed in secondary generation chondrocytes and its deficiency can alleviate FASN related senescent phenotypes and osteoarthritis progression. CircRREB1 impedes proteasome-mediated degradation of FASN by inhibiting acetylation-mediated ubiquitination. Meanwhile, CircRREB1 induces RanBP2-mediated SUMOylation of FASN and enhances its protein stability. CircRREB1-FASN axis inhibits FGF18 and FGFR3 mediated PI3K-AKT signal transduction, then increased p21 expression. Intra-articular injection of adenovirus–CircRreb1 reverses the protective effects in CircRreb1 deficiency mice. Further therapeutic interventions could have beneficial effects in identifying CircRREB1 as a potential prognostic and therapeutic target for age-related OA.

Abstract Background To develop an ultrasound scoring system for placenta accreta spectrum (PAS), evaluate its diagnostic value, and provide a practical approach to prenatal diagnosis of PAS. Methods A total of 532 pregnant women (n = 184 no PAS, n = 120 placenta accreta, n = 189 placenta increta, n = 39 placenta percreta) at high-risk for placenta accreta who delivered in the Third Affiliated Hospital of Zhengzhou University between January 2021 and December 2022 underwent prenatal ultrasound to evaluate placental invasion. An ultrasound scoring system that included placental and cervical morphology and history of cesarean section was created. Each feature was assigned a score of 0 ~ 2, according to severity. Thresholds for the total ultrasound score that discriminated between no PAS, placenta accreta, placenta increta, and placenta percreta were calculated. Results Univariate and multivariate regression analysis identified seven indicators of PAS that were included in the ultrasound scoring system, including placental location, placental thickness, presence/absence of the retroplacental space, thickness of the retroplacental myometrium, presence/absence of placental lacunae, retroplacental myometrial blood flow and history of cesarean section. Using the final ultrasound scoring system, no PAS is diagnosed at a total score

Abstract The secretory properties of cancer-associated fibroblasts (CAFs) play predominant roles in shaping a pro-metastatic tumor microenvironment. The present study demonstrated that SLIT2, an axon guidance protein, produced by CAFs and promoted gastric cancer (GC) metastasis in two gastric cancer cell lines (AGS and MKN45) by binding to roundabout guidance receptor 1 (ROBO1). Mass-spectrometry analysis revealed that ROBO1 could interact with NEK9, a serine/threonine kinase. And their mutual binding activities were further enhanced by SLIT2. Domain analysis revealed the kinase domain of NEK9 was critical in its interaction with the intracellular domain (ICD) of ROBO1, and it also directly phosphorylated tripartite motif containing 28 (TRIM28) and cortactin (CTTN) in AGS and MKN45 cells. TRIM28 function as a transcriptional elongation factor, which directly facilitate CTTN activation. In addition, Bioinformatics analysis and experimental validation identified transcriptional regulation of STAT3 and NF-κB p100 by TRIM28, and a synergetic transcription of CTTN by STAT3 and NF-κB p100 was also observed in AGS and MKN45. Therefore, CAF-derived SLIT2 increased the expression and phosphorylation levels of CTTN, which induced cytoskeletal reorganization and GC cells metastasis. A simultaneous increase in the expression levels of NEK9, TRIM28 and CTTN was found in metastatic GC lesions compared with paired non-cancerous tissues and primary cancer lesions via IHC and Multiplex IHC. The analysis of the data from a cohort of patients with GC revealed that increased levels of NEK9, TRIM28 and CTTN were associated with a decreased overall survival rate. On the whole, these findings revealed the connections of CAFs and cancer cells through SLIT2/ROBO1 and inflammatory signaling, and the key molecules involved in this process may serve as potential biomarkers and therapeutic targets for GC.