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Soil desertification is an important challenge in global soil management, and effectively and stably restoring soil function is an urgent problem. Using synthetic microbial communities (SynComs) is a burgeoning microbial strategy aimed at enhancing soil nutrients through functional synergies among diverse microorganisms; nevertheless, their effectiveness in restoring desertified soils remains unknown. In this study, we conducted a two-year field experiment using a SynCom constructed by in situ probiotic bacteria and set up control, chemical fertilizer, and combined SynCom–chemical fertilizer (combined fertilizer) treatments to investigate the linkage between microbial communities and soil multifunctionality in the soil surface layer (0–10 cm). Both the bacterial and fungal communities differed the most under the combined fertilizer treatment compared to the control. The bacterial communities differed more under treatments of the SynCom than the chemical fertilizer, while the fungal communities differed more under the chemical fertilizer treatment than the SynCom treatment. Regarding soil function, the SynCom strengthened the correlation between enzyme activities and both bacterial communities and functional properties. pH and available potassium were the main influencing factors under the chemical fertilizer and combined fertilizer treatments. The beta-diversity of the bacterial communities was significantly correlated with soil multifunctionality. Random forest analyses showed that the SynCom significantly enhanced the bacterial communities, driving soil multifunctionality, and that some potential microbial taxa drove multiple nutrient cycles simultaneously. In summary, the SynCom effectively increased the abundance of most carbon, nitrogen, and phosphorus functional genes as well as soil enzyme activities. The bacterial community composition contributed significantly to soil multifunctionality. Hence, the development of novel microbial agents holds significant potential for improving soil functionality and managing desertification.

The mathematical model of a flexible multistate switch (FMSS) exhibits nonlinear and strong coupling characteristics, whereas traditional power decoupling control makes it difficult to completely decouple the output power. The traditional proportional–integral control parameters are difficult to adjust, and their robustness and dynamic performance are poor, which affects the stability of the voltage of the power distribution network and feeder power. To address these problems, this study first converted the original system into a linear system via coordinate transformation using feedback-accurate linearization to decouple active and reactive currents. Thereafter, a super-twisting sliding mode control (ST-SMC) algorithm was introduced, and an adaptive quasi-super-twisting sliding mode control (AQST-SMC) algorithm comprising the quasi-sliding mode function and adaptive proportional term was proposed. An FMSS double closed-loop controller was designed to achieve improved vibration suppression and convergence speed. A three-port FMSS simulation model was developed using MATLAB/Simulink, and the simulation results show that the proposed control strategy enhances the robustness and dynamic performance of the system.

Developing clinically meaningful nanomedicines for cancer therapy requires the drugs to be effective, safe, simple, cheap, and easy to store. In the present work, we report that a simple cationic Fe(III)-rich salt of [FeIIICl(TMPPH2)][FeIIICl4]2 (Fe-TMPP) exhibits a superior anticancer performance on a broad spectrum of cancer cell lines, including breast, colorectal cancer, liver, pancreatic, prostate, and gastric cancers, with half maximal inhibitory concentration (IC50) values in the range of 0.098–3.97 μM (0.066–2.68 μg mL−1), comparable to the best-reported medicines. Fe-TMPP can form stand-alone nanoparticles in water without the need for extra surface modification or organic-solvent-assisted antisolvent precipitation. Critically, Fe-TMPP is TME-responsive (TME = tumor microenvironment), and can only elicit its function in the TME with overexpressed H2O2, converting H2O2 to the cytotoxic •OH to oxidize the phospholipid of the cancer cell membrane, causing ferroptosis, a programmed cell death process of cancer cells.

Temperature has a great influence on the stability of bearing performance. For the study of bearing steady-state temperature, this paper proposes a test method to quickly predict the steady-state temperature of the outer ring of a bearing, which solves the problems in traditional theoretical calculations and simulation analysis methods such as the large number of calculations, complex models, and large errors. Firstly, a mathematical prediction model is established according to the bearing temperature-rise law; then, a bearing steady-state temperature detection device is designed; and finally, the prediction model parameters are solved according to the experimental results, and experimental verification is carried out. It is shown that the prediction model has high accuracy under different load and speed conditions, and the error between the predicted steady-state temperature and the tested steady-state temperature is less than 0.7 °C. This prediction method reduces the single test time of the same speed to 60 min, which greatly improves the efficiency of the temperature detection test. The steady-state temperature model has important theoretical significance in guiding the study of the limiting speed of bearings.

As the prime candidate for plasma-facing materials (PFM), the response of tungsten (W) to thermal shock loads is an important research topic for future fusion devices. Under heat loads, the surface of tungsten plasma-facing materials (W-PFM) can experience thermal damage, including brittle cracking and fatigue cracks. Therefore, exploring solutions for thermal damage of W-PFM remains one of the current research focuses. We propose a novel approach to mitigate thermal radiation damage in PFM, namely, the stacked structure W-PFM. The surface thermal stress distribution of the stacked structure W-PFM under heat loads was simulated and analyzed by the finite element method. As the foil thickness decreases, both the peak thermal stresses in the normal direction (ND) and rolling direction (RD) decrease. When the thickness decreases to a certain value, the peak thermal stress in the RD decreases to about 1384 MPa and no longer decreases; while the peak thermal stress in the ND approaches 0 MPa and can be neglected. In the range of approximately 5–100 mm, the accumulated equivalent plastic strain decreases sharply as the thickness decreases; in other thickness ranges, it decreases slowly. Thermal fatigue experiments were conducted on the stacked structure W composed of W foils with different thicknesses and bulk W using an electron beam facility. The samples were applied with a power density of 30 MW/m2 for 10,000 and 20,000 pulses. The cracks on the surface of the stacked structure W extended along the ND direction, while on the surface of bulk W, besides the main crack in the ND direction, a crack network also formed. The experimental results were consistent with finite element simulations. When the pulse number was 10,000, as the thickness of the W foil decreased, the number and width of the cracks on the surface of the stacked structure W decreased. Only four small cracks were present on the surface of stacked structure W (0.05 mm). When the pulse number increased to 20,000, the plastic deformation and number of cracks on the surface of all samples increased. However, the stacked structure W (0.05 mm) only added one small crack and had the smallest surface roughness (Ra = 1.536 μm). Quantitative analysis of the fatigue cracks showed that the stacked structure W-PFM (0.05 mm) exhibited superior thermal fatigue performance.

This paper presents an ultra-wideband, low insertion loss, and high accuracy 6-bit digital step attenuator (DSA). To improve the accuracy of amplitude and phase shift of the attenuator, two innovative compensation structures are proposed in this paper: a series inductive compensation structure (SICS) designed to compensate for high frequency attenuation values and a small bit compensation structure (SBCS) intended for large attenuation bits. Additionally, we propose insertion loss reduction techniques (ILRTs) to reduce insertion loss. The fabricated 6-bit DSA core area is only 0.51 mm2, and it exhibits an attenuation range of 31.5 dB in 0.5 dB steps. Measurements reveal that the root-mean-square (RMS) attenuation and phase errors for the 64 attenuation states are within 0.18 dB and 7°, respectively. The insertion loss is better than 2.54 dB; the return loss is better than −17 dB; and the input 1 dB compression point (IP1 dB) is 29 dBm at IF 12 GHz. To the best of our knowledge, this chip presents the highest attenuation accuracy, the lowest insertion loss, the best IP1dB, and a good matching performance in the range of 2–22 GHz using the 0.25 μm GaAs p-HEMT process.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are associated with adverse health effects. This study examined the trend of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) levels in individuals with and without pre-existing comorbidities. We analyzed the characteristics of 13,887 participants across nine U.S. NHANES cycles (1999–2000 to 2017–2018) and calculated the geometric mean (GM) of PFOA and PFOS levels, standardized by sex and age. A joinpoint regression model was used to analyze the temporal trends of serum PFOA and PFOS levels. We observed declining PFOA and PFOS serum levels among adults in NHANES from 1999–2000 to 2017–2018. Serum PFOA and PFOS concentrations were higher in men, smokers, and individuals with pre-existing CKD, hyperlipidemia, CVD, and cancer. We observed faster decline rates in PFOA levels among individuals with diabetes and CKD and faster decline rates in PFOS levels among individuals with diabetes and those without CKD. This study provided evidence of varying levels and changing trends of PFOA and PFOS between groups with and without established chronic disease, highlighting the role of environmental chemicals in the onset and development of chronic diseases.

Structural health monitoring is an effective method to evaluate the safety status of dams. Measurement error is an important factor which affects the accuracy of monitoring data modeling. Processing the abnormal monitoring data before data analysis is a necessary step to ensure the reliability of the analysis. In this paper, we proposed a method to process the abnormal dam displacement monitoring data on the basis of matrix manipulation and Cuckoo Search algorithm. We first generate a scatter plot of the monitoring data and exported the matrix of the image. The scatter plot of monitoring data includes isolate outliers, clusters of outliers, and clusters of normal points. The gray scales of isolated outliers are reduced using Gaussian blur. Then, the isolated outliers are eliminated using Ostu binarization. We then use the Cuckoo Search algorithm to distinguish the clusters of outliers and clusters of normal points to identify the process line. To evaluate the performance of the proposed data processing method, we also fitted the data processed by the proposed method and by the commonly used 3-σ method using a regression model, respectively. Results indicate that the proposed method has a better performance in abnormal detection compared with the 3-σ method.

Antimicrobial peptides (AMPs) are vital components of innate immunotherapy. Existing approaches mainly rely on either deep learning for the automatic extraction of sequence features or traditional manual amino acid features combined with machine learning. The peptide sequence contains symmetrical sequence motifs or repetitive amino acid patterns, which may be related to the function and structure of the peptide. Recently, the advent of large language models has significantly boosted the representational power of sequence pattern features. In light of this, we present a novel AMP predictor called UniproLcad, which integrates three prominent protein language models—ESM-2, ProtBert, and UniRep—to obtain a more comprehensive representation of protein features. UniproLcad utilizes deep learning networks, encompassing the bidirectional long and short memory network (Bi-LSTM) and one-dimensional convolutional neural networks (1D-CNN), while also integrating an attention mechanism to enhance its capabilities. These deep learning frameworks, coupled with pre-trained language models, efficiently extract multi-view features from antimicrobial peptide sequences and assign attention weights to them. Through ten-fold cross-validation and independent testing, UniproLcad demonstrates competitive performance in the field of antimicrobial peptide identification. This integration of diverse language models and deep learning architectures enhances the accuracy and reliability of predicting antimicrobial peptides, contributing to the advancement of computational methods in this field.

RNA pseudouridine modification exists in different RNA types of many species, and it has a significant role in regulating the expression of biological processes. To understand the functional mechanisms for RNA pseudouridine sites, the accurate identification of pseudouridine sites in RNA sequences is essential. Although several fast and inexpensive computational methods have been proposed, the challenge of improving recognition accuracy and generalization still exists. This study proposed a novel ensemble predictor called PseUpred-ELPSO for improved RNA pseudouridine site prediction. After analyzing the nucleotide composition preferences between RNA pseudouridine site sequences, two feature representations were determined and fed into the stacking ensemble framework. Then, using five tree-based machine learning classifiers as base classifiers, 30-dimensional RNA profiles are constructed to represent RNA sequences, and using the PSO algorithm, the weights of the RNA profiles were searched to further enhance the representation. A logistic regression classifier was used as a meta-classifier to complete the final predictions. Compared to the most advanced predictors, the performance of PseUpred-ELPSO is superior in both cross-validation and the independent test. Based on the PseUpred-ELPSO predictor, a free and easy-to-operate web server has been established, which will be a powerful tool for pseudouridine site identification.

Ocean waves are one of the leading environmental factors that cause motion of the ocean’s structure. Wave prediction is of great significance for the safety of marine structures. The deterministic sea wave prediction (DSWP) has been focused on because it provided an accurate temporal wave surface. The propagation velocity of wave components is one of the critical problems in DSWP. In this paper, the research of propagation velocity is focused on. The Taylor expansion to wave number is used to prove that the group velocity is the propagation velocity of wave components. The simulated irregular long crest wave data is generated. Utilizing the simulated data, the calculated wave surfaces based on group velocity are consistent with the simulated results. Meanwhile, the comparisons of calculated results based on the group velocity and phase velocity are given. Then, a tank experiment is set to verify the prediction results. To further investigate the prediction performance under different conditions, the influences of environmental factors, including the wind speed, water depth and sea state are analyzed in this paper.

Herein, the morphological characteristics of submarine archipelagic aprons were presented for five guyots, Suda, Arnold, Lamont, Niulang, and Zhinyv, which are over 80 Ma years old and are located in the Marcus–Wake seamount group, northwestern Pacific Ocean. Nearly 28 landslide deposits were recognized using the bathymetry and backscatter intensity data collected from the studied guyots. Landslides and their deposits that surround seamounts are mostly related to the morphology of debris avalanches, scarps, gullies/channels, and bedforms. The morphology of the archipelagic aprons of the studied guyots indicates mutual landslide processes, including slump and distinct debris avalanches arising from a cohesive or cohesionless landslide material flow. The superimposition of debris flows and sedimentation dominates the recent stages of the studied guyots. The archipelagic aprons corresponding to convex-arc-shaped scarps exhibit larger domains compared to the invagination-arc-shaped scarps with similar lateral lengths. The scarp morphologies of the studied guyots are predominantly of the complex-arc shape, indicating multiple landslide events. Parallel and convergent gullies and channels are mostly found on the elongated landslide deposits, whereas divergent and radial gullies and channels are mostly distributed on the fan-shaped aprons. Ubiquitous sediment waves occurred on the bedforms of the distal archipelagic apron across the studied guyots because of sediment creep. Small-scale sediment waves were only observed in the channels on the aprons of the Suda guyot.

Mycobacterium tuberculosis (Mtb) is one of the major causes of human death. In its battle with humans, Mtb has fully adapted to its host and developed ways to evade the immune system. At the same time, the human immune system has developed ways to respond to Mtb. The immune system responds to viral and bacterial infections through a variety of mechanisms, one of which is alternative splicing. In this study, we summarized the overall changes in alternative splicing of the transcriptome after macrophages were infected with Mtb. We found that after infection with Mtb, cells undergo changes, including (1) directly reducing the expression of splicing factors, which affects the regulation of gene expression, (2) altering the original function of proteins through splicing, which can involve gene truncation or changes in protein domains, and (3) expressing unique isoforms that may contribute to the identification and development of tuberculosis biomarkers. Moreover, alternative splicing regulation of immune-related genes, such as IL-4, IL-7, IL-7R, and IL-12R, may be an important factor affecting the activation or dormancy state of Mtb. These will help to fully understand the immune response to Mtb infection, which is crucial for the development of tuberculosis biomarkers and new drug targets.

The natural flavonoid compound chrysin has promising anti-tumor effects. In this study, we aimed to investigate the mechanism by which chrysin inhibits the growth of non-small cell lung cancer (NSCLC). Through in vitro cell culture and animal models, we explored the impact of chrysin on the growth of NSCLC cells and the pro-cancer effects of tumor-associated macrophages (TAMs) and their mechanisms. We observed that M2-TAMs significantly promoted the growth and migration of NSCLC cells, while also markedly activating the autophagy level of these cells. Chrysin displayed a significant inhibitory effect on the growth of NSCLC cells, and it could also suppress the pro-cancer effects of M2-TAMs and inhibit their mediated autophagy. Furthermore, combining network pharmacology, we found that chrysin inhibited TAMs-mediated autophagy activation in NSCLC cells through the regulation of the CDK1/ULK1 signaling pathway, rather than the classical mTOR/ULK1 signaling pathway. Our study reveals a novel mechanism by which chrysin inhibits TAMs-mediated autophagy activation in NSCLC cells through the regulation of the CDK1/ULK1 pathway, thereby suppressing NSCLC growth. This discovery not only provides new therapeutic strategies for NSCLC but also opens up new avenues for further research on chrysin.

Introduction Obese patients are susceptible to hypoxaemia during procedural sedation. Propofol combined with low-dose opioids is commonly used as a sedation strategy, but it can exacerbate hypoxaemia by causing cardiopulmonary depression and airway obstruction, especially in obese patients. Remimazolam, a novel ultra-short-acting benzodiazepine, has minimal accumulative effects and less cardiorespiratory depression. This study aims to evaluate the safety and efficacy of combining remimazolam tosilate with low-dose fentanyl as an alternative option for procedural sedation in obese patients undergoing gastroscopy.Methods and analysis This randomised controlled trial (RCT) will be conducted in the Endoscopy Centre of the First Affiliated Hospital of Xiamen University, recruiting 174 participants scheduled for painless gastroscopy with a body mass index of 30–39.9 kg×m–2. All patients will be randomly divided into two groups in a 1:1 ratio. The sedation strategy of the intervention group is remimazolam tosilate combined with fentanyl, while the control group is propofol combined with fentanyl. The primary outcome is the incidence of hypoxaemia and the secondary outcomes include the time to ambulation, need for airway manoeuvres and rescue sedation, sleep quality, the incidence of sedation failure, adverse events and the cost of sedatives. All statistical tests will be performed using IBM SPSS V.20.0 statistical software. A p value

AbstractDitches are vital to water system data. To ease the task of matching multi-scale ditch data and enhance accuracy (Acc), it is essential to discern ditch data matching patterns. Despite its importance, limited research has been conducted on ditch matching patterns, and the primary reasons for variations in multi-scale geographical entities’ matching patterns remain underexplored. Here, we introduce a supervised graph neural network (GNN) method, targeting the direct analysis of 1:10,000 ditch characteristics to identify the matching patterns between 1:10,000 and 1:25,000 datasets. The ditch network is depicted as a graph structure, with nodes representing ditch segments and edges indicating their connections. Subsequently, each ditch segment’s geometric, semantic, and topological attributes are computed as node attributes, and their matching patterns with the 1:25,000 dataset are labeled as node annotations. Ditch segment matching patterns are then categorized using supervised learning. Experiments using Overijssel, Netherlands’ ditch data reveal that this method achieves a 97.3% classification Acc, outperforming other GNN methods by 25.6–26.3% and traditional machine learning methods by 33%. These findings underscore the efficacy and superiority of the proposed supervised GNN approach in pinpointing ditch matching patterns.

Trametes versicolor can produce aromatic flavor in growth and development, widely used in food fermentation. This study used a One-Factor-at-a-Time (OFAT) test and response surface analysis to study the optimum fermentation parameters of Rosa roxburghii tratt and coix seed yogurt by Trametes versicolor. The best fermentation process is as follows: skim milk powder 17 %, sucrose content 4 %, Rosa roxburghii tratt and coix seed liquid 36 %, fermentation temperature 39 °C, inoculum 2 %, strain ratio 2:1:1(LB12: BLH1: Q-1), fermentation time 9.5 h. Under this fermentation process, the sensory score was 82.11, the contents of vitamin C, GABA, and total live bacteria in this yogurt were 13.89, 2.58, and 1.02 times higher than in common yogurt. Correlation analyses showed a significant contribution of the leavening agent to the GABA content of yogurt. This study provides a foundation for producing Rosa roxburghii tratt and coix seed yogurt with high sensory and nutritional value.

Drought monitoring is crucial for assessing and mitigating the impacts of water scarcity on various sectors and ecosystems. Although traditional drought monitoring relies on soil moisture data, remote sensing technology has have significantly augmented the capabilities for drought monitoring. This study aims to evaluate the accuracy and applicability of two temperature vegetation drought indices (TVDI), TVDINDVI and TVDIEVI, constructed using the Normalized Difference Vegetation Index (NDVI) and the Enhanced Vegetation Index (EVI) vegetation indices for drought monitoring. Using Guangdong Province as a case, enhanced versions of these indices, developed through Savitzky–Golay filtering and terrain correction were employed. Additionally, Pearson correlation analysis and F-tests were utilized to determine the suitability of the Standardized Precipitation Index (SPI) and the Standardized Precipitation Evapotranspiration Index (SPEI) in correlation with TVDINDVI and TVDIEVI. The results show that TVDINDVI had more meteorological stations passing both significance test levels (P

Objectives: Circ_003686 is a novel_circRNA with abnormally low expression found in the samples of multiple myeloma bone disease (MBD) patients. The current research intended to investigate the effects of novel_circ_003686 in osteogenesis-induced differentiation of bone marrow mesenchymal stem cells (BMSCs) in MBD. Methods: BMSCs were extracted from MBD patients and normal participants, the pcDNA3.1 encoding the circ_003686 (ov-circ_003686), miR-142-5p-mimic/inhibitor and siRNA oligonucleotides targeting insulin like growth factor 1 (IGF1, si-IGF1) were applied to intervene circ_003686, miR-142-5p and IGF1 levels, respectively. Results: Results showed that ov-circ_003686 could mediate the osteogenesis-induced differentiation of MBD-BMSC, and luciferase assay and RIP experiments confirmed that circ_003686 could bind to miR-142-5p. MiR-142-5p-inhibitor helped osteogenesis-induced differentiation, while miR-142-5p-mimic inhibited osteogenesis-induced differentiation and reversed the promoting effect of ov-circ_003686, suggesting that circ_003686/miR-142-5p axis participated in osteogenesis-induced differentiation of MBD-BMSC. In addition, miR-142-5p binds to the target gene IGF1 and negatively adjust its expression. Si-IGF1 significantly inhibited the osteogenesis-induced differentiation and reversed the promotion effects of miR-142-5p-inhibitor and ov-circ_003686. Moreover, circ_003686/miR-142-5p/IGF1 axis meaningfully regulates protein expressions in the PI3K/AKT pathway. Conclusion: In conclusion, this research confirmed that circ_003686 regulated the osteogenesis-induced differentiation of MBD-BMSC by sponging miR-142-5p and mediating IGF1, and the PI3K/AKT pathway may also be involved.

Objective The objective of this study was to investigate the effects and mechanisms of adipose-derived stem cell-derived exosome (ADSCs-Exo) in treating premature ovarian failure (POF). Methods We constructed a POF mouse model through intraperitoneal injection of cyclophosphamide, followed by the administration of the autophagy inhibitor 3-methyladenine (3-MA). Pathological injury, follicle stimulating hormone (FSH), malondialdehyde (MDA), reactive oxygen species (ROS), estradiol (E2), superoxide dismutase (SOD), granulosa cell (GC) apoptosis, and autophagy were assessed. Exosomes isolated from ADSCs were used to treat POF in mice. The AMPK-mTOR pathway and its proteins (p-AMPK and p-mTOR) were evaluated. A POF cell model was established using cyclophosphamide-treated human ovarian granulosa-like tumor (KGN) cells. We administered ADSCs-Exo and rapamycin to validate the mechanism of ADSCs-Exo against POF. Results In POF mice, 3-MA treatment attenuated pathological injuries, decreased FSH, MDA, and ROS levels, and increased E2 and SOD levels. 3-MA treatment also inhibited GC apoptosis and autophagy. ADSCs-Exo alleviated pathological injuries, improved ovarian morphology and function, and reduced oxidative stress in POF mice. ADSCs-Exo inhibited GC apoptosis and autophagy. ADSCs-Exo downregulated the expression of AMPK/mTOR pathway proteins (p-AMPK and p-mTOR). In the POF cell model, ADSCs-Exo and rapamycin inhibited AMPK/mTOR-mediated autophagy. Conclusion ADSCs-Exo inhibits POF through the inhibition of autophagy and the AMPK/mTOR pathway. This study provides a potential target for the clinical treatment of POF.

The current study was conducted to determine the effects of dietary Radix bupleuri root extract (RBE) on the growth performance, muscle composition, immune responses, and microcystin-LR (MC-LR) stress resistance of juvenile red claw crayfish (Cherax quadricarinatus). Crayfish (0.28 ± 0.02 g) were fed experimental diets containing graded RBE levels as 0 (Diet 1), 0.2 (Diet 2), 0.4 (Diet 3), 0.6 (Diet 4), 0.8 (Diet 5) and 1.6 (Diet 6) g/kg RBE for 8 weeks. The results showed that specific growth rate (SGR) and weight gain rate (WGR) were significantly increased in the Diet 4 and Diet 5 groups. The content of muscle crude protein was significantly increased in the Diet 4 and Diet 5 groups, and the crude lipid content was significantly decreased in the Diet 5 group. Dietary RBE did not alter the structure of the hepatopancreas. Total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activities in hepatopancreas and plasma were significantly increased in Diet 4 and Diet 5 groups compared to the control group, while the malondialdehyde (MDA) content in hepatopancreas and plasma was significantly decreased in the Diet 5 group. Plasma alkaline phosphatase (AKP) activity was significantly higher in the Diet 3, Diet 4, Diet 5 and Diet 6 groups. Hepatopancreas and plasma PO activities were significantly increased in Diet 4 and Diet 5 groups. The mRNA levels of extracellular copper/zinc superoxide dismutase (ecCu, Zn-SOD), hemocyanin, C-type lysozyme (C-LZM), GPx, and selenium-dependent glutathione peroxidase (Se-GPx) were significantly up-regulated in the hepatopancreas of crayfish fed Diet 5 than those of the control group. After MC-LR challenge, the survival rates of crayfish in the Diet 4 and Diet 5 groups were significantly higher than the control group. The findings suggest that 0.6–0.8 g/kg of RBE can improve growth and muscle composition and enhance immunity and microcystin-LR resistance.

ABSTRACT Rice bacterial leaf blight (BLB) is the most destructive phyllosphere bacterial disease caused by Xanthomonas oryzae pv. oryzae. The effect of soil-borne diseases on the rhizosphere microbiome has been extensively investigated. However, the regulatory role of the phyllosphere disease BLB on the rhizosphere microbiome remains unclear. Here, we observed that BLB significantly altered the composition of the bacterial-fungal community in the rhizosphere, decreasing bacterial diversity but not fungal diversity. The scale of inter-kingdom networks in the rhizosphere microbiome of BLB-infected plants was more complex and broader than in healthy plants, while the bacterial community was more vulnerable to BLB than the fungal community. Indeed, the relative abundance of Streptomyces, Chitinophaga, Sphingomonas, and Bacillus was higher in the BLB rhizosphere, which can be explained by their keystone hub taxa status in the rhizosphere co-occurrence network. Null model analysis showed that the deterministic assembly of bacterial communities increased while that of fungi decreased. Additionally, the assembly of bacterial and fungal communities was significantly related to variations in BLB and soil nutrients, especially pH and available phosphorus. Random forest model results showed that the bacterial community in the rhizosphere had a strong potential for predicting BLB. Metagenomic analysis revealed that BLB had a considerable impact on the functional adaptation of the rhizosphere microbiome. Interestingly, the abundance of some functional genes involved in carbon, phosphorus, and methane metabolism increased drastically. IMPORTANCE Our results suggest that rhizosphere bacteria are more sensitive to bacterial leaf blight (BLB) than fungi. BLB infection decreased the diversity of the rhizosphere bacterial community but increased the complexity and size of the rhizosphere microbial community co-occurrence networks. In addition, the relative abundance of the genera Streptomyces, Chitinophaga, Sphingomonas, and Bacillus increased significantly. Finally, these findings contribute to the understanding of plant-microbiome interactions by providing critical insight into the ecological mechanisms by which rhizosphere microbes respond to phyllosphere diseases. In addition, it also lays the foundation and provides data to support the use of plant microbes to promote plant health in sustainable agriculture, providing critical insight into ecological mechanisms.

A new Rosa roxburghii Tratt (RRT) and coix seed (CS) beverage rich in multi-active ingredients was developed. Edible mushrooms and L. plantarum were selected for fermentation in stages. Some physicochemical properties, γ-aminobutyric acid (GABA), polysaccharides and sensory were studied during the T. versicolor and L. plantarum fermentation. T. versicolor increased the free amino acid through enzymatic protein digestion in the early growth stage and used these amino acids to synthesize its bacteriophage protein. T. versicolor and L. plantarum increased the polysaccharide and GABA of the fermentation broth. Vitamin C was retained as much as possible, with a slight loss occurring mainly in the aerobic fermentation stage of T. versicolor. Its less loss in exchange was for a higher value of T. versicolor polysaccharide, protein enhancement, and bitterness reduction. This study provides a reference for the deep processing of Guizhou's unique agricultural products and edible mushroom fermented beverage.

Purpose: This study was based on hepatocellular carcinoma (HCC) patients of early-stage to explore the diagnostic capability and possible production causes of anti-GNAS autoantibody. Methods: We evaluated the frequency of anti-GNAS autoantibody in sera from patients with early-stage HCC by enzyme-linked immunosorbent assay (ELISA) and the expression of GNAS protein in early-stage HCC tissues by immunohistochemistry. Western blotting (WB) and real-time polymerase chain reaction (RT-PCR) were utilized to examine the expressions of GNAS protein and mRNA in cell lines. GEO and International Cancer Genome Consortium (ICGC) databases were inquired to explore mRNA expression and mutation of GNAS in HCC tissues. Results: The positive rates of anti-GNAS autoantibody in HCC patients at clinical stage I (78.1 %) and clinical stage II (57.1 %) were all significantly higher than that in healthy control (20 %). There was also a significant difference in GNAS protein expression between HCC and its adjacent normal liver tissues. The results from WB and RT-PCR showed a significant difference at the mRNA level but no statistical difference at the protein level between HCC and normal liver cell lines. The difference in mRNA level between HCC and adjacent normal liver tissues was verified to be significant. Furthermore, the ICGC database demonstrated a 10.6 % mutation frequency for GNAS in HCC patients. Conclusion: The coordination of elevated anti-GNAS autoantibody, high expression of GNAS in the mRNA and protein levels in HCC, and high frequency of GNAS mutation indicates that anti-GNAS autoantibody may be used as an early indicator of HCC.

Summary: Mastitis, a common disease for female during lactation period that could cause a health risk for human or huge economic losses for animals, is mainly caused by S. aureus invasion. Here, we found that neutrophil recruitment via IL-17A-mediated signaling was required for host defense against S. aureus-induced mastitis in a mouse model. The rapid accumulation and activation of Vγ4+ γδ T cells in the early stage of infection triggered the IL-17A-mediated immune response. Interestingly, the accumulation and influence of γδT17 cells in host defense against S. aureus-induced mastitis in a commensal microbiota-dependent manner. Overall, this study, focusing on γδT17 cells, clarified innate immune response mechanisms against S. aureus-induced mastitis, and provided a specific response to target for future immunotherapies. Meanwhile, a link between commensal microbiota community and host defense to S. aureus mammary gland infection may unveil potential therapeutic strategies to combat these intractable infections.

ABSTRACTPulmonary arterial hypertension (PAH) is a disease with a high mortality and few treatment options to prevent the development of pulmonary vessel remodeling, pulmonary vascular resistance, and right ventricular failure. Canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is originally used in diabetes patients which could assist the glucose excretion and decrease blood glucose. Recently, a few studies have reported the protective effect of SGLT2 inhibitor on monocrotaline-induced PAH. However, the effects of canagliflozin on hypobaric hypoxia-induced PAH as well as its mechanism still unclear. In this study, we used hypobaric hypoxia-induced PAH mice model to demonstrate if canagliflozin could alleviate PAH and prevent pulmonary vessel remodeling. We found that daily canagliflozin administration significantly improved survival in mice with hypobaric hypoxia-induced PAH compared to vehicle control. Canagliflozin treatment significantly reduced right ventricular systolic pressure and increased pulmonary acceleration time determined by hemodynamic assessments. Canagliflozin significantly reduced medial wall thickening and decreased muscularization of pulmonary arterioles compared to vehicle treated mice. In addition, canagliflozin inhibited the proliferation and migration of pulmonary arterial smooth muscle cells through suppressing glycolysis and reactivating AMP-activated protein kinase signaling pathway under hypoxia condition. In summary, our findings suggest that canagliflozin is sufficient to inhibit pulmonary arterial remodeling which is a potential therapeutic strategy for PAH treatment.

During the COVID-19 pandemic, China has been the leading exporter and donor of COVID-19 vaccines in the world. Based on a survey of 460 Chinese participants conducted in mainland China in March 2021, the results showed that the participants’ value-expressive attitudes (i.e. their responsibility to help) and esteem attitudes (i.e. China's image and status) were strong predictors of their support for vaccine exports and donations, whereas attitudes related to prevention and a possible vaccine shortage in China were weak predictors. Fairness and ingroup loyalty were the major moral foundations of their support for such international efforts; the influence of fairness and ingroup loyalty was both direct and mediated by value-expressive and esteem attitudes. Collectively, the present results show that support for international efforts can be analysed from a moral, altruistic perspective and thus extend the previous theorising that focused on the transactional nature of international outreach efforts.

Microcystin-LR (MC-LR), the most prevalent cyanobacterial toxin, poses a serious threat to the survival of aquatic animals. Herein, crayfish (Cherax quadricarinatus) were treated with MC-LR at 33.06 μg kg−1 for 48 h, and the effects of MC-LR on behavior, histomorphology, oxidative stress, non-specific immunity, and gene expression were investigated to elucidate the molecular mechanisms underlying antioxidation and detoxification in crayfish. MC-LR caused vacuolation and disruption of crayfish hepatopancreatic cells, although no significant effect was observed on the structure of intestinal cells. Moreover, MC-LR increased the activity of antioxidant enzymes (SOD, CAT, GPx, GST) and up-regulated the expression of genes encoding antioxidant enzymes (ecCu,Zn-SOD, SOD, Se-GPx, GPx3P, GST). In addition, GSH was found depleted in the hepatopancreas and plasma. MC-LR activated the immune system, enhanced immunoenzyme activity (ACP, AKP) and induced the expression of immunity-related genes (C-LZM, proPO, hemocyanin). Furthermore, caspase and HSP70 genes were induced in the hepatopancreas of crayfish under MC-LR stress. Taken together, MC-LR was shown to cause a positive response in crayfish, and our findings suggested that the antioxidant activity and immune system play an important role in protecting crayfish from MC-LR stress by regulating gene expression and activities of antioxidant and immune enzymes.

A producing-fibrinolytic enzyme strain was isolated with high yield. The strain was identified as Bacillus amyloliquefaciens. B. amyloliquefaciens GUTU06 fibrinolytic enzyme was purified by acetone precipitation and reverse micelle. Acetone precipitation condition and reverse micelle condition were examined. Results showed that the total reverse micelle extraction efficiency was 64.49 % ± 1.6 %. The purification fold of the entire process reached 13.38. The optimum pH of purified enzyme is 5, and the optimum temperature is 45 °C. Fe3+ and K+ can enhance the fibrinolytic activity of the enzyme. Compared to commercial fibrinolytic enzymes such as urokinase and lumbrukinase, GUTU06 fibrinolytic enzymes have a lower pH optimal range and higher temperature stability. The molecular weight of the enzyme was approximately 28 kDa. Reverse micelle extraction with cetyl trimethylammonium bromide as a surfactant combined with acetone precipitation is suitable for separating and purifying fibrinolytic enzymes and a promising technique for obtaining active proteins.

High entropy alloys (HEAs) based on five or more elements have caught worldwide attention due to the excellent properties endowed by their unique structures. Compared with traditional alloys, HEAs have high strength, thermal stability, oxidation resistance, and corrosion resistance. In recent years, the rapid development of HEAs shed light on the designing of new alloy systems. Their mixed multi-metallic sites give rise to a great potential for catalytic applications. In this review, we briefly introduce the phase structures of HEAs and their four core effects. In addition, the latest advances regarding HEAs are systematically summarized, with emphasis on the synthesis methods and catalytic applications, such as thermal-driven catalysis and electrocatalysis. To sum up, the current progress, challenges and future prospects of HEAs are discussed, hoping to provide a valuable route to understand this research field.

African swine fever (ASF) is a highly contagious and acute hemorrhagic viral disease with high morbidity and mortality in domestic pigs and wild boars. The disease has become a global threat to the pig production industry and has caused enormous economic losses in many countries in recent years. However, the molecular mechanism underlying ASF virus (ASFV) entry of the host cells is not fully understood, which restricts the development of vaccines and antiviral-drugs of ASFV. In this study, we found that the host protein CD1d acts as a host factor, which mediates ASFV entry into the host cells. As the main capsid protein on the surface of ASFV virions, p72 can mediate viral entry. Using IP-MS assay, CD1d was identified as a binding partner of p72 on surface of ASFV virions. Knockdown of CD1d expression and blocking the cells with anti-pCD1d antibody, or incubating ASFV virions with soluble CD1d protein could significantly inhibit ASFV infection. CD1d is located on the membrane surface of primary porcine alveolar macrophages (PAMs) and mediates the virus entry via binding to p72. CD1d knockout or CD1d knockdown assay showed that CD1d could facilitate ASFV virions internalization via clathrin-mediated endocytosis (CME). Furthermore, CD1d interacts with EPS15 to mediate ASFV entry via clathrin-mediated endocytosis. Overall, our findings revealed that CD1d is a novel host-entry factor involved in ASFV internalization via the EPS15-clathrin endocytosis axis and a potential target for antiviral intervention.

Massa Medicata Fermentata (MMF) is widely applied in feed additives and human medicine. The stir-frying is a commonly used method for process of MMF, which will improve its efficacy in invigorating the spleen. However, the dynamic change of physical properties and ingredients during stir-frying remain un-elucidated. Here, the appearance color, pH values, UV–visible and fluorescence spectroscopy, content of volatile and non-volatile compounds of MMF at different process stage of stir-frying were measured. The results indicated that with increasing stir-frying time, the appearance color deepened, and pH value decreased, while the UV absorbance and fluorescence exhibited rising trends. Additionally, we identified four non-volatile compounds from MMF, and three of them showed gradual increase in content during stir-frying (from 0 to 30 min). Regarding the volatile compounds, the content of alcohols decreased, while aldehydes increased evidently after 30 min. These results demonstrated that the physicochemical properties, types of compounds and their content all significantly changed during stir-frying. The study provides insights regarding the change in substance and appearance, which will provide a guidance for the judgment of the degree of stir-frying MMF.

ABSTRACTBackground miR-454-3p is considered to have a crucial role in cancer progression, but the potential involvement in acute myeloid leukemia (AML) remains unclear.Methods Expression of miR-454-3p and ZEB2 mRNA and protein were quantified in AML cell lines. Cells were transfected with miR-454-3p inhibitor or mimic and cell growth was assessed by colony formation and CCK-8 assays and the cell cycle, apoptosis and autophagy were investigated by Western blotting, flow cytometry, immunofluorescence and 3-methyladenine (3-MA) treatment.Results miR-454-3p expression was attenuated in AML cells. miR-454-3p overexpression attenuated cell growth and stimulated cell cycle arrest, apoptosis and autophagy. Dual-luciferase reporter assays and bioinformatics analysis showed that AML progression was inhibited when miR-454-3p regulated ZEB2, an effect confirmed by rescue assays. 3-MA reduced the autophagy-inducing effect of ZEB2 knockdown and indicated that autophagy induced apoptosis. miR-454-3p downregulated p-mTOR/p-AKT levels in AML cells.Conclusion The novel role of miR-454-3p as a tumor inhibitor in AML via regulation of the ZEB2/AKT/mTOR axis was demonstrated, indicating miR-454-3p as a potential new molecular target for AML.

AbstractHow to achieve stable co-delivery of multiple phytochemicals is a common problem. This study focuses on the development, optimization and characterization of Huanglian-HouPo extract nanoemulsion (HLHPEN), with multiple components co-delivery, to enhance the anti-ulcerative colitis (UC) effects. The formulation of HLHPEN was optimized by pseudo-ternary phase diagram combined with Box-Behnken design. The physicochemical properties of HLHPEN were characterized, and its anti-UC activity was evaluated in DSS-induced UC mice model. Based on preparation process optimization, the herbal nanoemulsion HLHPEN was obtained, with the droplet size, PDI value, encapsulation efficiency (EE) for 6 phytochemicals (berberine, epiberberine, coptisine, bamatine, magnolol and honokiol) of 65.21 ± 0.82 nm, 0.182 ± 0.016, and 90.71 ± 0.21%, respectively. The TEM morphology of HLHPEN shows the nearly spheroidal shape of particles. The optimized HLHPEN showed a brownish yellow milky single-phase and optimal physical stability at 25 °C for 90 days. HLHPEN exhibited the good particle stability and gradual release of phytochemicals in SGF and SIF, to resist the destruction of simulated stomach and small intestine environment. Importantly, the oral administration of HLHPEN significantly restored the shrunk colon tissue length and reduced body weight, ameliorated DAI value and colon histological pathology, decreased the levels of inflammatory factors in DSS-induced UC mice model. These results demonstrated that HLHPEN had a significant therapeutic effect on DSS-induced UC mice, as a potential alternative UC therapeutic agent.

Background: Although vaccinations and antiviral drugs are widely used in the clinical treatment worldwide, there is little investigation on the clinical outcomes and effectiveness of oral Azvudine tablets (FNC) treatment in COVID-19 hospitalized patients. The previous data showed Azvudine treatment was closely related to reduced virus shedding time, but the potential role of Azvudine on inflammatory response is scarce. Thus, this study is to investigate inflammatory predictors and effectiveness of oral Azvudine tablets treatment in COVID-19 hospitalized patients. Methods: A total of 600 out of hospitalized patients were retrospectively collected over a 2-month period, of whom 60 out of hospitalized patients infected SARS-CoV-2. 32 of hospitalized patients who received Azvudine tablets were collected and the rest did not. Oral Azvudine tablets treatment: 5 mg/day for 7–14 days. We analyzed the routine blood tests, blood coagulation test, NT-proBNP, Troponin (cTNl), Creatine kinase MB (CK-MB) after oral Azvudine tablets treatment compared with that in before oral Azvudine tablets treatment. Also, we compared the CT chest and length of Stay after Azvudine treatment. Results: We found that the number and percentage of eosinophil increased significantly, but the levels of C-reactive protein (C-RP) and IL-6 reduced remarkably after Azvudine treatment. In blood coagulation tests, the results showed that activated partial thromboplastin time (APTT) (mean ± SEM: 2.950 ± 2.268s) and fibrinogen (mean ± SEM: 0.8910 ± 0.5134g/L) downregulated slightly, while there was similar in the level of D-Dimer (mean ± SEM: 0.1660 ± 0.3108 μg/mL) before and after Azvudine treatment. The expression of NT-proBNP reduced in Azvudine treatment (mean ± SEM: 897.1 ± 557.1pg/mL). Chest computed tomography (CT) scan reports also demonstrated that Azvudine treatment improved lung symptoms in COVID-19 hospitalized patients. Moreover, there is no difference in the average of length of stay in Azvudine treatment (the average of LOS days: 9.0) and no treatment (the average of LOS days: 9.0) Conclusion: Oral Azvudine tablets treatment was associated with decreased inflammatory response and improved blood coagulation function, which should be substantial clinical benefits in COVID-19 hospitalized patients.

Intralayer and interlayer excitons are fundamental quasiparticles that can appear simultaneously in transition metal dichalcogenide van der Waals heterostructures. The understanding and modulation of the interaction of interlayer and intralayer excitons are of great importance for both fundamental studies and device applications. Here, we demonstrate the modulation of photoluminescence (PL) emissions of interlayer and intralayer excitons in WSe2/WS2 heterostructures using different stacking configurations in a single sample, including with and without hexagonal boron nitride (hBN) encapsulation and different hBN spacing layers. By temperature dependent PL spectroscopy, we observed the suppression of interlayer exciton formation and exciton complexes at high temperatures due to enhanced phonon scattering. We also verify the formation of these states via power dependent spectroscopy. Our electric field and doping dependent PL studies reveal that the interlayer exciton peaks shift linearly with the applied gate voltage and the intralayer excitons of WSe2 (WS2) are dominant at high n-doping (p-doping). Our results contribute to the understanding of the interplay between interlayer and intralayer excitons in WSe2/WS2 heterostructures and could promote the related exitonic device applications.

BackgroundMycoplasma pneumoniae pneumonia (MPP), attributable to Mycoplasma pneumoniae (MP), represents a predominant form of community-acquired pneumonia in pediatric populations, thereby posing a significant threat to pediatric health. Given the burgeoning volume of research literature associated with pediatric MPP in recent years, it becomes imperative to undertake a bibliometric analysis aimed at delineating the current research landscape and emerging trends, thereby furnishing a framework for subsequent investigations.MethodsA comprehensive literature search targeting pediatric MPP was conducted in the Web of Science Core Collection. After the removal of duplicate entries through Endnote software, the remaining articles were subject to scientometric analysis via Citespace software, VOSviewer software and R language, focusing on variables such as publication volume, contributing nations, institutions and authors, references and keywords.ResultsA total of 1,729 articles pertinent to pediatric MPP were included in the analysis. China and the United States emerged as the nations with the highest publication output. Italian scholar Susanna Esposito and Japanese scholar Kazunobu Ouchi were the most influential authors in the domain of pediatric MPP. Highly-cited articles primarily focused on the epidemiological investigation of pediatric MPP, the clinical characteristics and treatment of macrolide-resistant MPP, and biomarkers for refractory Mycoplasma pneumoniae pneumonia (RMPP). From the corpus of 1,729 articles, 636 keywords were extracted and categorized into ten clusters: Cluster #0 centered on molecular-level typing of macrolide-resistant strains; Cluster #1 focused on lower respiratory tract co-infections; Clusters #2 and #6 emphasized other respiratory ailments caused by MP; Cluster #3 involved biomarkers and treatment of RMPP; Clusters #4 and #9 pertained to extrapulmonary complications of MPP, Clusters #5 and #7 addressed etiological diagnosis of MPP, and Cluster #8 explored pathogenic mechanisms.ConclusionsThe past few years have witnessed extensive attention directed towards pediatric MPP. Research in pediatric MPP principally revolves around diagnostic techniques for MP, macrolide resistance, complications of MPP, treatment and diagnosis of RMPP, and elucidation of pathogenic mechanisms. The present study provides pediatric clinicians and researchers with the research status and focal points in this field, thereby guiding the orientation of future research endeavors.

Ethnopharmacological relevance: Pinellia ternata (Thunb.) Breit. is a well-known perennial herb that is used in traditional medicine in China, Japan and Korea. It's drawing worldwide interests in medicinal applications owing such as anti-diarrhea, lipid-lowering, anti-tumor, anti-cough, expectorant, anti-gastric ulcer, etc. Aim of the study: This review aims to provide useful information on the botany, traditional uses, phytochemistry, pharmacology, toxicity and quality control of Pinellia ternata to help increase its efficiency. In addition, this review will discuss the future research trends and development prospects of this plant. Materials and methods: Data was obtained through a systematic search of published literature and online databases such as Google Scholar, Web of Science, PubMed, Science Direct, and Sci-Finder. The botanical names were confirmed using the World Flora Online and chemical structures were drawn using the ChemBio Draw Ultra Version 19.0 Software. Results: Pinellia ternata is distributed in regions of China and other areas. Pinellia ternata and its compound preparations can be used for cough, vomiting, gastric ulcer and other diseases. Approximately 212 chemical constituents have been isolated from Pinellia ternata, including alkaloids, volatile oils, amino acids, organic acids, flavonoids, cerebrosides, phenylpropanoids and other compounds. Considerable pharmacological experiments in vitro and in vivo have demonstrated that Pinellia ternata possessed antitumor effect, antitussive effects, antiasthmatic effects, increasing resistance to gastric ulcer, and antidiarrheal effect. However, these extracts can also lead to various toxicities such as irritant toxicity, cardiotoxicity, hepatotoxicity and embryonic toxicity. Considerable experiments have demonstrated that different processing methods and suitable compatibility with other herbs can effectively reduce the toxicities and increase the efficiency of Pinellia ternata. Conclusions: Pinellia ternata is an ancient herbal medicine with a broad spectrum of pharmacological activities that has been used for thousands of years in China. Future studies should perform an in-depth analyses of the pharmacokinetics and mechanisms of toxicity of Pinellia ternata. Quality standards should be developed to correspond to the various application methods to ensure the efficacy of drugs in actual treatment.

Aims: Nitrogen (N) supply and precipitation pattern (amount and frequency) both affect plant growth. However, N deposition is increasing and precipitation regimes are changing in the context of global change. An experiment was conducted to access how the growth of Robinia pseudoacacia, a widely distributed and cultivated N2-fixing alien species, is affected by both the pattern of precipitation and N supplies. Methods: Seedlings were grown in a glasshouse at four different N levels combined with different precipitation regimes, including three precipitation amounts, and two precipitation frequencies. After treatment for 75 days, plant height, biomass allocation, leaf and soil nutrient concentrations were measured. Results: Plants under high precipitation frequency had greater biomass compared with plants lower precipitation frequency, despite receiving the same amount of precipitation. Higher N supply reduced biomass allocation to nodules. Under low precipitation level, nodule growth and N2 fixation of R. pseudoacacia was more inhibited by high N deposition compared with plants under higher precipitation level. Even slightly N deposition under higher precipitation inhibited N2 fixation but it was insufficient to meet the N needs of the plants. Conclusions: Even at low levels, N deposition might inhibit N2 fixation of plants but low N in soil cannot meet the N requirements of plants, and caused N2 fixation limitation in plants during seedling stage. There was likely a transition from N2 fixation to acquisition of N from soil directly with root when N supply was increased.

Salvianolic acid A (Sal A), extracted from Danshen, has proven efficacy in preventing cardiovascular diseases. However, its effect on mitigating vascular damage caused by chronic kidney disease remains unclear. This study investigated the therapeutic effects and underlying mechanisms of Sal A in a rat model of 5/6 Nephrectomized (5/6Nx). The results of our study showed that Sal A effectively reduced the levels of kidney injury markers. Histopathological analysis revealed that Sal A dose-dependently attenuated arterial injury. The attenuation was characterized by the thinning of vascular endothelium and reduced endothelial cell hyperplasia, accompanied by decreased expression of OPN and C-Reaction Protein (CRP). Further investigations revealed that Sal A alleviated oxidative stress-induced vascular injury by activating the Phosphoinositide 3-kinase (PI3K)/Protein Kinase B(Akt)/Nuclear factor erythroid2-related factor 2(Nrf2)/Heme Oxygenase 1(HO-1) signaling pathway. Furthermore, Sal A inhibited inflammation by suppressing the Sirtuin-1(SIRT1)/Toll-like receptor 4(TLR4)/Nuclear factor kappa-B(NF-κB)/P38 signaling pathway and reducing the expression of pro-inflammatory cytokines. Our oxidative stress and inflammation cell models also supported these findings. In conclusion, Sal A treatment effectively attenuated vascular injury in 5/6Nx rats and exerted dual antioxidant and anti-inflammatory effects.

Objective: To investigate adverse events (AEs) associated with denosumab (Dmab) and zoledronic acid (ZA), compare their association strengths, and explore potential applications to provide clinical reference.Methods: We collected data from FAERS from January 2004 to November 2022 and mined AE signals for Dmab and ZA using ROR values. We compared signal intensity for same AEs and investigated off-label use. We also examined their AEs in adjuvant therapy for breast and prostate cancer.Results: 154,735 reports of primary suspect drugs were analyzed in the FAERS database (Dmab: 117,857; ZA: 36,878). Dmab and ZA had 333 and 1,379 AE signals, with 189 overlaps. The AEs of Dmab included death (ROR:3.478), osteonecrosis of jaw (ROR:53.025), back pain (ROR:2.432), tooth disorder (ROR:16.18), bone pain (ROR:6.523). For ZA, the AEs included osteonecrosis (ROR:104.866), death (ROR: 3.645), pain (ROR:3.963), osteonecrosis of jaw (ROR: 91.744), tooth extraction (ROR: 142.143). Among overlap signals, Dmab showed higher strength in exostosis of the jaw (ROR: 182.66 vs. 5.769), atypical fractures (ROR: 55.589 vs. 9.123), and atypical femur fractures (ROR:49.824 vs. 4.968). And ZA exhibited stronger associations in abscess jaw (ROR: 84.119 vs. 11.12), gingival ulceration (ROR: 74.125 vs. 4.827), increased bone formation (ROR: 69.344 vs. 3.218). Additionally, we identified 528 off-label uses for Dmab and 206 for ZA, with Dmab mainly used in prostate cancer (1.04%), breast cancer (1.03%), and arthritis (0.42%), while ZA in breast cancer (3.21%), prostate cancer (2.48%), and neoplasm malignant (0.52%). For Dmab in breast cancer treatment, AEs included death (11.6%), disease progression (3.3%), and neutropenia (2.7%), while for ZA included death (19.8%), emotional disorder (12.9%), osteomyelitis (11.7%). For prostate cancer treatment, Dmab`s AEs were death (8.9%), prostate cancer metastatic (1.6%), renal impairment (1.7%), while ZA`s included death (34.4%), general physical health deterioration (19.9%), and hemoglobin decreased (18.9%).Conclusion: Our analysis of FAERS database provided postmarketing surveillance data and revealed different strengths of reported AE signals between Dmab and ZA in some of their common AEs. It’s also worth noting that both drugs have potential off-label applications, which could introduce new AEs. This highlights the necessity for safety monitoring when using Dmab and ZA off-label.

Background & Aims: Receptor-interacting serine/threonine-protein kinase 3 (RIPK3) is a central player in triggering necroptotic cell death. However, whether macrophage RIPK3 may regulate NOD1-dependent inflammation and calcineurin/transient receptor potential cation channel subfamily M member 7 (TRPM7)-induced hepatocyte death in oxidative stress-induced liver inflammatory injury remains elusive. Methods: A mouse model of hepatic ischaemia–reperfusion (IR) injury, the primary hepatocytes, and bone marrow-derived macrophages were used in the myeloid-specific RIPK3 knockout (RIPK3M-KO) and RIPK3-proficient (RIPK3FL/FL) mice. Results: RIPK3M-KO diminished IR stress-induced liver damage with reduced serum alanine aminotransferase/aspartate aminotransferase levels, macrophage/neutrophil infiltration, and pro-inflammatory mediators compared with the RIPK3FL/FL controls. IR stress activated RIPK3, inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α), x-box binding protein 1 (XBP1), nucleotide-binding oligomerisation domain-containing protein 1 (NOD1), NF-κB, forkhead box O1 (Foxo1), calcineurin A, and TRPM7 in ischaemic livers. Conversely, RIPK3M-KO depressed IRE1α, XBP1, NOD1, calcineurin A, and TRPM7 activation with reduced serum tumour necrosis factor α (TNF-α) levels. Moreover, Foxo1M-KO alleviated IR-induced liver injury with reduced NOD1 and TRPM7 expression. Interestingly, chromatin immunoprecipitation coupled with massively parallel sequencing revealed that macrophage Foxo1 colocalised with XBP1 and activated its target gene Zc3h15 (zinc finger CCCH domain-containing protein 15). Activating macrophage XBP1 enhanced Zc3h15, NOD1, and NF-κB activity. However, disruption of macrophage Zc3h15 inhibited NOD1 and hepatocyte calcineurin/TRPM7 activation, with reduced reactive oxygen species production and lactate dehydrogenase release after macrophage/hepatocyte coculture. Furthermore, adoptive transfer of Zc3h15-expressing macrophages in RIPK3M-KO mice augmented IR-triggered liver inflammation and cell death. Conclusions: Macrophage RIPK3 activates the IRE1α–XBP1 pathway and Foxo1 signalling in IR-stress livers. The XBP1–Foxo1 interaction is essential for modulating target gene Zc3h15 function, which is crucial for the control of NOD1 and calcineurin-mediated TRPM7 activation. XBP1 functions as a transcriptional coactivator of Foxo1 in regulating NOD1-driven liver inflammation and calcineurin/TRPM7-induced cell death. Our findings underscore a novel role of macrophage RIPK3 in stress-induced liver inflammation and cell death, implying the potential therapeutic targets in liver inflammatory diseases. Impact and implications: Macrophage RIPK3 promotes NOD1-dependent inflammation and calcineurin/TRPM7-induced cell death cascade by triggering the XBP1–Foxo1 axis and its target gene Zc3h15, which is crucial for activating NOD1 and calcineurin/TRPM7 function, implying the potential therapeutic targets in stress-induced liver inflammatory injury.

Background A close relationship exists between obstructive sleep apnoea (OSA) and hypertension. However, the impact of hypertension on the prognostic significance of OSA in patients with acute coronary syndrome (ACS) remains unclear.Methods This is a post hoc analysis of the OSA-ACS project, which consecutively included patients with ACS and receiving overnight sleep study from June 2015 to January 2020. OSA was defined as AHI ≥15 events/hour. The primary outcome was major adverse cardiovascular and cerebrovascular events (MACCE), including a composite of cardiovascular death, myocardial infarction, stroke, ischemia-driven revascularisation or hospitalisation for unstable angina or heart failure.Results A total of 1927 patients with ACS were finally enrolled in this study. The mean patient age was 56.4±10.5 years. Among them, 1247 (64.7%) patients had hypertension, and 1014 (52.6%) patients had OSA. During 2.9 (1.5, 3.6) years of follow-up, OSA was associated with an increased risk of MACCE among patients with hypertension (HR=1.35, 95% CI 1.04 to 1.75, p=0.02), but not in patients without hypertension (HR=1.15, 95% CI 0.79 to 1.68, p=0.47). The interaction between OSA and hypertension for MACCE was not statistically significant (interaction p=0.29). For patients with pre-existing hypertension, OSA was associated with an increased risk of MACCE only among those with grade 3 hypertension (HR 1.54, 95% CI 1.12 to 2.13, p=0.008), but not those with grade 1 or 2 hypertension.Conclusions OSA was associated with an increased risk of MACCE following ACS in patients with hypertension, especially in patients with pre-existing severe hypertension. These findings highlight the importance of identifying OSA in ACS patients with hypertension.Trial registration number NCT03362385.

BackgroundThe association between exposure to trace elements mixture and the prevalence of kidney stones and the interactions between elements are unclear. The aim of this study was to explore the association between exposure to trace elements mixture and the prevalence of kidney stones and the interactions between the elements.MethodsA total of 1,244 participants (139 kidney stone formers and 1,105 non-stone former participants) in NHANES 2017–2018 were included. The exposure to trace elements was evaluated by measuring their concentration in urine samples. Three methods, Logistic regression, quantile-based g computation (qgcomp), and Bayesian kernel machine regression (BKMR), were used for analysis.ResultsAccording to the results from qgcomp and BKMR, a negative association was found between exposure to the 13 trace elements and the prevalence of kidney stones [OR = 0.50 (0.32, 0.78)]. Subgroup analysis revealed that Co, As, and iodine in the whole population, Co, As, and Ni in males, and Cs, iodine, and Sb in females, were most strongly associated with kidney stones. Kidney stone was found to be positively correlated with Co and negatively correlated with the other elements. Besides, there were significant interactions between Ni and Pb in the whole population, Co and iodine in males, and Pb and iodine in females.ConclusionThere was a negative association between exposure to the mixture of 13 trace elements and the prevalence of kidney stones.

IntroductionRadiation therapy is a common treatment option for Head and Neck Cancer (HNC), where the accurate segmentation of Head and Neck (HN) Organs-AtRisks (OARs) is critical for effective treatment planning. Manual labeling of HN OARs is time-consuming and subjective. Therefore, deep learning segmentation methods have been widely used. However, it is still a challenging task for HN OARs segmentation due to some small-sized OARs such as optic chiasm and optic nerve.MethodsTo address this challenge, we propose a parallel network architecture called PCG-Net, which incorporates both convolutional neural networks (CNN) and a Gate-Axial-Transformer (GAT) to effectively capture local information and global context. Additionally, we employ a cascade graph module (CGM) to enhance feature fusion through message-passing functions and information aggregation strategies. We conducted extensive experiments to evaluate the effectiveness of PCG-Net and its robustness in three different downstream tasks. ResultsThe results show that PCG-Net outperforms other methods, improves the accuracy of HN OARs segmentation, which can potentially improve treatment planning for HNC patients.DiscussionIn summary, the PCG-Net model effectively establishes the dependency between local information and global context and employs CGM to enhance feature fusion for accurate segment HN OARs. The results demonstrate the superiority of PCGNet over other methods, making it a promising approach for HNC treatment planning.

For the fully mechanized caving face, it is easy to cause significant surface subsidence and other related problems after large-scale mining of coal seams, we should take some measures to solve them. In this study, in order to further explore the movement pattern of overburden and the form of spatial development of separation after mining in a fully mechanized caving face, we combined the engineering practice of Tangshan mining area, took the T2294 and T2291 working faces as the engineering background and used the three methods of similar simulation, numerical simulation and field measurement to comprehensively study. The results show that in the first stage of working face mining, the separation can generally reach 0.31 times the mining thickness of the coal seam, and the maximum can reach 0.58 times the mining thickness; in the second stage, the width of the separation seam is narrow, and the separation is small. It generally takes 20–30 days for the separation to reach its maximum from initiation, which is equivalent to the working face advancing 70–100 m, and the corresponding horizon height is 200 m. The research results provide theoretical guidance and a basis of engineering practice for the safe mining of multiple working faces under the Jingshan railway. This study even provides a basic theoretical reference for the safe mining of a thick coal seam working face under similar engineering geological conditions.

Rift Valley fever phlebovirus (RVFV) is a zoonotic mosquito-transmitted arbovirus, presenting a serious threat to humans and animals. Susceptible hosts are of great significance for the prevention of RVFV. Appropriate animal models are helpful to better understand the onset and development of diseases, as well as the control measures and vaccine research. This review focuses on the role of animal hosts in the maintenance of the virus, and summarizes the host range of RVFV. We list some common animal models in the process of RVFV research, which would provide some important insights into the prevention and treatment of RVFV, as well as the study of Rift Valley fever (RVF) pathogenesis and vaccines.

Abstract The spike protein of SARS‐CoV‐2 hijacks the host angiotensin converting enzyme 2 (ACE2) to meditate its entry and is the primary target for vaccine development. Nevertheless, SARS‐CoV‐2 keeps evolving and the latest Omicron subvariants BQ.1 and XBB have gained exceptional immune evasion potential through mutations in their spike proteins, leading to sharply reduced efficacy of current spike‐focused vaccines and therapeutics. Compared with the fast‐evolving spike protein, targeting host ACE2 offers an alternative antiviral strategy that is more resistant to viral evolution and can even provide broad prevention against SARS‐CoV and HCoV‐NL63. Here, we use prime editor (PE) to precisely edit ACE2 at structurally selected sites. We demonstrated that residue changes at Q24/D30/K31 and/or K353 of ACE2 could completely ablate the binding of tested viruses while maintaining its physiological role in host angiotensin II conversion. PE‐mediated ACE2 editing at these sites suppressed the entry of pseudotyped SARS‐CoV‐2 major variants of concern and even SARS‐CoV or HCoV‐NL63. Moreover, it significantly inhibited the replication of the Delta variant live virus. Our work investigated the unexplored application potential of prime editing in high‐risk infectious disease control and demonstrated that such gene editing‐based host factor reshaping strategy can provide broad‐spectrum antiviral activity and a high barrier to viral escape or resistance.