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Background Inflammatory mediators in the synovial fluid (SF) play critical roles in the initiation and development of pain in knee osteoarthritis (KOA). However, data for inflammatory marker expression are conflicting, and the role of SF inflammatory mediators in neuropathic pain is not clear. Therefore, the aim of this study was to identify SF inflammatory mediators associated with nociceptive and neuropathic pain in KOA. Methods Levels of IL-1β, IL-6, TNF-α, macrophage colony-stimulating factor, MMP-3, MMP-13, metalloproteinase with thrombospondin motifs 5, calcitonin gene-related peptide, neuropeptide Y, substance P and bradykinin were measured using enzyme-linked immunosorbent assays in 86 patients. Nociceptive pain was assessed using the numeric rating scale (NRS), visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Neuropathic pain was determined using the PainDETECT questionnaire. Moreover, knee function was evaluated by the WOMAC score and range of motion (ROM) assessments. Radiological grade was defined using the Kellgren-Lawrence (K-L) grading scale. Results Pain scores measured using different methods correlated highly with each other. A worse K-L grade and knee function were associated with worse pain. Expression of IL-1β and IL-6 was increased in the early stage compared with the late stage. The NRS score correlated positively with age, K-L grade, and the WOMAC score and negatively with ROM and TNF-α expression. The VAS correlated positively with age, K-L grade, and the WOMAC score but negatively with ROM and levels of IL-1β, IL-6 and TNF-α. The WOMAC pain score did not correlate with any of the inflammatory mediators measured; it correlated only with ROM. The PainDETECT score correlated only with the WOMAC score. Expression of other inflammatory mediators did not correlate with any of the pain scores. Conclusions IL-1β, IL-6 and TNF-α play critical roles in pain in the early stage of KOA and correlate with pain. The catabolic enzymes and neuropeptides measured do not correlate with nociceptive and neuropathic pain. New biomarkers related to pain in the late stage need to be further investigated.

DNA methylation mediated by DNA methyltransferase is an important epigenetic process that regulates gene expression in mammals, which plays a key role in silencing certain genes, such as tumor suppressor genes, in cancer, and it has become a promising therapeutic target for cancer treatment. Similar to other epigenetic targets, DNA methyltransferase can also be modulated by chemical agents. Four agents have already been approved to treat hematological cancers. In order to promote the development of a DNA methyltransferase inhibitor as an anti-tumor agent, in the current review, we discuss the relationship between DNA methylation and tumor, the anti-tumor mechanism, the research progress and pharmacological properties of DNA methyltransferase inhibitors, and the future research trend of DNA methyltransferase inhibitors.

Spinal cord injury (SCI) is a chronic condition whereby persistent aberrant macrophage activation hinders the repair process. During acute trauma, dominant M1 macrophages produce high levels of reactive oxygen species (ROS), leading to increased apoptosis in neurons, glial cells, and oligodendrocytes. This study investigated the specific effects of a ROS-responsive hydrogel loaded with Apelin-13 (Apelin-13@ROS-hydrogel) on macrophage polarization and neuroinflammation, thereby exploring its role in boosting SCI repair. Apelin-13@ROS-hydrogel was prepared, and its ROS-scavenging capacities were evaluated using DPPH, H 2 O 2 , and ·O 2 - assays. The effects of Apelin-13@ROS-hydrogel on macrophage polarization, inflammatory mediators and oxidative stress were assessed in LPS-pre-treated microglia BV2 cells and an SCI rat model. Apelin-13 was downregulated in SCI rats. Treatment with Apelin-13 improved functional recovery and reduced inflammatory factors and M1 markers but increased the M2 marker Arg-1. Apelin-13@ROS-hydrogel showed significantly higher ROS-scavenging capacities compared to the control hydrogel. Apelin-13@ROS-hydrogel decreased pro-inflammatory mediators and increased anti-inflammatory mediators in BV2 cells. Apelin-13@ROS-hydrogel enhanced the healing process and neurological functions, reducing inflammatory factors and M1 markers while increasing Arg-1 levels by day 28 in SCI rats. Collectively, Apelin-13 enhances SCI repair through macrophage regulation, M1/M2 polarization, and neuroinflammation. The ROS-responsive hydrogel further amplifies these effects, offering a promising therapeutic strategy for SCI.

Based on the deep learning method, a network model that can quickly and accurately identify the species of Fritillaria cirrhosa species was constructed. The learning method based on deep residual convolutional neural network was used to input the unprocessed original image directly as input, and the features of the image were extracted through convolution and pooling operations. On this basis, the ResNet34 model was improved, and the additional fully connected layer was added in front of the Softmax classifier to improve the learning ability of the network model. Total of 3915 images of three kinds of Fritillaria cirrhosa were used as data sources for the experiments, among which 160 images of each type were randomly selected to form the validation set. The final training set recognition accuracy rate was 95.8%, the validation set accuracy rate reached 92.3%, and the test set accuracy rate was 88.7%. The image recognition method of Fritillaria cirrhosa based on deep learning proposed in this paper is effective and feasible, which can quickly and accurately identify the species of Fritillaria cirrhosa species, and provides a new idea for the intelligent recognition of Chinese medicinal materials.

Telenomus remus is a highly efficient biological control agent against Spodoptera frugiperda , owing to its capacity to successfully locate and parasitize inner layer eggs of egg masses. However, our previous studies have revealed its limited cold tolerance, a critical bottleneck in mass rearing of this wasp species. Understanding the cold tolerance mechanism of T. remus is crucial for improving rearing techniques, optimizing storage protocols, and enhancing the overall effectiveness of biological control strategies. Therefore, the overarching objectives of this study were to investigate the dynamic changes in mortality and cryoprotectant levels under different cold stress conditions, identify candidate genes and metabolites associated with cold tolerance, and elucidate the cold tolerance mechanisms in T. remus through physiological measurements, integrated transcriptomic and metabolomic analyses, and qRT-PCR validation. The results revealed that the survival rates of T. remus declined significantly with decreasing temperature. Interestingly, substantial accumulation of trehalose was observed under cold stress. Integrated multi-omics analysis indicated that the starch and sucrose metabolism pathway was crucial for mediating cold tolerance in T. remus . In this metabolic pathway, the expression levels of GAA (α-glucosidase) and GYS (glycogen synthase) exhibited a pronounced temperature-dependent upregulation. Collectively, these findings suggest that T. remus employs a cold-tolerance strategy centered on trehalose accumulation. This research advances our understanding of the molecular and biochemical foundations of cold adaptation in T. remus , and provides a theoretical basis for optimizing the storage strategies of T. remus biocontrol products.

As a typical natural predator of agricultural pests, the lady beetle, Coccinella septempunctata , has been commercially mass-reared and widely employed in in pest management. The lady beetles can enter a long-term reproductive diapause phase in response to short photoperiods and low temperatures, for maintaining population during the overwintering process. Insect diapause is a physiological adaptative strategy that is characterized by a cessation of ovarian development, lipid accumulation and extended lifespan. Diapause regulating improve the long-term storage of C. septempunctata and release of natural enemies at the right time. In our previous research, as a main output of the juvenile hormone pathway, Krüppel homolog 1 ( Kr-h1 ) was a key component of reproduction and diapause in C. septempunctata . However, the molecular mechanisms underlying the regulation of C. septempunctata reproduction and diapause by Kr-h1 transcription factor remains unknown. In this study, we utilized RNA-Sequencing to investigate the transcriptomic changes in C. septempunctata following RNA interference targeting the Kr-h1 gene. DEGs analysis revealed significant transcriptional alterations between the Kr-h1 knockdown group and the control group. Noteworthy findings include the downregulation of three genes related to reproduction ( follicle cell protein,vitelline membrane protein , and vitellogenin ) in the dsKr-h1 group, while genes involved in lipid metabolism, such as lipase and fatty acid synthase , were upregulated. These results suggested that Kr-h1 plays a critical role in the regulation of both reproductive processes and lipid metabolism in C. septempunctata . Our findings provided valuable insights into the molecular mechanisms regulating reproduction and diapause in C. septempunctata and contributed to the expanding understanding of the role of CsKr-h1 in insect physiology.

High temperature stress seriously affects the quality and yield of vegetable crops, especially cucumber ( Cucumis sativus L.). However, the metabolic dynamics and gene regulatory network of cucumber in response to high temperature stress remain poorly studied. In this study, we identified a heat-tolerant cucumber Gy14 and a heat-sensitive cucumber 32X. RNA-seq analysis of Gy14 and 32X under high temperature stress showed that some differentially expressed genes (DEGs) were related to the biosynthesis of secondary metabolites. Metabolomic analysis revealed that there were more phenylpropanoids and their downstream derivatives in Gy14 compared to that in 32X under Re_2d condition (2 normal days recovery after heat). Integrated analysis of transcriptome and metabolome revealed that these upregulated genes played a pivotal role in flavonoid biosynthesis. Moreover, high temperature stress significantly induced the expression of the gibberellin (GA) biosynthesis genes and exogenous application of GA 3 alleviated the damage of high temperature to cucumber seedlings. Together, these findings provided new insights into the transcriptome response and metabolomic reprogramming of cucumber against high temperature stress.

NETosis is a new form of cell death, marked by DNA chromatin release from dead neutrophils. While it aids in microbe defense, it may worsen inflammation in autoimmune diseases, causing tissue harm. The impact of NETosis on Anti-neutrophil Cytoplasmic Antibody-associated Glomerulonephritis (ANCA-GN) remains unexplored and requires investigation. First, a weighted gene co-expression network analysis (WGCNA) was conducted to uncover differential expression of neutrophil extranuclear trap-associated genes (DE-NETs) in ANCA-GN. The NETosisScore model was established through the single sample gene set enrichment analysis (ssGSEA), which categorized all patients into high-risk and low-risk groups. The accuracy of model was assessed by ROC curve. The biological function of various subgroups was explored through Gene Set Variation Analysis (GSVA), while the abundance of immune cell infiltration was measured with CIBERSORT. Furthermore, the key NETosis-related genes (NRGs) were identified using three machine learning algorithms, and their relationship with renal function was analyzed through the NephroseqV5 database. Through the application of qPCR and immunohistochemical staining techniques, the mRNA and protein expression levels of NRGs were determined in patients with ANCA-GN and control. A NETosisScore model was developed from 18 DE-NETs using the ssGSEA algorithm. The model's ability to predict ANCA-GN patients with a ROC AUC of 0.921. The high-risk group in ANCA-GN showed enrichment of immune-related pathways and greater infiltration of immune cells, as revealed by KEGG enrichment analysis and CIBERSORT. Using three machine learning algorithms, we identified six NRGs. Significant positive correlations were found between NRGs and CCR, macrophages, T-cell co-inhibition, and TIL. Further KEGG analysis revealed that the functions of NRGs may be closely related to the toll-like receptor signaling pathway. The levels of NRGs increased as kidney function declined and were positively correlated with Scr (serum creatinine) and negatively correlated with GFR (glomerular filtration rate), qPCR analysis showed increased expression of most NRGs in ANCA-GN patients. Furthermore, immunohistochemical staining confirmed higher expression of all NRGs in ANCA-GN patients. NETosisScore model accurately predicts high-risk patients in ANCA-GN with enriched immune pathways, 6 NRGs identified as potential biomarkers.

In hyperspectral image (HSI) reconstruction tasks, due to the lack of ground truth in real imaging processes, models are usually trained and validated on simulation datasets and then tested on real measurements captured by real HSI imaging systems. However, due to the gap between the simulation imaging process and the real imaging process, the best model validated on the simulation dataset may fail on real measurements. To obtain the best model for the real-world task, it is crucial to design a suitable no-reference HSI quality assessment metric to reflect the reconstruction performance of different models. In this paper, we propose a novel no-reference HSI quality assessment metric via ranking feature learning (R-NHSIQA), which calculates the Wasserstein distance between the distribution of the deep features of the reconstructed HSIs and the benchmark distribution. Additionally, by introducing the spectral self-attention mechanism, we propose a Spectral Transformer (S-Transformer) to extract the spatial-spectral representative deep features of HSIs. Furthermore, to extract quality-sensitive deep features, we use quality ranking as a pre-training task to enhance the representation capability of the S-Transformer. Finally, we introduce the Wasserstein distance to measure the distance between the distribution of the deep features and the benchmark distribution, improving the assessment capacity of our method, even with non-overlapping distributions. The experimental results demonstrate that the proposed metric yields consistent results with multiple full-reference image quality assessment (FR-IQA) metrics, validating the idea that the proposed metric can serve as a substitute for FR-IQA metrics in real-world tasks.

Background and Aims: Plasma interleukin (IL)-27 is an important mediator of acute hepatic injury (AHI) associated with sepsis. Mitochondria contribute to the proper regulation of macrophage phagocytosis. In this study, we investigated the effect of IL-27 on mitochondrial function and the antimicrobial response of macrophages in sepsis-associated AHI.Methods: Wild-type (WT) and IL-27 receptor WSX-1 deficient (IL-27R−/−) mice underwent cecal ligation and puncture (CLP). The severity of hepatic injury, inflammatory cytokine levels, hepatic pyroptosis, and bacterial load in the liver and blood were assessed 24 h after CLP. In vitro, RAW264.7 cells and peritoneal macrophages were treated with lipopolysaccharide (LPS) and/or IL-27. The phagocytosis and killing functions of macrophages were detected. Mitochondrial function and mitophagy were detected using western blot, glutathione (GSH)/malondialdehyde (MDA) content measurement, fluorescence staining, and JC-1 staining in vivo and in vitro. After treatment with nicotinamide mononucleotide (NMN, NAD + precursor), a pharmacologic agent that improves mitochondrial function, the inflammatory response, hepatic injury, and hepatic pyroptosis were assessed.Results: IL-27R−/− mice exhibited a marked reduction in hepatic injury, pyroptosis (based on cleaved GSDMD and cleaved Caspases 1 protein levels), and systemic inflammation (based on serum IL-6, IL-10, and TNF-α levels) compared to WT mice following CLP. After CLP, mice lacking IL-27R displayed significantly higher bacterial clearance and greater local infection control. Subsequent studies demonstrated that IL-27 directly impaired the LPS-induced bacterial phagocytosis, killing capacity, and mitochondrial function of macrophages. Finally, enhanced mitochondrial function using NMN in vivo significantly alleviated pathological liver injury and inflammation.Conclusions: These findings indicated that IL-27 impairs the bacterial phagocytosis capacity of macrophages by aggravating mitochondrial dysfunction to aggravate AHI during sepsis.