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Abstract Asthma is regarded as a chronic inflammation of the airway. Research has highlighted the significance of Vitamin D in asthma. This study explored the mechanism of vitamin D on asthma. The asthma mouse model was established by ovalbumin (OVA) sensitization and treated with vitamin D (50 or 100 ng/ml). The morphological changes of the airway were observed by HE staining. The serum IgE contents and MDA, ROS, and SOD expressions in the bronchoalveolar lavage fluid (BALF) were detected by ELISA. The Th17 and Treg cells were detected using flow cytometry. The RORγt and Foxp 3 expressions were detected by Reverse transcription quantitative polymerase chain reaction (RT‐qPCR). IL‐17, IL‐10, and TGF‐β1 expressions were detected using ELISA. The NF‐κB pathway was blocked using the NF‐κB pathway inhibitor, Andrographolide sulfonate. The NF‐κB pathway‐related indexes were detected by western blotting. After blockade of the NF‐κB pathway, the IL‐17, IL‐10, and TGF‐G1 expressions were detected. OVA‐sensitized asthma induced airway remodeling and elevated IgE content in mice, which was downregulated after vitamin D treatment. MDA and ROS were upregulated and SOD was downregulated in asthmatic mice, while vitamin D inverted the changes. Th17/Treg ratio was imbalanced, RORγt and IL‐17 were upregulated, and Foxp 3, IL‐10, and TGF‐β1 were downregulated after OVA sensitization, while vitamin D treatment inverted these changes and inhibited the NF‐κB‐p65 phosphorylation level. After blockade of the NF‐κB pathway, IL‐17 was downregulated and IL‐10 and TGF‐β1 were upregulated. In conclusion, vitamin D rectified the Th17/Treg balance and alleviated airway inflammation by inhibiting the NF‐κB pathway in asthmatic mice.

Respiration monitoring is a promising alternative to medical diagnosis of several diseases. However, current techniques of respiration monitoring often require expensive and cumbersome devices which greatly limit their medical applications. Here, we present a fully integrated wearable device consisting of a flexible LCP-copper interdigital electrode, a sensing layer and a wireless electrochemical analysis system. The developed humidity sensor exhibits a high sensitivity, a good repeatability and a rapid response/recover time. The long-term stability is over 30 days at different relative humidity. By integrating the flexible humidity sensor with miniaturized electrochemical analysis system (0.8 cm × 1.8 cm), response current concerning respiration can be wirelessly transmitted to App-assisted smartphone in real time. Furthermore, the fabricated humidity sensor can realize skin moisture monitoring in a touch-less way. The large-scale production of miniaturized flexible sensor (4 mm × 6 mm) has significantly contributed to commercial deployment.

We discovered a unique expression pattern of two histone methyltransferases Suv39h1 and Suv39h2 during 3T3-L1 adipogenesis, both of which preferentially catalyse the formation of H3K9 dimethylation (H3K9me2) and further H3K9 trimethylation (H3K9me3), a transcriptional repressive mark. The expression of Suv39h1 and Suv39h2 displayed a sharp increase at the early stage of 3T3-L1 differentiation, which peaked after differentiation induction, and then declined towards later stage of differentiation, suggesting a key role for these two histone methyltransferases in adipogenesis. Indeed, inactivating Suv39h1 or Suv39h2 via lentiviral shRNA knockdown inhibited adipogenesis, while overexpressing Suv39h1 promoted adipogenesis. Notably, overexpressing or knocking down Suv39h1 in 3T3-L1 cells was associated with reciprocal changes in the expression of Wnt10a, an anti-adipogenic regulator. Further, Wnt10a knockdown largely prevented the inhibitory effect of Suv39h1 on adipogenesis, indicating Wnt10a as a downstream target mediating Suv39h1’s action in adipogenesis. Mechanistically, our comprehensive approaches involving ChIP, co-immunoprecipitation and pyrosequencing analysis demonstrated that Suv39h1 may regulate Wnt10a expression via H3K9 methylation and interaction with DNA methyltransferase 1 (DNMT1) at the Wnt10a promoter, resulting in altered DNA methylation at the promoter. We conclude that Suv39h promotes adipogenesis by epigenetically down-regulating Wnt10a expression via H3K9me3 and DNA methylation at the Wnt10a promoter.Abbreviated title: Suv39h and 3T3-L1 Adipogenesis

The mechanisms underlying differential chemotherapeutic response to 5-fluorouracil are not fully known. Here, the authors show that ABDH5 regulates sensitivity to 5-fluorouracil in colorectal cancer by regulating lysosome function.

Nuclear factor kappa B (NF-κB), a key nuclear transcription factor, is associated with prognosis in a variety of human cancers. However, the clinical value of NF-κB in non-small cell lung cancer (NSCLC) is still controversial. Therefore, the aim of this meta-analysis was to obtain an accurate evaluation of the relationship between NF-κB expression and survival prognosis of NSCLC patients based on published articles. PubMed, EMBASE and Web of Science databases were systematically searched for potential articles. A total of 1159 patients from 7 eligible studies comparing prognostic significance of NF-κB expression levels in NSCLC were included in our meta-analysis. I2 statistic and P value were performed to evaluate heterogeneity. The results of analysis were presented as hazard ratio (HR) or odds ratios (OR) with 95% confidence interval (95% CI). Subgroup analysis based on ethnicity of NSCLC patients and NF-kB cellular localization within cancer cells were conducted to illustrate the potential discrepancy. Significant heterogeneity was considered at I2>50% and P

In this study, we assessed the salt tolerance of 38 wheat cultivars from primary wheat cultivation regions in China using a membership function value (MFV) during the germination and seedling emergence stages. Based on salt tolerance assessment, three contrasting groups were classified, with 10 tolerant, 23 moderately tolerant and 5 sensitive cultivars under low salt stress, and 4 tolerant, 25 moderately tolerant and 9 sensitive cultivars under high salt stress and in addition to Na+ and K+ homeostasis regulation, nitrogen efficient transfer from seed to plant tissues denoted the significant positive correlation with salt tolerance, confirming the importance of nutrient spectra organisation. Salt-tolerant and moderately tolerant cultivars had lower trait network modularity than salt-sensitive cultivars, demonstrating that wheat with different salt tolerance uses alternative strategies to cope with salt stress. These results were important for germplasm evaluation and variety breeding of salt tolerance in wheat.

Abstract Understanding criminal motives is crucial for analyzing criminal psychology and predicting judicial outcomes. Traditional methods for crime motive analysis are heavily based on statistical techniques, requiring specialized knowledge and substantial human resources. With the increasing availability of judicial data, such as legal documents, machine learning approaches hold great potential in this domain. However, a significant challenge is the lack of comprehensive datasets to train these models, and the distribution of crime motive categories in publicly available legal texts often exhibits a long-tailed imbalance. This imbalance can lead to model bias, where the model tends to predict more common criminal motives. To address these challenges, we collected 11,589 legal documents from China Judgements Online (2019–2024) to create a crime motive text dataset. To mitigate the long-tailed issue, we propose a Category-Aware Balanced Contrastive Learning (CA-BCL) method, which effectively enhances the model’s representation of long-tailed data. Specifically, CA-BCL first balances the sampling process to alleviate the class imbalance during prototype construction and then applies balanced contrastive learning to improve the model’s ability to generalize to long-tailed categories, leading to better overall classification performance. Our experimental results demonstrate that CA-BCL significantly outperforms existing text classification models in crime motive classification, while also showing strong generalization capabilities on standard text classification benchmark.

Abstract Seabuckthorn (Hippophae rhamnoides L.) is known for its medicinal properties in treating various diseases, including neurological conditions. However, the therapeutic effect of inhaled seabuckthorn seed oil (SSO) on Alzheimer’s disease (AD) remains not fully understood. This study explores the effects of nebulized inhalation of SSO in 9-month-old APP/PS1 mice over 21 days. The results showed that nebulized SSO improved memory and cognition. Using 7.0T MRI to monitor blood oxygenation level dependent (BOLD) signals revealed that SSO altered the Amplitude of Low Frequency Fluctuations (ALFF) and Regional Homogeneity (ReHo) signaling such as in the amygdala and substantia innominate, and hippocampus. Enzyme-linked immuno sorbent assay (ELISA) and pathological analyses indicated reduced neuroinflammation in plasma and brain, decreased neuronal necrosis, lower β-amyloid (Aβ) protein levels, reduced amyloid deposition, and increased tyrosine hydroxylase activity. Additionally, SSO promoted gut microbiota remodeling by increasing alpha diversity and boosting levels of probiotics such as Verrucomicrobia, Bifidobacterium, Prevotella, and Akkermansia, without adverse effects on lung tissue. Nebulized inhalation of SSO may slow AD progression by modulating inflammation and amyloid deposition. Nebulized inhalation offered a potential method for enhancing drug delivery across the blood-brain barrier with reduced systemic side effects.

Abstract Objective Cognitive impairment (CI) is a prevalent and significant health concern among patients undergoing maintenance hemodialysis (MHD). Recent studies have highlighted the growing interest in dynapenic abdominal obesity (DAO), which combines both low muscle strength and excess abdominal fat. Despite the increasing recognition of DAO, its association with CI in MHD patients remains uncertain. The objective of this study was to investigate the relationship between DAO and CI in MHD patients. Methods We conducted a multicenter, cross-sectional study in twenty dialysis centers, encompassing 3767 adult MHD patients. Participants were categorized into four distinct groups based on the criteria for abdominal obesity (AO), defined as waist circumference (WC) ≥ 90 cm for men and ≥ 85 cm for women, and dynapenia, characterized by handgrip strength (HGS)

Abstract Background Proteolysis targeting chimera (PROTAC), a novel drug discovery strategy, utilizes the ubiquitin–proteasome system to degrade target proteins in cells. While Western blotting, mass spectrometry, and Lumit Immunoassay have been instrumental in determining protein levels, the rapid screening of PROTACs continues to pose challenges, necessitating the development of alternative methodologies. Results We herein reported an alternative high-throughput method for screening PROTACs using a dual-reporter system expressing a Renilla luciferase (RLUC)-fused target protein and enhanced green fluorescent protein (EGFP). EGFP served as an internal reference and RLUC as an indicated target protein degradation. Rapid measurement of EGFP or RLUC light signals was achieved using a fluorescence/luminescence plate-based reader in the endpoint mode. The feasibility of the screening model was tested using ARV110, a clinical trial-stage PROTAC targeting the androgen receptor (AR). In EGFP/RLUC-tAR-expressing modal cells treated with varying concentrations of ARV110, normalized RLUC luminescence decreased dose-dependently, as confirmed via western blotting detection of AR expression. Then the platform was used to practically screen Sirtuin 2 (SIRT2) degraders from a small group of PROTACs that we built. Normalized RLUC luminescence changes in model cells expressing EGFP/RLUC-SIRT2 reflected the degradation efficiencies of PROTACs. Compounds 128 and 129 exhibited the highest degradation efficacies, leading to dose-dependent degradation of endogenous SIRT2 protein in the MCF-7 cell line and inducing cell growth arrest. Conclusions The dual-reporter system using both fluorescence and chemiluminescence was successfully constructed. Using this method, we identified effective candidate PROTACs against SIRT2. The dual-reporter system may accelerate drug discovery during PROTAC development.

We bias-corrected and assessed summer precipitation data over the Qinghai-Xizang Plateau （QXP） based on 18 models from the Coupled Model Intercomparison Project Phase 6 （CMIP6）.Our assessment of CMIP6 data， conducted for the period 1979-2014， centered on the performance of both the ensemble and individual models.We evaluated the CMIP6 data before and after bias correction， according to considering mean precipitation and extreme precipitation.The results highlight the correction method's dependence on ERA5 reanalysis data quality over the QXP.Although corrected mean summer precipitation over the QXP shows improvement in bias and bias rate， it exhibits inferior interannual time-varying characteristics compared to pre-corrected data.Most of the models were able to better simulate the spatial variability characteristics of mean precipitation over the QXP， gradually increasing from northwest to southeast from 1979 to 2014.Pre-correction precipitation data overestimates precipitation over the QXP with a bias rate of 60.4%， while corrected data is relatively underestimated with a deviation rate of -13.9%.The mean bias of the corrected data from ERA5 is only 0.003 mm·d-1， with a spatial correlation as high as 0.999.Spatial trend analysis of observed data indicates a slight increase in summer precipitation over most of the TP from 1979 to 2014， with a significant decreasing trend only along the eastern edge.Both pre- and post-corrected data generally capture this spatial distribution， though pattern correlation coefficients of most individual uncorrected CMIP6 models do not exceed 0.5.Comparing with the interannual variability of the precipitation data obtained from observations， the pre-corrected data overestimate the precipitation on the QXP， while the post-corrected data are underestimated in comparison with the observation results.Extreme precipitation is selected by determining the 95% thresholds， a revealing a spatial distribution similar to the mean annual precipitation， increasing from northwest to southeast.This feature is well captured by some models， such as MRI-ESM2-0 （The Meteorological Research Institute Earth System Model version 2.0） and ACCESS-CM2 （Australian Community Climate and Earth System Simulator Climate Model Version 2.0）.Earth System Simulator Climate Model Version 2）， the spatial correlation coefficients are 0.851 and 0.821， respectively， compared with the observations， but the spatial correlation of the corrected data decreases from 0.861 to 0.730， failing to accurately characterize the stepwise increase of extreme precipitation on the QXP.The deviation distribution of the corrected extreme precipitation data is similar to pre-correction data， with lower areas concentrated in the southern hinterland and eastern part of the QXP.The analysis of extreme precipitation contribution shows that both the observation results and the CMIP6 precipitation data indicate that the trend of extreme precipitation contribution is not obvious during 1979-2014.Among individual models， EC-Earth3-Veg （European Community Earth-Vegetation model version 3） and EC-Earth3 （European Community Earth Model version 3） and CanESM5 （The Canadian Earth System Model version 5） ranked high in several parameters， showing better simulation capability， while IPSL-CM6A-LR （Institute Pierre-Simon Laplace Climate Model 6A Low Resolution） ranked high in the mean precipitation deviation and extreme precipitation deviation.

Abstract Pathological retinal neovascularization (RNV) is one of the leading causes of blindness worldwide; however, its underlying mechanism remains unclear. Here, we found that the expression of endothelial protein C receptor (Epcr) was increased during RNV, and its ligand was elevated in the serum or vitreous body of patients with proliferative diabetic retinopathy. Deleting endothelial Epcr or using an EPCR-neutralizing antibody ameliorated pathological retinal angiogenesis. EPCR promoted endothelial heme catabolism and carbon monoxide release through heme oxygenase 1 (HO-1). Inhibition of heme catabolism by deleting endothelial Ho-1 or using an HO-1 inhibitor suppressed pathological angiogenesis in retinopathy. Conversely, supplementation with carbon monoxide rescued the angiogenic defects after endothelial Epcr or Ho-1 deletion. Our results identified EPCR-dependent endothelial heme catabolism as an important contributor to pathological angiogenesis, which may serve as a potential target for treating vasoproliferative retinopathy.

Abstract Discovering new molecular targets for non-small cell lung cancer (NSCLC) is critically important. Enhanced mitochondrial function can promote NSCLC progression by enabling metabolic reprogramming, resistance to apoptosis, and increased cell proliferation. Mitochondrial carrier homolog 2 (MTCH2), located in the outer mitochondrial membrane, is pivotal in regulating mitochondrial activities. This study examines MTCH2 expression and its functional role in NSCLC. Bioinformatic analysis showed that MTCH2 is overexpressed in NSCLC tissues, correlating with poor prognosis and other key clinical parameters of the patients. In addition, single-cell sequencing data revealed higher MTCH2 expression levels in cancer cells of NSCLC tumor mass. Moreover, MTCH2 is also upregulated in locally-treated NSCLC tissues and multiple primary/established human NSCLC cells. In various NSCLC cells, silencing MTCH2 via targeted shRNA or knockout (KO) using the CRISPR/Cas9 method significantly hindered cell proliferation, migration and invasion, while inducing apoptosis. MTCH2 knockdown or KO robustly impaired mitochondrial function, as indicated by reduced mitochondrial respiration, decreased complex I activity, lower ATP levels, lower mitochondrial membrane potential (mitochondrial depolarization), and increased reactive oxygen species (ROS) production. Conversely, ectopic overexpression of MTCH2 in primary NSCLC cells enhanced mitochondrial complex I activity and ATP production, promoting cell proliferation and migration. In vivo, the intratumoral injection of MTCH2 shRNA adeno-associated virus (aav) impeded the growth of subcutaneous xenografts of primary NSCLC cells in nude mice. In MTCH2 shRNA aav-injected NSCLC xenograft tissues, there was decreases in MTCH2 expression, mitochondrial complex I activity, ATP content, and the glutathione (GSH)/glutathione disulfide (GSSG) ratio, but increase in thiobarbituric acid reactive substances (TBAR) activity. Additionally, MTCH2 silencing led to reduced Ki-67 staining but increased apoptosis in NSCLC xenografts. Collectively, these findings demonstrate that overexpressed MTCH2 promotes NSCLC cell growth potentially through the maintenance of mitochondrial hyper-function, highlighting MTCH2 as a novel and promising therapeutic target for treating this disease.

Abstract The fuel-air mixing is of paramount importance in hypersonic air-breathing vehicles, and its performance is closely related to the fuel injection angle. This article presents an investigation into the influence of the injection angles on the flow and mixing processes in a supersonic combustor at low Mach supersonic inflow. Detailed flow characteristics are compared and analyzed, with a focus on instantaneous and average flows. Besides, several significant mixing parameters are thoroughly depicted. Results show that, in contrast to transverse injection, relatively strong fuel fluctuation is presented on the leeward side in comparison to the windward side in the near field for the inclined injection. Furthermore, the counter-rotating vortex pairs (CVP) are constricted by the inclination of the injection, giving rise to a decrease in jet-cavity interaction. Although inclined injection exhibits favorable performance in backpressure resistance at low Mach supersonic crossflow, it presents a greater challenge in terms of ignition, thus necessitating meticulous design considerations.

Abstract The N6-methyladenosine binding protein YTHDF1, often upregulated in cancer, promotes tumor growth and hinders immune checkpoint blockade treatment. A comprehensive understanding of the molecular mechanisms governing YTHDF1 protein stability is pivotal for enhancing clinical response rates and the effectiveness of immune checkpoint blockade in cancer patients. Here, we report that USP5 interacts with YTHDF1, stabilizing it by removing K11-linked polyubiquitination. Insulin activates mTORC1, phosphorylating USP5 and promoting its dimerization, which binds to and protects YTHDF1 from degradation. Conversely, the CUL7-FBXW8 E3 ligase promotes YTHDF1 degradation. Deficiency in YTHDF1 or USP5 increases PD-L1 expression and suppresses immune-related gene expression, facilitating immune evasion. Combining USP5 inhibition with anti-PD-L1 therapy enhances anti-tumor immunity, suggesting USP5 as a potential biomarker for patient stratification. This study reveals a ubiquitination-dependent regulation of YTHDF1, proposing USP5 inhibition alongside PD-(L)1 blockade as a promising cancer treatment strategy.

Abstract Background Depressive symptoms are a serious health issue that can cause profound, lifelong suffering for people who are affected by it. This study aimed to evaluate the effect of sarcopenia, oral frailty, and social frailty on depressive symptoms among Chinese participants aged ≥ 60 years old in China. Methods This research utilized a cross-sectional design and used convenience sampling to select participants from Anhui Province, China. Demographic questionnaire, SARC-F (Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls), OFI-8 (Oral Frailty Index-8), the HALFT (Help, Participation, Loneliness, Financial, Talk) scale, and PHQ-9 (Patient Health Questionnaire-9) were used to conduct the survey. A chi-square test was performed to evaluate the differences between categorical variables, spearman correlation analysis was used to find the correlation between depressive symptoms and factors. Four regression models were set up to evaluate the effect of factors on depressive symptoms and select the appropriate adjustment variables. Results Of 1453 participants, 33.5% had sarcopenia, 51.4% had oral frailty, 31.5% had pre-social frailty, 14.5% had social frailty, and 32.2% had depressive symptoms. Spearman correlation analysis indicated that depressive symptoms significantly correlated with sarcopenia (r = 0.415), oral frailty (r = 0.282), and social frailty (r = 0.410). In crude analysis, sarcopenia (OR = 0.179, 95%CI 0.141–0.227), oral frailty (OR = 3.946, 95%CI 3.101–5.021), pre-social frailty (OR = 4.449, 95%CI 3.401–5.818), and social frailty (OR = 12.552, 95%CI 8.833–17.837) were significantly associated with depressive symptoms in older adults. After adjusting for the covariates, sarcopenia (OR = 4.301, 95%CI 3.322–5.569), oral frailty (OR = 3.136, 95%CI 2.430–4.046), pre-social frailty (OR = 3.664, 95%CI 2.775–4.836) and social frailty (OR = 9.488, 95%CI 6.560-13.723) were significantly associated with depressive symptoms. (P

Objective: To investigate the effects of Alpiniae oxyphyllae Fructus (AOF) on renal lipid deposition in diabetic kidney disease (DKD) and elucidate its molecular mechanisms. Methods: The mechanism of AOF in treating DKD was explored by network pharmacological enrichment analysis, molecular docking, and molecular dynamics simulation. The effects of AOF on renal function and lipid deposition were assessed in a mouse model of DKD and high glucose-stressed HK-2 cells. Cell viability and lipid accumulation were detected by CCK8 and oil red O staining. The expressions of PPARα and fatty acid oxidation-related genes (ACOX1 and CPT1A) were detected by quantitative RT-PCR, Western blot, and immunofluorescence. Furthermore, PPARα knockdown was performed to examine the molecular mechanism of AOF in treating DKD. Results: Network pharmacological enrichment analysis, molecular docking, and molecular dynamics simulation showed that the active compounds in AOF targeted PPARα and thus transcriptionally regulated ACOX1 and CPT1A. AOF lowered blood glucose, improved dyslipidemia, and attenuated renal injury in DKD mice. AOF-containing serum accentuated high glucose-induced decrease in cell viability and ameliorated lipid accumulation. Additionally, it significantly upregulated the expression of PPARα, ACOX1, and CPT1A in both in vivo and in vitro experiments, which was reversed by PPARα knockdown. Conclusions: AOF may promote fatty acid oxidation via PPARα to ameliorate renal lipid deposition in DKD.

Abstract Background Chemical-induced acute lung injury is characterized by impaired epithelial regenerative capacity, leading to acute pulmonary edema. Numerous studies have investigated the therapeutic potential of endogenous stem cells with particular emphasis on alveolar type 2 epithelial (AEC2) cells owing to their involvement in lung cell renewal. Sox9, a transcription factor known for its role in maintaining stem cell properties and guiding cell differentiation, marks a subset of AEC2 cells believed to contribute to epithelial repair. However, the role of Sox9+AEC2 cells in the distal lung alveolar cells and the potential roles in chemically induced acute lung injury have never been explored. Methods In this study, we generated Sox9 flox/flox ;Sftpc Cre−ERT2 mice and examined the effects of Sox9+AEC2 cells on the pathophysiology of epithelial damage during chemical-induced acute lung injury. Subsequently, Sox9-Cre ERT2 Ai9 mice were used for lineage tracing to elucidate the repair mechanisms. Results Our findings revealed that Sox9+AEC2 cells endowed with stem cell properties induced cell proliferation during lung injury, predominantly in the damaged alveolar region. This process is accompanied by the regulation of inflammatory responses and orderly differentiation, thereby promoting epithelial regeneration. Conclusion These results provide compelling in vivo genetic evidence supporting the characterization of Sox9+AEC2 cells as bona fide lung epithelial stem cells, demonstrating their multipotency and self-renewal capabilities during lung repair and regeneration. The identification of Sox9+AEC2 cells as crucial contributors to the promotion of epithelial repair underscores their potential as therapeutic targets in chemical-induced acute lung injury.

Abstract Microplastics, as an emerging environmental pollutant, have received widespread attention for their potential impact on ecosystems and human health. Microplastics are defined as plastic particles less than 5 millimeters in diameter and can be categorized as primary and secondary microplastics. Primary microplastics usually originate directly from industrial production, while secondary microplastics are formed by the degradation of larger plastic items. Microplastics are capable of triggering cytotoxicity and chronic inflammation, and may promote cancer through mechanisms such as pro-inflammatory responses, oxidative stress and endocrine disruption. In addition, improved microplastics bring new perspectives to cancer therapy, and studies of microplastics as drug carriers are underway, showing potential for high targeting and bioavailability. Although current studies suggest an association between microplastics and certain cancers (e.g., lung, liver, and breast cancers), the long-term effects and specific mechanisms still need to be studied. This review aimed at exploring the carcinogenicity of microplastics and their promising applications in cancer therapy provides important directions for future research and emphasizes the need for multidisciplinary collaboration to address this global health challenge.

Abstract Neuropsychiatric adverse events (AEs) significantly impact the quality of life of patients using avapritinib. However, the majority of current data comes from pre-marketing, with limited real-world studies. Our research aimed to explore post-marketing data of avapritinib. We evaluated the signals of avapritinib-related neuropsychiatric AEs by data mining using the FDA Adverse Event Reporting System (FAERS). Reporting odds ratio (ROR) and information component (IC) were employed to quantify the signals from the first quarter of 2020 through the fourth quarter of 2023. Subsequently, stratified analyses were conducted to further explore the effect of different stratification schemes on the association between avapritinib and neuropsychiatric AEs. Finally, a combination medication analysis was conducted to explore the impact of the co-administration of neuropsychiatric AEs. A total of 2029 neuropsychiatric AEs were reported, and 49 signals were detected, of which 5 were determined to be new signals. Avapritinib was significantly associated with the occurrence of neuropsychiatric AEs (ROR: 1.52, 95% CI: 1.44–1.61; IC: 0.43, IC025: 0.35). The stratified analysis found that gender, age and eight preferred terms (PTs), including cerebral haemorrhage, may affect the severity of AEs. Combination medication analysis showed that combining avapritinib with 19 other medications, including prochlorperazine, may increase the risk of neuropsychiatric AEs. The median time-to-onset (TTO) of avapritinib-related neuropsychiatric AEs was 32 (interquartile range [IQR] 2-200) days, with about 65% of cases occurring within the first three months of treatment. An increase in the signal for neuropsychiatric AEs was identified in post-marketing studies of avapritinib. Clinicians are advised to remain vigilant for such events, particularly during the initial stages of treatment with avapritinib.

Abstract Biometallic ions play a crucial role in regulating the immune system. In recent years, cancer immunotherapy has become a breakthrough in cancer treatment, achieving good efficacy in a wide range of cancers with its specificity and durability advantages. However, existing therapies still face challenges, such as immune tolerance and immune escape. Biometallic ions (e.g. zinc, copper, magnesium, manganese, etc.) can assist in enhancing the efficacy of immunotherapy through the activation of immune cells, enhancement of tumor antigen presentation, and improvement of the tumor microenvironment. In addition, biometallic ions and derivatives can directly inhibit tumor cell progression and offer the possibility of effectively overcoming the limitations of current cancer immunotherapy by promoting immune responses and reducing immunosuppressive signals. This review explores the role and potential application prospects of biometallic ions in cancer immunotherapy, providing new ideas for future clinical application of metal ions as part of cancer immunotherapy and helping to guide the development of more effective and safe therapeutic regimens.

Abstract Background Acute myeloid leukemia (AML) is an aggressive hematological neoplasm. Little improvement in survival rates has been achieved over the past few decades. Necroptosis has relationship with certain types of malignancies outcomes. Here, we evaluated the diagnostic ability, prognostic capacity of necroptosis-related genes (NRGs) and the effect of their copy number variations (CNVs) in AML. Methods Necroptosis-related differentially expressed genes (NRDEGs) were identified after intersecting differentially expressed genes (DEGs) from the Gene Expression Omnibus(GEO) database with NRGs from GeneCards, the Molecular Signatures Database (MSigDB) and literatures. Machine learning was applied to obtain hub-NRDEGs. The expression levels of the hub-NRDEGs were validated in vitro. The mRNA-miRNA and mRNA-TF interaction networks with the hub-NRDEGs were screened using Cytoscape@. Single-sample gene set enrichment analysis (ssGSEA) was utilized to calculate correlations between the hub-NRDEGs and immune cells. CNV analysis of the hub-NRDEGs was carried out on the TCGA-LAML datasets from the TCGA database. Kaplan–Meier (K-M) survival analyses were utilized to evaluate the prognostic values along with Cox model. Results Six hub-NRDEGs (SLC25A5, PARP1, CTSS, ZNF217, NFKB1, and PYGL) were obtained and their expression changes derived from CNVs in AML were visualized. In total, 65 mRNA-miRNA and 80 mRNA-TF interaction networks with hub-NRDEGs were screened. The ssGSEA result showed the expression of RAPR1 was inversely related to CD56dim natural killer cells and the expression of CTSS was positive related to Myeloid-derived suppressor cells (MDSCs) in AML. The K-M results demonstrated that ZNF217 had significant difference in the duration of survival in AML patients. Cox regression models revealed that the hub-NRDEGs had better predictive power at year-1 and year-5. Conclusion These screened NRDEGs can be exploited as clinical prognostic predictions in AML patients, as well as potential biomarkers for diagnosis and therapeutic targeting.

Abstract Bacterial transcription activator-like effectors (TALEs) promote pathogenicity by activating host susceptibility (S) genes. To understand the pathogenicity and host adaptation of Xanthomonas citri pv. malvacearum (Xcm), we assemble the genome and the TALE repertoire of three recent Xcm Texas isolates. A newly evolved TALE, Tal7b, activates GhSWEET14a and GhSWEET14b, different from GhSWEET10 targeted by a TALE in an early Xcm isolate. Activation of GhSWEET14a and GhSWEET14b results in water-soaked lesions. Transcriptome profiling coupled with TALE-binding element prediction identify a pectin lyase gene as an additional Tal7b target, quantitatively contributing to Xcm virulence alongside GhSWEET14a/b. CRISPR-Cas9 gene editing supports the function of GhSWEETs in cotton bacterial blight and the promise of disrupting the TALE-binding site in S genes for disease management. Collectively, our findings elucidate the rapid evolution of TALEs in Xanthomonas field isolates and highlight the virulence mechanism wherein TALEs induce multiple S genes to promote pathogenicity.

Abstract Background Dysregulation of SF3A3 has been related to the development of many cancers. Here, we investigated the functional role of SF3A3 in hepatocellular carcinoma (HCC). Methods SF3A3 expression in HCC tissues and cell lines was examined using RT-qPCR. Changes in malignant behavior of HCC cells after downregulation of SF3A3 were assessed by EdU, colony formation, flow cytometry, wound healing, and Transwell invasion assays. Multiple datasets were combined to identify the upstream modifiers of SF3A3. The binding relationship between STIL and FOXM1 was explored by co-IP assay, and the effect of STIL and FOXM1 on the binding of FOXM1 at the SF3A3 promoter was detected by ChIP-qPCR assay. A xenograft tumor model was established to explore the changes of tumors in vivo, and the expression of Ki67, GPC3, and p53 in tumor tissues was detected by immunohistochemistry. Results SF3A3 and STIL were overexpressed in HCC tissues and cells, and downregulation of SF3A3 or STIL inhibited the malignant behavior of HCC cells by promoting the expression of p53. An interaction between STIL and FOXM1 regulated the SF3A3 expression in HCC cells. Knockdown of FOXM1 further enhanced the anti-tumor effects of STIL loss on HCC cells in vitro and in vivo, whereas SF3A3 overexpression overturned the impact of STIL loss on HCC cells in vitro and in vivo. Conclusions Our findings indicate that STIL/FOXM1 expedites HCC development by activating SF3A3, which highlights the importance of SF3A3 as a promising prognostic marker and therapeutic target for HCC.

Abstract Background Altered metabolism has become an important characteristic of cancer, and acyl-CoA dehydrogenase short-chain (ACADS), a regulator of lipid synthesis, is involved in carcinogenesis-associated metabolic pathways. DNA methylation is an important mechanism for silencing ACADS in various malignancies. However, the specific role of ACADS in hepatocellular carcinoma (HCC) pathogenesis remains poorly understood. Methods and results Using RNA sequencing data from different tumours in The Cancer Genome Atlas database, we observed that ACADS was downregulated and hypermethylated in HCC. Three potential CpG island sites (cg01535453, cg08618068, and cg10174836) were identified in the ACADS promoter. Through in vivo and in vitro experiments, we confirmed that cg08618068 was methylated in HCC. We defined this site as ACADS methylation site-2 (ACADS MS-2). Methylation of ACADS MS-2 was associated with worse survival, and mutation of MS-2 increased ACADS mRNA levels in five HCC cell lines. Sustained overexpression of ACADS not only suppressed the proliferation, migration, and invasion of HCC cells but also promoted immunogenic cell death (ICD) via the upregulation of calreticulin. Subsequently, we established a specific nomogram based on ACADS methylation levels to evaluate the 3- and 5-year overall survival rates of patients with HCC who underwent surgical resection. Conclusions Our work clarified that ACADS acts as a putative tumour suppressor in HCC and confirmed that a nomogram including ACADS methylation had good predictive performance in HCC. We also discovered a correlation between ACADS and ICD, suggesting that ACADS is an essential target for immunotherapy in HCC. Graphical Abstract

The stability of the Aluminum (Al) lattice fundamentally determines the properties of pure Al and its alloys, making it crucial for high-pressure research and alloy development. Through first-principles calculations, we investigated Al lattice behavior under general stress–strain conditions to establish comprehensive stability criteria under large strains. Our analysis revealed three hydrostatic lines representing fcc-Al, bcc-Al, and fct-Al phases under high compressive strain. Within 0-600 GPa, we calibrated two lattice stability criteria with corresponding instability lines, each characterizing a cubic-to-tetragonal transformation. At 110 GPa, bcc-Al transitions from a transitional to a stable phase, which explains the experimental observation of bcc-Al under high-pressure conditions. The relationship between lattice instability and hydrostatic lines generates a novel phase diagram revealing multiple-phase coexistence. These stability criteria govern various structural transformations of fcc-Al, including dislocation, twinning, and stacking faults. This methodological framework provides insights for lattice stability analysis across diverse metallic systems and alloy industries.

Background: This is the first study to evaluate the efficacy of short-term Spinal Cord Stimulation (st-SCS) versus debridement for treating Diabetic Foot Ulcers (DFU). Methods: We retrospectively analyzed records from DFU patients treated at our hospital. Patients were divided into two groups: 62 received st-SCS with debridement (SCS group), and 43 received only debridement (debridement group). We recorded ulcer area, Ankle-Brachial Index, sleep and life quality indices, foot temperature, and visual analog pain scale, and at 2 and 6 weeks post-operation, monitoring adverse events as well. Compared these indicators between the two groups, and changes in the SCS group were specifically analyzed at different time points. Results: Initially, both groups were comparable (P > 0.05). At 2 weeks postoperatively, the ulcer area reduction rate in the SCS group was higher than debridement group (24.37 % vs 12.77 %, P = 0.025), but this advantage disappeared by 6 weeks (P = 0.110). Compared to baseline, therapeutic indicators in the SCS group showed significant improvement at 2 weeks postoperatively and were significantly better than debridement group (P 0.05). The amputation rate was higher in the debridement group (16.28 % vs 3.23 %, P = 0.036), and there were no significant differences in complications (P=0.132). Conclusion: St-SCS shows significant early benefits over debridement in ulcer healing, pain relief, circulation improvement, and lower amputation rates. However, these benefits did not persist at 6 weeks post-treatment.

Rosa banksiae, known as Lady Banks' rose, is a perennial ornamental crop and a versatile herb in traditional Chinese medicine. Given the lack of genomic resources, we assembled a HiFi and Nanopore sequencing-derived 458.58 Mb gap-free telomere-to-telomere high-quality R. banksiae genome with a scaffold N50 = 63.90 Mb. The genome of R. banksiae exhibited no lineage-specific whole-genome duplication compared with other Rosaceae. The phylogenomic analysis of 13 Rosaceae and Arabidopsis through a comparative genomics study showed that numerous gene families were lineage-specific both before and after the diversification of Rosaceae. Some of these genes are candidates for new genes that have evolved from parental genes through fusion events. Fusion genes are divided into three types: Type-I and Type-II genes contain two parental genes that are generated by duplication, distributed in the same and different regions of the genome, respectively; and Type-III can only be detected in one parental gene. Here, Type-I genes are found to have more relaxed selection pressure and lower Ks values than Type-II, indicating that these newly evolved Type-I genes may play important roles in driving phenotypic evolution. Functional analysis exhibited that newly formed fusion genes can regulate the phenotype traits of plant growth and development, suggesting the functional significance of these genes. This study identifies new fusion genes that could be responsible for phenotype evolution and provides information on the evolutionary history of recently diverged species in the Rosa genus. Our data represents the major progress in understanding the new fusion genes evolution pattern of Rosaceae and provides an invaluable resource for phylogenomic studies in plants.

Abstract Deep language models (DLMs) have exhibited remarkable language understanding and generation capabilities, prompting researchers to explore the similarities between their internal mechanisms and human language cognitive processing. This study investigated the representational similarity (RS) between the abstractive summarization (ABS) models and the human brain and its correlation to the performance of ABS tasks. Specifically, representational similarity analysis (RSA) was used to measure the similarity between the representational patterns (RPs) of the BART, PEGASUS, and T5 models’ hidden layers and the human brain’s language RPs under different spatiotemporal conditions. Layer-wise ablation manipulation, including attention ablation and noise addition was employed to examine the hidden layers’ effect on model performance. The results demonstrate that as the depth of hidden layers increases, the models’ text encoding becomes increasingly similar to the human brain’s language RPs. Manipulating deeper layers leads to more substantial decline in summarization performance compared to shallower layers, highlighting the crucial role of deeper layers in integrating essential information. Notably, the study confirms the hypothesis that the hidden layers exhibiting higher similarity to human brain activity play a more critical role in model performance, with their correlations reaching statistical significance even after controlling for perplexity. These findings deepen our understanding of the cognitive mechanisms underlying language representations in DLMs and their neural correlates, potentially providing insights for optimizing and improving language models by aligning them with the human brain’s language-processing mechanisms.

Abstract Background The evidence indicates that functional training is beneficial for athletes’ physical and technical performance. However, a systematic review of the effects of functional training on athletes’ physical and technical performance is lacking. Therefore, this study uses a literature synthesis approach to evaluate the impact of functional training on the physical and technical performance of the athletic population and to extend and deepen the existing body of knowledge. Methods This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the researchers performed a systematic search of five international electronic databases using the predefined terms "functional training" and "athletes" on 15th November 2023: Web of Science, CINAHL PLUS, PubMed, Scopus, and SPORTDiscus. A PICOS approach was used to identify the following inclusion criteria: (1) athletes, (2) a functional training program, (3) an active control group, (4) a measure of physical and/or technical performance, and (5) randomized controlled studies. A methodological quality assessment of the original research was conducted using the Physiotherapy Evidence Database (Pedro) scale. The review was performed using the PRIMSA guidelines and registered in PROSPERO (ID: CRD42022347943). Results Of the 1059 potentially eligible studies identified, 28 studies met the inclusion criteria. The studies included were conducted on 819 athletes from 12 different countries and were published between 2011 and 2023. The assessment was performed on the Pedro scale, and the mean Pedro score for the included studies was 5.57 (moderate quality, ranging from 4 to 10). The eligibility study reported on 14 different types of sports, with 22 studies focusing on physical performance and 11 studies focusing on technical performance. These studies have shown that functional training can significantly improve the physical and technical performance of athlete populations, but in some studies, no significant difference in the data was observed between groups. Conclusion Functional training is an effective training method for enhancing the physical and technical performance of athlete populations. However, no significant difference in the data was observed between the functional training groups and the regular training group, which may be due to the duration of the training program, the different training experiences of the athletes, and the different focuses of the training regimens. Therefore, future studies should focus on the physical and technical performance of different sports groups with different types and durations of functional training programs to expand the current evidence base.

Time-domain modeling of the thermal deformation of crystal optics can help define acceptable operational ranges across the pulse-energy repetition-rate phase space. In this paper, we have studied the transient thermal deformation of a water-cooled diamond crystal for a cavity-based X-ray free-electron laser (CBXFEL), either an X-ray free-electron laser oscillator (XFELO) or a regenerative amplifier X-ray free-electron laser (RAFEL), by numerical simulations including finite-element analysis and advanced data processing. Pulse-by-pulse transient thermal deformation of a 50 µm-thick diamond crystal has been performed with X-ray pulse repetition rates between 50 kHz and 1 MHz. Results for temperature and thermal deformation have been compared with the results of transient analysis using a continuous wave (CW) power loading. Temperature and thermal deformation results from pulse-by-pulse transient analysis vary with time about the results for the CW case for the same average power. The variation amplitude increases with pulse energy and decreases with repetition rate. When the repetition rate increases to infinity, both temperature and thermal deformation converge to the results for the CW case. Two critical time scales for the operation of crystal optics in a CBXFEL are (1) first-turn time, i.e. the time for the XFEL pulse to complete the first turn around the cavity so that the crystal sees the recirculated XFEL pulse, and (2) period-end time, i.e. the time that the next electron bunch arrives for the amplification, so that the crystal outcouples the amplified FEL power. For the same average power, simulation results show that the crystal thermal deformation seen by the XFEL beam decreases with repetition rate at the first-turn time of a 300 m-long cavity and increases with repetition rate at the period-end time. For the wavefront preservation requirement of the crystal optics, a pulse-energy versus repetition-rate phase space has been established. The upper bounds of the pulse energy at both first-turn and period-end times decreases with repetition rate, especially at the period-end time. The upper bound of the thermal deformation of the crystal at the period-end time for any repetition frequency can be estimated from the CW case. For a water-cooled diamond crystal of dimension 5 mm × 5 mm × 0.05 mm, the time to reach a quasi steady-state is about 50 ms for temperature and 50 µs for thermal deformation

Abstract Background Early diagnosis of syphilis is vital for its effective control. This study aimed to develop an Artificial Intelligence (AI) diagnostic model based on radiomics technology to distinguish early syphilis from other clinical skin lesions. Methods The study collected 260 images of skin lesions caused by various skin infections, including 115 syphilis and 145 other infection types. 80% of the dataset was used for model development with 5-fold cross-validation, and the remaining 20% was used as a hold-out test set. The exact lesion region was manually segmented as Region of Interest (ROI) in each image with the help of two experts. 102 radiomics features were extracted from each ROI and fed into 11 different classifiers after deleting the redundant features using the Pearson correlation coefficient. Different image filters like Wavelet were investigated to improve the model performance. The area under the ROC curve (AUC) was used for evaluation, and Shapley Additive exPlanations (SHAP) for model interpretation. Results Among the 11 classifiers, the Gradient Boosted Decision Trees (GBDT) with the wavelet filter applied on the images demonstrated the best performance, offering the stratified 5-fold cross-validation AUC of 0.832 ± 0.042 and accuracy of 0.735 ± 0.043. On the hold-out test dataset, the model shows an AUC and accuracy of 0.792 and 0.750, respectively. The SHAP analysis shows that the shape 2D sphericity was the most predictive radiomics feature for distinguishing early syphilis from other skin infections. Conclusion The proposed AI diagnostic model, built based on radiomics features and machine learning classifiers, achieved an accuracy of 75.0%, and demonstrated potential in distinguishing early syphilis from other skin lesions.

Abstract This study aimed to develop and validate machine learning (ML) models to predict the occurrence of delayed hyponatremia after transsphenoidal surgery for pituitary adenoma. We retrospectively collected clinical data on patients with pituitary adenomas treated with transsphenoidal surgery between January 2010 and December 2020. From January 2021 to December 2022, patients with pituitary adenomas were prospectively enrolled. We trained seven ML models to predict delayed hyponatremia using the clinical variables in the training set. The final model was internally validated using a test set and a prospective dataset. The SHapley Additive exPlanations (SHAP) algorithm was used to determine the significance of each variable in the occurrence of delayed hyponatremia. In the training dataset, the best predictive performance was observed for XGBoost (area under the ROC curve; AUC = 0.821), followed by Random Forest (AUC = 0.8), Logistic Regression (AUC = 0.793), Support Vector Machine (AUC = 0.776), naïve Bayes (AUC = 0.774), K-Nearest Neighbors (AUC = 0.742), and Decision Tree (AUC = 0.717). The AUC of the XGBoost model for the test and prospective datasets are 0.831 and 0.785, respectively. The differences in pituitary stalk deviation angle, the “measurable pituitary stalk” length before and after surgery, and blood sodium concentration between preoperative and postoperative day 2 were important variables for predicting delayed hyponatremia as determined by the SHAP algorithm. The XGBoost model was best able to predict delayed hyponatremia after transsphenoidal surgery for pituitary adenomas. The differences in pituitary stalk deviation angle, pre- versus postoperative “measurable pituitary stalk” length, and pre- versus postoperative day 2 blood sodium concentrations were important variables for predicting delayed hyponatremia.

Abstract Objective The goal of this current research was to explore the impact of cancer-related fatigue on the quality of life among patients with cancer, as well as the multiple mediating roles of psychological coherence and stigma. Methods This study utilized a cross-sectional design. A questionnaire was administered between November 2022 and May 2023 to 364 patients with cancer in two tertiary hospitals in Jinzhou City, Liaoning Province, China. The questionnaires included the General Information Questionnaire, Cancer-Related Fatigue Questionnaire, Psychological Coherence Scale, Stigma Scale, and Quality of Life Questionnaire. SPSS 25.0 and PROCESS 3.5 macros were used for descriptive statistics and correlation analysis of the data, as well as multiple mediation effect tests. Results Cancer-related fatigue directly affects quality of life (β = -0.950, 95% CI = -1.138 to -0.763) and indirectly through three mediators: psychological coherence (β = -0.172, 12.58% of total effect), stigma (β = -0.193, 14.12% of total effect), and both psychological coherence and stigma (β = -0.052, 3.80% of total effect), totaling a 30.50% mediating effect. Conclusion Overall, psychological coherence and stigma may play an important mediating role between cancer-related fatigue and quality of life in patients with cancer. This suggests that alleviating cancer-related fatigue, while enhancing psychological coherence and reducing stigma, could be effective strategies for improving patients’ quality of life. Therefore, healthcare professionals and related professionals should pay attention to and adopt effective interventions to alleviate cancer-related fatigue, enhance psychological coherence, and reduce stigma, thereby contributing to the overall well-being and quality of life of patients with cancer.

Abstract Breast cancer prognosis is complicated by tumor heterogeneity. Traditional methods focus on cancer-specific gene signatures, but cross-cancer strategies that provide deeper insights into tumor homogeneity are rarely used. Immunotherapy, particularly immune checkpoint inhibitors, results from variable responses across cancers, offering valuable prognostic insights. We introduced a network-based transfer (NBT) of pan-cancer immunotherapy responses to enhance breast cancer prognosis using node embedding and heat diffusion algorithms, identifying gene signatures netNE and netHD. Our results showed that netHD and netNE outperformed seven established breast cancer signatures in prognostic metrics, with netHD excelling. All nine gene signatures were grouped into three clusters, with netHD and netNE enriching the immune-related interferon-gamma pathway. Stratifying TCGA patients into two groups based on netHD revealed significant immunological differences and variations in 20 of 50 cancer hallmarks, emphasizing immune-related markers. This approach leverages pan-cancer insights to enhance breast cancer prognosis, facilitating insight transfer and improving tumor homogeneity understanding. Abstract graph of network-based insights translating pan-cancer immunotherapy responses to breast cancer prognosis. This abstract graph illustrates the conceptual framework for transferring immunotherapy response insights from pan-cancer studies to breast cancer prognosis. It highlights the integration of PPI networks to bridge genetic data and clinical phenotypes. The network-based method facilitates the identification of prognostic gene signatures in breast cancer by leveraging immunotherapy response information, providing a novel perspective on tumor homogeneity and its implications for clinical outcomes.

Digital light processing (DLP)-based bioprinting technology holds immense promise for the advancement of hydrogel constructs in biomedical applications. However, creating high-performance hydrogel constructs with this method is still a challenge, as it requires balancing the physicochemical properties of the matrix while also retaining the cellular activity of the encapsulated cells. Herein, we propose a facile and practical strategy for the 3D bioprinting of high-performance hydrogel constructs through the in-situ birth of stem cell spheroids. The strategy is achieved by loading the cell/dextran microdroplets within gelatin methacryloyl (GelMA) emulsion, where dextran functions as a decoy to capture and aggregate the cells for bioprinting while GelMA enables the mechanical support without losing the structural complexity and fidelity. Post-bioprinting, the leaching of dextran results in a smooth curved surface that promotes in-situ birth of spheroids within hydrogel constructs. This process significant enhances differentiation potential of encapsulated stem cells. As a proof-of-concept, we encapsulate dental pulp stem cells (DPSCs) within hydrogel constructs, showcasing their regenerative capabilities in dentin and neovascular-like structures in vivo. The strategy in our study enables high-performance hydrogel tissue construct fabrication with DLP-based bioprinting, which is anticipated to pave a promising way for diverse biomedical applications.

Objectives: Vitrified bonded diamond grinding tools are widely used in the machining industry, but the high-temperature resistance of diamond is poor. Therefore, there are high requirements on sintering temperature, flowability, and thermal expansion coefficient of vitrified bond materials. The influence of the content of Al2O3, B2O3, and SiO2 in vitrified bond on its properties is investigated. By changing the content of these three components and comparing the changes in the properties of the bonds, a more suitable vitrified bond for diamond grinding tools is obtained. Methods: Using a ternary phase diagram, the content of Al2O3, B2O3, and SiO2 in the R2O-Al2O3-B2O3-SiO2 bond system is adjusted. Sixteen different formulas were designed to prepare 5 mm × 6 mm × 30 mm sample strips under a pressure of 5 MPa, and dried at 80 ℃ for 12 hours. The refractoriness of each group of bonds was measured using a standard refractory cone, the flowability of the bonds was measured using the plane flow method, and the thermal expansion coefficient of the bonds was determined. According to the refractoriness data determined by each formula, sintering was carried out at a temperature 60 ℃ higher than the refractoriness of the bond. A microcomputer-controlled electronic universal testing machine was used to determine the flexural strength of the bond using the three-point bending method. The microhardness of the bond was measured using a microhardness tester, and the microstructure of the bond was analyzed. Results: From the analysis of the measured performance data, it can be concluded that: (1) B2O3 has the effect of reducing the refractoriness in vitrified bonds, while SiO2 and Al2O3 increase the refractoriness of the bonds. Al2O3 has a greater impact on the refractoriness of the bonds than SiO2. (2) B2O3 has the effect of improving the flowability of bonds, while Al2O3 reduces the flowability of bonds. The thermal expansion coefficient and the flexural strength of the bond will vary depending on the content of Al2O3 and B2O3. When the Al2O3 content in the bond is high, the thermal expansion coefficient of the bond will first decrease and then increase with the increase of B2O3 content, and the flexural strength will first increase and then decrease with the increase of B2O3 content. When the Al2O3 content in the bond is low, the thermal expansion coefficient of the bond will increase with the increase of B2O3 content, and the flexural strength will decrease with the increase of B2O3 content. When the SiO2 content is fixed, the thermal expansion coefficient of the bond will increase with the increase of B2O3 content, and the flexural strength will increase with the increase of Al2O3 content. When the B2O3 content is fixed, the thermal expansion coefficient of the bond will increase with the increase of Al2O3 content, and the flexural strength will increase with the increase of B2O3 content. The influence of each component in the bond on the microhardness change of the bond is SiO2>B2O3>Al2O3. When the molar ratio of Al2O3+B2O3 to Na2O in the bond is less than 1, Al2O3 and B2O3 will combine with oxygen ions in Na2O to form [AlO4] and [BO4], which participate in the network structure of the bond and densify it. Breaking the dense network structure requires higher energy. Therefore, densification of the network structure in the bond can reduce its thermal expansion coefficient and improve its flexural strength and microhardness. When n(Al2O3+B2O3)/n(Na2O)>1, the oxygen ions in Na2O are insufficient, and Al2O3 and B2O3 form [AlO3] and [BO3] triangles, reducing the density of the network structure. The fluffy structure makes the network structure more sensitive to energy, increasing the thermal expansion coefficient of the bond and reducing its flexural strength and microhardness. Conclusions: A ternary phase diagram based on the content of Al2O3, B2O3, and SiO2 in the R2O-Al2O3-B2O3-SiO2 system bond can intuitively reflect the synergistic effect of the three components during sintering. The three components will exhibit different effects in bonds with different contents, and their impact on the performance of the bond will also be different. When designing the formula for vitrified bonds, it is necessary to consider the roles of different components in the bond and their interactions with other components.