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

Poly (methyl methacrylate) (PMMA) bone cement is one of the most commonly used biomaterials for augmenting/stabilizing osteoporosis-induced vertebral compression fractures (OVCFs), such as percutaneous vertebroplasty (PVP) and balloon kyphoplasty (BKP). However, its clinical applications are limited by its poor performance in high compressive modulus and weak bonding to bone. To address these issues, a bioactive composite bone cement was developed for the treatment of osteoporotic vertebral compression fractures, in which mineralized collagen (MC) was incorporated into the PMMA bone cement (MC-PMMA). The properties of PMMA and MC-PMMA composite bone cement were determined, including setting time, compressive modulus, adherence, proliferation, and osteogenic differentiation of rat bone mesenchymal stem cells. The properties of both cements were evaluated in an animal study (36 osteoporotic New Zealand female rabbits divided equally between the two bone cement groups; PVP at L5) and a small-scale and short-term clinical study (12 patients in each of the two bone cement groups; follow-up: 2 years). In terms of value for PMMA bone cement, the handling properties of MC-PMMA bone cement were not significantly different. However, both compressive strength and compressive modulus were found to be significantly lower. In the rabbit model study, at 8 and 12 weeks post-surgery, bone regeneration was more significant in MC-PMMA bone cement (cortical bone thickness, osteoblast area, new bone area, and bone ingrowth %; each significantly higher). In the clinical study, at a follow-up of 2 years, both the Visual Analogue Score and Oswestry Disability Index were significantly reduced when MC-PMMA cement was used. MC-PMMA bone cement demonstrated good adaptive mechanical properties and biocompatibility and may be a promising alternative to commercial PMMA bone cements for the treatment of osteoporotic vertebral fractures in clinical settings. While the present results for MC-PMMA bone cement are encouraging, further study of this cement is needed to explore its viability as an ideal alternative for use in PVP and BKP.

Myocardial ischemia/reperfusion (I/R) injury is associated with high mortality and morbidity, however, it has no curative treatment. Farrerol (FA), an active compound extracted from rhododendron, has antibacterial, anti-inflammatory, and antioxidant activities, but its effect and mechanism of FA in I/R injury remain unclear. Here, we found that FA alleviated myocardial I/R in vivo , and decreased the secretion of myocardial injury factors (CK-MB, LDH, troponin-1, and NT-proBNP) while inhibiting the release of inflammatory factors (IL-1β, IL-6, and TNF-α). FA could also alleviate excessive oxidative stress by elevating the level of antioxidant enzymes and reducing oxidation products; and decreased reduced the expression of apoptosis-associated proteins (cleaved caspase-3, Bax, and Bcl-2). However, inhibiting the autophagic pathway or knocking out the Nrf2 gene did not eliminate the myocardial protective effect of FA, but interestingly, macrophage clearance and Nlrp3 deficiency effectively blocked the myocardial protective effect of FA. In addition, FA suppressed NLRP3 inflammasome activation by interfering with NLRP3 and NEK7. In conclusion, these results support drug-targeted macrophage therapy for myocardial I/R and indicate that FA may be used as an immunomodulator in clinical therapy for myocardial I/R.

Since the glass outer screen of a cell phone is the main sensory part of the human eye when using a cell phone, the advantages and disadvantages of the cell phone screen directly affect people's sense of use. Therefore, the defect detection requirements for cell phone screens are high and need to meet the needs of high-volume factory inspection. Most of the traditional defect detection methods use visual methods, the detection results are overly dependent on the subjectivity and experience of workers, the efficiency of this method is low, and the accuracy is poor. Currently, machine learning-based detection methods are applied in numerous industries. In this paper, a faster Regional Convolutional Neural Network (R-CNN) with multi-head attention mechanism for defect detection of cell phone screen is proposed. To enhance the network's capability in extracting feature information, a four-head attention mechanism is added to the last convolutional layer of the ResNet50 network. An improved Region of Interest (ROI) Align is proposed to replace the original ROI Pooling to reduce the localization error of cell phone screen defects. Replace the original Rectified Linear Unit (ReLU) activation function with the Copy Exponential Linear Unit (CELU) activation function to expedite the convergence capability of the network. Finally, by comparing with other classical model training, the evaluation results indicate that the proposed method achieved an average accuracy of 95.71%, which is a 5.34% improvement compared to the original faster R-CNN network.

Immune checkpoint inhibitor-related diabetes mellitus (ICI-DM) is a rare complication that medical oncologists seldom encounter in routine practice. The sporadic nature and intrinsic complexity of ICI-DM make it challenging to analyze comprehensively in experimental settings. In this review, we examine phase 3 clinical trials on ICIs and published case reports of ICI-DM, aiming to summarize its incidence, clinical features, management, and prognosis. Phase 3 clinical trials reveal that the incidence of ICI-DM is higher with combination therapies, such as anti-PD-1 and anti-CTLA-4 or anti-PD-L1, compared to anti-PD-1 monotherapy. ICI-DM typically presents as severe hyperglycemia with a fulminant onset and is often associated with diabetic ketoacidosis, accompanied by unexpectedly low HbA1c and C-peptide levels. ICI-DM shares similarities with classic type 1 diabetes, particularly in terms of autoimmunity and genetic predisposition. This includes a high prevalence of islet autoantibodies and susceptibility to certain HLA haplotypes, often with concurrent endocrine gland dysfunction. This suggests that genetic susceptibility and exposure to ICIs may both be necessary for triggering islet autoimmunity and inducing ICI-DM. Notably, patients with positive islet autoantibodies, such as glutamic acid decarboxylase antibody and islet-associated antigen 2 antibody, tend to experience rapid onset of ICI-DM after ICI exposure. Although patients with ICI-DM generally show a high objective response rate to immunotherapy, a significant proportion also face the need to permanently discontinued treatment. Further research is urgently needed to determine whether permanent discontinuation of immunotherapy is necessary and whether this discontinuation negatively impacts overall survival.

Slapping the Table in Amazement is the unabridged English translation of the famous story collection Pai'an jingqi by Ling Mengchu (1580-1644), originally published in 1628. The forty lively stories gathered here present a broad picture of traditional Chinese society and include characters from all social levels. We learn of their joys and sorrows, their views about life and death, and their visions of the underworld and the supernatural.Ling was a connoisseur of popular literature and a seminal figure in the development of Chinese literature in the vernacular, which paved the way for the late-imperial Chinese novel. Slapping the Table in Amazement includes translations of verse and prologue stories as well as marginal and interlinear comments.

Background Phytohormones play pivotal roles in regulating floral development and secondary metabolite synthesis in saffron ( Crocus sativus L.). Results This study investigated the effects of gibberellin (GA), abscisic acid (ABA), cytokinin (CK), and strigolactone (SL) on floral differentiation, stigma quality, crocin yield, and endogenous hormonal dynamics. GA significantly accelerated floral bud differentiation and apical bud elongation during reproductive transition, increasing flower number by 23.5% compared to the control. While CK also enhanced flowering (17.6% increase), ABA and SL showed milder effects. Intriguingly, ABA treatment markedly elevated crocin content, boosting crocin 1 and 2 levels by 49.5% and 99.2%, respectively, and total crocin yield per corm by 1.7-fold-the highest among all treatments. Endogenous hormone levels were dynamically regulated, with GA and ABA treatments upregulating endogenous ABA. However, qRT–PCR analysis revealed downregulated expression of ABA biosynthesis genes ( ZEP and NCED ) under GA and ABA treatments. Conclusions These findings highlight GA as the most effective hormone for increasing flower number and ABA as the optimal choice for enhancing crocin content. This study provides actionable insights for hormone-mediated agronomic strategies to simultaneously improve saffron’s ornamental and medicinal value.

The illegal ivory trade has led to a sharp decline in wild elephant populations in recent decades, while mammoth ( Mammuthus primigenius ) ivory products have increasingly flooded the marketplace, complicating identification efforts by frontline law enforcement. Existing ivory identification methods face several challenges, including inconsistent accuracy due to sample quality, high costs, slow turnaround times, and destructive sample requirements. Currently, there is a lack of a fast, convenient, and highly effective solution to address these issues. To tackle these challenges, this study developed a novel, efficient, and accurate method for identifying and characterizing ivory products using ultra-performance liquid chromatography with a fluorescence detector (UPLC-FLR). The technique focuses on various organic small-molecule compounds in ivory that have been largely overlooked. A chemical fingerprint library was created using 72 African elephant and 69 mammoth ivory samples. Comprehensive comparative analyses, including principal component analysis, compound distribution analysis, proportion analysis, chord diagrams, and statistical significance tests, revealed significant differences between the organic compounds in the two sample groups, confirming the method’s reliability. Six widely used machine learning classification models were then applied to construct a discriminant model based on 11 key feature compounds among the 85 identified, with each model achieving 100% classification accuracy. Compared to the conventional ‘gold standard’ molecular biology method, this UPLC-based approach shortened detection time from 24 h to just 1 h, reduced the sample requirement by 50%, and cut costs by 90%, making it a more efficient, user-friendly solution for frontline law enforcement. Widespread adoption of this method in law enforcement could become a powerful tool in the fight against the illegal ivory trade.

In this paper, emulsions stabilized by Tremella fuciformis polysaccharides (TFP) were prepared and the physiochemical properties were assessed. Results showed that the TFP emulsions illustrated the highest emulsifying activity (EAI) and emulsifying stability (ESI) when the concentration of TFP and oil were 0.8% and 10% (wt%). The higher pH value was in favor of the emulsifying properties, while the addition of NaCl impaired the stability, and the greater the concentration, the lower the EAI and ESI. Besides, the emulsifying and rheological properties and stability analysis were evaluated in comparison with gum arabic, pectin, and carboxymethyl cellulose emulsions. It was discovered that TFP illustrated better storage and freeze-thaw stability, which was proved by the result of zeta-potential and particle size. The rheological measurement revealed that all the emulsions behaved as pseudoplastic fluids, while TFP displayed a higher viscosity. Meanwhile, TFP emulsions tended to form a more stable network structure according to the analysis of the parameters obtained from the Herschel–Bulkley model. FTIR spectra suggested that the O-H bond could be destructed without the formation of new covalent bonds during the emulsion preparation. Therefore, this study would be of great importance for the research of emulsions stabilized by TFP as a natural food emulsifier.

In this study, Tremella fuciformis polysaccharides (TFPs) were extracted by ultrasound-assisted enzymatic extraction (UAE) at different extraction parameters in order to explore the potential of ultrasound in intensifying the extraction yield. The effects of experimental conditions on the extraction yields were optimized using response surface methodology, with the optimal ultrasonic power of 700 W, temperature of 45 °C and time of 50 min. The kinetic analysis revealed that UAE significantly promoted the dissolution, diffusion and migration with the maximum yield of 26.39%, which was enhanced by 40.45% and 156.96% compared with individual ultrasonic extraction (UE) and enzymatic extraction (EE). According to the modified Fick’s second law of diffusion, the extraction process of TFPs illustrated a good linear correlation (R2 ≥ 0.9), and the rate constant gradually elevated as the temperature increased from 25 to 45 °C, while the presence of ultrasound exerted a vital role in extracting TFPs. Regarding to the thermodynamic results, the positive values of ΔH and ΔG demonstrated that UAE, UE and EE were endothermic and unspontaneous processes. This study provides a theoretical basis for polysaccharide extraction processing.