Objective To identify inflamm-aging related biomarkers in osteoarthritis(OA).Methods Microarray gene profiles of young and aging OA patients were obtained from the Gene Expression Omnibus(GEO)database and aging-related genes(ARGs)were obtained from the Human Aging Genome Resource(HAGR)database.The differentially expressed genes of young OA and older OA patients were screened and then intersected with ARGs to obtain the aging-related genes of OA.Enrichment analysis was performed to reveal the potential mechanisms of aging-related markers in OA.Three machine learning methods were used to identify core senescence markers of OA and the receiver operating characteristic(ROC)curve was used to assess their diagnostic performance.Peripheral blood mononuclear cells were collected from clinical OA patients to verify the expression of senescence-associated secretory phenotype(SASP)factors and senescence markers.Results A total of 45 senescence-related markers were obtained,which were mainly involved in the regulation of cellular senescence,the cell cycle,inflammatory response,etc.Through the screening with the three machine learning methods,5 core senescence biomarkers,including FOXO3,MCL1,SIRT3,STAG1,and S100A13,were obtained.A total of 20 cases of normal controls and 40 cases of OA patients,including 20 cases in the young patient group and 20 in the elderly patient group,were enrolled.Compared with those of the young patient group,C-reactive protein(CRP),interleukin(IL)-6,and IL-1β levels increased and IL-4 levels decreased in the elderly OA patient group(P＜0.01);FOXO3,MCL1,and SIRT3 mRNA expression decreased and STAG1 and S100A13 mRNA expression increased(P＜0.01).Pearson correlation analysis demonstrated that the selected markers were associated with some indicators,including erythrocyte sedimentation rate(ESR),IL-1β,IL-4,CRP,and IL-6.The area under the ROC curve of the 5 core aging genes was always greater than 0.8 and the C-index of the calibration curve in the nomogram prediction model was 0.755,which suggested the good calibration ability of the model.Conclusion FOXO3,MCL1,SIRT3,STAG1,and S100A13 may serve as novel diagnostic biomolecular markers and potential therapeutic targets for OA inflamm-aging.

Ascosphaera apis spores containing a dark-colored pigment infect honeybee larvae, resulting in a large-scale collapse of the bee colony due to chalkbrood disease. However, little is known about the pigment or whether it plays a role in bee infection caused by A. apis. In this study, the pigment was isolated by alkali extraction, acid hydrolysis, and repeated precipitation. Ultraviolet (UV) analysis revealed that the pigment had a color value of 273, a maximum absorption peak at 195 nm, and a high alkaline solubility (7.67%) and acid precipitability. Further chemical structure analysis of the pigment, including elemental composition, Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy, mass spectrometry, and nuclear magnetic resonance (NMR), proved that it was a eumelanin with a typical indole structure. The molecular formula of melanin is C₁₀H₆O₄N₂, and its molecular weight is 409 Da. Melanin has hydroxyl, carboxyl, amino, and phenolic groups that can potentially chelate to metal ions. Antioxidant function analyses showed that A. apis melanin had a high scavenging activity against superoxide, hydroxyl, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals, and a high reducing ability to Fe³⁺. Indirect immunofluorescence assay (IFA), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) analyses showed that A. apis melanin was located on the spore wall. The spore wall localization, antioxidant activity, and metal ion chelating properties of fungal melanin have been suggested to contribute to spore pathogenicity. However, further infection experiments showed that melanin-deficient spores did not reduce the mortality of bee larvae, indicating that melanin does not increase the virulence of A. apis spores. This study is the first report on melanin produced by A. apis, providing an important background reference for further study on its role in A. apis.
Animals ; Antioxidants/pharmacology* ; Larva ; Melanins ; Molecular Structure ; Onygenales

Gene-engineered T cells, represented by chimeric antigen receptor T cells (CAR-T cells), have achieved great success in hematological tumors, and gradually been applied in the clinical treatment of tumors. In 2017, two CD19-CAR products for hematological tumors were consecutively approved for marketing in America, and have shown powerful anti-tumor efficacy in non-solid tumor treatment. However, CAR-T cell therapy didn’t achieve expectant therapeutic efficacy in solid tumors due to complicated tumor microenvironment and restriction of surface tumor antigen. In addition, the cytotoxicity caused by off-target effects is more troublesome. To address these hurdles, more and more researchers have begun to explore new gene-edited T cells for solid tumor treatment, among which bispecific T cell engager T cell (BiTE T) has shown high anti-tumor efficacy in vitro evaluation and in vivo animal models and thus has attracted great attention. This review mainly discusses the current difficulties confronted by solid tumor treatment and the principles, characteristics and advantages of BiTE-T cell preparation.