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Abstract Background Osteoarthritis (OA) is the most common motor system disease in older people, characterized by a high incidence and significant social and economic burden. Women have a higher risk of OA, more severe clinical symptoms, and a higher rate of disabilities than men. However, the pathogenesis of OA remains unclear. Therefore, we screened for differentially expressed genes (DEGs) in OA patients of different sex and searched for new targets that may be involved in regulating the development of OA. Methods The study compared the expression of DEGs in synovial fluid exosomes between male and female patients with OA through RNA sequencing combined with bioinformatics analysis using public data. To evaluate the screened DEGs, synovial tissue and fluid samples were obtained from patients with OA who underwent joint replacement surgery. SiRNA-mediated knockdown in vitro experiments were performed to investigate the role of glycoprotein membrane 6B (GPM6B). Meanwhile, GPM6B gene knockout mice were used to assess the in vivo pathological roles of GPM6B in OA. Results The results revealed that GPM6B is a potential target associated with OA. Immunofluorescence staining demonstrated that GPM6B was expressed in fibroblast-like synoviocytes (FLS) and macrophage-like synoviocytes in patients with OA. In vitro experiments confirmed that GPM6B knockdown can reduce the expression of inflammatory factors in primary FLS from patients with OA. Under inflammatory conditions, GPM6B knockdown can reduce the expression of matrix metalloproteinases as well as proliferation of FLS. In addition, using a destabilization of the medial meniscus-induced OA model, we revealed that GPM6B is associated with OA progression in mice. Conclusion Thus, we provided evidence that GPM6B act as a new target associated with OA.

Abstract Brucellosis remains one of the most common zoonoses spread worldwide, inducing enormous economic losses to the livestock industry and posing serious health threats to humans. Brucellosis re-emerged in China in the mid-1990s and reached a historically high level in 2015. The National Brucellosis Prevention and Control Plan (NBPCP) was initiated from 2016 to 2020. However, the present epidemiological status in livestock has not been elucidated, and whether Brucella variation occurred remains unclear. This study performed an extensive serological investigation in ruminant livestock from 2019 to 2021 in central Gansu Province, China. In total, 11,296 samples from 337 farms were collected to detect the specific antibodies of Brucella. The yearly average serological prevalence of Brucella at the flock level and individual level declined from 11.32% to 8.26% and 1.17% to 0.57%, respectively. The apparent individual-level seroprevalence of small and large ruminants was 0.89% and 0.52%, respectively. The brucellosis distribution has shifted from pastoral areas to agro-pastoral areas. Flock size and gender may be major risks of Brucella infection. Then, the B. melitensis TZ strain was isolated from female Tibetan sheep blood cell lysates. Phonotypical characterization demonstrated that it belongs to B. melitensis. biovar 3, and multilocus sequencing typing results indicated that it belongs to ST8. The whole genome and subsequent phylogenetic analysis demonstrated that the B. melitensis TZ strain is genetically more closely related to the B. melitensis QH61 strain. The B. melitensis TZ strain has similar growth characteristics to the B. melitensis 16 M strain. Overall, our study suggests that after strengthening control and prevention measures based on the NBPCP, there is a very low prevalence or absence of B. melitensis in the central Gansu Province of China, and the genotype of an epidemic strain of Brucella in Northwest China is relatively stable.

Abstract Background Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a collagen receptor belonging to the immunoglobulin superfamily. Although previous studies have evaluated the biological role of LAIR in solid tumors, the precise mechanisms underlying the functions of LAIR-1 as a regulator of tumor biological functions remain unclear. Methods LAIR-1 expression was evaluated by immunohistochemical analysis using an osteosarcoma (OS) tissue microarray. Wound healing and transwell migration assays were performed to evaluate tumor cell migration. Quantitative real-time polymerase chain reaction (qPCR) and western blotting were conducted to detect the expression of epithelial–mesenchymal transition (EMT)-related molecules. RNA-sequencing (RNA-seq) was conducted to evaluate the mRNA expression profiles after overexpressing LAIR-1 in OS cells. Glucose transporter (Glut)1 expression in OS cells was evaluated by western blotting. Results LAIR-1 expression was significantly different between the T1 and T2 stages of OS tumors, and it inhibited OS cell migration. LAIR-1 expression was inversely correlated with the expression of Twist1, an EMT-associated transcription factor, via the Forkhead box O1 signal transduction pathway. Furthermore, RNA-seq and qPCR demonstrated that the expression of EMT energy metabolism-related molecules was significantly reduced after LAIR-1 overexpression. Conclusions LAIR-1 overexpression decreased the expression of Glut1 and inhibited the expression of EMT-related molecules in OS cells. These findings provide new insights into the molecular mechanism underlying OS progression.

Platelet-rich plasma (PRP) is a platelet-based application used to treat osteoarthritis (OA) clinically. The co-stimulatory molecule CD226 is expressed in T cells, NK cells, and also platelets. However, exact effects of CD226 on platelets and whether its expression level influences PRP efficacy are largely unknown. Here, CD226fl/flPF4-Cre mice were obtained from mating CD226 fl/fl mice with PF4-Cre mice. Blood samples and washed platelets were collected from the mice eyeballs to undergo routine blood tests and transmission electron microscopy. Differentially expressed proteins were detected by iTRAQ-based proteomics analysis. Animal OA models were established through surgical destabilization of the medial meniscus (DMM) for C57BL/6 wildtype mice, followed by PRP injection to evaluate the effects of platelet CD226 on PRP efficacy. The results showed that deletion of platelet CD226 increased the number of megakaryocytes (MKs) in bone marrow (BM) but reduced MKs in spleen, combined with significantly decreased platelet amounts, α-granule secretion, and reduced immature platelets; indicating that absence of platelet CD226 may disrupt MK/platelet homeostasis and arrested platelet release from MKs. Sequencing analysis showed abnormal ribosomal functions and much downregulated proteins in the absence of platelet CD226. Autophagy-related proteins were also reduced in the CD226-absent MKs/platelets. Moreover, deletion of platelet CD226 diminished the protective effects of PRP on DMM-induced cartilage lesions in mice, and PDGF restored it. Therefore, deficiency of platelet CD226 inhibited platelet maturation, secretion, and normal ribosomal functions, which may lead to depressed PRP efficacy on OA, suggesting that CD226 is required to regulate platelet growth, functions, and its application.

BackgroundOsteosarcoma (OS) is a highly malignant and aggressive bone tumor. This study was performed to explore the mechanisms of HuR (human antigen R) in the progression of OS.MethodsHuR expression levels in OS tissues and cells were detected by immunohistochemistry and western blotting. HuR siRNA was transfected into SJSA-1 OS cells to downregulate HuR expression, and then cell proliferation, migration, and epithelial-mesenchymal transition (EMT) were evaluated. RNA immunoprecipitation was performed to determine the association of the long non-coding RNA (lncRNA) XIST and argonaute RISC catalytic component (AGO) 2 with HuR. Fluorescence in situ hybridization analysis was performed to detect the expression of lncRNA XIST. Western blotting and immunofluorescence assays were performed to observe AGO2 expression after HuR or/and lncRNA XIST knockdown.ResultsKnockdown of HuR repressed OS cell migration and EMT. AGO2 was identified as a target of HuR and silencing of HuR decreased AGO2 expression. The lncRNA XIST was associated with HuR-mediated AGO2 suppression. Moreover, knockdown of AGO2 significantly inhibited cell proliferation, migration, and EMT in OS.ConclusionOur findings indicate that HuR knockdown suppresses OS cell EMT by regulating lncRNA XIST/AGO2 signaling.

The northern piedmont belt of the Taibei Sag is one of the oil rich structural belts in the Turpan-Hami Basin. Based on the interpretation of seismic cross sections and the analyses of discovered hydrocarbon accumulations, the geologic structure can be divided into six structural styles, thrust-imbricate structure, imbricate fan structure, thrust-opposite structure, pop-up structure, forward thrust structure and duplex structure. According to the study of the distribution regularity of the structural styles, the fold thrust belt controlled by three levels tectonic transform zones is characterized by zonation from the south to the north and segmentation from the west to the east, and it can be classified into thrust-nappe belt, breaking belt and frontal belt by mechanism of tectonic deformation. The leading edge with two accumulation forming models which are the leading edge pop-up model and the leading edge imbricate fan model is the most favorable hydrocarbon enriched belt in the northern margin of the Taibei Sag. The thrust-opposite structures in the rear edge of the deformable zone have good preservation, potential source kitchen on the footwall, higher fault dip, and good communication of sandbodies. They are the next favorable exploration structures. Key words: structural style, thrust faults system, structural deformation belt, tectonic transform zone, accumulation forming model