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Objective To explore the mechanism of peripheral neurons FcγRⅠ regulating pain caused by rheumatoid arthritis. Methods Rheumatoid arthritis models were established in 14 wild-type SD rats and 7 Fcgr1 conditional knockout rats. Wild-type rat control group (control group), rheumatoid arthritis group of wild-type rat (RA group) and rheumatoid arthritis group of Fcgr1 conditional knockout rat (RA+CKO group) were established. Pain behavior was used to detect the changes of mechanical pain threshold and thermal pain threshold 3 and 1 days before modeling and 3, 5, 7 and 9 days after modeling. The expression of Fcgr1 mRNA in dorsal root ganglion (DRG) of Fcgr1 conditional knockout rat was detected by fluorescence in situ hybridization. Immunofluorescence staining was used to detect the changes of IL-1β and IL-18 expression in the DRG and activation of glial cells in the spinal dorsal horn (SDH). Results Compared with the control group, the threshold of mechanical and thermal pain in RA group and (RA+CKO) group were decreased (P＜0.05), the mechanical and thermal pain thresholds of the (RA+CKO) group were significantly higher than of RA group(P＜0.05). Compared with the RA group, the expression of pNF-κB, NLRP3, IL-1β and IL-18 and the protein level of GFAP and Iba1 in the SDH of (RA+CKO) rats were significantly decreased (P＜0.05). Conclusions FcγRⅠ of DRG neurons may promote the synthesis and release of inflammatory cytokines IL-1β and IL-18 through NF-κB/NLRP3 pathway, and cause glial cells activation in the SDH, which may play a role in the mechanism causing pain of rheumatoid arthritis.

Ticks can carry multiple pathogens, and Inner Mongolia’s animal husbandry provides excellent environmental conditions for ticks. This study characterized the microbiome of ticks from different geographical locations in Inner Mongolia; 905 Dermacentor nuttalli and 36 Ixodes persulcatus were collected from sheep in three main pasture areas and from bushes within the forested area. Mixed DNA samples were prepared from three specimens from each region and tick species. Microbial diversity was analyzed by 16S rRNA sequencing, and α and β diversity were determined. The predominant bacterial genera were Rickettsia (54.60%), including Rickettsiales bacterium Ac37b (19.33%) and other Rickettsia (35.27%), Arsenophonus (11.21%), Candidatus Lariskella (10.84%), and Acinetobacter (7.17%). Rickettsia bellii was identified in I. persulcatus, while Rickettsiales bacterium Ac37b was found in D. nuttalli from Ordos and Chifeng. Potential Rickettsia and Anaplasma coinfections were observed in the Ordos region. Tick microbial diversity analysis in Inner Mongolia suggests that sheep at the sampling sites were exposed to multiple pathogens.

Tre2-Bub2-Cdc16 (TBC) proteins are conserved in eukaryotic organisms and function as negative feedback dominating the GAPs for Rab GTPases, while the function of TBC proteins in melanoma remains unclear. In this study, we observed the differential expression of 33 TBC genes in TCGA datasets classified by clinical features. Seven prognostic-associated TBC genes were identified by LASSO Cox regression analysis. Mutation analysis revealed distinctive frequency alteration in the seven prognostic-associated TBCs between cases with high and low scores. High-risk score and cluster 1 based on LASSO Cox regression and consensus clustering analysis were relevant to clinical features and unfavorable prognosis. GSVA analysis showed that prognostic-associated TBCs were related to metabolism and protein transport signaling pathway. Correlation analysis indicated the relationship between the prognostic-associated TBCs with RAB family members, invasion-related genes and immune cells. The prognostic nomogram model was well established to predict survival in melanoma. What’s more, interference of one of the seven TBC proteins TBC1D7 was confirmed to inhibit the proliferation, migration and invasion of melanoma cells in vitro. In summary, we preliminarily investigated the impact of TBCs on melanoma through multiple bioinformatics analysis and experimental validation, which is helpful for clarifying the mechanism of melanoma and the development of anti-tumor drugs.

Neuropathic pain is difficult to treat in clinical practice, and the underlying mechanisms are insufficiently elucidated. Previous studies have demonstrated that the neuronal Fc‐gamma‐receptor type I (FcγRI) of the dorsal root ganglion (DRG) mediates antigen‐specific pain. However, the mechanisms of neuronal FcγRI in neuropathic pain remain to be explored. Here, it is found that the activation of FcγRI‐related signals in primary neurons induces neuropathic pain in a rat model. This work first reveals that sciatic nerve injury persistently activates neuronal FcγRI‐related signaling in the DRG, and conditional knockout (CKO) of the FcγRI‐encoding gene Fcgr1 in rat DRG neurons significantly alleviates neuropathic pain after nerve injury. C‐reactive protein (CRP) is increased in the DRG after nerve injury, and CRP protein of the DRG evokes pain by activating neuronal FcγRI‐related signals. Furthermore, microinjection of naive IgG into the DRG alleviates neuropathic pain by suppressing the activation of neuronal FcγRI. These results indicate that the activation of neuronal CRP/FcγRI‐related signaling plays an important role in the development of neuropathic pain in chronic constriction injury (CCI) rats. The findings may provide novel insights into the neuroimmune responses after peripheral nerve injury and suggest potential therapeutic targets for neuropathic pain. [ABSTRACT FROM AUTHOR]

The anomalous Hall effect (AHE) and magneto-crystalline anisotropy (MCA) are investigated in epitaxial NixFe1−x thin films grown on MgO (001) substrates. The scattering independent term b of anomalous Hall conductivity shows obvious correlation with cubic magneto-crystalline anisotropy K1. When nickel content x decreasing, both b and K1 vary continuously from negative to positive, changing sign at about x = 0.85. Ab initio calculations indicate NixFe1−x has more abundant band structures than pure Ni due to the tuning of valence electrons (band fillings), resulting in the increased b and K1. This remarkable correlation between b and K1 can be attributed to the effect of band filling near the Fermi surface.

Chronic low-grade inflammation defines obesity as a metabolic disorder. Alterations in the structure of gut flora are strongly associated with obesity. Lactoferrin (LF) has a biological function in regulating intestinal flora. The present study aimed to investigate the therapeutic and anti-inflammatory effects of LF in obese mice based on intestinal flora. A total of 30 C57BL/6 mice were divided into three groups consisting of 10 mice each. Subsequently, one group was fed a normal diet (Group K), another group was fed a high-fat diet (Group M) and the remaining group switched from regular drinking to drinking 2% LF water (Group Z2) after 2 weeks of high-fat diet; all mice were fed for 12 weeks. After the experiment, the mouse blood lipid and lipopolysaccharide levels, levels of inflammatory factors and intestinal tight junction proteins were assessed. Mouse stool samples were analyzed using 16S ribosomal RNA sequencing. The results showed that LF reduced serum total cholesterol, triglycerides and low-density lipoprotein levels, elevated high-density lipoprotein levels, suppressed metabolic endotoxemia and attenuated chronic low-grade inflammatory responses in obese mice. In addition, LF upregulated zonula occludens-1 and occludin protein expression levels in the intestine, thereby improving intestinal barrier integrity. LF altered the intestinal microbial structure of obese mice, reduced the ratio of Firmicutes and an elevated ratio of Bacteroidota, modifying the bacterial population to the increased relative abundance of Alistipes, Acidobacteriota, Psychrobacter and Bryobacter. [ABSTRACT FROM AUTHOR]

Rhein is a key ingredient in many herbal remedies and is widely used. However, herbs containing rhein are frequently associated with poisoning incidents, especially in elderly subjects. Acute and subchronic toxicity of rhein in Kunming mice (KM) was investigated in this experiment. Acute toxicity tests showed a 40% lethality at a given rhein dose of 4000 mg/kg, and the LD50 of rhein was calculated by the bliss method to be greater than 2185.6 mg/kg. In subchronic toxicity, d-gal-induced aged and immature animals were randomized into three groups that were exposed to rhein of 0, 175, and 375 mg/kg/d for 75 days, respectively. No mortality was observed in immature mice group, whereas 55.5% (5/9) subjects in aged mice groups died in the high dosage group. AST, ALT, IL-6, TNF-α levels and typical histopathological changes indicate that rhein causes liver injury. In addition, our investigation explored possible hepatotoxic mechanisms of rhein and experimental results showed increased ROS production, NRF-2 and MDA levels and decreased SOD levels, demonstrating that rhein causes oxidative stress. MMP and mitochondrial swelling levels were able to assess the impact of rhein on mitochondrial function. Furthermore, the effect of rhein on apoptosis can be detected by flow cytometry. Our studies suggested that rhein induces oxidative stress leading to mitochondria dysfunction and apoptotic activation. Multidrug resistance protein (MRP) is an efflux transporter protein and is capable of transporting cellular oxidative stress-related substances. To further clarify the role of MRP in rhein induced oxidative stress, we examined MRP expression in the liver. However, the expression of MRP has no statistical significance. [ABSTRACT FROM AUTHOR]