Guanylate-binding protein 1 inhibits inflammatory factors produced by H5N1 virus through Its GTPase activity.

The combination of inflammatory factors resulting from an influenza A virus infection is one of the main causes of death in host animals. Studies have shown that guinea pig guanosine monophosphate binding protein 1 (guanylate-binding protein 1, gGBP1) can downregulate cytokine production induced by the influenza virus. Therefore, exploring the innate immune defense mechanism of GBP1 in the process of H5N1 influenza virus infection has important implications for understanding the pathogenic mechanism, disease prevention, and the control of influenza A virus infections. We found that, in addition to inhibiting the early replication of influenza virus, gGBP1 also inhibited the production of CCL2 and CXCL10 cytokines induced by the influenza virus as well as the proliferation of mononuclear macrophages induced by these cytokines. These findings further confirmed that gGBP1 inhibited the production of cytokines through its GTPase activity and cell proliferation through its C-terminal α-helix structure. This study revealed the effect of gGBP1 on the production of cellular inflammatory factors during influenza virus infection and determined the key amino acid residues that assist in the inhibitory processes mediated by gGBP1.

Microglial SIX2 suppresses lipopolysaccharide (LPS)-induced neuroinflammation by up-regulating FXYD2 expression.

Parkinson's disease (PD) is a severe neurodegenerative disease associated with the loss of dopaminergic (DA) neurons in the substantia nigra (SN). Although its pathogenesis remains unclear, microglia-mediated neuroinflammation significantly contributes to the development of PD. Here we showed that the sine oculis homeobox (SIX) homologue family transcription factors SIX2 exerted significant effects on neuroinflammation. The SIX2 protein, which is silenced during development, was reactivated in lipopolysaccharide (LPS)-treated microglia. The reactivated SIX2 in microglia mitigated the LPS induced inflammatory effects, and then reduced the toxic effect of conditioned media (CM) of microglia on co-cultured MES23.5 DA cells. Using the LPS-stimulated Cx3cr1-CreERT2 mouse model, we also demonstrated that the highly-expressed SIX2 in microglia obviously attenuated neuroinflammation and protected the DA neurons in SN. Further RNA-Seq analysis on the inflammatory activated microglia revealed that the SIX2 exerted these effects via up-regulating the FXYD domain containing ion transport regulator 2 (FXYD2). Taken together, our study demonstrated that SIX2 was an endogenous anti-inflammatory factor in microglia, and it exerted anti-neuroinflammatory effects by regulating the expression of FXYD2, which provides new ideas for anti-neuroinflammation in PD.

Associations of hearing loss and structural changes in specific cortical regions: a Mendelian randomization study.

INTRODUCTION: Previous studies have suggested a correlation between hearing loss (HL) and cortical alterations, but the specific brain regions that may be affected are unknown. METHODS: Genome-wide association study (GWAS) data for 3 subtypes of HL phenotypes, sensorineural hearing loss (SNHL), conductive hearing loss, and mixed hearing loss, were selected as exposures, and GWAS data for brain structure-related traits were selected as outcomes. The inverse variance weighted method was used as the main estimation method. RESULTS: Negative associations were identified between genetically predicted SNHL and brain morphometric indicators (cortical surface area, cortical thickness, or volume of subcortical structures) in specific brain regions, including the bankssts (ß = -0.006 mm, P = 0.016), entorhinal cortex (ß = -4.856 mm2, P = 0.029), and hippocampus (ß = -24.819 cm3, P = 0.045), as well as in brain regions functionally associated with visual perception, including the pericalcarine (ß = -10.009 cm3, P = 0.013). CONCLUSION: Adaptive changes and functional remodeling of brain structures occur in patients with genetically predicted HL. Brain regions functionally associated with auditory perception, visual perception, and memory function are the main brain regions vulnerable in HL.

New cassane-type alkaloids and diterpenoids from the pericarps of Caesalpinia bonduc.

The phytochemical investigation of the pericarps of Caesalpinia bonduc led to the isolation and identification of five new cassane-type alkaloids: caesalminines C - G (1-5) and six new diterpenoids: caesalbonducin K - P (6-11), along with seven known compounds (12-18). Compounds 1-5 were identified as a group of rare alkaloids possessing a tetracyclic cassane-type diterpenoid skeleton with a lactam D-ring instead of a typical furan or lactone moiety. The structures of 1-11 were elucidated on the basis of 1D and 2D NMR including HSQC, HMBC, COSY and NOESY, and other spectroscopic analyses. The cytotoxic activities of the isolated compounds were evaluated in the A431, A549 and U87MG cancer cell lines.

Differential absorption of cadmium and zinc by tobacco plants: Role of apoplastic pathway.

Cadmium (Cd) contamination presents a significant challenge in global agriculture. This study explores the efficacy of chemical induction, specifically using sodium chloride (NaCl), to limit Cd uptake in tobacco (Nicotiana tabacum) and assesses its impact on essential divalent metal ions (DMIs). We conducted a comprehensive analysis encompassing ion absorption, root histology, and biochemistry to understand the influence of this method. Our results revealed that NaCl induction led to a notable 30 % decrease in Cd absorption, while maintaining minimal impact on zinc (Zn) uptake. Intriguingly, the absence of essential DMIs, such as calcium (Ca), magnesium (Mg), and Zn, was found to diminish the plant's capacity to absorb Cd. Furthermore, moderate NaCl induction resulted in an increased diameter of the root stele and enhanced lignin content, indicating a restriction of Cd absorption through the apoplastic pathway. Conversely, a compensatory absorption mechanism via the symplastic pathway appeared to be activated in the absence of essential elements. These findings highlight the potential of chemical induction as a strategy to mitigate agricultural Cd risks, offering insights into the complex interplay between plant ion transport pathways and metal uptake regulation.

Prognosis of Elevated Mitral Valve Pressure Gradient After Transcatheter Edge-to-Edge Repair: Systematic Review and Meta-Analysis.

Elevation in mitral valve pressure gradient (MVPG) after mitral valve transcatheter edge-to-edge repair (M-TEER) is common, however, evidence on its prognosis is scarce and debatable. Thus, this study aims to investigate the impact of increased MVPG after M-TEER on outcomes. Studies reporting the associations between the elevated MVPG after M-TEER and outcomes were identified in a systematic search of published literatures. Associations were pooled by meta-analysis using a random-effects model. The primary outcome was the composite of all-cause mortality and heart failure (HF) hospitalization. Seven observational studies with 2,730 patients (mean age, 77.7 ± 9.3 years; male, 64.4%; functional mitral regurgitation [MR], 65.2%) were eligible for the present analysis. M-TEER was performed entirely using the MitraClip system (Abbott), followed by 29.7% of patients having increased MVPG. Elevated postprocedural MVPG was not associated with a higher risk of the primary outcome, compared to low MVPG [hazard ratio (HR) = 1.22; 95% confidence interval (CI) 0.95-1.58; p = 0.12; I2 = 53.5%). However, the prognosis of elevated MVPG was observed in degenerative MR patients (HR = 1.37; 95% CI 1.03-1.84; p = 0.03; I2 = 0%), whereas not in functional MR patients. Patients with low MVPG + high residual MR had a higher risk of the primary outcome than those with high MVPG + low residual MR after M-TEER (HR = 1.50; 95% CI 1.10-2.03; p = 0.01; I2 = 13%). In conclusion, elevated MVPG seems to predict adverse outcomes mainly in patients with degenerative MR. Future studies are needed to prove these findings.

RF-controlled mode-locking and optoelectronic pulse compressing with distributed selectable wavelengths.

Mode-locking in laser cavities has attracted great interest due to its wide range of applications in generating optical frequency combs and ultra-short pulse trains. Here, a mode-locked fiber laser with a distributed selectable wavelength feedback is proposed based on radio frequency maneuverability. The laser is capable of generating transform-limited pulses with a selectable wavelength and repetition rates by interrogating different reflectors through active modulation. Intriguing laser pulses were realized, which can have >930 times width compression ratio compared with the modulation signal and can be selectively locked to reflectors separated in centimeter scale.

A segmentation model to detect cevical lesions based on machine learning of colposcopic images.

Background: Semantic segmentation is crucial in medical image diagnosis. Traditional deep convolutional neural networks excel in image classification and object detection but fall short in segmentation tasks. Enhancing the accuracy and efficiency of detecting high-level cervical lesions and invasive cancer poses a primary challenge in segmentation model development. Methods: Between 2018 and 2022, we retrospectively studied a total of 777 patients, comprising 339 patients with high-level cervical lesions and 313 patients with microinvasive or invasive cervical cancer. Overall, 1554 colposcopic images were put into the DeepLabv3+ model for learning. Accuracy, Precision, Specificity, and mIoU were employed to evaluate the performance of the model in the prediction of cervical high-level lesions and cancer. Results: Experiments showed that our segmentation model had better diagnosis efficiency than colposcopic experts and other artificial intelligence models, and reached Accuracy of 93.29 %, Precision of 87.2 %, Specificity of 90.1 %, and mIoU of 80.27 %, respectively. Conclution: The DeepLabv3+ model had good performance in the segmentation of cervical lesions in colposcopic post-acetic-acid images and can better assist colposcopists in improving the diagnosis.

Incorporating ecosystem services into functional zoning and adaptive management of natural protected areas as case study of the Shennongjia region in China.

Against the background of global climate change and anthropogenic interference, studying the spatial and temporal heterogeneity of ecosystem services in important ecological function regions and rationally dividing the functional zones will help to promote the construction of the natural protected areas system dominated by national parks. The Shennongjia Region is an important candidate for China's national parks and one of the key pilots. Integrating the InVEST model, Getis-Ord Gi* index, hotspot analysis, GeoDetector and K-means clustering algorithm, we measured five ecosystem services interactions and delineate the functional zones. The results show that the spatial and temporal evolution of various ecosystem services in the Shennongjia Region between 2000 and 2020 was significant. All ecosystem services showed a decreasing and then increasing trend, except for carbon storage, which slowly declined. The ecological status of the region is in the process of polarization, with the local environment showed a trend of continuous deterioration. Water yield-habitat quality and carbon storage-water purification showed synergistic relationships; soil conservation showed trade-offs with water yield, carbon storage and water purification over a wide spatial range. The interaction between land surface temperature and vegetation cover was the most significant dominant factor. Hot spots for the comprehensive ecosystem services index were mainly located in the central and southern parts of the Shennongjia region and four types of ecosystem service functional zones were identified accordingly. This study is of great significance for maximizing the benefits of ecosystem service functions, the efficient allocation of environmental resources and the rational formulation of management policies in natural protected areas.

Anti-inflammatory, cardioprotective effect of gypenoside against isoproterenol-induced cardiac remodeling in rats via alteration of inflammation and gut microbiota.

BACKGROUND: Myocardial infarction (MI), commonly referred to as a heart attack, occurs when the blood flow to a portion of the heart is blocked, causing damage to the heart muscle. In this study, we scrutinized the cardioprotective effect of gypenoside against the isoproterenol (ISO)-induced myocardial injury (MI) in the rats. METHODS: Wistar rats were divided into four groups as follow: normal, gypenoside (10 mg/kg), ISO control, and ISO control treated with the gypenoside (2.5, 5, and 10 mg/kg). Various parameters were estimated such as infract size, hemodynamic, inflammatory, antioxidant, cardiac, cytokines, and apoptotic markers. We also estimated the gut microbiota in the faces of the experimental rats. Finally, heart tissue histopathology performed. RESULT: Dose-dependent treatment of gypenoside significantly (P < 0.001) reduced the infracted size along with suppression of the heart weight and heart ratio along with enhance the body weight. Gypenoside treatment considerably altered the level of cardiac parameters, cardiac membrane stabilizing enzyme, hemodynamic parameters, antioxidant, lipid parameters, hepatic parameters, renal parameters, inflammatory cytokines, and mediators. Gypenoside significantly (P < 0.001) suppressed the level of apoptotic markers such as caspase-3, caspase-6, and caspase-9. Gypenoside significantly (P < 0.001) altered the relative abundance of unclassified bacteria, Tenericutes, Candidatus_Saccharibacteria, Verrucomicrobia, Actinobacteria, Bacteroidetes, Firmicutes and suppressed the ratio of F/B. CONCLUSION: Gypenoside acts as a protective phytoconstituents against the ISO-induced myocardial infraction in the rats via alteration of gut microbiota, inflammatory, and oxidative stress.

Dephosphorylation of Six2Y129 protects tyrosine hydroxylase-positive cells in SNpc by regulating TEA domain 1 expression.

Parkinson's disease (PD) is a neurodegenerative disease characterized by selective loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). We recently reported that Six2 could reverse the degeneration of DA neurons in a dephosphorylation state. Here we further identified that Eya1 was the phosphatase of Six2 that could dephosphorylate the tyrosine 129 (Y129) site by forming a complex with Six2 in damaged DA cells. Dephosphorylated Six2 then translocates from the cytoplasm to the nucleus. Using ChIP-qPCR and dual luciferase assay, we found that dephosphorylated Six2 down-regulates TEA domain1 (Tead1) expression, thus inhibiting 6-hydroxydopamine (6-OHDA)-induced apoptosis in DA cells. Furthermore, we showed Six2Y129F/Tead1 signaling could protect against the loss of SNpc tyrosine hydroxylase-positive (TH+) cells and improve motor function in PD model rats. Our results demonstrate a dephosphorylation-dependent mechanism of Six2 that restores the degeneration of DA neurons, which could represent a potential therapeutic target for PD.

Clinical development of mRNA therapies against solid tumors.

The mRNA-based therapeutics have become the hot spot of biopharmaceutical industries in recent years. The landscape of this area is expanding from infectious disease to cancer, which needs to be summarized to provide data supports for industries and research institutions. Based on the Trialtrove database, a total of 108 clinical trials from 1999 to 2021 were retrospectively analyzed. We have demonstrated that the clinical development of mRNA therapies against solid tumors is still at an early stage. There are evolutions in delivery systems from the dendritic cell to the lipid-based platform and in encoding strategies from the fixed tumor antigens to the personalized neoantigens. The adjuvant or maintenance therapy and the combination treatment with checkpoint inhibitors are becoming the major clinical development orientation.

Digital light processing-bioprinted poly-NAGA-GelMA-based hydrogel lenticule for precise refractive errors correction.

Refractive disorder is the most prevalent cause of visual impairment worldwide. While treatment of refractive errors can bring improvement to quality of life and socio-economic benefits, there is a need for individualization, precision, convenience, and safety with the chosen method. Herein, we propose using pre-designed refractive lenticules based on poly-NAGA-GelMA (PNG) bio-inks photo-initiated by digital light processing (DLP)-bioprinting for correcting refractive errors. DLP-bioprinting allows PNG lenticules to have individualized physical dimensions with precision achievable to 10µm (µm). Material characteristics of PNG lenticules in tests included optical and biomechanical stability, biomimetical swelling and hydrophilic capability, nutritional and visual functionality, supporting its suitability as stromal implants. Cytocompatibility distinguished by morphology and function of corneal epithelial, stromal, and endothelial cells on PNG lenticules suggested firm adhesion, over 90% viability, phenotypic maintenance instead of excessive keratocyte-myofibroblast transformation.In-vitroimmune response analyzed by illumina RNA sequencing in human peripheral blood mononuclear cells indicated that PNG lenticules activated type-2 immunity, facilitating tissue regeneration and suppressing inflammation.In-vivoperformance assessed using intrastromal keratoplasty models in New Zealand white rabbits illustrated that implantation of PNG lenticules maintained stable optical pathway, induced controlled stromal bio-integration and regeneration, avoided complications such as stromal melt, interface scarring, etc, but exerted no adverse effects on the host. Postoperative follow-up examination on intraocular pressure, corneal sensitivity, and tear production remained unaffected by surgery up to 1-month post-implantation of PNG lenticules. DLP-bioprinted PNG lenticule is a bio-safe and functionally effective stromal implants with customizable physical dimensions, providing potential therapeutic strategies in correction of refractive errors.

[Pathogenesis of glucocorticoid-induced osteoporosis based on label-free mass proteomics].

OBJECTIVE: To explore pathogenesis of glucocortocoid-induced osteoporosis(GIOP) based on label-free mass proteomics. METHODS: Twevle female Sprague-Dawley(SD) rats were randomly divided into two groups, named as sham group and GIOP group. After one-week adaptive feeding, the rats of GIOP group were administered with dexamethasone via intramuscular injection according to 2.5 mg/kg weighting, while the rats of sham group were administered with the same amount of saline, twice a week. The tibias of each group were collected after 8-week modeling and made pathological sections to confirm the success of modeling. Three samples of each group were picked up to perform label-free mass proteomics. After quality control, differentially expressed proteins were identified according to qualitative and quantitative analyses. Then gene ontology(GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, cluster analysis as well as protein-protein interaction analysis were performed using bioinformatics analysis. RESULTS: Compared with sham group, the structure of bone trabecular in GIOP group showed abnormal arrangement, uneven distribution and obvious fragmentation, which could demonstrate successful modeling. A total of 47 differentially expressed proteins (DEPs) were identified including 20 up-regulated and 27 down-regulated proteins. The expression of protein nucleophosmin 1(NPM1), adipocyte plasma membrane associated protein (APMAP), cytochromec oxidase subunit 6A1 (COX6A1) and tartrate-resistant acid phosphatase (ACP5) showed a significant difference between two groups. KEGG results showed DEPs were enriched on metabolism-related pathways, immune-related pathways and AMP-activated kinase (AMPK) signaling pathway. CONCLUSION: Protein NPM1, APMAP, COX6A1 and ACP5 showed a close relationship with pathogenesis of GIOP, which could serve as potential biomarkers of GIOP. AMPK signaling pathway played an important role in the occurrence and development of GIOP, which could be regarded as potential signaling pathway to treatment GIOP.

Anaerobic fermentation featuring wheat bran and rice bran realizes the clean transformation of Chinese cabbage waste into livestock feed.

Rapid aerobic decomposition and a high cost/benefit ratio restrain the transformation of Chinese cabbage waste into livestock feed. Herein, anaerobically co-fermenting Chinese cabbage waste with wheat bran and rice bran at different dry matter levels (250, 300, 350 g/kg fresh weight) was employed to achieve the effective and feasible clean transformation of Chinese cabbage waste, and the related microbiological mechanisms were revealed by high-throughput sequencing technology. The bran treatments caused an increase in pH value (4.75-77.25%) and free amino acid content (12.09-152.66%), but a reduction in lactic acid concentration (54.58-77.25%) and coliform bacteria counts (15.91-20.27%). In addition, the wheat bran treatment improved the levels of short-chain fatty acids, nonprotein nitrogen, water-soluble carbohydrates and antioxidant activity and reduced the ammonia nitrogen contents. In contrast, the rice bran treatment decreased the levels of acetic acid, water-soluble carbohydrates, nonprotein nitrogen, ammonia nitrogen, and antioxidant activities. Microbiologically, the bran treatments stimulated Pediococcus, Lactobacillus, Enterobacter, and Weissella but inhibited Lactococcus and Leuconostoc, which were the primary organic acid producers reflected by the redundancy analysis. In addition, Chinese cabbage waste fermented with wheat bran at 350 g/kg fresh weight or with rice bran at 300 g/kg fresh weight increased the scale and complexity of bacteriome, promoted commensalism or mutualism and upregulated the global metabolism pathways, including carbohydrate and amino acid metabolisms. Furthermore, the bran treatments resulted in an increase in bacterial communities that were facultatively anaerobic, biofilm-formed, Gram-negative, potentially pathogenic and stress-tolerant. Collectively, the bran treatments inhibited effluent formation and protein degradation and improved nutrient preservation but reduced organic acid production during the anaerobic fermentation, which is linked to the variations in the bacteriome, indicating that the constructed fermentation system should be further optimized.

Effects of citric acid and heterofermentative inoculants on anaerobic co-fermentation of Chinese cabbage waste and wheat bran.

The effects of Lactobacillus buchneri, Lactobacillus hilgardii and citric acid on organic acid production, substrate consumption, protein degradation and microbial community were investigated in this study. The results indicated that combined inoculants induced a significant increase in levels of lactic acid (43 g/kg dry matter), acetic acid (14 g/kg dry matter), butyric acid (5 g/kg dry matter), total organic acid (60 g/kg dry matter) and ammonia nitrogen (20 g/kg total nitrogen). Furthermore, citric acid addition into the combined inoculants caused a significant increase in levels of acetic acid (12 g/kg dry matter), water-soluble carbohydrate (12 g/kg dry matter) and a reduction in ammonia nitrogen formation (22 g/kg total nitrogen). Microbiologically, combining inoculants and citric acid enriched Lactobacillus buchneri and Lactobacillus hilgardii and upregulated the functional pathways related to acid production and resistance. Collectively, combining citric acid and heterofermentative inoculants was beneficial to recycle Chinese cabbage waste in producing organic acids.

Strong charge carrier scattering at grain boundaries of PbTe caused by the collapse of metavalent bonding.

Grain boundaries (GBs) play a significant role in controlling the transport of mass, heat and charge. To unravel the mechanisms underpinning the charge carrier scattering at GBs, correlative microscopy combined with local transport measurements is realized. For the PbTe material, the strength of carrier scattering at GBs depends on its misorientation angle. A concomitant change in the barrier height is observed, significantly increasing from low- to high-angle GBs. Atom probe tomography measurements reveal a disruption of metavalent bonding (MVB) at the dislocation cores of low-angle GBs, as evidenced by the abrupt change in bond-rupture behavior. In contrast, MVB is completely destroyed at high-angle GBs, presumably due to the increased Peierls distortion. The collapse of MVB is accompanied by a breakdown of the dielectric screening, which explains the enlarged GB barrier height. These findings correlate charge carrier scattering with bonding locally, promising new avenues for the design of advanced functional materials.

Forensic characteristics and genetic substructure analysis of the Handan Han population, Northern China.

We analysed the forensic characteristics and substructure of the Handan Han population based on 36 Y-STR (short tandem repeat) and Y-SNP (single nucleotide polymorphism) markers. The two most dominant haplogroups in Handan Han, O2a2b1a1a1-F8 (17.95%) and O2a2b1a2a1a (21.51%), and their abundant downstream branches, reflected the strong expansion of the precursor of the Hans in Handan. The present results enrich the forensic database and explore the genetic relationships between Handan Han and other neighbouring and/or linguistically close populations, which suggests that the current concise overview of the Han intricate substructure remains oversimplified.

Metabotropic glutamate receptor 5-mediated inhibition of inward-rectifying K+ channel 4.1 contributes to orofacial ectopic mechanical allodynia following inferior alveolar nerve transection in male mice.

Inward-rectifying K+ channel 4.1 (Kir4.1), which regulates the electrophysiological properties of neurons and glia by affecting K+ homeostasis, plays a critical role in neuropathic pain. Metabotropic glutamate receptor 5 (mGluR5) regulates the expression of Kir4.1 in retinal Müller cells. However, the role of Kir4.1 and its expressional regulatory mechanisms underlying orofacial ectopic allodynia remain unclear. This study aimed to investigate the biological roles of Kir4.1 and mGluR5 in the trigeminal ganglion (TG) in orofacial ectopic mechanical allodynia and the role of mGluR5 in Kir4.1 regulation. An animal model of nerve injury was established via inferior alveolar nerve transection (IANX) in male C57BL/6J mice. Behavioral tests indicated that mechanical allodynia in the ipsilateral whisker pad lasted at least 14 days after IANX surgery and was alleviated by the overexpression of Kir4.1 in the TG, as well as intraganglionic injection of an mGluR5 antagonist (MPEP hydrochloride) or a protein kinase C (PKC) inhibitor (chelerythrine chloride); Conditional knockdown of the Kir4.1 gene downregulated mechanical thresholds in the whisker pad. Double immunostaining revealed that Kir4.1 and mGluR5 were co-expressed in satellite glial cells in the TG. IANX downregulated Kir4.1 and upregulated mGluR5 and phosphorylated PKC (p-PKC) in the TG; Inhibition of mGluR5 reversed the changes in Kir4.1 and p-PKC that were induced by IANX; Inhibition of PKC activation reversed the downregulation of Kir4.1 expression caused by IANX (p < .05). In conclusion, activation of mGluR5 in the TG after IANX contributed to orofacial ectopic mechanical allodynia by suppressing Kir4.1 via the PKC signaling pathway.

Characterization of pathogenic synovial IL-17A-producing CD8+ T cell subsets in collagen-induced arthritis.

Using a murine collagen-induced arthritis model, we characterized the heterogeneity of synovial CD8+ T cells based on the expression of chemokine receptors, cytokines, and nuclear transcription factors. Four subsets, i.e. CXCR3-CCR4- cells, CXCR3+CCR4- cells, CXCR3+CCR4+ cells, and CXCR3-CCR4+ cells, were present in synovial CD8+CD62L-CCR6+IL-23R+CCR10- T cells. CXCR3-CCR4- cells belonged to exhausted CD8+ T cells. CXCR3+CCR4- cells were Tc17.1 cells expressing both IL-17A and IFN-γ. CXCR3+CCR4+ cells were transitional Tc17.1 cells expressing IL-17A but lower IFN-γ, and CXCR3-CCR4+ cells were Tc17 cells expressing IL-17A but no IFN-γ. Transitional Tc17.1 cells can differentiate into Tc17.1 cells in vitro under the instruction of IL-12. Tc17.1 cells and transitional Tc17.1 cells strongly induced the expression of pro-inflammatory mediators in synovial fibroblasts, whereas Tc17 cells were less potent in doing so. IFN-γ was involved in the higher pathogenicity of Tc17.1 cells and transitional Tc17.1 cells on synovial fibroblasts. This study expands the understanding of Tc17 biology by unveiling the phenotypic and functional heterogeneity of synovial IL-17A-expressing CD8+ T cells. These heterogeneous IL-17A-expressing CD8+ T cells could be novel therapeutic targets in future arthritis treatment.