Group 3 innate lymphoid cells promotes Th17 cells differentiation in rheumatoid arthritis.

OBJECTIVES: To investigate the correlation between innate lymphoid cell (ILC) subsets with T-helper (Th) cells and to explore the effect of ILCs on T cells in rheumatoid arthritis (RA). METHODS: We analysed the frequencies of ILC subsets in RA patients with varying disease activity and their correlation with Th cell subsets. We further investigated this correlation in various organs of collagen-induced arthritis (CIA) mice. The effects of ILCs on CD4+ T cells were determined by in vitro cell co-culture experiments. RESULTS: ILCs were less frequent in RA patients than in healthy controls, with higher levels of group 3 ILCs (ILC3s) in RA (p<0.05). ILC3s correlated positively with Th1 and Th17 cells in RA peripheral blood (p<0.05). In the peripheral blood, spleen, and lymph nodes of CIA, ILC3s decreased and then increased during arthritis progression. ILC3s correlated positively with Th1 and Th17 cells in the spleen and lymph nodes of CIA (p<0.05). NKp46+ ILC3s in the spleen positively correlated with Th1 and Th17 cells (p<0.05). Under Th17 cell differentiation conditions, co-culturing CIA-derived ILC3s directly with naive CD4+ T cells promoted Th17 differentiation and increased IL-17 secretion. However, co-culturing through a transwell insert impeded Th17 differentiation without affecting IL-17 secretion. CONCLUSIONS: ILC3s positively correlated with Th1 and Th17 cells in RA. In CIA, the frequencies of ILC3s changed with disease development and showed a positive correlation with Th1 and Th17 cells. ILC3s may facilitate the differentiation of Th17 cells through direct cell-cell contact.

DKK-1 and Its Influences on Bone Destruction: A Comparative Study in Collagen-Induced Arthritis Mice and Rheumatoid Arthritis Patients.

Dickkopf-1 (DKK-1) has been considered a master regulator of bone remodeling. As precursors of osteoclasts (OCs), myeloid-derived suppressor cells (MDSCs) were previously shown to participate in the process of bone destruction in rheumatoid arthritis (RA). However, the role of DKK-1 and MDSCs in RA is not yet fully understood. We investigated the relevance between the level of DKK-1 and the expression of MDSCs in different tissues and joint destruction in RA patients and collagen-induced arthritis (CIA) mouse models. Furthermore, the CIA mice were administered recombinant DKK-1 protein. The arthritis scores, bone destruction, and the percentage of MDSCs in the peripheral blood and spleen were monitored. In vitro, the differentiation of MDSCs into OCs was intervened with recombinant protein and inhibitor of DKK-1. The number of OCs differentiated and the protein expression of the Wnt/ß-catenin signaling pathway were explored. The level of DKK-1 positively correlates with the frequency of MDSCs and bone erosion in RA patients and CIA mice. Strikingly, recombinant DKK-1 intervention significantly exacerbated arthritis scores and bone destruction, increasing the percentage of MDSCs in the peripheral blood and spleen in CIA mice. In vitro experiments showed that recombinant DKK-1 promoted the differentiation of MDSCs into OCs, reducing the expression of ß-catenin and TCF4 and increasing the expression of CyclinD1. In contrast, the DKK-1 inhibitor had the opposite effect. Our findings highlight that DKK-1 promoted MDSCs expansion in RA and enhanced the differentiation of MDSCs into OCs via targeting the Wnt/ß-catenin pathway, aggravating the bone destruction in RA.

CoS2@C catalyzes polysulfide conversion to promote the rate and cycling performances of lithium-sulfur batteries.

Lithium-sulfur (Li-S) batteries have been considered one of the most promising candidates for next-generation energy storage devices due to their high theoretical energy density and low cost. Nonetheless, the practical application of Li-S batteries is still inhibited by their lithium polysulfide (LiPS) shuttling and sluggish redox kinetics, which cause rapid capacity decay and inferior rate performance. Hence, anchoring LiPSs and catalyzing their conversion reactions are imperative to enhance the performance of Li-S batteries. In this work, one-dimensional (1D) porous carbon-encapsulated CoS2 (CoS2@C) fiber structures were prepared through a simple two-step hydrothermal reaction and they exhibited a robust LiPS trapping ability and rapid catalytic conversion of LiPSs. The formed three-dimensional (3D) architecture (CoS2@C/MWCNT) facilitates the physical adsorption of LiPSs and rapid ion transport. The electrode exhibited a high initial capacity of 1329.5 mA h g-1 at a current density of 0.1 C and a reversible capacity of 1060.6 mA h g-1 after 100 cycles, with an 80% capacity retention rate. Meanwhile, the decay rate of the electrode is 0.048% per cycle at 1 C and after 500 cycles. With a sulfur loading of 3 mg cm-2, the capacity retention rate is approximately 83.7% after 80 cycles.

Mid-Term Outcomes of Cemented or Uncemented Total Hip Arthroplasty for Failed Proximal Femoral Nail Antirotation Following Intertrochanteric Femur Fractures: A Retrospective Observational Study.

Introduction: The aim of this retrospective study was to assess the clinical outcomes of cemented or uncemented total hip arthroplasty (CTHA or UTHA) following prior failed proximal femoral nail antirotation (PFNA) fixation in patients with intertrochanteric femur fractures (IFFs). Materials and methods: Data from 244 patients with IFFs who experienced a conversion of PFNA to CTHA (n = 120) or to UTHA (n = 124) due to screw cut-out, mal/nonunion, or osteonecrosis during 2008-2018 were retrospectively analyzed. Follow-up occurred 1, 3, 6, and 12 months postoperatively and yearly thereafter. The primary outcome was the incidence of orthopedic complications; the secondary outcome was the Harris hip score (HHS). Results: The median follow-up was 60 months (range, 50-67 months). The incidences of orthopedic complications were 10% in the PFNA to CTHA group and 19.3% in the PFNA to UTHA group (P = .040). Significant differences were also observed regarding the incidence of prosthesis revision (1.7% for PFNA to CTHA vs 7.2% for PFNA to UTHA, P = .036). From the three years after conversion surgery to the final follow-up, significant differences were detected in HHS between groups (each P < .05). At the final follow-up, a statistically significant difference was detected in the HHS (79.54±18.85 for PFNA to CTHA vs. 75.26±18.27 for PFNA to UTHA, P = .014). Conclusion: The results of the study may demonstrate a significant statistical advantage with respect to the orthopedic complication rate and HHS in favor of CTHA compared to UTHA in patients with failed PFNA.

Simultaneous achievement of defect passivation and carrier transport promotion by using emerald salt for methylammonium-free perovskite solar cells.

Defect passivation along with promoted charge transport is potentially an effective but seldom exploited strategy for high-performance perovskite solar cells (PSCs). Herein, the in situ defect passivation and carrier transport improvement are simultaneously realized by introducing a conductive polymer (i.e., emerald salt, ES) into the precursor solution of methylammonium (MA)-free perovskites. The interaction between ES and uncoordinated Pb2+ reduces defect density to suppress the non-radiative recombination. Moreover, ES can act as a "carrier driver" to promote the carrier transport due to its conductive feature, resulting in efficient PSC devices with a decent power conversion efficiency (PCE) of 23.0%, which is among the most efficient MA-free PSCs. The ES-based unencapsulated devices show superior stability, retaining 89.1% and 83.8% of their initial PCEs when subjected to 35 ± 5% relative humidity (RH) storage and 85 °C thermal aging for 1000 h, respectively. To further assess the large-area compatibility of our strategy, 5 × 5 cm2 mini modules were also fabricated, delivering an impressive efficiency of 19.3%. This work sheds light on the importance of conductive additives in boosting cell performance by playing multiple roles in passivating defects, retarding the moisture invasion, and enhancing and balancing charge transport.

Analysis on infestation and related ecology of chigger mites on large Chinese voles (Eothenomys miletus) in five provincial regions of Southwest China.

Based on a long-term field investigation in the five provincial regions of Southwest China between 2001 and 2019, the present paper studied the infestation and related ecology of chigger mites (chiggers) on the large Chinese vole (Eothenomys miletus), an endemic and dominant rodent species in the regions. A total of 52331 chiggers were collected from 2661 voles, and 52261 mites were identified as 185 species and 13 genera in the family Trombiculidae with very high species diversity. The identified 185 chigger species on E. miletus (a single rodent species) even exceeded those recorded in some countries. The overall infestation prevalence (P m  = 53.96%), mean abundance (MA = 19.64) and mean intensity (MI = 36.39) on E. miletus were much higher than those on some other rodent species in the same regions. Although the species composition showed a moderate similarity (J = 0.63) between male and female hosts (E. miletus), the infestation indices (P m  = 56.25%, MA = 21.67) of chiggers on male hosts were higher than those on the females (P m  = 51.23%, MA = 17.09) (P < 0.05). Two dominant chigger species, Leptotrombidium scutellare (C r  = 19.17%) and L. sinicum (C r  = 11.06%), showed an aggregated distribution pattern among different individuals of their host E. miletus, and a relatively high degree of positive association existed between the two dominant chigger species with PCC = 0.57, DI = 0.60 and OI = 0.62 (x 2  = 857.46, P < 0.001). Leptotrombidium densipunctatum, Walchia koi, Helenicula hsui, L. scutellare and W. ewingi showed a high degree of environmental adaptability to their environments with high niche breadths. The theoretical curve of the species abundance distribution of chigger community on E. miletus was successfully fitted with Preston's lognormal distribution model. Based on the theoretical curve fitting, the expected total number of chigger species on E. miletus was roughly estimated to be 223 species, and 38 chigger species were probably missed in the sampling investigation.

Hierarchical-morphology metafabric for scalable passive daytime radiative cooling.

Incorporating passive radiative cooling structures into personal thermal management technologies could effectively defend humans against intensifying global climate change. We show that large-scale woven metafabrics can provide high emissivity (94.5%) in the atmospheric window and high reflectivity (92.4%) in the solar spectrum because of the hierarchical-morphology design of the randomly dispersed scatterers throughout the metafabric. Through scalable industrial textile manufacturing routes, our metafabrics exhibit desirable mechanical strength, waterproofness, and breathability for commercial clothing while maintaining efficient radiative cooling ability. Practical application tests demonstrated that a human body covered by our metafabric could be cooled ~4.8°C lower than one covered by commercial cotton fabric. The cost-effectiveness and high performance of our metafabrics present substantial advantages for intelligent garments, smart textiles, and passive radiative cooling applications.

Downregulation of Mfn2 participates in manganese-induced neuronal apoptosis in rat striatum and PC12 cells.

Manganese (Mn) is a widely distributed trace element that is essential for normal brain function and development. However, chronic exposure to excessive Mn has been known to lead to neuronal loss and manganism, a disease with debilitating motor and cognitive deficits, whose clinical syndrome resembling idiopathic Parkinson's disease (IPD). However, the precise molecular mechanism underlying Mn neurotoxicity remains largely unclear. Accumulating evidence indicates that abnormal mitochondrial functionality is an early and causal event in Mn-induced neurodegeneration and apoptosis. Here, we investigated whether Mitofusin 2 (Mfn2), a highly conserved dynamin-related protein (DRP), played a role in the regulation of Mn-induced neuronal apoptosis. We revealed that Mfn2 was significantly dysregulated in rat striatum and PC12 neuronal-like cells following Mn exposure. Western blot analysis revealed that the expression of Mfn2 was remarkably decreased following different concentrations of Mn exposure. Immunohistochemistry analysis confirmed a remarkable downregulation of Mfn2 in rat striatum after Mn exposure. Immunofluorescent staining showed that Mfn2 was expressed predominantly in neurons, and neuronal loss of Mfn2 was associated with the expression of active caspase-3 following Mn exposure. Importantly, overexpression of Mfn2 apparently attenuated Mn-induced neuronal apoptosis. Notably, treatment with caspase-3 inhibitor Ac-DEVD-CH could not rescue Mn-induced downregulation of Mfn2, suggesting that Mn-induced mfn2 occurs prior to neuronal apoptosis. Taken together, these results indicated that down-regulated expression of Mfn2 might contribute to the pathological processes underlying Mn neurotoxicity.

Zinc deficiency impairs the renewal of hippocampal neural stem cells in adult rats: involvement of FoxO3a activation and downstream p27(kip1) expression.

Zinc plays an important role in the development and maintenance of central neural system. Zinc deficiency has been known to alter normal brain function, whose molecular mechanism remains largely elusive. In the present study, we established a zinc deficiency-exposed rat model, and, using western blot and immunohistochemical analyses, found that the expression of FoxO3a and p27(kip1) was remarkably up-regulated in the rat brain hippocampus. Immunofluorescence assay showed that FOXO3a and p27(kip1) were significantly co-localized with nestin, the marker of neural stem cells (NSCs). Furthermore, we identified that the proportion of proliferating NSCs was markedly decreased in zinc-deficient rat hippocampaus. Using C17.2 neural stem cells, it was revealed that exposure to zinc chelator N,N,N',N'-tetrakis-(2-pyridylmethy) ethylenediamine induced the expression of FoxO3a and p27(kip1) , which coincided with reduced NSC proliferation. Furthermore, depletion of FoxO3a inhibited p27(kip1) expression and restored the growth of NSCs. On the basis of these data, we concluded that FoxO3a/p27(kip1) signaling might play a significant role in zinc deficiency-induced growth impairment of NSCs and consequent neurological disorders. We describe here that zinc deficiency induces the proliferative impairment of hippocampal neural stem cells partially through the activation of FOXO3a-p27 axis in rats. Neural progenitor cells exhibited significantly up-regulated expression of FOXO3a and p27 after zinc deficiency in vivo and in vitro. Depletion of FOXO3a ameliorates zinc deficiency-induced expression of p27 and growth impairment of neural stem cells. We provide novel insight into the mechanisms underlying zinc deficiency-induced neurological deficits.

Reactive oxygen species mediate nitric oxide production through ERK/JNK MAPK signaling in HAPI microglia after PFOS exposure.

Perfluorooctane sulfonate (PFOS), an emerging persistent contaminant that is commonly encountered during daily life, has been shown to exert toxic effects on the central nervous system (CNS). However, the molecular mechanisms underlying the neurotoxicity of PFOS remain largely unknown. It has been widely acknowledged that the inflammatory mediators released by hyper-activated microglia play vital roles in the pathogenesis of various neurological diseases. In the present study, we examined the impact of PFOS exposure on microglial activation and the release of proinflammatory mediators, including nitric oxide (NO) and reactive oxidative species (ROS). We found that PFOS exposure led to concentration-dependent NO and ROS production by rat HAPI microglia. We also discovered that there was rapid activation of the ERK/JNK MAPK signaling pathway in the HAPI microglia following PFOS treatment. Moreover, the PFOS-induced iNOS expression and NO production were attenuated after the inhibition of ERK or JNK MAPK by their corresponding inhibitors, PD98059 and SP600125. Interestingly, NAC, a ROS inhibitor, blocked iNOS expression, NO production, and activation of ERK and JNK MAPKs, which suggested that PFOS-mediated microglial NO production occurs via a ROS/ERK/JNK MAPK signaling pathway. Finally, by exposing SH-SY5Y cells to PFOS-treated microglia-conditioned medium, we demonstrated that NO was responsible for PFOS-mediated neuronal apoptosis.

Perfluorooctane sulfonate mediates microglial activation and secretion of TNF-α through Ca²âº-dependent PKC-NF-кB signaling.

Perfluorooctane sulfonate (PFOS), a ubiquitous pollutant widely found in the environment and biota, can cause numerous adverse effects on human health. In recent years, PFOS's toxic effects on the central nervous system (CNS) have been shown. However, we still have a lot to study in the underlying molecular mechanism of PFOS's neurotoxicity. Microglia, the innate immune cells of CNS, are critically implicated in various neurological diseases caused by pro-inflammatory mediators. In our research, we found that HAPI microglia secreted tumor necrosis factor-alpha (TNF-α) after PFOS exposure in time-dependent and dose-dependent way. We also discovered that intracellular concentration of free Ca(2+) ([Ca(2+)]i) significantly increased after PFOS treatments. It was noteworthy here the secretion of TNF-α mediated by PFOS was blocked by Ca(2+) inhibitor and protein kinase C (PKC) inhibitor. Besides these, we had learned as well that PFOS brought about the up-regulation of phosphorylated nuclear factor kappa B (NF-кB) p65 expression and accelerated degradation of NF-κB inhibitor alpha (IкBα), however, these effects could be attenuated or blocked by Ca(2+) inhibitor and PKC inhibitor. Finally, through treating SH-SY5Y cells with PFOS-treated microglial conditioned medium, we demonstrated that TNF-α mediated neuronal apoptosis. To sum up, our research had shown, for the first time, that the distinct TNF-α secretion brought by PFOS in HAPI microglia, was achieved through the Ca(2+)-dependent PKC-NF-кB signaling, subsequently participating in neuronal loss.

The downregulation of Wnt/ß-catenin signaling pathway is associated with zinc deficiency-induced proliferative deficit of C17.2 neural stem cells.

Zinc is an essential nutrient that is important for normal brain development. Zinc deficiency has been linked to aberrant neurological development and functioning. However, the molecular mechanisms underlying Zinc deficiency-induced neurological disorders remain largely elusive. In the present study, we showed that the proliferation of C17.2 neural stem cells (NSCs) was evidently impaired after exposed to low levels of Zinc chelator, N,N,N',N'-tetrakis-(2-pyridylmethy) ethylenediamine (TPEN). In addition, we found that TPEN-induced proliferative deficit of NSCs was related with significant downregulation of Wnt/ß-catenin signaling. Zinc deficiency impaired the proliferation of neural stem cells in dose- and time-dependent manners. Western blot revealed that the levels of p-Ser9-glycogensynthase kinase-3ß (p-GSK-3ß) and ß-catenin were remarkably downregulated during TPEN-induced C17.2 proliferative impairment. Moreover, immunofluorescent analysis indicated that the level of nuclear ß-catenin was apparently decreased following TPEN exposure. Furthermore, application with GSK-3ß inhibitor lithium chloride (LiCl) reversed TPEN-induced downregulation of ß-catenin and impairment of cell proliferation. Flow cytometry analysis also showed that TPEN-induced impairment of NSC proliferation could be reversed by LiCl. Taken together, these findings suggested that the disturbance of canonical Wnt/ß-catenin signaling pathway partially accounted for Zinc deficiency-induced proliferative impairment of NSCs.