Dual modifying of MAVS at lysine 7 by SIRT3-catalyzed deacetylation and SIRT5-catalyzed desuccinylation orchestrates antiviral innate immunity.

To effectively protect the host from viral infection while avoiding excessive immunopathology, the innate immune response must be tightly controlled. However, the precise regulation of antiviral innate immunity and the underlying mechanisms remain unclear. Here, we find that sirtuin3 (SIRT3) interacts with mitochondrial antiviral signaling protein (MAVS) to catalyze MAVS deacetylation at lysine residue 7 (K7), which promotes MAVS aggregation, as well as TANK-binding kinase I and IRF3 phosphorylation, resulting in increased MAVS activation and enhanced type I interferon signaling. Consistent with these findings, loss of Sirt3 in mice and zebrafish renders them more susceptible to viral infection compared to their wild-type (WT) siblings. However, Sirt3 and Sirt5 double-deficient mice exhibit the same viral susceptibility as their WT littermates, suggesting that loss of Sirt5 in Sirt3-deficient mice may counteract the increased viral susceptibility displayed in Sirt3-deficient mice. Thus, we not only demonstrate that SIRT3 positively regulates antiviral immunity in vitro and in vivo, likely via MAVS, but also uncover a previously unrecognized mechanism by which SIRT3 acts as an accelerator and SIRT5 as a brake to orchestrate antiviral innate immunity.

Soil nematode abundance and functional group composition at a global scale.

Soil organisms are a crucial part of the terrestrial biosphere. Despite their importance for ecosystem functioning, few quantitative, spatially explicit models of the active belowground community currently exist. In particular, nematodes are the most abundant animals on Earth, filling all trophic levels in the soil food web. Here we use 6,759 georeferenced samples to generate a mechanistic understanding of the patterns of the global abundance of nematodes in the soil and the composition of their functional groups. The resulting maps show that 4.4 ± 0.64 × 1020 nematodes (with a total biomass of approximately 0.3 gigatonnes) inhabit surface soils across the world, with higher abundances in sub-Arctic regions (38% of total) than in temperate (24%) or tropical (21%) regions. Regional variations in these global trends also provide insights into local patterns of soil fertility and functioning. These high-resolution models provide the first steps towards representing soil ecological processes in global biogeochemical models and will enable the prediction of elemental cycling under current and future climate scenarios.

Disruption of sirtuin 7 in zebrafish facilitates hypoxia tolerance.

SIRT7 is a member of the sirtuin family proteins with nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase activity, which can inhibit the activity of hypoxia-inducible factors independently of its enzymatic activity. However, the role of SIRT7 in affecting hypoxia signaling in vivo is still elusive. Here, we find that sirt7-null zebrafish are more resistant to hypoxic conditions, along with an increase of hypoxia-responsive gene expression and erythrocyte numbers, compared with their wildtype siblings. Overexpression of sirt7 suppresses the expression of hypoxia-responsive genes. Further assays indicate that sirt7 interacts with zebrafish hif-1αa, hif-1αb, hif-2αa, and hif-2αb to inhibit their transcriptional activity and mediate their protein degradation. In addition, sirt7 not only binds to the hypoxia responsive element of hypoxia-inducible gene promoters but also causes a reduction of H3K18Ac on these promoters. Sirt7 may regulate hypoxia-responsive gene expression through its enzymatic and nonenzymatic activities. This study provides novel insights into sirt7 function and sheds new light on the regulation of hypoxia signaling by sirt7.

Deletion of prolyl hydroxylase domain-containing enzyme 3 (phd3) in zebrafish facilitates hypoxia tolerance.

Prolyl hydroxylase domain (PHD)-containing enzyme 3 (PHD3) belongs to the Caenorhabditis elegans gene egl-9 family of prolyl hydroxylases. PHD3 catalyzes proline hydroxylation of hypoxia-inducible factor α (HIF-α) and promotes HIF-α proteasomal degradation through coordination with the pVHL complex under normoxic conditions. However, the relationship between PHD3 and the hypoxic response is not well understood. In this study, we used quantitative real-time PCR assay and O-dianisidine staining to characterize the hypoxic response in zebrafish deficient in phd3. We found that the hypoxia-responsive genes are upregulated and the number of erythrocytes was increased in phd3-null zebrafish compared with their wild-type siblings. On the other hand, we show overexpression of phd3 suppresses HIF-transcriptional activation. In addition, we demonstrate phd3 promotes polyubiquitination of zebrafish hif-1/2α proteins, leading to their proteasomal degradation. Finally, we found that compared with wild-type zebrafish, phd3-null zebrafish are more resistant to hypoxia treatment. Therefore, we conclude phd3 has a role in hypoxia tolerance. These results highlight the importance of modulation of the hypoxia signaling pathway by phd3 in hypoxia adaptation.

SET7 methylates the deubiquitinase OTUB1 at Lys 122 to impair its binding to E2 enzyme UBC13 and relieve its suppressive role on ferroptosis.

The deubiquitinating enzyme OTUB1 possesses canonical deubiquitinase (DUB) activity and noncanonical, catalytic-independent activity, which has been identified as an essential regulator of diverse physiological processes. Posttranslational modifications of OTUB1 affect both its DUB activity and its noncanonical activity of binding to the E2 ubiquitin-conjugation enzyme UBC13, but further investigation is needed to characterize the full inventory of modifications to OTUB1. Here, we demonstrate that SET7, a lysine monomethylase, directly interacts with OTUB1 to catalyze OTUB1 methylation at lysine 122. This modification does not affect DUB activity of OTUB1 but impairs its noncanonical activity, binding to UBC13. Moreover, we found using cell viability analysis and intracellular reactive oxygen species assay that SET7-mediated methylation of OTUB1 relieves its suppressive role on ferroptosis. Notably, the methylation-mimic mutant of OTUB1 not only loses the ability to bind to UBC13 but also relieves its suppressive role on Tert-Butyl hydroperoxide-induced cell death and Cystine starvation/Erastin-induced cellular reactive oxygen species. Collectively, our data identify a novel modification of OTUB1 that is critical for inhibiting its noncanonical activity.

SIRT5 impairs aggregation and activation of the signaling adaptor MAVS through catalyzing lysine desuccinylation.

RLR-mediated type I IFN production plays a pivotal role in innate antiviral immune responses, where the signaling adaptor MAVS is a critical determinant. Here, we show that MAVS is a physiological substrate of SIRT5. Moreover, MAVS is succinylated upon viral challenge, and SIRT5 catalyzes desuccinylation of MAVS. Mass spectrometric analysis indicated that Lysine 7 of MAVS is succinylated. SIRT5-catalyzed desuccinylation of MAVS at Lysine 7 diminishes the formation of MAVS aggregation after viral infection, resulting in the inhibition of MAVS activation and leading to the impairment of type I IFN production and antiviral gene expression. However, the enzyme-deficient mutant of SIRT5 (SIRT5-H158Y) loses its suppressive role on MAVS activation. Furthermore, we show that Sirt5-deficient mice are resistant to viral infection. Our study reveals the critical role of SIRT5 in limiting RLR signaling through desuccinylating MAVS.

A PAM-Free One-Step Asymmetric RPA and CRISPR/Cas12b Combined Assay (OAR-CRISPR) for Rapid and Ultrasensitive DNA Detection.

Current research endeavors have focused on the combination of various isothermal nucleic acid amplification methods with CRISPR/Cas systems, aiming to establish a more sensitive and reliable molecular diagnostic approach. Nevertheless, most assays adopt a two-step procedure, complicating manual operations and heightening the risk of contamination. Efforts to amalgamate both assays into a single-step procedure have faced challenges due to their inherent incompatibility. Furthermore, the presence of the protospacer adjacent motif (PAM) motif (e.g., TTN or TTTN) in the target double-strand DNA (dsDNA) is an essential prerequisite for the activation of the Cas12-based method. This requirement imposes constraints on crRNA selection. To overcome such limitations, we have developed a novel PAM-free one-step asymmetric recombinase polymerase amplification (RPA) coupled with a CRISPR/Cas12b assay (OAR-CRISPR). This method innovatively merges asymmetric RPA, generating single-stranded DNA (ssDNA) amenable to CRISPR RNA binding without the limitations of the PAM site. Importantly, the single-strand cleavage by PAM-free crRNA does not interfere with the RPA amplification process, significantly reducing the overall detection times. The OAR-CRISPR assay demonstrates sensitivity comparable to that of qPCR but achieves results in a quarter of the time required by the latter method. Additionally, our OAR-CRISPR assay allows the naked-eye detection of as few as 60 copies/µL DNA within 8 min. This innovation marks the first integration of an asymmetric RPA into one-step CRISPR-based assays. These advancements not only support the progression of one-step CRISPR/Cas12-based detection but also open new avenues for the development of detection methods capable of targeting a wide range of DNA targets.

Evolutionarily conserved core microbiota as an extended trait in nitrogen acquisition strategy of herbaceous species.

Microbiota have co-evolved with plants over millions of years and are intimately linked to plants, ranging from symbiosis to pathogenesis. However, our understanding of the existence of a shared core microbiota across phylogenetically diverse plants remains limited. A common garden field experiment was conducted to investigate the rhizosphere microbial communities of phylogenetically contrasting herbaceous families. Through a combination of metagenomic sequencing, analysis of plant economic traits, and soil biochemical properties, we aimed to elucidate the eco-evolutionary role of the core rhizosphere microbiota in light of plant economic strategies. We identified a conserved core microbiota consisting of 278 taxa that was closely associated with the phylogeny of the plants studied. This core microbiota actively participated in multiple nitrogen metabolic processes and showed a strong correlation with the functional potential of rhizosphere nitrogen cycling, thereby serving as an extended trait in the plant nitrogen acquisition. Furthermore, our examination of simulated species loss revealed the crucial role of the core microbiota in maintaining the rhizosphere community's network stability. Our study highlighted that the core microbiota, which exhibited a phylogenetically conserved association with plants, potentially represented an extension of the plant phenotype and played an important role in nitrogen acquisition. These findings held implications for the utilization of microbiota-mediated plant functions.

An integrated fast-slow plant and nematode economics spectrum predicts soil organic carbon dynamics during natural restoration.

Aboveground and belowground attributes of terrestrial ecosystems interact to shape carbon (C) cycling. However, plants and soil organisms are usually studied separately, leading to a knowledge gap regarding their coordinated contributions to ecosystem C cycling. We explored whether integrated consideration of plant and nematode traits better explained soil organic C (SOC) dynamics than plant or nematode traits considered separately. Our study system was a space-for-time natural restoration chronosequence following agricultural abandonment in a subtropical region, with pioneer, early, mid and climax stages. We identified an integrated fast-slow trait spectrum encompassing plants and nematodes, demonstrating coordinated shifts from fast strategies in the pioneer stage to slow strategies in the climax stage, corresponding to enhanced SOC dynamics. Joint consideration of plant and nematode traits explained more variation in SOC than by either group alone. Structural equation modeling revealed that the integrated fast-slow trait spectrum influenced SOC through its regulation of microbial traits, including microbial C use efficiency and microbial biomass. Our findings confirm the pivotal role of plant-nematode trait coordination in modulating ecosystem C cycling and highlight the value of incorporating belowground traits into biogeochemical cycling under global change scenarios.

Endoplasmic Reticulum Stress Activates the Inflammasome via NLRP3- and Caspase-2-Driven Mitochondrial Damage.

Endoplasmic reticulum (ER) stress is observed in many human diseases, often associated with inflammation. ER stress can trigger inflammation through nucleotide-binding domain and leucine-rich repeat containing (NLRP3) inflammasome, which might stimulate inflammasome formation by association with damaged mitochondria. How ER stress triggers mitochondrial dysfunction and inflammasome activation is ill defined. Here we have used an infection model to show that the IRE1α ER stress sensor regulates regulated mitochondrial dysfunction through an NLRP3-mediated feed-forward loop, independently of ASC. IRE1α activation increased mitochondrial reactive oxygen species, promoting NLRP3 association with mitochondria. NLRP3 was required for ER stress-induced cleavage of caspase-2 and the pro-apoptotic factor, Bid, leading to subsequent release of mitochondrial contents. Caspase-2 and Bid were necessary for activation of the canonical inflammasome by infection-associated or general ER stress. These data identify an NLRP3-caspase-2-dependent mechanism that relays ER stress to the mitochondria to promote inflammation, integrating cellular stress and innate immunity.

Quantifying Chemical Reactions and Interfacial Properties at Buried Polymer/Polymer Interfaces.

Maleic anhydride (MAH)-modified polymers are used as tie layers for binding dissimilar polymers in multilayer polymer films. The MAH chemistry which promotes adhesion is well characterized in the bulk; however, only recently has the interfacial chemistry been studied. Sum frequency generation vibrational spectroscopy (SFG) is an interfacial spectroscopy technique which provides detailed information on interfacial chemical reactions, species, and molecular orientations and has been essential for characterizing the MAH chemistry in both nylon and ethyl vinyl alcohol copolymer (EVOH) model systems and coextruded multilayer films. Here, we further characterize the interfacial chemistry between MAH-modified polyethylene tie layers and both EVOH and nylon by investigating the model systems over a range of MAH concentrations. We can detect the interfacial chemical reaction products between MAH and the barrier layer at MAH concentrations of ≥0.022 wt % for nylon and ≥0.077 wt % for EVOH. Additionally, from the concentration-dependent reaction reactant/product SFG peak positions and the product imide or ester/acid C═O group tilt angles extracted from the polarization-dependent SFG spectra, we quantitatively observe concentration-dependent changes to both the interfacial chemistry and interfacial structure. The interfacial chemistry and molecular orientation as a function of MAH concentration are well correlated with the adhesion strength, providing important quantitative information for the future design of MAH-modified tie layers for a variety of important applications.

B and N Codoped Cellulose-Supported Ag-/Bi-Doped Mo(S,O)3 Trimetallic Sulfo-Oxide Catalyst for Photocatalytic H2 Evolution Reaction and 4-Nitrophenol Reduction.

Cellulose plays a significant role in designing efficient and stable cellulose-based metallic catalysts, owing to its surface functionalities. Its hydroxyl groups are used as anchor sites for the nucleation and growth of metallic nanoparticles and, as a result, improve the stability and catalytic activity. Meanwhile, cellulose is also amenable to surface modifications to be more suitable for incorporating and stabilizing metallic nanoparticles. Herein, the Ag-/Bi-doped Mo(S,O)3 trimetallic sulfo-oxide anchored on B and N codoped cellulose (B-N-C) synthesized by a facile approach showed excellent stability and catalytic activity for PHER at 573.28 µmol/h H2 with 25 mg of catalyst under visible light, and 92.3% of the 4-nitrophenol (4-NP) reduction was achieved within 135 min by in situ-generated protons. In addition to B and N codoping, our use of the calcination method for B-N-C preparation further increases the structural disorders and defects, which act as anchoring sites for Ag-/Bi-doped Mo(S,O)3 nanoparticles. The Ag-/Bi-doped Mo(S,O)3@B-N-C surface active site also stimulates H2O molecule adsorption and activation kinetics and reduces the photogenerated charge carrier's recombination rate. The Mo4+ → Mo6+ electron hopping transport and the O 2p and Bi 6s orbital overlap facilitate the fast electron transfer by enhancing the electron's lifetime and photoinduced charge carrier mobility, respectively. In addition to acting as a support, B-N-C provides a highly conductive network that enhances charge transport, and the relocated electron in B-N-C activates the H2O molecule, which enables Ag-/Bi-doped Mo(S,O)3@B-N-C to have appreciable PHER performance.

Elucidating the Changes in Molecular Structure at the Buried Interface of RTV Silicone Elastomers during Curing.

Silicone elastomers are widely used in many industrial applications, including coatings, adhesives, and sealants. Room-temperature vulcanized (RTV) silicone, a major subcategory of silicone elastomers, undergoes molecular structural transformations during condensation curing, which affect their mechanical, thermal, and chemical properties. The role of reactive hydroxyl (-OH) groups in the curing reaction of RTV silicone is crucial but not well understood, particularly when multiple sources of hydroxyl groups are present in a formulated product. This work aims to elucidate the interfacial molecular structural changes and origins of interfacial reactive hydroxyl groups in RTV silicone during curing, focusing on the methoxy groups at interfaces and their relationship to adhesion. Sum frequency generation (SFG) vibrational spectroscopy is an in situ nondestructive technique used in this study to investigate the interfacial molecular structure of select RTV formulations at the buried interface at different levels of cure. The primary sources of hydroxyl groups required for interfacial reactions in the initial curing stage are found to be those on the substrate surface rather than those from the ingress of ambient moisture. The silylation treatment of silica substrates eliminates interfacial hydroxyl groups, which greatly impact the silicone interfacial behavior and properties (e.g., adhesion). This study establishes the correlation between interfacial molecular structural changes in RTV silicones and their effect on adhesion strength. It also highlights the power of SFG spectroscopy as a unique tool for studying chemical and structural changes at RTV silicone/substrate interface in situ and in real time during curing. This work provides valuable insights into the interfacial chemistry of RTV silicone and its implications for material performance and application development, aiding in the development of improved silicone adhesives.

Let-7c-3p suppresses lens epithelial-mesenchymal transition by inhibiting cadherin-11 expression in fibrotic cataract.

Fibrotic cataract, including anterior subcapsular cataract (ASC) and posterior capsule opacification, always lead to visual impairment. Epithelial-mesenchymal transition (EMT) is a well-known event that causes phenotypic alterations in lens epithelial cells (LECs) during lens fibrosis. Accumulating studies have demonstrated that microRNAs are important regulators of EMT and fibrosis. However, the evidence explaining how microRNAs modulate the behavior and alter the cellular phenotypes of the lens epithelium in fibrotic cataract is insufficient. In this study, we found that hsa-let-7c-3p is downregulated in LECs in human ASC in vivo as well as in TGFß2-induced EMT in vitro, indicating that hsa-let-7c-3p may participate in modulating the profibrotic processes in the lens. We then demonstrated that overexpression of hsa-let-7c-3p markedly suppressed human LEC proliferation and migration and attenuated TGFß2-induced EMT and injury-induced ASC in a mouse model. In addition, hsa-let-7c-3p mediated lens fibrosis by directly targeting the CDH11 gene, which encodes cadherin-11 protein, an important mediator in the EMT signaling pathway. It decreased cadherin-11 protein expression at the posttranscriptional level but not at the transcriptional level by binding to a specific site in the 3-untranslated region (3'-UTR) of CDH11 mRNA. Moreover, blockade of cadherin-11 expression with a specific short hairpin RNA reversed TGFß2-induced EMT in LECs in vitro. Collectively, these data demonstrated that hsa-let-7c-3p plays a clear role in attenuating ASC development and may be a novel candidate therapeutic for halting fibrosis and maintaining vision.

Establishment and Validation of Prognostic Nomograms for Patients with Metastatic Pulmonary Large Cell Neuroendocrine Carcinoma.

PURPOSE: Metastatic pulmonary large cell neuroendocrine carcinoma (LCNEC) is an aggressive cancer with generally poor outcomes. Effective methods for predicting survival in patients with metastatic LCNEC are needed. This study aimed to identify independent survival predictors and develop nomograms for predicting survival in patients with metastatic LCNEC. PATIENTS AND METHODS: We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database, identifying patients with metastatic LCNEC diagnosed between 2010 and 2017. To find independent predictors of cancer-specific survival (CSS), we performed Cox regression analysis. A nomogram was developed to predict the 6-, 12-, and 18-month CSS rates of patients with metastatic LCNEC. The concordance index (C-index), area under the receiver operating characteristic (ROC) curves (AUC), and calibration curves were adopted with the aim of assessing whether the model can be discriminative and reliable. Decision curve analyses (DCAs) were used to assess the model's utility and benefits from a clinical perspective. RESULTS: This study enrolled a total of 616 patients, of whom 432 were allocated to the training cohort and 184 to the validation cohort. Age, T staging, N staging, metastatic sites, radiotherapy, and chemotherapy were identified as independent prognostic factors for patients with metastatic LCNEC based on multivariable Cox regression analysis results. The nomogram showed strong performance with C-index values of 0.733 and 0.728 for the training and validation cohorts, respectively. ROC curves indicated good predictive performance of the model, with AUC values of 0.796, 0.735, and 0.736 for predicting the 6-, 12-, and 18-month CSS rates of patients with metastatic LCNEC in the training cohort, and 0.795, 0.801, and 0.780 in the validation cohort, respectively. Calibration curves and DCAs confirmed the nomogram's reliability and clinical utility. CONCLUSION: The new nomogram was developed for predicting CSS in patients with metastatic LCNEC, providing personalized risk evaluation and aiding clinical decision-making.

Diluted PEDOT:PSS for high-performance organic light-emitting devices with thermally activated delayed fluorescence emitters.

Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is a widely used conductive polymer in organic light-emitting devices. However, its strong acidity and fluorescence quenching effect seriously affect the overall device performance. We report a cost-effective method to address the above concerns by diluting PEDOT:PSS with deionized water, which effectively reduced the film thickness and the acidity. Therefore, the fluorescence quenching occurring at the interface was alleviated. Using the modified PEDOT:PSS as the hole injection layer, the external quantum efficiency of the device could be effectively improved by a factor of 81%, reaching a considerably higher value of 23.5%, compared with the device consisting of the original PEDOT:PSS solution used as received.

Molecular behavior of silicone adhesive at buried polymer interface studied by molecular dynamics simulation and sum frequency generation vibrational spectroscopy.

Silicones have excellent material properties and are used extensively in many applications, ranging from adhesives and lubricants to electrical insulation. To ensure strong adhesion of silicone adhesives to a wide variety of substrates, silane-based adhesion promotors are typically blended into the silicone adhesive formulation. However, little is known at the molecular level about the true silane adhesion promotion mechanism, which limits the ability to develop even more effective adhesion promoters. To understand the adhesion promotion mechanism of silane molecules at the molecular level, this study has used sum frequency generation vibrational spectroscopy (SFG) to determine the behavior of (3-glycidoxypropyl)trimethoxy silane (γ-GPS) at the buried interface between poly(ethylene terephthalate) (PET) and a bulk silicone adhesive. To complement and extend the SFG results, atomistic molecular dynamics (MD) simulations were applied to investigate molecular behavior and interfacial interaction of γ-GPS at the silicone/PET interface. Free energy computations were used to study the γ-GPS interaction in the sample system and determine the γ-GPS interfacial segregation mechanism. Both experiments and simulations consistently show that γ-GPS molecules prefer to segregate at the interface between PET and PDMS. The methoxy groups on γ-GPS molecules orient toward the PDMS polymer phase. The consistent picture of interfacial structure emerging from both simulation and experiment provides enhanced insight on how γ-GPS behaves in the silicone - PET system and illustrates why γ-GPS could improve the adhesion of silicone adhesive, leading to further understanding of silicone adhesion mechanisms useful in the design of silicone adhesives with improved performance.

Visible-Light-Induced and Iodoform-Promoted Functionalization of Ether with Secondary Sulfonyl Amides.

An iodoform-promoted functionalization of ether with secondary sulfonyl amides under visible-light irradiation was developed toward synthesis of hemiaminal skeleton with good to excellent isolated yields. The characterization of the isolated ether and iodoform complex revealed regioselective hydrogen atom transfer to initiate carbon radical formation and enabled the amination reaction with the sulfonamide.

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.

Multicomponent reactions to access S-aryl dithiocarbamates via an electron donor-acceptor complex under open-to-air conditions.

A simple and efficient transition-metal/photocatalyst-free visible-light-driven one-pot three-component reaction between thianthrenium salts, carbon disulfide and amines under an air atmosphere for the preparation of biologically relevant S-aryl dithiocarbamates is developed. This methodology is robust and scalable, and exhibits a broad substrate scope and excellent functional group tolerance. Of note, a wide range of primary aliphatic amines bearing different groups are suitable for this strategy. The synthetic utility was further demonstrated by a two-step one-pot multi-component reaction and photo-flow decagram-scale synthesis. Preliminary mechanistic studies suggest that the association of the dithiocarbamate anion with thianthrenium salts formed an electron donor-acceptor complex, which upon excitation with visible light produced an aryl radical via single-electron transfer.