ABSTRACT:High-salt diet (HSD) has emerged as a prevalent environmental factor that exacerbates chronic inflammation and insulin resistance in obesity-associated type 2 diabetes (T2D) by modulating macrophage polarization, metabolic reprogramming, and epigenetic imprinting. Current evidence demonstrates that HSD activates p38/mitogen-activated protein kinase (MAPK), nuclear factor kappa-B (NF-κB), and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome signaling pathways, by which it drives macrophage polarization toward a proinflammatory M1 phenotype while inducing a glycolysis-dominant metabolic shift, thereby establishing a persistent "metabolic memory". Moreover, HSD orchestrates metabolic memory in macrophages through coordinated epigenetic machinery, including histone modifications (Trimethylation of histone H3 at lysine 4 [H3K4me3] and Acetylation of histone H3 at lysine 27 [H3K27ac]), DNA methylation, and noncoding RNAs (e.g., long non-coding RNA MALAT1 and miR-155), leading to sustained inflammatory phenotypes. In multiple metabolic organs (e.g., adipose tissue, liver, pancreas, and gut), the HSD-macrophage axis aggravates systemic insulin resistance through shared proinflammatory signaling and other tissue-specific mechanisms. Most importantly, therapeutic strategies targeting the NLRP3 inflammasome, metabolic pathways, and epigenetic alterations offer novel approaches for managing metabolic inflammation. Future investigations are encouraged to leverage lineage tracing, single-cell sequencing, and spatial multi-omics technologies to advance the development of precision medicine for macrophage-associated metabolic disorders.

BackgroundPulmonary fibrosis (PF) is an irreversible and lethal lung disease characterized by progressive scarring lacking safe and effective treatment options. Recent studies have underscored the role of macrophage polarization in fibrotic progression, yet the role of kynurenine (Kyn), a metabolite of tryptophan (Trp), in macrophages during PF progression remains elusive.MethodsLiquid Chromatography-tandem Mass Spectrometry (LC-MS) analysis was used to detect tryptophan metabolism changes in the serum of PF patients and control subjects. Macrophage-specific Ido1 or Ahr deletion mice was utilized to explored the role of Kyn in the bleomycin-induced fibrotic mouse model and ChIP sequence was employed to elucidate the mechanism by which Kyn inhibits pro-fibrotic macrophage activation.ResultsWe identified Kyn, Trp levels and Kyn/Trp ratio (KTR) were notably elevated in the serum of patients with different types of PF and these alterations were inversely correlated with lung function. Although such elevation might appear pathogenic, our functional studies demonstrate that Kyn exerts protective effects in PF, akin to brain natriuretic peptide in heart failure. Macrophage-specific deletion of Ido1 or aryl hydrocarbon receptor (AhR, the receptor of Kyn) exacerbated bleomycin-induced PF, while exogenous Kyn supplementation mitigated disease severity. Mechanistically, Kyn bound to the AhR, facilitating its nuclear translocation, where it promoted Slc39a10 transcription to increase the intracellular levels of zinc ion, thereby inhibiting profibrotic macrophage differentiation. Intriguingly, pirfenidone was noted with high potency to suppress Kyn production and our studies demonstrated that administration of Kyn along with pirfenidone effectively enhanced the therapeutic efficacy against PF.ConclusionsIn summary, these findings reveal a previously unrecognized Kyn-AhR-SLC39A10-Zn2+ signaling axis that governs macrophage polarization in PF, and unveiled the importance of Trp metabolism in PF pathogenesis, which could be novel therapeutic strategies against PF.

To investigate the potential of recombinant protein disulfide isomerase (PDI) as a raw material for skin-repair cosmetics, an engineered PDI-producing strain was constructed using the Pichia pastoris X33 expression system. The target protein was obtained through methanol-induced expression and anion-exchange chromatography purification, and its cytotoxicity and pro-adhesive effects on human skin fibroblasts (HSFs) were evaluated. The results showed that the purified recombinant PDI protein had an apparent molecular weight of approximately 55.7 kDa. Treatment with 0.04–5 µmol/L recombinant PDI for 24 h did not affect cell viability. On culture surfaces coated with 62.5 nmol/L recombinant human fibronectin (rhFN) or 31.25 nmol/L recombinant human collagen (rhC), the addition of 250 nmol/L recombinant PDI increased the HSF adhesion area ratio to approximately 2.1-fold that of the rhFN-alone group (p < 0.0001) and 1.9-fold that of the rhC-alone group (p < 0.0001). Collectively, the recombinant PDI protein exhibits good biocompatibility and pro-adhesive activity, demonstrating its potential as a candidate raw material for skin-repair cosmetics.

SUMOylation is an evolutionary conserved regulatory mechanism, in which Ubc9 is the only E2 conjugating enzyme. Previous studies demonstrated that SUMOylation is involved in multiple biological processes, but its role in dendritic cells (DCs) remains to be fully addressed. Herein in this report, we found that DCs deficient in Ubc9 protected mice from dextran sulfate sodium (DSS)-induced colitis, as evidenced by the ameliorated weight loss, colon length, and disrupted colon structure. Mechanistically, Ubc9 mediated SUMOylation of RBPJ, by which it stabilized RBPJ from ubiquitin-mediated degradation to enhance its transcriptional activity, while Ciita, a critical transcription factor, is a direct target downstream of RBPJ, which forms an enhanceosome complex to transcribe the expression of MHC II genes. Therefore, loss of Ubc9 abolished RBPJ SUMOylation, which was coupled with reduced Ciita transcription, thereby attenuating the expression of MHC class II genes. As a consequence of defective MHC II expression, Ubc9-/- DCs were featured by the impaired capability to process antigen and to prime effector CD4+ T cells, thereby protecting mice from DSS-induced colitis. Together, our results shed novel insight into the understanding of SUMOylation in the regulation of DC functions in pathological conditions.

Sebum plays a dual role in skin homeostasis, maintaining barrier function and providing antimicrobial defense. However, its dysregulation drives the pathophysiology of common skin diseases. This review explains that abnormal sebum secretion promotes acne vulgaris by inducing follicular occlusion and Cutibacterium acnes (C. acnes) proliferation, while altered composition impairs the epidermal barrier. Key factors such as high-glycemic diets, androgen fluctuations, and environmental conditions significantly influence sebaceous gland activity. The underlying molecular mechanisms involve inflammatory and hormonal pathways, including dysregulation of peroxisome proliferator-activated receptor gamma (PPARγ) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. We conducted a systematic literature search using keywords related to sebum physiology and pathology. This review also discusses emerging therapeutic targets and the potential of advanced sebaceous gland models for future research. This synthesis provides a theoretical foundation for developing targeted interventions in dermatology and cosmetics.

Suppressing immune responses promotes allograft survival but also favours tumour progression and recurrence. Selectively suppressing allograft rejection while maintaining or even enhancing antitumor immunity is challenging. Here, we show loss of allograft-related rejection in mice deficient in Setdb1, an H3K9 methyltransferase, while antitumor immunity remains intact. RNA sequencing shows that Setdb1-deficiency does not affect T-cell activation or cytokine production but induces an increase in Treg-cell-associated gene expression. Depletion of Treg cells impairs graft acceptance in Setdb1-deficient mice, indicating that the Treg cells promote allograft survival. Surprisingly, Treg cell-specific Setdb1 deficiency does not prolong allograft survival, suggesting that Setdb1 may function prior to Foxp3 induction. Using single-cell RNA sequencing, we find that Setdb1 deficiency induces a new Treg population in the thymus. This subset of Treg cells expresses less IL-1R2 and IL-18R1. Mechanistically, during Treg cell induction, Setdb1 is recruited by transcription factor ATF and altered histone methylation. Our data thus define Setdb1 in T cells as a hub for Treg cell differentiation, in the absence of which suppressing allograft rejection is uncoupled from maintaining antitumor immunity.

Among different age groups, middle-aged individuals are particularly susceptible to obesity, with a 22% higher risk of all-cause mortality. However, the underlying mechanisms remain unclear. In this study, we identify adipose progenitor cells (APCs) in the white adipose tissue (WAT) of middle-aged subjects as potential causes of midlife obesity. Specifically, the extracellular vesicles (EVs) derived from APCs display an impaired ability to mitigate the inflammaging of adipose tissue macrophages (ATMs) in middle-aged individuals. Mechanistically, these EVs, lacking miR-145-5p, fail to suppress the expression of L-selectin in ATMs, thereby facilitating their M1 program via the NF-κB signaling pathway. In contrast, EVs from young APCs effectively inhibit M1 macrophage polarization. Accordingly, targeted liposomes are designed to deliver miR-145-5p mimics to ATMs, which effectively prevent the obesity in middle-aged mice. Collectively, our findings highlight the role of APC-derived EVs in midlife obesity and propose miR-145-5pas a promising therapeutic target for clinical applications. Middle-aged individuals are more susceptible to obesity, but the mechanisms are unclear. Here, the authors show that extracellular vesicles from adipose progenitor cells in middle-aged individuals lack miR-145-5p, driving inflammation, and that restoring miR-145-5p could prevent midlife obesity.

Coix seed, a well-known traditional Chinese medicine, has been extensively used for its anti-aging properties. However, the biological mechanism of its polysaccharides remains unclear. This study systematically investigated the anti-aging effects and mechanism of purified Coix seed polysaccharide (CP1) for the first time. The structural analysis revealed that CP1 mainly consists of glucose linked by α-(1 → 4) and α-(1 → 6) glycosidic bonds and has an average molecular weight of 8.855 kDa. Further, CP1 exhibited strong scavenging activity of approximately 55.85 % against 1,1-diphenyl-2-trinitrobenzohydrazine, 71.30 % against 2,2'-bis-(3-ethylbenzothiazolin-6-sulfonic acid) diammonium salt, and 68.40 % against hydroxyl radicals. In Caenorhabditis elegans, CP1 significantly extended the lifespan by 3-5 days (p < 0.001) and increased the survival by 78 % under oxidative stress condition (p < 0.001). In addition, CP1 suppressed the activity of senescence-associated β-galactosidase in zebrafish (p < 0.001) and reduced DNA damage in human skin fibroblasts (p < 0.001). Mechanistically, CP1 mainly activates the p-AMPK/RICTOR/CREB3 pathway by interacting with PARP-1. Taken together, this study performs the structural characterization of a glucan polysaccharide from Coix seed and its anti-aging effects in different models. These findings can provide a theoretical basis and candidate molecule for anti-aging therapies.

A six-coordination stable structure of Ni2+ with two carboxylate ligands and two sulfur atoms in side chains of ethylene-propylene copolymers can be constructed to form 3D physically cross-linked networks according to a density functional theory simulation. The reversibly cross-linked polar ethylene/propylene/5-ethylidene-2-norbornene copolymer elastomers (rcEPDMs) with triple noncovalent cross-linking sites of hydrogen bonds, ionic aggregation, and 6-coordination Ni2+ bonds can be successfully in situ prepared by the reaction of carboxyl functionalized EPDM with NiCl26H2O in the presence of tetrabutylammonium hydroxide. The rcEPDM networks with Ni2+ having a coordination number of 6 (rcEPDM-Ni2+) show much higher cross-linking density than their analogues with Zn2+ having a coordination number of 4 (rcEPDM-Zn2+), which is confirmed by swelling experiments and Mooney-Rivlin analysis. The rcEPDM-Ni2+ networks exhibit a much higher tensile strength of 19.0 MPa at an elongation of 587% than rcEPDM-Zn2+ networks (6.8 MPa at 777%). The mechanical properties of rcEPDM-Ni2+ networks containing triple cross-linking sites are superior to those of networks containing hydrogen and coordination bonds as well as those containing ionic aggregation and coordination bonds. The hysteresis energy of rcEPDM-Ni2+ networks increases by 19 times, and the strain recovery reaches 95% when the strain gradually increases from 50% to 400%, which is attributed to the synergy of noncovalent cross-linking sites. The hysteresis energy of rcEPDM-Ni2+ network is 66% higher than that of rcEPDM-Zn2+ networks at 400% strain, due to the formation of a more stable and dense six-coordination structure of rcEPDM-Ni2+ networks. To the best of our knowledge, this is the first example of renewable triple noncovalently cross-linked polar EPDM with high strength and outstanding strain recovery using Ni2+-carboxylate coordination bonds. The renewable cross-linked EPDM elastomers would have potential applications in organic-inorganic composite materials, bonding agents, sealing parts, and reusable elastomers.

Background: N 6-methyladenosine (m6A) modification plays a crucial role in various physiological processes by regulating mRNA biology. However, the exact impact of m6A modification on macrophages in adipose tissues under obese settings remains to be further elucidated. Methods: We established macrophage-specific Wtap-deficient mice to explore the effects of Wtap on obesity and metabolic disorders induced by high-fat diet (HFD) in mice. The molecular targets were explored by MeRIP-qPCR, and the metabolomic assays were performed to detect the alteration of relevant metabolites. Results: Wilms tumor 1-associated protein (WTAP), one of the m6A "writers", was downregulated in adipose tissue macrophages (ATMs) from obese individuals and negatively correlated with clinical metabolic traits. Depletion of Wtap in mouse macrophages exacerbated the metabolic consequences of high-fat diet (HFD) induced obesity. Additionally, energy expenditure and adipose beiging were considerably lower in Wtap-deficient mice in response to cold exposure. Mechanistic study revealed that WTAP-mediated m6A modification of isocitrate dehydrogenase 1 (Idh1) transcripts enhanced its stability and translation in macrophages leading to α-ketoglutarate (α-KG) production. Alpha-KG further supported alternative activation of macrophages by metabolic reprogramming. Conclusions: Our data support that Wtap modulates HFD-induced macrophages through interfering with the IDH1-α-KG axis, and highlight the importance of WTAP-mediated m6A modification in maintaining alternative macrophage activation, proposing potential targets for the regulation of obesity and related metabolic diseases.

Skeletal muscle is a critical organ in maintaining homoeostasis against metabolic stress, and histone post-translational modifications are pivotal in those processes. However, the intricate nature of histone methylation in skeletal muscle and its impact on metabolic homoeostasis have yet to be elucidated. Here, we report that mitochondria-rich slow-twitch myofibers are characterized by significantly higher levels of H3K36me2 along with repressed expression of Kdm2a, an enzyme that specifically catalyses H3K36me2 demethylation. Deletion or inhibition of Kdm2a shifts fuel use from glucose under cold challenge to lipids under obese conditions by increasing the proportion of mitochondria-rich slow-twitch myofibers. This protects mice against cold insults and high-fat-diet-induced obesity and insulin resistance. Mechanistically, Kdm2a deficiency leads to a marked increase in H3K36me2 levels, which then promotes the recruitment of Mrg15 to the Esrrg locus to process its precursor messenger RNA splicing, thereby reshaping skeletal muscle metabolic profiles to induce slow-twitch myofiber transition. Collectively, our data support the role of Kdm2a as a viable target against metabolic stress. Kdm2a demethylates H3K36me2 to mediate fast-to-slow-twitch myofiber transition and reshape skeletal muscle metabolic flexibility under metabolic stress conditions.

Dysregulated T cell activation underpins the immunopathology of rheumatoid arthritis (RA), yet the machineries that orchestrate T cell effector program remain incompletely understood. Herein, we leveraged bulk and single-cell RNA sequencing data from RA patients and validated protein disulfide isomerase family A member 3 (PDIA3) as a potential therapeutic target. PDIA3 is remarkably upregulated in pathogenic CD4 T cells derived from RA patients and positively correlates with C-reactive protein level and disease activity score 28. Pharmacological inhibition or genetic ablation of PDIA3 alleviates RA-associated articular pathology and autoimmune responses. Mechanistically, T cell receptor signaling triggers intracellular calcium flux to activate NFAT1, a process that is further potentiated by Wnt5a under RA settings. Activated NFAT1 then directly binds to the Pdia3 promoter to enhance the expression of PDIA3, which complexes with STAT1 or PKM2 to facilitate their nuclear import for transcribing T helper 1 (Th1) and Th17 lineage-related genes, respectively. This non-canonical regulatory mechanism likely occurs under pathological conditions, as PDIA3 could only be highly induced following aberrant external stimuli. Together, our data support that targeting PDIA3 is a vital strategy to mitigate autoimmune diseases, such as RA, in clinical settings.

Adipose tissue macrophages (ATMs) play important roles in maintaining adipose tissue homeostasis and orchestrating metabolic inflammation. Given the extensive functional heterogeneity and phenotypic plasticity of ATMs, identification of the authentically pathogenic ATM subpopulation under obese setting is thus necessitated. Herein, we performed single-nucleus RNA sequencing (snRNA-seq) and unraveled a unique maladaptive ATM subpopulation defined as ATF4hiPDIA3hiACSL4hiCCL2hi inflammatory and metabolically activated macrophages (iMAMs), in which PDIA3 is required for the maintenance of their migratory and pro-inflammatory properties. Mechanistically, ATF4 serves as a metabolic stress sensor to transcribe PDIA3, which then imposes a redox control on RhoA activity and strengthens the pro-inflammatory and migratory properties of iMAMs through RhoA-YAP signaling. Administration of Pdia3 small interfering RNA (siRNA)-loaded liposomes effectively repressed adipose inflammation and high-fat diet (HFD)-induced obesity. Together, our data support that strategies aimed at targeting iMAMs by suppressing PDIA3 expression or activity could be a viable approach against obesity and metabolic disorders in clinical settings.

High salt (HS) consumption is a risk factor for multiple autoimmune disorders via disturbing immune homeostasis. Nevertheless, the exact mechanisms by which HS exacerbates rheumatoid arthritis (RA) pathogenesis remain poorly defined. Herein, we found that heightened phosphorylation of PDPK1 and SGK1 upon HS exposure attenuated FoxO1 expression to enhance the glycolytic capacity of CD4 T cells, resulting in strengthened Th17 but compromised Treg program. GSK2334470 (GSK), a dual PDPK1/SGK1 inhibitor, effectively mitigated the HS -induced enhancement in glycolytic capacity and the overproduction of IL -17A. Therefore, administration of GSK markedly alleviated HS -exacerbated RA progression in collageninduced arthritis (CIA) model. Collectively, our data indicate that HS consumption subverts Th17/Treg homeostasis through the PDPK1-SGK1-FoxO1 signaling, while GSK could be a viable drug against RA progression in clinical settings.

Danggui-Jianzhong decoction (DGJZ) is a famous classical traditional Chinese medicine formula, which ingredients are complex and the quality is difficult to control. Our study aimed to identify the overall chemical profile of DGJZ qualitatively by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and UPLC. A total of 77 components, including terpenoids, flavonoids, phenolic acids, gingerols and other components, were firstly detected and characterized by UPLC-Q-TOF-MS and 18 peaks marked after analyzing the UPLC fingerprint. Finally, paeoniflorin, liquiritin, ferulic acid, cinnamic acid, glycyrrhizic acid and 6-gingerol were quantified, which was validated in terms of linearity, precision, accuracy, repeatability and recovery. Taken together, the chemical constitutes of DGJZ were systematically identified and a reliable quantitative method coupled with fingerprint analysis was successfully employed for evaluating the holistic quality, which will provide a robust foundation for the quality control of DGJZ.

Background Finding a new promising plant antioxidant to combat or prevent cardiovascular disease remains a major challenge for researchers. Lychee pericarp, which includes a variety of polyphenols, is a prospective source of botanical antioxidants.Purpose In response to this issue, we assessed the effect of lychee bark extract on oxygen radical scavenging capacity and separate vascular protective ability in vivo.Methods In the current study, the lychee pericarp enrichment product (RLP) was obtained by optimizing an extraction method and separated using modern separation methods. The structure of the isolated compounds was assessed using 1H-NMR, 13C-NMR, and electrospray ionization-mass spectrometry, and the content of polyphenols obtained from the extract was quantified using the area normalization method. In addition, the capacity of RLP to scavenge oxygen radicals in vitro was assessed using the DPPH (1,1-diphenyl-2-picrylhydrazyl) and T-AOC (total antioxidant capacity) techniques. Furthermore, an isoprenaline hydrochloride (ISO)-induced rat model of acute myocardial ischemia was established, and four biochemical indicators were used to assess the effect of lychee bark extract on oxygen radical scavenging capacity and cardiovascular protective ability in vivo.Results RLP extraction produced 11 chemicals, 6 of which were structurally assessed. Quantitative analysis revealed that epicatechin, PC-C(epicatechin-(4 beta down arrow 8,2 beta down arrow O down arrow 7)-epicatechin-(4 beta down arrow 8)-epicatechin), type A proanthocyanidin trimer, proanthocyanidin A2, and type B proanthocyanidin dimer were the most abundant polyphenols. The in vitro DPPH and T-AOC findings revealed that RLP exhibited strong free radical scavenging activity, approximately 1.5-fold that of vitamin C. The four biochemical indicators confirmed the antioxidant activity and cardiovascular protective ability of RLP in vivo.Conclusion RLP has good in vivo and in vitro antioxidant activity, confirming lychee pericarp as a prospective source of botanical antioxidants.

Background Fluvoxamine is one of the selective serotonin reuptake inhibitors (SSRIs) that are regarded as the first-line drugs to manage mental disorders. It has been also recognized with the potential to treat inflammatory diseases and viral infection. However, the effect of fluvoxamine on autoimmune diseases, particularly type 1 diabetes (T1D) and the related cellular and molecular mechanisms, are yet to be addressed. Method Herein in this report, we treated NOD mice with fluvoxamine for 2 weeks starting from 10-week of age to dissect the impact of fluvoxamine on the prevention of type 1 diabetes. We compared the differences of immune cells between 12-week-old control and fluvoxamine-treated mice by flow cytometry analysis. To study the mechanism involved, we extensively examined the characteristics of CD4 + T cells with fluvoxamine stimulation using RNA-seq analysis, real-time PCR, Western blot, and seahorse assay. Furthermore, we investigated the relevance of our data to human autoimmune diabetes. Result Fluvoxamine not only delayed T1D onset, but also decreased T1D incidence. Moreover, fluvoxamine-treated NOD mice showed significantly attenuated insulitis coupled with well-preserved β cell function, and decreased Th1 and Th17 cells in the peripheral blood, pancreatic lymph nodes (PLNs), and spleen. Mechanistic studies revealed that fluvoxamine downregulated glycolytic process by inhibiting phosphatidylinositol 3-kinase (PI3K)-AKT signaling, by which it restrained effector T (Teff) cell differentiation and production of proinflammatory cytokines. Conclusion Collectively, our study supports that fluvoxamine could be a viable therapeutic drug against autoimmunity in T1D setting.

High salt (HS) consumption is a risk factor for multiple autoimmune disorders via disturbing immune homeostasis. Nevertheless, the exact mechanisms by which HS exacerbates rheumatoid arthritis (RA) pathogenesis remain poorly defined. Herein, we found that heightened phosphorylation of PDPK1 and SGK1 upon HS exposure attenuated FoxO1 expression to enhance the glycolytic capacity of CD4 T cells, resulting in strengthened Th17 but compromised Treg program. GSK2334470 (GSK), a dual PDPK1/SGK1 inhibitor, effectively mitigated the HS-induced enhancement in glycolytic capacity and the overproduction of IL-17A. Therefore, administration of GSK markedly alleviated HS-exacerbated RA progression in collagen-induced arthritis (CIA) model. Collectively, our data indicate that HS consumption subverts Th17/Treg homeostasis through the PDPK1-SGK1-FoxO1 signaling, while GSK could be a viable drug against RA progression in clinical settings.

As one kind of plant-derived extracellular vesicle, turmeric-derived exosome-like nanoparticles (TELNs) are composed of proteins, lipids, nucleic acids, and small-molecule compounds, which possess good biocompatibility and safety. They are especially rich in information from the “mother plant”, which provides more applications in biological fields. In this study, we isolated and purified TELNs using differential centrifugation and ultracentrifugation and systematically detected their physicochemical properties using multi-omics. The TELNs possessed a typical teacup-like exosome morphology, and the extraction rate was approximately 1.71 ± 0.176 mg/g. The average particle size was 183.2 ± 10.9 nm, and the average zeta potential was −17.6 ± 1.19 mV. They were rich in lipids, mainly phosphatidylethanolamine (PE) (17.4%), triglyceride (TG) (12.3%), phosphatidylinositol (PI) (9.82%), and phosphatidylcholine (PC) (7.93%). All of them are the key lipids in the exosomes. The protein content was approximately 12% (M/M), mainly curcumin synthase and other proteins involved in secondary metabolite biosynthesis. In addition, there are critical essential genes for curcumin biosynthesis, such as curcumin synthase (CURS) and diketocoenzyme A synthase (DCS). More importantly, a greater variety of small-molecule compounds, primarily curcumin and curcumin analogs such as demethoxycurcumin and volatile oleoresins such as curcuminoids, have now been revealed. In conclusion, TELNs were successfully isolated, containing 0.17% (M/M) turmeric and a large amount of chemical information, the same as the parent-of-origin plant. This is the first time combining multi-omics to analyze the characteristics and nature of the TELNs, which laid a solid material foundation for the further development of turmeric.

The regulation of autoimmunity against pancreatic islet β cells for type 1 diabetes (T1D) onset is still unclear. NOD/ShiLtJ (NOD) mice are prone to the onset of autoimmune diabetes, but its congenic strain, ALR/Lt (ALR), is not. Here we show that dendritic cells (DC) in ALR mice have impaired migratory and T-cell priming capability. Genomic comparative analysis maps a 33-bp deletion in the ALR Myosin IXb (Myo9b) gene when compared with NOD genome; meanwhile, data from knock-in models show that this ALR Myo9b allele impairs phenotypic and functional maturation of DCs, and prevents the development and progression of spontaneous autoimmune diabetes in NOD mice. In parallel, while the ALR 33-bp deletion of Myo9b is not conserved in human, we find a MYO9B R133Q polymorphism associating with increased risk of T1D and enhanced DC function in patients with T1D. Our results thus hint that alterations in Myo9b may contribute to altered DC function and autoimmune diabetes onset.