PDIA3 orchestrates effector T cell program by serving as a chaperone to facilitate the non-canonical nuclear import of STAT1 and PKM2.

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.

Preparation and characterization of porous corn starch-based antibacterial sustained-release intelligent film.

A novel porous corn starch-based antibacterial sustained-release intelligent film was prepared with the porous corn starch as the substrate, purple corn cob anthocyanin (PCA) as the indicator, and tangerine peel essential oil as the antibacterial agent, and its properties were studied. The results showed that the porous corn starch-based antimicrobial sustained-release indicator film had good mechanical strength, surface hydrophobicity and light transmittance. The tensile strength of the sustained-release indicator film (PLSt-12) prepared by porous corn starch with an enzymatic hydrolysis time of 12 h was 14.35 MPa and the elongation at break was 6.55 %. The water contact angle was 89.10°, and the water vapor transmittance was 6.62 × 10-4 g·mm2·s-1·Pa-1. The PLSt-12 was brown at pH 10 and had a sensitive color response. The PLSt-12 reduced the release rate of anthocyanins by 25.01 %, and the sustained-release mechanism was non-Fick diffusion. It showed a significant color change when the pork quality deteriorated, which can be used to monitor the freshness of the pork. This type of antibacterial sustained-release intelligent film had considerable application potential in indicating food freshness.

GSK2334470 attenuates high salt-exacerbated rheumatoid arthritis progression by restoring Th17/Treg homeostasis.

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.

PDIA3 defines a novel subset of adipose macrophages to exacerbate the development of obesity and metabolic disorders.

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.

[Study on Polygonum multi florum Thunb and extracts by DRIFTS and atr-ftir].

The diffuse-reflectance FTIR spectroscopy (DRIFTS) and attenuated total reflection FTIR (ATR-FTIR) were used to study polygonum multi florum Thumb and its extracts. The result shows that when acetone is used as extraction agent, the contents of extracts in polygonum multi florum Thunb's phloem are highest, those in polygonum multi florum Thunb's xylem are the lowest. Compared with DRIFTS and ATR-FTIR, it can be found that there are some differences between polygonum multi florum Thunb and its extracts. There are two gentle absorption peaks at 3 576 and 3 147 cm(-1) respectively for polygonum multi florum Thunb, while there is a strong absorption peak at 3 351 cm(-1) for its extracts, showing that there may be more OH... active ingredients in polygonum multi florum Thunb's extracts. Meanwhile, polygonum multiflorum Thunb has strong absorption peaks at 931, 859, 766 and 709 cm(-1) respectively, while its extracts have no resembling absorption peaks. It also shows that the extracts are active ingredients.

[Characterization of pesticide residual dynamics by in situ attenuated total reflection FTIR].

In-situ attenuated total reflection FTIR (in situ ATR-FTIR) was used for the dynamic research on the residual of pesticide. The in-situ characterization of dichlorvos and orthene on the tomatoes' surface shows that the dichlorvos has obvious volatility and its degradation amount is 80% 20 minutes after spraying. Meanwhile, the ATR-FTIR shows that the strong absorption peak of dichlorvos at 1 734 cm(-1) turns to negative peaks and the absorption peaks at 3 073 cm(-1) significantly abate. The absorption peaks at 1 277 cm(-1) become weak and red shift (30 cm(-1)) shows that the dichlorvos may be hydrolyzed to some extent. While the absorption peaks of orthene show no change 120 minute after spraying. It shows that the orthene is relatively stable.

The preparation and characterization of nanocomposite film reinforced by modified cellulose nanocrystals.

In the present study, in order to improve the properties of nanostarch-based nanocomposite film for food packaging, a type of nanocomposite film based on corn nanostarch (CNS) as the matrix and modified cellulose nanocrystals (modified-CNCs) as the reinforcement was prepared using a solution casting method. The cellulose nanocrystals (CNCs) were modified by a two-step method in which they were initially crosslinked with citric acid, and subsequently amidated with chitosan. Then, a type of CNS/modified-CNCs nanocomposite film with different content levels of modified-CNC were prepared and characterized using Fourier Transform Infrared spectroscopy (FTIR); X-ray Photoelectron Spectroscopy (XPS); X-Ray Diffraction (XRD); Differential Scanning Calorimetry (DSC); and Scanning Electron Microscopy (SEM). It was observed that when compared with the pure CNS film, the 8.0 wt% modified-CNCs loaded nanostarch-based nanocomposite film had displayed a 230.0% increase in tensile strength. And the moisture absorption ability had decreased by 25.6%; water vapor permeability had decreased by 87.4%; and the water contact angle value had increased by 18.1%. Also the results of this experimental study had revealed that the CNS/modified-CNCs nanocomposite film had displayed better antimicrobial activities against E. coli and S. aureus bacteria when compared with the pure CNS film.