Roles of TRP and PIEZO receptors in autoimmune diseases.

Autoimmune diseases are pathological autoimmune reactions in the body caused by various factors, which can lead to tissue damage and organ dysfunction. They can be divided into organ-specific and systemic autoimmune diseases. These diseases usually involve various body systems, including the blood, muscles, bones, joints and soft tissues. The transient receptor potential (TRP) and PIEZO receptors, which resulted in David Julius and Ardem Patapoutian winning the Nobel Prize in Physiology or Medicine in 2021, attracted people's attention. Most current studies on TRP and PIEZO receptors in autoimmune diseases have been carried out on animal model, only few clinical studies have been conducted. Therefore, this study aimed to review existing studies on TRP and PIEZO to understand the roles of these receptors in autoimmune diseases, which may help elucidate novel treatment strategies.

Corrigendum: Optimizing window size and directional parameters of GLCM texture features for estimating rice AGB based on UAVs multispectral imagery.

[This corrects the article DOI: 10.3389/fpls.2023.1284235.].

Research progress of engineered mesenchymal stem cells and their derived exosomes and their application in autoimmune/inflammatory diseases.

Autoimmune/inflammatory diseases affect many people and are an important cause of global incidence and mortality. Mesenchymal stem cells (MSCs) have low immunogenicity, immune regulation, multidifferentiation and other biological characteristics, play an important role in tissue repair and immune regulation and are widely used in the research and treatment of autoimmune/inflammatory diseases. In addition, MSCs can secrete extracellular vesicles with lipid bilayer structures under resting or activated conditions, including exosomes, microparticles and apoptotic bodies. Among them, exosomes, as the most important component of extracellular vesicles, can function as parent MSCs. Although MSCs and their exosomes have the characteristics of immune regulation and homing, engineering these cells or vesicles through various technical means, such as genetic engineering, surface modification and tissue engineering, can further improve their homing and other congenital characteristics, make them specifically target specific tissues or organs, and improve their therapeutic effect. This article reviews the advanced technology of engineering MSCs or MSC-derived exosomes and its application in some autoimmune/inflammatory diseases by searching the literature published in recent years at home and abroad.

Immunomodulatory effects of umbilical mesenchymal stem cell-derived exosomes on CD4+ T cells in patients with primary Sjögren's syndrome.

BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune disease that leads to the destruction of exocrine glands and multisystem lesions. Abnormal proliferation, apoptosis, and differentiation of CD4+ T cells are key factors in the pathogenesis of pSS. Autophagy is one of the important mechanisms to maintain immune homeostasis and function of CD4+ T cells. Human umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exos) may simulate the immunoregulation of MSCs while avoiding the risks of MSCs treatment. However, whether UCMSC-Exos can regulate the functions of CD4+ T cells in pSS, and whether the effects via the autophagy pathway remains unclear. METHODS: The study analyzed retrospectively the peripheral blood lymphocyte subsets in pSS patients, and explored the relationship between lymphocyte subsets and disease activity. Next, peripheral blood CD4+ T cells were sorted using immunomagnetic beads. The proliferation, apoptosis, differentiation, and inflammatory factors of CD4+ T cells were determined using flow cytometry. Autophagosomes of CD4+ T cells were detected using transmission electron microscopy, autophagy-related proteins and genes were detected using western blotting or RT-qPCR. RESULTS: The study demonstrated that the peripheral blood CD4+ T cells decreased in pSS patients, and negatively correlated with disease activity. UCMSC-Exos inhibited excessive proliferation and apoptosis of CD4+ T cells in pSS patients, blocked them in the G0/G1 phase, inhibited them from entering the S phase, reduced the Th17 cell ratio, elevated the Treg ratio, inhibited IFN-γ, TNF-α, IL-6, IL-17A, and IL-17F secretion, and promoted IL-10 and TGF-ß secretion. UCMSC-Exos reduced the elevated autophagy levels in the peripheral blood CD4+ T cells of patients with pSS. Furthermore, UCMSC-Exos regulated CD4+ T cell proliferation and early apoptosis, inhibited Th17 cell differentiation, promoted Treg cell differentiation, and restored the Th17/Treg balance in pSS patients through the autophagy pathway. CONCLUSIONS: The study indicated that UCMSC-Exos exerts an immunomodulatory effect on the CD4+ T cells, and maybe as a new treatment for pSS.

Synthesis of 5,6-Dihydrophenanthridines via Palladium-Catalyzed Intramolecular Dehydrogenative Coupling of Two Aryl C-H Bonds.

5,6-Dihydrophenanthridines are common aza heterocycle frameworks of natural products and pharmaceuticals. Herein, we reported the first palladium-catalyzed intramolecular C-H/C-H dehydrogenative coupling reaction of two simple arenes to generate 5,6-dihydrophenanthridines. The approach features a broad substrate scope and good tolerance of functional groups, offering an efficient alternative synthesis route for important 5,6-dihydrophenanthridine compounds.

Optimizing window size and directional parameters of GLCM texture features for estimating rice AGB based on UAVs multispectral imagery.

Aboveground biomass (AGB) is a crucial physiological parameter for monitoring crop growth, assessing nutrient status, and predicting yield. Texture features (TFs) derived from remote sensing images have been proven to be crucial for estimating crops AGB, which can effectively address the issue of low accuracy in AGB estimation solely based on spectral information. TFs exhibit sensitivity to the size of the moving window and directional parameters, resulting in a substantial impact on AGB estimation. However, few studies systematically assessed the effects of moving window and directional parameters for TFs extraction on rice AGB estimation. To this end, this study used Unmanned aerial vehicles (UAVs) to acquire multispectral imagery during crucial growth stages of rice and evaluated the performance of TFs derived with different grey level co-occurrence matrix (GLCM) parameters by random forest (RF) regression model. Meanwhile, we analyzed the importance of TFs under the optimal parameter settings. The results indicated that: (1) the appropriate window size for extracting TFs varies with the growth stages of rice plant, wherein a small-scale window demonstrates advantages during the early growth stages, while the opposite holds during the later growth stages; (2) TFs derived from 45° direction represent the optimal choice for estimating rice AGB. During the four crucial growth stages, this selection improved performance in AGB estimation with R2 = 0.76 to 0.83 and rRMSE = 13.62% to 21.33%. Furthermore, the estimation accuracy for the entire growth season is R2 =0.84 and rRMSE =21.07%. However, there is no consensus regarding the selection of the worst TFs computation direction; (3) Correlation (Cor), Mean, and Homogeneity (Hom) from the first principal component image reflecting internal information of rice plant and Contrast (Con), Dissimilarity (Dis), and Second Moment (SM) from the second principal component image expressing edge texture are more important to estimate rice AGB among the whole growth stages; and (4) Considering the optimal parameters, the accuracy of texture-based AGB estimation slightly outperforms the estimation accuracy based on spectral reflectance alone. In summary, the present study can help researchers confident use of GLCM-based TFs to enhance the estimation accuracy of physiological and biochemical parameters of crops.

Circular RNAs: Emerging players in the pathogenesis of keloid.

Circular RNAs (circRNAs) are a new type of non-coding RNAs originating from precursor messenger RNAs. Recent research has confirmed that circRNAs play a significant role in various biological and pathological processes, including cell viability, migration, and apoptosis. Emerging studies have demonstrated that the deregulated circRNA-miRNA-mRNA interaction network plays a key role in the development of many diseases. Increasing evidence has highlighted the role of ncRNAs (mainly miRNAs and lncRNAs) in the pathogenesis of keloids. Recently, several publications also indicated that circRNAs contribute to keloid development. The discovery of circRNAs changed the current understanding of the biology of keloids It is crucial to elucidate a circRNA-miRNA-mRNA network to understand the pathological mechanism of keloids. In the present review, we summarize the aberrant expression of regulatory roles of circRNAs in keloids. We discuss the potential clinical application of circRNAs in the diagnosis and treatment of keloids.

Exploiting the role of T cells in the pathogenesis of Sjögren's syndrome for therapeutic treatment.

Sjögrens syndrome (SS) is caused by autoantibodies that attack proprioceptive salivary and lacrimal gland tissues. Damage to the glands leads to dry mouth and eyes and affects multiple systems and organs. In severe cases, SS is life-threatening because it can lead to interstitial lung disease, renal insufficiency, and lymphoma. Histological examination of the labial minor salivary glands of patients with SS reveals focal lymphocyte aggregation of T and B cells. More studies have been conducted on the role of B cells in the pathogenesis of SS, whereas the role of T cells has only recently attracted the attention of researchers. This review focusses on the role of various populations of T cells in the pathogenesis of SS and the progress made in research to therapeutically targeting T cells for the treatment of patients with SS.

MicroRNAs: Emerging players in the pathogenesis of vitiligo.

Vitiligo is an autoimmune skin disease characterized by presence of pale patchy areas of depigmentation. MicroRNAs (miRNAs) are important regulators of gene expression and play significant roles in diverse biological and pathological processes. Accumulating evidence has shown that miRNAs were differentially expressed in skin lesions and peripheral blood mononuclear cells of patients with vitiligo. In particular, miRNAs are significantly correlated with the development and progression of vitiligo. The abundance of some miRNAs in serum was also correlated with the vitiligo lesion severity, indicating that miRNAs might serve as prognostic biomarkers. Importantly, the direct involvement of miRNAs in the pathogenesis of vitiligo has been demonstrated. For example, increased expression of miR-25 contributes to vitiligo through promoting the dysfunction and oxidative stress-induced destruction of melanocytes. However, there are limited studies on the function and mechanism of deregulated miRNAs in vitiligo. Further studies are required to establish clinical applications of miRNAs for vitiligo. More in-depth investigations of miRNAs are needed for the understanding of the pathogenesis of vitiligo and the development of novel therapeutic targets. This present review summarizes the current literature on the deregulation and pathogenic roles of miRNAs in vitiligo. We also highlight the potential clinical applications of miRNAs in patients with vitiligo.

Emerging roles of long non-coding RNAs in keloids.

Keloids are pathologic wound healing conditions caused by fibroblast hyperproliferation and excess collagen deposition following skin injury or irritation, which significantly impact patients by causing psychosocial and functional distress. Extracellular matrix (ECM) deposition and human fibroblast proliferation represents the main pathophysiology of keloid. Long non-coding RNAs (LncRNAs) play important roles in many biological and pathological processes, including development, differentiation and carcinogenesis. Recently, accumulating evidences have demonstrated that deregulated lncRNAs contribute to keloids formation. The present review summarizes the researches of deregulated lncRNAs in keloid. Exploring lncRNA-based methods hold promise as new effective therapies against keloid.

Molecular identification and functional exploration of interleukin-20 in snakehead (Channa argus) involved in bacterial invasion and the proliferation of head kidney leukocytes.

As an inflammatory cytokine of the interleukin-20 (IL-20) subfamily, IL-20 has various functions in immune defenses, inflammatory diseases, tissue regeneration, cancer, and metabolism. Although the characteristics and functions of mammalian IL-20 have been clarified, those of fish IL-20 remain unclear. In this study, the IL-20 gene from the snakehead Channa argus (shIL-20) was cloned and functionally characterized. Similar to the IL-20 homologues of other species, the shIL-20 has a five exon/four intron structure in the coding region. The open reading frame of shIL-20 consists of 528 base pairs and encodes 175 amino acids (aa), including a signal peptide (aa 1-24) and a mature peptide (aa 25-175). The mature shIL-20 protein has six conserved cysteine residues, which occur in the IL-20 proteins of all species analyzed, and an additional cysteine residue (Cys-82) found only in the IL-20 proteins of several teleosts. The modeled tertiary structure of shIL-20 is similar with that of Homo sapiens IL-20. The shIL-20 was expressed constitutively in all the tissues analyzed, and its transcription was induced in the spleen and head kidney by Aeromonas schubertii and Nocardia seriolae in vivo and in head kidney leukocytes (HKLs) by lipoteichoic acid, lipopolysaccharide, and polyinosinic-polycytidylic acid in vitro. The recombinant shIL-20 protein induced the transcription of tumor necrosis factor α1 (TNF-α1), TNF-α2, IL-1ß, and endogenous shIL-20, and promoted the proliferation of HKLs. In conclusion, these findings demonstrate that shIL-20 participates in the immune response to bacterial invasion and promotes leukocyte proliferation, offering new insights into the functions of fish IL-20 during pathogen invasion.

Research status and future prospects of extracellular vesicles in primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is a diffuse connective tissue disease characterized by the invasion of exocrine glands such as lacrimal and salivary glands, abnormal proliferation of T and B lymphocytes, and infiltration of tissue lymphocytes. With the development of modern medicine, although research on the pathogenesis, diagnosis, and treatment of pSS has made significant progress, its pathogenesis has not been fully understood. Meanwhile, in the era of individualized treatment, it remains essential to further explore early diagnosis and treatment methods. Exosomes, small vesicles containing proteins and nucleic acids, are a subtype of extracellular vesicles secreted by various cells and present in various body fluids. Exosomes contribute to a variety of biological functions, including intercellular signal transduction and pathophysiological processes, and may play a role in immune tolerance. Therefore, exosomes are key to understanding the pathogenesis of diseases. Exosomes can also be used as a therapeutic tool for pSS because of their biodegradability, low immunogenicity and toxicity, and the ability to bypass the blood-brain barrier, implying the prospect of a broad application in the context of pSS. Here, we systematically review the isolation, identification, tracing, and mode of action of extracellular vesicles, especially exosomes, as well as the research progress in the pathogenesis, diagnosis, and treatment of pSS.

Characterization of snakehead (Channa argus) interleukin-21: Involvement in immune defense against two pathogenic bacteria, in leukocyte proliferation, and in activation of JAK-STAT signaling pathway.

Interleukin-21 (IL-21), a crucial immune regulatory molecule, belongs to the common γ-chain family of type I cytokines, and exerts pleiotropic effects on multiple immune cell types in mammals. However, the characteristics and functions of fish IL-21 remain unclear. To further investigate the molecular mechanism of IL-21 in teleosts, we first cloned and identified the IL-21 gene (designated shIL-21) of the snakehead (Channa argus). The full-length open reading frame of shIL-21 is 438 bp in length, and encodes a predicted protein of 145 amino acid residues. A sequence analysis showed that shIL-21 has the typical structural characteristics of other IL-21 proteins, containing four α-helices and four conserved cysteine residues. In a phylogenetic analysis, shIL-21 clustered within a subgroup of IL-21 proteins from other teleost species and shared its closest evolutionary relationship with that of Lates calcarifer. The expression analysis showed that shIL-21 was ubiquitously expressed in all the healthy snakehead tissues tested, albeit at different levels. After infection with Nocardia seriolae or Aeromonas schubertii, the relative expression of shIL-21 was mainly upregulated in the head kidney and spleen in vivo. Similarly, after stimulation with the three pathogen analogues lipoteichoic acid, lipopolysaccharides, and polyinosinic-polycytidylic acid, the expression of shIL-21 was also induced in head kidney leukocytes in vitro. A recombinant shIL-21 protein was expressed and purified, and promoted the proliferation of head kidney leukocytes, induced the expression of genes encoding critical signaling molecules in the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway, including JAK1, JAK3, STAT1, and STAT3, and induced the expression of endogenous shIL-21 and genes encoding several key proinflammatory cytokines (tumor necrosis factor-α, interferon-γ, and IL-1ß). Taken together, these preliminary findings suggest that shIL-21 is involved in the immune defense against bacterial infection, in leukocyte proliferation, and in the activation of the JAK-STAT pathway. They thus extend the functional studies of IL-21 in teleosts.

Synthesis of Aporphine Analogues via Palladium-Catalyzed Intramolecular Aryl-Aryl Dehydrogenative Coupling.

Reported herein is an intramolecular dehydrogenative coupling of two inert aryl C-H bonds for the synthesis of aporphine analogues. The process represents a novel tool for the preparation of aporphines via palladiun-catalyzed C-H bond activation. The present reaction is compatible with various functional groups, and the coupling products have been further applied for the synthesis of natural products aporphine and zenkerine.

Photocatalyzed Csp3-Csp3 cross-dehydrogenative coupling of N-Boc-tetrahydroisoquinolines with α,ß-unsaturated ketones.

A novel photocatalyzed cross-dehydrogenative coupling reaction of N-Boc-tetrahydroisoquinolines with α,ß-unsaturated ketones has been developed. This research provides an easy access to a variety of C1-substituted tetrahydroisoquinolines, which can be further transformed into benzo[a]-quinolizine-2-ones, the skeletons of natural products with a wide range of biological activities. The load of the photocatalyst is low and the oxidant is inexpensive and less toxic.

High-Sensitivity and Ultrafast-Response Ethanol Sensors Based on Graphene Oxide.

Ethanol sensors with ultrafast response and high sensitivity have attracted much attention to be applied to daily industrial production processes. In this work, graphene oxide-aniline (GOA) sensors are proposed to meet the requirements of detecting ethanol concentration. Graphene oxide is an outstanding material that has excellent electrical and thermal conductivity, large specific surface area, and high carrier mobility. Because of its special bonding reactions, GOA has advantages of good dispersibility, good electrical conductivity, insolubility in water, and strong plasticity. When testing ethanol concentration with sensors, there will be a lag time, which determines the sensitivity of the sensors. To the best of our knowledge, the GOA sensors in this work have the fastest response time, which is only 27 ms. The GOA ethanol sensors show a good ethanol sensing performance, including excellent sensitivity, cycle stability, and long-term stability.

Synthesis of trifluoromethylthioesters from aldehydes via a visible light-promoted radical process.

We report herein an efficient, economical, and scalable trifluoromethylthiolation of aldehydes to generate trifluoromethylthioesters via a visible light-promoted radical process. The transformation features cheap reagents, simple operation, a broad substrate scope, and especially no metal involved in the reaction. Trifluoromethylthiolations of several complex aldehyde-containing bioactive compounds have been realized; thus the approach has the potential to be an important tool for the late-stage functionalization of advanced synthetic intermediates and bioactive molecules, and should have many applications in medicinal chemistry.

Synthesis of difluoromethylselenoesters from aldehydes via a radical process.

Difluoromethylselenoester compounds, another important kind of organoselenium compounds, are reported herein for the first time. They can be efficiently synthesized from aldehydes and BnSeCF2H. The synthetic method features mild reaction conditions, broad substrate scope, good tolerance of functional groups, and importantly, no metal is involved in the reaction.

CeO2-Supported Pt Catalysts Derived from MOFs by Two Pyrolysis Strategies to Improve the Oxygen Activation Ability.

Functional metal organic framework (MOF) derivatives have attracted tremendous attention as promising catalysts for various reactions. The thermal decomposition strategies have a vital effect on the structures and physicochemical properties of functional MOF derivatives. Nevertheless, what effect does the pyrolysis strategy have on MOF derivatives need further study. In this work, one-step (under dry air) and two-step (first under N2 and then dry air) pyrolysis are chosen to prepare the functional ceria-based MOF derivatives with novel hierarchical pore structure. In comparison with the derivatives prepared by one-step pyrolysis, the two-step pyrolysis composites exhibit better catalytic activity for toluene oxidation due to the higher contents of surface absorbed oxygen species and surface oxygen vacancies. The reusability and durability test demonstrates perfect stability of such functional MOF derivatives. The in-situ UV Raman reveals that two-step strategy is favorable for enhancing the gaseous oxygen activation ability of the functional MOF derivatives. Those findings may instruct the synthesis of functional MOF derivatives via different pyrolysis strategies as well as afford a further understanding of the crucial role of oxygen vacancies.

Synthesis of (E,E)-Dienones and (E,E)-Dienals via Palladium-Catalyzed γ,δ-Dehydrogenation of Enones and Enals.

A new strategy for the synthesis of conjugated (E,E)-dienones and (E,E)-dienals via a palladium-catalyzed aerobic γ,δ-dehydrogenation of enones and enals has been developed. The method can be employed in the direct and efficient synthesis of various (E,E)-dienones and (E,E)-dienals, including non-substituted α-, ß-, and γ- and/or δ-substituted (E,E)-dienones and (E,E)-dienals. The protocol is featured by the ready accessibility and elaboration of the starting materials, good functional group compatibility, and mild reaction conditions. Furthermore, the reaction is of complete E,E-stereoselectivity and uses molecular oxygen as the sole clean oxidant.