AnWRKY29 and AnHSP90 synergistically modulate trehalose levels in a desert shrub leaves during osmotic stress.

Trehalose, a biological macromolecule with osmotic adjustment properties, plays a crucial role during osmotic stress. As a psammophyte, Ammopiptanthus nanus relies on the accumulation of organic solutes to respond to osmotic stress. We utilized virus-induced gene silencing technology for the first time in the desert shrub A. nanus to confirm the central regulatory role of AnWRKY29 in osmotic stress, as it controls the transcription of AnTPS11 (trehalose-6-phosphate synthase 11). Further investigation has shown that AnHSP90 may interact with AnWRKY29. The AnHSP90 gene is sensitive to osmotic stress, underscoring its pivotal role in orchestrating the response to such adverse conditions. By directly targeting the W-box element within the AnTPS11 promoter, AnWRKY29 effectively enhances the transcriptional activity of AnTPS11, which is facilitated by AnHSP90. This discovery highlights the critical role of AnWRKY29 and AnHSP90 in enabling organisms to adapt to and cope effectively with osmotic stress, which can be a crucial factor in A. nanus survival and overall ecological resilience. Collectively, uncovering the molecular mechanisms underlying the osmotic responses of A. nanus is paramount for comprehending and augmenting the osmotic tolerance mechanisms of psammophyte shrub plants.

Cutaneous nerve fibers participate in the progression of psoriasis by linking epidermal keratinocytes and immunocytes.

Recent studies have illustrated that psoriatic lesions are innervated by dense sensory nerve fibers. Psoriatic plaques appeared to improve after central or peripheral nerve injury. Therefore, the nervous system may play a vital role in psoriasis. We aimed to clarify the expression of nerve fibers in psoriasis and their relationship with immune cells and keratinocytes, and to explore the effect of skin nerve impairment. Our results illustrated that nerve fibers in psoriatic lesions increased and were closely innervated around immune cells and keratinocytes. RNA-seq analysis showed that peripheral sensory nerve-related genes were disrupted in psoriasis. In spinal cord hemi-section mice, sensory impairment improved psoriasiform dermatitis and inhibited the abnormal proliferation of keratinocytes. Botulinum toxin A alleviated psoriasiform dermatitis by inhibiting the secretion of calcitonin gene-related peptide. Collectively, cutaneous nerve fibers participate in the progression of psoriasis by linking epidermal keratinocytes and immunocytes. Neurological intervention may be a new treatment strategy for psoriasis.

Mupirocin blocks imiquimod-induced psoriasis-like skin lesion by inhibiting epidermal isoleucyl-tRNA synthetase.

BACKGROUND: The Isoleucyl-tRNA synthetase (IARS) catalyzes isoleucine to the corresponding tRNA, maintaining the accuracy of gene translation. Its role in psoriasis has been not investigated so far. In this study, we aimed to investigate the mechanisms underlying the efficacy of IARS inhibitor, mupirocin, treatment for psoriasis. METHODS: The expression of IARS was determined by immunofluorescence, Western blot and qRT-PCR in normal healthy control- and psoriatic human skin. An imiquimod (IMQ) -induced psoriasis-like skin disease model was used to study the phenotypes changed by an IARS inhibitor, mupirocin (MUP). Endotypes were analyzed by RNA-seq, R&D Luminex multi-factor technique, ELISA, immunofluorescence and flow cytometry. Additionally, the effect of MUP on epidermal keratinocytes (KCs) were conducted in-vitro in primary cultured human KCs. RESULTS: We found the expression of IARS was higher in psoriatic skin than in healthy controls. In IMQ-induced psoriasis-like C57BL/6 J mouse model, MUP reversed IMQ-induced keratinocytes proliferation, expression of inflammatory cytokines and infiltration of immune cells. Furthermore, in cultured human keratinocytes, MUP inhibited proliferation, but promoted apoptosis, which may be related with STAT3 signaling pathway. CONCLUSION: Our finding of blocking the infiltration of immune cells by inhibiting the formation of IARS, could be one mechanism to explain the effect of MUP in the treatment of psoriasis. Developing strategies targeting suppression IARS should open new perspectives for the treatment of psoriasis. Video Abstract.

Spontaneous diametric-drive acceleration initiated by a single beam in a photonic lattice.

We demonstrate that a single Gaussian-like beam can self-bend during nonlinear propagation in a uniform photonic lattice. The two components of the beam experiencing normal and anomalous diffractions spontaneously separate and form a pair in a diametric-drive acceleration due to nonlinear action. Such a diametric drive generally describes a jointly accelerating behavior of two beams analogous to positive- and negative-mass objects. The influences of the initial momentum of the input beam and the nonlinear strength are considered in this process. We further realize a self-bending propagation for a partially coherent light beam and discuss the impact of incoherence on the acceleration strength.

Unveiling Chiral Phase Evolution in Rabi Oscillations from a Photonic Setting.

Rabi oscillation, originally proposed in nuclear magnetic resonance, is a well-known phenomenon associated with a driven two-level system. Although magnetic fields typically can bring about chirality into unusual phenomena such as chiral edge states in the quantum Hall effect, it is not clear if chirality exists in Rabi oscillations. Here we unveil the intrinsic chirality carried by the phase in a Rabi problem. For opposite detuning of the driving field, the phase evolution of the probability amplitude exhibits a mirror symmetry. Consequently, constructive or destructive interference of two off-resonant Rabi processes under different initial conditions is level dependent and symmetry protected. Experimentally, we demonstrate such features in a photonic setting with adjustable detuning, yet our results may prove pertinent to the study of similar phenomena in other driven two-level systems beyond photonics.

Increased CCL24 and CXCL7 levels in the cerebrospinal fluid of patients with neurosyphilis.

BACKGROUND: Monocytes are recruited into the cerebrospinal fluid (CSF) of patients with neurosyphilis, suggesting abnormal chemokine expression. We aimed to investigate the aberrant expression of chemokines in the CSF of these patients. METHODS: CSF and serum samples were collected from patients with neurosyphilis between July 2017 and June 2019 in the Dermatology Department, Second Affiliated Hospital of Zhejiang University. Differences in the expression of 38 chemokines between patients with and without neurosyphilis were detected using RayBio® Human Chemokine Antibody Array C1. CCL24 and CXCL7 levels in the patients' CSF and serum were further measured using RayBio® CCL24 and CXCL7 ELISA kits. RESULTS: Ninety-three CSF and serum samples of patients with syphilis were collected. Antibody array analysis showed that the CSF levels of CCL24 (P = .0185), CXCL7 (P < .0001), CXCL13 (P < .0001), CXCL10 (P < .0001), and CXCL8 (P < .0001) were significantly higher in patients with than without neurosyphilis. ELISA confirmed significantly higher CCL24 and CXCL7 levels in the CSF of patients with than without neurosyphilis (CCL24: 6.082 ± 1.137 pg/mL vs 1.773 ± 0.4565 pg/mL, P = .0037; CXCL7: 664.3 ± 73.19 pg/mL vs 431.1 ± 90.54 pg/mL, P = .0118). Increased CCL24 and CXCL7 expression was seen throughout all neurosyphilis stages, had moderate diagnostic efficiency for neurosyphilis, and correlated poorly with CSF cell count and Venereal Disease Research Laboratory titer. CSF CCL24 levels also correlated poorly with CSF protein concentration. CONCLUSION: Abnormally high CSF chemokines levels may play a role in the pathogenesis of neurosyphilis.

Exosomal microRNA profiles from serum and cerebrospinal fluid in neurosyphilis.

OBJECTIVE: Changes in microRNAs (miRNAs) in the cerebrospinal fluid (CSF) are associated with different neurological diseases. Since alternations of miRNAs in neurosyphilis are insufficiently investigated, we analysed miRNAs in the CSF of patients suffering from neurosyphilis. METHODS: Exosomes were isolated from serum and CSF. Levels of 44 miRNAs were determined using quantitative real-time PCR-based miRNA array. RESULTS: In patients with neurosyphilis (NSP), miR-590-5p, miR-570-3p and miR-570-5p were upregulated in the CSF and serum, when compared with patients with syphilis without neurosyphilis (SP). miR-590-5p and miR-570-3p were significantly upregulated (p<0.001). The expression of miR-21-5p was upregulated only in the CSF of NSP. Significant downregulation was observed for miR-93-3p in the CSF and serum of NSP. No statistical difference was found in the expression of miR-7-5p, miR-1307-5p, miR-203a-3p, miR-16, miR-23b-3p and miR-27b-5p in the CSF and serum of NSP and SP. CONCLUSION: For the first time, regulation profiles in miRNA in the CSF and serum were analysed in NSP. We found significant differences in upregulation and downregulation. Therefore, miRNAs may be potential biomarkers for the presence of neurosyphilis.

TCR-induced, PKC-θ-mediated NF-κB activation is regulated by a caspase-8-caspase-9-caspase-3 cascade.

It has been documented that caspase-8, a central player in apoptosis, is also crucial for TCR-mediated NF-κB activation. However, whether other caspases are also involved this process is unknown. In this report, we showed that in addition to caspase-8, caspase-9 is required for TCR-mediated NF-κB activation. Caspase-9 induces activation of PKC-θ, phosphorylation of Bcl10 and NF-κB activation in a caspase-3-dependent manner, but it appears that Bcl10 phosphorylation is uncoupled from NF-κB activation. Furthermore, caspase-8 lies upstream of caspase-9 during T cell activation. Therefore, TCR ligation elicits a caspase cascade involving caspase-8, caspase-9 and caspase-3 which initiates PKC-θ-dependent pathway leading to NF-κB activation and PKC-θ-independent Bcl10 phosphorylation which limits NF-kB activity.

Ethyl vinyl ketone activates oxidative and calcium burst and CML8-ACA8 participates in calcium recovery in Arabidopsis leaves.

Plants produce ethyl vinyl ketone (evk) in response to biotic stress, but the evk's identification and downstream defense response remain unclear. In this paper, it is predicted by docking for the first time that evk can be recognized by RBOH protein and assist the electron transfer of RBOHD/RBOHF by binding to its FAD or NADPH binding site. Surface plasmon resonance (SPR) binding assay shows that evk indeed bind to RBOHD. Here, we show that evk treatment increased H2O2 and intracellular calcium concentrations in Arabidopsis thaliana mesophyll cells, as observed by confocal laser scanning microscopy and non-invasive micro-test technology, and that H2O2 signaling functioned upstream of Ca2+ signaling. Yeast two-hybrid, firefly luciferase complementation imaging, and in vitro pull-down assays demonstrated that the ACA8 (AUTOINHIBITED Ca2+-ATPASE, ISOFORM 8)-CML8 (CALMODULIN-LIKE 8) interaction promoted Ca2+ efflux to return Ca2+ levels to the resting state.

Enhancing plant defensins in a desert shrub: Exploring a regulatory pathway of AnWRKY29.

A distinct family of plant-specific WRKY transcription factors plays a crucial role in modulating responses to biotic and abiotic stresses. In this investigation, we unveiled a signaling pathway activated in the desert shrub Ammopiptanthus nanus during feeding by the moth Spodoptera exigua. The process involves a Ca2+ flux that facilitates interaction between the protein kinase AnCIPK12 and AnWRKY29. AnWRKY29 directly interacts with the promoters of two key genes encoding AnPDF1 and AnHsfB1, involved in the biosynthesis of plant defensins. Consequently, AnWRKY29 exerts its transcriptional regulatory function, influencing plant defensins biosynthesis. This discovery implies that A. nanus can bolster resistance against herbivorous insects like S. exigua by utilizing this signaling pathway, providing an effective natural defense mechanism that supports its survival and reproductive success.

Early signaling enhance heat tolerance in Arabidopsis through modulating jasmonic acid synthesis mediated by HSFA2.

Given the detrimental impact of global warming on crop production, it is particularly important to understand how plants respond and adapt to higher temperatures. Using the non-invasive micro-test technique and laser confocal microscopy, we found that the cascade process of early signals (K+, H2O2, H+, and Ca2+) ultimately resulted in an increase in the cytoplasmic Ca2+ concentration when Arabidopsis was exposed to heat stress. Quantitative real-time PCR demonstrated that heat stress significantly up-regulated the expression of CAM1, CAM3 and HSFA2; however, after CAM1 and CAM3 mutation, the upregulation of HSFA2 was reduced. In addition, heat stress affected the expression of LOX3 and OPR3, which was not observed when HSFA2 was mutated. Luciferase reporter gene expression assay and electrophoretic mobility shift assay showed that HSFA2 regulated the expression of both genes. Determination of jasmonic acid (JA) content showed that JA synthesis was promoted by heat stress, but was damaged when HSFA2 and OPR3 were mutated. Finally, physiological experiments showed that JA reduced the relative electrical conductivity of leaves, enhanced chlorophyll content and relative water content, and improved the survival rate of Arabidopsis under heat stress. Together, our results reveal a new pathway for Arabidopsis to sense and transmit heat signals; HSFA2 is involved in the JA synthesis, which can act as a defensive compound improving Arabidopsis heat tolerance.

Biologics protect psoriasis patients from being exacerbated by COVID-19 infection.

Background: Patients with psoriasis may experience an exacerbation in symptoms following COVID-19 infection. After abandoning 'zero COVID' strategies, China experienced a surge of Omicron infections. Objectives: We aimed to investigate psoriasis exacerbation in psoriatic patients with COVID-19, following treatment with three different biologics, adalimumab, secukinumab, and ixekizumab. Methods: We performed a prospective study (n = 209) at our hospital between November 01, 2022, and February 15, 2023. We defined △ PASI as post-COVID-19 PASI minus pre-COVID-19 PASI. Two endpoints were set in this study. △ PASI >0 was defined as exacerbation of psoriasis after infection. △ PASI >3 was defined as a severe exacerbation of psoriasis symptoms after infection. In addition, serum OAS1, OAS2, and OAS3 were also assessed. Results: Results showed that the severity of psoriasis can worsen after COVID-19 infection, and a smaller proportion of patients taking biologics developed worsening psoriasis compared to those not using biologics; however, only the patients taking ixekizumab demonstrated a statistically significant difference (p < 0.05), while those taking adalimumab or secukinumab didn't. What's more, the use of biological agents suppressed the serum OAS2 and OAS3 at low levels and elevated the serum OAS1 level in patients with psoriasis. Conclusions: This study provided new insights into the protective role of biological agents in patients with psoriasis who were infected with COVID-19, and we proposed that psoriatic patients treated with biologics should continue with the treatment during the COVID-19 pandemic.

Glycyl-tRNA Synthetase Induces Psoriasis-Like Skin by Facilitating Skin Inflammation and Vascular Endothelial Cell Angiogenesis.

Psoriasis is characterized by excessive keratinocyte proliferation and immunocyte infiltration, but the underlying pathogenesis remains unclear. Aminoacyl-tRNA synthetases are universally expressed enzymes that catalyze the first step of protein synthesis. Glycyl-tRNA synthetase (GARS) is a member of the aminoacyl-tRNA synthetase family. In addition to its canonical function, we found that GARS was overexpressed in the serum and skin lesions of patients with psoriasis. Moreover, GARS was highly expressed in human skin keratinocytes, and GARS knockdown in keratinocytes suppressed cell proliferation and promoted apoptosis through NF-κB/MAPK signaling pathway. Moreover, intradermal injection of recombinant GARS protein caused skin thickening, angiogenesis, and IFN/TNF-driven skin inflammation. Intriguingly, the reported functional receptor for GARS, cadherin 6 (CDH6), was specifically expressed in vascular endothelial cells, and we found that keratinocyte-derived GARS promotes inflammation and angiogenesis of vascular endothelial cells through CDH6. In addition, intradermal injection of GARS aggravated the phenotype and angiogenesis in imiquimod-induced psoriasiform dermatitis models, whereas the psoriatic phenotype and angiogenesis were relieved after knockdown of GARS by adeno-associated virus. Taken together, the results of this study identify the critical role of GARS in the pathogenesis of psoriasis and suggest that blocking GARS may be a therapeutic approach for alleviating psoriasis.

SPRY1 Deficiency in Keratinocytes Induces Follicular Melanocyte Stem Cell Migration to the Epidermis through p53/Stem Cell Factor/C-KIT Signaling.

The function and survival of melanocytes is regulated by an elaborate network of paracrine factors synthesized mainly by epidermal keratinocytes (KCs). KCs and melanocytes respond to UV exposure by eliciting a tanning response. However, how KCs and melanocytes interact in the absence of UV exposure is unknown. In this study, we demonstrate that after SPRY1 knockout in epidermal KCs, melanocyte stem cells in the hair follicle exit the niche without depleting the pool of these cells. We also found that melanocyte stem cells migrate to the epidermis in a p53/stem cell factor/C-KIT-dependent manner induced by a tanning-like response resulting from SPRY1 loss in epidermal KCs. Once there, these cells differentiate into functional melanocytes. These findings provide an example in which the migration of melanocyte stem cells to the epidermis is due to loss of SPRY1 in epidermal KCs and show the potential for developing therapies for skin pigmentation disorders by manipulating melanocyte stem cells.

Expression of ß-catenin and AXIN2 in ameloblastomas.

AIM OF THE STUDY: To investigate the expression status and association of ß-catenin and AXIN2 in ameloblastoma. MATERIAL AND METHODS: 30 ameloblastoma specimens and 10 normal oral mucosa tissues were enrolled in the study. The protein and RNA levels of ß-catenin and AXIN2 were detected by immunohistochemistry staining, Western blot, and real-time PCR analysis. The relationship between ß-catenin and AXIN2 protein and clinico-pathological parameters and prognosis was subsequently determined. RESULTS: The results show that ß-catenin mRNA expression was 1.24-fold higher in ameloblastomas than that in normal mucosa tissues, but AXIN2 mRNA expression was 0.47-fold lower in ameloblastomas than that in normal mucosa tissues (p < 0.05). The Western blot results show that ß-catenin and AXIN2 protein in ameloblastomas had a significantly higher level than normal mucosa tissues (p < 0.05). Immunohistochemical staining of ß-catenin and AXIN2 protein in ameloblastoma was expressed at a higher level than normal oral mucosa (p < 0.05). CONCLUSIONS: AXIN2 and ß-catenin play an important role in the tumorigenesis and progression of ameloblastoma.

AnWRKY29 from the desert xerophytic evergreen Ammopiptanthus nanus improves drought tolerance through osmoregulation in transgenic plants.

As a significant transcription factor family in plants, WRKYs have a crucial role in responding to different adverse environments. They have been repeatedly demonstrated to contribute to drought resistance. However, no systematic exploration of the WRKY family has been reported in the evergreen shrub Ammopiptanthus nanus under drought conditions. Here, we showed that AnWRKY29 expression is strongly induced under drought stress. AnWRKY29 belongs to the group IIe of WRKY gene family. To characterize the function of AnWRKY29, we generated transgenic plants overexpressing this gene in Arabidopsis thaliana. We determined that AnWRKY29 overexpression of mainly improves the drought resistance of transgenic plants to water stress by reducing water loss, preventing electrolyte leakage, and increasing the absorption of inorganic ions. In addition, the AnWRKY29 transgenic plants synthesized more trehalose under water stress. The overexpression of AnWRKY29 also enhanced the antioxidant and osmoregulation capacity of transgenic plants by increasing the activities of catalase, peroxidase and superoxide dismutase, thus increasing the scavenging of reactive oxygen species and propylene glycol synthesis aldehyde oxidase. In summary, our study shows that AnWRKY29 plays an important role in the drought tolerance pathway in plants.

DORN1 and GORK regulate stomatal closure in Arabidopsis mediated by volatile organic compound ethyl vinyl ketone.

Evk (ethyl vinyl ketone) is a signal substance for plant defense, but little is known about how evk mediates stomatal closure. Through stomatal biology experiments, we found that evk can mediate stomatal closure, and stomatal closure is weakened when DORN1 (DOES NOT RESPOND TO NUCLEOTIDES 1) and GORK (GATED OUTWARDLY-RECTIFYING K+ CHANNEL) are mutated. In addition, it was found by non-invasive micro-test technology (NMT) that the K+ efflux mediated by evk was significantly weakened when DORN and GORK were mutated. Yeast two-hybrid (Y2H), firefly luciferase complementation imaging (LCI), and in vitro pull-down assays demonstrated that DORN1 and GORK could interact in vitro and in vivo. It was found by molecular docking that evk could combine with MRP (Multidrug Resistance-associated Protein), thus affecting ATP transport, promoting eATP (extracellular ATP) concentration increase and realizing downstream signal transduction. Through inoculation of botrytis cinerea, it was found that evk improved the antibacterial activity of Arabidopsis thaliana. As revealed by reverse transcription quantitative PCR (RT-qPCR), the expression of defense related genes was enhanced by evk treatment. Evk is a potential green antibacterial drug.

Integrated analysis of transcriptomics and metabolomics of peach under cold stress.

Low temperature is one of the environmental factors that restrict the growth and geographical distribution of peach (Prunus persica L. Batsch). To explore the molecular mechanisms of peach brunches in response to cold, we analyzed the metabolomics and transcriptomics of 'Donghe No.1' (cold-tolerant, CT) and '21st Century' (cold-sensitive, CS) treated by different temperatures (-5 to -30°C) for 12 h. Some cold-responsive metabolites (e.g., saccharides, phenolic acids and flavones) were identified with upregulation only in CT. Further, we identified 1991 cold tolerance associated genes in these samples and they were significantly enriched in the pathways of 'galactose metabolism', 'phenylpropanoid biosynthesis' and 'flavonoids biosynthesis'. Weighted gene correlation network analysis showed that soluble sugar, flavone, and lignin biosynthetic associated genes might play a key role in the cold tolerance of peach. In addition, several key genes (e.g., COMT, CCR, CAD, PER and F3'H) were substantially expressed more in CT than CS under cold stress, indicating that they might be major factors during the adaptation of peach to low temperature. This study will not only improve our understanding towards the molecular mechanisms of peach trees under cold stress but also contribute to the screening and breeding program of peach in the future.