Melatonin confers tolerance to nitrogen deficiency through regulating MdHY5 in apple plants.

Nitrogen (N) is an essential nutrient for crop growth and development, significantly influencing both yield and quality. Melatonin (MT), a known enhancer of abiotic stress tolerance, has been extensively studied. However, its relationship with nutrient stress, particularly N deficiency, and the underlying regulatory mechanisms of MT on N absorption remain unclear. In this study, exogenous MT treatment was found to improve the tolerance of apple plants to N deficiency. Apple plants overexpressing the MT biosynthetic gene N-acetylserotonin methyltransferase 9 (MdASMT9) were used to further investigate the effects of endogenous MT on low-N stress. Overexpression of MdASMT9 improved the light harvesting and heat transfer capability of apple plants, thereby mitigating the detrimental effects of N deficiency on the photosynthetic system. Proteomic and physiological data analyses indicated that MdASMT9 overexpression enhanced the trichloroacetic acid cycle and positively modulated amino acid metabolism to counteract N-deficiency stress. Additionally, both exogenous and endogenous MT promoted the transcription of MdHY5, which in turn bound to the MdNRT2.1 and MdNRT2.4 promoters and activated their expression. Notably, MT-mediated promotion of MdNRT2.1 and MdNRT2.4 expression through regulating MdHY5, ultimately enhancing N absorption. Taken together, these findings shed light on the association between MdASMT9-mediated MT biosynthesis and N absorption in apple plants under N-deficiency conditions.

Age-dependent changes in leaf size in apple are governed by a cytokinin-integrated module.

Plants undergo various age-dependent changes in leaf morphology during juvenile to adult vegetative stage. However, the precise molecular mechanisms governing these changes in apple (Malus domestica) remain unknown. Here, we showed that CYTOKININ OXIDASE/DEHYDROGENASE5 (MdCKX5), an age-dependent gene, encodes a functional CKX enzyme and serves as the common downstream target of SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factor MdSPL14 and WRKY transcription factor MdWRKY24 to control the degradation of cytokinin (CK). As the target of mdm-microRNA156a, MdSPL14 interacts with MdWRKY24 to coordinately repress the transcription of MdCKX5 by forming the age-mediated mdm-miR156a-MdSPL14-MdWRKY24 module, which regulates age-dependent changes in CK during the juvenile-to-adult phase transition. We further demonstrated that MdARR6, a type-A ARABIDOPSIS RESPONSE REGULATOR (ARR), is a negative feedback regulator in the CK signaling pathway. Silencing of MdARR6 in apple resulted in large leaves with smaller epidermal cells and a greater number of epidermal cells. Biochemical analysis showed that the mdm-miR156a-MdSPL14-MdWRKY24 module acts as a transcriptional repressor to directly regulate MdARR6 expression, thus controlling the age-dependent changes in leaf size by reducing CK responses. These findings established a link between the age pathway and CK signaling and revealed the molecular mechanism underlying age-dependent changes during the juvenile-to-adult phase transition; our results also provide targets for the genetic improvement of the vegetative phase transition in apple.

Divergent suicidal symptomatic activations converge on somato-cognitive action network in depression.

Individuals with depression have the highest lifetime prevalence of suicide attempts (SA) among mental illnesses. Numerous neuroimaging studies have developed biomarkers from task-related neural activation in depressive patients with SA, but the findings are inconsistent. Empowered by the contemporary interconnected view of depression as a neural system disorder, we sought to identify a specific brain circuit utilizing published heterogeneous neural activations. We systematically reviewed all published cognitive and emotional task-related functional MRI studies that investigated differences in the location of neural activations between depressive patients with and without SA. We subsequently mapped an underlying brain circuit functionally connecting to each experimental activation using a large normative connectome database (n = 1000). The identified SA-related functional network was compared to the network derived from the disease control group. Finally, we decoded this convergent functional connectivity network using microscale transcriptomic and chemo-architectures, and macroscale psychological processes. We enrolled 11 experimental tasks from eight studies, including depressive patients with SA (n = 147) and without SA (n = 196). The heterogeneous SA-related neural activations localized to the somato-cognitive action network (SCAN), exhibiting robustness to little perturbations and specificity for depression. Furthermore, the SA-related functional network was colocalized with brain-wide gene expression involved in inflammatory and immunity-related biological processes and aligned with the distribution of the GABA and noradrenaline neurotransmitter systems. The findings demonstrate that the SA-related functional network of depression is predominantly located at the SCAN, which is an essential implication for understanding depressive patients with SA.

SAP deletion promotes malignant insulinoma progression by inducing CXCL12 secretion from CAFs via the CXCR4/p38/ERK signalling pathway.

Malignant insulinoma is an extremely rare type of functioning pancreatic neuroendocrine tumour with a high degree of malignancy and a high incidence of metastasis. However, it is still unclear how malignant insulinomas develop and metastasize. Serum amyloid P component (SAP), a member of the pentraxin protein family, is an acute-phase protein secreted by liver cells. The role of SAP in insulinoma and the related mechanism are still unknown. To determine the effect of SAP on insulinoma, we crossed Rip1-Tag2 mice, which spontaneously develop insulinoma, and SAP knockout (KO) mice to generate Rip1-Tag2;SAP-/- mice. We found that SAP deletion significantly promoted the growth, invasion and metastasis of malignant insulinoma through C-X-C motif chemokine ligand 12 (CXCL12) secreted by cancer-associated fibroblasts (CAFs). Further study showed that SAP deletion promoted CXCL12 secretion by CAFs through the CXCR4/p38/ERK signalling pathway. These findings reveal a novel role and mechanism of SAP in malignant insulinoma and provide direct evidence that SAP may be a therapeutic agent for this disease.

MdASMT9-mediated melatonin biosynthesis enhances basal thermotolerance in apple plants.

High temperatures negatively impact the yield and quality of fruit crops. Exogenous melatonin (MT) application has been shown to enhance heat tolerance, but the response of endogenous MT to heat stress, particularly in perennial fruit trees, remains unclear. The present study investigated the effects of high temperatures on transgenic apple plants overexpressing the MT biosynthesis gene N-acetylserotonin methyltransferase 9 (MdASMT9). Endogenous MT protected transgenic plants from heat stress by increasing antioxidant enzyme activity and scavenging reactive oxygen species (ROS), and protecting the chloroplasts from damage. Application of MT and overexpression of MdASMT9 also reduced abscisic acid accumulation through promoting MdWRKY33-mediated transcriptional inhibition of MdNCED1 and MdNCED3, thus inducing stomatal opening for better heat dissipation. Furthermore, MT-enhanced autophagic activity through promoting MdWRKY33-mediated transcriptional enhancement of MdATG18a under heat stress. These findings provide new insights into the regulation of endogenous MT and its role in improving basal thermotolerance in perennial fruit trees.

Screening of broad-host expression promoters for shuttle expression vectors in non-conventional yeasts and bacteria.

BACKGROUND: Non-conventional yeasts and bacteria gain significance in synthetic biology for their unique metabolic capabilities in converting low-cost renewable feedstocks into valuable products. Improving metabolic pathways and increasing bioproduct yields remain dependent on the strategically use of various promoters in these microbes. The development of broad-spectrum promoter libraries with varying strengths for different hosts is attractive for biosynthetic engineers. RESULTS: In this study, five Yarrowia lipolytica constitutive promoters (yl.hp4d, yl.FBA1in, yl.TEF1, yl.TDH1, yl.EXP1) and five Kluyveromyces marxianus constitutive promoters (km.PDC1, km.FBA1, km.TEF1, km.TDH3, km.ENO1) were selected to construct promoter-reporter vectors, utilizing α-amylase and red fluorescent protein (RFP) as reporter genes. The promoters' strengths were systematically characterized across Y. lipolytica, K. marxianus, Pichia pastoris, Escherichia coli, and Corynebacterium glutamicum. We discovered that five K. marxianus promoters can all express genes in Y. lipolytica and that five Y. lipolytica promoters can all express genes in K. marxianus with variable expression strengths. Significantly, the yl.TEF1 and km.TEF1 yeast promoters exhibited their adaptability in P. pastoris, E. coli, and C. glutamicum. In yeast P. pastoris, the yl.TEF1 promoter exhibited substantial expression of both amylase and RFP. In bacteria E. coli and C. glutamicum, the eukaryotic km.TEF1 promoter demonstrated robust expression of RFP. Significantly, in E. coli, The RFP expression strength of the km.TEF1 promoter reached ∼20% of the T7 promoter. CONCLUSION: Non-conventional yeast promoters with diverse and cross-domain applicability have great potential for developing innovative and dynamic regulated systems that can effectively manage carbon flux and enhance target bioproduct synthesis across diverse microbial hosts.

Direct Construction of 1,4-Dihydropyridazines and Pyrazoles via Annulation of Alkyl 2-Aroyl-1-chlorocyclopropanecarboxylates.

An efficient and chemodivergent synthesis of highly functionalized 1,4-dihydropyridazines and pyrazoles has been accomplished via base-promoted annulation between hydrazones and alkyl 2-aroyl-1-chlorocyclopropanecarboxylates, respectively. This transition-metal-free domino reaction proceeded rapidly under mild basic conditions, affording potentially bioactive 1,4-dihydropyridazine and pyrazole derivatives in moderate yields. The conversion of 1,4-dihydropyridazine to pyrazole was confirmed by adjusting the quantity of the base.

BaTiO3 Catalyzed Ultrasonic-Driven Piezoelectric-Induced Reversible Addition-Fragmentation Chain-Transfer Polymerization in Aqueous Media.

Compared with normal stimulus such as light and heat, ultrasonic possesses much deeper penetration into tissues and organs and has lower scattering in heterogeneous systems as a noninvasive stimulus. Reversible addition-fragmentation chain-transfer polymerization (RAFT) in aqueous media is performed in a commercial ultrasonic wash bath with 40 kHz frequency ultrasonic, in the presence of piezoelectric tetragonal BaTiO3 (BTO) nanoparticles. Owing to the electron transfer from BTO under the ultrasonic action, the water can be decomposed to produce hydroxyl radical (HO•) and initiate the RAFT polymerization (piezo-RAFT). The piezo-RAFT polymerization exhibits features of controllable and livingness, such as linear increase of molar mass and narrow molar mass distributions (Mw/Mn < 1.20). Excellent temporal control of the polymerization and the chain fidelity of polymers are illustrated by "ON and OFF" experiment and chain extension, separately. Moreover, this ultrasonic-driven piezoelectric-induced RAFT polymerization in aqueous media can be directly used for the preparation of piezoelectric hydrogel which have potential application for stress sensor.

Isoliensinine activated the Nrf2/GPX4 pathway to inhibit glutamate-induced ferroptosis in HT-22 cells.

Isoliensinine (ISO), a natural compound, is a bibenzyl isoquinoline alkaloid monomer in lotus seed, which has strong antioxidant and free radical scavenging activities. The oxidative toxicity caused by glutamic acid overdose is one of the important mechanisms of nerve cell injury, and the oxidative toxicity caused by glutamic acid is related to ferroptosis. This study aims to establish a glutamate-induced injury model of mouse hippocampal neurons HT-22 cells, and investigate the protective effect of ISO on the neurotoxicity of glutamate-induced HT-22 cells. The results showed that ISO inhibited glutamate-induced ferroptosis of neuronal cells through nuclear factor E2-related factor 2/glutathione peroxidase 4 (Nrf2/GPX4) signaling pathway. Pretreatment of HT-22 cells with ISO significantly reduced glutamate-induced cell death. Ferroptosis inhibitors have the same effect. ISO inhibited the decrease of mitochondrial membrane potential detection and the increase of iron content induced by glutamate, the increase of malondialdehyde and reactive oxygen species in cytoplasm and lipid, and protected the activities of GPx and superoxide dismutase enzymes. In addition, WB showed that glutamic acid could induce the upregulated expression of long-chain esteryl coA synthase 4 (ACSL4) protein and the downregulated expression of SLC7A11 and GPX4 protein in HT-22 cells, while ISO could prevent the abnormal expression of these proteins induced by glutamic acid. The nuclear translocation of Nrf2 in HT-22 cells was increased, and the expression of downstream heme oxygenase-1 protein was upregulated. In summary, ISO protects HT-22 cells from glutamate-induced ferroptosis through a novel mechanism of the Nrf2/GPX4 signaling pathway.

Optimum investment strategy for hydrogen-based steelmaking project coupled with multiple uncertainties.

The large-scale application of hydrogen steelmaking technology is expected to substantially accelerate the decarbonization process of the iron and steel industry. However, hydrogen steelmaking projects are still in the experimental or demonstration stage, and scientific investment decision-making methods are urgently needed to support the large-scale development of the technology. When assessing the investment value, existing studies usually only consider the intrinsic project value under a specific pathway, while ignoring the option value under realistic multiple uncertainties in terms of technology, market, and policy, leading to an underestimation of the investment value. To address this issue, this study constructs a real options model to explore the optimal investment timing and revenue of the hydrogen steelmaking project, by taking into account multi-dimensional uncertainties stemming from price fluctuations in the steel market, the development of the carbon market, and technological advances. Additionally, the impacts of various subsidy policies on the investment strategy are also investigated. Least Squares Monte Carlo method is applied to overcome computational challenges posed by dynamic programming under multi-dimensional uncertainties. The results show that: (i) Investment is not recommended based on current crude steel price and hydrogen price. (ii) When the annual reduction rate of hydrogen price reaches 5%, the optimal investment timing would advance to 2036. (iii) On this basis, with the introduction of a 20% green hydrogen subsidy policy, the optimal investment timing would be further brought forward to 2033. The implementation of tax incentives would significantly increase the investment value. The investment value would surge from 170 million CNY to 262 million CNY as the tax rate decreases from 20% to zero. The findings could provide reasonable suggestions for investment decisions under realistic volatile environments, as well as scientific references for policy design, thus facilitating the large-scale and high-level development of hydrogen-based steelmaking technology.

Effect of stakeholder pressure on environmental performance: Do virtual CSR, green credit, environmental and social reputation matter?

In today's globalized and interconnected world, businesses operate within an interconnected network with various stakeholders. Among these stakeholders, the pressure from consumers, investors, regulators, and communities for corporations to adopt environmentally responsible practices has intensified significantly. Therefore, this study investigates the relationship between stakeholder pressure and environmental performance (EP) in Pakistan's manufacturing sector while examining the potential moderating roles of environmental reputation, social reputation, virtual CSR, and green credit. Data was gathered by convenience sampling and a cross-sectional research approach. A structural questionnaire was given to 376 employees of manufacturing firms that are listed on the Pakistan Stock Exchange (PSE). The research hypotheses were tested using PLS-SEM techniques, which examined the interactions between these variables. The results reveal that stakeholder pressure significantly influences the environmental performance of manufacturing firms. Environmental reputation and virtual CSR negatively moderate the relationship between stakeholder pressure and EP. Moreover, social reputation and green credit positively moderate the relationship between stakeholder pressure and EP. These results contribute to the existing literature by shedding light on how stakeholder pressure influences firms' environmental behavior. Practical implications include integrating virtual CSR strategies, securing green financing options, and building strong environmental and social reputations to effectively respond to stakeholder demands and improve environmental performance.

Resource utilization of MSWI fly ash supporting TiO2/BiOCl nanocomposite for enhanced photocatalytic degradation of sodium isopropyl xanthate: Mechanism and performance evaluation.

The removal of organic pollutants in water environments and the resource utilization of solid waste are two pressing issues around the world. Facing the increasing pollution induced by discharge of mining effluents containing sodium isopropyl xanthate (SIPX), in this work, municipal solid waste incineration fly ash (MSWI FA) was pretreated by hydrothermal method to produce stabilized FA, which was then innovatively used as support for the construction of FA/TiO2/BiOCl nanocomposite (FTB) with promoted photocatalytic activity under visible light and natural sunlight. When the content of FA was 20 wt% and the mass ratio of TiO2 to BiOCl was 4:6, a remarkable performance for the optimal FTB (20-FTB-2) was achieved. Characterizations demonstrated that TiO2 and BiOCl uniformly dispersed on FA contributing to high surface area and broad light adsorption of FTB, which exhibits excellent adsorption capacity and light response ability. Build in electric field formed in the interface of TiO2/BiOCl heterojunction revealed by density functional theory calculations accelerated the separation of photoinduced e- and h+, leading to high efficiency for SIPX degradation. The synergetic effect combined with adsorption and photocatalytic degradation endowed 20-FTB-2 superior SIPX removal efficiency over 99% within 30 min under visible light and natural sunlight irradiation. The photocatalytic degradation pathways of SIPX were determined through theoretical calculations and characterizations, and the toxic byproduct CS2 was effectively eliminated through oxidation of •O2-. For 20-FTB-2, reusability of photocatalyst was showed by cycle tests, also the concentrations of main heavy metals (Pb, Zn, Cu, Cr, and Cd) in the liquid phases released during photocatalyst preparation process (< 1 mg/L) and photodegradation process (< 8.5 µg/L) proved the satisfactory stability with low toxicity. This work proposed a novel strategy to develop efficient and stable support-based photocatalysts by utilizing MSWI FA and realize its resource utilization.

Treatment of tetracycline in an aqueous solution with an iron-biochar/periodate system: Influencing factors and mechanisms.

In this study, a potassium ferrate (K2FeO4)-modified biochar (Fe-BC) was prepared and characterized. Afterwards, Fe-BC was applied to activated periodate (PI) to degrade tetracycline (TC), an antibiotic widely used in animal farming. The degradation effects of different systems on TC were compared and the influencing factors were investigated. In addition, several reactive oxygen species (ROS) generated by the Fe-BC/PI system were identified, and TC degradation pathways were analyzed. Moreover, the reuse performance of Fe-BC was evaluated. The results exhibited that the Fe-BC/PI system could remove almost 100% of TC under optimal conditions of [BC] = 1.09 g/L, initial [PI] = 3.29 g/L, and initial [TC] = 20.3 mg/L. Cl-, HCO3-, NO3-, and humic acid inhibited TC degradation to varying degrees in the Fe-BC/PI system due to their quenching effects on ROS. TC was degraded into intermediates and even water and carbon dioxide by the synergistic effect of ROS generated and Fe on the BC surface. Fe-BC was reused four times, and the removal rate of TC was still maintained above 80%, indicating the stable nature of Fe-BC.

Mechanisms of the Masquelet technique to promote bone defect repair and its influencing factors.

The Masquelet technique, also known as the induced membrane technique, is a surgical technique for repairing large bone defects based on the use of a membrane generated by a foreign body reaction for bone grafting. This technique is not only simple to perform, with few complications and quick recovery, but also has excellent clinical results. To better understand the mechanisms by which this technique promotes bone defect repair and the factors that require special attention in practice, we examined and summarized the relevant research advances in this technique by searching, reading, and analysing the literature. Literature show that the Masquelet technique may promote the repair of bone defects through the physical septum and molecular barrier, vascular network, enrichment of mesenchymal stem cells, and high expression of bone-related growth factors, and the repair process is affected by the properties of spacers, the timing of bone graft, mechanical environment, intramembrane filling materials, artificial membrane, and pharmaceutical/biological agents/physical stimulation.

Semi-supervised segmentation of metal-artifact contaminated industrial CT images using improved CycleGAN.

Accurate segmentation of industrial CT images is of great significance in industrial fields such as quality inspection and defect analysis. However, reconstruction of industrial CT images often suffers from typical metal artifacts caused by factors like beam hardening, scattering, statistical noise, and partial volume effects. Traditional segmentation methods are difficult to achieve precise segmentation of CT images mainly due to the presence of these metal artifacts. Furthermore, acquiring paired CT image data required by fully supervised networks proves to be extremely challenging. To address these issues, this paper introduces an improved CycleGAN approach for achieving semi-supervised segmentation of industrial CT images. This method not only eliminates the need for removing metal artifacts and noise, but also enables the direct conversion of metal artifact-contaminated images into segmented images without the requirement of paired data. The average values of quantitative assessment of image segmentation performance can reach 0.96645 for Dice Similarity Coefficient(Dice) and 0.93718 for Intersection over Union(IoU). In comparison to traditional segmentation methods, it presents significant improvements in both quantitative metrics and visual quality, provides valuable insights for further research.

An optimized filter design approach for enhancing imaging quality in industrial linear accelerator.

BACKGROUND: The polychromatic X-rays generated by a linear accelerator (Linac) often result in noticeable hardening artifacts in images, posing a significant challenge to accurate defect identification. To address this issue, a simple yet effective approach is to introduce filters at the radiation source outlet. However, current methods are often empirical, lacking scientifically sound metrics. OBJECTIVE: This study introduces an innovative filter design method that optimizes filter performance by balancing the impact of ray intensity and energy on image quality. MATERIALS AND METHODS: Firstly, different spectra under various materials and thicknesses of filters were obtained using GEometry ANd Tracking (Geant4) simulation. Subsequently, these spectra and their corresponding incident photon counts were used as input sources to generate different reconstructed images. By comprehensively comparing the intensity differences and noise in images of defective and non-defective regions, along with considering hardening indicators, the optimal filter was determined. RESULTS: The optimized filter was applied to a Linac-based X-ray computed tomography (CT) detection system designed for identifying defects in graphite materials within high-temperature gas-cooled reactor (HTR), with defect dimensions of 2 mm. After adding the filter, the hardening effect reduced by 22%, and the Defect Contrast Index (DCI) reached 3.226. CONCLUSION: The filter designed based on the parameters of Average Difference (AD) and Defect Contrast Index (DCI) can effectively improve the quality of defect images.

Chromatin accessibility uncovers KRAS-driven FOSL2 promoting pancreatic ductal adenocarcinoma progression through up-regulation of CCL28.

BACKGROUND: The epigenetic mechanisms involved in the progression of pancreatic ductal adenocarcinoma (PDAC) remain largely unexplored. This study aimed to identify key transcription factors (TFs) through multiomics sequencing to investigate the molecular mechanisms of TFs that play critical roles in PDAC. METHODS: To characterise the epigenetic landscape of genetically engineered mouse models (GEMMs) of PDAC with or without KRAS and/or TP53 mutations, we employed ATAC-seq, H3K27ac ChIP-seq, and RNA-seq. The effect of Fos-like antigen 2 (FOSL2) on survival was assessed using the Kaplan-Meier method and multivariate Cox regression analysis for PDAC patients. To study the potential targets of FOSL2, we performed Cleavage Under Targets and Tagmentation (CUT&Tag). To explore the functions and underlying mechanisms of FOSL2 in PDAC progression, we employed several assays, including CCK8, transwell migration and invasion, RT-qPCR, Western blotting analysis, IHC, ChIP-qPCR, dual-luciferase reporter, and xenograft models. RESULTS: Our findings indicated that epigenetic changes played a role in immunosuppressed signalling during PDAC progression. Moreover, we identified FOSL2 as a critical regulator that was up-regulated in PDAC and associated with poor prognosis in patients. FOSL2 promoted cell proliferation, migration, and invasion. Importantly, our research revealed that FOSL2 acted as a downstream target of the KRAS/MAPK pathway and recruited regulatory T (Treg) cells by transcriptionally activating C-C motif chemokine ligand 28 (CCL28). This discovery highlighted the role of an immunosuppressed regulatory axis involving KRAS/MAPK-FOSL2-CCL28-Treg cells in the development of PDAC. CONCLUSION: Our study uncovered that KRAS-driven FOSL2 promoted PDAC progression by transcriptionally activating CCL28, revealing an immunosuppressive role for FOSL2 in PDAC.

LAZY3 interacts with LAZY2 to regulate tiller angle by modulating shoot gravity perception in rice.

Starch biosynthesis in gravity-sensing tissues of rice shoot determines the magnitude of rice shoot gravitropism and thus tiller angle. However, the molecular mechanism underlying starch biosynthesis in rice gravity-sensing tissues is still unclear. We characterized a novel tiller angle gene LAZY3 (LA3) in rice through map-based cloning. Biochemical, molecular and genetic studies further demonstrated the essential roles of LA3 in gravity perception of rice shoot and tiller angle control. The shoot gravitropism and lateral auxin transport were defective in la3 mutant upon gravistimulation. We showed that LA3 encodes a chloroplast-localized tryptophan-rich protein associated with starch granules via Tryptophan-rich region (TRR) domain. Moreover, LA3 could interact with the starch biosynthesis regulator LA2, determining starch granule formation in shoot gravity-sensing tissues. LA3 and LA2 negatively regulate tiller angle in the same pathway acting upstream of LA1 to mediate asymmetric distribution of auxin. Our study defined LA3 as an indispensable factor of starch biosynthesis in rice gravity-sensing tissues that greatly broadens current understanding in the molecular mechanisms underlying the starch granule formation in gravity-sensing tissues, and provides new insights into the regulatory mechanism of shoot gravitropism and rice tiller angle.

The CXCL12-CXCR4-NLRP3 axis promotes Schwann cell pyroptosis and sciatic nerve demyelination in rats.

Studies have shown that the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome is detrimental to the functional recovery of the sciatic nerve, but the regulatory mechanisms of the NLRP3 inflammasome in peripheral nerves are unclear. C-X-C motif chemokine 12 (CXCL12) can bind to C-X-C chemokine receptor type 4 (CXCR4) and participate in a wide range of nerve inflammation by regulating the NLRP3 inflammasome. Based on these, we explore whether CXCL12-CXCR4 axis regulates the NLRP3 inflammasome in the peripheral nerve. We found that CXCR4/CXCL12, NLRP3 inflammasome-related components, pyroptosis-related proteins and inflammatory factors in the sciatic nerve injured rats were markedly increased compared with the sham-operated group. AMD3100, a CXCR4 antagonist, reverses the activation of NLRP3 inflammasome, Schwann cell pyroptosis and sciatic nerve demyelination. We further treated rat Schwann cells with LPS (lipopolysaccharide) and adenosine triphosphate (ATP) to mimic the cellular inflammation model of sciatic nerve injury, and the results were consistent with those in vivo. In addition, both in vivo and in vitro experiments demonstrated that AMD3100 treatment reduced the phosphorylation of nuclear factor κB (NF-κB) and the expression of thioredoxin interacting protein (TXNIP), which contributes to activating NLRP3 inflammasome. Therefore, our findings suggest that, after sciatic nerve injury, CXCL12-CXCR4 axis may promote Schwann cell pyroptosis and sciatic nerve demyelination through activating NLRP3 inflammasome and slow the recovery process of the sciatic nerve.

Transcriptomic and functional analysis provides molecular insights into multicellular trichome development.

Trichomes, the hair-like structures located on aerial parts of most vascular plants, are associated with a wide array of biological processes and affect the economic value of certain species. The processes involved in unicellular trichome formation have been well-studied in Arabidopsis (Arabidopsis thaliana). However, our understanding of the morphological changes and the underlying molecular processes involved in multicellular trichome development is limited. Here, we studied the dynamic developmental processes involved in glandular and nonglandular multicellular trichome formation in cucumber (Cucumis sativus L.) and divided these processes into five sequential stages. To gain insights into the underlying mechanisms of multicellular trichome formation, we performed a time-course transcriptome analysis using RNA-sequencing analysis. A total of 711 multicellular trichome-related genes were screened and a model for multicellular trichome formation was developed. The transcriptome and co-expression datasets were validated by reverse transcription-quantitative PCR and in situ hybridization. In addition, virus-induced gene silencing analysis revealed that CsHOMEOBOX3 (CsHOX3) and CsbHLH1 are involved in nonglandular trichome elongation and glandular trichome formation, respectively, which corresponds with the transcriptome data. This study presents a transcriptome atlas that provides insights into the molecular processes involved in multicellular trichome formation in cucumber and can be an important resource for future functional studies.