NF-YC15 transcription factor activates ethylene biosynthesis and improves cassava disease resistance.

The nuclear factor Y (NF-Y) transcription factors play important roles in plant development and physiological responses. However, the relationship between NF-Y, plant hormone and plant stress resistance in tropical crops remains unclear. In this study, we identified MeNF-YC15 gene in the NF-Y family that significantly responded to Xanthomonas axonopodis pv. manihotis (Xam) treatment. Using MeNF-YC15-silenced and -overexpressed cassava plants, we elucidated that MeNF-YC15 positively regulated disease resistance to cassava bacterial blight (CBB). Notably, we illustrated MeNF-YC15 downstream genes and revealed the direct genetic relationship between MeNF-YC15 and 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase (MeACO1)-ethylene module in disease resistance, as evidenced by the rescued disease susceptibility of MeNF-YC15 silenced cassava plants with ethylene treatment or overexpressing MeACO1. In addition, the physical interaction between 2C-type protein phosphatase 1 (MePP2C1) and MeNF-YC15 inhibited the transcriptional activation of MeACO1 by MeNF-YC15. In summary, MePP2C1-MeNF-YC15 interaction modulates ethylene biosynthesis and cassava disease resistance, providing gene network for cassava genetic improvement.

Cassava phosphatase PP2C1 modulates thermotolerance via fine-tuning dephosphorylation of antioxidant enzymes.

Global warming is an adverse environmental factor that threatens crop yields and food security. 2C-type protein phosphatases (PP2Cs), as core protein phosphatase components, play important roles in plant hormone signaling to cope with various environmental stresses. However, the function and underlying mechanism of PP2Cs in the heat stress response remain elusive in tropical crops. Here, we report that MePP2C1 negatively regulated thermotolerance in cassava (Manihot esculenta Crantz), accompanied by the modulation of reactive oxygen species (ROS) accumulation and the underlying antioxidant enzyme activities of catalase (CAT) and ascorbate peroxidase (APX). Further investigation found that MePP2C1 directly interacted with and dephosphorylated MeCAT1 and MeAPX2 at serine (S) 112 and S160 residues, respectively. Moreover, in vitro and in vivo assays showed that protein phosphorylation of MeCAT1S112 and MeAPX2S160 was essential for their enzyme activities, and MePP2C1 negatively regulated thermotolerance and redox homeostasis by dephosphorylating MeCAT1S112 and MeAPX2S160. Taken together, this study illustrates the direct relationship between MePP2C1-mediated protein dephosphorylation of MeCAT1 and MeAPX2 and ROS accumulation in thermotolerance to provide insights for adapting to global warming via fine-tuning thermotolerance of the tropical crop cassava.

Fabrication and property evaluation of calcium-oxide-loaded microcapsules during supplemental heat-based exploitation of natural gas hydrates.

The exploitation of natural gas hydrates (NGHs) by traditional methods is far lower than the commercial target. Calcium oxide (CaO)-based in situ supplemental heat combined with depressurization is a novel method for effectively exploiting NGHs. In this study, we propose an in situ supplemental heat method with the sustained-release CaO-loaded microcapsules coated with polysaccharide film. The modified CaO-loaded microcapsules were coated with polysaccharide films using covalent layer-by-layer self-assembly and wet modification process, with (3-aminopropyl) trimethoxysilane as the coupling agent and modified cellulose and chitosan as the shell materials. Microstructural characterization and elemental analysis of the microcapsules verified the change in the surface composition during the fabrication process. We found that the overall particle size distribution was within the range of 1-100 µm, corresponding to the particle size distribution in the reservoir. Furthermore, the sustained-release microcapsules exhibit controllable exothermic behavior. The decomposition rates of the NGHs under the effect of CaO and CaO-loaded microcapsules coated with one and three layers of polysaccharide films were 36.2, 17.7, and 11.1 mmol h-1, respectively, while the exothermic time values were 0.16, 1.18, and 6.68 h, respectively. Finally, we propose an application method based on sustained-release CaO-loaded microcapsules used for the supplemental heat-based exploitation of NGHs.

UBE3D Is Involved in Blue Light-Induced Retinal Damage by Regulating Double-Strand Break Repair.

Purpose: Age-related macular degeneration (AMD) is currently the leading cause of blindness worldwide. Previously, we identified ubiquitin-protein ligase E3D (UBE3D) as an AMD-associated protein for East Asian populations, and here we further demonstrate that UBE3D could be associated with DNA damage response. Methods: The established I-SceI-inducible GFP reporter system was used to explore the effect of UBE3D on homologous recombination. Immunoprecipitation-mass spectrometry (MS) was used to explore potential UBE3D-interacting proteins and validated with coimmunoprecipitation assays and the pulldown assays. Micrococcal nuclease (MNase) assays were used to investigate the function of UBE3D on heterochromatin de-condensation upon DNA damage. An aged mouse model of blue light-induced eye damage was constructed, and electroretinography (ERG) and optical coherence tomography (OCT) were performed to compare the differences between wild-type and UBE3D+/- mice. Results: First, we show that GFP-UBE3D is recruited to damage sites by PCNA, through a PCNA-interacting protein (PIP) box. Furthermore, UBE3D interacts with KAP1 via R377R378 and oxidation of the AMD-associated V379M mutation abolishes KAP1-UBE3D binding. By MNase assays, UBE3D depletion reduces the chromatin relaxation levels upon DNA damage. In addition, UBE3D depletion renders less KAP1 recruitment. Compared with wild type, blue light induces less damage in UBE3D+/- mice as measured by ERG and OCT, consistent with our biochemical results. Conclusions: Hence, we propose that one potential mechanism that UBE3D-V379M contributes to AMD pathogenesis might be via defective DNA damage repair linked with oxidative stress and our results offered a potential direction for the treatment of AMD.

Molecular Simulation of Interactions between High-Molecular-Polymer Flocculation Gel for Oil-Based Drilling Fluid and Clay Minerals.

China has abundant shale gas resources with great potential, which may serve as a significant support for the development of a "low-carbon economy". Domestic shale gas resources are buried deeply and difficult to exploit due to some prevalent issues, such as long horizontal sections, severe development of reservoir fractures, strong sensitivity to water, borehole instability, etc. Compared to water-based drilling fluids, oil-based drilling fluid exhibits better inhibition and good lubricity and is thus broadly used in shale gas drilling, but it is confronted with the challenge of removing the harmful solid phase. Selective chemical flocculation is one of the most effective methods of removing the harmful solid phase in oil-based drilling fluid. In this study, interactions between the flocculation gel for oil-based drilling fluid and clay minerals were investigated by molecular simulation, which revealed the molecular-scale selectivity of the flocculation gel for rock cuttings with negative charges. Calculations showed that the flocculation gel is highly effective for the flocculation of negatively charged cuttings, but it is ineffective for flocculating neutral cuttings. The flocculation gel is not very effective for cuttings with high hydrophilicity, and it is totally ineffective for flocculating cuttings with poor hydrophilicity. Within a limited concentration range, the flocculation effect can be enhanced by increasing the flocculation gel concentration. The performance of the flocculation gel declined at elevated temperatures.

Current Understanding of Hydrogel for Drug Release and Tissue Engineering.

Due to their good absorption, satisfactory biocompatibility, and high safety, hydrogels have been widely used in the field of biomedicine, including for drug delivery and tissue regeneration. In this review, we introduce the characteristics and crosslinking methods of natural and synthetic hydrogels. Then, we highlight the design and principle of intelligent hydrogels (i.e., responsive hydrogels) used for drug release. Moreover, we introduce the application of the application of hydrogels in drug release and tissue engineering, and the limitations and research directions of hydrogel in drug release and tissue engineering are also considered. We hope that this review can provide a reference for follow-up studies in related fields.

PP2C1 fine-tunes melatonin biosynthesis and phytomelatonin receptor PMTR1 binding to melatonin in cassava.

Melatonin is an important molecule in both animals and plants, regulating circadian rhythms and stress responses. Therefore, the improvement of melatonin accumulation not only strengthens the function of melatonin but also improves stress resistance in crops. Although melatonin biosynthetic enzymes have been identified through reverse genetics previously, an investigation of melatonin level-related genes through forward genetics in plants has yet to be performed. In this study, a genome-wide association study using cassava natural population of 298 genetic resources identified melatonin accumulation 1 (MA1), which regulates the natural variation of melatonin levels in cassava. We found that MA1 encodes type 2C protein phosphatase 1 (PP2C1), which serves as a negative regulator of melatonin levels in cassava. MePP2C1 physically interacts with MeRAV1/2 and MeWRKY20 and dephosphorylates them at serine (S) 35 residue, S34 residue, and S176 residue, respectively, thereby hindering their transcriptional activation on downstream melatonin biosynthetic genes. Notably, MePP2C1 interacts with phytomelatonin receptor MePMTR1 and dephosphorylates it at S11 residue, repressing its binding to melatonin. In summary, this study demonstrates that MePP2C1 as MA1 plays dual roles in negatively regulating both melatonin accumulation and signaling, extending the understanding of the molecular mechanism underlying melatonin accumulation and signaling through forward genetics in plants.

LSD3 mediates the oxidative stress response through fine-tuning APX2 activity and the NF-YC15-GSTs module in cassava.

Reactive oxygen species (ROS) overproduction leads to oxidative damage under almost all stress conditions. Lesion-Simulating Disease (LSD), a zinc finger protein, is an important negative regulator of ROS accumulation and cell death in plants. However, the in vivo role of LSD in cassava (Manihot esculenta) and the underlying molecular mechanisms remain elusive. Here, we found that MeLSD3 is essential for the oxidative stress response in cassava. MeLSD3 physically interacted with ascorbate peroxidase 2 (MeAPX2), thereby promoting its enzymatic activity. In addition, MeLSD3 also interacted with the nuclear factor YC15 (MeNF-YC15), which also interacted with nuclear factor YA2/4 (MeNF-YA2/4) and nuclear factor YB18 (MeNF-YB18) to form an MeNF-YC15-MeNF-YA2/4-MeNF-YB18 complex. Notably, MeLSD3 positively modulated the transcriptional activation of the MeNF-YC15-MeNF-YA2/4-MeNF-YB18 complex by interacting with the CCAAT boxes of the promoters of glutathione S-transferases U37/U39 (MeGST-U37/U39), activating their transcription. When one or both of MeLSD3 and the MeNF-YC15-MeNF-YA2/4-MeNF-YB18 complex were co-silenced, cassava showed decreased oxidative stress resistance, while overexpression of MeGST-U37/U39 alleviated the oxidative stress-sensitive phenotype of these silenced plants. This study illustrates the dual roles of MeLSD3 in promoting MeAPX2 activity and MeNF-YC15-MeGST-U37/U39 regulation, which underlie the oxidative stress response in cassava.

Phytomelatonin as a central molecule in plant disease resistance.

Melatonin is an essential phytohormone in the regulation of many plant processes, including during plant development and in response to stress. Pathogen infections cause serious damage to plants and reduce agricultural production. Recent studies indicate that melatonin plays important roles in alleviating bacterial, fungal, and viral diseases in plants and post-harvest fruits. Herein, we summarize information related to the effects of melatonin on plant disease resistance. Melatonin, reactive oxygen species, and reactive nitrogen species form a complex loop in plant-pathogen interaction to regulate plant disease resistance. Moreover, crosstalk of melatonin with other phytohormones including salicylic acid, jasmonic acid, auxin, and abscisic acid further activates plant defense genes. Melatonin plays an important role not only in plant immunity but also in alleviating pathogenicity. We also summarize the known processes by which melatonin mediates pathogenicity via negatively regulating the expression levels of genes related to cell viability as well as virulence-related genes. The multiple mechanisms underlying melatonin influences on both plant immunity and pathogenicity support the recognition of the essential nature of melatonin in plant-pathogen interactions, highlighting phytomelatonin as a critical molecule in plant immune responses.

Asthma Promotes Choroidal Neovascularization via the Transforming Growth Factor Beta1/Smad Signalling Pathway in a Mouse Model.

INTRODUCTION: The association between age-related macular degeneration and asthma is controversial. Transforming growth factor beta (TGF-ß), which plays a critical role in asthma, has been extensively studied with regard to its function in choroidal neovascularization (CNV). In the present study, we aimed to investigate the role of TGF-ß and the possible mechanism of CNV formation complicated with asthma and to explore the effect of a TGF-ß inhibitor on CNV development in asthma mouse models. METHODS: Laser-induced CNV and ovalbumin-induced asthma mouse models were divided into 5 groups: control group, acute asthma group, chronic asthma group, inhibitor-treated acute asthma group, and inhibitor-treated chronic asthma group. The gene expression patterns of angiogenic cytokines, vascular endothelial growth factor (VEGF) receptors and inflammasomes in the control group, acute asthma group, and chronic asthma group were detected using a QuantiGene Plex 6.0 Reagent System. Fundus fluorescein angiography and histology of CNV lesions stained with haematoxylin-eosin were performed to evaluate CNV formation. Quantitative real-time PCR and western blotting were used to assess TGF-ß1, TGF-ß2, and VEGF expression and Smad2/3, AKT, p38 MAPK, and ERK1/2 signal transduction and phosphorylation in retinal and choroidal tissues from each group. RESULTS: In this study, we verified that laser treatment led to more CNV and vascular leakage in asthmatic mice than that in control mice. The changes were particularly notable in the chronic asthma group. The respective TGF-ß1, VEGF, and phosphorylated Smad2/3 (p-Smad2/3) mRNA and protein levels in retinal and choroidal tissues were significantly upregulated in both the acute and chronic asthma groups. After injection of a TGF-ß inhibitor, a distinct decline in VEGF, TGF-ß1, and p-Smad2/3 protein and mRNA levels was observed, and the mean CNV area also decreased. CONCLUSION: We provide new evidence that asthma could be a risk factor for CNV development via the TGF-ß1/Smad signalling pathway. A TGF-ß inhibitor can be applied as a useful, adjunctive therapeutic strategy for preventing CNV formation in asthmatic patients.

Fine-tuning of pathogenesis-related protein 1 (PR1) activity by the melatonin biosynthetic enzyme ASMT2 in defense response to cassava bacterial blight.

Melatonin is widely involved in plant disease resistance through modulation of immune responses. Pathogenesis-related (PR) proteins play important roles in plant immune responses. However, the direct association between melatonin biosynthetic enzyme and PR protein remains elusive in plants. In this study, we found that N-acetylserotonin O-methyltransferase 2 (MeASMT2) physically interacted with MePR1 in vitro and in vivo, thereby promoting the anti-bacterial activity of MePR1 against Xanthomonas axonopodis pv. manihotis (Xam). Consistently, MeASMT2 improved the effect of MePR1 on positively regulating cassava disease resistance. In addition, we found that type 2C protein phosphatase 1 (MePP2C1) interacted with MeASMT2 to interfere with MePR1-MeASMT2 interaction, so as to inhibiting the effect of MeASMT2 and MePR1 on positively regulating cassava disease resistance. In contrast to the increased transcripts of MeASMT2 and MePR1 in response to Xam infection, the transcript of MePP2C1 was decreased upon Xam infection. Therefore, disease activated MeASMT2 was released from disease inhibited MePP2C1, so as to improving the anti-bacterial activity of MePR1, resulting in improved immune response. In summary, this study illustrates the dynamic modulation of the MePP2C1-MeASMT2-MePR1 module on cassava defense response against cassava bacterial blight (CBB), extending the understanding of the correlation between melatonin biosynthetic enzyme and PR in plants.

Phosphorylation of RAV1/2 by KIN10 is essential for transcriptional activation of CAT6/7, which underlies oxidative stress response in cassava.

Related to ABI3/VP1 (RAV) transcription factors have important roles in plant stress responses; however, it is unclear whether RAVs regulates oxidative stress response in cassava (Manihot esculenta). In this study, we report that MeRAV1/2 positively regulate oxidative stress resistance and catalase (CAT) activity in cassava. Consistently, RNA sequencing (RNA-seq) identifies three MeCATs that are differentially expressed in MeRAV1/2-silenced cassava leaves. Interestingly, MeCAT6 and MeCAT7 are identified as direct transcriptional targets of MeRAV1/2 via binding to their promoters. In addition, protein kinase MeKIN10 directly interacts with MeRAV1/2 to phosphorylate them at Ser45 and Ser44 residues, respectively, to promote their direct transcriptional activation on MeCAT6 and MeCAT7. Site mutation of MeRAV1S45A or MeRAV2S44A has no significant effect on the activities of MeCAT6 and MeCAT7 promoters or on oxidative stress resistance. In summary, this study demonstrates that the phosphorylation of MeRAV1/2 by MeKIN10 is essential for its direct transcriptional activation of MeCAT6/7 in response to oxidative stress.

MeRAV5 promotes drought stress resistance in cassava by modulating hydrogen peroxide and lignin accumulation.

Cassava, an important food and energy crop, is relatively more resistant to drought stress than other crops. However, the molecular mechanism underlying this resistance remains elusive. Herein, we report that silencing a drought stress-responsive transcription factor MeRAV5 significantly reduced drought stress resistance, with higher levels of hydrogen peroxide (H2 O2 ) and less lignin during drought stress. Yeast two-hybrid, pull down and bimolecular fluorescence complementation (BiFC) showed that MeRAV5 physically interacted with peroxidase (MePOD) and lignin-related cinnamyl alcohol dehydrogenase 15 (MeCAD15) in vitro and in vivo. MeRAV5 promoted the activities of both MePOD and MeCAD15 to affect H2 O2 and endogenous lignin accumulation respectively, which are important in drought stress resistance in cassava. When either MeCAD15 or MeRAV5 was silenced, or both were co-silenced, cassava showed lower lignin content and drought-sensitive phenotype, whereas exogenous lignin alkali treatment increased drought stress resistance and alleviated the drought-sensitive phenotype of these silenced cassava plants. This study documents that the modulation of H2 O2 and lignin by MeRAV5 is essential for drought stress resistance in cassava.

Lighting the way: advances in transcriptional regulation and integrative crosstalk of melatonin biosynthetic enzymes in cassava.

The role of melatonin biosynthetic enzymes has been well studied. However, the transcriptional regulation of melatonin biosynthetic enzymes and their integrative crosstalk with other signaling pathways remain elusive. Here, we summarize recent progress in the functional analysis of melatonin biosynthetic enzymes and the major sites of melatonin synthesis in plants. We focus on the dual roles of melatonin biosynthetic enzymes in melatonin biosynthesis and in the crosstalk between melatonin and autophagy, antioxidant signaling, and stress responses in cassava. We highlight the transcriptional regulation and integrative protein complex of melatonin biosynthetic enzymes, and then raise the challenge of uncovering their precise regulation and crosstalk.

The dual interplay of RAV5 in activating nitrate reductases and repressing catalase activity to improve disease resistance in cassava.

Cassava bacterial blight (CBB) caused by Xanthomonas axonopodis pv. manihotis (Xam) seriously affects cassava yield. Nitrate reductase (NR) plays an important role in plant nitrogen metabolism in plants. However, the in vivo role of NR and the corresponding signalling pathway remain unclear in cassava. In this study, we isolated MeNR1/2 and revealed their novel upstream transcription factor MeRAV5. We also identified MeCatalase1 (MeCAT1) as the interacting protein of MeRAV5. In addition, we investigated the role of MeCatalase1 and MeRAV5-MeNR1/2 module in cassava defence response. MeNRs positively regulates cassava disease resistance against CBB through modulation of nitric oxide (NO) and extensive transcriptional reprogramming especially in mitogen-activated protein kinase (MAPK) signalling. Notably, MeRAV5 positively regulates cassava disease resistance through the coordination of NO and hydrogen peroxide (H2 O2 ) level. On the one hand, MeRAV5 directly activates the transcripts of MeNRs and NO level by binding to CAACA motif in the promoters of MeNRs. On the other hand, MeRAV5 interacts with MeCAT1 to inhibit its activity, so as to negatively regulate endogenous H2 O2 level. This study highlights the precise coordination of NR activity and CAT activity by MeRAV5 through directly activating MeNRs and interacting with MeCAT1 in plant immunity.

Simultaneous Diagnosis of Severity and Features of Diabetic Retinopathy in Fundus Photography Using Deep Learning.

Deep learning methods for diabetic retinopathy (DR) diagnosis are usually criticized as being lack of interpretability in the diagnostic result, thus limiting their application in clinic. Simultaneous prediction of DR related features during the DR severity diagnosis is able to resolve this issue by providing supporting evidence (i.e. DR related features) for the diagnostic result (i.e. DR severity). In this study, we propose a hierarchical multi-task deep learning framework for simultaneous diagnosis of DR severity and DR related features in fundus images. A hierarchical structure is introduced to incorporate the casual relationship between DR related features and DR severity levels. In the experiments, the proposed approach was evaluated on two independent testing sets using quadratic weighted Cohen's kappa coefficient, receiver operating characteristic analysis, and precision-recall analysis. A grader study was also conducted to compare the performance of the proposed approach with those of general ophthalmologists with different levels of experience. The results demonstrate that the proposed approach could improve the performance for both DR severity diagnosis and DR related feature detection when comparing with the traditional deep learning-based methods. It achieves performance close to general ophthalmologists with five years of experience when diagnosing DR severity levels, and general ophthalmologists with ten years of experience for referable DR detection.

CAMTA3 negatively regulates disease resistance through modulating immune response and extensive transcriptional reprogramming in cassava.

As one of the important crops in the world, cassava production is seriously threatened by Xanthomonas axonopodis pv. manihotis (Xam) all year round. Calmodulin-binding transcription activators (CAMTAs) play key roles in biotic stress and abiotic stress in plants, however, their roles in cassava remain elusive. In this study, six MeCAMTAs were identified, and MeCAMTA3 with the highest induction upon Xam infection was confirmed as a transcription factor that binds to the vCGCGb motif. MeCAMTA3 negatively regulates plant disease resistance against Xam. On the one hand, MeCAMTA3 negatively regulated endogenous salicylic acid and reactive oxygen species accumulation, pathogenesis-related genes MePRs' transcripts and callose deposition during cassava-Xam interaction but not under control conditions. On the other hand, RNA sequencing showed extensive transcriptional reprogramming by MeCAMTA3, especially 18 genes with a vCGCGb motif in the promoter region in hormone signaling, antioxidant signaling and other disease resistance signaling. Notably, chromatin immunoprecipitation-polymerase chain reaction showed that eight of these genes might be directly regulated by MeCAMTA3 through transcriptional repression. In summary, MeCAMTA3 negatively regulates plant disease resistance against cassava bacterial blight through modulation of multiple immune responses during cassava-Xam interaction and extensive transcriptional reprogramming.

Melatonin synthesis enzymes interact with ascorbate peroxidase to protect against oxidative stress in cassava.

Melatonin is an important indole amine hormone in animals and plants. The enzymes that catalyse melatonin synthesis positively regulate plant stress responses through modulation of the accumulation of reactive oxygen species (ROS). However, the relationship between melatonin biosynthetic enzymes and ROS-scavenging enzymes has not been characterized. In this study, we demonstrate that two enzymes of the melatonin synthesis pathway in Manihot esculenta (MeTDC2 and MeASMT2) directly interact with ascorbate peroxidase (MeAPX2) in both in vitro and in vivo experiments. Notably, in the presence of MeTDC2 and MeASMT2, MeAPX2 showed significantly higher activity and antioxidant capacity than the purified MeAPX2 protein alone. These findings indicate that MeTDC2-MeAPX2 and MeASMT2-MeAPX2 interactions both activate APX activity and increase antioxidant capacity. In addition, the combination of MeTDC2, MeASMT2, and MeAPX2 conferred improved resistance to hydrogen peroxide in Escherichia coli. Moreover, this combination also positively regulates oxidative stress tolerance in cassava. Taken together, these findings not only reveal a direct interaction between MeTDC2, MeASMT2, and MeAPX2, but also highlight the importance of this interaction in regulating redox homoeostasis and stress tolerance in cassava.

Gelsemine, a natural alkaloid extracted from Gelsemium elegans Benth. alleviates neuroinflammation and cognitive impairments in Aß oligomer-treated mice.

INTRODUCTION: Gelsemine is a natural alkaloid extracted from Gelsemium elegans Benth., a traditional Chinese medicinal herb. Gelsemine has been shown to penetrate the brain, and could produce neurological activities, such as anxiolytic and neuralgia-alleviating effects, suggesting that this natural compound might be used for treating nervous system diseases. RESULTS: In this study, we have found, for the first time, that gelsemine at low concentrations (5-10 µg/kg) significantly alleviated cognitive impairments induced by ß-amyloid (Aß) oligomer, a main neurotoxin of Alzheimer's disease (AD). In addition, gelsemine substantially prevented Aß oligomer-induced over-activation of microglia and astrocytes, indicating that gelsemine might reduce AD-related gliosis. Consistently, gelsemine inhibited the over-expression of pro-inflammatory cytokines, including interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in the brain of mice. Moreover, gelsemine largely increased the expression of pSer9-glycogen synthase kinase-3ß (GSK3ß), and decreased the hyper-phosphorylation of tau protein as evidenced by Western blotting analysis. Furthermore, gelsemine prevented Aß oligomer-induced reduction of PSD-95, a representative post-synaptic protein. CONCLUSION: All these results directly demonstrated the anti-Aß oligomer neuroprotective properties of gelsemine, opening a novel perspective for the development of gelsemine-based therapeutics against Aß-associated neurodegeneration disorders, including AD in particular.

The dual roles of melatonin biosynthesis enzymes in the coordination of melatonin biosynthesis and autophagy in cassava.

Both autophagy and melatonin play important roles in plant development and stress response. However, the direct correlation between autophagy and melatonin as well as the underlying mechanism remains elusive in plants. In this study, we discovered that the expression of three autophagy-associated genes (MeATG8b, 8c, and 8e) and autophagic activity were induced by exogenous melatonin treatment in cassava. In addition, three melatonin biosynthesis enzymes (tryptophan decarboxylase 2 (MeTDC2), N-aceylserotonin O-methyltransferase 2 (MeASMT2), and MeASMT3) positively regulate endogenous melatonin level and autophagic activity. Further investigation showed that these melatonin biosynthesis enzymes interacted with MeATG8b/8c/8e in vivo and in vitro. Consistently, MeTDC2, MeASMT2, and MeASMT3 also positively regulate endogenous melatonin level and autophagic activity in cassava. Notably, overexpression of MeATG8b, 8c, and 8e facilitated the protein expression level of MeTDC2, MeASMT2, and MeASMT3 in vivo. Taken together, melatonin synthesis enzymes (MeTDC2, MeASMT2/3) interact with MeATG8b/8c/8e and thus coordinate the dynamics of melatonin biosynthesis and autophagic activity in cassava, highlighting the links between melatonin biosynthesis and autophagic activity in cassava.