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Parkinson's disease (PD) is a neurological disorder. Recently, celastrol (Cel) has been reported to have neuroprotective properties. We investigated the protective effects of Cel on PD in a cell model with 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in PC12 cells and further addressed the underlying protective mechanisms of Cel.PC12 cells were treated with 6-OHDA, and Cel was added to the medium at various concentrations. The CCK-8 assay, Hoechst/PI staining, and flow cytometry analysis were performed to detect cellular viability and apoptosis. Mitochondrial membrane potential (MMP) was examined by JC-1 staining. ROS level was quantified by ROS staining. The effects of Cel on the expression of miR-146a and PI3K/Akt/mTOR pathway were then clarified using real-time PCR and Western blotting. Moreover, a miR-146a mimic was synthesized and transfected into PC12 cells to further determine the mechanisms of Cel's neuronal protection against 6-OHDA-induced neurotoxicity.Cel greatly improved cell viability and lessened apoptosis. Flow cytometry showed that Cel especially inhibited early apoptosis. Cel also obviously restored the MMP and decreased ROS level destroyed by 6-OHDA. Moreover, 6-OHDA increased the expression of miR-146a and decreased pAkt/mTOR protein levels, whereas Cel reversed these changes. In particular, miR-146a targeted and inhibited the expression of PI3K, an upstream molecule of Akt/mTOR. Transfection of 6-OHDA-treated neurons with miR-146a mimic notably attenuated Cel's protective effects.There were no animal experiments in our study.Cel exerts neuroprotective activity against 6-OHDA-caused neurotoxicity by regulating miR-146a/PI3K/Akt/mTOR pathway, which provides a potential application of Cel for treating neurodegenerative diseases.

Tobacco has a strong cadmium (Cd) enrichment capacity, meaning that it can absorb large quantities from the environment, but too much Cd will cause damage to the plant. It is not yet clear how the plant can dynamically respond to Cd stress. Here, we performed a temporal transcriptome analysis of tobacco roots under Cd treatment from 0 to 48 h. The number of differentially expressed genes (DEGs) was found to change significantly at 3 h of Cd treatment, which we used to define the early and middle stages of the Cd stress response. The gene ontology (GO) term analysis indicates that genes related to photosynthesis and fatty acid synthesis were enriched during the early phases of the stress response, and in the middle phase biological process related to metal ion transport, DNA damage repair, and metabolism were enriched. It was also found that plants use precursor mRNA (pre-mRNA) processes to first resist Cd stress, and with the increasing of Cd treatment time, the overlapped genes number of DEGs and DAS increased, suggesting the transcriptional levels and post-transcriptional level might influence each other. This study allowed us to better understand how plants dynamically respond to cadmium stress at the transcriptional and post-transcriptional levels and provided a reference for the screening of Cd-tolerant genes in the future.

With the rapid development of sequencing technology, scientists have been able to study and acquire a better understanding of non-coding RNAs (ncRNAs). Circular RNAs (circRNAs), a unique class of ncRNAs with a special loop structure, have been found to possess modulatory properties with respect to various biological processes, such as interacting with nucleic acids or proteins. In addition to their tissue-specific expression and high conservation across species, circRNAs are abundant and dynamically expressed in the nervous system, especially in nerve synapse, indicating their potential regulation in synaptic plasticity or neuronal disorders. In this review, we discuss the characteristics of circRNAs and their common biological functions, as well as their significant role in neurodevelopment, drug addiction and neurodegenerative diseases, aiming to guide further disease diagnoses and efficient therapy.

The pectin methylesterases (PMEs) play multiple roles in regulating plant development and responses to various stresses. In our study, a total of 121 PME genes were identified in the tobacco genome, which were clustered into two groups based on phylogenetic analysis together with Arabidopsis members. The investigations of gene structure and conserved motif indicated that exon/intron and motif organizations were relatively conserved in each group. Additionally, several stress-related elements were identified in the promoter region of these genes. The survey of duplication events revealed that segmental duplications were critical to the expansion of the PME gene family in tobacco. The expression profiles analysis revealed that these genes were expressed in various tissues and could be induced by diverse abiotic stresses. Notably, NtPME029 and NtPME043, were identified as homologues with AtPME3 and AtPME31, respectively. Furthermore, NtPME029 was highly expressed in roots and the over-expression of the NtPME029 gene could promote the development of roots. While NtPME043 could be induced by salt and ABA treatments, and the over-expression of the NtPME043 gene could significantly enhance the salt-stress tolerance in tobacco. Overall, these findings may shed light on the biological and functional characterization of NtPME genes in tobacco.

The brain circuit projecting from the ventral tegmental area (VTA) to the lateral shell nucleus accumbens (NAcLat) has a key role in methamphetamine (MA) addiction. As different VTA dopamine (DA) neuronal subpopulations participate in different neuronal circuits, it is still a challenge to isolate these DA subtype cells. Using retrograde tracing, Patch-seq in MA-addicted mice, we isolated the DA neurons of the VTA-NAcLat circuit and profiled its gene expression. We found that in this circuit the KCNQ3 (Kv7.3) gene, encoding K+ channel protein, was among the differentially expressed genes. Injection of the Kv7.3 channels agonist ICA069673 or overexpression of Kv7.3 channels in the VTA-NacLat circuit could reverse MA addiction. Furthermore, enhancement of Kv7.3 channels activity decreased neural oscillation, neuronal excitability, synaptic plasticity and DA release in the VTA-NacLat circuit of MA-addicted mice. Activation of Kv7.3 channels in the VTA may become a potential novel treatment strategy for MA addiction.

Recently, the role of the gut microbiota in the context of drug addiction has attracted the attention of researchers; however, the specific effects and underlying mechanisms require further exploration. To accomplish this, C57BL/6 mice were firstly treated with methamphetamine (MA). Conditioned place preference (CPP) behavior changes, gut permeability and function, microglial activation, and inflammatory cytokine expression were systematically analyzed in antibiotics-treated mice with microbiota depletion and in fecal microbiota transplantation mice with microbiota reconstitution. MA treatment altered microbiota composition and caused gut dysbiosis. Depletion of gut microbiota with antibiotics inhibited MA-induced CPP formation, and fecal microbiota transplantation reversed this inhibition. Mechanistic analyses indicated that antibiotic treatment decreased gut permeability and neuroinflammation, while fecal microbiota transplantation offset the impact of antibiotic treatment. Additionally, MA-induced microglial activation was suppressed by antibiotics but restored by microbiota transplantation, and this correlated well with the CPP score. Compared to antibiotic treatment, microbiota transplantation significantly increased 5-HT4 receptor expression in both the nucleus accumbens and the hippocampus. Furthermore, when fecal microbiota from healthy mice was transplanted into MA-treated mice, the CPP scores decreased. Our results provide a novel avenue for understanding MA addiction and suggest a potential future intervention strategy.

Repeated administration of methylamphetamine (MA) induces MA addiction, which is featured by awfully unpleasant physical and emotional experiences after drug use is terminated. Neurophysiological studies show that the lateral hypothalamus (LH) is involved in reward development and addictive behaviors. Here, we show that repeated administration of MA activates the expression of c-Fos in LH neurons responding to conditioned place preference (CPP). Chemogenetic inhibition of the LH can disrupt the addiction behavior, demonstrating that the LH plays an important role in MA-induced reward processing. Critically, MA remodels the neurons of LH synaptic plasticity, increases intracellular calcium level, and enhances spontaneous current and evoked potentials of neurons compared to the saline group. Furthermore, overexpression of the potassium voltage-gated channel subfamily Q member 3 (Kcnq3) expression can reverse the CPP score and alleviate the occurrence of addictive behaviors. Together, these results unravel a new neurobiological mechanism underlying the MA-induced addiction in the lateral hypothalamus, which could pave the way toward new and effective interventions for this addiction disease.

The putative mechanisms underlying the efficacy of the US Food and Drug Administration-approved antipsychotic drug paliperidone for the treatment of schizophrenia deserve additional investigation, which is the aim of the present animal study.The behavioral activities of mice were recorded in the open field test and light-dark box test. The effects of paliperidone on MK-801-induced neuronal damage in the prefrontal cortex were tested by flow cytometry, TUNEL staining assays, and ROS staining assays. The neuroprotective effects of paliperidone on neural dendrites and synapses were evaluated using Golgi staining and Sholl analysis. An adenovirus vector containing a CaThe data showed that MK-801 caused stereotyped behavior in mice and induced synaptic damage and dendritic spine impairment compared with the control, whereas paliperidone ameliorated these changes. Moreover, paliperidone reversed MK-801-induced decreases in PP2A and PTEN levels in prefrontal cortical neurons. Furthermore, in primary cultured cortical neurons and HT-22 cells, paliperidone inhibited cell apoptosis caused by MK-801. In particular, pretreatment with the PP2A inhibitor LB-100 significantly restrained the protective effects of paliperidone on MK-801-treated neurons and on locomotor activity and stereotypical behavior of mice.Whether other proteins are involved in this pathway and how the pathway works have not been revealed.Our data show that paliperidone alleviates neuronal damage induced by MK-801 via the PP2A/PTEN pathway.

Drug memory is associated with drug-taking experience and environmental cues, which mainly contribute to addiction. Recent studies report that glycogenolysis-derived lactate from astrocyte transport to neurons is necessary for long-term potentiation and memory formation instead of its function as an energy substrate. However, the role of astrocyte-neuron lactate transfer in neuronal plasticity and methamphetamine (METH)-induced addiction memory consolidation and retrieval, especially the underlying mechanisms, are not clear. C57BL/6 J mice trained for METH-induced conditioned place preference (CPP) were stereotaxically injected with the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) into the dorsal hippocampus (dHPC) 15 min before training. The CPP score was recorded, and neuronal synaptic plasticity was detected with Golgi staining. The neuronal Ca

The NAC (NAM, ATAF1/2, and CUC2) family acts as one of the largest families of the transcription factor in the plant kingdom and was revealed to function as the important regulators in various environmental stresses. However, a few studies were reported about the biofunctions of the NAC transcription factor in tobacco. In the current study, we characterized a novel NAC transcription factor encoding the gene NtNAC053 in tobacco, which was significantly up-regulated when exposed to salt and drought treatments. The results of cis-acting elements analysis suggested that the promoter region of NtNAC053 gene possesses a number of stress-responsive elements, and this gene could be induced by exogenous abscisic acid (ABA) treatment. Moreover, the NtNAC053–GFP fusion protein was localized in the cell nucleus and possessed a transactivation domain in its C-terminal, implying that NtNAC053 may undertake as a transcriptional activator in tobacco. Notably, the overexpression of NtNAC053 in tobacco resulted in hypersensitivity to ABA treatment. Furthermore, these overexpression lines showed significantly enhanced tolerances to drought and salt stresses. Under salt and drought stresses, these overexpression lines possessed higher superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities. Interestingly, the expressions of putative stress-related genes, including NtCOR15A, NtRAB18, NtDREB1A, NtERF5, NtKAT2, and NtERD11, were up-regulated in these overexpression lines when subjected to salt and drought stresses. The clues provided in our study suggested that the NtNAC053 gene encodes a novel NAC transcription factor and could confer the drought and salt stress tolerances by inspiring the downstream stress-responsive genes and antioxidant system in tobacco.

Although there are several diagnostic modalities for tuberculous pleurisy, there is still a lack of easy, cost-effective, and rapid methods for confirming the diagnosis. In order to facilitate clinicians to diagnose patients with tuberculous pleurisy at an early stage, help patients to obtain treatment early, and reduce lung damage, it is hoped that new techniques will be available in the future to help diagnose tuberculous pleurisy rapidly in the clinic. To this end, this paper investigates the problem of bidirectional consistency based on event-triggered iterative learning. Firstly, a dynamic linearized data model of TB pleurisy intelligent system is established using compact-form dynamic linearization method, and a parameter estimation algorithm of TB pleurisy data model is proposed; then, based on this data model, an output observer and a dead zone controller are designed, and an event-triggered distributed model-free iterative learning bidirectional consistency control strategy is constructed by combining with signal graph theory. In this paper, 112 patients with pleural effusion were collected, including 76 patients with confirmed or clinically diagnosed tuberculous pleural effusion and 36 patients with nontuberculous pleural effusion. Pleural effusion T-SPOT.TB, blood T-SPOT.TB, pleural effusion Xpert MTB/RIF, and pleural effusion adenosine deaminase (ADA) tests were performed before treatment in the included patients. The sensitivity of pleural effusion T-SPOT.TB was higher than that of peripheral blood T-SPOT.TB (76.32%, 58/76), pleural effusion Xpert MTB/RIF (65.79%, 50/76), and pleural effusion ADA (28.95%, 22/76); the differences were statistically significant (x2 = 14.74, 25.22, and 76.45, P

Two kinds of hydrophobic coatings on ZE41A magnesium alloy are successfully synthesized using hydrothermal method. The surface morphologies, wettability and anti-corrosion properties of hydrophobic coatings are investigated by the method of scanning electron microscopy, X-ray diffraction and electrochemical corrosion tests. Results show that the sample treated in stearic acid ethanol solution with addition of NiSO4 exhibits a morphology possessing large numbers of fine flower-like micro/nano structures, which results in better hydrophobicity and better corrosion resistance.

Intelligent perception network, suitable for the interconnection and integration of material distribution information equipment in product assembly workshops, information sharing between equipment, and data interaction between equipment and servers. The areas involved include automated material distribution, integrated logistics operation management and control, digital measurement and intelligent control. This article first describes the proposed intelligent perception network and the existing material distribution methods, analyzes the realization of intelligent perception networks of different architectures, and then proposes a set of material distribution methods for the particularity of logistics distribution in the aviation workshop. The method is driven by the process flow, and conducts dynamic and refined management of the entire process of material storage, storage, transfer, and inventory, and real-time monitoring of the type, quantity, and status of materials through intelligent terminal equipment, handheld terminals and NFC communication equipment, Storage location and other specific information; secondly, with the goal of minimizing delivery time and delivery cost, according to the material requirements of each station of the production line, the convolutional neural network method is used to design the optimal material distribution plan. Finally, build a software and hardware platform and realize the operation of the convolutional neural network on embedded devices to complete the entire workshop material distribution process.

Alzheimer's disease (AD) is a common neurodegenerative disease that accounts for approximately 70% of dementia. Following the global escalation of the aging process, the morbidity of AD is increasing rapidly. The current treatment for AD is mainly limited to medications, such as acetylcholinesterase inhibitors. However, the efficacy of acetylcholinesterase inhibitors in improving memory and cognitive functions is not satisfactory. It is a challenge to find an effective alternative therapy for ameliorating AD symptoms. As an important therapeutic technique in traditional Chinese medicine, acupuncture has been proved effective in treating many neurologic diseases including AD. The efficacy of acupuncture is also acknowledged by the National Institutes of Health of the United States. Here, we summarized the effectiveness of acupuncture for treating AD. Especially, the role of acupuncture at certain acupuncture points in modulating the brain function through meridians activity based on Chinese meridian theory is discussed. How acupuncture at a certain acupoint can improve AD symptoms is also described. Furthermore, the possible molecular mechanisms of acupuncture for AD are reviewed, and the role of acupuncture in modulating signaling molecules in neural protection and homeostasis is highlighted. This study may help to understand the theoretical basis and potential molecular mechanisms of acupuncture therapy for AD.针灸治疗阿尔茨海默病:有效性和潜在的分子机制 摘要 阿尔茨海默病是一种常见的老年神经系统退行性疾病，占据约70%的痴呆患者。随着全球老龄化进程的加剧，阿尔茨海默病的发病率迅速增长。目前的阿尔茨海默病的治疗局限于部分药物，例如乙酰胆碱酯酶抑制剂等，然而这些药物在改善记忆和认知功能的效果并不令人满意。因此，寻找能延缓或减轻阿尔茨海默病症状的有效治疗方法是一大挑战。针灸治疗，是传统中医药的一项重要治疗技术，已证实在包括阿尔茨海默病在内的多种神经源性疾病中有显著疗效。在此，我们将总结针灸治疗阿尔茨海默病的临床效果。尤其从中医经络理论的角度，总结针灸穴位的选穴理论基础。以及在临床实践中，针灸这些穴位如何改善阿尔茨海默病的症状，并且，本文还综述了针灸治疗阿尔茨海默病的分子机制，阐述针灸相应穴位后在降低β-淀粉样蛋白聚积，tau蛋白磷酸化以及减轻神经炎症和细胞凋亡等过程中相关的分子通路。本文将帮助我们理解针灸治疗阿尔茨海默病的中医理论基础和潜在的分子机制。.

The bZIP proteins comprise one of the largest transcription factor families and play important roles in plant growth and development, senescence, metabolic reactions, and stress responses. In this study, 49 bZIP transcription factor-encoding genes (StbZIP genes) on the potato genome were identified and analyzed. The 49 StbZIP genes, which are located on 12 chromosomes of the potato genome, were divided into 11 subgroups together with their Arabidopsis homologs based on the results of phylogenetic analysis. Gene structure and protein motif analysis revealed that members from the same subgroup often possessed similar exon/intron structures and motif organizations, further supporting the results of the phylogenetic analysis. Syntenic analysis indicated the existence of gene duplication events, which might play an important role in the expansion of the bZIP gene family in potato. Expressions of the StbZIP genes were analyzed in a variety of tissues via RNA-Seq data, suggesting functional diversity. Several StbZIP genes were found to be induced by different stress conditions. For example, the expression of StbZIP25, the close homolog of AtbZIP36/ABF2, was significantly upregulated by salt stress treatments. The StbZIP25 protein was found to be located in the nucleus and function as a transcriptional activator. Overexpression of StbZIP25 enhanced salt tolerance in Arabidopsis. The results from this study imply potential roles of the bZIP family genes in the stress response of potato.

For semi-crystalline material such as poly(lactic acid) (PLA), it is not easy to accelerate its crystallization, let alone to improve the flame retardancy and mechanical properties meanwhile. In this paper, a furan-phosphamide derivative (POCFA) was synthesized using furfurylamine (FA) and phosphorus oxychloride (POC). The POCFA was used as a flame retardant and nucleating agent in PLA. The flame retardancy and thermal stability of PLA/POCFA composites were investigated by the limited oxygen index (LOI), UL-94 vertical burning tests, cone calorimeter tests, and thermal gravity analysis (TGA). A small 2 wt% loading of POCFA increases the LOI of PLA from 19.4 vol% to 29.6 vol% and achieves the UL-94 V0 rating. The POCFA decreases the amount of flammable gaseous compounds and increases the condensed components resulting in positive effect on transesterification, crosslinking and char formation of PLA chains. Moreover, the POCFA improves the crystallization rate and crystallinity of PLA indicating it is a good nucleation agent. In addition, the tensile strength of the PLA/POCFA composites is also improved.

Methamphetamine (METH) has been a worldwide health threat for years. Recent studies have reported that circular RNA (circRNA) are highly abundant and dynamically expressed in brain. However, connections between circRNA and METH-induced neurotoxicity remains indefinite. In the present study, primary cortical neurons were treated with METH in vitro. We profiled circRNA via high-throughput RNA sequencing and identified 2458 circRNAs. Bioinformatics analysis was performed to predict potential functions of these circRNAs which revealed several relevant pathways including 'morphine addiction' that may contribute to the pathogenesis of neuronal damage by METH. Especially, a METH-addicted mouse model was established with conditional place preference paradigm for validation of screened circRNAs. At last, we established co-expression networks of circRNAs with miRNAs and mRNAs to exhibit potential association among them. In conclusion, we firstly unveiled a role of circRNAs in METH-induced neuronal damage and METH addiction.

With the continuous improvement of hardware product performance and data processing capability and the rapid development of network communication technology, the intelligent technology of computer systems is becoming more and more mature, and the intelligence of manufacturing has become the focus of people's attention. The intelligent performance of manufacturing is to use the knowledge obtained from data analysis to make inferences and decisions to solve problems, and the Cyber-Physical System (CPS) supports the deep integration of informationization and industrialization by integrating advanced information technology and automatic control technology, such as perception, computation, communication, control, etc. Although there has been great progress in the research of CPS, it has been widely used in the development of computer systems. Despite significant progress in CPS research, some key issues have yet to be fully addressed at the shop floor level, including dynamic reorganization and local intelligence. These issues have hindered the research on the intelligence of complex processes. For progress units of complex processes, this study proposes a CPS-based smart progress unit (SPU) construction method. In order to improve machining efficiency and quality consistency, this study proposes a multi-source data acquisition technique and a multi-objective optimization algorithm to process the data within the machining unit. Finally, this study takes the paddle boring process as an example, and designs hardware and software systems to automate the paddle boring process and meet the needs of automation and intelligent transformation of the paddle boring process.

Alcohol addiction can cause brain dysfunction and many other diseases. Recently, increasing evidences have suggested that gut microbiota plays a vital role in regulating alcohol addiction. However, the exact mechanism has not yet been elucidated. Here, our study focused on the intestinal bacteria alternations and their correlations with alcohol-induced neuropsychic behaviors. When consuming alcohol over 3-week period, animals gradually displayed anxiety/depression-like behaviors. Moreover, 16S rRNA sequencing showed significant intestinal microflora dysbiosis and distinct community composition. Actinobacteria and Cyanobacteria were both increased at the phylum level. At the genus level, Adlercreutzia spp., Allobaculum spp., and Turicibacter spp. were increased whereas Helicobacter spp. was decreased. We also found that the distances in inner zone measured by open field test and 4% (v/v) alcohol preference percentages were significantly correlated with Adlercreutzia spp. The possible mechanisms were explored and we found the expression of brain-derived neurotrophic factor (BDNF) and α1 subunit of γ-aminobutyric acid A receptor (Gabra1) were both decreased in prefrontal cortex (PFC). Especially, further correlation analyses demonstrated that decreased Adlercreutzia spp. was positively correlated with alcohol preference and negatively correlated with anxiety-like behavior and BDNF/Gabra1 changes in PFC. Similar relationships were observed between Allobaculum spp. and alcohol preference and BDNF changes. Helicobacter spp. and Turicibacter spp. were also correlated with PFC BDNF and hippocampus Gabra1 level. Taken together, our study showed that gut microbiota dysbiosis during chronic alcohol exposure was closely correlated with alcohol-induced neuropsychic behaviors and BDNF/Gabra1 expression, which provides a new perspective for understanding underlying mechanisms in alcohol addiction. © 2018 BioFactors, 45(2):187-199, 2019.

The inflorescence deficient in abscission-like (IDL) genes have been shown to play critical roles in floral organ abscission, lateral root formation and various stress responses in Arabidopsis. The IDL gene family has been characterized in a number of plant species, while limited information is available about IDL genes of tobacco. In the current study, 15 NtIDL members were identified in the tobacco genome, and were classified into six groups together with IDL members from other species. Evolution analysis suggested that the NtIDL members form group VI might have originated from duplication events. Notably, NtIDL06 shared high similarities with AtIDA in the EPIP sequence, and its encoding gene was highly expressed in the abscission zone of flowers at late developmental stages, implying that NtIDL06 might regulate tobacco flower abscission. In addition, the results from cis-elements analysis of promoters and expression after stress treatments suggested that NtIDL members might be involved in various stress responses of tobacco. The results from this study provide information for further functional analysis related to flower abscission and stress responses of NtIDL genes.

Melatonin (MLT) is widely used to treat sleep disorders although the underlying mechanism is still elusive. In mice, using wheel-running detection, we found that exogenous MLT could completely recover the period length prolonged by N-methyl-D-aspartate receptor (NMDAR) impairment due to the injection of the NMDAR antagonist MK-801, a preclinical model of psychosis. The analysis of the possible underlying mechanisms indicated that MLT could regulate the homeostatic state in the ventrolateral preoptic nucleus (VLPO) instead of the circadian process in the suprachiasmatic nucleus (SCN). In addition, our data showed that MK-801 decreased Ca2+ -related CaMKII expression and CREB phosphorylation levels in the VLPO, and MLT could rescue these intracellular impairments but not NMDAR expression levels. Accordingly, Gcamp6 AAV virus was injected in-vivo to further monitor intracellular Ca2+ levels in the VLPO, and MLT demonstrated a unique ability to increase Ca2+ fluorescence compared with MK-801-injected mice. Additionally, using the selective melatonin MT2 receptor antagonist 4-Phenyl-2-Propionamidotetralin (4P-PDOT), we discovered that the pharmacological effects of MLT upon NMDAR impairments were mediated by melatonin MT2 receptors. Using electroencephalography/electromyography (EEG/EMG) recordings we observed that the latency to the first non-rapid eye movement (NREM) sleep episode was delayed by MK-801, and MLT was able to recover this delay. In conclusion, exogenous MLT by acting upon melatonin MT2 receptors rescues sleep phase delayed by NMDAR impairment via increasing intracellular Ca2+ signaling in the VLPO, suggesting a regulatory role of the neurohormone on the homeostatic system.

Alzheimer’s disease (AD) is an age-related neurodegenerative disease with multiple predisposing factors and complicated pathogenesis. Aβ peptide is one of the most important pathogenic factors in the etiology of AD. Accumulating evidence indicates that the imbalance of Aβ production and Aβ clearance in the brain of AD patients leads to Aβ deposition and neurotoxic Aβ oligomer formation. Melatonin shows a potent neuroprotective effect and can prevent or slow down the progression of AD, supporting the view that melatonin is a potential therapeutic molecule for AD. Melatonin modulates the regulatory network of secretase expression and affects the function of secretase, thereby inhibiting amyloidogenic APP processing and Aβ production. Additionally, melatonin ameliorates Aβ-induced neurotoxicity and probably promotes Aβ clearance through glymphatic-lymphatic drainage, BBB transportation and degradation pathways. In this review, we summarize and discuss the role of melatonin against Aβ-dependent AD pathogenesis. We explore the potential cellular and molecular mechanisms of melatonin on Aβ production and assembly, Aβ clearance, Aβ neurotoxicity and circadian cycle disruption. We summarize multiple clinical trials of melatonin treatment in AD patients, showing that melatonin has a promising effect on improving sleep quality and cognitive function. This review aims to stimulate further research on melatonin as a potential therapeutic agent for AD.

At present, the Internet of Things has become a hot area of global concern and is considered to be another major scientific and technological innovation after the Internet. The Internet of Things can be analyzed from two aspects, one is to access the Internet, and the other is the connection between things. The Industrial Internet of Things, as a new type of industrial ecosystem, collects resources and data during the industrial production process by using miniature low-cost controllers and high-bandwidth wireless networks to achieve flexible configuration of manufacturing raw materials and improve resource utilization. The Industrial Internet of Things not only includes traditional software elements, but also requires hardware controllers and sensors, as well as cloud service platforms, to ultimately achieve intelligent manufacturing. The Industrial Internet of Things based on MQTT adopts the method of upper computer (WeChat applet) + server (Alibaba Cloud Server) + lower computer (WiFi module ESP8266 NodeMcu) to realize data collection and control of industrial production process. Based on OPC UA protocol, The Industrial Internet of Things, by designing an intelligent node device based on embedded Linux system, uses Qt to build the OPC UA protocol. OPC UA is a C / S architecture real-time database framework. By building an OPC UA Client on a handheld terminal device, An OPC UA Serve is set up on the smart terminal device, and the information collected by the handheld terminal is sent to the smart terminal. At the same time, multiple smart terminals are connected through the OPC UA protocol to perform data interaction and information transfer. At the same time, an edge computing algorithm is embedded in the smart terminal, and a large amount of data collected is processed for analysis, screening, and calculation. At the same time, the processed information is transmitted or processed. Reduce data interactions between data sources and data centers, and reduce the amount of information transmitted and stored.

Melatonin (MLT) is widely used to treat sleep disorders although the underlying mechanism is still elusive. In mice, using wheel-running detection, we found that exogenous MLT could completely recover the period length prolonged by N-methyl-D-aspartate receptor (NMDAR) impairment due to the injection of the NMDAR antagonist MK-801, a preclinical model of psychosis. The analysis of the possible underlying mechanisms indicated that MLT could regulate the homeostatic state in the ventrolateral preoptic nucleus (VLPO) instead of the circadian process in the suprachiasmatic nucleus (SCN). In addition, our data showed that MK-801 decreased Ca

Rotenone is a common pesticide and has been reported as one of the risk factors for Parkinson disease. Rotenone can cause neuronal death or apoptosis through inducing oxidative injury and inhibiting mitochondrial function. As a natural polyphenolic compound, resveratrol possesses the antioxidant capacity and neuroprotective effect. However, the mechanism underlying the neuroprotective effect of resveratrol against rotenone-induced neurotoxicity remains elusive. Here, we treated PC12 cells with rotenone to induce neurotoxicity, and the neurotoxic cells were subjected to resveratrol treatment. The CCK8 and LDH activity assays demonstrated that resveratrol could suppress neurotoxicity induced by rotenone (P

Alzheimer's disease (AD) is a kind of neurodegenerative disorder associated with age. Investigations suggest that amyliod-β (Aβ) is implicated in the pathogenesis of AD. The accumulation of Aβ in the brain causes oxidative stress and synaptic toxicity, leads to synaptic dysfunction and neuronal death. Previous investigations suggest that melatonin an endogenous hormone can counteract Aβ-induced neurotoxicity. However, the molecular mechanisms of Aβ-induced toxicity and melatonin treatment remain elusive. Studies indicate that microRNA-132 is crucial for neuronal survival and plays a key role in the pathological process of AD. Moreover, PTEN and FOXO3a two key targets of miR-132 are upregulated in the AD brain. Here, we exposed the primary cultured cortical neurons with Aβ25-35 and treated with melatonin. Our investigations demonstrated that Aβ25-35 exposure significantly decreased the expression of miR-132 and elevated the expression of PTEN and FOXO3a. Whereas, melatonin treatment could rescue the expression of miR-132 and downregulate the level of PTEN and FOXO3a. Moreover, melatonin blocked the nuclear translocation of FOXO3a and thereby suppressed its pro-apoptotic pathways. In addition, our investigations suggested that the over-expression of miR-132 could block Aβ-induced neurotoxicity. We also found that VO-OHpic (PTEN inhibitor) could counteract Aβ-induced neuronal damage, and LY294002 (AKT inhibitor) suppressed the protective effect of melatonin. Together, these results indicate that melatonin exerts its neuroprotective effect in Aβ-induced neurotoxicity via miR-132/PTEN/AKT/FOXO3a pathway. © 2018 BioFactors, 44(6):609-618, 2018.

Signal demodulation method of a frequency output resonant gyroscope is studied in this study. It has been a major problem of frequency micro gyroscopes. The detection elements of frequency gyroscopes are two double-ended tuning forks (DETF). The vibratory response of DETF is a periodic signal modulated by both amplitude and frequency. According to the characteristic that the amplitude and frequency of the gyro signal vary continuously with time, the signal demodulation algorithm is designed based on instantaneous frequency analysis. Hilbert transform is used to solve the instantaneous frequency. The algorithm is programmed in digital signal processor (DSP) and a test circuit board is made. Experimental test demonstrates that the demodulation circuit has a high precision and linearity, and the correlation coefficient between input signals and demodulation results achieves as much as 0.99999998. The demodulation method is proved to be feasible. This study provides a new train of thought for the study of the signal demodulation method of frequency micro gyroscopes and brings a new direction for the signal analysis of resonant sensors.

It is difficult to strengthen and toughen epoxy resin (EP) and concurrently obtain good flame retardancy. A novel flame retardant marked as TFD was prepared by tyrosine (Tyr), furfuraldehyde (FA) and 9,10-Dihydro-9-oxa-10-phosphaphenanthrene 10-oxide (DOPO) and co-cured with EP. Only 6 wt% TFD makes EP achieve UL-94 V0 and limited oxygen index (LOI) value 32.4 vol% revealing the high flame retardant efficiency. Furthermore, the tensile and impact strength of EP-8TFD are 29.3 % and 84.4 % higher than that of EP indicating strengthening and toughening effect of TFD. TFD can chemically bond into EP networks via its carboxyl and phenolic hydroxyl reacting with EP leading to good tensile properties. The high rigidity of DOPO forms holes between molecular chains, which eliminates stress concentration and improves impact strength. The strength, toughness and flame retardancy of EP are regulated by simple molecular structure, which provides a good idea for integration of structure and performance.

Schizophrenia is a devastating mental disease with social deficit as its core component of negative symptoms, which could be induced in rodents by dizocilpine (MK-801), a noncompetitive NMDA receptor antagonist. NMDA receptors are highly expressed during the postnatal period. However, less attention has been paid to the effects of postnatal MK-801 administration on social interaction. In this study, we evaluated the effects of postnatal administration of MK-801 on social interaction and explored the possible mechanisms. Postnatal day-7 mice were intraperitoneally injected with MK-801 twice daily for 5 days, and their social interaction repertoire was monitored by a computerized video in the 10th week. The contact event, relative position event, stop-state, and dynamic event were analyzed with MiceProfiler automatic idTracker system. The results showed that MK-801 reduced the number of the contact events, relative position events, and stop-states, while increased the number and duration of dynamic events. These changes implied that MK-801-injected mice had indifference and lower motivation in social interaction and could be a useful model for studies on the social deficit of schizophrenia. The prefrontal cortex is the key region for social interaction behaviors. Slice patch clamp was performed to analyze the cellular excitability of prefrontal cortical neurons after postnatal treatment with MK-801 in mice. The results demonstrated that MK-801 injection reduced the frequency and amplitude of action potentials, but increased the frequency of miniature inhibitory postsynaptic currents. These data illustrated that the excitability of neurons in the prefrontal cortex was inhibited. Finally, immunoblotting data demonstrated that MK-801 significantly decreased the levels of sirtuin 1 (SIRT1) and phosphorylated protein kinase B (p-PKB) in the prefrontal cortex (both P

Mesocortical dopaminergic (DA) subtype neurons specifically project to the prefrontal cortex, which is closely related with schizophrenia. Mesocortical DA neurons have unique physiological characteristics that are different from those of mesostriatal and mesolimbic DA neurons. Paliperidone, an atypical antipsychotic, is currently used to treat schizophrenia and has better therapeutic effects than typical antipsychotics. However, the underlying physiological mechanism remains unclear. To explore the effects of paliperidone on mesocortical DA neuron activity, here, we retrogradely labeled these cells with fluorescent microsphere retrobeads, and the electrophysiological changes were recorded in whole-cell recordings in rat midbrain slices with or without paliperidone. The data showed that paliperidone (20μmol/L) increased the spontaneous firing rates of labeled mesocortical neurons (P

Cell walls are basically complex with dynamic structures that are being involved in several growth and developmental processes, as well as responses to environmental stresses and the defense mechanism. Pectin is secreted into the cell wall in a highly methylesterified form. It is able to perform function after the de-methylesterification by pectin methylesterase (PME). Whereas, the pectin methylesterase inhibitor (PMEI) plays a key role in plant cell wall modification through inhibiting the PME activity. It provides pectin with different levels of degree of methylesterification to affect the cell wall structures and properties. The PME activity was analyzed in six tissues of Sorghum bicolor, and found a high level in the leaf and leaf sheath. PMEI families have been identified in many plant species. Here, a total of 55 pectin methylesterase inhibitor genes (PMEIs) were identified from S. bicolor whole genome, a more detailed annotation of this crop plant as compared to the previous study. Chromosomal localization, gene structures and sequence characterization of the PMEI family were analyzed. Moreover, cis-acting elements analysis revealed that each PMEI gene was regulated by both internal and environmental factors. The expression patterns of each PMEI gene were also clustered according to expression pattern analyzed in 47 tissues under different developmental stages. Furthermore, some SbPMEIs were induced when treated with hormonal and abiotic stress. Taken together, these results laid a strong foundation for further study of the functions of SbPMEIs and pectin modification during plant growth and stress responses of cereal.

Recent studies have revealed that the gut microbiota participates in the psychiatric behavior changes in disorders associated with alcohol. But it still remains unknown whether alcoholism is involved in changes in gut microbiota and its underlying mechanism is also not clear. Here, we tested the gut microbiota of patients with alcoholism and conducted fecal microbiota transplantation (FMT) from patients with alcoholism to C57BL/6J mice whose gut microbiota had been sharply suppressed with antibiotics (ABX). Then we evaluated their alcohol preference degree, anxiety, and depression-like behaviors and social interaction behaviors, together with molecular changes in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). Our data indicated that the gut microbiota of patients with alcoholism was drastically different from those of the healthy adults. The abundance of p_Firmicutes was significantly increased whereas p_Bacteroidetes was decreased. Compared to mice transplanted with fecal microbiota from healthy male adults, the mice accepting fecal microbiota from patients with alcoholism showed (a) anxiety-like and depression-like behaviors, (b) decreased social interaction behaviors, (c) spontaneous alcohol preference, and (d) decreased brain-derived neurotrophic factor (BDNF), alpha 1 subunit of GABA type A receptor (α1GABAA R) in mPFC and decreased metabotropic glutamate receptors 1 (mGluR1), protein kinase C (PKC) e in NAc. Overall, our results suggest that fecal microbiota from patients with alcoholism did induce a status like alcohol dependence in C57BL/6J mice. The decreased expression of BDNF, α1GABAA R, and mGluR1/ PKC e may be the underlying mechanism.

l-Lactate is emerging as a crucial regulatory nexus for energy metabolism in the brain and signaling transduction in synaptic plasticity, memory processes, and drug addiction instead of being merely a waste by-product of anaerobic glycolysis. In this review, the role of lactate in various memory processes, synapse plasticity and drug addiction on the basis of recent studies is summarized and discussed. To this end, three main parts are presented: first, lactate as an energy substrate in energy metabolism of the brain is described; second, lactate as a novel signaling molecule in synaptic plasticity, neural circuits, memory, and drug addiction is described; and third, in light of the above descriptions, it is plausible to speculate that lactate is predominantly a signaling molecule in specific memory processes and partly acts as an energy substrate. The future perspective in lactate signaling involving microglia and associated precise signaling pathways in the brain is highlighted.

Alcohol addiction can cause brain dysfunction and threatens both individuals and society. Recently, emerging studies have suggested the dysbiosis of gut microbiota induced by alcohol exposure contributed to the reward-seeking behaviors as well as anxiety, depression. In the current study, animal model of chronic alcohol exposure was established by providing mice with gradient concentrations of alcohol from 2%, 4%, and 6% to 8% for 21 days. Moreover, three fecal microbiota transplantation (FMT) plans were innovatively designed to explore the potential effects of FMT from 3 healthy donors on alcohol-induced neuropsychic behaviors. To our knowledge, for the first time, we found that anxiety and depression after alcohol intake were gradually relieved with the extension of transplantation. Although the two-week FMT starting at the end of alcohol treatment had few effects, the transplantation started at 8% ethanol exposure alleviated alcohol-induced depression in tail suspension test. More importantly, accompanied by three-week exposure, the five-week FMT significantly decreased anxiety-like behaviors in open field test and depression in tail suspension test. These data validated the role of gut microbiota in alcohol addiction and indicated the modulation of healthy donor FMT on alcohol-related anxiety and depression, providing a new target for treating alcohol addiction by targeting microbiota.

The NAC (NAM, ATAF1/2, and CUC2) transcription factors comprise one of the largest transcription factor families in plants and play important roles in stress responses. However, little is known about the functions of potato NAC family members. Here we report the cloning of a potato NAC transcription factor gene StNAC053, which was significantly upregulated after salt, drought, and abscisic acid treatments. Furthermore, the StNAC053-GFP fusion protein was found to be located in the nucleus and had a C-terminal transactivation domain, implying that StNAC053 may function as a transcriptional activator in potato. Notably, Arabidopsis plants overexpressing StNAC053 displayed lower seed germination rates compared to wild-type under exogenous ABA treatment. In addition, the StNAC053 overexpression Arabidopsis lines displayed significantly increased tolerance to salt and drought stress treatments. Moreover, the StNAC053-OE lines were found to have higher activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) under multiple stress treatments. Interestingly, the expression levels of several stress-related genes including COR15A,DREB1A, ERD11, RAB18, ERF5, and KAT2, were significantly upregulated in these StNAC053-overexpressing lines. Taken together, overexpression of the stress-inducible StNAC053 gene could enhance the tolerances to both salt and drought stress treatments in Arabidopsis, likely by upregulating stress-related genes.

Zinc finger homeodomain (ZF-HD) transcription factors play significant roles in plant growth and responses to environmental stresses. In this study, 32 ZF-HD genes identified in the tobacco (Nicotiana tabacum L.) genome were divided into six groups according to phylogenetic analysis with Arabidopsis and tomato ZF-HD members. An examination of gene structures and conserved motifs revealed the relatively conserved exon/intron structures and motif organization within each subgroup. In addition, various stress-related elements are found in the promoter region of these genes. The expression profiling analysis revealed that NtZF-HD genes expressed in different tissues and could be induced by several abiotic stresses. Notably, NtZF-HD21 was highly expressed in response to the drought treatments. Subcellular localization analysis and a virus-induced gene silencing (VIGS) experiment were performed to investigate the potential functions of NtZF-HD21. The subcellular localization indicated that NtZF-HD21 is a nuclear protein. Furthermore, gene silencing of the NtZF-HD21 gene reduced the drought resistance of tobacco. These findings provide insights for further biological functional analyses of the NtZF-HD genes in tobacco.

Polyamide 6 (PA6) has potential safety hazards in many fields due to its intrinsic flammability. In this paper, furan-phosphamide (POCFA) was introduced into PA6 to regulate its flame retardancy and mechanical properties via multiple reactions between them. The results showed that 5 wt% POCFA makes PA6 achieve the UL-94 V0 rating and a LOI 27.2 vol%. The mechanical properties of PA6 were decreased after processing, but these properties can recover after a period of time. This is caused by the multiple reactions between POCFA and PA6 during processing and application. Firstly, POCFA catalyzes the degradation of PA6 resulting in the decrease of molecular weight and the increase of fluidity, which improves the flame retardancy of PA6 by melting-away mode. Secondly, the reactions between POCFA and PA6 graft furan ring onto PA6 chain, thus Diels-Alder addition reactions can occur between different furan rings, which extend the molecular chain of PA6, and improve the mechanical properties. This work provides a good method to balance the flame retardancy and mechanical properties of PA6 composites.

Axonal degeneration is a common pathological change of neurogenical disease which often arises before the neuron death. But it had not found any effective method to protect axon from degeneration. In this study we intended to confirm the protective effect of nicotinamide adenine dinucleotide (NAD), investigate the optimal administration dosage and time of NAD, and identify the relationship between silence signal regulating factor 1 (SIRT1) and axonal degeneration. An axonal degeneration model was established using dorsal root ganglion (DRG) neurons injured by vincristine to observe the protective effects of NAD to the injured axons. In addition, the potential contribution of the SIRT1 in axonal degeneration was also investigated. Through the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, immunochemistry staining, axons counting and length measuring, transmission electron microscope (TEM) observation, we demonstrated that NAD played an important role in preventing axonal degeneration. Further study revealed that the expression of SIRT1 and phosphorylated Akt1 (p-Akt1) was up-regulated when NAD was added into the culturing medium. Taking together, our results demonstrated that NAD might delay the axonal degeneration through SIRT1/Akt1 pathways.

The Modbus/TCP protocol cannot guarantee the real-time capability. A token ring scheduling algorithm that featured by priority to provide the real-time response to the Modbus/TCP messages is designed. The average response delay on a μC/OS-II + ARM7 platform is 1.117 ms, which is better than most average response delay reported in current researches that aim at improving the real-time performance of Modbus/TCP, and, it reaches the level of Powerlink working in open mode. Finally, a weighted token ring scheduling algorithm and a weight-variable token ring scheduling algorithm are proposed. The two algorithms can meet the demand of customizable and changeable time delay in advanced application.

This paper presents the architecture and optimization verification of a designed mode-mismatching gyroscope prototype made with fused silica in atmospheric pressure. The gyroscope prototype uses the decoupling frame and double-ended tuning fork (DETF) to achieve high sensitivity and quality factor. This structure can suppress residual quadrature error due to fabrication errors and imperfections. The angle rate-sensitive elements of the proposed gyroscope prototype with quasi-digital FM output are two DETF resonators resulting in differential implementation. We describe the principle of operation characterization of our micromechanical vibratory rate gyroscope based on resonant sensing of the Coriolis force and establish mathematical model called multi-parameters excitation system dynamics of Mathieu equation based on our previous work. We specify and quantify the impact functions of mechanical parameters on the properties of gyroscopes and identify sensitivity and limitation of sensitivity and bandwidth each other. A sample-based stochastic model is established to investigate the influence of different uncertain structure size on gyroscope performance. According to the uncertainty analysis, we modify the previous gyroscope structure, and then the parameters and structure of the improved third version gyroscope are obtained. This research can provide a reference for design and optimization of the structure size to improve robustness and performance of resonant angle rate sensor.

Current studies have illustrated that circular RNAs (circRNAs) are a vital part of non-coding RNA (ncRNAs) species and highly abundant and dynamically expressed in brain. However, the exact mechanisms by which circRNAs modulate methamphetamine (METH)-induced neuronal damage still remain largely unexplored. Consistent with our previous study, the expression of circHomer1 was significantly up-regulated after METH treatment in HT-22 cells. We confirmed its loop structure by detection of its back-splice junction with qRT-PCR product via sequence. Moreover, circHomer1 was resistant against RNase R digestion compared with its linear mRNA Homer1. Inhibition of circHomer1 expression indeed alleviated METH-induced neurotoxicity, with lower apoptosis rate via flow cytometry and cleaved Caspase3 protein level. Furthermore, we speculated that Bbc3 functioned as a target of circHomer1 based on computational algorithm, and knockdown of circHomer1 actually reduced Bbc3 expression at the mRNA and protein level. Besides, suppression of Bbc3 decreased the reactive oxygen species (ROS) level and radio of PI-positive cells. Furthermore, we analyzed the correlation in pairs among circHomer1, Bbc3 and behaviors in well-developed METH-addicted models using Pearson's correlation coefficient, which implied an important role of circHomer1 and Bbc3 in addictive behaviors. In all, we for the first time identified a novel circRNA, circHomer1 and our results suggested that circHomer1 regulated METH-induced lethal process by suppressing the Bbc3 expression.

Two phosphorus-nitrogen flame retardants were synthesized by using chlodiphenylphosphine (CDP) or diphenylphosphinyl chloride (DPP) and cytosine (Cy), respectively. The products are marked as CCDP and CDPP, and characterized by using Fourier transform infrared spectra (FT-IR), 31P and 1H nuclear magnetic resonance and thermogravimetric analysis (TGA). The CCDP and CDPP were used to modify the flame retardancy of polyamide 6 (PA6). The results indicated that 6 wt% CCDP and CDPP both make PA6 achieve the UL-94 V-0 rating and improve its LOI value. The degradation behavior was studied by TG-IR, melt volume-flow rate, etc. The results revealed that both CCDP and CDPP promote the degradation of PA6 and improve its flame retardancy by melting away. The CCDP tends to work in the gas phase and the CDPP in the condensed phase. In addition, in order to reduce the effect of flame retardant on the mechanical properties of PA6, CDPP was coated with epoxy resin. The results showed that the flame retardancy decrease after coating. Finally, melamine cyanurate was blended with the CDPP coated by epoxy to adjust the comprehensive properties of PA6 composite, and excellent flame retardancy and mechanical properties are obtained.

The social deficit is a prevailing symptom in stress-induced depression. Although social interaction behavior has been widely studied in humans and rodents, it is imprecise to record the social behavior between two free-moving mice via perusal. In the present study, we applied an approach to analyze the social behavior in mice using a software named "MiceProfiler." C57BL/6J mice were stressed via chronic restraint stress (CRS) and housed in three populations of different sizes as follows: single, three in a cage, and six in a cage. The MiceProfiler was used to analyze the video of behavioral repertoire and, the result showed that stressed and single housed mice exhibited more social interaction both in the contact time and contact activities. Furthermore, we investigated the effect of CRS on social behavior when the mice were housed in larger populations size (three or six in a cage) and found that, the CRS procedure promoted social interaction. However, the larger population size resulted in the less total contact time, less time of head-tail, and moving in an opposite way. Besides, the CRS mice showed less social avoidance while the mice from a larger population presented less active contact. And the CRS mice also exhibited a higher social hierarchy compared with the control. Our data indicated that mild restraint stress might increase the intercommunication between mice. Collectively, our findings provided a new evidence for social behavior study and the MiceProfiler could be a new tool to measure the social behaviors of rodents.

E3 ubiquitin ligases are the most expanded components of the ubiquitin proteasome system (UPS). They mediate the recognition of substrates and later transfer the ubiquitin (Ub) of the system. Really Interesting New Gene (RING) finger proteins characterized by the RING domain, which contains 40–60 residues, are thought to be E3 ubiquitin ligase. RING-finger proteins play significant roles in plant growth, stress resistance, and signal transduction. In this study, we mainly describe the structural characteristics, classifications, and subcellular localizations of RING-finger proteins, as well the physiological processes of RING-finger proteins in plant growth and development. We also summarize the functions of plant RING-finger proteins in plant stress resistance. Finally, further research on plant RING-finger proteins is suggested, thereby establishing a strong foundation for the future study of plant RING-finger proteins.