ABSTRACT
BACKGROUND: Epilepsy is a neurological disorder characterized by recurrent seizures and is often unresponsive to current treatment options. Ferroptosis, a recently defined iron-dependent regulated cell death, has been suggested as a potential therapeutic target for epilepsy due to its association with oxidative stress. Additionally, circRNA SLC8A1 (circSLC8A1) has been implicated in various neurological disorders and oxidative stress-related diseases but its involvement in epilepsy progression, particularly in relation to ferroptosis and oxidative stress, remains unclear. METHODS: qRT-PCR, Western blot, IHC and ELISA assays were employed to validate the relative expression of targeted genes and proteins. The levels of ROS, iron, LOP and GSH were detected by commercial kits. RNA pull-down and RIP assays were employed to detect the interactions among circSLC8A1, FUS and ATF3. A rat epilepsy model was established for further in vivo confirmation. RESULTS AND CONCLUSION: In this study, we investigated the potential involvement of circSLC8A1 in epilepsy progression and its connection to ferroptosis and oxidative stress. Our findings demonstrate that circSLC8A1 triggers neuronal ferroptosis by stabilizing ATF3 mRNA expression through recruitment with FUS. The induced neuronal ferroptosis contributes to epilepsy progression. These results enhance our understanding of epilepsy pathogenesis and may provide insights for the development of novel therapeutic strategies.
Subject(s)
Epilepsy , Ferroptosis , Animals , Rats , Epilepsy/genetics , Ferroptosis/genetics , Hippocampus , Iron , RNA Stability , RNA, Circular/genetics , RNA-Binding Protein FUS/metabolismABSTRACT
The numerous naturally-fragmented sky islands (SIs) in the Hengduan Mountains Region (HMR) of southwestern China constitute discontinuous landscapes where montane habitats are isolated by dry-hot valleys which have fostered exceptional species diversification and endemicity. However, studies documenting the crucial role of SI on the speciation dynamics of native freshwater organisms are scarce. Here we used a novel set of comprehensive genetic markers (24 nuclear DNA sequences and complete mitogenomes), morphological characters, and biogeographical information to reveal the evolutionary history and speciation mechanisms of a group of small-bodied montane potamids in the genus Tenuipotamon. Our results provide a robustly supported phylogeny, and suggest that the vicariance events of these montane crabs correlate well with the emergence of SIs due to the uplift of the HMR during the Late Oligocene. Furthermore, ancestrally, mountain ridges provided corridors for the dispersal of these montane crabs that led to the colonization of moist montane-specific habitats, aided by past climatic conditions that were the crucial determinants of their evolutionary history. The present results illustrated that the mechanisms isolating SIs are reinforced by the harsh-dry isolating climatic features of dry-hot valleys separating SIs and continue to affect local diversification. This offers insights into the causes of the high biodiversity and endemism shown by the freshwater crabs of the HMR-SIs in southwestern China.
Subject(s)
Brachyura , Animals , Phylogeny , Brachyura/genetics , China , Biodiversity , Fresh WaterABSTRACT
Emerging findings point to a role for C1q/TNF-related protein 4 (CTRP4) in feeding in mammals. However, it remains unknown whether CTRP4 regulates feeding in fish. This study aimed to determine the feeding regulation function of CTRP4 in Siberian sturgeon (Acipenser baerii). In this study, the Siberian sturgeon ctrp4 (Abctrp4) gene was cloned, and Abctrp4 mRNA was shown to be highly expressed in the hypothalamus. In the hypothalamus, Abctrp4 mRNA decreased during fasting and reversed after refeeding. Subsequently, we obtained the AbCTRP4 recombinant protein by prokaryotic expression and optimized the expression and purification conditions. Siberian sturgeon (81.28 ± 14.75 g) were injected intraperitoneally using 30, 100, and 300 ng/g Body weight (BW) AbCTRP4 to investigate its effect on feeding. The results showed that 30, 100, and 300 ng/g BW of the AbCTRP4 significantly reduced the cumulative food intake of Siberian sturgeon at 1, 3, and 6 h. Finally, to investigate the potential mechanism of CTRP4 feeding inhibition, 300 ng/g BW AbCTRP4 was injected intraperitoneally. The findings demonstrated that AbCTRP4 treatment for 1 h significantly promoted the mRNA levels of anorexigenic peptides (pomc, cart, and leptin) while suppressing the mRNA abundances of orexigenic peptides (npy and agrp).In addition, the jak2/stat3 pathway in the hypothalamus was significantly activated after 1 h of AbCTRP4 treatment. In conclusion., this study confirms the anorexigenic effect of CTRP4 in Siberian sturgeon.
Subject(s)
Appetite , Complement C1q , Animals , Appetite/genetics , Complement C1q/metabolism , Complement C1q/pharmacology , Eating/physiology , Fishes/physiology , Peptides/genetics , Peptides/pharmacology , Peptides/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Mammals/metabolismABSTRACT
Gastrin is an important intragastrointestinal hormone, but reports on its regulation of feeding behavior in fish are still scarce. This study aimed to determine the feeding regulatory function of gastrin in sturgeon. In this study, a gastrin/cholecystokinin-like peptide was identified in the genomes of sturgeon and proved to be gastrin by evolutionary tree analysis. Tissue distribution of gastrin and its receptor, cholecystokinin receptor B (CCKRB), showed that both had high mRNA abundance in the hypothalamus and gastrointestinal tract. In the duodenum, gastrin and CCKRB mRNAs were reduced at 1 h of fasting, and both were also observed in the stomach and hypothalamus in response to changes in feeding status. Sulfated gastrin 17 is the major form of gastrin in vivo. Therefore, we investigated the effect of sulfated gastrin 17 on feeding by intraperitoneal injection into Siberian sturgeon using sulfated gastrin 17. The results showed that gastrin 17 significantly reduced the cumulative feeding of Siberian sturgeon in the short term (1, 3 and 6 h) and long term (1, 2, 3, 4, 5 and 7 days). Finally, we explored the potential mechanism of feeding inhibition after intraperitoneal injection of gastrin 17 for 7 consecutive days. The results showed that gastrin 17 treatment significantly increased the mRNA levels of anorexigenic peptides (cart, cck and pyy), while it had no significant effect on the mRNA abundance of orexigenic peptides (npy and agrp). In addition, gastrin 17 treatment significantly affected the expression of appetite signaling pathways in the hypothalamus, such that the mRNA expression of ampkα1 was significantly reduced, whereas the mRNA abundance of stat3, mtor and s6k was significantly increased. In conclusion, the present study confirmed the anorectic effect of gastrin on Siberian sturgeon.
Subject(s)
Fishes , Gastrins , Receptor, Cholecystokinin B , Animals , Gastrins/metabolism , Fishes/physiology , Fishes/metabolism , Receptor, Cholecystokinin B/metabolism , Receptor, Cholecystokinin B/genetics , Feeding Behavior/drug effects , RNA, Messenger/metabolism , RNA, Messenger/genetics , Hypothalamus/metabolismABSTRACT
Mentha canadensis, as a plant with medicinal and culinary uses, holds significant economic value. Jasmonic acid signaling repressor JAZ protein has a crucial role in regulating plant response to adversity stresses. The M. canadensis McJAZ8 gene is cloned and analyzed for protein characterization, protein interactions, and expression patterns, so as to provide genetic resources for molecular breeding of M. canadensis for stress tolerance. This experiment will analyze the protein structural characteristics, subcellular localization, protein interactions, and gene expression of McJAZ8 using bioinformatics, yeast two-hybrid(Y2H), transient expression in tobacco leaves, qRT-PCR, and other technologies. The results show that:(1)The full length of the McJAZ8 gene is 543 bp, encoding 180 amino acids. The McJAZ8 protein contains conserved TIFY and Jas domains and exhibits high homology with Arabidopsis thaliana AtJAZ1 and AtJAZ2.(2)The McJAZ8 protein is localized in the nucleus and cytoplasm.(3)The Y2H results show that McJAZ8 interacts with itself or McJAZ1/3/4/5 proteins to form homologous or heterologous dimers.(4)McJAZ8 is expressed in different tissue, with the highest expression level in young leaves. In terms of leaf sequence, McJAZ8 shows the highest expression level in the fourth leaf and the lowest expression level in the second leaf.(5) In leaves and roots, the expression of McJAZ8 is upregulated to varying degrees under methyl jasmonate(MeJA), drought, and NaCl treatments. The expression of McJAZ8 shows an initial upregulation followed by a downregulation pattern under CdCl_2 treatment. In leaves, the expression of McJAZ8 tends to gradually decrease under CuCl_2 treatment, while in roots, it initially decreases and then increases before decreasing again. In both leaves and roots, the expression of McJAZ8 is downregulated to varying degrees under AlCl_(3 )treatment. This study has enriched the research on jasmonic acid signaling repressor JAZ genes in M. canadensis and provided genetic resources for the molecular breeding of M. canadensis.
Subject(s)
Cyclopentanes , Gene Expression Profiling , Mentha , Oxylipins , Transcription Factors/genetics , Transcription Factors/metabolism , Computational Biology , Gene Expression Regulation, Plant , Plant Proteins/metabolism , Phylogeny , Stress, Physiological/geneticsABSTRACT
Mentha canadensis is a traditional Chinese herb with great medicinal and economic value. Abscisic acid(ABA) receptor PYLs have important roles in plant growth and development and response to adversity. The M. canadensis McPYL4 gene was cloned, and its protein characteristics, gene expression, and protein interactions were analyzed, so as to provide genetic resources for genetic improvement and molecular design breeding for M. canadensis resistance. Therefore, the protein characteristics, subcellular localization, gene expression pattern, and protein interactions of McPYL4 were analyzed by bioinformatics analysis, transient expression of tobacco leaves, RT-qPCR, and yeast two-hybrid(Y2H) techniques. The results showed that the McPYL4 gene was 621 bp in length, encoding 206 amino acids, and its protein had the conserved structural domain of SRPBCC and was highly homologous with Salvia miltiorrhiza SmPYL4. McPYL4 protein was localized to the cell membrane and nucleus. The McPYL4 gene was expressed in all tissue of M. canadensis, with the highest expression in roots, followed by leaves, and it showed a pattern of up-regulation followed by down-regulation in leaves 1-8. In both leaves and roots, the McPYL4 gene responded to the exogenous hormones ABA, MeJA, and the treatments of drought, AlCl_3, NaCl, CdCl_2, and CuCl_2. Moreover, McPYL4 was up-regulated for expression in both leaves and roots under the MeJA treatment, as well as in leaves treated with AlCl_3 stress for 1 h, whereas McPYL4 showed a tendency to be down-regulated in both leaves and roots under other treatments. Protein interactions showed that McPYL4 interacted with AtABI proteins in an ABA-independent manner. This study demonstrated that McPYL4 responded to ABA, JA, and several abiotic stress treatments, and McPYL4 was involved in ABA signaling in M. canadensis and thus in the regulation of leaf development and various abiotic stresses in M. canadensis.
Subject(s)
Abscisic Acid , Mentha , Abscisic Acid/pharmacology , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Leaves/genetics , Plant Leaves/metabolism , Cloning, Molecular , Gene Expression Regulation, Plant , Stress, Physiological/genetics , DroughtsABSTRACT
We found that an out-of-plane vertical electric field of 1.0â V/Ang helps to maintain the thermodynamic and kinetic stability of monolayer CdI2.The results indicated that the electric field modulates monolayer CdI2 to produce the Mexican-hat electronic state and the giant Stark effect of the vertical electric field on monolayer CdI2 originates from electric field lifting its conduction band. The results based on HSE06 + SOC calculations show that electric field induces strong spin polarization, leading to significant energy level splitting and spin flipping in the valence band. Based on GW0 + BSE, the electric field broadens effective optical response range of monolayer CdI2, the new peak in the optical absorption spectrum under electric field indicates that electric field helps to diminish excitonic effect of monolayer CdI2.
ABSTRACT
Oxidative stress plays a significant role in the development of Parkinson's disease (PD). Previous studies implicate nuclear receptor subfamily 4 group A member 1 (NR4A1) in oxidative stress associated with PD. However, the molecular mechanism underlying the regulation of NR4A1 expression remains incompletely understood. In the present study, a PD cell model was established by using 1-methyl-4-phenylpyridinium (MPP+) in SH-SY5Y cells. Cell viability and apoptosis were assessed by using CCK-8 assay and flow cytometry, respectively. The activities of LDH and SOD, and ROS generation were used as an indicators of oxidative stress. ChIP-PCR was performed to detect the interaction between Yin Yang 1 (YY1) and the NR4A1 promoter. MPP+ treatment inhibited SH-SY5Y cell viability in a dose- and time-dependent manner. NR4A1 and YY1 expression were decreased in MPP+-treated SH-SY5Y cells. Increasing NR4A1 or YY1 alleviated MPP+-induced apoptosis and oxidative stress in SH-SY5Y cells, whereas reduction of NR4A1 aggravated MPP+-induced cell injury. Transcription factor YY1 facilitated NR4A1 expression by binding with NR4A1 promoter. In addition, in MPP+-treated SH-SY5Y cells, the inhibition of NR4A1 to apoptosis and oxidative stress was further enhanced by overexpression of YY1. The reduction of NR4A1 led to an elevation of apoptosis and oxidative stress in MPP+-induced SH-SY5Y cells, and this effect was partially reversed by the overexpression of YY1. In conclusion, YY1 suppresses MPP+-induced apoptosis and oxidative stress in SH-SY5Y cells by binding with NR4A1 promoter and boosting NR4A1 expression. Our findings suggest that NR4A1 may be a candidate target for PD treatment.HIGHLIGHTSNR4A1 and YY1 are decreased in MPP+-treated SH-SY5Y cells.NR4A1 prevents oxidative stress and apoptosis in MPP+-treated SH-SY5Y cells.YY1 binds with NR4A1 promoter and increases NR4A1 expression.YY1 enhances the inhibition of NR4A1 to SH-SY5Y cell apoptosis and oxidative stress.
Subject(s)
Neuroblastoma , Parkinson Disease , Humans , Apoptosis , Nuclear Receptor Subfamily 4, Group A, Member 1/genetics , Oxidative Stress , Yin-YangABSTRACT
BACKGROUND: The entomogenous fungus Beauveria bassiana is used as a biological insecticide worldwide, wild B. bassiana strains with high pathogenicity in the field play an important role in controlling insect pests via not only screening of highly virulent strains but also natural infection, but the pathogenicity degeneration of wild strains severely affected aforementioned effects. Previous studies have showed that multiple factors contributed to this phenomenon. It has been extensively proved that the mycovirus infection caused hypovirulence of phytopathogenic fungi, which has been used for plant disease biocontrol. However, it remains unknown whether the mycovirus epidemics is a key factor causing hypovirulence of B. bassiana naturally in the field. METHODS: Wild strains of B. bassiana were collected from different geographic locations in Jilin Province, China, to clarify the epidemic and diversity of the mycoviruses. A mycovirus Beauveria bassiana chrysovirus 2 (BbCV2) we have previously identified was employed to clarify its impact on the pathogenicity of host fungi B. bassiana against the larvae of insect pest Ostrinia furnacalis. The serological analysis was conducted by preparing polyclonal antibody against a BbCV2 coat protein, to determine whether it can dissociate outside the host fungal cells and subsequently infect new hosts. Transcriptome analysis was used to reveal the interactions between viruses and hosts. RESULTS: We surprisingly found that the mycovirus BbCV2 was prevalent in the field as a core virus in wild B. bassiana strains, without obvious genetic differentiation, this virus possessed efficient and stable horizontal and vertical transmission capabilities. The serological results showed that the virus could not only replicate within but also dissociate outside the host cells, and the purified virions could infect B. bassiana by co-incubation. The virus infection causes B. bassiana hypovirulence. Transcriptome analysis revealed decreased expression of genes related to insect epidermis penetration, hypha growth and toxin metabolism in B. bassiana caused by mycovirus infection. CONCLUSION: Beauveria bassiana infected by hypovirulence-associated mycovirus can spread the virus to new host strains after infecting insects, and cause the virus epidemics in the field. The findings confirmed that mycovirus infection may be an important factor affecting the pathogenicity degradation of B. bassiana in the field.
Subject(s)
Beauveria , Fungal Viruses , Animals , Virulence/genetics , Fungal Viruses/genetics , Beauveria/genetics , Gene Expression Profiling , LarvaABSTRACT
Beauveria bassiana, an entomopathogenic fungus, is used for arthropod pest control worldwide. Here, we report the discovery and characterization of a novel double-stranded RNA (dsRNA) mycovirus, Beauveria bassiana chrysovirus 2 (BbCV-2), isolated from a Chinese B. bassiana strain. The genome sequence of the virus was determined by metagenomic sequencing, RT-PCR, and RACE cloning and was found to consist of four dsRNA segments that are 3441 bp, 2779 bp, 2925 bp, and 2688 bp long, respectively. Each dsRNA segment contains a single ORF. The ORF of dsRNA1 encodes a 1114-amino-acid (aa) protein (123.4 kDa) with a conserved RNA-dependent RNA polymerase (RdRp) motif, the sequence of which showed the highest identity of only 16.13% to that of Beauveria bassiana chrysovirus-1 (BbCV-1). The ORF of dsRNA2 encodes an 805-aa coat protein (CP) (84.7 kDa). The ORFs of dsRNAs 3 and 4 encodes proteins of undetermined function. The virus is a new member of the family Chrysoviridae from B. bassiana.
Subject(s)
Beauveria , RNA Viruses , Beauveria/genetics , Genome, Viral , Open Reading Frames , Phylogeny , RNA Viruses/genetics , RNA, Double-Stranded/genetics , RNA, Viral/geneticsABSTRACT
A novel double-stranded RNA virus was isolated and identified from Beauveria bassiana Vuillemin, derived from the muscardine cadaver of an Ostrinia furnacalis larva in China. The virus contains six dsRNAs, and each viral dsRNA contains only one open reading frame (ORF). As in other polymycoviruses, dsRNA1 encodes an RNA-dependent RNA polymerase (RdRp), dsRNA3 encodes a methyltransferase (MTR), and dsRNA4 encodes a proline-alanine-serine-rich protein. A BLASTp search revealed that the viral RdRp domain showed 79.43%, 79.04%, and 59.05% sequence identity to Beauveria bassiana polymycovirus 2 and 3 (BbPmV-2, BbPmV-3) and Magnaporthe oryzae polymycovirus 1 (MoPmV-1), respectively. Phylogenetic analysis based on RdRp sequences showed that the phylogenetically closest relatives of this virus are BbPmV-2, BbPmV-3, and MoPmV-1. This virus, along with previously ill-defined polymycoviruses (BbPmV-2 and BbPmV-3), appears to belong to an as-yet-unestablished species. The findings further suggest that the virus is a new member of the genus Polymycovirus within the family Polymycoviridae, and we have named it "Beauveria bassiana polymycovirus 4" (BbPmV-4). However, the sixth dsRNA is a defective RNA with the same sequence as that of dsRNA4 except for a deletion of 312 bp from nt 185 to nt 496, but it still contains a complete ORF. To our knowledge, this is the first report of the existence of a defective RNA in a polymycovirus.
Subject(s)
Beauveria , RNA Viruses , Beauveria/genetics , Genome, Viral , Open Reading Frames , Phylogeny , RNA Viruses/genetics , RNA, Double-Stranded/genetics , RNA, Viral/geneticsABSTRACT
In order to explore the photocatalytic hydrogen production efficiency of the MoS2/WSe2 heterostructure (A2-MWS4) as a photocatalyst, it is highly desirable to study the photogenerated exciton dissociation related to photocatalysis. The electronic properties, optical absorption, and lattice dynamic properties of A2-MWS4 were investigated using a first-principles approach. The results show that the type II energy band alignment of A2-MWS4 facilitates the dissociation of photogenerated excitons (electrons and holes). The highly localized d-state electrons of A2-MWS4 induce the formation of internal potentials that promote the dissociation of photogenerated excitons. The hot carrier diffuses its extra energy into the lattice by scattering with phonons and forms a hot spot in the lattice while releasing phonons, which are dragged away from the hot spot by Ridley decay to promote exciton dissociation. These findings could provide insights for research studies on photochemical reactions and photovoltaic devices.
ABSTRACT
OBJECTIVES: The alteration of vimentin-containing cells (VCCs) proliferation, differentiation, and migration in the brain stem of amyotrophic lateral sclerosis (ALS)-like transgenic mice (Tg(SOD1*G93A)1Gur mice) (TG mice) and wild-type mice (WT mice) at the different disease stages of TG mice was studied in this study. The aims of this study were to investigate the change features of proliferation, differentiation, and migration of endogenous neural precursor cells (NPCs) and to explore the potential effects of NPCs on restoring degenerated neurons in ALS. METHODS: The proliferation, differentiation, and migration of VCCs in both different anatomic regions and neural cells of brain stem at the different stages including pre-onset (60-70 days), onset (90-100 days), and progression (120-130 days) stages of TG mice and in WT mice (control) were examined using the immunofluorescence technology. RESULTS: VCCs were mainly distributed in the around (peripheral) central canal (CC) and the nuclei of brain stem in adult WT mice. VCCs proliferated and differentiated into astrocytes and directionally migrated from the around CC to the nuclei of brain stem, and then to the ventral part of damaged regions in brain stem at the pre-onset, onset, and progression stages of TG mice. CONCLUSIONS: The data suggest that NPCs widely distributed in the brain stem of adult TG mice can differentiate into astrocytes and migrate into damaged brain regions. This response might be a potential mechanism to repair degenerated motor neurons and restore dysfunctional neural circuitry in ALS.
ABSTRACT
Various mechanisms are involved in plant disease resistance mediated by entomopathogenic fungi; however, the role of plant endophytic microbes in disease resistance is unknown. In the present study, we showed that the disease incidence of northern corn leaf blight caused by Exserohilum turcicum (Et) on maize was reduced significantly by soil inoculation with Beauveria bassiana (Bb). Meanwhile, B. bassiana colonization and E. turcicum infection increased the diversity and abundance and diversity of endophytic bacteria and fungi, respectively, while the abundance of endophytic bacterial of the Bb + Et treatment decreased significantly compared with that of Et treatment alone. However, Bb + Et treatment increased the relative abundance of plant beneficial bacteria significantly, for example, Burkholderia and Pseudomonas. Network analyses showed that the microbiome complexity increased after soil inoculation with B. bassiana. Taken together, these results revealed the potential mechanism by which entomopathogenic fungi exert biological control of maize leaf spot disease.
Subject(s)
Beauveria , Disease Resistance , Bacteria , Plant Diseases , PlantsABSTRACT
PURPOSE: Facial skin fibroblasts imposed with cyclic stretch at 10% magnitude display considerable mechanotransduction properties and biochemical reactions in our previous study. However, it is poorly understood how these shared traits are fully parallel to the common features across all fibroblasts derived from different skin-based anatomical regions in response to cyclic stretch stimulation. Thus, the purpose of this study was to evaluate the effects of various cyclic stretches on fibroblasts derived from multiple anatomical skin sites of human bodies, and the optimal stretch magnitude was defined based on the changes to cell mechanical behavior. METHODS: Fibroblasts from skin areas of the scalp, anterior chest, suprapubic, axilla, and planta were cultured and characterized in vitro. Cyclic stretch at 0%, 5%, 10%, 15%, and 20% magnitudes was imposed at a loading frequency of 0.1 Hz for 48 hours, and thereafter, the mechanical behavior and biochemical reaction of the dermal fibroblasts were analyzed. RESULTS: Dermal fibroblasts from various anatomical sites preconditioned with varying cyclic stretch led to an evident increase in the cell proliferation ability, the expression of integrin ß1 and p130 Crk-associated substrate messenger RNA and protein, and the productions of type I collagen and transforming growth factor ß1, most importantly in a strain magnitude-dependent manner with the peak appearing in the range of 10% to 15% magnitude cyclic stretch. CONCLUSIONS: These findings may facilitate the subsequent studies on the conversion of normal skin fibroblasts into hypertrophic scar cells, which should be considered in an interpretation of the mechanisms of hypertrophic scarring and skin mechanics.
Subject(s)
Cell Proliferation/physiology , Cicatrix, Hypertrophic/metabolism , Fibroblasts/metabolism , Mechanotransduction, Cellular/physiology , Transforming Growth Factor beta1/metabolism , Analysis of Variance , Cells, Cultured , Cicatrix, Hypertrophic/pathology , Collagen/metabolism , Fibroblasts/pathology , Humans , Immunoblotting , Real-Time Polymerase Chain Reaction/methods , Skin/pathologyABSTRACT
Transient receptor potential (TRP) channels in the spinal dorsal horn lamina II (substantia gelatinosa; SG), which are involved in the modulation of nociceptive transmission, have not yet been fully examined in property. Activation of the TRP channels by various plant-derived chemicals results in an increase in the spontaneous release of L-glutamate onto the SG neurons. We examined the effects of a monoterpene ketone (-)-carvone (contained in spearmint) and its stereoisomer (+)-carvone (in caraway) on glutamatergic spontaneous excitatory transmission in SG neurons of adult rat spinal cord slices by using the whole-cell patch-clamp technique. (-)-Carvone and (+)-carvone increased the frequency of spontaneous excitatory postsynaptic current (sEPSC) in a reversible and concentration-dependent manner with a small increase in its amplitude. Half-maximal effective concentrations of (-)-carvone and (+)-carvone in increasing sEPSC frequency were 0.70 mM and 0.72 mM, respectively. The (-)-carvone but not (+)-carvone activity was inhibited by a TRPV1 antagonist capsazepine. On the other hand, the (+)-carvone but not (-)-carvone activity was inhibited by a TRPA1 antagonist HC-030031. These results indicate that (-)-carvone and (+)-carvone activate TRPV1 and TRPA1 channels, respectively, resulting in an increase in spontaneous L-glutamate release onto SG neurons, with almost the same efficacy. Such a difference in TRP activation between the stereoisomers may serve to know the properties of TRP channels in the SG.
Subject(s)
Glutamic Acid/metabolism , Monoterpenes/pharmacology , Substantia Gelatinosa/drug effects , Substantia Gelatinosa/physiology , Transient Receptor Potential Channels/agonists , Acetanilides/pharmacology , Animals , Capsaicin/analogs & derivatives , Capsaicin/pharmacology , Cyclohexane Monoterpenes , Excitatory Postsynaptic Potentials/drug effects , Male , Monoterpenes/chemistry , Neurons/drug effects , Neurons/physiology , Patch-Clamp Techniques , Purines/pharmacology , Rats , Rats, Sprague-Dawley , Stereoisomerism , Substantia Gelatinosa/cytology , Synaptic Transmission/drug effects , TRPA1 Cation Channel , TRPC Cation Channels/agonists , TRPC Cation Channels/antagonists & inhibitors , TRPV Cation Channels/agonists , TRPV Cation Channels/antagonists & inhibitors , Transient Receptor Potential Channels/antagonists & inhibitorsABSTRACT
Addition of organic compounds containing O/N heteroatoms to aqueous electrolytes such as ZnSO4 (ZS) solutions is one of the effective strategies to inhibit Zn anode dendrites and side reactions. However, addressing the stability of Zn plating/stripping at high current densities and areal capacities by this method is still a challenge, especially in capacitors known for high power and long life. Herein, an organic heterocyclic compound of 1, 4, 7, 10-tetraazacyclododecane (TC) containing four symmetrically distributed N atoms is employed as ZS additive, expanding the life of Zn anodes from ≈ 30 h to 1000 and 240 h at deep plating/stripping conditions of 10 and 20 mA cm-2/mAh cm-2, respectively; the cumulative capacity is as high as 5.0 Ah cm-2 with 99% Coulombic efficiency, far exceeding reported additives. TC with higher binding energies than H2O for Zn species tends to adsorb to Zn (002) in a lying manner and participate in the solvation shell of Zn2+, thus avoiding Zn dendrites and side-reaction damage, especially at high current densities. The TC-endowed Zn anode's stability under such extreme conditions is verified in Zn-ion capacitors (i.e., > 94.6% capacity retention after 28 000 cycles), providing new insights into the development of high-power Zn-based energy storage devices.
ABSTRACT
Oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are essential for the development of excellent bifunctional electrocatalysts, which are key functions in clean energy production. The emphasis of this study lies in the rapid design and investigation of 153 MN4-graphene (Gra)/ MXene (M2NO) electrocatalysts for ORR/OER catalytic activity using machine learning (ML) and density functional theory (DFT). The DFT results indicated that CoN4-Gra/Ti2NO had both good ORR (0.37 V) and OER (0.30 V) overpotentials, while TiN4-Gra/M2NO and MN4-Gra/Cr2NO had high overpotentials. Our research further indicated orbital spin polarization and d-band centers far from the Fermi energy level, affecting the adsorption energy of oxygen-containing intermediates and thus reducing the catalytic activity. The ML results showed that the gradient boosting regression (GBR) model successfully predicted the overpotentials of the monofunctional catalysts RhN4-Gra/Ti2NO (ORR, 0.39 V) and RuN4-Gra/W2NO (OER, 0.45 V) as well as the overpotentials of the bifunctional catalyst RuN4-Gra/W2NO (ORR, 0.39 V; OER, 0.45 V). The symbolic regression (SR) algorithm was used to construct the overpotential descriptors without environmental variable features to accelerate the catalyst screening and shorten the trial-and-error costs from the source, providing a reliable theoretical basis for the experimental synthesis of MXene heterostructures.
ABSTRACT
In this work, we demonstrate the immunocapture and on-line fluorescence immunoassay of protein and virus based on porous polymer monoliths (PPM) in microfluidic devices. Poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) [poly(GMA-co-EGDMA)] monoliths were successfully synthesized in the polydimethylsiloxane (PDMS) microfluidic channels by in situ UV-initiated free radical polymerization. After surface modification, PPM provides a high-surface area and specific affinity 3D substrate for immunoassays. Combining with well controlled microfluidic devices, the direct immunoassay of IgG and sandwich immunoassay of inactivated H1N1 influenza virus using 5 µL sample has been accomplished, with detection limits of 4 ng mL(-1) and less than 10 pg mL(-1), respectively. The enhanced detection sensitivity is due to both high surface area of PPM and flow-through design. The detection time was obviously decreased mainly due to the shortened diffusion distance and improved convective mass transfer inside the monolith, which accelerates the reaction kinetics between antigen and antibody. This work provides a novel microfluidic immunoassay platform with high efficiency thereby enabling fast and sensitive immunoassay.
Subject(s)
Dimethylpolysiloxanes/chemistry , Immunoassay/instrumentation , Immunoglobulin G/analysis , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza, Human/virology , Microfluidic Analytical Techniques/instrumentation , Equipment Design , Ethylene Glycols , Humans , Influenza A Virus, H1N1 Subtype/immunology , Methacrylates/chemical synthesis , Methacrylates/chemistry , Polymerization , Porosity , Sensitivity and SpecificityABSTRACT
OBJECTIVE: To investigate the alteration of PV interneurons in ALS mainly focusing its dynamic changes and its relationship with motor neurons and ErbB4 signaling. METHODS: SOD1G93A mice were used as ALS model. ALS animals were divided into different groups according to birth age: symptomatic prophase (50~60 days), symptomatic phase (90~100 days), and symptomatic progression (130~140 days). Immunofluorescence was performed for measurement of PV-positive interneurons, MMP-9, ChAT, NeuN and ErbB4. RT-qPCR and western blot were used to determine the expression of PV and MMP-9. RESULTS: PV expression was remarkably higher in the anterior horn of gray matter compared with posterior horn and area in the middle of gray matter in control mice. In ALS mice, PV, MMP-9 and ErbB4 levels were gradually decreased along with onset. PV, MMP-9 and ErbB4 levels in ALS mice were significantly down-regulated than control mice after onset, indicating the alteration of PV interneurons, FαMNs and ErbB4. SαMNs levels only decreased remarkably at symptomatic progression in ALS mice compared with control mice, while γMNs levels showed no significant change during whole period in all mice. MMP-9 and ErbB4 were positively correlated with PV. NRG1 treatment significantly enhanced the expression of ErBb4, PV and MMP-9 in ALS mice. CONCLUSION: PV interneurons decrease is along with FαMNs and ErbB4 decrease in ALS mice.