Genes involved in chemosensation are essential for odorant-mediated insect behaviors. Odorant receptors(ORs) bind and respond to pheromones and plant volatiles, regulating insect behaviors such as mating and host-plan...Genes involved in chemosensation are essential for odorant-mediated insect behaviors. Odorant receptors(ORs) bind and respond to pheromones and plant volatiles, regulating insect behaviors such as mating and host-plant selection, while ionotropic receptors(IRs), which are present at lower levels in insects than ORs, influence ion channels, especially in agricultural pests. Asian corn borer, Ostrinia furnacalis, is the main pest of maize that causes huge economic losses in Asia. Twenty-one Ofur IRs have been identified, but none has been characterized. In this study, tissue-specific expression profiling, phylogenetic analysis, and electroantennography(EAG) analysis were applied to characterize the evolution, expression, and the potential function of Ofur IRs. It was found that 20 Ofur IRs were highly expressed in the antennae, except for Ofur IR75p3, whereas 10 and nine Ofur IRs were highly expressed in the proboscis and genitalia, respectively, indicating that these Ofur IRs were functionally associated with feeding and oviposition. EAG results showed that seven acids elicited responses in the antennae of O. furnacalis and that 2-oxopentanoic acid displayed a significant femalebiased response. Combined with the phylogenetic analysis, 10 Ofur IRs in clade 4 were roughly predicted to be candidate receptors for 2-oxopentanoic acid and other tested acids. These results provide basic information about Ofur IRs and may help advance the knolwedge on the olfactory system of O. furnacalis.展开更多
Microspheres containing Pioglitazone hydrochloride were prepared by the ionotropic external gelation method, using sodium alginate with four mucoadhesive polymers namely sodium carboxy methyl cellulose, hydroxy propyl...Microspheres containing Pioglitazone hydrochloride were prepared by the ionotropic external gelation method, using sodium alginate with four mucoadhesive polymers namely sodium carboxy methyl cellulose, hydroxy propyl methyl cellulose, carbopol 934 P and cellulose acetate phthalate as coat materials. Ionotropic gelation is a method to prepare microspheres using combination of Ca<sup>2+</sup> as cationic components and alginate as anion. The practical yield of prepared microspheres using the ionotropic gelation technique was between 172 mg and 604 mg. The result of the Chi-squared test carried out between the actual (practical) and expected (theoretical) yields showed no significant difference (P < 0.05) which indicated that the ionotropic gelation technique could be successfully employed to prepare pioglitazone microspheres using sodium alginate, sodium carboxy methyl cellulose, carbopol 934 P, HPMC, cellulose acetate butyrate polymers. The drug entrapment efficiency of prepared microspheres showed between 56.12% ± 3.86% to 84.68% ± 2.93% which was significantly higher for ionotropic gelation technique. The highest drug entrapment was found in formulation PMI 8. Swelling index is the capability of a polymer to swell before the drug is released which influences the rate and mechanism of drug release from the polymer matrix. The swelling index of prepared microspheres was in the range of 68% ± 4.52% to 87% ± 0.98%. Pioglitazone HCl microspheres showed controlled release of drug without initial peak level achieving. This type of properties in Pioglitazone HCl microspheres used to decrease side effects, reduce dosing frequency and improve patient compliances. From the all batches PMI 8 is considered the best formulation, because among all other formulations, it shows better extent of drug release up to 82.12% (18 h), good entrapment efficiency (84.68%) and the ex-vivo wash-off test shows the best mucoadhesive property. The in vitro drug release studies do up to 18 h. As observed from the various plots, most of the formulations followed the Korsmeyer-Peppas model.展开更多
Ionotropic receptors(IRs)were first found in Drosophila melanogaster,and derive from ionotropic glutamate receptors(iGluRs),which are implicated in detecting acids,ammonia,amine,temperature and humidity.Although IRs a...Ionotropic receptors(IRs)were first found in Drosophila melanogaster,and derive from ionotropic glutamate receptors(iGluRs),which are implicated in detecting acids,ammonia,amine,temperature and humidity.Although IRs are involved in sensing acid odors in a few insects,such as D.melanogaster,Aedes aegypti,and Manduca sexta,the function of IRs in Helicoverpa armigera is still unknown.IR8a was confirmed to be a co-receptor associated with acid detection.From the results of phylogenetic analysis,HarmIR8a displayed high similarity compared to homologs in D.melanogaster,M.sexta,and A.aegypti,suggesting that HarmIR8a might have a consistent function as a co-receptor for acid detection.In this study,clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)-mediated genome editing was implemented to knockout HarmIR8a for in vivo functional analysis.Electrophysiological and behavioral assays were performed to compare the differences between HarmIR8a knockout mutants and wild type individuals.From electroantennogram(EAG)analysis,we found that wild type H.armigera adults could detect short-chain carboxylic acids.In addition,wind tunnel experiments showed that 1%acetic acid attracted wild type H.armigera adults.However,acid sensing and attraction were reduced or abolished in the HarmIR8a knockout mutants.Our data suggest that HarmIR8a is important for H.armigera to detect short-chain carboxylic acids and mediate attraction behavior to acetic acid.展开更多
Phenylacetaldehyde(PAH),an aromatic compound,is present in a diverse range of fruits including overripe bananas and prickly pear cactus,the two major host fruits for Drosophila melanogaster.PAH acts as a potent ligand...Phenylacetaldehyde(PAH),an aromatic compound,is present in a diverse range of fruits including overripe bananas and prickly pear cactus,the two major host fruits for Drosophila melanogaster.PAH acts as a potent ligand for the ionotropic receptor 84a(IR84a)in the adult fruit fly and it is detected by the IR84a/IR8a heterotetrameric complex.Its role in the male courtship behavior through IR84a as an environmental aphrodisiac is of additional importance.In D.melanogaster,two distinct kinds of olfactory receptors,that is,odorant receptors(ORs)and ionotropic receptors(IRs),perceive the odorant stimuli.They display unique structural,molecular,and functional characteristics in addition to having different evolutionary origins.Traditionally,olfactory cues detected by the ORs such as ethyl acetate,1-butanol,isoamyl acetate,1-octanol,4-methylcyclohexanol,etc.classified as aliphatic esters and alcohols have been employed in olfactory classical conditioning using fruit flies.This underlines the participation of OR-activated olfactory pathways in learning and memory formation.Our study elucidates that likewise ethyl acetate(EA)(an OR-responsive odorant),PAH(an IR-responsive aromatic compound)too can form learning and memory when associated with an appetitive gustatory reinforcer.The association of PAH with sucrose(PAH/SUC)led to learning and formation of the long-term memory(LTM).Additionally,the Orco^(1),Ir84a^(MI00501),and Ir8a^(1)mutant flies were used to confirm the exclusive participation of the IR84a/IR8a complex in PAH/SUC olfactory associative conditioning.These results highlight the involvement of IRs via an IR-activated pathway in facilitating robust olfactory behavior.展开更多
Recent advances in neuroscience have illuminated the central role of glutamate dysregulation in various neurological disorders.The glutamatergic system has emerged as a central player in the pathophysiology of various...Recent advances in neuroscience have illuminated the central role of glutamate dysregulation in various neurological disorders.The glutamatergic system has emerged as a central player in the pathophysiology of various neurological disorders.The dysregulation of glutamate signaling,leading to excitotoxicity and neuronal cell death,has been a focal point in understanding the underlying mechanisms of these conditions.This has prompted a paradigm shift in neuroprotection research,with a growing emphasis on targeting ionotropic glutamate receptors(iGluRs)to restore glutamatergic homeostasis.This review provides a comprehensive overview of recent advancements in the field of iGluR-targeted neuroprotection.We further investigate the implications of glutamate dysregulation in the central nervous system(CNS)disorders,highlighting the complex interplay between excitotoxicity and neuroprotection.We elucidate the multifaceted factors that render neurons vulnerable to excitotoxic damage,emphasizing the need for innovative therapeutic approaches.This review provides an extensive survey of the burgeoning field of iGluR-targeted neuroprotection.It showcases the significant potential of a wide array of compounds,encompassing both natural and synthetic agents,to modulate iGluRs and ameliorate excitotoxicity and oxidative stress-induced neuronal damage.These compounds have demonstrated impressive neuroprotective effects in diverse experimental models,from glutamate-induced toxicity to traumatic brain injuries.We advocate for further research and clinical investigations to harness the full therapeutic potential of iGluR modulation,heralding a promising era in neuroprotection and CNs disorder management.展开更多
Correction to:Cellular and Molecular Immunology https://doi.org/10.1038/s41423-020-0421-z,published online 20 April 2020 The authors have agreed to add Parmis Blomgran(Linköping University,Department of Orthopedi...Correction to:Cellular and Molecular Immunology https://doi.org/10.1038/s41423-020-0421-z,published online 20 April 2020 The authors have agreed to add Parmis Blomgran(Linköping University,Department of Orthopedics and Sports Medicine,Linkoping,Sweden)as co-author of this study.The updated order of authors will be:Md Abdul Alim,Mirjana Grujic,Paul W Ackerman,Per Kristiansson,Parmis Blomgran,Pernilla Eliasson,Magnus Peterson,Gunnar Pejler.展开更多
AMPA Receptor and PET Tracer Limitation.The alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid receptor(AMPAR)is a subtype of ionotropic glutamate receptor.It functions as a ligand-gated ion channel and is primar...AMPA Receptor and PET Tracer Limitation.The alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid receptor(AMPAR)is a subtype of ionotropic glutamate receptor.It functions as a ligand-gated ion channel and is primarily responsible for rapidly transmitting the signal from glutamate in the central nervous system[1].This receptor plays a crucial role in various cognitive functions including learning,memory,cognition,synaptic plasticity,and neurodevelopment.AMPARs are typically composed of four subunits,namely GluA1,GluA2,GluA3,and GluA4,which can form homo-or hetero-tetramers.These subunits bind directly or indirectly to various scaffolding proteins such as transmembrane AMPA receptor regulatory proteins(TARPs).展开更多
In order to improve the substrate diffusion properties and stability of an immobilized enzyme alginate microgels modified with TiO2 nanoparticles were employed as the enzyme immobilizing support.Ionotropic gelation wa...In order to improve the substrate diffusion properties and stability of an immobilized enzyme alginate microgels modified with TiO2 nanoparticles were employed as the enzyme immobilizing support.Ionotropic gelation was applied for the preparation of hybrid gels while Ca2＋ Ce3＋ Ni2＋Cu2＋and Fe3＋were employed as the crosslinkers.Papain was selected as the model enzyme. UV-Vis spectroscopy was employed to investigate the activity of papain to evaluate kinetics and stability.Analysis results show that the highest affinity the lowest Michaelis-Menten constant Km =11.0 mg/mL and the highest stability are obtained when using Cu2＋as the crosslinker.The effect of the mass ratio of TiO2 to papain on the stability and leakage of papain is also investigated and the results show that 10∶1 TiO2∶papain is optimal because the proper use of TiO2 can reduce enzyme leakage and ensure enzyme stability.Preparing Cu/alginate/TiO2 hybrid gels via ionotropic gelation can provide a satisfactory diffusion capability and enzyme stability.展开更多
Specific and sustained release of nutrients from capsules to the gastrointestinal tract has attracted many attentions in the field of food and drug delivery.In this work,we reported a monoaxial dispersion electrospray...Specific and sustained release of nutrients from capsules to the gastrointestinal tract has attracted many attentions in the field of food and drug delivery.In this work,we reported a monoaxial dispersion electrospraying-ionotropic gelation technique to prepare multicore millimeter-sized spherical capsules for specific and sustained release of fish oil.The spherical capsules had diameters from 2.05 mm to 0.35 mm with the increased applied voltages.The capsules consisted of uniform(at applied voltages of≤10 k V)or nonuniform(at applied voltages of>10 k V)multicores.The obtained capsules had reasonable loading ratios(9.7%-6.3%)due to the multicore structure.In addition,the obtained capsules had specific and sustained release behaviors of fish oil into the small intestinal phase of in vitro gastrointestinal tract and small intestinal tract models.The simple monoaxial dispersion electrospraying-ionotropic gelatin technique does not involve complicated preparation formulations and polymer modification,which makes the technique has a potential application prospect for the fish oil preparations and the encapsulation of functional active substances in the field of food and drug industries.展开更多
Trigeminal neuralgia is a debilitating condition,and the pain easily spreads to other parts of the face.Here,we established a mouse model of partial transection of the infraorbital nerve(pT-ION)and found that the Conn...Trigeminal neuralgia is a debilitating condition,and the pain easily spreads to other parts of the face.Here,we established a mouse model of partial transection of the infraorbital nerve(pT-ION)and found that the Connexin 36(Cx36)inhibitor mefloquine caused greater alleviation of pT-ION-induced cold allodynia compared to the reduction of mechanical allodynia.Mefloquine reversed the pT-IONinduced upregulation of Cx36,glutamate receptor ionotropic kainate 2(GluK2),transient receptor potential ankyrin 1(TRPA1),and phosphorylated extracellular signal regulated kinase(p-ERK)in the trigeminal ganglion.Cold allodynia but not mechanic al allodynia induced by pT-ION or by virusmediated overexpression of Cx36 in the trigeminal ganglion was reversed by the GluK2 antagonist NS 102,and knocking down Cx36 expression in Nav1.8-expressing nociceptors by injecting virus into the orofacial skin area of Nav1.8-Cre mice attenuated cold allodynia but not mechanic al allodynia.In conclusion,we show that Cx36 contributes greatly to the development of orofacial pain hypersensitivity through GluK2,TRPA1,and p-ERK signaling.展开更多
Objective:Oral slow and sustained release drug delivery system can release their drug content with a controlled manner,producing a desirable blood serum level,reduction in drug toxicity and improving the patient compl...Objective:Oral slow and sustained release drug delivery system can release their drug content with a controlled manner,producing a desirable blood serum level,reduction in drug toxicity and improving the patient compliance by prolonging dosing intervals.The major drawback of orally administered drug like diltiazem as a calcium channel blocker for the treatment of angina pectoris,arrhythmia and hypertension.Its has higher aqueous solubility and shorter elimination half-life.Methods:To overcome these drawbacks associated with diltiazem,an attempt has been made to develop a sustained release dosage form of diltiazem embedded alginate microbeads by ionotropic gelation technique employing various concentrations of polymer and keeping the drug concentration constant.Results:The beads were characterized for its particle size,drug content and in vitro release studies. The results revealed that the surface adhering drug was found to release immediately and a steady state of release was obtained up to 12 h from all the batches.The results indicated there was an inverse relationship between the concentration of alginate and drug release.The drug release was found to follow non-fickian diffusion obeying first order kinetics.Conclusion:The developed alginate microbeads offered a sustained release of diltiazem. Hence,the formulated microbeads were found to be potential,cost effective,possess satisfactory in vitro release studies.展开更多
OBJECTIVE AMPA-subtype iono⁃tropic glutamate receptors(iGluRs)mediate fast excitatory synaptic transmission in the mammali⁃an central nervous system(CNS).It plays the key role in many central nerves disorder such as e...OBJECTIVE AMPA-subtype iono⁃tropic glutamate receptors(iGluRs)mediate fast excitatory synaptic transmission in the mammali⁃an central nervous system(CNS).It plays the key role in many central nerves disorder such as epilepsy,depression and schizophrenia.Star⁃gazin(STZ,also named TARP-γ2),as the first TARPs found in CNS,potentiates AMPAR activity by attenuating deactivation and desensitization,enhancing recovery from desensitization,and facilitating agonist affinity and efficacy.However,it is still not fully understanding howγ-2 modu⁃late AMPAR gating.METHODS AND RESULTS The desensitization for different mutation of AMPAR andγ-2 was compared.It was shown that the electric attraction was involved in the interaction of AMPAR andγ-2.In addition,the interaction of KGK motif in ligand binding domain and pre-M1 chain of AMPAR and EX1 ofγ-2 modulate AMPAR opening and desensitization.Substitution of these charged residues had sur⁃prisingly effects on AMPAR desensitization kinet⁃ics.CONCLUSION The electric attraction has two impacts on the channels gating process the first destablizing the receptor closed state and enabling the channel opening,the second pro⁃moting the channels entering desensitization state upon the channel opening.展开更多
The formation and application of polymeric nanomaterials is great demand in science,industry,biotechnology,and medicine due to the possibility of achieving a significant improvement in the physicochemical,mechanical,a...The formation and application of polymeric nanomaterials is great demand in science,industry,biotechnology,and medicine due to the possibility of achieving a significant improvement in the physicochemical,mechanical,and barrier properties of polymers and using them as drug carriers and fillers,which is especially promising for biodegradable polymers such as chitosan and their derivatives.The article presents methods for creating polymer nanostructures based on polysaccharides and,in particular,chitosan.Obtaining nanostructured samples of chitosan using the approaches of chemical transformation and modification of polysaccharides is an urgent scientific problem,the solution of which makes it possible to obtain new polymer systems of great practical interest.The medical aspects of the use of polymer carriers based on chitosan for the treatment of various diseases are discussed.The unique specificity of the properties of chitosan and nanomaterials derived from it,with the properties inherent in this natural polymer,can serve as a promising future,especially in the field of medicine.展开更多
Insects often face both conditions with sufficient nutrients and conditions of undernutrition in the field.Through gustatory receptors,insects sense nutrients and regulate their physiological functions such as feeding...Insects often face both conditions with sufficient nutrients and conditions of undernutrition in the field.Through gustatory receptors,insects sense nutrients and regulate their physiological functions such as feeding and reproduction.However,it remains unclear whether signaling pathways activated by gustatory receptors depend on the concentration of nutrients and whether the difference in signaling pathways directly affects insects’physiological functions.Herein,we found that a sugar gustatory receptor,NlGr11,from the brown planthopper(BPH),Nilaparvata lugens,activated G protein-coupled signaling and ionotropic pathways when bound to high galactose concentration.BPHs subsequently demonstrated longer feeding times,feeding loads,and higher vitellogenin(NlVg)expression than BPHs exposed to high galactose concentrations,which only activated the ionotropic pathway.For the first time,our findings link plant nutrient conditions,signaling pathways activated by nutrients,and their gustatory receptors,and nutrient dose-dependent feeding efficacy and vitellogenin(Vg)expression in an insect.This will help us to better understand the molecular mechanism for insect feeding strategies on plants at different stages of nutritional conditions.展开更多
Encapsulation of potential bioactive natural substances is a promising preservation method for the natural additives over the synthetic antixodiants. In this study, ionic gelation has been used to encapsulate the Mori...Encapsulation of potential bioactive natural substances is a promising preservation method for the natural additives over the synthetic antixodiants. In this study, ionic gelation has been used to encapsulate the Moringa oleifera leaf extract in biopolymers. Automatic solvent extraction was used to extract active material from the plant. Then, the active material was covered by chitosan/alginate via ionic gelation. Ionic gelation system was designed and optimized by Central Composite design of Response Surface Method (RSM). Exposure time to gelling medium (10–30 min), sodium alginate concentration (1%–2%, w/v) and chitosan concentration (0.5%–1%, w/v) were process parameters to be optimized for the maximum encapsulation efficiency concerning total phenolic content (EETPC ), rutin (major individual compound) concentration and inhibition effect of the capsules against DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) free radical. Particle shape and morphology of the dried microcapsules show that the capsules obtained are quite spherical, uniform and have a regular structure depending on stereo-microscope and scanning electron microscopy (SEM) analyzes.展开更多
As the global population ages,research on the pathogenesis and treatment options for older patients with dementia has become increasingly important.Vascular dementia(VaD),the second most frequent type of dementia,is c...As the global population ages,research on the pathogenesis and treatment options for older patients with dementia has become increasingly important.Vascular dementia(VaD),the second most frequent type of dementia,is characterized by vascular impairment caused by inadequate blood supply to the brain.VaD is a complex neurological disorder involving multiple cells and signaling pathways,and its prevention and treatment pose clinical challenges with significant behavioral implications.Glutamate,the most abundant amino acid in the brain,plays a critical role as an excitatory neurotransmitter,impacting cognitive function,learning,and memory.Abnormal glutamate metabolism has been closely linked to dementia,and reduced blood flow to the brain can lead to excessive glutamate accumulation,resulting in neuronal death.This article highlights the connection between VaD and glutamate metabolism,aiming to identify better methods for preventing and treating VaD via regulating glutamate metabolism.展开更多
基金supported by the National Natural Science Foundation of China(31701859,31725023 and 31621064)。
文摘Genes involved in chemosensation are essential for odorant-mediated insect behaviors. Odorant receptors(ORs) bind and respond to pheromones and plant volatiles, regulating insect behaviors such as mating and host-plant selection, while ionotropic receptors(IRs), which are present at lower levels in insects than ORs, influence ion channels, especially in agricultural pests. Asian corn borer, Ostrinia furnacalis, is the main pest of maize that causes huge economic losses in Asia. Twenty-one Ofur IRs have been identified, but none has been characterized. In this study, tissue-specific expression profiling, phylogenetic analysis, and electroantennography(EAG) analysis were applied to characterize the evolution, expression, and the potential function of Ofur IRs. It was found that 20 Ofur IRs were highly expressed in the antennae, except for Ofur IR75p3, whereas 10 and nine Ofur IRs were highly expressed in the proboscis and genitalia, respectively, indicating that these Ofur IRs were functionally associated with feeding and oviposition. EAG results showed that seven acids elicited responses in the antennae of O. furnacalis and that 2-oxopentanoic acid displayed a significant femalebiased response. Combined with the phylogenetic analysis, 10 Ofur IRs in clade 4 were roughly predicted to be candidate receptors for 2-oxopentanoic acid and other tested acids. These results provide basic information about Ofur IRs and may help advance the knolwedge on the olfactory system of O. furnacalis.
文摘Microspheres containing Pioglitazone hydrochloride were prepared by the ionotropic external gelation method, using sodium alginate with four mucoadhesive polymers namely sodium carboxy methyl cellulose, hydroxy propyl methyl cellulose, carbopol 934 P and cellulose acetate phthalate as coat materials. Ionotropic gelation is a method to prepare microspheres using combination of Ca<sup>2+</sup> as cationic components and alginate as anion. The practical yield of prepared microspheres using the ionotropic gelation technique was between 172 mg and 604 mg. The result of the Chi-squared test carried out between the actual (practical) and expected (theoretical) yields showed no significant difference (P < 0.05) which indicated that the ionotropic gelation technique could be successfully employed to prepare pioglitazone microspheres using sodium alginate, sodium carboxy methyl cellulose, carbopol 934 P, HPMC, cellulose acetate butyrate polymers. The drug entrapment efficiency of prepared microspheres showed between 56.12% ± 3.86% to 84.68% ± 2.93% which was significantly higher for ionotropic gelation technique. The highest drug entrapment was found in formulation PMI 8. Swelling index is the capability of a polymer to swell before the drug is released which influences the rate and mechanism of drug release from the polymer matrix. The swelling index of prepared microspheres was in the range of 68% ± 4.52% to 87% ± 0.98%. Pioglitazone HCl microspheres showed controlled release of drug without initial peak level achieving. This type of properties in Pioglitazone HCl microspheres used to decrease side effects, reduce dosing frequency and improve patient compliances. From the all batches PMI 8 is considered the best formulation, because among all other formulations, it shows better extent of drug release up to 82.12% (18 h), good entrapment efficiency (84.68%) and the ex-vivo wash-off test shows the best mucoadhesive property. The in vitro drug release studies do up to 18 h. As observed from the various plots, most of the formulations followed the Korsmeyer-Peppas model.
基金This work was funded by National Natural Science Foundation of China(31725023 and 31861133019)Shenzhen Science and Technology Program(Grant No.KQTD20180411143628272).
文摘Ionotropic receptors(IRs)were first found in Drosophila melanogaster,and derive from ionotropic glutamate receptors(iGluRs),which are implicated in detecting acids,ammonia,amine,temperature and humidity.Although IRs are involved in sensing acid odors in a few insects,such as D.melanogaster,Aedes aegypti,and Manduca sexta,the function of IRs in Helicoverpa armigera is still unknown.IR8a was confirmed to be a co-receptor associated with acid detection.From the results of phylogenetic analysis,HarmIR8a displayed high similarity compared to homologs in D.melanogaster,M.sexta,and A.aegypti,suggesting that HarmIR8a might have a consistent function as a co-receptor for acid detection.In this study,clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)-mediated genome editing was implemented to knockout HarmIR8a for in vivo functional analysis.Electrophysiological and behavioral assays were performed to compare the differences between HarmIR8a knockout mutants and wild type individuals.From electroantennogram(EAG)analysis,we found that wild type H.armigera adults could detect short-chain carboxylic acids.In addition,wind tunnel experiments showed that 1%acetic acid attracted wild type H.armigera adults.However,acid sensing and attraction were reduced or abolished in the HarmIR8a knockout mutants.Our data suggest that HarmIR8a is important for H.armigera to detect short-chain carboxylic acids and mediate attraction behavior to acetic acid.
基金funding of Researchers Supporting Project Number(RSPD2023R710)from King Saud University,Riyadh,Saudi Arabia.
文摘Phenylacetaldehyde(PAH),an aromatic compound,is present in a diverse range of fruits including overripe bananas and prickly pear cactus,the two major host fruits for Drosophila melanogaster.PAH acts as a potent ligand for the ionotropic receptor 84a(IR84a)in the adult fruit fly and it is detected by the IR84a/IR8a heterotetrameric complex.Its role in the male courtship behavior through IR84a as an environmental aphrodisiac is of additional importance.In D.melanogaster,two distinct kinds of olfactory receptors,that is,odorant receptors(ORs)and ionotropic receptors(IRs),perceive the odorant stimuli.They display unique structural,molecular,and functional characteristics in addition to having different evolutionary origins.Traditionally,olfactory cues detected by the ORs such as ethyl acetate,1-butanol,isoamyl acetate,1-octanol,4-methylcyclohexanol,etc.classified as aliphatic esters and alcohols have been employed in olfactory classical conditioning using fruit flies.This underlines the participation of OR-activated olfactory pathways in learning and memory formation.Our study elucidates that likewise ethyl acetate(EA)(an OR-responsive odorant),PAH(an IR-responsive aromatic compound)too can form learning and memory when associated with an appetitive gustatory reinforcer.The association of PAH with sucrose(PAH/SUC)led to learning and formation of the long-term memory(LTM).Additionally,the Orco^(1),Ir84a^(MI00501),and Ir8a^(1)mutant flies were used to confirm the exclusive participation of the IR84a/IR8a complex in PAH/SUC olfactory associative conditioning.These results highlight the involvement of IRs via an IR-activated pathway in facilitating robust olfactory behavior.
文摘Recent advances in neuroscience have illuminated the central role of glutamate dysregulation in various neurological disorders.The glutamatergic system has emerged as a central player in the pathophysiology of various neurological disorders.The dysregulation of glutamate signaling,leading to excitotoxicity and neuronal cell death,has been a focal point in understanding the underlying mechanisms of these conditions.This has prompted a paradigm shift in neuroprotection research,with a growing emphasis on targeting ionotropic glutamate receptors(iGluRs)to restore glutamatergic homeostasis.This review provides a comprehensive overview of recent advancements in the field of iGluR-targeted neuroprotection.We further investigate the implications of glutamate dysregulation in the central nervous system(CNS)disorders,highlighting the complex interplay between excitotoxicity and neuroprotection.We elucidate the multifaceted factors that render neurons vulnerable to excitotoxic damage,emphasizing the need for innovative therapeutic approaches.This review provides an extensive survey of the burgeoning field of iGluR-targeted neuroprotection.It showcases the significant potential of a wide array of compounds,encompassing both natural and synthetic agents,to modulate iGluRs and ameliorate excitotoxicity and oxidative stress-induced neuronal damage.These compounds have demonstrated impressive neuroprotective effects in diverse experimental models,from glutamate-induced toxicity to traumatic brain injuries.We advocate for further research and clinical investigations to harness the full therapeutic potential of iGluR modulation,heralding a promising era in neuroprotection and CNs disorder management.
文摘Correction to:Cellular and Molecular Immunology https://doi.org/10.1038/s41423-020-0421-z,published online 20 April 2020 The authors have agreed to add Parmis Blomgran(Linköping University,Department of Orthopedics and Sports Medicine,Linkoping,Sweden)as co-author of this study.The updated order of authors will be:Md Abdul Alim,Mirjana Grujic,Paul W Ackerman,Per Kristiansson,Parmis Blomgran,Pernilla Eliasson,Magnus Peterson,Gunnar Pejler.
基金supported by the National Natural Science Foundation of China(32371066)the Guangdong Basic and Applied Basic Research Foundation(2022A1515010134)+1 种基金the Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(NYKFKT2019009)the Shenzhen Technological Research Center for Primate Translational Medicine(XMHT20220104005).
文摘AMPA Receptor and PET Tracer Limitation.The alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid receptor(AMPAR)is a subtype of ionotropic glutamate receptor.It functions as a ligand-gated ion channel and is primarily responsible for rapidly transmitting the signal from glutamate in the central nervous system[1].This receptor plays a crucial role in various cognitive functions including learning,memory,cognition,synaptic plasticity,and neurodevelopment.AMPARs are typically composed of four subunits,namely GluA1,GluA2,GluA3,and GluA4,which can form homo-or hetero-tetramers.These subunits bind directly or indirectly to various scaffolding proteins such as transmembrane AMPA receptor regulatory proteins(TARPs).
基金The National Natural Science Foundation of China(No.21005016)the Foundation of Educational Commission of Jiangsu Province(No.JHB2011-2)
文摘In order to improve the substrate diffusion properties and stability of an immobilized enzyme alginate microgels modified with TiO2 nanoparticles were employed as the enzyme immobilizing support.Ionotropic gelation was applied for the preparation of hybrid gels while Ca2＋ Ce3＋ Ni2＋Cu2＋and Fe3＋were employed as the crosslinkers.Papain was selected as the model enzyme. UV-Vis spectroscopy was employed to investigate the activity of papain to evaluate kinetics and stability.Analysis results show that the highest affinity the lowest Michaelis-Menten constant Km =11.0 mg/mL and the highest stability are obtained when using Cu2＋as the crosslinker.The effect of the mass ratio of TiO2 to papain on the stability and leakage of papain is also investigated and the results show that 10∶1 TiO2∶papain is optimal because the proper use of TiO2 can reduce enzyme leakage and ensure enzyme stability.Preparing Cu/alginate/TiO2 hybrid gels via ionotropic gelation can provide a satisfactory diffusion capability and enzyme stability.
基金supported by research grants from the National Key R&D Program(2019YFD0902003)。
文摘Specific and sustained release of nutrients from capsules to the gastrointestinal tract has attracted many attentions in the field of food and drug delivery.In this work,we reported a monoaxial dispersion electrospraying-ionotropic gelation technique to prepare multicore millimeter-sized spherical capsules for specific and sustained release of fish oil.The spherical capsules had diameters from 2.05 mm to 0.35 mm with the increased applied voltages.The capsules consisted of uniform(at applied voltages of≤10 k V)or nonuniform(at applied voltages of>10 k V)multicores.The obtained capsules had reasonable loading ratios(9.7%-6.3%)due to the multicore structure.In addition,the obtained capsules had specific and sustained release behaviors of fish oil into the small intestinal phase of in vitro gastrointestinal tract and small intestinal tract models.The simple monoaxial dispersion electrospraying-ionotropic gelatin technique does not involve complicated preparation formulations and polymer modification,which makes the technique has a potential application prospect for the fish oil preparations and the encapsulation of functional active substances in the field of food and drug industries.
基金the National Natural Science Foundation of China(81971056,31600852,81771202,and 81873101)the Innovative Research Team of Highlevel Local Universities in Shanghai+3 种基金the Foundation of Science,Technology and Innovation Commission of Shenzhen Municipality(JCYJ20180302153701406)the National Key R&D Program of China(2017YFB0403803)the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJLab。
文摘Trigeminal neuralgia is a debilitating condition,and the pain easily spreads to other parts of the face.Here,we established a mouse model of partial transection of the infraorbital nerve(pT-ION)and found that the Connexin 36(Cx36)inhibitor mefloquine caused greater alleviation of pT-ION-induced cold allodynia compared to the reduction of mechanical allodynia.Mefloquine reversed the pT-IONinduced upregulation of Cx36,glutamate receptor ionotropic kainate 2(GluK2),transient receptor potential ankyrin 1(TRPA1),and phosphorylated extracellular signal regulated kinase(p-ERK)in the trigeminal ganglion.Cold allodynia but not mechanic al allodynia induced by pT-ION or by virusmediated overexpression of Cx36 in the trigeminal ganglion was reversed by the GluK2 antagonist NS 102,and knocking down Cx36 expression in Nav1.8-expressing nociceptors by injecting virus into the orofacial skin area of Nav1.8-Cre mice attenuated cold allodynia but not mechanic al allodynia.In conclusion,we show that Cx36 contributes greatly to the development of orofacial pain hypersensitivity through GluK2,TRPA1,and p-ERK signaling.
文摘Objective:Oral slow and sustained release drug delivery system can release their drug content with a controlled manner,producing a desirable blood serum level,reduction in drug toxicity and improving the patient compliance by prolonging dosing intervals.The major drawback of orally administered drug like diltiazem as a calcium channel blocker for the treatment of angina pectoris,arrhythmia and hypertension.Its has higher aqueous solubility and shorter elimination half-life.Methods:To overcome these drawbacks associated with diltiazem,an attempt has been made to develop a sustained release dosage form of diltiazem embedded alginate microbeads by ionotropic gelation technique employing various concentrations of polymer and keeping the drug concentration constant.Results:The beads were characterized for its particle size,drug content and in vitro release studies. The results revealed that the surface adhering drug was found to release immediately and a steady state of release was obtained up to 12 h from all the batches.The results indicated there was an inverse relationship between the concentration of alginate and drug release.The drug release was found to follow non-fickian diffusion obeying first order kinetics.Conclusion:The developed alginate microbeads offered a sustained release of diltiazem. Hence,the formulated microbeads were found to be potential,cost effective,possess satisfactory in vitro release studies.
文摘OBJECTIVE AMPA-subtype iono⁃tropic glutamate receptors(iGluRs)mediate fast excitatory synaptic transmission in the mammali⁃an central nervous system(CNS).It plays the key role in many central nerves disorder such as epilepsy,depression and schizophrenia.Star⁃gazin(STZ,also named TARP-γ2),as the first TARPs found in CNS,potentiates AMPAR activity by attenuating deactivation and desensitization,enhancing recovery from desensitization,and facilitating agonist affinity and efficacy.However,it is still not fully understanding howγ-2 modu⁃late AMPAR gating.METHODS AND RESULTS The desensitization for different mutation of AMPAR andγ-2 was compared.It was shown that the electric attraction was involved in the interaction of AMPAR andγ-2.In addition,the interaction of KGK motif in ligand binding domain and pre-M1 chain of AMPAR and EX1 ofγ-2 modulate AMPAR opening and desensitization.Substitution of these charged residues had sur⁃prisingly effects on AMPAR desensitization kinet⁃ics.CONCLUSION The electric attraction has two impacts on the channels gating process the first destablizing the receptor closed state and enabling the channel opening,the second pro⁃moting the channels entering desensitization state upon the channel opening.
文摘The formation and application of polymeric nanomaterials is great demand in science,industry,biotechnology,and medicine due to the possibility of achieving a significant improvement in the physicochemical,mechanical,and barrier properties of polymers and using them as drug carriers and fillers,which is especially promising for biodegradable polymers such as chitosan and their derivatives.The article presents methods for creating polymer nanostructures based on polysaccharides and,in particular,chitosan.Obtaining nanostructured samples of chitosan using the approaches of chemical transformation and modification of polysaccharides is an urgent scientific problem,the solution of which makes it possible to obtain new polymer systems of great practical interest.The medical aspects of the use of polymer carriers based on chitosan for the treatment of various diseases are discussed.The unique specificity of the properties of chitosan and nanomaterials derived from it,with the properties inherent in this natural polymer,can serve as a promising future,especially in the field of medicine.
基金supported by the National Natural Science Foundation of China(31730073,U1401212)Guizhou Science and Technology Project(qiankeheji-zk[2021]General 135).
文摘Insects often face both conditions with sufficient nutrients and conditions of undernutrition in the field.Through gustatory receptors,insects sense nutrients and regulate their physiological functions such as feeding and reproduction.However,it remains unclear whether signaling pathways activated by gustatory receptors depend on the concentration of nutrients and whether the difference in signaling pathways directly affects insects’physiological functions.Herein,we found that a sugar gustatory receptor,NlGr11,from the brown planthopper(BPH),Nilaparvata lugens,activated G protein-coupled signaling and ionotropic pathways when bound to high galactose concentration.BPHs subsequently demonstrated longer feeding times,feeding loads,and higher vitellogenin(NlVg)expression than BPHs exposed to high galactose concentrations,which only activated the ionotropic pathway.For the first time,our findings link plant nutrient conditions,signaling pathways activated by nutrients,and their gustatory receptors,and nutrient dose-dependent feeding efficacy and vitellogenin(Vg)expression in an insect.This will help us to better understand the molecular mechanism for insect feeding strategies on plants at different stages of nutritional conditions.
文摘Encapsulation of potential bioactive natural substances is a promising preservation method for the natural additives over the synthetic antixodiants. In this study, ionic gelation has been used to encapsulate the Moringa oleifera leaf extract in biopolymers. Automatic solvent extraction was used to extract active material from the plant. Then, the active material was covered by chitosan/alginate via ionic gelation. Ionic gelation system was designed and optimized by Central Composite design of Response Surface Method (RSM). Exposure time to gelling medium (10–30 min), sodium alginate concentration (1%–2%, w/v) and chitosan concentration (0.5%–1%, w/v) were process parameters to be optimized for the maximum encapsulation efficiency concerning total phenolic content (EETPC ), rutin (major individual compound) concentration and inhibition effect of the capsules against DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) free radical. Particle shape and morphology of the dried microcapsules show that the capsules obtained are quite spherical, uniform and have a regular structure depending on stereo-microscope and scanning electron microscopy (SEM) analyzes.
基金National Natural Science Foundation of China,Grant/AwardNumbers:82204376,82360710The Basic Ability Enhancement Program for Young and Middle-aged Teachers of Guangxi,Grant/AwardNumber:2022KY0505+2 种基金Fundof Guangxi ResearchandInnovationBasefor Basic and Clinical Application of Nerve Injury and RepairProject,Grant/AwardNumber:ZY21195042ResearchProject Fund forDrug Safety of Guangxi Food and Drug Administration,Grant/AwardNumber:GUIYA JINKESUZISHU[2023]No.008Guangxi Science and Technology Project,Grant/AwardNumber:AD171290015。
文摘As the global population ages,research on the pathogenesis and treatment options for older patients with dementia has become increasingly important.Vascular dementia(VaD),the second most frequent type of dementia,is characterized by vascular impairment caused by inadequate blood supply to the brain.VaD is a complex neurological disorder involving multiple cells and signaling pathways,and its prevention and treatment pose clinical challenges with significant behavioral implications.Glutamate,the most abundant amino acid in the brain,plays a critical role as an excitatory neurotransmitter,impacting cognitive function,learning,and memory.Abnormal glutamate metabolism has been closely linked to dementia,and reduced blood flow to the brain can lead to excessive glutamate accumulation,resulting in neuronal death.This article highlights the connection between VaD and glutamate metabolism,aiming to identify better methods for preventing and treating VaD via regulating glutamate metabolism.
