ABSTRACT
The study of salicylideneaniline (SA) and its derivatives is critical due to their special photophysical properties and environmental sensitivity. In this work, the density time-dependent functional theory (TDDFT) and complete-active-space self-consistent-field (CASSCF) methods were carried out to calculate the substituent effect on excited-state properties and dynamics of SA derivatives. We found the para-substitution triggers the excited-state intramolecular proton transfer (ESIPT) reaction, exhibiting the dual-fluorescent phenomena. However, the meta- and ortho-substitutions impel the non-radiative transition process along the minimum energy conical intersection (MECI), forming the twisted intramolecular charge transfer (TICT) state to prevent ESIPT. This investigation of substituent effects on the photochemical processes and photophysical properties will provide the benchmarks for the design of fluorescent materials.
ABSTRACT
The current study combined sentence plausibility judgment and self-paced reading tasks to examine the comprehension strategies and processing patterns of Chinese deaf individuals when comprehending written Chinese sentences with syntactic-semantic cue conflicts. Similar to findings from previous crosslinguistic studies on deaf readers, the Chinese deaf readers showed great variability in their comprehension strategies, with only 38% robustly relying on syntactic cues. Regardless of their overall comprehension preferences, the deaf readers all showed additional processing efforts as reflected by longer reading time at the verb regions when they relied on the syntactic cues. Those with less robust reliance on syntactic cues also showed longer reading time at the verb regions even when they relied on the semantic cues, suggesting sensitivity to the syntactic cues regardless of the comprehension strategy. These findings suggest that deaf readers in general endure more processing burden while resolving conflicting syntactic and semantic cues, likely due to their overall high reliance on semantic information during sentence comprehension. Increased processing burden thus may contribute to an overall tendency of over-reliance on semantic cues when comprehending sentences with cue conflicts.
Subject(s)
Comprehension , Deafness , Reading , Semantics , Humans , Comprehension/physiology , Deafness/psychology , Male , Female , Adult , Young Adult , China , Cues , Language , East Asian PeopleABSTRACT
Although imine reductase (IRED)-catalyzed reductive amination is promising for the synthesis of alkylated chiral amines, precisely regulating the stereoselectivity of IRED remains a great challenge. Herein, focusing on the residues directly in contact with the ketone moiety, we applied structure-guided semi-rational design to obtain the triple-mutant I149Y/L200H/W234K. This mutant showed high stereoselectivity, of up to >99% (S), toward reductive amination of N-Boc-4-oxo-azepane and different amines, and to the best of our knowledge is the first biocatalyst developed for asymmetric synthesis of chiral azepane-4-amines.
ABSTRACT
Mesanophrys sp. is a parasitic ciliate that invades and destroys the hemocytes of the swimming crab (Portunus trituberculatus). In the present study, we employed an in vitro model to elucidate how Mesanophrys sp. destroys crab hemocytes. We also evaluated the relationship between the parasite's density, the destruction rate of the hemocytes, and the rapid proliferation pattern of parasites in host crabs. We found that the survival rate and cell integrity of crab hemocytes decreased with an increase in Mesanophrys sp. density, depicting a negative correlation between hemocyte viability and parasite density. Further analyses revealed that crab hemocytes could resist destruction by a low density (10 ind/mL) of Mesanophrys sp. for a long time (60 h). Mesanophrys sp. and its culture medium (containing the ciliate secretions) destroy the host hemocytes. The natural population growth rate of Mesanophrys sp. decreased with an increase in the parasite density, but the Mesanophrys sp. density did not affect the generation time of the parasites. In summary, Mesanophrys sp. can destroy crab hemocytes, and the degree of destruction is directly proportional to the parasite density. The resistance of crab hemocytes to Mesanophrys sp. decreased gradually with an increase in the parasite density.
Subject(s)
Brachyura , Ciliophora , Oligohymenophorea , Parasites , Animals , Brachyura/parasitology , Hemocytes , Swimming , Virulence , Host-Parasite InteractionsABSTRACT
Wheat stripe rust (WSR) is a foliar disease that causes destructive damage in the wheat production context. Accurately estimating the severity of WSR in the autumn growing stage can help to objectively monitor the disease incidence level of WSR and predict the nationwide disease incidence in the following year, which have great significance for controlling its nationwide spread and ensuring the safety of grain production. In this study, to address the low accuracy and the efficiency of disease index estimation by traditional methods, WSR-diseased areas are segmented based on Segformer, and the macro disease index (MDI) is automatically calculated for the measurement of canopy-scale disease incidence. The results obtained with different semantic segmentation algorithms, loss functions, and data sets are compared for the segmentation effect, in order to address the severe class imbalance in disease region segmentation. We find that: (1) The results of the various models differed significantly, with Segformer being the best algorithm for WSR segmentation (rust class F1 score = 72.60%), based on the original data set; (2) the imbalanced nature of the data has a significant impact on the identification of the minority class (i.e., the rust class), for which solutions based on loss functions and re-weighting of the minority class are ineffective; (3) data augmentation of the minority class or under-sampling of the original data set to increase the proportion of the rust class greatly improved the F1-score of the model (rust class F1 score = 86.6%), revealing that re-sampling is a simple and effective approach to alleviating the class imbalance problem. Finally, the MDI was used to evaluate the models based on the different data sets, where the model based on the augmented data set presented the best performance (R2 = 0.992, RMSE = 0.008). In conclusion, the deep-learning-based semantic segmentation method, and the corresponding optimization measures, applied in this study allow us to achieve pixel-level accurate segmentation of WSR regions on wheat leaves, thus enabling accurate assessment of the degree of WSR disease under complex backgrounds in the field, consequently providing technical support for field surveys and calculation of the disease level.
Subject(s)
Basidiomycota , Triticum , Disease Resistance , Plant Diseases , Plant LeavesABSTRACT
ß-1,3-glucans, natural polysaccharide groups, exert immunomodulatory effects to improve the innate response and disease resistance in aquatic species and mammals. However, this ß-glucan stimulant is yet to be assayed in swimming crab (Portunus trituberculatus) hemocytes. In this study, we explored the immunomodulatory effect of ß-1,3-glucans (derived from Euglena gracilis) via in vitro 24 h stimulation assays in swimming crab hemocytes. We found that this algal ß-1,3-glucans in crab hemocytes significantly elevated cellular enzymes related parameters, including phenoloxidase (PO), lysozyme, acid phosphatase (ACP) activities, and superoxide anion generation (O2-) rate both at intracellular (P < 0.05) and extracellular (P < 0.05) levels. Besides, alkaline phosphatase (AKP) in hemocytes exhibited no significant differences across the groups (P > 0.05). ß-glucan significantly influenced (P < 0.05) the activities of the antioxidant enzyme, superoxide dismutase (SOD) in hemocytes. Moreover, the relative mRNA expression of numerous immune-related genes, including proPO, TLR-2, Alf-1, NOX, Lysozyme, Crustin-1, and Cuznsod, was significantly higher stimulated hemocytes than in control (P < 0.05). We also reported the dose-dependent antiparasitic activity against Mesanophyrs sp., in stimulated hemocytes than in the control (P < 0.05). The present study collectively demonstrated that ß-glucan potentially stimulates innate immunity by elevating cellular enzyme responses and up-regulating the mRNA expression of genes associated with crab innate immunity. Thus, ß-glucan is a promising immunostimulant for swimming crab farming in crustaceans aquaculture.
Subject(s)
Brachyura/parasitology , Ciliophora/physiology , Euglena gracilis/chemistry , beta-Glucans/pharmacology , Animals , Antioxidants/pharmacology , Brachyura/drug effects , Brachyura/immunology , Ciliophora/drug effects , Host-Parasite Interactions/drug effects , beta-Glucans/chemistryABSTRACT
Effective therapies for Methamphetamine (METH) induced stereotyped behavior are still being explored. It is unclear whether Neuropeptide S (NPS) is involved in the mechanism of METH-induced stereotyped behavior. In the contemporary behavioral study, pretreatment with NPS reduces stereotyped circling significantly, but didn't have any impact on the total incidence of stereotypy and stereotyped sniffing and biting induced by METH (10 mg/kg). When METH (10 mg/kg) was administered to rats, the level of NPS in the cerebrospinal fluid was not affected, but pretreatment with NPS reversed METH-induced glutamate release in the hippocampus and striatum. The findings suggest that NPS receptor system is likely to involve in the METH-overdose-induced behaviors.
Subject(s)
Central Nervous System Stimulants/pharmacology , Methamphetamine/pharmacology , Neuropeptides/pharmacology , Stereotyped Behavior/drug effects , Animals , Behavior, Animal/drug effects , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Glutamic Acid/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Male , Rats , Rats, Sprague-DawleyABSTRACT
The COVID-19 pandemic is spreading globally. COVID-19 has an effect on the systemic state, cardiopulmonary function and primary disease of patients undergoing surgery. COVID-19's high contagiousness makes anesthesia and intraoperative management more difficult. This expert consensus aims to comprehensively introduce the application of perioperative ultrasound in COVID-19 patients, including pulmonary ultrasound and anesthesia management, ultrasound and airway management, ultrasound-guided regional anesthesia and echocardiography for COVID-19 patients.
Subject(s)
Anesthesia/methods , Betacoronavirus , Coronavirus Infections/diagnostic imaging , Perioperative Care/methods , Pneumonia, Viral/diagnostic imaging , Ultrasonography/methods , Airway Management/methods , Anesthesia, Conduction/methods , COVID-19 , Cardiovascular Diseases/complications , Cardiovascular Diseases/diagnostic imaging , Coronavirus Infections/complications , Coronavirus Infections/transmission , Echocardiography/methods , Hemodynamics , Humans , Lung/diagnostic imaging , Lung Diseases/diagnostic imaging , Lung Diseases/microbiology , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/transmission , SARS-CoV-2 , Tracheotomy/methods , Ultrasonography, Interventional/methods , Ventilator Weaning/methodsABSTRACT
Fifteen polyketides, including four new compounds, isoversiol F (1), decumbenone D (2), palitantin B (7), and 1,3-di-O-methyl-norsolorinic acid (8), along with 11 known compounds (3-6 and 9-15), were isolated from the deep-sea-derived fungus Aspergillus versicolor SH0105. Their structures and absolute configurations were determined by comprehensive spectroscopic data, including 1D and 2D NMR, HRESIMS, and ECD calculations, and it is the first time to determine the absolute configuration of known decumbenone A (6). All of these compounds were evaluated for their antimicrobial activities against four human pathogenic microbes and five fouling bacterial strains. The results indicated that 3,7-dihydroxy-1,9-dimethyldibenzofuran (14) displayed obvious inhibitory activity against Staphylococcus aureus (ATCC 27154) with the MIC value of 13.7 µM. In addition, the antioxidant assays of the isolated compounds revealed that aspermutarubrol/violaceol-I (15) exhibited significant 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity with the IC50 value of 34.1 µM, and displayed strong reduction of Fe3+ with the ferric reducing antioxidant power (FRAP) value of 9.0 mM under the concentration of 3.1 µg/mL, which were more potent than ascorbic acid.
Subject(s)
Anti-Bacterial Agents/pharmacology , Aspergillus/metabolism , Free Radical Scavengers/pharmacology , Polyketides/pharmacology , Anti-Bacterial Agents/isolation & purification , Free Radical Scavengers/isolation & purification , Geologic Sediments/microbiology , Microbial Sensitivity Tests , Polyketides/isolation & purification , Protein Conformation , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & development , Structure-Activity RelationshipABSTRACT
A novel perylenequinone-related compound, alternatone A (1), with an unprecedented tricyclo[6.3.1.02,7] dodecane skeleton, together with three known perylenequinones, altertoxin I (2), stemphyperylenol (3), and alterperylenol (4), was isolated from the soft-coral-derived fungus Alternaria alternata L3111'. Their structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic analysis, electronic circular dichroism calculations, and X-ray diffraction data. Compound 4 showed cytotoxicity against A-549, HCT-116, and HeLa cell lines with IC50 values of 2.6, 2.4, and 3.1 µM, respectively. A possible biosynthetic pathway of 1 was proposed.
Subject(s)
Alternaria/chemistry , Anthozoa/microbiology , Perylene/analogs & derivatives , Quinones/chemistry , Quinones/pharmacology , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antibiotics, Antineoplastic/chemistry , Antibiotics, Antineoplastic/pharmacology , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Microbial Sensitivity Tests , Models, Molecular , Molecular Structure , Perylene/chemistry , Perylene/pharmacology , X-Ray DiffractionABSTRACT
Six new sordarin tetracyclic diterpene glycosides, moriniafungins B-G (1-6), and a new sordaricin tetracyclic diterpene, sordaricin B (8), together with two known analogues, moriniafungin (7) and sordaricin (9), were isolated from the zoanthid-derived fungus Curvularia hawaiiensis TA26-15. The structures of the new compounds were elucidated by comprehensive analyses of spectroscopic data, including 1D and 2D NMR and MS data. Compounds 1-6 represent the first case of sordarins from marine-derived fungi possessing a sordarose with a spiro 1,3-dioxolan-4-one ring, which is rare in the nature. Compound 4 showed antifungal activity against Candida albicans ATCC10231 with an MIC value of 2.9 µM.
Subject(s)
Ascomycota/chemistry , Dioxolanes/chemistry , Diterpenes/isolation & purification , Glycosides/chemistry , Indenes/isolation & purification , Diterpenes/chemistry , Indenes/chemistry , Molecular Structure , Spectrum Analysis/methodsABSTRACT
Wheat stripe rust caused by Puccinia striiformis f. sp. tritici is one of the most destructive diseases of wheat worldwide. Sichuan Province plays an important role in interregional epidemics in China. Application of host resistance is important in disease management, and efficient approaches to evaluate resistance level are necessary to obtain useful varieties. In this study, 100 wheat cultivars (lines) growing in Sichuan were selected to evaluate their resistance to stripe rust. Field experiments were conducted with a mixture of three P. striiformis f. sp. tritici races for inoculations at seeding and adult stages in the 2014 to 2015 season and the 2016 to 2017 season. Leaf samplings were conducted four times during the latent period at early growth stage of wheat. The sampled leaves were processed to extract DNA. The DNA of both wheat and P. striiformis f. sp. tritici was quantified using real-time quantitative polymerase chain reaction, and the molecular disease index (MDI) was used to evaluate the resistance level. The area under the disease progress curve in terms of disease index (AUDPC-DI) was obtained for each studied cultivar (line) in the fields. Among the 100 studied cultivars (lines), 61% of them showed seedling resistance, and 63 and 65% showed adult resistance in the 2014 to 2015 and 2016 to 2017 seasons, respectively, based on the infection type. High consistency in resistance grouping by cluster analysis as the percentage of the studied cultivar (line) belonging to the same group based on AUDPC-DI data and based on MDI data was obtained. The correlations between AUDPC-DI and MDI from samples collected on 9 and 14 or 15 days after inoculation during the latent period were all significant at P < 0.01. This study provided a new and efficient method for evaluation of varietal resistance to wheat stripe rust.
Subject(s)
Basidiomycota , Disease Resistance , Triticum , Basidiomycota/physiology , Breeding , China , Cluster Analysis , DNA, Fungal/genetics , DNA, Plant/genetics , Seedlings/microbiology , Triticum/genetics , Triticum/microbiologyABSTRACT
In this paper, a new kind of carbon steel (CS) and stainless steel (SS) galvanic sensor system was developed for the study of rebar corrosion in different pore solution conditions. Through the special design of the CS and SS electronic coupons, the electronic resistance (ER) method and zero resistance ammeter (ZRA) technique were used simultaneously for the measurement of both the galvanic current and the corrosion depth. The corrosion processes in different solution conditions were also studied by linear polarization resistance (LPR) and the measurements of polarization curves. The test result shows that the galvanic current noise can provide detailed information of the corrosion processes. When localized corrosion occurs, the corrosion rate measured by the ER method is lower than the real corrosion rate. However, the value measured by the LPR method is higher than the real corrosion rate. The galvanic current and the corrosion current measured by the LPR method shows linear correlation in chloride-containing saturated Ca(OH)2 solution. The relationship between the corrosion current differences measured by the CS electronic coupons and the galvanic current between the CS and SS electronic coupons can also be used to evaluate the localized corrosion in reinforced concrete.
ABSTRACT
Two new naphthalenones, corynenones A and B (1 and 2), and one new depsidone, corynesidone E (3), together with one known depsidone, corynesidone A (4) and two known diphenyl ethers, corynethers A (5) and B (6), were isolated from the sponge-derived fungus Corynespora cassiicola XS-20090I7. Their structures including absolute configurations were determined by spectroscopic data and electronic circular dichroism (ECD) spectra. Compounds 4 and 5 showed cytotoxicity against human promyelocytic leukemia HL-60 and human cervical carcinoma HeLa cell lines.
Subject(s)
Depsides/isolation & purification , Lactones/isolation & purification , Naphthalenes/isolation & purification , Porifera/microbiology , Saccharomycetales/chemistry , Animals , Cell Proliferation/drug effects , Cell Survival/drug effects , Circular Dichroism , Depsides/chemistry , Depsides/pharmacology , HL-60 Cells , HeLa Cells , Humans , Lactones/chemistry , Lactones/pharmacology , Molecular Structure , Naphthalenes/chemistry , Naphthalenes/pharmacologyABSTRACT
Physalis alkekengi L.var. franchetii (Mast.) Makino (PAF) is an important edible and medicinal plant resource in China. Historically, phytochemical studies have primarily examined the calyx and fruit due to their long-standing use in traditional Chinese medicine for their ability to clear heat and detoxify. Metabolites and bioactivities of other parts such as the leaves, stems and roots, are rarely studied. The study involved conducting metabolic profiling of five plant parts of PAF using UPLC-Q-Orbitrap-HRMS analysis, in conjunction with two bioactivity assays. A total of 95 compounds were identified, including physalins, flavonoids, sucrose esters, phenylpropanoids, nitrogenous compounds and fatty acids. Notably, 14 aliphatic sucrose esters, which are potentially novel compounds, were initially identified. Furthermore, one new aliphatic sucrose ester was purified and its structure was elucidated by 1D and 2D NMR analysis. The hierarchical clustering analysis and principal component analysis showed the close clustering of the root and stem, suggesting similarities in their chemical composition, whereas the leaf, calyx and fruit clustered more distantly. Orthogonal partial least-squares discriminant analysis results showed that 41 compounds potentially serve as marker compounds for distinguishing among plant parts. Variations in activity were observed among the plant parts during the comparative evaluation with biological assays. The calyx, leaf and fruit extracts showed stronger antibacterial and anti-inflammatory activities than the stem and root extracts, and 19 potential biomarkers were identified by S-plot analysis for the observed activities, including chlorogenic acid, luteolin, cynaroside, physalin A, physalin F, physalin J, apigetrin, quercetin-3ß-D-glucoside and five ASEs, which likely explain the observed potent bioactivity.
ABSTRACT
Antibiotic-associated diarrhea (AAD) is a common side effect of antibiotic therapy, characterized by intestinal inflammation which reduces the quality of life of patients. Xianglian Pill (XLP) has long been used to treat abdominal pain, diarrhea, bacillary dysentery and enteritis. Studies found that XLP has curative effect on AAD; however, the chemical constituents and mechanism of XLP have not been fully elucidated because of the lack of in vitro and in vivo studies. In this study, ultra-high performance liquid chromatography mass spectrometry method (UPLC-Q-Exactive-Orbitrap-HRMS) was used to examine the components of the XLP. Then, the binding between active compounds and the key targets was studied using network pharmacology and molecular docking. A comparative tissue distribution study was established for the simultaneous determination of the 10 active components in healthy and AAD mouse models. Forty-six components were characterized from XLP. According to the network pharmacology degree value, a prediction was made that encompassed 42 components and 14 core targets, which were intricately involved in crucial biological pathways, such as the AGE-RAGE signaling, cellular senescence, and MAPK signaling. Tissue distribution analysis showed that the 10 components were widely distributed in the heart, liver, spleen, lungs, kidneys, small intestine, and large intestine of mice, with varying concentrations in healthy and AAD mice. Molecular docking analysis also indicated that the active compounds in the tissue distribution could bind tightly to key targets of network pharmacological studies. This study provides a reference for further investigations of the relationships between the chemical components and pharmacological activities of XLP.
Subject(s)
Anti-Bacterial Agents , Diarrhea , Disease Models, Animal , Drugs, Chinese Herbal , Molecular Docking Simulation , Animals , Mice , Diarrhea/chemically induced , Diarrhea/drug therapy , Male , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Tissue Distribution , Network Pharmacology/methodsABSTRACT
The fabrics commonly used in architectural decorative materials pose significant fire hazards due to their flammability and rapid fire spread. Moreover, the traditional fire-alarm systems may fail to function properly in complex fire environments owing to power supply disruptions. In this study, we developed a low-cost and eco-friendly flame-retardant conductive fabric-based triboelectric nanogenerator (FCF-TENG) by integrating flame-retardant conductive nylon fabric and polytetrafluoroethylene soaked cotton fabric. This nanogenerator exhibits excellent flame-retardant properties and remarkable energy-harvesting capabilities. The nylon fabric, treated with layer-by-layer self-assembly method, possesses outstanding self-extinguishing capability and melt-dripping resistance. Additionally, the electrical performance of FCF-TENG significantly improves, with a 10-fold boost in conductivity, and the open-circuit voltage increases by 84% to 92 V. Besides, by incorporating the rectifier circuit, the FCF-TENG is capable of completely charging a 1 µF capacitor within 30 s. Furthermore, the FCF-TENG was successfully applied as a self-powered sensor in the fire-alarm system and served as a safety exit indicator for evacuees and fire rescue. This work presents an effective and innovative application of multifunctional smart textiles for energy harvesting and self-powered sensing.
ABSTRACT
Stripe rust of wheat is caused by the fungal pathogen Puccinia striiformis f. sp. tritici (Pst). Breeding durably resistant wheat varieties by disrupting the susceptibility (S) gene has an important impact on the control of wheat stripe rust. Mingxian169 (MX169) showed strong stripe rust susceptibility to all the races of Pst. However, molecular mechanisms and responsive genes underlying susceptibility of the wheat variety MX169 to Pst have not been elucidated. Here, we utilized next-generation sequencing technology to analyze transcriptomics data of "MX169" and high-resistance wheat "Zhong4" at 24, 48, and 120 h post-inoculation (hpi) with Pst. Comparative transcriptome analysis revealed 3,494, 2,831, and 2,700 differentially expressed genes (DEGs) at different time points. We observed an upregulation of DEGs involved in photosynthesis, flavonoid biosynthesis, pyruvate metabolism, thiamine metabolism, and other biological processes, suggesting their involvement in MX169's response to Pst. DEGs encoding transcription factors were also identified. Our study suggested the potential susceptibility gene resources in MX169 related to stripe rust response could be valuable for understanding the mechanisms involved in stripe rust susceptibility and for improving wheat resistance to Pst. IMPORTANCE: Our study suggests the potential susceptibility gene resources in MX169 related to stripe rust response could be valuable for understanding the mechanisms involved in stripe rust susceptibility and for improving wheat resistance to Pst.
Subject(s)
Disease Resistance , Plant Diseases , Puccinia , Transcriptome , Triticum , Triticum/microbiology , Triticum/genetics , Triticum/immunology , Plant Diseases/microbiology , Plant Diseases/immunology , Plant Diseases/genetics , Disease Resistance/genetics , Gene Expression Regulation, Plant , Gene Expression Profiling , High-Throughput Nucleotide Sequencing , Basidiomycota/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
AIMS: General anesthesia has been used in surgical procedures for approximately 180 years, yet the precise mechanism of anesthetic drugs remains elusive. There is significant anatomical connectivity between the ventral tegmental area (VTA) and the prelimbic cortex (PrL). Projections from VTA dopaminergic neurons (VTADA ) to the PrL play a role in the transition from sevoflurane anesthesia to arousal. It is still uncertain whether the prelimbic cortex pyramidal neuron (PrLPyr ) and its projections to VTA (PrLPyr -VTA) are involved in anesthesia-arousal regulation. METHODS: We employed chemogenetics and optogenetics to selectively manipulate neuronal activity in the PrLPyr -VTA pathway. Electroencephalography spectra and burst-suppression ratios (BSR) were used to assess the depth of anesthesia. Furthermore, the loss or recovery of the righting reflex was monitored to indicate the induction or emergence time of general anesthesia. To elucidate the receptor mechanisms in the PrLPyr -VTA projection's impact on anesthesia and arousal, we microinjected NMDA receptor antagonists (MK-801) or AMPA receptor antagonists (NBQX) into the VTA. RESULTS: Our findings show that chemogenetic or optogenetic activation of PrLPyr neurons prolonged anesthesia induction and promoted emergence. Additionally, chemogenetic activation of the PrLPyr -VTA neural pathway delayed anesthesia induction and promoted anesthesia emergence. Likewise, optogenetic activation of the PrLPyr -VTA projections extended the induction time and facilitated emergence from sevoflurane anesthesia. Moreover, antagonizing NMDA receptors in the VTA attenuates the delayed anesthesia induction and promotes emergence caused by activating the PrLPyr -VTA projections. CONCLUSION: This study demonstrates that PrLPyr neurons and their projections to the VTA are involved in facilitating emergence from sevoflurane anesthesia, with the PrLPyr -VTA pathway exerting its effects through the activation of NMDA receptors within the VTA.
Subject(s)
Receptors, N-Methyl-D-Aspartate , Ventral Tegmental Area , Ventral Tegmental Area/metabolism , Sevoflurane/pharmacology , Receptors, N-Methyl-D-Aspartate/metabolism , Dopaminergic Neurons/metabolism , Pyramidal Cells , Anesthesia, General , ArousalABSTRACT
Depression has emerged as the predominant psychiatric affliction affecting individuals. Prior research has substantiated the antidepressant properties exhibited by numerous anesthetics. Sevoflurane, a widely utilized inhalant anesthetic in clinical practice, remains relatively uncharted in terms of its specific antidepressant effects. In this study, we used open field test, forced swimming test and novelty-suppressed feeding test to investigate the anxiety and depression-like behaviors in C57BL/6 mice following the inhalation of sevoflurane. We then used western blotting to scrutinized the expression levels of proteins associated with the brain-derived neurotrophic factor (BDNF)-tryosine receptor kinase B (TrkB) pathway in the hippocampus and prefrontal cortex. To further investigate whether sevoflurane exerts antidepressant-like effects via the BDNF-TrkB pathway, we downregulated TrkB expression by administering siRNA into the lateral ventricle. We found that the inhalation of 2.5 % sevoflurane exerted a significant antidepressant-like effect, accompanied by an elevation in p-TrkB expression levels in the hippocampus and prefrontal cortex. Intriguingly, this antidepressant-like effect was abrogated following the downregulation of TrkB expression through the microinjection of siRNA into the lateral ventricle. In conclusion, this study provides evidence supporting the notion that sevoflurane exerts its antidepressant-like effect via the BDNF-TrkB signaling pathway.