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1.
J Physiol ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953534

RESUMO

The central histaminergic system has a pivotal role in emotional regulation and psychiatric disorders, including anxiety, depression and schizophrenia. However, the effect of histamine on neuronal activity of the centrolateral amygdala (CeL), an essential node for fear and anxiety processing, remains unknown. Here, using immunostaining and whole-cell patch clamp recording combined with optogenetic manipulation of histaminergic terminals in CeL slices prepared from histidine decarboxylase (HDC)-Cre rats, we show that histamine selectively suppresses excitatory synaptic transmissions, including glutamatergic transmission from the basolateral amygdala, on both PKC-δ- and SOM-positive CeL neurons. The histamine-induced effect is mediated by H3 receptors expressed on VGLUT1-/VGLUT2-positive presynaptic terminals in CeL. Furthermore, optoactivation of histaminergic afferent terminals from the hypothalamic tuberomammillary nucleus (TMN) also significantly suppresses glutamatergic transmissions in CeL via H3 receptors. Histamine neither modulates inhibitory synaptic transmission by presynaptic H3 receptors nor directly excites CeL neurons by postsynaptic H1, H2 or H4 receptors. These results suggest that histaminergic afferent inputs and presynaptic H3 heteroreceptors may hold a critical position in balancing excitatory and inhibitory synaptic transmissions in CeL by selective modulation of glutamatergic drive, which may not only account for the pathophysiology of psychiatric disorders but also provide potential psychotherapeutic targets. KEY POINTS: Histamine selectively suppresses the excitatory, rather than inhibitory, synaptic transmissions on both PKC-δ- and SOM-positive neurons in the centrolateral amygdala (CeL). H3 receptors expressed on VGLUT1- or VGLUT2-positive afferent terminals mediate the suppression of histamine on glutamatergic synaptic transmission in CeL. Optogenetic activation of hypothalamic tuberomammillary nucleus (TMN)-CeL histaminergic projections inhibits glutamatergic transmission in CeL via H3 receptors.

2.
Transpl Immunol ; 86: 102095, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39038741

RESUMO

Renal transplantation is the preferred treatment option for patients with end-stage renal disease (ESRD) in a clinical setting. Antibody mediated rejection (AMR) is one of the leading causes of graft dysfunction. To address the current shortcomings in the early diagnosis and treatment of AMR in clinical practice, this article analyzes the distribution of different circulating T follicular helper (cTfh) cell subtypes and B cell subpopulations in peripheral blood and detects the cytokine levels of chemokine ligand 13 (CXCL13), interleukin-21 (IL-21), and interleukin-4 (IL-4) related to cTfh cells in peripheral blood of kidney transplant recipients. Moreover, we also explore the correlation between cTfh cells, peripheral blood memory B cells, and AMR, their value as early predictive indicators of AMR, and explore potential therapeutic targets for AMR patients. Our results indicate that the proportion of cTfh cells increased at the onset of AMR, which plays an important role in antigen-specific B-cell immune regulation. Activation of cTfh cells in AMR patients correlates with phenotypes of memory B cells and plasma blasts. cTfh cells and memory B cells have promising diagnostic efficacies and predictive values for AMR. The proportion of cTfh cells to CD4+ T cells and the proportion of memory B cells to CD19+ B cells are correlated with serum creatinine levels, indicating that cTfh cells and memory B cells may be involved in the progression of AMR. In addition, the CXCL13, IL-21, and IL-4, which were associated with cTfh cells, may be involved in the onset of AMR.

3.
Stem Cell Res Ther ; 15(1): 143, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38764049

RESUMO

BACKGROUND: Spinal cord injury (SCI) is a debilitating illness in humans that causes permanent loss of movement or sensation. To treat SCI, exosomes, with their unique benefits, can circumvent limitations through direct stem cell transplantation. Therefore, we utilized Gelfoam encapsulated with exosomes derived from human umbilical cord mesenchymal stem cells (HucMSC-EX) in a rat SCI model. METHODS: SCI model was established through hemisection surgery in T9 spinal cord of female Sprague-Dawley rats. Exosome-loaded Gelfoam was implanted into the lesion site. An in vivo uptake assay using labeled exosomes was conducted on day 3 post-implantation. Locomotor functions and gait analyses were assessed using Basso-Beattie-Bresnahan (BBB) locomotor rating scale and DigiGait Imaging System from weeks 1 to 8. Nociceptive responses were evaluated through von Frey filament and noxious radiant heat tests. The therapeutic effects and potential mechanisms were analyzed using Western blotting and immunofluorescence staining at week 8 post-SCI. RESULTS: For the in vivo exosome uptake assay, we observed the uptake of labeled exosomes by NeuN+, Iba1+, GFAP+, and OLIG2+ cells around the injured area. Exosome treatment consistently increased the BBB score from 1 to 8 weeks compared with the Gelfoam-saline and SCI control groups. Additionally, exosome treatment significantly improved gait abnormalities including right-to-left hind paw contact area ratio, stance/stride, stride length, stride frequency, and swing duration, validating motor function recovery. Immunostaining and Western blotting revealed high expression of NF200, MBP, GAP43, synaptophysin, and PSD95 in exosome treatment group, indicating the promotion of nerve regeneration, remyelination, and synapse formation. Interestingly, exosome treatment reduced SCI-induced upregulation of GFAP and CSPG. Furthermore, levels of Bax, p75NTR, Iba1, and iNOS were reduced around the injured area, suggesting anti-inflammatory and anti-apoptotic effects. Moreover, exosome treatment alleviated SCI-induced pain behaviors and reduced pain-associated proteins (BDNF, TRPV1, and Cav3.2). Exosomal miRNA analysis revealed several promising therapeutic miRNAs. The cell culture study also confirmed the neurotrophic effect of HucMSCs-EX. CONCLUSION: Implantation of HucMSCs-EX-encapsulated Gelfoam improves SCI-induced motor dysfunction and neuropathic pain, possibly through its capabilities in nerve regeneration, remyelination, anti-inflammation, and anti-apoptosis. Overall, exosomes could serve as a promising therapeutic alternative for SCI treatment.


Assuntos
Modelos Animais de Doenças , Exossomos , Células-Tronco Mesenquimais , Neuralgia , Ratos Sprague-Dawley , Traumatismos da Medula Espinal , Animais , Traumatismos da Medula Espinal/terapia , Exossomos/metabolismo , Neuralgia/terapia , Neuralgia/metabolismo , Ratos , Feminino , Humanos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Locomoção , Esponja de Gelatina Absorvível , Cordão Umbilical/citologia
4.
SAGE Open Med Case Rep ; 12: 2050313X241252371, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38803359

RESUMO

The occurrence of multiple primary malignancies in a single patient has been relatively rare. We report here the case of a 71-year-old man with three primary tumors of lung cancer, intrahepatic cholangiocarcinoma, and prostate cancer, and a preliminary study of the mechanisms by which multiple primary tumors develop at the genetic level. Because of the late stage of the patient's condition, large tumor burden, and poor physical status, the patient survived only a few months. In the case presented herein, cholangiocarcinoma, lung cancer, and prostate cancer were found simultaneously, and the pathogenic sites are not related. Whole-exome sequencing was performed on the pathological tissues to explore the mechanism that may underlie multiple primary cancers at the genetic level. Several gene mutations were found in this case. They involved cell proliferation, cell cycle regulation, genetic stability, metabolism, cell invasion, angiogenesis, cell apoptosis, and other pathways. It can be preliminarily inferred that the mechanism underlying multiple primary tumors is related to the abnormality of tumor-promoting and suppressing pathways.

5.
Genes Genet Syst ; 992024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38417894

RESUMO

Homeostasis is essential for muscle repair and regeneration after skeletal muscle exercise. This study investigated the role of methyltransferase-like 21C (METTL21C) in skeletal muscle of mice after exercise and the potential mechanism. First, muscle samples were collected at 2, 4 and 6 weeks after exercise, and liver glycogen, muscle glycogen, blood lactic acid and triglyceride were assessed. Moreover, the expression levels of autophagy markers and METTL21C in skeletal muscle were analyzed. The results showed that the expression levels of METTL21C and MYH7 in the gastrocnemius muscle of mice in the exercise group were significantly higher after exercise than those in the control group, which suggested that long-term exercise promoted the formation of slow-twitch muscle fibers in mouse skeletal muscle. Likewise, the autophagy capacity was enhanced with the prolongation of exercise in muscles. The findings were confirmed in mouse C2C12 cells. We discovered that knockdown of Mettl21c reduced the expression of MYH7 and the autophagy level in mouse myoblasts. These findings indicate that METTL21C promotes skeletal muscle homeostasis after exercise by enhancing autophagy, and also contributes to myogenic differentiation and the formation of slow muscle fibers.


Assuntos
Autofagia , Metiltransferases , Fibras Musculares de Contração Lenta , Cadeias Pesadas de Miosina , Condicionamento Físico Animal , Animais , Camundongos , Linhagem Celular , Metiltransferases/metabolismo , Metiltransferases/genética , Camundongos Endogâmicos C57BL , Desenvolvimento Muscular , Fibras Musculares de Contração Lenta/metabolismo , Músculo Esquelético/metabolismo , Mioblastos/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Cadeias Pesadas de Miosina/genética
6.
Neuron ; 112(7): 1165-1181.e8, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38301648

RESUMO

Physical exercise is known to reduce anxiety, but the underlying brain mechanisms remain unclear. Here, we explore a hypothalamo-cerebello-amygdalar circuit that may mediate motor-dependent alleviation of anxiety. This three-neuron loop, in which the cerebellar dentate nucleus takes center stage, bridges the motor system with the emotional system. Subjecting animals to a constant rotarod engages glutamatergic cerebellar dentate neurons that drive PKCδ+ amygdalar neurons to elicit an anxiolytic effect. Moreover, challenging animals on an accelerated rather than a constant rotarod engages hypothalamic neurons that provide a superimposed anxiolytic effect via an orexinergic projection to the dentate neurons that activate the amygdala. Our findings reveal a cerebello-limbic pathway that may contribute to motor-triggered alleviation of anxiety and that may be optimally exploited during challenging physical exercise.


Assuntos
Ansiolíticos , Animais , Ansiedade/metabolismo , Hipotálamo , Cerebelo , Transtornos de Ansiedade
7.
Acta Pharmacol Sin ; 45(3): 517-530, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37880339

RESUMO

Malignant ventricular arrhythmia (VA) after myocardial infarction (MI) is mainly caused by myocardial electrophysiological remodeling. Brahma-related gene 1 (BRG1) is an ATPase catalytic subunit that belongs to a family of chromatin remodeling complexes called Switch/Sucrose Non-Fermentable Chromatin (SWI/SNF). BRG1 has been reported as a molecular chaperone, interacting with various transcription factors or proteins to regulate transcription in cardiac diseases. In this study, we investigated the potential role of BRG1 in ion channel remodeling and VA after ischemic infarction. Myocardial infarction (MI) mice were established by ligating the left anterior descending (LAD) coronary artery, and electrocardiogram (ECG) was monitored. Epicardial conduction of MI mouse heart was characterized in Langendorff-perfused hearts using epicardial optical voltage mapping. Patch-clamping analysis was conducted in single ventricular cardiomyocytes isolated from the mice. We showed that BRG1 expression in the border zone was progressively increased in the first week following MI. Cardiac-specific deletion of BRG1 by tail vein injection of AAV9-BRG1-shRNA significantly ameliorated susceptibility to electrical-induced VA and shortened QTc intervals in MI mice. BRG1 knockdown significantly enhanced conduction velocity (CV) and reversed the prolonged action potential duration in MI mouse heart. Moreover, BRG1 knockdown improved the decreased densities of Na+ current (INa) and transient outward potassium current (Ito), as well as the expression of Nav1.5 and Kv4.3 in the border zone of MI mouse hearts and in hypoxia-treated neonatal mouse ventricular cardiomyocytes. We revealed that MI increased the binding among BRG1, T-cell factor 4 (TCF4) and ß-catenin, forming a transcription complex, which suppressed the transcription activity of SCN5A and KCND3, thereby influencing the incidence of VA post-MI.


Assuntos
Infarto do Miocárdio , Camundongos , Animais , Infarto do Miocárdio/metabolismo , Arritmias Cardíacas/genética , Miocárdio/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Miócitos Cardíacos/metabolismo
8.
Heliyon ; 9(9): e19765, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37809742

RESUMO

Sewage sludge (SS) is an environmental issue due to its high organic content and ability to release hazardous substances. Most of the treatments available are biological, thermal hydrolysis, mechanical (ultrasound, high pressure, and lysis), chemical with oxidation (mainly ozonation), and alkali pre-treatments. Other treatment methods include landfill, wet oxidation, composting, drying, stabilization, incineration, pyrolysis, carbonization, liquefaction, gasification, and torrefaction. Some of these SS disposal methods damage the ecosystem and underutilize the potential resource value of SS. These challenges must be overcome with an innovative technique for the improvement of SS's nutritional value, energy content, and usability. This review proposes plasma pyrolysis and anaerobic digestion (AD) as promising SS treatment technologies. Plasma pyrolysis pre-treats SS to make it digestible by AD bacteria and immobilizes the heavy metals. The addition of Char to the upstream AD process increases the quantity and quality of biogas produced while enhancing the nutrients in the digestate. These two processes are integrated at high temperatures, thus creating concerns about their energy demand. These challenges are offset by the generated energy that can run the treatment plant or be sold to the grid, generating additional cash. Plasma pyrolysis wastes can also be converted into biochar, organic fertilizer, or soil conditioner. These combined technologies' financial sustainability depends on the treatment facility's circumstances and location. Plasma pyrolysis and AD can treat SS sustainably and provide nutrients and resources. This paper explains the co-process treatment route's techno-economic prospects, challenges, and recommendations for the future application of SS valorization and resource recovery.

9.
BMC Med ; 21(1): 348, 2023 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-37679672

RESUMO

BACKGROUND: Full-cohort and sibling-comparison designs have yielded inconsistent results about the impacts of caesarean delivery on offspring health outcomes, with the effect estimates from the latter being more likely directed towards the null value. We hypothesized that the seemingly conservative results obtained from the sibling-comparison design might be attributed to inadequate adjustment for non-shared confounders between siblings, particularly maternal age at delivery. METHODS: A systematic review and meta-analysis was first conducted. PubMed, Embase, and the Web of Science were searched from database inception to April 6, 2022. Included studies (1) examined the association of caesarean delivery, whether elective or emergency, with offspring health outcomes; (2) simultaneously conducted full-cohort and sibling-comparison analyses; and (3) reported adjusted effect estimates with 95% confidence intervals (95% CIs). No language restrictions were applied. Data were extracted by 2 reviewers independently. Three-level meta-analytic models were used to calculate the pooled odds ratios (ORs) and 95% CIs for caesarean versus vaginal delivery on multiple offspring health outcomes separately for full-cohort and sibling-comparison designs. Subgroup analyses were performed based on the method of adjustment for maternal age at delivery. A simulation study was then conducted. The simulated datasets were generated with some key parameters derived from the meta-analysis. RESULTS: Eighteen studies involving 21,854,828 individuals were included. The outcomes assessed included mental and behavioral disorders; endocrine, nutritional and metabolic diseases; asthma; cardiorespiratory fitness; and multiple sclerosis. The overall pooled OR for estimates from the full-cohort design was 1.14 (95% CI: 1.11 to 1.17), higher than that for estimates from the sibling-comparison design (OR = 1.08; 95% CI: 1.02 to 1.14). Stratified analyses showed that estimates from the sibling-comparison design varied considerably across studies using different methods to adjust for maternal age at delivery in multivariate analyses, while those from the full-cohort design were rather stable: in studies that did not adjust maternal age at delivery, the pooled OR of full-cohort vs. sibling-comparison design was 1.10 (95% CI: 0.99 to 1.22) vs. 1.06 (95% CI: 0.85 to 1.31), in studies adjusting it as a categorical variable, 1.15 (95% CI: 1.11 to 1.19) vs. 1.07 (95% CI: 1.00 to 1.15), and in studies adjusting it as a continuous variable, 1.12 (95% CI: 1.05 to 1.19) vs. 1.12 (95% CI: 0.98 to 1.29). The severe underestimation bias related to the inadequate adjustment of maternal age at delivery in sibling-comparison analyses was fully replicated in the simulation study. CONCLUSIONS: Sibling-comparison analyses may underestimate the association of caesarean delivery with multiple offspring health outcomes due to inadequate adjustment of non-shared confounders, such as maternal age at delivery. Thus, we should be cautious when interpreting the seemingly conservative results of sibling-comparison analyses in delivery-related studies.


Assuntos
Asma , Irmãos , Feminino , Gravidez , Humanos , Cesárea , Parto Obstétrico , Avaliação de Resultados em Cuidados de Saúde
10.
Prog Mol Biol Transl Sci ; 199: 63-107, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37678982

RESUMO

Human pluripotent stem cells (human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs)) have unlimited proliferative potential, whereas adult stem cells such as bone marrow-derived stem cells and adipose-derived stem cells have problems with aging. When hPSCs are intended to be cultured on feeder-free or xeno-free conditions without utilizing mouse embryonic fibroblasts or human fibroblasts, they cannot be cultured on conventional tissue culture polystyrene dishes, as adult stem cells can be cultured but should be cultivated on material surfaces grafted or coated with (a) natural or recombinant extracellular matrix (ECM) proteins, (b) ECM protein-derived peptides and specific synthetic polymer surfaces in xeno-free and/or chemically defined conditions. This review describes current developing cell culture biomaterials for the proliferation of hPSCs while maintaining the pluripotency and differentiation potential of the cells into 3 germ layers. Biomaterials for the cultivation of hPSCs without utilizing a feeder layer are essential to decrease the risk of xenogenic molecules, which contributes to the potential clinical usage of hPSCs. ECM proteins such as human recombinant vitronectin, laminin-511 and laminin-521 have been utilized instead of Matrigel for the feeder-free cultivation of hPSCs. The following biomaterials are also discussed for hPSC cultivation: (a) decellularized ECM, (b) peptide-grafted biomaterials derived from ECM proteins, (c) recombinant E-cadherin-coated surface, (d) polysaccharide-immobilized surface, (e) synthetic polymer surfaces with and without bioactive sites, (f) thermoresponsive polymer surfaces with and without bioactive sites, and (g) synthetic microfibrous scaffolds.


Assuntos
Células-Tronco Adultas , Laminina , Animais , Camundongos , Adulto , Humanos , Laminina/farmacologia , Fibroblastos , Materiais Biocompatíveis/farmacologia , Proliferação de Células
11.
World J Gastroenterol ; 29(29): 4557-4570, 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37621756

RESUMO

BACKGROUND: Hydrogen sulfide (H2S) is a recently discovered gaseous neurotransmitter in the nervous and gastrointestinal systems. It exerts its effects through multiple signaling pathways, impacting various physiological activities. The nucleus tractus solitarius (NTS), a vital nucleus involved in visceral sensation, was investigated in this study to understand the role of H2S in regulating gastric function in rats. AIM: To examine whether H2S affects the nuclear factor kappa-B (NF-κB) and transient receptor potential vanilloid 1 pathways and the neurokinin 1 (NK1) receptor in the NTS. METHODS: Immunohistochemical and fluorescent double-labeling techniques were employed to identify cystathionine beta-synthase (CBS) and c-Fos co-expressed positive neurons in the NTS during rat stress. Gastric motility curves were recorded by inserting a pressure-sensing balloon into the pylorus through the stomach fundus. Changes in gastric motility were observed before and after injecting different doses of NaHS (4 nmol and 8 nmol), physiological saline, Capsazepine (4 nmol) + NaHS (4 nmol), pyrrolidine dithiocarbamate (PDTC, 4 nmol) + NaHS (4 nmol), and L703606 (4 nmol) + NaHS (4 nmol). RESULTS: We identified a significant increase in the co-expression of c-Fos and CBS positive neurons in the NTS after 1 h and 3 h of restraint water-immersion stress compared to the expressions observed in the control group. Intra-NTS injection of NaHS at different doses significantly inhibited gastric motility in rats (P < 0.01). However, injection of saline, first injection NF-κB inhibitor PDTC or transient receptor potential vanilloid 1 (TRPV1) antagonist Capsazepine or NK1 receptor blockers L703606 and then injection NaHS did not produce significant changes (P > 0.05). CONCLUSION: NTS contains neurons co-expressing CBS and c-Fos, and the injection of NaHS into the NTS can suppress gastric motility in rats. This effect may be mediated by activating TRPV1 and NK1 receptors via the NF-κB channel.


Assuntos
Sulfeto de Hidrogênio , Animais , Ratos , Sulfeto de Hidrogênio/farmacologia , NF-kappa B , Núcleo Solitário , Desidratação
12.
Pharmacol Res ; 191: 106773, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37068531

RESUMO

Specific medications to combat cerebellar ataxias, a group of debilitating movement disorders characterized by difficulty with walking, balance and coordination, are still lacking. Notably, cerebellar microglial activation appears to be a common feature in different types of ataxic patients and rodent models. However, direct evidence that cerebellar microglial activation in vivo is sufficient to induce ataxia is still lacking. Here, by employing chemogenetic approaches to manipulate cerebellar microglia selectively and directly, we found that specific chemogenetic activation of microglia in the cerebellar vermis directly leads to ataxia symptoms in wild-type mice and aggravated ataxic motor deficits in 3-acetylpyridine (3-AP) mice, a classic mouse model of cerebellar ataxia. Mechanistically, cerebellar microglial proinflammatory activation induced by either chemogenetic M3D(Gq) stimulation or 3-AP modeling hyperexcites Purkinje cells (PCs), which consequently triggers ataxia. Blockade of microglia-derived TNF-α, one of the most important proinflammatory cytokines, attenuates the hyperactivity of PCs driven by microglia. Moreover, chemogenetic inhibition of cerebellar microglial activation or suppression of cerebellar microglial activation by PLX3397 and minocycline reduces the production of proinflammatory cytokines, including TNF-α, to effectively restore the overactivation of PCs and alleviate motor deficits in 3-AP mice. These results suggest that cerebellar microglial activation may aggravate the neuroinflammatory response and subsequently induce dysfunction of PCs, which in turn triggers ataxic motor deficits. Our findings thus reveal a causal relationship between proinflammatory activation of cerebellar microglia and ataxic motor symptoms, which may offer novel evidence for therapeutic intervention for cerebellar ataxias by targeting microglia and microglia-derived inflammatory mediators.


Assuntos
Ataxia Cerebelar , Camundongos , Animais , Ataxia Cerebelar/induzido quimicamente , Células de Purkinje/fisiologia , Microglia , Fator de Necrose Tumoral alfa/farmacologia , Cerebelo , Citocinas
13.
Cerebellum ; 22(5): 888-904, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36040660

RESUMO

The classical motor center cerebellum is one of the most consistent structures of abnormality in autism spectrum disorders (ASD), and neuropeptide oxytocin is increasingly explored as a potential pharmacotherapy for ASD. However, whether oxytocin targets the cerebellum for therapeutic effects remains unclear. Here, we report a localization of oxytocin receptor (OXTR) in Purkinje cells (PCs) of cerebellar lobule Crus I, which is functionally connected with ASD-implicated circuits. OXTR activation neither affects firing activities, intrinsic excitability, and synaptic transmission of normal PCs nor improves abnormal intrinsic excitability and synaptic transmission of PCs in maternal immune activation (MIA) mouse model of autism. Furthermore, blockage of OXTR in Crus I in wild-type mice does not induce autistic-like social, stereotypic, cognitive, and anxiety-like behaviors. These results suggest that oxytocin signaling in Crus I PCs seems to be uninvolved in ASD pathophysiology, and contribute to understanding of targets and mechanisms of oxytocin in ASD treatment.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Camundongos , Animais , Receptores de Ocitocina , Ocitocina , Células de Purkinje
14.
Front Microbiol ; 14: 1286682, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38179451

RESUMO

Introduction: ß-Glucosidase serves as the pivotal rate-limiting enzyme in the cellulose degradation process, facilitating the hydrolysis of cellobiose and cellooligosaccharides into glucose. However, the widespread application of numerous ß-glucosidases is hindered by their limited thermostability and low glucose tolerance, particularly in elevated-temperature and high-glucose environments. Methods: This study presents an analysis of a ß-glucosidase gene belonging to the GH1 family, denoted lqbg8, which was isolated from the metagenomic repository of Hehua hot spring located in Tengchong, China. Subsequently, the gene was cloned and heterologously expressed in Escherichia coli BL21(DE3). Post expression, the recombinant ß-glucosidase (LQBG8) underwent purification through a Ni affinity chromatography column, thereby enabling the in-depth exploration of its enzymatic properties. Results: LQBG8 had an optimal temperature of 70°C and an optimum pH of 5.6. LQBG8 retained 100 and 70% of its maximum activity after 2-h incubation periods at 65°C and 70°C, respectively. Moreover, even following exposure to pH ranges of 3.0-10.0 for 24 h, LQBG8 retained approximately 80% of its initial activity. Notably, the enzymatic prowess of LQBG8 remained substantial at glucose concentrations of up to 3 M, with a retention of over 60% relative activity. The kinetic parameters of LQBG8 were characterized using cellobiose as substrate, with Km and Vmax values of 28 ± 1.9 mg/mL and 55 ± 3.2 µmol/min/mg, respectively. Furthermore, the introduction of LQBG8 (at a concentration of 0.03 mg/mL) into a conventional cellulase reaction system led to an impressive 43.7% augmentation in glucose yield from corn stover over a 24-h period. Molecular dynamics simulations offered valuable insights into LQBG8's thermophilic nature, attributing its robust stability to reduced fluctuations, conformational changes, and heightened structural rigidity in comparison to mesophilic ß-glucosidases. Discussion: In summation, its thermophilic, thermostable, and glucose-tolerant attributes, render LQBG8 ripe for potential applications across diverse domains encompassing food, feed, and the production of lignocellulosic ethanol.

15.
Heliyon ; 8(12): e12004, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36506353

RESUMO

The yield of winter wheat in Shandong Province is of great significance for ensuring regional and national food security. To reduce the risk of production loss, the WOFOST model was used to simulate the winter wheat growth to obtain the quantitative and dynamic information. Based on the observational data, a moisture control experiment and the trial and error method, the applicability and drought simulation of the WOFOST model were evaluated for winter wheat growth. For the simulation of the seedling period, flowering period, and maturity period of winter wheat in Shandong Province, the R2 were 0.95, 0.69, and 0.68 respectively. The D-index were 0.99, 0.89, and 0.86 respectively. The mean absolute error (mAE) were 1.3, 4.3, and 4.1 respectively. And the nRMSE were 0.65%, 4.3%, and 3.2%, respectively. For the yield simulation, the R2, D-index, mean relative error (mRE), and nRMSE were 0.48, 0.82, 10.5% and 12.8%, respectively. For the yield simulation under drought stress, the R2, D-index, mRE, and nRMSE were 0.77, 0.93, 7.1%, and 7.4%, respectively. An evaluation index system was built through four different degrees of drought treatment between the jointing period and the flowering period. With the aggravation of drought, the growth indicators about the total above ground production (TAGP), maximum leaf area index (MAXLAI), total dry weight of leaves (TWLV), and total dry weight of stems (TWST) decreasing by 13.6-41.0%, 37.8-56.5%, 19.4-42.1%, and 20.3-51.2%, respectively. The results showed that this model could adequately simulate the formation process of yield under both normal and drought conditions.

16.
Front Psychol ; 13: 876933, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36160504

RESUMO

The popularization of intelligent machines such as service robot and industrial robot will make human-machine interaction, an essential work mode. This requires employees to adapt to the new work content through learning. However, the research involved human-machine interaction that how influences the employee's learning is still rarely. This paper was to reveal the relationship between human-machine interaction and employee's learning from the perspective of job characteristics and competence perception of employees. We sent questionnaire to 500 employees from 100 artificial intelligence companies in China and received 319 valid and complete responses. Then, we adopted a hierarchical regression for the test. Empirical results show that human-machine interaction has a U-shaped curvilinear relationship with employee learning, and employee's vitality mediates the curvilinear relationship. In addition, job characteristics (skill variety and job autonomy) moderate the U-shaped curvilinear relationship between human-machine interaction and employee's vitality, especially the results of moderating effects varying with employee's competence perception. Exploring the mechanism of the effect of human-machine interaction on employee's learning enriches the socially embedded model. Moreover, it provides managerial implications how to enhance individual adaptability with the introduction of AI into firms. However, our research focuses more on the impact of human-machine interaction on employees at the initial stage of AI development, and the level of machine intelligence in various industries will reach a high degree of autonomy in the future. The future research can explore the impact of human-machine interaction on individual's behavior at different stages, and the results may vary depending on the technologies mastered by different individuals. The study has theoretical and practical significance to human-machine interaction literature by underscoring the important of individual's behavior among individuals with different skills.

17.
Micron ; 161: 103326, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35932631

RESUMO

"Thermal expansion and cold contraction" are common occurrences in nature. Resulting from "thermal expansion and cold contraction" reaction, strain effect is created, which affects the oxygen reduction reaction (ORR) activities of fuel cell catalysts. Nevertheless, the "thermal expansion and cold contraction" effects of catalysts have rarely been investigated. Herein, the influence of "thermal expansion and cold contraction" strains upon ORR activities of NiO/CoO catalysts is investigated. Experimental and first-principles calculations reveal that, when NiO/CoO are synthesized and used as catalysts under low temperature ice/water environment, there is virtually no strain effect created, and abundant active sites contribute to the good low temperature ORR activities of NiO/CoO catalysts (onset potential: 0.736 V, halfwave potential: 0.659 V). When high temperature synthesized NiO/CoO catalysts are used at low temperature, however, small amounts of active sites are created. Moreover, the adsorption activity of NiO(222) and CoO(311) stepped active sites are weakened by compressive strain of lattice contraction, which reduces their ORR activities. The "low temperature synthesis and low temperature catalysis" route proposed by this paper paves a new road for the synthesis and design of low-temperature catalysts.

18.
Biomed Pharmacother ; 153: 113344, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35780620

RESUMO

Betahistine and gastrodin are the first-line medications for vestibular disorders in clinical practice, nevertheless, their amelioration effects on vestibular dysfunctions still lack direct comparison and their unexpected extra-vestibular effects remain elusive. Recent clinical studies have indicated that both of them may have effects on the gastrointestinal (GI) tract. Therefore, we purposed to systematically compare both vestibular and GI effects induced by betahistine and gastrodin and tried to elucidate the mechanisms underlying their GI effects. Our results showed that betahistine and gastrodin indeed had similar therapeutic effects on vestibular-associated motor dysfunction induced by unilateral labyrinthectomy. However, betahistine reduced total GI motility with gastric hypomotility and colonic hypermotility, whereas gastrodin did not influence total GI motility with only slight colonic hypermotility. In addition, betahistine, at normal dosages, induced a slight injury of gastric mucosa. These GI effects may be due to the different effects of betahistine and gastrodin on substance P and vasoactive intestinal peptide secretion in stomach and/or colon, and agonistic/anatgonistic effects of betahistine on histamine H1 and H3 receptors expressed in GI mucosal cells and H3 receptors distributed on nerves within the myenteric and submucosal plexuses. Furthermore, treatment of betahistine and gastrodin had potential effects on gut microbiota composition, which could lead to changes in host-microbiota homeostasis in turn. These results demonstrate that gastrodin has a consistent improvement effect on vestibular functions compared with betahistine but less effect on GI functions and gut microbiota, suggesting that gastrodin may be more suitable for vestibular disease patients with GI dysfunction.


Assuntos
Receptores Histamínicos H3 , Vestíbulo do Labirinto , Animais , Álcoois Benzílicos , beta-Histina/farmacologia , beta-Histina/uso terapêutico , Glucosídeos , Camundongos , Receptores Histamínicos H3/metabolismo , Núcleos Vestibulares/metabolismo , Vestíbulo do Labirinto/metabolismo
20.
Sci Rep ; 12(1): 10139, 2022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35710740

RESUMO

Precise customer requirements acquisition is the primary stage of product conceptual design, which plays a decisive role in product quality and innovation. However, existing customer requirements mining approaches pay attention to the offline or online customer comment feedback and there has been little quantitative analysis of customer requirements in the analogical reasoning environment. Latent and innovative customer requirements can be expressed by analogical inspiration distinctly. In response, this paper proposes a semantic analysis-driven customer requirements mining method for product conceptual design based on deep transfer learning and improved latent Dirichlet allocation (ILDA). Initially, an analogy-inspired verbal protocol analysis experiment is implemented to obtain detailed customer requirements descriptions of elevator. Then, full connection layers and a softmax layer are added to the output-end of Chinese bidirectional encoder representations from Transformers (BERT) pre-training language model. The above deep transfer model is utilized to realize the customer requirements classification among functional domain, behavioral domain and structural domain in the customer requirement descriptions of elevator by fine-tuning training. Moreover, the ILDA is adopted to mine the functional customer requirements that can represent customer intention maximally. Finally, an effective accuracy of customer requirements classification is acquired by using the BERT deep transfer model. Meanwhile, five kinds of customer requirements of elevator and corresponding keywords as well as their weight coefficients in the topic-word distribution are extracted. This work can provide a novel research perspective on customer requirements mining for product conceptual design through natural language processing.


Assuntos
Algoritmos , Semântica , Idioma , Processamento de Linguagem Natural , Resolução de Problemas
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