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BACKGROUND: Sulfate-reducing bacteria (SRB) is a potential pathogen usually detected in patients with gastrointestinal diseases. Hydrogen sulfide (H2S), a metabolic byproduct of SRB, was considered the main causative agent that disrupted the morphology and function of gut epithelial cells. Associated study also showed that flagellin from Desulfovibrio vulgaris (DVF), the representative bacterium of the Desulfovibrio genus, could exacerbate colitis due to the interaction of DVF and LRRC19, leading to the secretion of pro-inflammatory cytokines. However, we still have limited understanding about the change of gut microbiota (GM) composition caused by overgrowth of SRB and its exacerbating effects on colitis. RESULTS: In this study, we transplanted D. vulgaris into the mice treated with or without DSS, and set a one-week recovery period to investigate the impact of D. vulgaris on the mice model. The outcomes showed that transplanted D. vulgaris into the normal mice could cause the gut inflammation, disrupt gut barrier and reduce the level of short-chain fatty acids (SCFAs). Moreover, D. vulgaris also significantly augmented DSS-induced colitis by exacerbating the damage of gut barrier and the secretion of inflammatory cytokines, for instance, IL-1ß, iNOS, and TNF-α. Furthermore, results also showed that D. vulgaris could markedly change GM composition, especially decrease the relative abundance of SCFAs-producing bacteria. Additionally, D. vulgaris significantly stimulated the growth of Akkermansia muciniphila probably via its metabolic byproduct, H2S, in vivo. CONCLUSIONS: Collectively, this study indicated that transplantation of D. vulgaris could cause gut inflammation and aggravate the colitis induced by DSS.
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The wheat scab caused by Fusarium graminearum (F. graminearum) has seriously affected the yield and quality of wheat in China. In this study, gallic acid (GA), a natural polyphenol, was used to synthesize three azole-modified gallic acid derivatives (AGAs1-3). The antifungal activity of GA and its derivatives against F. graminearum was studied through mycelial growth rate experiments and field efficacy experiments. The results of the mycelial growth rate test showed that the EC50 of AGAs-2 was 0.49 mg/mL, and that of AGAs-3 was 0.42 mg/mL. The biological activity of AGAs-3 on F. graminearum is significantly better than that of GA. The results of field efficacy tests showed that AGAs-2 and AGAs-3 significantly reduced the incidence rate and disease index of wheat scab, and the control effect reached 68.86% and 72.11%, respectively. In addition, preliminary investigation was performed on the possible interaction between AGAs-3 and F. graminearum using density functional theory (DFT). These results indicate that compound AGAs-3, because of its characteristic of imidazolium salts, has potential for use as a green and environmentally friendly plant-derived antifungal agent for plant pathogenic fungi.
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Antifúngicos , Azóis , Fusarium , Ácido Gálico , Triticum , Fusarium/efeitos dos fármacos , Fusarium/crescimento & desenvolvimento , Ácido Gálico/química , Ácido Gálico/farmacologia , Antifúngicos/farmacologia , Antifúngicos/química , Triticum/microbiologia , Azóis/farmacologia , Azóis/química , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Testes de Sensibilidade MicrobianaRESUMO
Non-invasive therapies such as photodynamic therapy (PDT) and chemodynamic therapy (CDT) have received wide attention due to their low toxicity and side effects, but their efficacy is limited by the tumor microenvironment (TME), and monotherapy cannot achieve satisfactory efficacy. In this work, a multifunctional nanoparticle co-assembled from oleanolic acid (OA), chlorin e6 (Ce6) and hemin was developed. The as-constructed nanoparticle named OCH with diameters of around 130 nm possessed good biostability, pH/GSH dual-responsive drug release properties, and remarkable cellular internalization and tumor accumulation capabilities. OCH exhibited prominent catalytic activities to generate â¢OH, deplete GSH, and produce O2 to overcome the hypoxia TME, thus potentiating the photodynamic and chemodynamic effect. In addition, OCH can induce the occurrence of ferroptosis in both ferroptosis-sensitive and ferroptosis-resistant cancer cells. The multi-pronged effects of OCH including hypoxia alleviation, GSH depletion, ferroptosis induction, CDT and PDT effects jointly facilitate excellent anticancer effects in vitro and in vivo. Hence, this work will advance the development of safe and effective clinically transformable nanomedicine by employing clinically-applied agents to form drug combinations for efficient multi-pronged combination cancer therapy.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Terapia Combinada , Neoplasias/tratamento farmacológico , Liberação Controlada de Fármacos , Hipóxia , Nanomedicina , Microambiente Tumoral , Linhagem Celular Tumoral , Peróxido de HidrogênioRESUMO
In the current prevalent complex electromagnetic (EM) environment, intelligent methods for versatile and integrated control of EM waves using compact devices are both essential and challenging. These varied wave control objectives can at times conflict with one another, such as the need for broad absorption to remain inconspicuous, while also requiring enhanced backward scattering for highly reliable tracing and secure communication. To address these sophisticated challenges, a microwave-frequency reconfigurable tri-mode metasurface (RTMM) is introduced. The proposed innovation enables three distinct operational modes: broadband low observation, enhanced EM wave tracing, and backscatter communication over a wide-angle range by simple control of the PIN diodes embedded in each meta-atom. The proof-of-concept demonstration of the fabricated prototype verified the switchable tri-mode performance of the RTMM. This proposed RTMM can be adapted to various applications, including EM shielding, target detection, and secure communication in complex and threatening EM environments, paving the way for environmentally-adaptive EM wave manipulation.
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Photothermal therapy (PTT) has attracted extensive attention in cancer treatment. Heptamethine cyanine dyes with near-infrared (NIR) absorption performance have been investigated for PTT. However, they are often accompanied by poor photostability, suboptimal photothermal conversion and limited therapeutic efficacy. The photophysical properties of fluorescent organic salts can be tuned through counterion pairing. However, whether the counterion can influence the photostability and photothermal properties of heptamethine cyanine salts has not been clarified. In this work, we investigated the effects of eleven counter anions on the physical and photothermal properties of NIR-II heptamethine cyanine salts with the same heptamethine cyanine cation. The anions have great impacts on the physiochemical properties of dyes in solution including aggregation, photostability and photothermal conversion efficiency. The physical tuning enables the control over the cytotoxicity and phototoxicity of the dyes. The selected salts have been demonstrated to significantly suppress 4T1 breast tumor growth with low toxicity. The findings that the counterion has great effects on the photothermal properties of cationic NIR-II heptamethine cyanine dyes will provide a reference for the preparation of improved photothermal agents through counterion pairing with possible translation to humans.
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Carbocianinas , Terapia Fototérmica , Sais , Humanos , Sais/farmacologia , Corantes/química , Ânions , Corantes Fluorescentes/farmacologia , Corantes Fluorescentes/químicaRESUMO
Climate change is a non-traditional security crisis affecting the global economy and diplomatic progress. In order to curtail carbon emissions and alleviate the perils of climate change at their roots, urban green innovation (UGI) has emerged as a pivotal technological solution. Using the expansion of the Yangtze River Delta urban agglomeration in China as a case study, this paper develops a quasi-experimental model to analyze the effects of regional integration policies on UGI. The main findings are: (1) Regional integration policies significantly enhance UGI and their impact is more pronounced with the expansion of urban agglomerations; (2) Regional integration policies contribute to the advancement of exploitative green innovation while tending to diminish exploratory green innovation; (3) The green innovation effects (GIEs) created by the expansion of regional integration policies are largely influenced by governmental mechanisms on environmental governance as well as residents' green preferences. Based on these findings, recommendations are put forward to promote UGI from the perspective of policy implementation.
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Conservação dos Recursos Naturais , Política Ambiental , Carbono , China , Políticas , Rios , Cidades , Desenvolvimento EconômicoRESUMO
The probiotic bacterium Escherichia coli Nissle 1917 (EcN) holds significant promise for use in clinical and biological industries. However, the reliance on antibiotics to maintain plasmid-borne genes has overshadowed its benefits. In this study, we addressed this issue by engineering the endogenous cryptic plasmids pMUT1 and pMUT2. The non-essential elements were removed to create more stable derivatives pMUT1NRâ³ and pMUT2HBCâ³. Synthetic promoters by integrating binding motifs on sigma factors were further constructed and applied for expression of Bacteroides thetaiotaomicron heparinase III and the biosynthesis of ectoine. Compared to traditional antibiotic-dependent expression systems, our newly constructed antibiotic-free expression systems offer considerable advantages for clinical and synthetic biology applications.
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When performing stent intervention for iliac vein compression syndrome, the operator selects the appropriate stent and determines its implantation depth according to the type and severity of iliac vein stenosis in the patient. However, there is still uncertainty regarding how the structure of the stent and its implantation depth affect hemodynamics at the site of lesion. In this paper, we analyzed three commonly used stents (Vena stent from Venmedtch, Venovo from Bard, and Smart stent from Cordis) with different implantation depths (0, 10, 20 mm) using computational fluid dynamics (CFD). We focused on evaluating hemorheological parameters such as time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), etc., within one pulsatile cycle after stent implantation. The correlation between geometric parameters of the stents and hemodynamic indicators was assessed using Pearson correlation coefficient (r), which was further validated through PIV velocity measurement experiment. The results revealed that an increase in implantation depth led to a more pronounced disturbance effect on blood flow at bifurcation for densely arranged support body-type stents. This effect was particularly significant during periods of smooth blood flow. On the other hand, crown-shaped Vena stents exhibited relatively less disruption to blood flow post-implantation. Implantation depth showed a strong negative correlation with TAWSS but a strong positive correlation with OSI and RRT. These findings suggest an increased risk of thrombosis at iliac vein bifurcation following stent placement. Amongst all three tested stents, Vena Stent demonstrated more favorable periodic parameters after implantation compared to others. These results provide valuable theoretical insights into understanding contralateral circulation thrombosis associated with iliac vein stenting.
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Veia Ilíaca , Trombose , Humanos , Veia Ilíaca/cirurgia , Hemodinâmica , Stents/efeitos adversosRESUMO
The effects of ultrasonic parameters and treatment conditions on the in vitro cellular experiments of sonodynamic therapy (SDT) have not been fully studied. Exploring the factors that affect the efficacy of SDT can provide a reference for screening effective sonosensitizers in vitro. The aim of this work is to investigate the factors that affected the SDT effects in cancer cells. Cancer cells in culture plates were exposed to ultrasound and sonosensitizers. The intracellular drug concentration was measured by using flow cytometry and the cell viability was determined by MTT assay. The SDT effects of cancer cells treated with different ultrasonic parameters under the same sonosensitizer concentration were different. The ultrasonic parameters, intracellular drug concentration, drug treatment time, cell amount, and cell status could affect the sonodynamic therapeutic effects. It is necessary to select appropriate ultrasound conditions and optimize the cellular status to make the results of the in vitro cellular experiments more reliable.
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Neoplasias , Terapia por Ultrassom , Humanos , Terapia por Ultrassom/métodos , Ultrassom , Espécies Reativas de Oxigênio , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Linhagem Celular TumoralRESUMO
Acute respiratory tract infections (ARTI) are caused by respiratory pathogens and range from asymptomatic infections to severe respiratory diseases. These diseases can be life threatening with high morbidity and mortality worldwide. Under the pandemic of coronavirus disease 2019 (COVID-19), little has been reported about the pathogen etiologies and epidemiology of patients suffering from ARTI of all age in Xiamen. Region-specific surveillance in individuals with ARTI of all ages was performed in Xiamen from January 2020 to October 2022. Here, we observed the epidemiological characteristics of thirteen pathogens within ARTI patients and further revealed the difference of that between upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI). In total 56.36 % (2358/4184) of the ARTI patients were positive for at least one respiratory pathogen. Rhinovirus (RVs, 29.22 %), influenza A (FluA, 19.59 %), respiratory syncytial virus (RSV, 18.36 %), metapneumovirus (MPV, 13.91 %), and adenovirus (ADV, 10.31 %) were the five leading respiratory pathogens. Respiratory pathogens displayed age- and season-specific patterns, even between URTI and LRTI. Compared with other groups, a higher proportion of FluA (52.17 % and 68.75 %, respectively) infection was found in the adult group and the elder group, while the lower proportion of RVs (14.11 % and 11.11 %) infection was also observed in them. Although ARTI cases circulated throughout the year, RVs, FluB, and BoV peaked in autumn, and FluA circulated more in summer. Besides, the co-infectious rate was 8.7 % with the most common for RVs. Logistic regression analyses revealed the correlations between respiratory pathogens and disease types. These results are essential for replenishing epidemiological characteristics of common respiratory pathogens that caused ARTI in Xiamen during the epidemic of COVID-19, and a better understanding of it might optimize the local prevention and clinical control.
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Ongoing extensive research in the field of gut microbiota (GM) has highlighted the crucial role of gut-dwelling microbes in human health. These microbes possess 100 times more genes than the human genome and offer significant biochemical advantages to the host in nutrient and drug absorption, metabolism, and excretion. It is increasingly clear that GM modulates the efficacy and toxicity of drugs, especially those taken orally. In addition, intra-individual variability of GM has been shown to contribute to drug response biases for certain therapeutics. For instance, the efficacy of cyclophosphamide depends on the presence of Enterococcus hirae and Barnesiella intestinihominis in the host intestine. Conversely, the presence of inappropriate or unwanted gut bacteria can inactivate a drug. For example, dehydroxylase of Enterococcus faecalis and Eggerthella lenta A2 can metabolize L-dopa before it converts into the active form (dopamine) and crosses the blood-brain barrier to treat Parkinson's disease patients. Moreover, GM is emerging as a new player in personalized medicine, and various methods are being developed to treat diseases by remodeling patients' GM composition, such as prebiotic and probiotic interventions, microbiota transplants, and the introduction of synthetic GM. This review aims to highlight how the host's GM can improve drug efficacy and discuss how an unwanted bug can cause the inactivation of medicine.
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The efficacy and biosafety of sonodynamic therapy (SDT) are closely related to the properties of sonosensitizers. Inorganic sonosensitizers with high chemical stability and low dark toxicity are generally limited by slow metabolism and accumulation in vivo. Combined treatment strategies by inducing more redox imbalance are expected to improve the efficacy of sonodynamic antitumor therapy. Herein, we report the development of ultra-small iron-doped zinc oxide nanoparticles (FZO NPs) to achieve synergistic sono-chemodynamic therapy and low accumulation in vivo. The surface of FZO NPs with diameter of 5 nm was modified with 3-aminopropyltriethoxysilane and polyethylene glycol 600 to obtain FZO-ASP with good aqueous stability. FZO-ASP with iron doping could trigger Fenton reaction and induce ferroptosis in cancer cells. With the assistance of ultrasonic energy, FZO-ASP demonstrated enhanced inhibitory effects on proliferation of various cancer cells and murine breast tumor growth than undoped counterpart. In addition, FZO-ASP injected intravenously could be effectively excreted in vivo and showed no obvious cumulative toxicity to the treated mice. Hence, this type of ultra-small iron-doped zinc oxide nanoparticles could serve as a safe and efficient sonosensitizer agent for synergistic sono-chemodynamic cancer therapy.
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Ferroptose , Nanopartículas , Neoplasias , Óxido de Zinco , Animais , Camundongos , Óxido de Zinco/farmacologia , Nanopartículas/química , Zinco/farmacologia , Linhagem Celular Tumoral , Ferro/química , Neoplasias/tratamento farmacológicoRESUMO
With technological advancements, radiotherapy (RT) has become an effective non-surgical treatment for hepatocellular carcinoma (HCC), comprehensively improving the local control rate of patients with HCC. However, some patients with HCC still experience radio-resistance, cancer recurrence, and distant metastasis following RT. Our previous study has revealed that hexokinase 2 (HK2), a potent oncogene, was overexpressed in radio-resistant HCC cell lines; however, its role in HCC radio-resistance remains elusive. Here, we confirmed the upregulation of HK2 in HCC tissue, which is related to unfavorable prognosis in patients with HCC, and demonstrated that HK2 exerts a radio-resistant role by attenuating apoptosis and promoting proliferation in HCC cell lines. HK2 downregulation combined with ionizing radiation showed an excellent synergistic lethal effect. Mechanistically, HK2 alleviated ionizing radiation-mediated apoptosis by complexing with pro-apoptotic protein aminoacyl tRNA synthetase complex interacting multifunctional protein 2 (AIMP2) while enhancing its autophagic lysosomal-dependent degradation, thereby increasing radio-resistance of HCC. Pharmacologically, ketoconazole, an FDA-approved antifungal drug, served as an inhibitor of HK2 and synergistically enhanced the efficacy of RT. Our results indicated that HK2 played a vital role in radio-resistance and could be a potential therapeutic target for improving RT efficacy in HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Autofagia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Hexoquinase/genética , Hexoquinase/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/metabolismo , Recidiva Local de Neoplasia , Proteínas Nucleares/farmacologiaRESUMO
Background: As a principal cause of mortality and disability worldwide, stroke imposes considerable burdens on society and effects on the lives of patients, families, and communities. Owing to their growing global popularity, health-related applications (apps) offer a promising approach to stroke management but show a knowledge gap regarding mobile apps for stroke survivors. Methods: This review was conducted across the Android and iOS app stores in September-December 2022 to identify and describe all apps targeting stroke survivors. Apps were included if they were designed for stroke management and contained at least one of the following components: medication taking, risk management, blood pressure management, and stroke rehabilitation. Apps were excluded if they were unrelated to health, not in Chinese or English, or the targeted users were healthcare professionals. The included apps were downloaded, and their functionalities were investigated. Results: The initial search yielded 402 apps, with 115 eligible after title and description screening. Some apps were later excluded due to duplicates, registration problems, or installation failures. In total, 83 apps were included for full review and evaluated by three independent reviewers. Educational information was the most common function (36.1%), followed by rehabilitation guidance (34.9%), communication with healthcare providers (HCPs), and others (28.9%). The majority of these apps (50.6%) had only one functionality. A minority had contributions from an HCP or patients. Conclusion: With the widespread accessibility and availability of smartphone apps across the mHealth landscape, an increasing number of apps targeting stroke survivors are being released. One of the most important findings is that the majority of the apps were not specifically geared toward older adults. Many of the currently available apps lack healthcare professionals' and patients' involvement in their development, and most offer limited functionality, thus requiring further attention to the development of customized apps.
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Ferroptosis is a newly detected iron-dependent form of regulated cell death. Sono-photodynamic therapy (SPDT) can generate reactive oxygen species (ROS) and induce cell death under light and ultrasound. Due to the complexity of tumor physiology and pathology, single-modality often fails to achieve a satisfactory therapeutic effect. The development of a formulation platform with integration of multiple therapeutic modalities using a simple and convenient method is still a challenge. Here, we report the facile construction of a ferritin-based nanosensitizer FCD by co-encapsulating chlorin e6 (Ce6) and dihydroartemisinin (DHA) in horse spleen ferritin, and was employed for synergistic ferroptosis and SPDT. Ferritin in FCD can release Fe3+ under acidic conditions and Fe3+ can be reduced to Fe2+ in the presence of glutathione (GSH). The Fe2+ can react with hydrogen peroxide (H2O2) to produce harmful hydroxyl radicals. Furthermore, a large amount of ROS can be generated via the reaction of Fe2+ with DHA and by simultaneously irradiation of FCD with both light and ultrasound. More importantly, the depletion of GSH by FCD could decrease glutathione peroxidase 4 (GPX4) and increase lipid peroxidation (LPO) levels, thereby inducing ferroptosis. Therefore, by integrating the advantageous GSH-depletion capacity, ROS generation ability, and ferroptosis induction capability into one single nanosystem, FCD can serve as a promising platform for combined chemo-sono-photodynamic therapy of cancer.
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Ferroptose , Neoplasias , Animais , Cavalos , Ferro/metabolismo , Ferritinas , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/metabolismo , Glutationa/metabolismoRESUMO
Many artificial organelles or subcellular compartments have been developed to tune gene expression, regulate metabolic pathways, or endow new cell functions. Most of these organelles or compartments were built using proteins or nucleic acids as building blocks. In this study, we demonstrated that capsular polysaccharide (CPS) retained inside bacteria cytosol assembled into mechanically stable CPS compartments. The CPS compartments were able to accommodate and release protein molecules but not lipids or nucleic acids. Intriguingly, we found that the CPS compartment size responds to osmotic stress and this compartment improves cell survival under high osmotic pressures, which was similar to the vacuole functionalities. By fine-tuning the synthesis and degradation of CPS with osmotic stress-responsive promoters, we achieved dynamic regulation of the size of CPS compartments and the host cells in response to external osmotic stress. Our results shed new light on developing prokaryotic artificial organelles with carbohydrate macromolecules.
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Polissacarídeos , Vacúolos , Pressão Osmótica , Bactérias , Células ProcarióticasRESUMO
Post-translational modification (PTM) is crucial for many biological events, such as the modulation of bone metabolism. Phosphorylation and O-GlcNAcylation are two examples of PTMs that can occur at the same site in the protein: serine and threonine residues. This phenomenon may cause crosstalk and possible interactions between the molecules involved. Protein phosphatase 2 A (PP2A) is widely expressed throughout the body and plays a major role in dephosphorylation. At the same location where PP2A acts, O-GlcNAc transferase (OGT) can introduce uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) molecules and mediates O-GlcNAc modifications. To examine the effects of PP2A inhibition on OGT localization and expression, osteoblastic MC3T3-E1 cells were treated with Okadaic Acid (OA), a potent PP2A inhibitor. In the control cells, OGT was strictly localized in the nucleus. However, OGT was observed diffusely in the cytoplasm of the OA-treated cells. This change in localization from the nucleus to the cytoplasm resulted from an increase in mitochondrial OGT expression and translocation of the nucleocytoplasmic isoform. Furthermore, knockdown of PP2A catalytic subunit α isoform (PP2A Cα) significantly affected OGT expression (p < 0.05), and there was a correlation between PP2A Cα and OGT expression (r = 0.93). These results suggested a possible interaction between PP2A and OGT, which strengthens the notion of an interaction between phosphorylation and O-GlcNAcylation.
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Proteína Fosfatase 2 , Processamento de Proteína Pós-Traducional , Proteína Fosfatase 2/metabolismo , Ácido Okadáico/farmacologia , N-Acetilglucosaminiltransferases/metabolismo , Isoformas de Proteínas/metabolismo , Acetilglucosamina/metabolismoRESUMO
Neural dynamics are altered in the primary visual cortex (V1) during critical period monocular deprivation (MD). Synchronization of neural oscillations is pertinent to physiological functioning of the brain. Previous studies have reported chronic disruption of V1 functional properties such as ocular dominance, spatial acuity, and binocular matching after long-term monocular deprivation (LTMD). However, the possible neuromodulation and neural synchrony has been less explored. Here, we investigated the difference between juvenile and adult experience-dependent plasticity in mice from intracellular calcium signals with fluorescent indicators. We also studied alterations in local field potentials power bands and phase-amplitude coupling (PAC) of specific brain oscillations. Our results showed that LTMD in juveniles causes higher neuromodulatory changes as seen by high-intensity fluorescent signals from the non-deprived eye (NDE). Meanwhile, adult mice showed a greater response from the deprived eye (DE). LTMD in juvenile mice triggered alterations in the power of delta, theta, and gamma oscillations, followed by enhancement of delta-gamma PAC in the NDE. However, LTMD in adult mice caused alterations in the power of delta oscillations and enhancement of delta-gamma PAC in the DE. These markers are intrinsic to cortical neuronal processing during LTMD and apply to a wide range of nested oscillatory markers.
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Visão Monocular , Córtex Visual , Animais , Camundongos , Visão Monocular/fisiologia , Privação Sensorial/fisiologia , Córtex Visual/fisiologia , Dominância Ocular , Neurônios/fisiologia , Plasticidade Neuronal/fisiologiaRESUMO
As one of the most abundant neuropeptides in the central nervous system, cholecystokinin (CCK) has been suggested to be associated with higher brain functions, including learning and memory. In this review, we examined the potential role of the CCK system in declarative memory. First, we summarized behavioral studies that provide evidence for an important role of CCK in two forms of declarative memory-fear memory and spatial memory. Subsequently, we examined the electrophysiological studies that support the diverse roles of CCK-2 receptor activation in neocortical and hippocampal synaptic plasticity, and discussed the potential mechanisms that may be involved. Last but not least, we discussed whether the reported CCK-mediated synaptic plasticity can explain the strong influence of the CCK signaling system in neocortex and hippocampus dependent declarative memory. The available research supports the role of CCK-mediated synaptic plasticity in neocortex dependent declarative memory acquisition, but further study on the association between CCK-mediated synaptic plasticity and neocortex dependent declarative memory consolidation and retrieval is necessary. Although a direct link between CCK-mediated synaptic plasticity and hippocampus dependent declarative memory is missing, noticeable evidence from morphological, behavioral, and electrophysiological studies encourages further investigation regarding the potential role of CCK-dependent synaptic plasticity in hippocampus dependent declarative memory.
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Colecistocinina , Neocórtex , Plasticidade Neuronal/fisiologia , Hipocampo/fisiologia , Memória EspacialRESUMO
Metallothionein (MT) is a multifunctional inducible protein in animals, plants, and microorganisms. MT is rich in cysteine residues (10-30%), can combine with metal ions, has a low molecular weight, and plays an essential biological role in various stages of the growth and development of organisms. Due to its strong ability to bind metal ions and scavenge free radicals, metallothionein has been used in medicine, health care, and other areas. Zinc is essential for plant growth, but excessive zinc (Zn) is bound to poison plants, and cadmium (Cd) is a significant environmental pollutant. A high concentration of cadmium can significantly affect the growth and development of plants and even lead to plant death. In this study, the human metallothionein gene HsMT1L under the control of the CaMV 35S constitutive promoter was transformed into tobacco, and the tolerance and accumulation capacity of transgenic tobacco plants to Zn and Cd were explored. The results showed that the high-level expression of HsMT1L in tobacco could significantly enhance the accumulation of Zn2+ and Cd2+ in both the aboveground parts and the roots compared to wild-type tobacco plants and conferred a greater tolerance to Zn and Cd in transgenic tobacco. Subcellular localization showed that HsMT1L was localized to the nucleus and cytoplasm in the tobacco. Our study suggests that HsMT1L can be used for the phytoremediation of soil for heavy metal removal.