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1.
Nano Lett ; 24(17): 5342-5350, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38630899

RESUMO

CuInS2 (CIS) quantum dots (QDs) represent an important class of colloidal materials with broad application potential, owing to their low toxicity and unique optical properties. Although coating with a ZnS shell has been identified as a crucial method to enhance optical performance, the occurrence of cation exchange has historically resulted in the unintended formation of Cu-In-Zn-S alloyed QDs, causing detrimental blueshifts in both absorption and photoluminescence (PL) spectral profiles. In this study, we present a facile one-pot synthetic strategy aimed at impeding the cation exchange process and promoting ZnS shell growth on CIS core QDs. The suppression of both electron-phonon interaction and Auger recombination by the rigid ZnS shell results in CIS/ZnS core/shell QDs that exhibit a wide near-infrared (NIR) emission coverage and a remarkable PL quantum yield of 92.1%. This effect boosts the fabrication of high-performance, QD-based NIR light-emitting diodes with the best stability of such materials so far.

2.
Front Hum Neurosci ; 18: 1338765, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38415279

RESUMO

Previous neuroimaging studies have revealed abnormal brain networks in patients with major depressive disorder (MDD) in emotional processing. While any cognitive task consists of a series of stages, little is yet known about the topology of functional brain networks in MDD for these stages during emotional face recognition. To address this problem, electroencephalography (EEG)-based functional brain networks of MDD patients at different stages of facial information processing were investigated in this study. First, EEG signals were collected from 16 patients with MDD and 18 age-, gender-, and education-matched normal subjects when performing an emotional face recognition task. Second, the global field power (GFP) method was employed to divide group-averaged event-related potentials into different stages. Third, using the phase transfer entropy (PTE) approach, the brain networks of MDD patients and normal individuals were constructed for each stage in negative and positive face processing, respectively. Finally, we compared the topological properties of brain networks of each stage between the two groups using graph theory approaches. The results showed that the analyzed three stages of emotional face processing corresponded to specific neurophysiological phases, namely, visual perception, face recognition, and emotional decision-making. It was also demonstrated that depressed patients showed abnormally decreased characteristic path length at the visual perception stage of negative face recognition and normalized characteristic path length in the stage of emotional decision-making during positive face processing compared to healthy subjects. Furthermore, while both the MDD and normal groups' brain networks were found to exhibit small-world network characteristics, the brain network of patients with depression tended to be randomized. Moreover, for patients with MDD, the centro-parietal region may lose its status as a hub in the process of facial expression identification. Together, our findings suggested that altered emotional function in MDD patients might be associated with disruptions in the topological organization of functional brain networks during emotional face recognition, which further deepened our understanding of the emotion processing dysfunction underlying MDD.

3.
Chem Sci ; 15(4): 1449-1471, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38274053

RESUMO

The expertise accumulated in deep neural network-based structure prediction has been widely transferred to the field of protein-ligand binding pose prediction, thus leading to the emergence of a variety of deep learning-guided docking models for predicting protein-ligand binding poses without relying on heavy sampling. However, their prediction accuracy and applicability are still far from satisfactory, partially due to the lack of protein-ligand binding complex data. To this end, we create a large-scale complex dataset containing ∼9 M protein-ligand docking complexes for pre-training, and propose CarsiDock, the first deep learning-guided docking approach that leverages pre-training of millions of predicted protein-ligand complexes. CarsiDock contains two main stages, i.e., a deep learning model for the prediction of protein-ligand atomic distance matrices, and a translation, rotation and torsion-guided geometry optimization procedure to reconstruct the matrices into a credible binding pose. The pre-training and multiple innovative architectural designs facilitate the dramatically improved docking accuracy of our approach over the baselines in terms of multiple docking scenarios, thereby contributing to its outstanding early recognition performance in several retrospective virtual screening campaigns. Further explorations demonstrate that CarsiDock can not only guarantee the topological reliability of the binding poses but also successfully reproduce the crucial interactions in crystalized structures, highlighting its superior applicability.

4.
5.
BMC Oral Health ; 23(1): 857, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37957648

RESUMO

BACKGROUND: To explore the relationship between changes in salivary cytokine levels and the occurrence of white spot lesions in adolescents receiving clear aligner orthodontic treatment and investigate the predictive value of various factors for lesion occurrence. METHODS: We retrospectively analyzed sixthy eight adolescent in the permanent dentition period, who received clear aligner orthodontics in our hospital were randomly divided into two groups according to the occurrence or aggravation of white spot lesions after treatment. The general condition of the oral cavity was analyzed, saliva was collected, and inflammation-related cytokines with varying transcription levels between groups were screened by transcriptome analysis. The expression levels of inflammatory cytokines in the saliva of the patients in the two groups were measured, and the risk factors for white spot lesions were screened by correlation analysis and binary logistic regression analysis. The value of the independent and combined application of risk factors for predicting the occurrence of white spot lesions in adolescent patients after invisible orthodontic treatment was analyzed by receiver operating characteristic (ROC) curve analysis. RESULTS: Transcriptome and GO and KEGG pathway analyses showed that there were differences in the transcription levels of inflammatory cytokines such as CXCL1, CXCL2, CXCL8, CCL3, CCL4, IL-1ß and IL-2 between groups. The levels of CXCL8, CCL3, CCL4, IL-1ß and IL-2 in the saliva of patients with white spot lesions were significantly higher in patients after invisible orthodontic treatment (P < 0.05). Correlation analysis and binary logistic regression analysis showed that elevated levels of CXCL8, IL-1ß and IL-2 were independent risk factors for the occurrence of white spot lesions (P < 0.05). CXCL8 had the highest independent predictive value for the occurrence of white spot lesions (AUC = 0.773, P < 0.05), and the combination of IL-1ß and IL-2 was also of high value in predicting the occurrence of white spot lesions. CONCLUSION: After invisible orthodontic treatment, the oral microenvironment, including inflammatory cytokine levels, in adolescent patients changes; in particular, the levels of inflammatory cytokines such as CXCLs and ILs change. CXCL8 expression is significantly associated with the occurrence of white spot lesions and is an important potential target for the prevention and treatment of white spot lesions in the future.


Assuntos
Cárie Dentária , Aparelhos Ortodônticos Removíveis , Humanos , Adolescente , Cárie Dentária/prevenção & controle , Interleucina-2 , Estudos Retrospectivos , Citocinas
6.
BMC Pediatr ; 23(1): 516, 2023 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-37845615

RESUMO

Sepsis is a life-threatening multiple-organ injury caused by disordered host immune response to microbial infection. However, the correlation between gut microbiota dysbiosis and immune indicators remains unexplored. To address this gap in knowledge, we carried out 16 S rDNA sequencing, analyzed clinical fecal samples from children with sepsis (n = 30) and control children (n = 25), and obtained immune indicators, including T cell subtypes (CD3+, CD3+CD4+, CD3+CD8+, and CD4/CD8), NK cells, cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ), and immunoglobulin indices (IgA, IgE, IgM and IgG). In addition, we analyzed the correlation between gut microbiota dysbiosis and immune indicators, and evaluated the clinical discriminatory power of discovered bacterial biomarkers. We found that children with sepsis exhibited gut bacterial dysbiosis and low alpha diversity. The Spearman's rank correlation coefficient suggested that Rhodococcus erythropolis had a significantly positive correlation with IFN-γ and CD3+ T cells. Klebsiella pneumoniae and Streptococcus mitis were significantly correlated with NK cells. Bacteroides uniformis was significantly positively correlated with IgM and erythrocyte sedimentation rate, and Eubacterium eligens was significantly positively correlated with IL-4 and CD3+CD8+ T cells. The biomarkers discovered in this study had strong discriminatory power. These changes in the gut microbiome may be closely related to immunologic dysfunction and to the development or exacerbation of sepsis. However, a large sample size is required for verification.


Assuntos
Microbioma Gastrointestinal , Sepse , Humanos , Criança , Microbioma Gastrointestinal/fisiologia , Linfócitos T CD8-Positivos , Disbiose , Interleucina-4 , Bactérias/genética , Biomarcadores , Imunoglobulina M
7.
Brain Sci ; 13(10)2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37891761

RESUMO

The eye region conveys considerable information regarding an individual's emotions, motivations, and intentions during interpersonal communication. Evidence suggests that the eye regions of an individual expressing emotions can capture attention more rapidly than the eye regions of an individual in a neutral affective state. However, how attentional resources affect the processing of emotions conveyed by the eye regions remains unclear. Accordingly, the present study employed a dual-target rapid serial visual presentation task: happy, neutral, or fearful eye regions were presented as the second target, with a temporal lag between two targets of 232 or 696 ms. Participants completed two tasks successively: Task 1 was to identify which species the upright eye region they had seen belonged to, and Task 2 was to identify what emotion was conveyed in the upright eye region. The behavioral results showed that the accuracy for fearful eye regions was lower than that for neutral eye regions under the condition of limited attentional resources; however, accuracy differences across the three types of eye regions did not reach significance under the condition of adequate attentional resources. These findings indicate that preferential processing of fearful expressions is not automatic but is modulated by available attentional resources.

8.
Ecotoxicol Environ Saf ; 267: 115617, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37866109

RESUMO

The antidiabetic pharmaceutical metformin (MET) is largely unmetabolized by the human body. Its residues are readily detectable in various aquatic environments and may have adverse impacts on the growth and survival of aquatic species. To date, its toxicological effects have scarcely been explored in non-fish species. Here, we exposed the tadpoles of black-spotted pond frog (Pelophylax nigromaculatus) to different concentrations (0, 1, 10 and 100 µg/L) of MET for 30 days and measured the body size, intestinal microbiota and metabolites to evaluate potential effects of MET exposure in amphibian larvae. MET exposure did not affect the growth and intestinal microbial diversity of tadpoles. However, intestinal microbial composition changed significantly, with some pathogenic bacteria (e.g., bacterial genera Salmonella, Comamonas, Stenotrophomonas, Trichococcus) increasing and some beneficial bacteria (e.g., Blautia, Prevotella) decreasing in MET-exposed tadpoles. The levels of some intestinal metabolites associated with growth and immune performance also changed significantly following MET exposure. Overall, our results indicated that exposure to MET, even at environmentally relevant concentrations, would cause intestinal microbiota dysbiosis and metabolite alteration, thereby influencing the health status of non-target aquatic organisms, such as amphibians.


Assuntos
Microbioma Gastrointestinal , Metformina , Humanos , Animais , Metformina/toxicidade , Anuros , Hipoglicemiantes , Disbiose , Larva
9.
ACS Omega ; 8(30): 27323-27332, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37546631

RESUMO

At present, polyethylene pipeline is widely used in urban gas projects, but a relatively mature and reliable nondestructive testing technology has not been formed. Therefore, it is urgent to develop a new nondestructive testing technology to meet the increasing demand for inspection of non-metallic pipes. The terahertz testing technology and related equipment have played an increasingly important role in the nondestructive testing of many nonmetallic structures, but they have not been applied to polyethylene (PE) pipes. In this work, terahertz time-domain spectroscopy was used to detect prefabricated defects inside the PE pipe specimens. The results show that the terahertz nondestructive testing technology can be used to detect common defects in nonblack PE pipes with a detection error of less than 10%. Higher-power terahertz devices can detect defects in black PE pipe, while lower-power terahertz devices cannot. Because the black PE pipe contains carbon and has a strong absorption of terahertz waves. The penetration of lower-power terahertz devices to the black PE pipe is not enough, resulting in a low resolution of the imaging. The results of this work may promote the progress of the nondestructive testing technology of nonmetallic pipelines.

10.
J Cancer Res Clin Oncol ; 149(15): 13995-14014, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37543978

RESUMO

BACKGROUND: Colorectal cancer is the second leading cause of cancer-related deaths, which imposes a significant societal burden. Regular screening and emerging molecular tumor markers have important implications for detecting the progression and development of colorectal cancer. Disulfidptosis is a newly defined type of programmed cell death triggered by abnormal accumulation of disulfide compounds in cells that stimulate disulfide stress. Currently, there is no relevant discussion on this mechanism and colorectal cancer. METHODS: We classified the disulfidptosis-related subtypes of colorectal cancer using bioinformatics methods. Through secondary clustering of differentially expressed genes between subtypes, we identified characteristic genes of the disulfidptosis subtype, constructed a prognostic model, and searched for potential biomarkers through clinical validation. RESULTS: Using disulfidptosis-related genes collected from the literature, we classified colorectal cancer patients from public databases into three subtypes. The differentially expressed genes between subtypes were clustered into three gene subtypes, and eight characteristic genes were screened to construct a prognostic model. CONCLUSION: The disulfidptosis mechanism has important value in the classification of colorectal cancer patients, and characteristic genes selected based on this mechanism can serve as a new potential biological marker for colorectal cancer.

11.
J Clin Invest ; 133(18)2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37561576

RESUMO

The nucleus accumbens (NAc) is the most promising target for drug use disorder treatment. Deep brain stimulation (DBS) of NAc is effective for drug use disorder treatment. However, the mechanisms by which DBS produces its therapeutic effects remain enigmatic. Here, we define a behavioral cutoff criterion to distinguish depressive-like behaviors and non-depressive-like behaviors in mice after morphine withdrawal. We identified a basolateral amygdala (BLA) to NAc D1 medium spiny neuron (MSN) pathway that controls depressive-like behaviors after morphine withdrawal. Furthermore, the paraventricular nucleus of thalamus (PVT) to NAc D2 MSN pathway controls naloxone-induced acute withdrawal symptoms. Optogenetically induced long-term potentiation with κ-opioid receptor (KOR) antagonism enhanced BLA to NAc D1 MSN signaling and also altered the excitation/inhibition balance of NAc D2 MSN signaling. We also verified that a new 50 Hz DBS protocol reversed morphine withdrawal-evoked abnormal plasticity in NAc. Importantly, this refined DBS treatment effectively alleviated naloxone-induced withdrawal symptoms and depressive-like behaviors and prevented stress-induced reinstatement. Taken together, the results demonstrated that input- and cell type-specific synaptic plasticity underlies morphine withdrawal, which may lead to novel targets for the treatment of opioid use disorder.


Assuntos
Analgésicos Opioides , Síndrome de Abstinência a Substâncias , Camundongos , Animais , Analgésicos Opioides/farmacologia , Núcleo Accumbens/metabolismo , Receptores de Dopamina D2 , Morfina/efeitos adversos , Naloxona/farmacologia , Naloxona/metabolismo , Síndrome de Abstinência a Substâncias/terapia , Receptores de Dopamina D1/metabolismo , Camundongos Endogâmicos C57BL
12.
Brain Res ; 1812: 148407, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37182687

RESUMO

DNA methylation is one of the epigenetic mechanisms involved in opioid use disorder. GAD2 is a key catalyticase in gamma amino butyric acid (GABA) synthesis from glutamate, that is implicated in opioid-induced rewarding effect. To reveal the relationship and the underlying mechanism between GAD2 gene methylation and opioid use disorder, we first examined and compared the methylation levels in the promoter region of the GAD2 gene in peripheral blood between 120 patients with opioid use disorder and 110 healthy controls by using a targeted approach. A diagnostic model with methylation biomarkers was established to distinguish opioid use disorder and healthy control groups. Correlations between methylation levels in the promoter region of the GAD2 gene and the duration and dosage of opioid use were then determined. Finally, the transcription factors that potentially bind to the target sequences including the detected CpG sites were predicted with the JASPAR database. Our results demonstrated that hypermethylation in the promoter region of the GAD2 gene was associated with opioid use disorder. A diagnostic model based on 10 methylation biomarkers could distinguish the opioid use disorder and healthy control groups. Several correlations between methylation levels in the GAD2 gene promoter and the duration and dosage of opioid use were observed. Transcription factors TFAP2A, Arnt and Runx1 were predicted to bind to the target sequences including several CpG sites detected in the present study in the GAD2 gene promoter. Our findings highlight and extend the role of DNA methylation in the GAD2 gene in opioid use disorder.


Assuntos
Analgésicos Opioides , Transtornos Relacionados ao Uso de Opioides , Humanos , Metilação de DNA , Regiões Promotoras Genéticas/genética , Fatores de Transcrição/genética , Transtornos Relacionados ao Uso de Opioides/genética , Ilhas de CpG
13.
Biomolecules ; 13(4)2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37189431

RESUMO

Antisense long noncoding RNA (as-lncRNA) is a lncRNA transcribed in reverse orientation that is partially or completely complementary to the corresponding sense protein-coding or noncoding genes. As-lncRNAs, one of the natural antisense transcripts (NATs), can regulate the expression of their adjacent sense genes through a variety of mechanisms, affect the biological activities of cells, and further participate in the occurrence and development of a variety of tumours. This study explores the functional roles of as-lncRNAs, which can cis-regulate protein-coding sense genes, in tumour aetiology to understand the occurrence and development of malignant tumours in depth and provide a better theoretical basis for tumour therapy targeting lncRNAs.


Assuntos
RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Carcinogênese/genética
14.
Asian J Androl ; 2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36891937

RESUMO

Accumulating evidence has revealed many clues that regular aerobic exercise benefits brain health and behaviors. The aims of this study were to explore the effect of aerobic exercise on ejaculatory behaviors, as well as to make a preliminary assessment of aerobic exercise as a complementary strategy to dapoxetine treatment in rapid ejaculators. Copulatory tests of rats and a treadmill training protocol were performed in this study. In total, 12 rapid ejaculators were selected on the basis of ejaculation distribution theory and randomly assigned to 4 groups: control (Ctrol) group, aerobic exercise (Ex) group, dapoxetine (Dapo) group, and Ex+Dapo group. We evaluated the changes in ejaculatory parameters in the 4 groups. Variations in biological markers, including serum corticosterone, serotonin (5-HT), and brain-derived neurotrophic factor (BDNF) of the raphe nucleus, were determined by enzyme-linked immunosorbent assay (ELISA). The primary finding of our study was that both aerobic exercise and acute dapoxetine could enhance ejaculation control and prolong ejaculation latency in rapid ejaculator rats. The ejaculation delay effect of aerobic exercise was nearly equivalent to that of acute dapoxetine. In addition, both aerobic exercise and dapoxetine treatment could lead to increased expression of BDNF and 5-HT in the raphe nucleus of rapid ejaculators. Moreover, the two interventions, when applied together, may further upregulate the expression of BDNF-5-HT duo in a complementary manner. This study highlights the positive effects of aerobic exercise on ejaculation control. Regular aerobic exercise might be a promising complementary treatment to dapoxetine in rats.

15.
World J Microbiol Biotechnol ; 39(5): 116, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36918451

RESUMO

Vibrio splendidus is a ubiquitous pathogen that causes various diseases in aquaculture with a wide range of hosts. In our previous studies, we showed that L-glutamic acid was the optimal carbon source that could revive V. splendidus persister cells. In our present study, single cell observation under microscopy showed that V. splendidus could revive using L-glutamic acid as carbon source. A proteomic analysis was carried out to further illustrate the initial wake up of persister cells with L-glutamic acid. To collect the initially revived cells, SDS-PAGE was used to determine the revived time. The total proteins from the persister cells and the revived cells were analyzed using LC‒MS/MS. A total of 106 proteins, including 42 downregulated proteins and 64 upregulated proteins, were identified. GO analysis of the differentially expressed proteins (DEPs) showed that biological processes, including protein complex assembly, protein oligomerization, and arginine metabolism; cellular components, including extracellular membrane, plasma membrane and ribosome; and molecular functions, including the activities of arginine binding and structural constituent of ribosome, were enriched. KEGG analysis showed that lipopolysaccharide biosynthesis, porphyrin and chlorophyll metabolism, and peptidoglycan biosynthesis were upregulated, while the ribosome was downregulated. This is the first time to study the initial wake up of persister cells based on proteomic analysis, and the results revealed the main pathways involved in the early resuscitation of V. splendidus persister cells.


Assuntos
Ácido Glutâmico , Vibrio , Ácido Glutâmico/metabolismo , Proteômica , Cromatografia Líquida , Espectrometria de Massas em Tandem , Vibrio/metabolismo , Proteínas/metabolismo , Arginina/metabolismo
16.
ACS Omega ; 8(7): 6402-6410, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36844554

RESUMO

Compressor outlets are subject to high temperatures and vibrations; when pipelines are subject to such conditions, degradation of the anticorrosive layer on the pipeline is likely. Fusion-bonded epoxy (FBE) powder coating is the most common type of anticorrosion coatings on compressor outlet pipelines. It is necessary to study the reliability of anticorrosive layers in compressor outlet pipelines. In this paper, a service reliability test method for the corrosion-resistant coatings of compressor outlet pipelines of natural gas stations is proposed. Testing involving the simultaneous exposure of the pipeline to high temperatures and vibrations is conducted to evaluate, on a compressed timescale, the applicability and service reliability of FBE coatings. The failure mechanism of FBE coatings exposed to high temperatures and vibrations is analyzed. It is found that, due to the influence of initial imperfections in the coatings, FBE anticorrosion coatings typically do not meet the standard requirements for use in compressor outlet pipelines. After simultaneous exposure to high temperatures and vibrations, the impact resistance, abrasion resistance, and bending resistance of the coatings are found not to meet the requirements for their intended applications. It is therefore suggested that FBE anticorrosion coatings be used with extreme caution in compressor outlet pipelines.

17.
J Org Chem ; 88(6): 3539-3554, 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36825676

RESUMO

The traditional methods for the synthesis of phosphinate esters use phosphorus trichloride (PCl3) as the phosphorous source, resulting in procedures that are often highly polluting and energy intensive. The search for an alternative approach that is both mild and environmentally friendly is a challenging, yet highly rewarding task in modern chemistry. Herein, we use an inorganic phosphorous-containing species, NaH2PO2, to serve as the source of phosphorous that participates directly in the nickel-catalyzed selective alkyne hydrophosphonylation reaction. The transformation was achieved in a multicomponent fashion and at room temperature, and most importantly, the H-phosphinate product generated is an advanced intermediate which can be readily converted into diverse phosphinate derivatives, including those bearing new P-C, P-S, P-N, P-Se, and P-O bonds, thus providing a complimentary method to classic phosphinate ester synthesis techniques.

18.
Aquat Toxicol ; 256: 106415, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36746075

RESUMO

The ecotoxicological and environmental impacts of glyphosate-based herbicides have received considerable attention due to their extensive use globally. However, the potential for adverse effects in cultured non-fish vertebrate species are commonly ignored. In this study, effects on growth, indicators of functional performance, gut microbial diversity, liver antioxidant responses and metabolite profiles were evaluated in soft-shelled turtle hatchlings (Pelodiscus sinensis) exposed to different concentrations of glyphosate-isopropylammonium (0, 0.02, 0.2, 2 and 20 mg/L). No significant changes in growth or functional performance (food intake, swimming speed), gut microbiota, and liver antioxidant responses (SOD and CAT activities, MDA content) were observed in exposed turtles. However, hepatic metabolite profiles revealed distinct perturbations that primarily involved amino acid metabolism in turtles exposed to environmentally relevant concentrations. Overall, our results suggested that metabolite profiles may be more sensitive than phenotypic or general physiological endpoints and gut microbiota profiling, and indicate a potential mechanism of hepatotoxicity caused by glyphosate-isopropylammonium based on untargeted metabolomics analysis. Furthermore, the toxicity of glyphosate at environmentally relevant concentrations might be relatively minor in aquatic turtle species.


Assuntos
Tartarugas , Poluentes Químicos da Água , Animais , Antioxidantes , Poluentes Químicos da Água/toxicidade , Glicina/toxicidade , Glifosato
19.
Cell ; 186(3): 591-606.e23, 2023 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-36669483

RESUMO

Dysregulation of the immune system is a cardinal feature of opioid addiction. Here, we characterize the landscape of peripheral immune cells from patients with opioid use disorder and from healthy controls. Opioid-associated blood exhibited an abnormal distribution of immune cells characterized by a significant expansion of fragile-like regulatory T cells (Tregs), which was positively correlated with the withdrawal score. Analogously, opioid-treated mice also showed enhanced Treg-derived interferon-γ (IFN-γ) expression. IFN-γ signaling reshaped synaptic morphology in nucleus accumbens (NAc) neurons, modulating subsequent withdrawal symptoms. We demonstrate that opioids increase the expression of neuron-derived C-C motif chemokine ligand 2 (Ccl2) and disrupted blood-brain barrier (BBB) integrity through the downregulation of astrocyte-derived fatty-acid-binding protein 7 (Fabp7), which both triggered peripheral Treg infiltration into NAc. Our study demonstrates that opioids drive the expansion of fragile-like Tregs and favor peripheral Treg diapedesis across the BBB, which leads to IFN-γ-mediated synaptic instability and subsequent withdrawal symptoms.


Assuntos
Interferon gama , Transtornos Relacionados ao Uso de Opioides , Síndrome de Abstinência a Substâncias , Linfócitos T Reguladores , Animais , Camundongos , Analgésicos Opioides/administração & dosagem , Interferon gama/metabolismo , Transtornos Relacionados ao Uso de Opioides/metabolismo , Transtornos Relacionados ao Uso de Opioides/patologia
20.
Microb Pathog ; 175: 105981, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36642286

RESUMO

Vibrio splendidus, a gram-negative bacterium that is ubiquitously present in marine environments, has been increasingly deemed an important opportunistic pathogen of marine animals. In this study, the biofilm formation of V. splendidus was quantitatively determined and morphologically characterized. Three stages of biofilm formation, including adhesion, aggregation and maturation were observed in the biofilm formed by V. splendidus. The inhibitory effect of exogenous bis (3',5')-cyclic dimeric guanosine monophosphate (c-di-GMP) on the biofilm formation from the scratch and preformed established biofilms of V. splendidus was determined. When 200 µmol/L c-di-GMP was added, the quantity of biofilm decreased by 88.1% or 66.7% under the two conditions. To explore the preliminary mechanism of exogenous c-di-GMP on the biofilm formed by V. splendidus, proteomic analysis was performed. GO enrichment analysis showed that exogenous c-di-GMP upregulated biological processes, including the tricarboxylic acid cycle, oxidation‒reduction reactions and organonitrogen compound catabolism and significantly downregulated tRNA threonylcarbamoyladenosine modification, protein dephosphorylation, and lactate transmembrane transporter activity. Sequence-specific DNA binding activity was the most markedly downregulated molecular function. KEGG analysis showed that the valine, leucine and isoleucine degradation pathway was the most enriched pathway, followed by nitrogen metabolism, among the 20 upregulated pathways. Among the downregulated pathways, a nonribosomal peptide structure pathway and the streptomycine, polyketide sugar unit, acarbose and validamycin biosynthesis pathways were significantly enriched. Our present study provides basic data for the biofilm formation of V. splendidus and the preliminary inhibitory mechanism of exogenous c-di-GMP on the biofilm formation of V. splendidus.


Assuntos
Proteômica , Vibrio cholerae , Vibrio cholerae/genética , GMP Cíclico/metabolismo , Biofilmes , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica
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