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1.
Cell ; 185(13): 2265-2278.e14, 2022 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-35568034

RESUMO

Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed the protein subunit vaccine ZF2001 based on the dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, we developed a chimeric RBD-dimer vaccine approach to adapt SARS-CoV-2 variants. A prototype-Beta chimeric RBD-dimer was first designed to adapt the resistant Beta variant. Compared with its homotypic forms, the chimeric vaccine elicited broader sera neutralization of variants and conferred better protection in mice. The protection of the chimeric vaccine was further verified in macaques. This approach was generalized to develop Delta-Omicron chimeric RBD-dimer to adapt the currently prevalent variants. Again, the chimeric vaccine elicited broader sera neutralization of SARS-CoV-2 variants and conferred better protection against challenge by either Delta or Omicron SARS-CoV-2 in mice. The chimeric approach is applicable for rapid updating of immunogens, and our data supported the use of variant-adapted multivalent vaccine against circulating and emerging variants.


Assuntos
COVID-19 , Vacinas , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Camundongos , SARS-CoV-2/genética
2.
Anal Chem ; 96(28): 11353-11365, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38970480

RESUMO

Biothiols play essential roles in maintaining normal physiological functions, resisting oxidative stress, and protecting cell health. Establishing an effective and reliable sensor array for the accurate quantification and discrimination of diverse biothiols is extremely meaningful. In this work, Ag/Mn3O4, Ag3PO4, and Ag3Cit with excellent oxidase-mimetic activity and surface-enhanced Raman scattering (SERS)-enhanced features have been prepared and loaded onto Whatman filter paper (WFP) to build SERS paper chips as three sensing channels, which can induce 3,3',5,5'-tetramethylbenzidine (TMB) oxidation to SERS-active reporters (TMBox) and concurrently generate prominent SERS signals. Nevertheless, the addition of biothiols can suppress conversion from TMB to TMBox, which can cause the reduction of the SERS signal from TMBox. Interestingly, each SERS sensing channel can generate different TMBox signals' variations due to differences in the oxidative inhibition abilities of diverse biothiols and exclusive properties of each paper chip, which can be plotted as specific fingerprint patterns of each biothiol and further translated into intuitive two-dimensional (2D) clustering profiles through linear discriminant analysis (LDA) and hierarchical cluster analysis (HCA) techniques for precise identification of these six biothiols with the minimum concentration of 1 µM. More importantly, this SERS sensor array is exploited for the precise quantification of intracellular glutathione (GSH), and can differentiate between normal and cancer cells based on different intracellular GSH contents and even identify different types of tumor cells, demonstrating its powerful application prospects in disease diagnosis.


Assuntos
Papel , Prata , Análise Espectral Raman , Compostos de Sulfidrila , Análise Espectral Raman/métodos , Humanos , Compostos de Sulfidrila/análise , Compostos de Sulfidrila/química , Prata/química , Nanopartículas Metálicas/química , Propriedades de Superfície , Nanoestruturas/química , Oxirredução , Benzidinas/química , Linhagem Celular Tumoral
3.
J Transl Med ; 22(1): 469, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760791

RESUMO

BACKGROUND: Colorectal cancer (CRC) remains a major global health challenge, with high incidence and mortality rates. The role of long noncoding RNAs (lncRNAs) in cancer progression has received considerable attention. The present study aimed to investigate the function and mechanisms underlying the role of lncRNA RP11-197K6.1, microRNA-135a-5p (hsa-miR-135a-5p), and DLX5 in CRC development. METHODS: We analyzed RNA sequencing data from The Cancer Genome Atlas Colorectal Cancer dataset to identify the association between lncRNA RP11-197K6.1 and CRC progression. The expression levels of lncRNA RP11-197K6.1 and DLX5 in CRC samples and cell lines were determined by real-time quantitative PCR and western blotting assays. Fluorescence in situ hybridization was used to confirm the cellular localization of lncRNA RP11-197K6.1. Cell migration capabilities were assessed by Transwell and wound healing assays, and flow cytometry was performed to analyze apoptosis. The interaction between lncRNA RP11-197K6.1 and miR-135a-5p and its effect on DLX5 expression were investigated by the dual-luciferase reporter assay. Additionally, a xenograft mouse model was used to study the in vivo effects of lncRNA RP11-197K6.1 on tumor growth, and an immunohistochemical assay was performed to assess DLX5 expression in tumor tissues. RESULTS: lncRNA RP11-197K6.1 was significantly upregulated in CRC tissues and cell lines as compared to that in normal tissues, and its expression was inversely correlated with patient survival. It promoted the migration and metastasis of CRC cells by interacting with miR-135a-5p, alleviated suppression of DLX5 expression, and facilitated tumor growth. CONCLUSION: This study demonstrated the regulatory network and mechanism of action of the lncRNA RP11-197K6.1/miR-135a-5p/DLX5 axis in CRC development. These findings provided insights into the molecular pathology of CRC and suggested potential therapeutic targets for more effective treatment of patients with CRC.


Assuntos
Movimento Celular , Neoplasias Colorretais , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio , Camundongos Nus , MicroRNAs , RNA Longo não Codificante , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Animais , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Masculino , Feminino , Apoptose/genética , Proliferação de Células/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Sequência de Bases , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Camundongos , RNA Endógeno Competitivo
4.
Bioorg Med Chem Lett ; 110: 129878, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38977107

RESUMO

A novel class of pleuromutilin derivatives possessing 1,2,3-triazole as the linker connected to phenyl analogues were designed. The antibacterial properties of the prepared compounds were assessed in vitro against five strains (E. coli, S. aureus, S. epidermidis, and E. faecalis). Most of the tested compounds displayed potent antibacterial activities against gram-positive bacteria and 14-O-[2-(4-((2,4-dinitrophenoxy)-methyl-1H-1,2,3-triazol-1-yl) acetamide)-2-methylpropan-2-yl) thioacetyl]mutilin (7c) exerted antibacterial activities against S. aureus, MRSA and S. epidermidis with MIC values 0.0625 µg/mL, representing 64-fold, 4-fold and 8-fold higher than tiamulin respectively. Compound 6e, 7c and 8c were chosen to carry out killing kinetics, which exhibited concentration-dependent effect. Subsequently, molecular modeling was conducted to further explore the binding of compound 6e, 7a, 7c, 8c and tiamulin with 50S ribosomal subunit from deinococcus radiodurans. The investigation revealed that the main interactions between compound 7c and the ribosomal residues were three hydrogen bonds, π-π, and p-π conjugate effects. Additionally, the free binding energy and docking score of 7c with the ribosome demonstrated the lowest values of -11.90 kcal/mol and -7.97 kcal/mol, respectively, consistent with its superior antibacterial activities.

5.
Cereb Cortex ; 33(15): 9313-9324, 2023 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-37310187

RESUMO

Auditory steady-state response underlying gamma oscillations (gamma-ASSR) have been explored in patients with major depressive disorder (MDD), while ignoring the spatiotemporal dynamic characteristics. This study aims to construct dynamic directed brain networks to explore the disruption of spatiotemporal dynamics underlying gamma-ASSR in MDD. This study recruited 29 MDD patients and 30 healthy controls for a 40 Hz auditory steady-state evoked experiment. The propagation of gamma-ASSR was divided into early, middle, and late time interval. Partial directed coherence was applied to construct dynamic directed brain networks based on graph theory. The results showed that MDD patients had lower global efficiency and out-strength in temporal, parietal, and occipital regions over three time intervals. Additionally, distinct disrupted connectivity patterns occurred in different time intervals with abnormalities in the early and middle gamma-ASSR in left parietal regions cascading forward to produce dysfunction of frontal brain regions necessary to support gamma oscillations. Furthermore, the early and middle local efficiency of frontal regions were negatively correlated with symptom severity. These findings highlight patterns of hypofunction in the generation and maintenance of gamma-band oscillations across parietal-to-frontal regions in MDD patients, which provides novel insights into the neuropathological mechanism underlying gamma oscillations associated with aberrant brain network dynamics of MDD.


Assuntos
Transtorno Depressivo Maior , Humanos , Encéfalo , Mapeamento Encefálico , Lobo Parietal , Comunicação , Imageamento por Ressonância Magnética/métodos
6.
Environ Res ; 251(Pt 2): 118664, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38499222

RESUMO

The extensive use of mineral fertilizers has a negative impact on the environment, whereas wastewater and microalgal biomass can provide crops with nutrients such as nitrogen, phosphorus, and potassium, and have the potential to be used as a source of fertilizers in circular agriculture. In this study, a step-by-step resource utilization study of algae-containing wastewater generated from microalgae treatment of swine wastewater was carried out. When wheat seedlings were cultivated in the effluent after microalgae separation, the root fresh weight, seedling fresh weight, and total seedling length were increased by 3.44%, 14.45%, and 13.64%, respectively, compared with that of the algae-containing wastewater, and there was no significant difference in seedling fresh weight, total seedling length, maximum quantum yields of PSII photochemistry (Fv/Fm), and performance index (PIABS) from that of the Hogland solution group, which has the potential to be an alternative liquid fertilizer. Under salt stress, microalgae extract increased the contents of GA3, IAA, ABA, and SA in wheat seedlings, antioxidant enzymes maintained high activity, and the PIABS value increased. Low-dose microalgae extract (1 mL/L) increased the root fresh weight, seedling fresh weight, longest seedling length, and total seedling length by 30.73%, 31.28%, 16.43%, and 28.85%, respectively. Algae extract can act as a plant biostimulant to regulate phytohormone levels to attenuate the damage of salt stress and promote growth.


Assuntos
Biomassa , Microalgas , Plântula , Triticum , Águas Residuárias , Triticum/crescimento & desenvolvimento , Triticum/efeitos dos fármacos , Microalgas/crescimento & desenvolvimento , Microalgas/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Plântula/efeitos dos fármacos , Animais , Águas Residuárias/química , Suínos , Tolerância ao Sal , Fertilizantes/análise , Eliminação de Resíduos Líquidos/métodos
7.
J Proteome Res ; 22(9): 2936-2949, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37611228

RESUMO

Sleep loss is associated with cognitive dysfunction. However, the detailed mechanisms remain unclear. In this study, we established a para-chlorophenylalanine (PCPA)-induced insomniac mouse model with impaired cognitive function. Mass-spectrometry-based proteomics showed that the expression of 164 proteins was significantly altered in the hippocampus of the PCPA mice. To identify critical regulators among the potential markers, a transcriptome-wide association screening was performed in the BXD mice panel. Among the candidates, the expression of pleiotrophin (Ptn) was significantly associated with cognitive functions, indicating that Ptn-mediates sleep-loss-induced cognitive impairment. Gene co-expression analysis further revealed the potential mechanism by which Ptn mediates insomnia-induced cognitive impairment via the MAPK signaling pathway; that is, the decreased secretion of Ptn induced by insomnia leads to reduced binding to Ptprz1 on the postsynaptic membrane with the activation of the MAPK pathway via Fos and Nr4a1, further leading to the apoptosis of neurons. In addition, Ptn is genetically trans-regulated in the mouse hippocampus and implicated in neurodegenerative diseases in human genome-wide association studies. Our study provides a novel biomarker for insomnia-induced cognitive impairment and a new strategy for seeking neurological biomarkers by the integration of proteomics and systems genetics.


Assuntos
Disfunção Cognitiva , Distúrbios do Início e da Manutenção do Sono , Humanos , Animais , Camundongos , Estudo de Associação Genômica Ampla , Proteômica , Disfunção Cognitiva/genética , Sono
8.
Am J Transplant ; 23(3): 336-352, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36695693

RESUMO

Acute rejection (AR) is an important factor that leads to poor prognosis after liver transplantation (LT). Macrophage M1-polarization is an important mechanism in AR development. MicroRNAs play vital roles in disease regulation; however, their effects on macrophages and AR remain unclear. In this study, rat models of AR were established following LT, and macrophages and peripheral blood mononuclear cells were isolated from rats and humans, respectively. We found miR-449a expression to be significantly reduced in macrophages and peripheral blood mononuclear cells. Overexpression of miR-449a not only inhibited the M1-polarization of macrophages in vitro but also improved the AR of transplant in vivo. The mechanism involved inhibiting the noncanonical nuclear factor-kappaB (NF-κB) pathway. We identified procollagen-lysine1,2-oxoglutarate5-dioxygenase 1 (PLOD1) as a target gene of miR-449a, which could reverse miR-449a's inhibition of macrophage M1-polarization, amelioration of AR, and inhibition of the NF-κB pathway. Overall, miR-449a inhibited the NF-κB pathway in macrophages through PLOD1 and also inhibited the M1-polarization of macrophages, thus attenuating AR after LT. In conclusion, miR-449a and PLOD1 may be new targets for the prevention and mitigation of AR.


Assuntos
Transplante de Fígado , MicroRNAs , Animais , Humanos , Ratos , Leucócitos Mononucleares/metabolismo , Macrófagos/metabolismo , MicroRNAs/genética , NF-kappa B/metabolismo , Pró-Colágeno/metabolismo , Pró-Colágeno/farmacologia
9.
Langmuir ; 39(36): 12740-12753, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37651224

RESUMO

Paraffin and octadecyltrichlorosilane (OTS) coatings can alleviate collisions between alkali-metal atoms and cell walls and then prolong the atomic spin-polarization lifetime. The surface structure and collision effects of these antirelaxation coatings, as well as the methods to avoid antirelaxation invalidity, have been the focus of researchers. This study investigated the thermolability of coating surface structure and the collision interactions between alkali metal atoms and coatings, considering the influence of various coating preparation factors, where this collision interaction is indirectly analyzed by measuring the collision energy dissipation between an atomic force microscopy (AFM) probe and the atoms on the coating surface. We found that appropriate evaporation time, carbochain length, and postannealing process can enhance the thermostability of the paraffin coating and eliminate its morphological defects. Furthermore, the OTS/water concentration, the soaking time, and the type of solvent have different levels of influence on the cluster formation and the thermostability of the OTS coatings. Moreover, the antirelaxation performance of coatings has been shown to be characterized by counting the energy dissipated when the AFM probe collides with the antirelaxation coating, replacing the conventional light-atom interaction- based method for measuring the relaxation characteristics, but requiring specific coating preparation factors to be maintained.

10.
Saudi Pharm J ; 31(11): 101801, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37829191

RESUMO

Background: Limited data exists on the use of rivaroxaban for the treatment of pediatric patients. This report presents a case of probable rivaroxaban-induced Erythema Multiforme in Children. Case Summary: A female patient aged 5.5 years with antiphospholipid syndrome (APS) was administered oral rivaroxaban tablets 2.5 mg twice a day for 16 days. Subsequently, the patient developed a slight itching sensation on both feet and buttocks without an apparent cause. The following day, erythema multiforme appeared across the body in a scattered pattern. The erythema presented higher than the skin surface and partially merged into areas of the skin. Following an increase in the extent and degree of the erythema, all oral medications were ceased. Treatment with dexamethasone sodium phosphate injection, mometasone furoate cream, and mucopolysaccharide polysulfate cream resulted in an improvement of erythema multiforme. The erythema diminished and did not deteriorate subsequent to changing from rivaroxaban tablets to warfarin sodium tablets, and receiving nadroparin calcium injection.

11.
Pers Ubiquitous Comput ; 27(3): 783-792, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-33564287

RESUMO

The outbreak of the new type of coronavirus pneumonia (COVID-19) has caused a huge impact on the world. In this case, only by adhering to the prevention and control methods of early diagnosis, early isolation, and early treatment, can the spread of the virus be prevented to the greatest extent. This article uses artificial intelligence-assisted medical imaging diagnosis as the research object, combines artificial intelligence and CT medical imaging diagnosis, introduces an intelligent COVID-19 detection system, and uses it to achieve COVID-19 disease screening and lesion evaluation. CT examination has the advantages of fast speed and high accuracy, which can provide a favorable basis for clinical diagnosis. This article collected 32 lung CT scan images of patients with confirmed COVID-19. Two professional radiologists analyzed the CT images using traditional imaging diagnostic methods and artificial intelligence-assisted imaging diagnostic methods, and the comparison showed the gap between the two methods. According to experiments, CT imaging diagnosis assisted by artificial intelligence only takes 0.744 min on average, which can save a lot of time and cost compared with the average time of 3.623 min for conventional diagnosis. In terms of comprehensive test accuracy, it can be concluded that the combination of artificial intelligence and imaging diagnosis has extremely high application value in COVID-19 diagnosis.

12.
Anal Chem ; 94(4): 2298-2304, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35040308

RESUMO

The development of a versatile and sensitive analytical biomarker detection platform is important for both early diagnosis and treatment of diseases. In the present study, we propose a novel fluorescence-based, ultrasensitive, and label-free biomarker detection platform. This platform relies on a flexible probe design compatible for multiple biomarker identification and Exo-III enzyme-triggered cascade signal amplification. We have validated that this label-free platform exhibits high sensitivity and specificity. Indeed, this platform exhibited brilliant analytical performance in qualifying a carcinoembryonic antigen and small extracellular vesicles (sEVs). It also shows excellent capability in multiplexing mapping of surface proteins of various cancer-derived sEVs. Therefore, we believe that the proposed sensing platform has great potential for clinical diagnosis and anticancer drug development.


Assuntos
Técnicas Biossensoriais , Exodesoxirribonucleases , Exodesoxirribonucleases/metabolismo , Limite de Detecção , Técnicas de Amplificação de Ácido Nucleico
13.
Soft Matter ; 18(14): 2829-2841, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35332906

RESUMO

A novel kind of inhibitor-loaded polyaniline (PANI) microcapsule was prepared by Pickering emulsion photopolymerization using polyaniline particles as the Pickering emulsifier. In our strategy, water-dispersible polyaniline nanoparticles were firstly synthesized using a micelle template method and used to stabilize oil-in-water emulsions, in which the oil phase contained photo-crosslinkable and pH sensitive monomers and a photo-initiator. Under UV light, the pH-responsive monomers underwent photo-polymerization and crosslinking and converted to microcapsule shells. During this process, polyaniline nanoparticles were trapped in the microcapsule shells, leading to the formation of PANI microcapsules. The structure and morphology of the synthesized PANI microcapsules were analyzed using FTIR spectroscopy, SEM, and EDX mapping. The inhibitor (mercaptobenzothiazole, MBT) was subsequently incorporated into the PANI microcapsule as a functional core and demonstrated pH-sensitive releasing behavior. With the anti-corrosive PANI as the microcapsule wall and the inhibitor MBT as the core, the as-prepared MBT loaded PANI (MBT@PANI) microcapsule could afford dual corrosion protection, allowing smart protection of metals when exposed to corrosive conditions. The MBT@PANI microcapsules were embedded in UV-cured coating for protecting steel. The corrosion protection performance of the coating with MBT@PANI microcapsules was evaluated using the electrochemical impedance spectroscopy technique and salt spray test, which demonstrated the synergistic inhibition effect of the PANI wall and the loaded MBT in improving anti-corrosion performance of the coating.

14.
Med Vet Entomol ; 36(4): 511-515, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35801679

RESUMO

Haemaphysalis longicornis is an obligate haematophagous ectoparasite, transmitting a variety of pathogens, which brings great damage to human health and animal husbandry development. Lipocalins (LIP) are a family of proteins that transport small hydrophobic molecules and also involve in immune regulation, such as the regulation of cell homeostasis, inhibiting the host's inflammatory response and resisting the contractile responses in host blood vessels. Therefore, it is one of the candidate antigens for vaccines. Based on previous studies, we constructed the recombinant plasmid pcDNA3.1-HlLIP of LIP homologue from H. longicornis (HlLIP). ELISA results showed that rabbits immunized with pcDNA3.1-HlLIP produced higher anti-rHlLIP antibody levels compared with the pcDNA3.1 group, indicating that pcDNA3.1-HlLIP induced the humoral immune response of host. Adult H. longicornis infestation trial in rabbits demonstrated that the engorgement weight, oviposition and hatchability of H. longicornis fed on rabbits immunized with pcDNA3.1-HlLIP decreased by 7.07%, 14.30% and 11.70% respectively, compared with that of the pcDNA3.1 group. In brief, DNA vaccine of pcDNA3.1-HlLIP provided immune protection efficiency of 30% in rabbits. This study demonstrated that pcDNA3.1-HlLIP can partially protect rabbits against H. longicornis, and it is possible to develop a new candidate antigen against ticks.


Assuntos
Ixodidae , Infestações por Carrapato , Carrapatos , Vacinas de DNA , Feminino , Coelhos , Humanos , Animais , Vacinas de DNA/metabolismo , Infestações por Carrapato/prevenção & controle , Infestações por Carrapato/veterinária , Lipocalinas/metabolismo , Ixodidae/metabolismo
15.
Anal Chem ; 93(26): 9036-9040, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34161075

RESUMO

Circulating tumor cells (CTCs) play a pivotal role in the early diagnosis of pheochromocytoma (PCC). Herein, we fabricated a new dual-targeting nanoprobe for coinstantaneous identification of rare PCC-CTCs from peripheral blood via targeting the norepinephrine transporter (NET) and somatostatin receptor SSTR2 overexpressed on the surface of PCC cells. Meta-iodobenzylguanidine (MIBG) functionalized magnetic Fe3O4 and octreotide (DOTA) decorated signal amplification Ag@SiO2 nanosphere were used to capture and detect PCC-CTCs by binding to NET and SSTR2. The proposed dual-targeting sensor achieved good reproducibility and high sensitivity for the monitoring of PC12 in the concentration range from 5 to 5 × 104 cells mL-1, with detection limits of 2 cell/mL. This strategy opens a new approach for simple, sensitive, and rapid determination of PCC biomarkers, which shows great potential in early diagnosis, prognosis, and therapeutic evaluation of PCC.


Assuntos
Neoplasias das Glândulas Suprarrenais , Células Neoplásicas Circulantes , Feocromocitoma , Diagnóstico Precoce , Humanos , Feocromocitoma/diagnóstico , Reprodutibilidade dos Testes , Dióxido de Silício
16.
BMC Psychiatry ; 21(1): 280, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074266

RESUMO

BACKGROUND: Subclinical depression (ScD) is a prevalent condition associated with relatively mild depressive states, and it poses a high risk of developing into major depressive disorder (MDD). However, the neural pathology of ScD is still largely unknown. Identifying the spontaneous neural activity involved in ScD may help clarify risk factors for MDD and explore treatment strategies for mild stages of depression. METHODS: A total of 34 ScD subjects and 40 age-, sex-, and education-matched healthy controls were screened from 1105 college students. The amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) of resting-state fMRI were calculated to reveal neural activity. Strict statistical strategies, including Gaussian random field (GRF), false discovery rate (FDR), and permutation test (PT) with threshold-free cluster enhancement (TFCE), were conducted. Based on the altered ALFF and ReHo, resting-state functional connectivity (RSFC) was further analyzed using a seed-based approach. RESULTS: The right precuneus and left middle frontal gyrus (MFG) both showed significantly increased ALFF and ReHo in ScD subjects. Moreover, the left hippocampus and superior frontal gyrus (SFG) showed decreased ALFF and increased ReHo, respectively. In addition, ScD subjects showed increased RSFC between MFG and hippocampus compared to healthy controls, and significant positive correlation was found between the Beck Depression Inventory-II (BDI-II) score and RSFC from MFG to hippocampus in ScD group. CONCLUSION: Spontaneous neural activities in the right precuneus, left MFG, SFG, and hippocampus were altered in ScD subjects. Functional alterations in these dorsolateral prefrontal cortex and default mode network regions are largely related to abnormal emotional processing in ScD, and indicate strong associations with brain impairments in MDD, which provide insight into potential pathophysiology mechanisms of subclinical depression.


Assuntos
Transtorno Depressivo Maior , Encéfalo , Depressão , Transtorno Depressivo Maior/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Lobo Parietal/diagnóstico por imagem , Córtex Pré-Frontal , Estudantes
17.
Neurobiol Learn Mem ; 171: 107210, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32145408

RESUMO

Epigenetic mechanisms of learning and memory are particularly interesting topics in neuroscience that have recently been investigated. As shown in our previous study, IQGAP1, a scaffolding protein of MAPK, is involved in fear memory through interactions with GluN2A-containing NMDA receptors and the ERK1/2 cascade. However, researchers have not determined whether histone posttranslational modifications are regulated by the IQGAP1/ERK signaling pathway. We performed in vivo studies using IQGAP1-/- and IQGAP1+/+ mice to provide insights into the specific functions of IQGAP1 in memory processes and the precise mechanisms underlying its regulatory effects. IQGAP1-/- mice exhibited impaired fear memory, decreased levels of phosphorylated ERK1/2 and histone H3S10, decreased acetylation of H3K14, and decreased c-Fos expression in the hippocampus compared to IQGAP1+/+ mice after fear conditioning. HDAC2 was significantly enriched at the c-fos gene promoter in IQGAP1-/- mice. Correspondingly, the disruption of the epigenetic regulation induced by ERK1/2 signaling through an intra-hippocampal injection of the MEK antagonist U0126 or GluN2A-selective pharmacological antagonist NVP-AAM077 blocked context-dependent memory formation, while no changes were observed after treatment with the GluN2B-selective antagonist Ro25-6981. The administration of SAHA, a non-specific HDAC inhibitor, or knock-down of HDAC2 with shHDAC2-AAV in the dorsal hippocampus significantly rescued the impaired fear memory formation, H3S10 phosphorylation, H3K14 acetylation, and c-Fos expression in IQGAP1-/- mice. Thus, we postulated that the IQGAP1/ERK-dependent mechanism regulating histone posttranslational modifications via HDAC2 potentially underlies memory formation.


Assuntos
Medo/fisiologia , Histona Desacetilase 2/metabolismo , Memória/fisiologia , Processamento de Proteína Pós-Traducional/fisiologia , Proteínas Ativadoras de ras GTPase/metabolismo , Animais , Butadienos/farmacologia , Inibidores Enzimáticos/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Medo/efeitos dos fármacos , Histona Desacetilase 2/genética , Histonas/metabolismo , Memória/efeitos dos fármacos , Camundongos , Camundongos Knockout , Nitrilas/farmacologia , Fosforilação/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Quinoxalinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Proteínas Ativadoras de ras GTPase/genética
18.
Biomacromolecules ; 21(12): 5222-5232, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-33215500

RESUMO

Medical glue represents a suitable tool to stop wound bleeding, seal wounds, bond tissues, or implant materials. However, the development of a medical glue for durable underwater bonding remains a challenge. Herein, we developed a hydrophobic hyperbranched polymer-based medical glue with water-resistant bonding ability. Specifically, the hyperbranched polythioether (HBPTE) with abundant terminal thiol groups was first prepared through a simple one-pot thiol-Michael polyaddition reaction. Due to the hyperbranched molecular structure, HBPTE is a liquid material under room temperature, thus enabling the manufacturing of a photocurable HBPTE glue by the direct addition of poly(ethylene glycol) dimethacrylate and a photoinitiator without introduction of a solvent. This solventless HBPTE glue exhibited a maximum underwater adhesive strength of 36 kPa on porcine skin compared to only <10 kPa of the commercial fibrin glue and cyanoacrylate glue. Moreover, since the hydrophobic cross-linked network resists penetration of water, the HBPTE glue minimally swelled (2-10%) and could maintain a glass sheet structure bonded together even after 2 weeks underwater. Furthermore, an in vitro cytotoxicity test showed that the HBPTE glue did not leak any cytotoxic substances and allowed for proliferation of L929 cells on its surface. Moreover, hemocompatibility tests indicated that the HBPTE glue was nonhemolytic and did not induce thrombosis. This HBPTE glue exhibited promising characteristics to potentially find use as an underwater soft tissue adhesive or sealant.


Assuntos
Polímeros , Adesivos Teciduais , Animais , Adesivo Tecidual de Fibrina , Teste de Materiais , Suínos , Água
19.
Anal Bioanal Chem ; 412(6): 1317-1324, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31927600

RESUMO

Herein, a dual-emission metal-organic framework based ratiometric fluorescence nanoprobe was reported for detecting copper(II) ions. In particular, carbon dots (CDs) and gold nanoclusters (AuNCs) were embedded into ZIF-8 (one of the classical metal-organic frameworks) to form CDs/AuNCs@ZIF-8 nanocomposites, which exhibited dual-emission peaks at UV excitation. In the presence of Cu2+, the fluorescence attributed to AuNCs can be rapidly quenched, while the fluorescence of CDs serves as reference with undetectable changes. Therefore, the CDs/AuNCs@ZIF-8 nanocomposites were utilized as a ratiometric fluorescence nanoprobe for sensitive and selective detection of Cu2+. A good linear relationship between the ratiometric fluorescence signal of CDs/AuNCs@ZIF-8 and Cu2+ concentration was obtained in the range of 10-3-103 µM, and the detection limit was as low as 0.3324 nM. The current ratiometric fluorescence nanoprobe showed promising prospects in cost-effective and rapid determination of Cu2+ ions with good sensitivity and selectivity. Furthermore, this nanoprobe has been successfully applied for the quantitative detection of Cu2+ in serum samples, indicating its value of practical application. Graphical abstract Carbon dots (CDs) and gold nanoclusters (AuNCs) were embedded into metal-organic frameworks (ZIF-8) to form CDs/AuNCs@ZIF-8 nanocomposites, which exhibited dual-emission peaks at 365 nm excitation. In the presence of Cu2+, the fluorescence emission peak at 574 nm can rapidly respond by quenching, while the fluorescence at 462 nm serves as reference with undetectable changes.


Assuntos
Carbono/química , Cobre/análise , Ouro/química , Nanopartículas Metálicas/química , Estruturas Metalorgânicas/química , Pontos Quânticos/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Cobre/sangue , Humanos , Limite de Detecção
20.
Small ; 15(13): e1900099, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30811830

RESUMO

Fast and highly efficient enrichment and separation of glycoproteins is essential in many biological applications, but the lack of materials with high capture capacity, fast, and efficient enrichment/separation makes it a challenge. Here, a temperature-responsive core cross-linked star (CCS) polymer with boronate affinity is reported for fast and efficient enriching and separating of glycoproteins from biological samples. The temperature-responsive CCS polymers containing boronic acid in its polymeric arms and poly(N-isopropyl acrylamide) in its cross-linked core are prepared using reversible addition-fragmentation chain transfer polymerization via an "arm-first" methodology. The soluble boronate polymeric arms of the CCS polymers provide a homogeneous reaction system and facilitate interactions between boronic acid and glycoproteins, which leads to a fast binding/desorption speed and high capture capacity. Maximum binding capacity of the prepared CCS polymer for horseradish peroxidase is determined to be 210 mg g-1 , which can be achieved within 20 min. More interestingly, the temperature-responsive CCS polymers exhibit rapid reversible thermal-induced volume phase transition by increasing the temperature from 15 to 30 °C, resulting in a facile and convenient sample collection and recovery for the target glycoproteins. Finally, the temperature-responsive CCS polymer is successfully applied to enrichment of low abundant glycoproteins.


Assuntos
Ácidos Borônicos/química , Glicoproteínas/análise , Polímeros/química , Temperatura , Adsorção , Animais , Bovinos , Difusão Dinâmica da Luz , Polímeros/síntese química , Ligação Proteica , Espectroscopia de Prótons por Ressonância Magnética , Soroalbumina Bovina/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectroscopia de Infravermelho com Transformada de Fourier
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