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1.
Cell ; 182(1): 73-84.e16, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32425270

RESUMO

The COVID-19 pandemic urgently needs therapeutic and prophylactic interventions. Here, we report the rapid identification of SARS-CoV-2-neutralizing antibodies by high-throughput single-cell RNA and VDJ sequencing of antigen-enriched B cells from 60 convalescent patients. From 8,558 antigen-binding IgG1+ clonotypes, 14 potent neutralizing antibodies were identified, with the most potent one, BD-368-2, exhibiting an IC50 of 1.2 and 15 ng/mL against pseudotyped and authentic SARS-CoV-2, respectively. BD-368-2 also displayed strong therapeutic and prophylactic efficacy in SARS-CoV-2-infected hACE2-transgenic mice. Additionally, the 3.8 Å cryo-EM structure of a neutralizing antibody in complex with the spike-ectodomain trimer revealed the antibody's epitope overlaps with the ACE2 binding site. Moreover, we demonstrated that SARS-CoV-2-neutralizing antibodies could be directly selected based on similarities of their predicted CDR3H structures to those of SARS-CoV-neutralizing antibodies. Altogether, we showed that human neutralizing antibodies could be efficiently discovered by high-throughput single B cell sequencing in response to pandemic infectious diseases.


Assuntos
Anticorpos Monoclonais/isolamento & purificação , Anticorpos Neutralizantes/isolamento & purificação , Linfócitos B/imunologia , Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Análise de Célula Única , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/química , Anticorpos Monoclonais/metabolismo , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/metabolismo , COVID-19 , Convalescença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Camundongos , Pandemias , Análise de Sequência de RNA , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Éxons VDJ
2.
Cell ; 167(5): 1385-1397.e11, 2016 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-27863250

RESUMO

The association of histone modification changes with autism spectrum disorder (ASD) has not been systematically examined. We conducted a histone acetylome-wide association study (HAWAS) by performing H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) on 257 postmortem samples from ASD and matched control brains. Despite etiological heterogeneity, ≥68% of syndromic and idiopathic ASD cases shared a common acetylome signature at >5,000 cis-regulatory elements in prefrontal and temporal cortex. Similarly, multiple genes associated with rare genetic mutations in ASD showed common "epimutations." Acetylome aberrations in ASD were not attributable to genetic differentiation at cis-SNPs and highlighted genes involved in synaptic transmission, ion transport, epilepsy, behavioral abnormality, chemokinesis, histone deacetylation, and immunity. By correlating histone acetylation with genotype, we discovered >2,000 histone acetylation quantitative trait loci (haQTLs) in human brain regions, including four candidate causal variants for psychiatric diseases. Due to the relative stability of histone modifications postmortem, we anticipate that the HAWAS approach will be applicable to multiple diseases.


Assuntos
Transtorno do Espectro Autista/genética , Cerebelo/metabolismo , Código das Histonas , Córtex Pré-Frontal/metabolismo , Locos de Características Quantitativas , Lobo Temporal/metabolismo , Acetilação , Transtorno do Espectro Autista/metabolismo , Autopsia , Imunoprecipitação da Cromatina , Elementos Facilitadores Genéticos , Humanos , Regiões Promotoras Genéticas , Fatores de Transcrição/metabolismo
3.
Nature ; 613(7943): 274-279, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36631650

RESUMO

The development of next-generation electronics requires scaling of channel material thickness down to the two-dimensional limit while maintaining ultralow contact resistance1,2. Transition-metal dichalcogenides can sustain transistor scaling to the end of roadmap, but despite a myriad of efforts, the device performance remains contact-limited3-12. In particular, the contact resistance has not surpassed that of covalently bonded metal-semiconductor junctions owing to the intrinsic van der Waals gap, and the best contact technologies are facing stability issues3,7. Here we push the electrical contact of monolayer molybdenum disulfide close to the quantum limit by hybridization of energy bands with semi-metallic antimony ([Formula: see text]) through strong van der Waals interactions. The contacts exhibit a low contact resistance of 42 ohm micrometres and excellent stability at 125 degrees Celsius. Owing to improved contacts, short-channel molybdenum disulfide transistors show current saturation under one-volt drain bias with an on-state current of 1.23 milliamperes per micrometre, an on/off ratio over 108 and an intrinsic delay of 74 femtoseconds. These performances outperformed equivalent silicon complementary metal-oxide-semiconductor technologies and satisfied the 2028 roadmap target. We further fabricate large-area device arrays and demonstrate low variability in contact resistance, threshold voltage, subthreshold swing, on/off ratio, on-state current and transconductance13. The excellent electrical performance, stability and variability make antimony ([Formula: see text]) a promising contact technology for transition-metal-dichalcogenide-based electronics beyond silicon.

4.
EMBO J ; 43(12): 2308-2336, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38760574

RESUMO

How cells coordinate morphogenetic cues and fate specification during development remains a fundamental question in organogenesis. The mammary gland arises from multipotent stem cells (MaSCs), which are progressively replaced by unipotent progenitors by birth. However, the lack of specific markers for early fate specification has prevented the delineation of the features and spatial localization of MaSC-derived lineage-committed progenitors. Here, using single-cell RNA sequencing from E13.5 to birth, we produced an atlas of matched mouse mammary epithelium and mesenchyme and reconstructed the differentiation trajectories of MaSCs toward basal and luminal fate. We show that murine MaSCs exhibit lineage commitment just prior to the first sprouting events of mammary branching morphogenesis at E15.5. We identify early molecular markers for committed and multipotent MaSCs and define their spatial distribution within the developing tissue. Furthermore, we show that the mammary embryonic mesenchyme is composed of two spatially restricted cell populations, and that dermal mesenchyme-produced FGF10 is essential for embryonic mammary branching morphogenesis. Altogether, our data elucidate the spatiotemporal signals underlying lineage specification of multipotent MaSCs, and uncover the signals from mesenchymal cells that guide mammary branching morphogenesis.


Assuntos
Linhagem da Célula , Células Epiteliais , Glândulas Mamárias Animais , Células-Tronco Mesenquimais , Animais , Camundongos , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/embriologia , Glândulas Mamárias Animais/metabolismo , Feminino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Diferenciação Celular , Células-Tronco Multipotentes/citologia , Células-Tronco Multipotentes/metabolismo , Fator 10 de Crescimento de Fibroblastos/metabolismo , Fator 10 de Crescimento de Fibroblastos/genética , Morfogênese , Análise de Célula Única , Mesoderma/citologia , Mesoderma/metabolismo , Mesoderma/embriologia
5.
Nature ; 605(7908): 69-75, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35508774

RESUMO

Two-dimensional transition-metal dichalcogenides (TMDs) are of interest for beyond-silicon electronics1,2. It has been suggested that bilayer TMDs, which combine good electrostatic control, smaller bandgap and higher mobility than monolayers, could potentially provide improvements in the energy-delay product of transistors3-5. However, despite advances in the growth of monolayer TMDs6-14, the controlled epitaxial growth of multilayers remains a challenge15. Here we report the uniform nucleation (>99%) of bilayer molybdenum disulfide (MoS2) on c-plane sapphire. In particular, we engineer the atomic terrace height on c-plane sapphire to enable an edge-nucleation mechanism and the coalescence of MoS2 domains into continuous, centimetre-scale films. Fabricated field-effect transistor (FET) devices based on bilayer MoS2 channels show substantial improvements in mobility (up to 122.6 cm2 V-1 s-1) and variation compared with FETs based on monolayer films. Furthermore, short-channel FETs exhibit an on-state current of 1.27 mA µm-1, which exceeds the 2028 roadmap target for high-performance FETs16.

6.
Proc Natl Acad Sci U S A ; 119(51): e2206938119, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36508663

RESUMO

Correlations in gene expression are used to infer functional and regulatory relationships between genes. However, correlations are often calculated across different cell types or perturbations, causing genes with unrelated functions to be correlated. Here, we demonstrate that correlated modules can be better captured by measuring correlations of steady-state gene expression fluctuations in single cells. We report a high-precision single-cell RNA-seq method called MALBAC-DT to measure the correlation between any pair of genes in a homogenous cell population. Using this method, we were able to identify numerous cell-type specific and functionally enriched correlated gene modules. We confirmed through knockdown that a module enriched for p53 signaling predicted p53 regulatory targets more accurately than a consensus of ChIP-seq studies and that steady-state correlations were predictive of transcriptome-wide response patterns to perturbations. This approach provides a powerful way to advance our functional understanding of the genome.


Assuntos
Redes Reguladoras de Genes , Proteína Supressora de Tumor p53 , Proteína Supressora de Tumor p53/genética , Perfilação da Expressão Gênica , Transcriptoma , Transdução de Sinais , Análise de Célula Única/métodos
7.
Am J Physiol Endocrinol Metab ; 326(6): E776-E790, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38568153

RESUMO

Obesity has become a major risk of global public health. SMEK1 is also known as a regulatory subunit of protein phosphatase 4 (PP4). Both PP4 and SMEK1 have been clarified in many metabolic functions, including the regulation of hepatic gluconeogenesis and glucose transporter gene expression in yeast. Whether SMEK1 participates in obesity and the broader metabolic role in mammals is unknown. Thus, we investigated the function of SMEK1 in white adipose tissue and glucose uptake. GWAS/GEPIA/GEO database was used to analyze the correlation between SMEK1 and metabolic phenotypes/lipid metabolism-related genes/obesity. Smek1 KO mice were generated to identify the role of SMEK1 in obesity and glucose homeostasis. Cell culture and differentiation of stromal-vascular fractions (SVFs) and 3T3-L1 were used to determine the mechanism. 2-NBDG was used to measure the glucose uptake. Compound C was used to confirm the role of AMPK. We elucidated that SMEK1 was correlated with obesity and adipogenesis. Smek1 deletion enhanced adipogenesis in both SVFs and 3T3-L1. Smek1 KO protected mice from obesity and had protective effects on metabolic disorders, including insulin resistance and inflammation. Smek1 KO mice had lower levels of fasting serum glucose. We found that SMEK1 ablation promoted glucose uptake by increasing p-AMPKα(T172) and the transcription of Glut4 when the effect on AMPK-regulated glucose uptake was due to the PP4 catalytic subunits (PPP4C). Our findings reveal a novel role of SMEK1 in obesity and glucose homeostasis, providing a potential new therapeutic target for obesity and metabolic dysfunction.NEW & NOTEWORTHY Our study clarified the relationship between SMEK1 and obesity for the first time and validated the conclusion in multiple ways by combining available data from public databases, human samples, and animal models. In addition, we clarified the role of SMEK1 in glucose uptake, providing an in-depth interpretation for the study of its function in glucose metabolism.


Assuntos
Proteínas Quinases Ativadas por AMP , Adipogenia , Glucose , Camundongos Knockout , Obesidade , Transdução de Sinais , Animais , Masculino , Camundongos , Células 3T3-L1 , Adipogenia/genética , Tecido Adiposo Branco/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Glucose/metabolismo , Resistência à Insulina , Doenças Metabólicas/metabolismo , Doenças Metabólicas/genética , Doenças Metabólicas/etiologia , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/genética , Fosfoproteínas Fosfatases
8.
Int Arch Allergy Immunol ; 185(5): 425-435, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38432211

RESUMO

INTRODUCTION: Clinical management of asthma remains as a prevalent challenge. Monotropein (MON) is a naturally occurring cyclic enol ether terpene glycoside with medical application potential. This study aims to evaluate the potential therapeutic effects of MON in the mouse model of chronic asthma. METHODS: An ovalbumin (OVA)-induced asthmatic mouse model was established to evaluate the therapeutic effect of MON at different doses (20, 40, and 80 mg/kg). The potential involvement of protein kinase B (AKT)/nuclear factor kappa B (NF-κB) pathway in the effect of MON was investigated by the administration of an AKT activator SC79. Histological changes in pulmonary tissues were examined by hematoxylin and eosin staining. The profiles of inflammatory cytokines (interleukin [IL]-4, IL-5, IL-13, and tumor necrosis factor [TNF]-α) in bronchoalveolar lavage fluid (BALF), and OVA-specific IgE in blood samples were analyzed by enzyme-linked immunosorbent assay (ELISA). The oxidative stress in the lung tissues was determined by measuring malondialdehyde level. The phosphorylation activation of AKT and NF-κB was examined by immunoblotting in the lung tissues. RESULTS: MON treatment suppressed the infiltration of inflammatory cells in the airways of OVA-induced asthma mice and reduced the thickness of the bronchial wall and smooth muscle layer in a dose-dependent manner. MON treatment also reduced the levels of OVA-specific IgE in serum and cytokines in BALF in asthma-induced mice, and attenuated the oxidative stress in the lung tissues. OVA induced the phosphorylation of AKT and NF-κB proteins in the lung tissues of asthmatic mice, which was significantly suppressed by MON treatment. The co-administration of AKT activator SC79 impaired the therapeutic effect of MON on asthma-induced mice. CONCLUSION: Our data demonstrated the potential therapeutic effect of MON on asthmatic mouse model, suggesting that MON attenuated the inflammatory and oxidative damages in ling tissues by dampening the AKT/NF-κB signaling pathway.


Assuntos
Asma , Citocinas , Modelos Animais de Doenças , NF-kappa B , Ovalbumina , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Animais , Asma/tratamento farmacológico , Asma/induzido quimicamente , Asma/metabolismo , Asma/patologia , NF-kappa B/metabolismo , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Citocinas/metabolismo , Feminino , Pulmão/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Camundongos Endogâmicos BALB C , Imunoglobulina E/sangue , Estresse Oxidativo/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/citologia
9.
J Comput Assist Tomogr ; 48(2): 226-232, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37965776

RESUMO

OBJECTIVE: This study aimed to investigate changes of computed tomography pulmonary angiography (CTPA)-derived parameters in older adults with acute pulmonary embolism (APE). METHODS: According to the pulmonary artery obstruction index (PAOI), patients with APE were divided into the A1 (PAOI ≥30%, n = 57) and A2 (PAOI <30%, n = 40) groups. Participants without APE were placed in group B (n = 170). The left atrial (LA) and left ventricular (LV) parameters among the three groups were compared, and the parameter changes in the 44 patients with APE were analyzed before and after treatment. The correlation between APE severity and the parameters was analyzed using correlation analysis. RESULTS: The left-to-right diameters (LR) of LA, and LR × anteroposterior diameters (AP) of LA and LV: A1 < A2 < B; LR of LV: A1 < A2, B; AP of LA and LV: A1, A2 < B. After treatment, LR and LR × AP of the LA and LV were significantly increased in the group A1 and LR of the LV and LR × AP of the LA and LV were elevated in the group A2. Acute pulmonary embolism severity was closely associated with LR × AP ( r = -0.557) and LR ( r = -0.477) of LA. CONCLUSIONS: With an increase in the degree of obstruction, older adults had a smaller LA and LV. Furthermore, the LR and LR × AP values of the LA were significantly decreased. These results contribute to in-time risk stratification.


Assuntos
Hominidae , Embolia Pulmonar , Humanos , Animais , Idoso , Angiografia por Tomografia Computadorizada/métodos , Embolia Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Angiografia/métodos , Doença Aguda , Estudos Retrospectivos
10.
Neurosurg Rev ; 47(1): 293, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38914867

RESUMO

BACKGROUND: The bone holes in the skull during surgical drainage were accurately located at the site of the MMA. The MMA was severed, and the hematoma was removed intraoperatively; furthermore, surgical drainage removed the pathogenic factors of CSDH. This study aimed to describe and compare the results of the new treatment with those of traditional surgical drainage, and to investigate the relevance of this approach. METHODS: From December 2021 to June 2023, 72 patients were randomly assigned to the observation group and the control group. The control group was treated with traditional surgical drainage, while the observation group was treated with DSA imaging to accurately locate the bone holes drilled in the skull on the MMA trunk before traditional surgical drainage. The MMA trunk was severed during the surgical drainage of the hematoma. The recurrence rate, time of indwelling drainage tube, complications, mRS, and other indicators of the two groups were compared, and the changes of cytokine components and imaging characteristics of the patients were collected and analyzed. RESULTS: Overall, 27 patients with 29-side hematoma in the observation group and 45 patients with 48-side hematoma in the control group were included in the study. The recurrence rate was 0/29 in the observation group and 4/48 in the control group, indicating that the recurrence rate in the observation group was lower than in the control group (P = .048). The mean indwelling time of the drainage tube in the observation group was 2.04 ± 0.61 days, and that in the control group was 2.48 ± 0.61 days. The indwelling time of the drainage tube in the observation group was shorter than in the control group (P = .003). No surgical complications were observed in the observation group or the control group. The differences in mRS scores before and after operation between the observation group and the control group were statistically significant (P < .001). The concentrations of cytokine IL6/IL8/IL10/VEGF in the hematoma fluid of the observation and control groups were significantly higher than those in venous blood (P < .001). After intraoperative irrigation and drainage, the concentrations of cytokines (IL6/IL8/IL10/VEGF) in the subdural hematoma fluid were significantly lower than they were preoperatively. In the observation group, the number of MMA on the hematoma side (11/29) before STA development was higher than that on the non-hematoma side (1/25), and the difference was statistically significant (P = .003). CONCLUSION: In patients with CSDH, accurately locating the MMA during surgical trepanation and drainage, severing the MMA during drainage, and properly draining the hematoma, can reduce the recurrence rate and retention time of drainage tubes, thereby significantly improving the postoperative mRS Score without increasing surgical complications.


Assuntos
Drenagem , Hematoma Subdural Crônico , Artérias Meníngeas , Humanos , Hematoma Subdural Crônico/cirurgia , Masculino , Drenagem/métodos , Feminino , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Artérias Meníngeas/cirurgia , Adulto , Idoso de 80 Anos ou mais , Craniotomia/métodos
11.
Foodborne Pathog Dis ; 21(1): 61-67, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37856143

RESUMO

Cronobacter sakazakii is an opportunistic foodborne pathogen that mainly infects infants and immunocompromised people, with a high mortality rate. However, the efficient transformation method of this bacterium has not been systematically reported. In this study, we developed a fast and efficient transformation method for C. sakazakii by cold sucrose treatment. Compared with CaCl2 or glycerol treatment, the transformation efficiency of this method is significantly high when bacteria were cultured overnight at 42°C before cold sucrose treatment. Furthermore, applying this method, we successfully knocked out the pppA gene by direct electroporation. Collectively, our study provides a simple, time-saving, and efficient method for competent cell preparation of C. sakazakii, which is conducive to the further research of C. sakazakii.


Assuntos
Cronobacter sakazakii , Cronobacter , Lactente , Humanos , Cronobacter sakazakii/genética , Hospedeiro Imunocomprometido , Sacarose
12.
Small ; 19(5): e2204998, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36461696

RESUMO

Uneven and insufficient encapsulation caused by surface tension between supporting and phase change materials (PCMs) can be theoretically avoided if the encapsulation process co-occurs with the formation of supporting materials in the same environment. Herein, for the first time, a one-pot one-step (OPOS) protocol is developed for synthesizing TiO2 -supported PCM composite, in which porous TiO2 is formed in situ in the solvent of melted PCMs and directly produces the desired thermal energy storage materials with the completion of the reaction. The preparation features straightforward operation and high environmental metrics with no emission, requires only stirring and heating without the addition of organic solvent or catalyst. Moreover, the preparation process can be easily scaled-up at the laboratory. Because of the OPOS protocol and porous TiO2 inside, the as-obtained PCM composite possesses a 66.5% encapsulation ratio and 166.8% thermal conductivity enhancement compared to pristine unsupported PCMs, with 94.7% light-to-thermal conversion efficiency and promising bacterial inhibition activity without any leakage.

13.
Plant Biotechnol J ; 21(11): 2374-2388, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37596974

RESUMO

Ethylene plays an essential role in the development of cotton fibres. Ethylene biosynthesis in plants is elaborately regulated by the activities of key enzymes, 1-aminocyclopropane-1-carboxylate oxidase (ACO) and 1-aminocyclopropane-1-carboxylate synthase (ACS); however, the potential mechanism of post-translational modification of ACO and ACS to control ethylene synthesis in cotton fibres remains unclear. Here, we identify an E3 ubiquitin ligase, GhXB38D, that regulates ethylene biosynthesis during fibre elongation in cotton. GhXB38D gene is highly expressed in cotton fibres during the rapid elongation stage. Suppressing GhXB38D expression in cotton significantly enhanced fibre elongation and length, accompanied by the up-regulation of genes associated with ethylene signalling and fibre elongation. We demonstrated that GhXB38D interacts with the ethylene biosynthesis enzymes GhACS4 and GhACO1 in elongating fibres and specifically mediates their ubiquitination and degradation. The inhibition of GhXB38D gene expression increased the stability of GhACS4 and GhACO1 proteins in cotton fibres and ovules, resulting in an elevated concentration of ethylene. Our findings highlight the role of GhXB38D as a regulator of ethylene synthesis by ubiquitinating ACS4 and ACO1 proteins and modulating their stability. GhXB38D acts as a negative regulator of fibre elongation and serves as a potential target for enhancing cotton fibre yield and quality through gene editing strategy.


Assuntos
Fibra de Algodão , Etilenos , Ubiquitina-Proteína Ligases/genética , Ubiquitinação , Regulação da Expressão Gênica de Plantas , Gossypium/genética
14.
Phys Rev Lett ; 130(12): 126801, 2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-37027865

RESUMO

The increasing miniaturization of electronics requires a better understanding of material properties at the nanoscale. Many studies have shown that there is a ferroelectric size limit in oxides, below which the ferroelectricity will be strongly suppressed due to the depolarization field, and whether such a limit still exists in the absence of the depolarization field remains unclear. Here, by applying uniaxial strain, we obtain pure in-plane polarized ferroelectricity in ultrathin SrTiO_{3} membranes, providing a clean system with high tunability to explore ferroelectric size effects especially the thickness-dependent ferroelectric instability with no depolarization field. Surprisingly, the domain size, ferroelectric transition temperature, and critical strain for room-temperature ferroelectricity all exhibit significant thickness dependence. These results indicate that the stability of ferroelectricity is suppressed (enhanced) by increasing the surface or bulk ratio (strain), which can be explained by considering the thickness-dependent dipole-dipole interactions within the transverse Ising model. Our study provides new insights into ferroelectric size effects and sheds light on the applications of ferroelectric thin films in nanoelectronics.

15.
Neurochem Res ; 48(6): 1648-1662, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36745269

RESUMO

Apelin is a natural ligand for the G protein-coupled receptor APJ, and the apelin/APJ system is widely distributed in vivo. Among the apelin family, apelin-13 is the major apelin isoform in the central nervous system and cardiovascular system, and is involved in the regulation of various physiopathological mechanisms such as apoptosis, neuroinflammation, angiogenesis, and oxidative stress. Apelin is currently being extensively studied in the nervous system, and apelin-13 has been shown to be associated with the onset and progression of a variety of neurological disorders, including stroke, neurodegenerative diseases, epilepsy, spinal cord injury (SCI), and psychiatric diseases. This study summarizes the pathophysiological roles of apelin-13 in the development and progression of neurological related diseases.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular , Doenças do Sistema Nervoso , Humanos , Apelina , Receptores de Apelina , Doenças do Sistema Nervoso/tratamento farmacológico , Receptores Acoplados a Proteínas G
16.
J Nat Prod ; 86(9): 2193-2205, 2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37589667

RESUMO

Sixteen new quinolizidine alkaloids (QAs), named ormosianines A-P (1-16), and 18 known congeners (17-34) were isolated from the stems and leaves of Ormosia yunnanensis. The structures were elucidated based on spectroscopic analyses and electron circular dichroism (ECD) calculations. Structurally, ormosianines A (1) and B (2) are the first examples of cytisine and Ormosia-type alkaloids with the cleavage of the piperidine ring. Results of the acetylcholinesterase (AChE) inhibitory assay revealed that the pentacycline Ormosia-type QAs, including 1, 16, 24, and 27-29, are good AChE inhibitors. Ormosianine A (1) exhibited more potent AChE inhibitory activity with an IC50 value of 1.55 µM. Molecular docking revealed that 1 might bind to the protein 1DX4, forming two hydrogen bonds with residues SER-238 and HIS-480.


Assuntos
Alcaloides , Fabaceae , Acetilcolinesterase/metabolismo , Alcaloides Quinolizidínicos , Simulação de Acoplamento Molecular , Estrutura Molecular , Alcaloides/química , Dicroísmo Circular , Fabaceae/química , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química
17.
BMC Med Imaging ; 23(1): 54, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-37041532

RESUMO

OBJECTIVES: This paper analyzed the feasibility of reducing venous air emboli introduced during tube connection in computed tomography angiography (CTA) through a modified method of saline test injection. METHODS: A total of 386 cases of patients undergoing coronary CTA examination were randomly arranged into a control group (199 patients underwent conventional saline injection before the CTA examination) and a case group (187 patients underwent modified saline injection before the CTA examination). The two groups were compared for the location (Fisher's exact test), number (χ2 test), and diameter (Mann-Whitney rank sum test) of the air emboli along the inflow direction of contrast agent within the scan. RESULTS: The occurrence rate was 10.55% in the control group and 3.74% in the case group respectively, with a statistically different significance (P = 0.010). In the case group, there were 7 cases of small-grade venous air emboli. In the control group, there were 15 cases of small-grade venous air emboli and 6 cases of moderate-grade venous air emboli. No cases of large-grade venous air emboli were found in both groups. CONCLUSIONS: The use of this modified method of saline test injection before CTA examination is able to effectively decrease the occurrence of venous air emboli introduced during tube connection, which has some certain practical significance.


Assuntos
Angiografia por Tomografia Computadorizada , Embolia Aérea , Humanos , Angiografia por Tomografia Computadorizada/métodos , Meios de Contraste , Coração , Tomografia Computadorizada por Raios X
18.
J Pediatr Nurs ; 69: 101-107, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36709685

RESUMO

PURPOSE: Although burnout recently emerged as a harmful syndrome in parents, no instrument has been validated to suitably assess burnout among parents of children with cancer in China. In this study, we aimed to psychometrically validate the Shirom-Melamed Burnout Questionnaire (SMBQ) among Chinese parents of children with cancer. DESIGN AND METHODS: We conducted a cross-sectional survey of 380 parents of children with cancer to psychometrically validate the SMBQ. Content validity, construct validity, convergent validity, discriminant validity, criterion-related validity, diagnosis accuracy, internal consistency, and test-retest reliability were evaluated. RESULTS: The Chinese version of the SMBQ demonstrated adequate internal consistency, good test-retest reliability, good content validity, excellent convergent and discriminant validity, and appropriate criterion-related validity. Using the parental burnout assessment as a reference criterion, the area under the curve was 0.903. The optimal cut-off point for the SMBQ was 4.833. The factor model of the SMBQ used in Chinese parents of children with cancer had a good fit. The survey revealed that Chinese parents of children with cancer experienced a high level of burnout (3.86 ± 1.03). CONCLUSIONS: The Chinese version of SMBQ was reliable and valid for assessing burnout in parents of children with cancer. Parents of children with cancer experienced a high level of burnout in China. IMPLICATIONS FOR PRACTICE: This SMBQ can be used in Chinese clinical and research settings to investigate burnout in parents who have children with cancer. Further research could examine the predictive validity and validity.


Assuntos
Esgotamento Profissional , Neoplasias , Humanos , Criança , Reprodutibilidade dos Testes , Estudos Transversais , Psicometria , Esgotamento Psicológico/diagnóstico , Esgotamento Profissional/diagnóstico , Neoplasias/diagnóstico , Inquéritos e Questionários , Pais , China
19.
Int J Mol Sci ; 24(20)2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37895170

RESUMO

N-acetyl sugar amidotransferase (NASAT) is involved in the lipopolysaccharide (LPS) biosynthesis pathway that catalyzes the formation of the acetamido moiety (sugar-NC(=NH)CH3) on the O-chain. So far, little is known about its structural and functional properties. Here, we report the crystal structure of an N-acetyl sugar amidotransferase from Legionella pneumophila (LpNASAT) at 2.33 Å resolution. LpNASAT folds into a compact basin-shaped architecture with an unusually wide and open putative substrate-binding pocket and a conserved zinc ion-binding tetracysteine motif. The pocket contains a Rossmann-like fold with a PP-loop, suggesting that the NASAT-catalyzed amidotransfer reaction probably requires the conversion of ATP to AMP and PPi. Our data provide structural insights into the NASAT family of proteins, and allow us to possibly identify its functionally important regions.


Assuntos
Lipopolissacarídeos , Açúcares , Bactérias/metabolismo , Proteínas de Bactérias/metabolismo
20.
Molecules ; 28(7)2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37050041

RESUMO

As a star material in conducting polymers, a polypyrrole coating was assembled onto the surface of 316 stainless steel by an electrochemical method. In the next step, the composite layer consisting of carbon nitride nanosheets (CNNS) and polymethyl methacrylate (PMMA) was sprayed. The corrosion manner of composite coatings in a simulated proton-exchange membrane fuel cell (PEMFC) environment was evaluated. The results show that the final coating generated at a voltage of 1.0 has demonstrated the optimized corrosion resistance. The polypyrrole layer improves the corrosion resistance of the stainless steel substrate, and the CNNS/PMMA coating further strengthens the physical barrier effect of the coating in corrosive solutions.

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