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1.
J Hazard Mater ; 423(Pt B): 127128, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34534804

RESUMO

Effectively harnessing renewable and inexhaustible solar radiation for energy conversion has attracted significant research interest in the past decade. Solar thermal conversion, as a ubiquitous phenomenon, can be implemented to evaporate water and concurrently boost photocatalytic performance for addressing freshwater scarcity and energy crisis. Most recently, solar water evaporation accompanied by photocatalytic degradation, sterilization, and hydrogen production has been proposed as a promising avenue to endow new vitality into the field of clean water and energy production. Driven by the advances of rationally designed solar-powered functional materials, a large variety of photothermal-coupled photocatalysis technologies have been exploited. In this context, it is imperative to summarize the recent progress and discuss the challenges in this multidisciplinary field. Herein, we overview photothermal materials based on various fundamental principles and highlight emerging applications in the areas of solar water evaporation, water purification, and solar-driven energy production. Furthermore, the challenges and perspectives toward both fundamental research and practical applications are also proposed. It is envisioned that this review can provide insightful suggestions to further advance the development of integrated solar thermal driven water evaporation and photocatalytic systems to fulfill concurrent energy conversion and environmental applications.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34592751

RESUMO

Across adolescence, individuals enrich their concrete, empathic, context-specific interpretations of social-world happenings with abstract, situation-transcending, systems-level considerations-invoking values, bigger implications, and broader emotional perspectives. To investigate neural mechanisms involved in abstract construals versus concrete construals, and effects of emotional engagement on these mechanisms, 65 middle-adolescents aged 14-18 reacted to compelling video mini-documentaries during private, open-ended interviews and again during fMRI. Following calls to diversify samples, participants were ethnically diverse low-SES urban adolescents performing well in school. Participants spontaneously produced both concrete and abstract construals in the interview, and tendencies to produce each varied independently. As hypothesized, participants who made more abstract construals showed greater subsequent Default Mode Network (DMN) activity; those who made more concrete construals showed greater Executive Control Network (ECN) activity. Findings were independent of IQ, SES, age and gender. Within individuals, DMN activation, especially when individuals were reporting strong emotional engagement, and ECN deactivation, together predicted an abstract construal to a trial. Additionally, brief ECN activation early in the trial strengthened the DMN-abstraction relationship. Findings suggest a neural mechanism for abstract social thought in adolescence. They also link adolescents' natural construals of social situations to distinct networks' activity, and suggest separable sociocognitive traits that may vary across youth.

3.
Virol Sin ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34558014

RESUMO

Japanese encephalitis virus (JEV) is a leading cause of viral encephalitis in endemic regions of Asia. The neurotropism of JEV and its high-efficiency replication in neurons are the key events for pathogenesis. Revealing the interplay between virus and host cells in metabolic facet is of great importance both for unraveling the pathogenesis mechanisms and providing novel antiviral targets. This study took advantage of the integration analysis of metabolomics and transcriptomics to depict the metabolic profiles of neurons during the early stage of JEV infection. Increased glycolysis and its branched pentose phosphate pathway (PPP) flux and impaired oxidative phosphorylation (OXPHOS) in glucose utilization, and the catabolic patterns of lipid metabolism were created to facilitate the biosynthesis of precursors needed for JEV replication in neurons. Pharmacological inhibitions of both glycolysis pathway and PPP in neurons suggested its indispensable role in maintaining the optimal propagation of JEV. In addition, analysis of metabolomic-transcriptomic regulatory network showed the pivotal biological function of lipid metabolism during JEV infection. Several pro-inflammatory lipid metabolites were significantly up-regulated and might partially be responsible for the progression of encephalitis. These unique metabolic reprogramming features might give deeper insight into JEV infected neurons and provide promising antiviral approaches targeting metabolism.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34487862

RESUMO

Arabidopsis thaliana is an important and long-established model species for plant molecular biology, genetics, epigenetics, and genomics. However, the latest version of reference genome still contains significant number of missing segments. Here, we report a high-quality and almost complete Col-0 genome assembly with two gaps (Col-XJTU) using combination of Oxford Nanopore Technology ultra-long reads, PacBio high-fidelity long reads, and Hi-C data. The total genome assembly size is 133,725,193 bp, introducing 14.6 Mb of novel sequences compared to the TAIR10.1 reference genome. All five chromosomes of Col-XJTU assembly are highly accurate with consensus quality (QV) scores > 60 (ranging from 62 to 68), which are higher than those of TAIR10.1 reference (QV scores ranging from 45 to 52). We have completely resolved chromosome (Chr) 3 and Chr5 in a telomere-to-telomere manner. Chr4 has been completely resolved except the nucleolar organizing regions, which comprise long repetitive DNA fragments. The Chr1 centromere (CEN1), reportedly around 9 Mb in length, is particularly challenging to assemble due to the presence of tens of thousands of CEN180 satellite repeats. Using the cutting-edge sequencing data and novel computational approaches, we assembled about 4 Mb of sequence for CEN1 and a 3.5-Mb-long CEN2. We investigated the structure and epigenetics of centromeres. We detected four clusters of CEN180 monomers, and found that the centromere-specific histone H3-like protein (CENH3) exhibits a strong preference for CEN180 cluster 3. Moreover, we observed hypomethylation patterns in CENH3-enriched regions. We believe that this high-quality genome assembly, Col-XJTU, would serve as a valuable reference to better understand the global pattern of centromeric polymorphisms, as well as genetic and epigenetic features in plants.

6.
J Exp Med ; 218(9)2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34342641

RESUMO

Activation of NLRP3 inflammasome is precisely controlled to avoid excessive activation. Although multiple molecules regulating NLRP3 inflammasome activation have been revealed, the checkpoints governing NLRP3 inflammasome activation remain elusive. Here, we show that activation of NLRP3 inflammasome is governed by GSTO1-promoted ASC deglutathionylation in macrophages. Glutathionylation of ASC inhibits ASC oligomerization and thus represses activation of NLRP3 inflammasome in macrophages, unless GSTO1 binds ASC and deglutathionylates ASC at ER, under control of mitochondrial ROS and triacylglyceride synthesis. In macrophages expressing ASCC171A, a mutant ASC without glutathionylation site, activation of NLRP3 inflammasome is GSTO1 independent, ROS independent, and signal 2 less dependent. Moreover, AscC171A mice exhibit NLRP3-dependent hyperinflammation in vivo. Our results demonstrate that glutathionylation of ASC represses NLRP3 inflammasome activation, and GSTO1-promoted ASC deglutathionylation at ER, under metabolic control, is a checkpoint for activating NLRP3 inflammasome.

7.
Curr Protoc ; 1(8): e174, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34351700

RESUMO

Chromatin Interaction Analysis Using Paired-End Tag Sequencing (ChIA-PET) is an established method to map protein-mediated chromatin interactions. A limitation, however, is that it requires a hundred million cells per experiment, which hampers its broad application in biomedical research, particularly in studies in which it is impractical to obtain a large number of cells from rare samples. To reduce the required input cell number while retaining high data quality, we developed an in situ ChIA-PET protocol, which requires as few as 1 million cells. Here, we describe detailed step-by-step procedures for performing in situ ChIA-PET from cultured cells, including both an experimental protocol for sample preparation and data generation and a computational protocol for data processing and visualization using the ChIA-PIPE pipeline. As the protocol significantly simplifies the experimental procedure, reduces ligation noise, and decreases the required input of cells compared to previous versions of ChIA-PET protocols, it can be applied to generate high-resolution chromatin contact maps mediated by various protein factors for a wide range of human and mouse primary cells. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Sample preparation and data generation Support Protocol: Bridge linker preparation Basic Protocol 2: Data processing and visualization.


Assuntos
Cromatina , Técnicas Genéticas , Animais , Linhagem Celular , Interpretação Estatística de Dados , Humanos , Camundongos , Análise de Sequência de DNA
8.
Pediatr Cardiol ; 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34350506

RESUMO

Dilated cardiomyopathy (DCM) is a myocardial disease characterized by bilateral or left ventricular cardiac dilation and systolic dysfunction that can lead to heart failure and sudden cardiac death in children. Many studies have focused on genetic variation in DCM-related genes in adult populations; however, the mutational landscape in pediatric DCM patients remains undetermined, especially in the Chinese population. We applied next-generation sequencing (NGS) technology to genetically analyze 46 pediatric DCM patients to reveal genotype-phenotype correlations. Our results indicated DCM-associated pathogenic mutations in 10 genes related to the structure or function of the sarcomere, desmosome, and cytoskeleton. We also identified 6 pathogenic mutations (5 novel) in the Titin (TTN) gene that resulted in truncated TTN variants in 6 (13%) out of 46 patients. Correlations between TTN mutations and clinical outcomes were assessed. Our data indicate that one-third of pediatric DCM cases are caused by genetic mutations. The role of TTN variants should not be underestimated in pediatric DCM and age-dependent pathogenic penetrance of these mutations should be considered for familial DCM cases. We argue that genetic testing of DCM cases is valuable for predicting disease severity, prognosis, and recurrence risk, and for screening first-degree relatives.

9.
Chemistry ; 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34350652

RESUMO

A series of novel osmaindenes 1-6 bearing different substituents (CF3 , H, I, Br, OCH3 , N(Ph)2 ) has been synthesized by nucleophilic reaction of water with the corresponding aromatic osmanaphthalyne complexes. All osmaindenes 1-6 have been characterized by elemental analysis (EA) and nuclear magnetic resonance (NMR) spectroscopy, although the low solubilities of 3 and 4 precluded the accumulation of their 13 C NMR spectra. Osmaindenes 2, 3 and 5 have also been characterized by single-crystal X-ray diffraction analysis. Subsequently, through solid-state fluorescence spectroscopy, mechanochromic studies, and powder X-ray diffraction (XRD) analysis, we found that osmaindenes 1-6 fluoresce at wavelengths in the range 500-800 nm, while also displaying reversible mechanochromic properties. The solid-state fluorescence emission of 1 after grinding extends into the near-infrared region. This research provides new insight into the design and synthesis of metallic materials with excellent mechanochromic properties.

10.
Stem Cell Res ; 56: 102514, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34464855

RESUMO

Parkinson's disease (PD) is a neurodegenerative disease caused by environmental and genetic factors. The identified PD genes include SNCA, LRRK2, Parkin, DJ-1, PINK1, and ATP13A2. Mutations in the glucocerebrosidase (GBA) gene were reported to be associated with PD in different ethnic populations. Here we generated a novel induced pluripotent stem cell (iPSC) line LCPHi001-A from a PD patient carrying RecNciI mutation (c.1448 T > C, c.1483G > C, and c.1497G > C) in GBA by non-integrative episomal plasmids. The LCPHi001-A line expressed pluripotency markers, displayed differentiation capacity to three germ layers in vivo, and had the normal karyotype.

11.
Ecotoxicol Environ Saf ; 223: 112608, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34365214

RESUMO

The application of nitrogen fertilizers in the rice-crab co-culture system may expose juvenile Eriocheir sinensis to high ammonia concentrations within a short period of time, potentially causing death. Currently, the molecular mechanism underlying ammonia toxicity in juvenile Eriocheir sinensis remains poorly understood. This study compared the effects of 24 h exposure to different total ammonia-N concentrations (0, 10.47, and 41.87 mg/L) on antioxidant enzyme activities and tandem mass tag (TMT)-based proteomics in the hepatopancreas of juvenile Eriocheir sinensis. During the experiment, water temperature and pH were maintained at 20.4 ± 1.4 °C and 7.69 ± 0.46, respectively. Proteomic data demonstrated that Eriocheir sinensis used different metabolic regulatory mechanisms to adapt to varying ammonia conditions. The tricarboxylic acid (TCA) cycle, glycogen degradation, and oxidative phosphorylation showed marginally upregulated trends under low ammonia exposure. High ammonia stress caused downregulation of the TCA cycle and provided energy by enhancing oxidative phosphorylation, fatty acid beta oxidation, gluconeogenesis, and glycogen degradation. The detoxification of ammonia into urea and glutamine was suppressed under high ammonia stress. Finally, ammonia exposure induced oxidative stress and caused protein damage. Antioxidant enzyme activity analysis further revealed that exposure to high concentrations of ammonia may induce more severe oxidative stress. This study provides a global perspective on the mechanisms underlying ammonia exposure-induced metabolic changes and stress damage in juvenile Eriocheir sinensis.


Assuntos
Braquiúros , Amônia/toxicidade , Animais , Antioxidantes , Hepatopâncreas , Proteômica
12.
Emerg Microbes Infect ; 10(1): 1683-1690, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34348599

RESUMO

At the end of 2019, A new type of beta-CoV, SARS-CoV-2 emerged and triggered the COVID-19 pandemic, which spread overwhelmingly around the world in less than a year. However, the origin and direct ancestral viruses of SARS-CoV-2 remain unknown. RaTG13, a novel coronavirus found in bats in China's Yunnan Province, is the closest relative virus of the SARS-CoV-2 identified so far. In this study, a new SARS-CoV-2 related virus, provisionally named PrC31, was discovered in Yunnan province by retrospectively analyse bat next generation sequencing (NGS) data of intestinal samples collected in 2018. PrC31 shared 90.7% and 92.0% nucleotide identities to the genomes of SARS-CoV-2 and the bat SARSr-CoV ZC45, respectively. Sequence alignment of PrC31 showed that several genomic regions, especially orf1a and orf8 had the highest homology with those corresponding genomic regions of SARS-CoV-2 than any other related viruses. Phylogenetic analysis indicated that PrC31 shared a common ancestor with SARS-CoV-2 in evolutionary history. The differences between the PrC31 and SARS-CoV-2 genomes were mainly manifested in the spike genes. The amino acid homology between the receptor binding domains of PrC31 and SARS-CoV-2 was only 64.2%. Importantly, recombination analysis revealed that PrC31 underwent multiple complex recombination events (including three recombination breakpoints) involving the SARS-CoV and SARS-CoV-2 sub-lineages, indicating that PrC31 evolved from yet-to-be-identified intermediate recombination strains. Combined with previous studies, it is revealed that the beta-CoVs may possess a more complex recombination mechanism than we thought.


Assuntos
Quirópteros/virologia , Recombinação Genética , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Sequência de Aminoácidos , Animais , China , Genoma Viral , Filogenia , SARS-CoV-2/classificação , Alinhamento de Sequência , Proteínas Virais/genética
13.
Artigo em Inglês | MEDLINE | ID: mdl-34284134

RESUMO

The development of new biomarkers or therapeutic targets for cancer immunotherapies requires deep understanding of T cells. To date, the complete landscape and systematic characterization of long noncoding RNAs (lncRNAs) in T cells in cancer immunity are lacking. Here, by systematically analyzing full-length single-cell RNA sequencing (scRNA-seq) data of more than 20,000 libraries of T cells across three cancer types, we provide the first comprehensive catalog and the functional repertoires of lncRNAs in human T cells. Specifically, we developed a custom pipeline for de novo transcriptome assembly and obtained a novel lncRNA catalog containing 9433 genes. This increased the number of current human lncRNA catalog by 16% and nearly doubled the number of lncRNAs expressed in T cells. We found that a portion of expressed genes in single T cells were lncRNAs which had been overlooked by the majority of previous studies. Based on metacell maps constructed by the MetaCell algorithm that partitions scRNA-seq datasets into disjointed and homogenous groups of cells (metacells), 154 signature lncRNAs were identified. They associated with effector, exhausted, and regulatory T cell states. 84 of them were functionally annotated based on the co-expression network, indicating that lncRNAs might broadly participate in the regulation of T cell functions. Our findings provide a new point of view and resource for investigating the mechanisms of T cell regulation in cancer immunity as well as for novel cancer-immune biomarker development and cancer immunotherapies.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34224879

RESUMO

Complex structural variants (CSVs) are genomic alterations that have more than two breakpoints and are considered as the simultaneous occurrence of simple structural variants. However, detecting the compounded mutational signals of CSVs is challenging through a commonly used model-match strategy. As a result, there has been limited progress for CSV discovery compared with simple structural variants. We systematically analyzed the multi-breakpoint connection feature of CSVs, and proposed Mako, utilizing a bottom-up guided model-free strategy, to detect CSVs from paired-end short-read sequencing. Specifically, we implemented a graph-based pattern growth approach, where the graph depicts potential breakpoint connections, and pattern growth enables CSV detection without pre-defined models. Comprehensive evaluations on both simulated and real datasets revealed that Mako outperformed other algorithms. Notably, validation rates of CSV on real data based on experimental and computational validations as well as manual inspections are around 70%, where the medians of experimental and computational breakpoint shift are 13bp and 26bp, respectively. Moreover, the Mako CSV subgraph effectively characterized the breakpoint connections of a CSV event and uncovered a total of 15 CSV types, including two novel types of adjacent segments swap and tandem dispersed duplication. Further analysis of these CSVs also revealed the impact of sequence homology in the formation of CSVs. Mako is publicly available at https://github.com/xjtu-omics/Mako.

15.
ACS Nano ; 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34110789

RESUMO

Improving evaporation rate is extremely important to promote the application of solar steam generation in clean water production through seawater desalination. However, the theoretical evaporation rate limit of a normal two-dimensional (2D) photothermal evaporator is only about 1.46 kg m-2 h-1. While 3D evaporators can break the limit, they require much more raw materials. In this work, an effective approach for achieving high-yield solar steam generation via the synergy of 2D nanostructure-embedded all-in-one hybrid hydrogel evaporator and surface patterning is reported. This improved surface-patterned evaporator is able to simultaneously lower the enthalpy of vaporization and induce the Marangoni effect near the evaporation surface, thus delivering a high evaporation rate of 3.62 kg m-2 h-1, which is more than twice the theoretical limit of the normal 2D photothermal evaporator. This hybrid hydrogel offers a cost-effective and energy-efficient pathway to mitigate clean water shortages.

16.
Nat Commun ; 12(1): 3348, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099728

RESUMO

Lead halide perovskites have exhibited excellent performance in solar cells, LEDs and detectors. Thermal properties of perovskites, such as heat capacity and thermal conductivity, have rarely been studied and corresponding devices have barely been explored. Considering the high absorption coefficient (104~105 cm-1), low specific heat capacity (296-326 J kg-1 K-1) and small thermal diffusion coefficient (0.145 mm2 s-1), herein we showcase the successful use of perovskite in optoacoustic transducers. The theoretically calculated phonon spectrum shows that the overlap of optical phonons and acoustic phonons leads to the up-conversion of acoustic phonons, and thus results in experimentally measured low thermal diffusion coefficient. The assembled device of PDMS/MAPbI3/PDMS simultaneously achieves broad bandwidths (-6 dB bandwidth: 40.8 MHz; central frequency: 29.2 MHz), and high conversion efficiency (2.97 × 10-2), while all these parameters are the record values for optoacoustic transducers. We also fabricate miniatured devices by assembling perovskite film onto fibers, and clearly resolve the fine structure of fisheyes, which demonstrates the strong competitiveness of perovskite based optoacoustic transducers for ultrasound imaging.

17.
Cardiol Young ; : 1-6, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34180388

RESUMO

OBJECTIVES: This study aims to investigate the pathogenic gene variant in a family with hypertrophic cardiomyopathy by using whole-exome sequencing and to explore the relationship between the gene variant and clinical phenotype. METHODS: Peripheral blood was collected from a family with hypertrophic cardiomyopathy, and deoxyribonucleic acid was extracted. The possible pathogenic genes were detected by whole-exome sequencing, and the variant was verified by Sanger sequencing. Functional change in the variant was predicted by bioinformatics software. Clinical data of the family members are analysed simultaneously. RESULTS: The proband carries a novel heterozygous nonsense variant of MYBPC3:c.2731G > T (p.E911X). The analysis of amino acid conservation suggests that the variation is highly conserved. The three-dimensional protein structure shows that the variant in MYBPC3 results in the incompleteness of the fibronectintype-III2 (p872-967) domain and deletion of Ig-like C2-type 6 (p971-1065) and fibronectin type-III 3 and Ig-like C2-type 7 (p1181-1274) domains, in which p1253-1268 is predicted to have a transmembrane helix structure. Clinical data indicate that the phenotypes of variant carriers with hypertrophic cardiomyopathy are diverse, suggesting the functional damages to the protein of MYBPC3. CONCLUSION: The phenotypes of variant carriers with hypertrophic cardiomyopathy caused by the novel variant in MYBPC3: c.2731G > T (p.E911X) exhibit variable severity and clinical manifestations. Whole-exome sequencing can be used to comprehensive screen hypertrophic cardiomyopathy genes and provide a strong basis for early screening and accurate diagnosis and treatment of hypertrophic cardiomyopathy in children.

18.
BMC Musculoskelet Disord ; 22(1): 551, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34134690

RESUMO

BACKGROUND: The infra-acetabular screw which is placed from the pubis to the ischium can be used as a special positional screw of the posterior column of the acetabulum. This study was performed to simulate the surgical procedure and obtain the ideal insertion point, diameter, length and angle of the screw through the method of axial perspective in Chinese patients. METHODS: We randomly collected the pelvic computed tomography (CT) scans of 200 adults. DICOM-formatted CT-scan images were imported into Mimics software to establish the 3D digital model of the right semi-pelvic was established. A virtual cylinder representing the screw was placed from the pubis to the ischium to fix the posterior column. The largest secure diameter and length of the virtual screw were measured and the position of the insertion point and the directions of the screw were also researched. RESULTS: The screw insertion safe zone exhibits an irregular shape of "tear drop" in the reconstructed pelvic model. The mean maximum diameter of screws was 5.01 ± 1.28 mm, and the mean maximum length of screws was 93.99 ± 8.92 mm. The screw insertion corridor with the least diameter 3.5 mm was found in 94 of 100 males (94%) and 86 of 100 females (86%). We found gender-dependent differences for the mean maximum diameter and the maximum length of the screw. There was statistically significant difference between genders in the position of insertion point. CONCLUSIONS: In this study, we suggest an individual preoperative 3D reconstruction simulation to develop better screw placement plans, which provides a valuable guideline for seeking the largest secure corridor of infra-acetabular screw. Further biomechanical studies are needed to verify the function of the screw.


Assuntos
Acetábulo , Fraturas Ósseas , Acetábulo/diagnóstico por imagem , Acetábulo/cirurgia , Adulto , Parafusos Ósseos , Feminino , Fixação Interna de Fraturas , Humanos , Ísquio , Masculino , Tomografia Computadorizada por Raios X
19.
Epigenomics ; 13(13): 1057-1075, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34114472

RESUMO

Aim: Fulminant myocarditis (FM) has neither validated biomarkers nor well-established therapy. Roles of tRNA-derived small RNAs (tsRNAs) in FM remain unknown. Materials & methods: Small RNA sequencing was conducted in plasma from children with FM during acute and convalescent phase and matched healthy volunteers. Data were validated by quantitative real-time PCR in larger sample-sized groups and in vitro. Functional analysis was performed to explore the roles. Results: tiRNA-Gln-TTG-001 was overexpressed in children with FM during acute phase, and the generation and extracellular release of tiRNA-Gln-TTG-001 were higher after myocarditis-mimicked activity in vitro. Several pathways might participate in the pathogenesis of FM. Conclusion: tsRNAs may play an important role in FM, and tiRNA-Gln-TTG-001 might represent a novel and promising biomarker and therapeutic target.

20.
J Chem Neuroanat ; 115: 101967, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33992725

RESUMO

Previous studies have demonstrated that the activation of delta opioid receptors is neuroprotective against neonatal hypoxia-ischemia (HI) brain injury. The aim of this study was to investigate the neuroprotective effects of biphalin, a dimeric opioid peptide, in a mouse model of neonatal HI and the underlying mechanisms. On postnatal day 10, mouse pups were subjected to unilateral carotid artery ligation followed by 1 h of hypoxia (10 % O2 in N2). For treatment, biphalin (5 mg/kg, 10 mg/kg, 20 mg/kg) was administered intraperitoneally immediately after HI. The opioid antagonist naloxone or phosphatidylinositol-3-kinase inhibitor Ly294002 was administered to determine the underlying mechanisms. Infarct volume, brain edema, phosphorylated Akt and apoptosis-related proteins levels were evaluated by using a combination of 2,3,5-triphenyltetrazolium chloride staining, brain water content and Western blotting at 24 h after HI. The long-term effects of biphalin were evaluated by brain atrophy measurement, Nissl staining and neurobehavioral tests at 3 weeks post-HI. Biphalin (10 mg/kg) significantly reduced the infarct volume and ameliorated brain edema. Biphalin also had long-term protective effects against the loss of ipsilateral brain tissue and resulted in improvements in neurobehavioral outcomes. However, naloxone or Ly294002 abrogated the neuroprotective effects of biphalin. Furthermore, biphalin treatment significantly preserved phosphorylated Akt expression, increased Bcl-2 levels, and decreased Bax and cleaved caspase 3 levels after HI. These effects were also reversed by naloxone and Ly294002 respectively. In conclusion, biphalin protects against HI brain injury in neonatal mice, which might be through activation of the opioid receptor/phosphatidylinositol-3-kinase/Akt signaling pathway.

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