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1.
Am J Hum Genet ; 110(4): 638-647, 2023 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-36990086

RESUMO

Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common intractable disease that causes spinal stenosis and myelopathy. We have previously conducted genome-wide association studies for OPLL and identified 14 significant loci, but their biological implications remain mostly unclear. Here, we examined the 12p11.22 locus and identified a variant in the 5' UTR of a novel isoform of CCDC91 that was associated with OPLL. Using machine learning prediction models, we determined that higher expression of the novel CCDC91 isoform was associated with the G allele of rs35098487. The risk allele of rs35098487 showed higher affinity in the binding of nuclear proteins and transcription activity. Knockdown and overexpression of the CCDC91 isoform in mesenchymal stem cells and MG-63 cells showed paralleled expression of osteogenic genes, including RUNX2, the master transcription factor of osteogenic differentiation. The CCDC91 isoform directly interacted with MIR890, which bound to RUNX2 and decreased RUNX2 expression. Our findings suggest that the CCDC91 isoform acts as a competitive endogenous RNA by sponging MIR890 to increase RUNX2 expression.


Assuntos
Ossificação do Ligamento Longitudinal Posterior , Osteogênese , Humanos , Osteogênese/genética , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Estudo de Associação Genômica Ampla , Ossificação do Ligamento Longitudinal Posterior/genética , Ossificação do Ligamento Longitudinal Posterior/metabolismo , RNA não Traduzido
2.
Am J Hum Genet ; 110(7): 1068-1085, 2023 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-37352860

RESUMO

ERI1 is a 3'-to-5' exoribonuclease involved in RNA metabolic pathways including 5.8S rRNA processing and turnover of histone mRNAs. Its biological and medical significance remain unclear. Here, we uncover a phenotypic dichotomy associated with bi-allelic ERI1 variants by reporting eight affected individuals from seven unrelated families. A severe spondyloepimetaphyseal dysplasia (SEMD) was identified in five affected individuals with missense variants but not in those with bi-allelic null variants, who showed mild intellectual disability and digital anomalies. The ERI1 missense variants cause a loss of the exoribonuclease activity, leading to defective trimming of the 5.8S rRNA 3' end and a decreased degradation of replication-dependent histone mRNAs. Affected-individual-derived induced pluripotent stem cells (iPSCs) showed impaired in vitro chondrogenesis with downregulation of genes regulating skeletal patterning. Our study establishes an entity previously unreported in OMIM and provides a model showing a more severe effect of missense alleles than null alleles within recessive genotypes, suggesting a key role of ERI1-mediated RNA metabolism in human skeletal patterning and chondrogenesis.


Assuntos
Exorribonucleases , Histonas , Humanos , Exorribonucleases/genética , Histonas/genética , Mutação de Sentido Incorreto/genética , RNA Ribossômico 5,8S , RNA , RNA Mensageiro/genética
3.
Nature ; 580(7801): 124-129, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32238941

RESUMO

Pluripotent stem cells are increasingly used to model different aspects of embryogenesis and organ formation1. Despite recent advances in in vitro induction of major mesodermal lineages and cell types2,3, experimental model systems that can recapitulate more complex features of human mesoderm development and patterning are largely missing. Here we used induced pluripotent stem cells for the stepwise in vitro induction of presomitic mesoderm and its derivatives to model distinct aspects of human somitogenesis. We focused initially on modelling the human segmentation clock, a major biological concept believed to underlie the rhythmic and controlled emergence of somites, which give rise to the segmental pattern of the vertebrate axial skeleton. We observed oscillatory expression of core segmentation clock genes, including HES7 and DKK1, determined the period of the human segmentation clock to be around five hours, and demonstrated the presence of dynamic travelling-wave-like gene expression in in vitro-induced human presomitic mesoderm. Furthermore, we identified and compared oscillatory genes in human and mouse presomitic mesoderm derived from pluripotent stem cells, which revealed species-specific and shared molecular components and pathways associated with the putative mouse and human segmentation clocks. Using CRISPR-Cas9-based genome editing technology, we then targeted genes for which mutations in patients with segmentation defects of the vertebrae, such as spondylocostal dysostosis, have been reported (HES7, LFNG, DLL3 and MESP2). Subsequent analysis of patient-like and patient-derived induced pluripotent stem cells revealed gene-specific alterations in oscillation, synchronization or differentiation properties. Our findings provide insights into the human segmentation clock as well as diseases associated with human axial skeletogenesis.


Assuntos
Relógios Biológicos/fisiologia , Desenvolvimento Embrionário/fisiologia , Células-Tronco Pluripotentes/citologia , Somitos/citologia , Somitos/crescimento & desenvolvimento , Anormalidades Múltiplas/genética , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/deficiência , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Relógios Biológicos/genética , Desenvolvimento Embrionário/genética , Edição de Genes , Regulação da Expressão Gênica no Desenvolvimento/genética , Glicosiltransferases/deficiência , Glicosiltransferases/genética , Hérnia Diafragmática/genética , Humanos , Técnicas In Vitro , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Camundongos , Fenótipo , Somitos/metabolismo , Fatores de Tempo
4.
J Am Chem Soc ; 146(5): 3075-3085, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38174850

RESUMO

Billions of populations are suffering from the supply-demand imbalance of clean water, resulting in a global sustainability crisis. Membrane desalination is a promising method to produce fresh water from saline waters. However, conventional membranes often encounter challenges related to low water permeation, negatively impacting energy efficiency and water productivity. Herein, we achieve ultrafast desalination over the newly developed alkadiyne-pyrene conjugated frameworks membrane supported on a porous copper hollow fiber. With membrane distillation, the membrane exhibits nearly complete NaCl rejection (>99.9%) and ultrahigh fluxes (∼500 L m-2 h-1) from the seawater salinity-level NaCl solutions, which surpass the commercial polymeric membranes with at least 1 order of magnitude higher permeability. Experimental and theoretical investigations suggest that the large aspect ratio of membrane pores and the high evaporation area contribute to the high flux, and the graphene-like hydrophobic surface of conjugated frameworks exhibits complete salt exclusion. The simulations also confirm that the intraplanar pores of frameworks are impermeable for water and ions.

5.
Anal Chem ; 96(27): 10911-10919, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38916969

RESUMO

The integration of electrochemistry with nuclear magnetic resonance (NMR) spectroscopy recently offers a powerful approach to understanding oxidative metabolism, detecting reactive intermediates, and predicting biological activities. This combination is particularly effective as electrochemical methods provide excellent mimics of metabolic processes, while NMR spectroscopy offers precise chemical analysis. NMR is already widely utilized in the quality control of pharmaceuticals, foods, and additives and in metabolomic studies. However, the introduction of additional and external connections into the magnet has posed challenges, leading to signal deterioration and limitations in routine measurements. Herein, we report an anti-interference compact in situ electrochemical NMR system (AICISENS). Through a wireless strategy, the compact design allows for the independent and stable operation of electrochemical NMR components with effective interference isolation. Thus, it opens an avenue toward easy integration into in situ platforms, applicable not only to laboratory settings but also to fieldwork. The operability, reliability, and versatility were validated with a series of biomimetic assessments, including measurements of microbial electrochemical systems, functional foods, and simulated drug metabolisms. The robust performance of AICISENS demonstrates its high potential as a powerful analytical tool across diverse applications.


Assuntos
Técnicas Eletroquímicas , Espectroscopia de Ressonância Magnética , Espectroscopia de Ressonância Magnética/métodos , Tecnologia sem Fio
6.
J Hum Genet ; 69(7): 321-327, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38565611

RESUMO

Spondylocostal dysostosis (SCDO) encompasses a group of skeletal disorders characterized by multiple segmentation defects in the vertebrae and ribs. SCDO has a complex genetic etiology. This study aimed to analyze and identify pathogenic variants in a fetus with SCDO. Copy number variant sequencing and whole exome sequencing were performed on a Chinese fetus with SCDO, followed by bioinformatics analyses, in vitro functional assays and a systematic review on the reported SCDO cases with LFNG pathogenic variants. Ultrasound examinations in utero exhibited that the fetus had vertebral malformation, scoliosis and tethered cord, but rib malformation was not evident. We found a novel homozygous variant (c.1078 C > T, p.R360C) within the last exon of LFNG. The variant was predicted to cause loss of function of LFNG by in silico prediction tools, which was confirmed by an in vitro assay of LFNG enzyme activity. The systematic review listed a total of 20 variants of LFNG in SCDO. The mutational spectrum spans across all exons of LFNG except the last one. This study reported the first Chinese case of LFNG-related SCDO, revealing the prenatal phenotypes and expanding the mutational spectrum of the disorder.


Assuntos
Sequenciamento do Exoma , Humanos , Feminino , Feto/anormalidades , Gravidez , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Mutação , Meningomielocele/genética , Meningomielocele/diagnóstico por imagem , Variações do Número de Cópias de DNA , Povo Asiático/genética , População do Leste Asiático , Hérnia Diafragmática
7.
Am J Med Genet A ; : e63631, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647383

RESUMO

Craniofacial microsomia (CFM), also known as the oculo-auriculo-vertebral spectrum, is a congenital disorder characterized by hypoplasia of the mandible and external ear due to tissue malformations originating from the first and second branchial arches. However, distinguishing it from other syndromes of branchial arch abnormalities is difficult, and causal variants remain unidentified in many cases. In this report, we performed an exome sequencing analysis of a Brazilian family with CFM. The proband was a 12-month-old boy with clinical findings consistent with the diagnostic criteria for CFM, including unilateral mandibular hypoplasia, microtia, and external auditory canal abnormalities. A heterozygous de novo nonsense variant (c.713C>G, p.S238*) in PUF60 was identified, which was predicted to be pathogenic in silico. PUF60 has been reported as a causal gene in Verheij syndrome, but not in CFM. Although the boy showed craniofacial abnormalities and developmental delay that overlapped with Verheij syndrome, the facial asymmetry with unilateral hypoplasia of the mandible observed in this case did not match the previously reported phenotypes of PUF60 variants. Our findings expand the phenotypic range of PUF60 variants that cover CFM and Verheij syndrome.

8.
Environ Sci Technol ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860911

RESUMO

Foliar assimilation of elemental mercury (Hg0) from the atmosphere plays a critical role in the global Hg biogeochemical cycle, leading to atmospheric Hg removal and soil Hg insertion. Recent studies have estimated global foliar Hg assimilation; however, large uncertainties remained due to coarse accounting of observed foliar Hg concentrations, posing a substantial challenge in constraining the global Hg budget. Here, we integrated a comprehensive observation database of foliar Hg concentrations and machine learning algorithms to predict the first spatial distribution of foliar Hg concentrations on a global scale, contributing to the first estimate of global Hg pools in foliage. The global average of foliar Hg concentrations was estimated to be 24.0 ng g-1 (7.5-56.5 ng g-1), and the global total in foliar Hg pools reached 4561.3 Mg (1455.2-9062.8 Mg). The spatial distribution showed the hotspots in tropical regions, including the Amazon, Central Africa, and Southeast Asia. A range of 2268.5-2727.0 Mg yr-1 was estimated for annual foliar Hg assimilation accounting for the perennial continuous assimilation by evergreen vegetation foliage. The first spatial maps of foliar Hg concentrations and Hg pools may aid in understanding the global biogeochemical cycling of Hg, especially in the context of climate change and global vegetation greening.

9.
BMC Vet Res ; 20(1): 109, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38500165

RESUMO

BACKGROUND: Endometritis is a common bovine postpartum disease. Rapid endometrial repair is beneficial for forming natural defense barriers and lets cows enter the next breeding cycle as soon as possible. Selenium (Se) is an essential trace element closely related to growth and development in animals. This study aims to observe the effect of Se on the proliferation of bovine endometrial epithelial cells (BEECs) induced by lipopolysaccharide (LPS) and to elucidate the possible underlying mechanism. RESULTS: In this study, we developed a BEECs damage model using LPS. Flow cytometry, cell scratch test and EdU proliferation assay were used to evaluate the cell cycle, migration and proliferation. The mRNA transcriptions of growth factors were detected by quantitative reverse transcription-polymerase chain reaction. The activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Wnt/ß-catenin pathways were detected by Western blotting and immunofluorescence. The results showed that the cell viability and BCL-2/BAX protein ratio were significantly decreased, and the cell apoptosis rate was significantly increased in the LPS group. Compared with the LPS group, Se promoted cell cycle progression, increased cell migration and proliferation, and significantly increased the gene expressions of TGFB1, TGFB3 and VEGFA. Se decreased the BCL-2/BAX protein ratio, promoted ß-catenin translocation from the cytoplasm to the nucleus and activated the Wnt/ß-catenin and PI3K/AKT signaling pathways inhibited by LPS. CONCLUSIONS: In conclusion, Se can attenuate LPS-induced damage to BEECs and promote cell proliferation and migration in vitro by enhancing growth factors gene expression and activating the PI3K/AKT and Wnt/ß-catenin signaling pathways.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Selênio , Feminino , Bovinos , Animais , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/farmacologia , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/metabolismo , Selênio/farmacologia , Selênio/metabolismo , beta Catenina/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteína X Associada a bcl-2/farmacologia , Via de Sinalização Wnt , Células Epiteliais , Proliferação de Células , Apoptose
10.
Artigo em Inglês | MEDLINE | ID: mdl-38430147

RESUMO

Objective: The primary objective of this systematic review and meta-analysis was to assess the effectiveness of postoperative drainage in reducing the incidence of Surgical Site Hemorrhage (SSH) and Surgical Site Infections (SSI) in patients undergoing posterior spinal surgery. Methods: We conducted a comprehensive search of four electronic databases, including PubMed, Embase, Web of Science, and Cochrane Library, to identify relevant studies. Only Randomized Controlled Trials (RCT) focusing on patients diagnosed preoperatively with non-infectious spinal diseases and undergoing posterior spinal surgery were included. The meta-analysis examined the efficacy of postoperative drainage in reducing SSH and SSI incidence. Quality assessment was performed using the Cochrane Collaboration's Risk of Bias tool. Statistical analyses were conducted to evaluate heterogeneity and publication bias. Results: A total of seven studies met the inclusion criteria for SSH analysis, while six studies were included in the SSI analysis. The findings revealed a significant reduction in the incidence of SSH in patients with postoperative drainage, with a Relative Risk (RR) of 0.35 (95% CI: 0.20 to 0.62, P < .01). However, no statistically significant impact was observed on the incidence of SSI (RR: 0.97, 95% CI: 0.36 to 2.59, P = .81). Funnel plot symmetry and Egger's linear regression test confirmed the absence of significant publication bias. Conclusions: The use of postoperative drainage in posterior spinal surgery is recommended to significantly reduce the risk of SSH. However, its effectiveness in preventing SSI remains inconclusive and requires further investigation. These can inform clinical decision-making and potentially improve patient outcomes.

11.
Reprod Domest Anim ; 59(6): e14647, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38924282

RESUMO

Endometritis is a common postpartum disease in cows. It delays uterine involution and impairs normal physiological function. This can result in long-term or even lifelong infertility and cause significant losses to the dairy farming industry. Traditional treatments like antibiotics possess certain shortcomings, such as antibiotic residues, the abuse of antibiotics, and increased antimicrobial resistance of pathogens. Alternative treatment strategies are needed to minimize the utilization of antibiotics in dairy production. As an essential trace element in animals, selenium (Se) plays a vital role in regulating immune function, the inflammatory response, and oxidative stress, affecting the speed and completeness of tissue repair. This paper reviewed previous studies to analyse the potential of Se in the prevention and treatment of bovine endometritis, aiming to provide a new direction to increase production capacity in the future.


Assuntos
Doenças dos Bovinos , Endometrite , Selênio , Animais , Bovinos , Endometrite/veterinária , Endometrite/prevenção & controle , Endometrite/tratamento farmacológico , Feminino , Selênio/uso terapêutico , Selênio/administração & dosagem , Selênio/farmacologia , Doenças dos Bovinos/prevenção & controle , Doenças dos Bovinos/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos
12.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(2): 131-138, 2024 Feb 15.
Artigo em Zh | MEDLINE | ID: mdl-38436309

RESUMO

OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.


Assuntos
Empiema , Hidrocefalia , Meningite Pneumocócica , Derrame Subdural , Lactente , Feminino , Masculino , Humanos , Criança , Recém-Nascido , Adolescente , Meningite Pneumocócica/tratamento farmacológico , Meningite Pneumocócica/epidemiologia , Meropeném , Vancomicina , Levofloxacino , Linezolida , Moxifloxacina , Estudos Retrospectivos , Rifampina , Streptococcus pneumoniae , Cloranfenicol
13.
J Cell Mol Med ; 27(10): 1373-1383, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37042086

RESUMO

The bovine uterus is susceptible to infection, and the elevated cortisol level due to stress are common in cows after delivery. The essential trace element selenium plays a pivotal role in the antioxidant and anti-inflammatory defence system of body. This study investigated whether selenium supplementation protected endometrial cells from inflammation in the presence of high-level cortisol. The primary bovine endometrial epithelial cells were subjected to Escherichia coli lipopolysaccharide to establish cellular inflammation model. The gene expression of inflammatory mediators and proinflammatory cytokines was measured by quantitative PCR. The key proteins of NF-κB and MAPK signalling pathways were detected by Western blot and immunofluorescence. The result showed that pre-treatment of Na2 SeO3 (1, 2 and 4 µΜ) decreased the mRNA expression of proinflammatory genes, inhibited the activation of NF-κB and suppressed the phosphorylation of extracellular signal-regulated kinase, P38MAPK and c-Jun N-terminal kinase. This inhibition of inflammation was more apparent in the presence of high-level cortisol (30 ng/mL). These results indicated that selenium has an anti-inflammatory effect, which is mediated via NF-κB and MAPK signalling pathways and is augmented by cortisol in bovine endometrial epithelial cells.


Assuntos
NF-kappa B , Selênio , Feminino , Bovinos , Animais , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Hidrocortisona/farmacologia , Selênio/farmacologia , Inflamação/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Células Epiteliais/metabolismo , Sistema de Sinalização das MAP Quinases
14.
BMC Plant Biol ; 23(1): 73, 2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36732696

RESUMO

BACKGROUND: Cadmium (Cd) is a highly toxic element for plant growth. In plants, hydrogen sulfide (H2S) and methylglyoxal (MG) have emerged as vital signaling molecules that regulate plant growth processes under Cd stress. However, the effects of sodium hydrosulfide (NaHS, a donor of H2S) and MG on Cd uptake, physiological responses, and gene expression patterns of Salix to Cd toxicity have been poorly understood. Here, Salix matsudana Koidz. seedlings were planted in plastic pot with applications of MG (108 mg kg- 1) and NaHS (50 mg kg- 1) under Cd (150 mg kg- 1) stress. RESULTS: Cd treatment significantly increased the reactive oxygen species (ROS) levels and malondialdehyde (MDA) content, but decreased the growth parameters in S. matsudana. However, NaHS and MG supplementation significantly decreased Cd concentration, ROS levels, and MDA content, and finally enhanced the growth parameters. Cd stress accelerated the activities of antioxidative enzymes and the relative expression levels of stress-related genes, which were further improved by NaHS and MG supplementation. However, the activities of monodehydroascorbate reductase (MDHAR), and dehydroascorbate reductase (DHAR) were sharply decreased under Cd stress. Conversely, NaHS and MG applications restored the MDHAR and DHAR activities compared with Cd-treated seedlings. Furthermore, Cd stress decreased the ratios of GSH/GSSG and AsA/DHA but considerably increased the H2S and MG levels and glyoxalase I-II system in S. matsudana, while the applications of MG and NaHS restored the redox status of AsA and GSH and further improved glyoxalase II activity. In addition, compared with AsA, GSH showed a more sensitive response to exogenous applications of MG and NaHS and plays more important role in the detoxification of Cd. CONCLUSIONS: The present study illustrated the crucial roles of H2S and MG in reducing ROS-mediated oxidative damage to S. matsudana and revealed the vital role of GSH metabolism in regulating Cd-induced stress.


Assuntos
Sulfeto de Hidrogênio , Salix , Cádmio/metabolismo , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/metabolismo , Aldeído Pirúvico/metabolismo , Salix/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/metabolismo , Estresse Oxidativo , Glutationa/metabolismo , Plântula/metabolismo
15.
J Virol ; 96(9): e0033622, 2022 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-35404082

RESUMO

Epstein-Barr virus (EBV), the first identified human tumor virus, is etiologically associated with various kinds of malignant and benign diseases, accounting for 265,000 cancer incident cases and 164,000 cancer deaths in 2017. EBV prophylactic vaccine development has been gp350 centered for several decades. However, clinical studies show that gp350-centered vaccines fail to prevent EBV infection. Advances in the EBV infection mechanisms shed light on gB and gHgL, the two key components of the infection apparatus. In this study, for the first time, we utilized recombinant vesicular stomatitis virus (VSV) to display EBV gB (VSV-ΔG-gB/gB-G) or gHgL (VSV-ΔG-gHgL). In vitro studies confirmed successful virion production and glycoprotein presentation on the virion surface. In mouse models, VSV-ΔG-gB/gB-G or VSV-ΔG-gHgL elicited potent humoral responses. Neutralizing antibodies elicited by VSV-ΔG-gB/gB-G were prone to prevent B cell infection, while those elicited by VSV-ΔG-gHgL were prone to prevent epithelial cell infection. Combinatorial vaccination yields an additive effect. The ratio of endpoint neutralizing antibody titers to the endpoint total IgG titers immunized with VSV-ΔG-gHgL was approximately 1. The ratio of IgG1/IgG2a after VSV-ΔG-gB/gB-G immunization was approximately 1 in a dose-dependent, adjuvant-independent manner. Taken together, VSV-based EBV vaccines can elicit a high ratio of epithelial and B lymphocyte neutralizing antibodies, implying their unique potential as EBV prophylactic vaccine candidates. IMPORTANCE Epstein-Barr virus (EBV), one of the most common human viruses and the first identified human oncogenic virus, accounted for 265,000 cancer incident cases and 164,000 cancer deaths in 2017 as well as millions of nonmalignant disease cases. So far, no prophylactic vaccine is available to prevent EBV infection. In this study, for the first time, we reported the VSV-based EBV vaccines presenting two key components of the EBV infection apparatus, gB and gHgL. We confirmed potent antigen-specific antibody generation; these antibodies prevented EBV from infecting epithelial cells and B cells, and the IgG1/IgG2a ratio indicated balanced humoral-cellular responses. Taken together, we suggest VSV-based EBV vaccines are potent prophylactic candidates for clinical studies and help eradicate numerous EBV-associated malignant and benign diseases.


Assuntos
Infecções por Vírus Epstein-Barr , Vesiculovirus , Vacinas Virais , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Infecções por Vírus Epstein-Barr/prevenção & controle , Herpesvirus Humano 4/fisiologia , Imunidade Humoral , Imunoglobulina G/sangue , Camundongos , Vesiculovirus/genética , Vacinas Virais/imunologia
16.
J Med Virol ; 95(5): e28793, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37212266

RESUMO

Epstein-Barr virus (EBV) infection is prevalent in global population and associated with multiple malignancies and autoimmune diseases. During the infection, EBV-harbored or infected cell-expressing antigen could elicit a variety of antibodies with significant role in viral host response and pathogenesis. These antibodies have been extensively evaluated and found to be valuable in predicting disease diagnosis and prognosis, exploring disease mechanisms, and developing antiviral agents. In this review, we discuss the versatile roles of EBV antibodies as important biomarkers for EBV-related diseases, potential driving factors of autoimmunity, and promising therapeutic agents for viral infection and pathogenesis.


Assuntos
Doenças Autoimunes , Infecções por Vírus Epstein-Barr , Esclerose Múltipla , Humanos , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Anticorpos Antivirais , Doenças Autoimunes/complicações , Antivirais/uso terapêutico
17.
Opt Express ; 31(12): 20265-20273, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37381425

RESUMO

The degradation of AlGaN-based UVC LEDs under constant temperature and constant current stress for up to 500 hrs was analyzed in this work. During each degradation stage, the two-dimensional (2D) thermal distributions, I-V curves, optical powers, combining with focused ion beam and scanning electron microscope (FIB/SEM), were thoroughly tested and analyzed the properties and failure mechanisms of UVC LEDs. The results show that: 1) the opto-electrical characteristics measured before/during stress indicate that the increased leakage current and the generation of stress-induced defects increase the non-radiative recombination in the early stress stage, resulting in a decrease in optical power; 2) the increase of temperature caused by the deterioration of the Cr/Al layer of p-metal after 48 hrs of stress aggravates the optical power in UVC LEDs. The 2D thermal distribution in conjunction with FIB/SEM provide a fast and visual way to precisely locate and analyze the failure mechanisms of UVC LEDs.

18.
Neurochem Res ; 48(5): 1382-1394, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36460840

RESUMO

BACKGROUND: Ischemic stroke is a very dangerous disease with high incidence, fatality and disability rate in human beings. Massive evidence has indicated that oxidative stress and inflammation are intimately correlated with progression of ischemic stroke. Additionally, LncRNAs were reported to be involved in ischemic stroke. Here, we aim to explore the effects and molecular mechanism of lncRNA OIP5-AS1 on oxidative stress and inflammation in ischemic stroke. METHODS: HMC3 and SH-SY5Y cells were under the condition of oxygen-glucose deprivation/reoxygenation (OGD/R) treatment to establish cell models of ischemic stroke. Commercial kits were employed to detect the indicators of oxidative stress including ROS, MDA and SOD. The expression of OIP5-AS1, miR-155-5p and IRF2BP2 mRNA was determined using RT-qPCR. The protein levels of inflammatory factors including TNF-α, IL-1ß and IL-6 and IRF2BP2 were assessed by western blot and/or ELISA. Luciferase activity assay was employed to validate their correlations among OIP5-AS1, miR-155-5p and IRF2BP2. RESULTS: In OGD/R-induced HMC3 and SH-SY5Y cells, the expression of OIP5-AS1 and IRF2BP2 was reduced while miR-155-5p was elevated. OGD/R induction promoted oxidative stress and inflammatory response in HMC3 and SH-SY5Y cells, while OIP5-AS1 or IRF2BP2 sufficiency as well as miR-155-5p inhibitor attenuated OGD/R-induced these influences. In addition, IRF2BP2 knockdown abolished the suppressive impacts of OIP5-AS1 overexpression on oxidative stress and inflammatory response in OGD/R-induced HMC3 and SH-SY5Y cells. Mechanistically, OIP5-AS1 enhanced IRF2BP2 expression via sponging miR-155-5p. CONCLUSION: OIP5-AS1 suppressed oxidative stress and inflammatory response to alleviate cell injury caused by OGD/R induction in HMC3 and SH-SY5Y cells through regulating miR-155-5p/IRF2BP2 axis, which might offer novel targeted molecules for ischemic stroke therapy.


Assuntos
AVC Isquêmico , MicroRNAs , Neuroblastoma , Humanos , MicroRNAs/metabolismo , Inflamação/genética , Estresse Oxidativo , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição/metabolismo
19.
Nanotechnology ; 34(36)2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37257443

RESUMO

Carbon nanotube (CNT) materials show large degradation in tensile strength when they are exposed in chemically active environments due to the loss of inter-tube bonding. Here, we report the suppression of such degradation by chemical vapor infiltration of amorphous carbon into CNT films. The amorphous carbon generated by the thermal decomposition of the gaseous hydrocarbon of acetylene is firmly bonded on the CNT sidewalls and intersections. Based on the improved inter-tube bonding and restriction of inter-tube sliding, the tensile strength of the film is improved to be 3 times of the original level. More importantly, the bonding is so strong and stable that the high tensile strength remains with little loss even in harsh wet environments such as boiling alcoholic, acidic, alkaline solutions and seawater. Such harsh environments-tolerant properties, which were rarely observed before, could open new windows for the CNT/C composite material to be applied from functional devices to structural components under extreme corrosive conditions.

20.
Environ Sci Technol ; 57(33): 12442-12452, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37506289

RESUMO

Soil stores a large amount of mercury (Hg) that has adverse effects on human health and ecosystem safety. Significant uncertainties still exist in revealing environmental drivers of soil Hg accumulation and predicting global Hg distribution owing to the lack of field data from global standardized analyses. Here, we conducted a global standardized field survey and explored a holistic understanding of the multidimensional environmental drivers of Hg accumulation in global surface soils. Hg content in surface soils from our survey ranges from 3.8 to 618.2 µg kg-1 with an average of 74.0 µg kg-1 across the globe. Atmospheric Hg deposition, particularly vegetation-induced elemental Hg0 deposition, is the major source of surface soil Hg. Soil organic carbon serves as the major substrate for sequestering Hg in surface soils and is significantly influenced by agricultural management, litterfall, and elevation. For human activities, changing land-use could be a more important contributor than direct anthropogenic emissions. Our prediction of a new global Hg distribution highlights the hot spots (high Hg content) in East Asia, the Northern Hemispheric temperate/boreal regions, and tropical areas, while the cold spots (low Hg content) are in arid regions. The holistic understanding of multidimensional environmental drivers helps to predict the Hg distribution in global surface soils under a changing global environment.


Assuntos
Mercúrio , Poluentes do Solo , Humanos , Mercúrio/análise , Solo/química , Ecossistema , Carbono , Monitoramento Ambiental
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