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1.
Nature ; 620(7972): 145-153, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37468639

RESUMO

Human-specific genomic changes contribute to the unique functionalities of the human brain1-5. The cellular heterogeneity of the human brain6,7 and the complex regulation of gene expression highlight the need to characterize human-specific molecular features at cellular resolution. Here we analysed single-nucleus RNA-sequencing and single-nucleus assay for transposase-accessible chromatin with sequencing datasets for human, chimpanzee and rhesus macaque brain tissue from posterior cingulate cortex. We show a human-specific increase of oligodendrocyte progenitor cells and a decrease of mature oligodendrocytes across cortical tissues. Human-specific regulatory changes were accelerated in oligodendrocyte progenitor cells, and we highlight key biological pathways that may be associated with the proportional changes. We also identify human-specific regulatory changes in neuronal subtypes, which reveal human-specific upregulation of FOXP2 in only two of the neuronal subtypes. We additionally identify hundreds of new human accelerated genomic regions associated with human-specific chromatin accessibility changes. Our data also reveal that FOS::JUN and FOX motifs are enriched in the human-specifically accessible chromatin regions of excitatory neuronal subtypes. Together, our results reveal several new mechanisms underlying the evolutionary innovation of human brain at cell-type resolution.


Assuntos
Evolução Molecular , Giro do Cíngulo , Animais , Humanos , Núcleo Celular/metabolismo , Cromatina/genética , Cromatina/metabolismo , Conjuntos de Dados como Assunto , Genoma Humano/genética , Genômica , Giro do Cíngulo/citologia , Giro do Cíngulo/metabolismo , Macaca mulatta/genética , Neurônios/classificação , Neurônios/citologia , Oligodendroglia/citologia , Oligodendroglia/metabolismo , Pan troglodytes/genética , Análise da Expressão Gênica de Célula Única , Células-Tronco/citologia , Transposases/metabolismo , Montagem e Desmontagem da Cromatina
2.
Nano Lett ; 24(27): 8410-8417, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38920331

RESUMO

Nanodevices that function in specific organs or cells are one of the ultimate goals of synthetic biology. The recent progress in DNA nanotechnology such as DNA origami has allowed us to construct nanodevices to deliver a payload (e.g., drug) to the tumor. However, delivery to specific organs remains difficult due to the fragility of the DNA nanostructure and the low targeting capability of the DNA nanostructure. Here, we constructed tough DNA origami that allowed us to encapsulate the DNA origami into lipid-based nanoparticles (LNPs) under harsh conditions (low pH), harnessing organ-specific delivery of the gene of interest (GOI). We found that DNA origami-encapsulated LNPs can increase the functionality of payload GOIs (mRNA and siRNA) inside mouse organs through the contribution from different LNP structures revealed by cryogenic electron microscope (Cryo-EM). These data should be the basis for future organ-specific gene expression control using DNA origami nanodevices.


Assuntos
DNA , Nanotecnologia , DNA/química , Animais , Camundongos , Nanotecnologia/métodos , Nanoestruturas/química , Nanopartículas/química , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética , RNA Mensageiro/genética , RNA Mensageiro/química , Regulação da Expressão Gênica , Especificidade de Órgãos , Conformação de Ácido Nucleico , Lipídeos/química
3.
Genes Dev ; 31(21): 2121-2135, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29196536

RESUMO

The molecular mechanisms underlying human brain evolution are not fully understood; however, previous work suggested that expression of the transcription factor CLOCK in the human cortex might be relevant to human cognition and disease. In this study, we investigated this novel transcriptional role for CLOCK in human neurons by performing chromatin immunoprecipitation sequencing for endogenous CLOCK in adult neocortices and RNA sequencing following CLOCK knockdown in differentiated human neurons in vitro. These data suggested that CLOCK regulates the expression of genes involved in neuronal migration, and a functional assay showed that CLOCK knockdown increased neuronal migratory distance. Furthermore, dysregulation of CLOCK disrupts coexpressed networks of genes implicated in neuropsychiatric disorders, and the expression of these networks is driven by hub genes with human-specific patterns of expression. These data support a role for CLOCK-regulated transcriptional cascades involved in human brain evolution and function.


Assuntos
Proteínas CLOCK/genética , Proteínas CLOCK/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Redes Reguladoras de Genes/genética , Neurônios/fisiologia , Linhagem Celular , Movimento Celular/genética , Epigênese Genética/genética , Técnicas de Silenciamento de Genes , Humanos , Neocórtex/metabolismo , Transtornos do Neurodesenvolvimento/genética , Neurônios/citologia
4.
J Cell Sci ; 135(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34854883

RESUMO

Septins, a family of GTP-binding proteins that assemble into higher order structures, interface with the membrane, actin filaments and microtubules, and are thus important regulators of cytoarchitecture. Septin 9 (SEPT9), which is frequently overexpressed in tumors and mutated in hereditary neuralgic amyotrophy (HNA), mediates the binding of septins to microtubules, but the molecular determinants of this interaction remained uncertain. We demonstrate that a short microtubule-associated protein (MAP)-like motif unique to SEPT9 isoform 1 (SEPT9_i1) drives septin octamer-microtubule interaction in cells and in vitro reconstitutions. Septin-microtubule association requires polymerizable septin octamers harboring SEPT9_i1. Although outside of the MAP-like motif, HNA mutations abrogate this association, identifying a putative regulatory domain. Removal of this domain from SEPT9_i1 sequesters septins on microtubules, promotes microtubule stability and alters actomyosin fiber distribution and tension. Thus, we identify key molecular determinants and potential regulatory roles of septin-microtubule interaction, paving the way to deciphering the mechanisms underlying septin-associated pathologies. This article has an associated First Person interview with the first author of the paper.


Assuntos
Septinas , Fibras de Estresse , Humanos , Proteínas Associadas aos Microtúbulos , Microtúbulos/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Septinas/genética , Septinas/metabolismo , Fibras de Estresse/metabolismo
5.
Helicobacter ; 29(4): e13079, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38984661

RESUMO

BACKGROUND: Eradicating Helicobacter pylori infection by bismuth quadruple therapy (BQT) is effective. However, the effect of BQT and subsequent fecal microbiota transplant (FMT) on the gut microbiota is less known. MATERIALS AND METHODS: This prospective randomized controlled trial was conducted at a tertiary hospital in China from January 2019 to October 2020, with the primary endpoints the effect of BQT on the gut microbiota and the effect of FMT on the gut microbiota after bismuth quadruple therapy eradication therapy. A 14-day BQT with amoxicillin and clarithromycin was administered to H. pylori-positive subjects, and after eradication therapy, patients received a one-time FMT or placebo treatment. We then collected stool samples to assess the effects of 14-day BQT and FMT on the gut microbiota. 16 s rDNA and metagenomic sequencing were used to analyze the structure and function of intestinal flora. We also used Gastrointestinal Symptom Rating Scale (GSRS) to evaluate gastrointestinal symptom during treatment. RESULTS: A total of 30 patients were recruited and 15 were assigned to either FMT or placebo groups. After eradication therapy, alpha-diversity was decreased in both groups. At the phylum level, the abundance of Bacteroidetes and Firmicutes decreased, while Proteobacteria increased. At the genus level, the abundance of beneficial bacteria decreased, while pathogenic bacteria increased. Eradication therapy reduced some resistance genes abundance while increased the resistance genes abundance linked to Escherichia coli. While they all returned to baseline by Week 10. Besides, the difference was observed in Week 10 by the diarrhea score between two groups. Compared to Week 2, the GSRS total score and diarrhea score decreased in Week 3 only in FMT group. CONCLUSIONS: The balance of intestinal flora in patients can be considerably impacted by BQT in the short term, but it has reverted back to baseline by Week 10. FMT can alleviate gastrointestinal symptoms even if there was no evidence it promoted restoration of intestinal flora.


Assuntos
Antibacterianos , Bismuto , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Infecções por Helicobacter , Helicobacter pylori , Humanos , Infecções por Helicobacter/terapia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Transplante de Microbiota Fecal/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Helicobacter pylori/efeitos dos fármacos , Adulto , Antibacterianos/uso terapêutico , Estudos Prospectivos , Bismuto/uso terapêutico , Quimioterapia Combinada , China , Amoxicilina/uso terapêutico , Claritromicina/uso terapêutico , Resultado do Tratamento , Idoso , Fezes/microbiologia
6.
J Neuroeng Rehabil ; 21(1): 164, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39294678

RESUMO

INTRODUCTIN: Improper gait patterns, impaired balance and foot drop consistently plague stroke survivors, preventing them from walking independently and safely. Neuromuscular electrical stimulation (NMES) technology can help patients reactivate their muscles and regain motor coordination. This study aims to systematically review and summarize the evidence for the potential benefits of NMES on the improvement of gait patterns after stroke. EVIDENCE ACQUISITION: PubMed, Cochrane Library, Embase, Science Direct and Web of Science were systematically searched until April 2024, to identify randomized controlled trials with the following criteria: stroke survivors as participants; NMES as intervention; conventional rehabilitation as a comparator; and gait assessment, through scales or quantitative parameters, as outcome measures. EVIDENCE SYNTHESIS: 29 publications involving 1711 patients met the inclusion criteria. Meta-analysis showed no significant differences in Ten-meter walk test, Fugl-Meyer assessment lower extremity, Modified Ashworth Assessment and asymmetry between the NMES group and the control group. Besides, NMES was associated with changes in outcome indicators such as quantitative gait analysis speed [SMD = 0.53, 95% CI (0.20, 0.85), P = 0.001], cadence [SMD = 0.76, 95% CI (0.32, 1.20), P = 0.0008], affected side step length [SMD = 0.73, 95% CI (0.16, 1.31), P = 0.01], angle of ankle dorsiflexion [WMD = 1.57, 95% CI (0.80, 2.33), P < 0.0001], Six-Minute Walk Test [WMD = 14.83, 95% CI (13.55, 16.11), P<0.00001]. According to the PEDro scale, 21 (72.4%) studies were of high quality and 8 were of moderate quality (27.6%). CONCLUSIONS: Taken together, the review synthesis indicated that NMES might play a potential role in stroke-induced walking dysfunction. And NMES may be superior for survivors in the chronic phase than the acute and subacute phases, and the efficacy of short sessions received by patients was greater than that of those who participated in a longer session. Additionally, further comparisons of the effects of NMES with different types or stimulation frequencies may provide unexpected benefits.


Assuntos
Terapia por Estimulação Elétrica , Transtornos Neurológicos da Marcha , Equilíbrio Postural , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Fenômenos Biomecânicos , Terapia por Estimulação Elétrica/métodos , Marcha/fisiologia , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Transtornos Neurológicos da Marcha/reabilitação , Equilíbrio Postural/fisiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia , Reabilitação do Acidente Vascular Cerebral/métodos
7.
BMC Med Educ ; 24(1): 509, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715008

RESUMO

BACKGROUND: In this era of rapid technological development, medical schools have had to use modern technology to enhance traditional teaching. Online teaching was preferred by many medical schools. However due to the complexity of intracranial anatomy, it was challenging for the students to study this part online, and the students were likely to be tired of neurosurgery, which is disadvantageous to the development of neurosurgery. Therefore, we developed this database to help students learn better neuroanatomy. MAIN BODY: The data were sourced from Rhoton's Cranial Anatomy and Surgical Approaches and Neurosurgery Tricks of the Trade in this database. Then we designed many hand gesture figures connected with the atlas of anatomy. Our database was divided into three parts: intracranial arteries, intracranial veins, and neurosurgery approaches. Each section below contains an atlas of anatomy, and gestures represent vessels and nerves. Pictures of hand gestures and atlas of anatomy are available to view on GRAVEN ( www.graven.cn ) without restrictions for all teachers and students. We recruited 50 undergraduate students and randomly divided them into two groups: using traditional teaching methods or GRAVEN database combined with above traditional teaching methods. Results revealed a significant improvement in academic performance in using GRAVEN database combined with traditional teaching methods compared to the traditional teaching methods. CONCLUSION: This database was vital to help students learn about intracranial anatomy and neurosurgical approaches. Gesture teaching can effectively simulate the relationship between human organs and tissues through the flexibility of hands and fingers, improving anatomy interest and education.


Assuntos
Bases de Dados Factuais , Educação de Graduação em Medicina , Gestos , Neurocirurgia , Humanos , Neurocirurgia/educação , Educação de Graduação em Medicina/métodos , Estudantes de Medicina , Neuroanatomia/educação , Ensino , Feminino , Masculino
8.
J Environ Manage ; 368: 122219, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39153322

RESUMO

This study, aimed at exploring low-maintenance, high-diversity, and sustainable greening strategies for residential areas, conducted a comprehensive survey and analysis of spontaneous plants in residential green spaces in Fuzhou City, documenting 361 species. Employing methods such as variance partitioning, Canonical Correspondence Analysis (CCA), and ecological niche analysis, we investigated the environmental factors influencing the distribution and composition of these plants, as well as their interrelationships. The study found that the composition of spontaneous plants in residential green spaces differs from other urban environments, with a high proportion of alien species (43.77%) due to influences such as resident activities, including a large number of ornamental and edible plants. Maintenance level, urbanization gradient, and green space ratio are common factors affecting the composition and distribution of spontaneous plants in urban environments, while unique residential socio-economic factors like building age, housing prices, and population density significantly affect the spontaneous plants in residential green spaces. The overall dominant plant community shows a significant positive association, indicating a relatively stable stage of succession. Although competition among most species is not significant and interspecific connectivity is weak, the presence of seven dominant invasive species intensifies competition. Based on these findings, the study proposes several specific sustainable management measures: adopting the concept of New Naturalistic Ecological Planting Design, selecting native spontaneous plants with strong adaptability, and constructing plant communities that are ecologically stable and have ornamental value by mimicking natural ecosystems. Additionally, specific methods for managing specific invasive species in residential green spaces using competitive replacement control methods are proposed. These measures aim to promote the health and sustainable development of urban residential green spaces.


Assuntos
Ecossistema , Desenvolvimento Sustentável , China , Conservação dos Recursos Naturais/métodos , Plantas , Urbanização , Cidades , Biodiversidade , Espécies Introduzidas
9.
Angew Chem Int Ed Engl ; 63(28): e202405438, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38682249

RESUMO

The alkaline oxygen evolution reaction (OER) is a promising avenue for producing clean fuels and storing intermittent energy. However, challenges such as excessive OH- consumption and strong adsorption of oxygen-containing intermediates hinder the development of alkaline OER. In this study, we propose a cooperative strategy by leveraging both nano-scale and atomically local electric fields for alkaline OER, demonstrated through the synthesis of Mn single atom doped CoP nanoneedles (Mn SA-CoP NNs). Finite element method simulations and density functional theory calculations predict that the nano-scale local electric field enriches OH- around the catalyst surface, while the atomically local electric field improves *O desorption. Experimental validation using in situ attenuated total reflection infrared and Raman spectroscopy confirms the effectiveness of the nano-scale and atomically electric fields. Mn SA-CoP NNs exhibit an ultra-low overpotential of 189 mV at 10 mA cm-2 and stable operation over 100 hours at ~100 mA cm-2 during alkaline OER. This innovative strategy provides new insights for enhancing catalyst performance in energy conversion reactions.

10.
J Biol Chem ; 298(5): 101928, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35413284

RESUMO

We have recently purified mammalian sterile 20 (STE20)-like kinase 3 (MST3) as a kinase for the multifunctional kinases, AMP-activated protein kinase-related kinases (ARKs). However, unresolved questions from this study, such as remaining phosphorylation activities following deletion of the Mst3 gene from human embryonic kidney cells and mice, led us to conclude that there were additional kinases for ARKs. Further purification recovered Ca2+/calmodulin-dependent protein kinase kinases 1 and 2 (CaMKK1 and 2), and a third round of purification revealed mitogen-activated protein kinase kinase kinase kinase 5 (MAP4K5) as potential kinases of ARKs. We then demonstrated that MST3 and MAP4K5, both belonging to the STE20-like kinase family, could phosphorylate all 14 ARKs both in vivo and in vitro. Further examination of all 28 STE20 kinases detected variable phosphorylation activity on AMP-activated protein kinase (AMPK) and the salt-inducible kinase 3 (SIK3). Taken together, our results have revealed novel relationships between STE20 kinases and ARKs, with potential physiological and pathological implications.


Assuntos
Proteínas Serina-Treonina Quinases , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Camundongos , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/isolamento & purificação , Proteínas Serina-Treonina Quinases/metabolismo
11.
J Biol Chem ; 298(5): 101929, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35413286

RESUMO

The AMP-activated protein kinase (AMPK) and AMPK-related kinase salt-inducible kinase 3 (SIK3) regulate many important biological processes ranging from metabolism to sleep. Liver kinase B1 is known to phosphorylate and activate both AMPK and SIK3, but the existence of other upstream kinases was unclear. In this study, we detected liver kinase B1-independent AMPK-related kinase phosphorylation activities in human embryonic kidney cells as well as in mouse brains. Biochemical purification of this phosphorylation activity uncovered mammalian sterile 20-like kinase 3 (MST3). We demonstrate that MST3 from human embryonic kidney cells could phosphorylate AMPK and SIK3 in vivo. In addition, recombinant MST3 expressed in and purified from Escherichia coli could directly phosphorylate AMPK and SIK3 in vitro. Moreover, four other members of the MST kinase family could also phosphorylate AMPK or SIK3. Our results have revealed new kinases able to phosphorylate and activate AMPK and SIK3.


Assuntos
Proteínas Quinases Ativadas por AMP , Proteínas Serina-Treonina Quinases , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Camundongos , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/isolamento & purificação , Proteínas Serina-Treonina Quinases/metabolismo
12.
Small ; 19(18): e2206218, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36670078

RESUMO

By introducing different contents of Bi adatoms to the surface of monolayer graphene, the carrier concentration and their dynamics have been effectively modulated as probed directly by the time- and angle-resolved photoemission spectroscopy technique. The Bi adatoms are found to assist acoustic phonon scattering events mediated by supercollisions as the disorder effectively relaxes the momentum conservation constraint. A reduced carrier multiplication has been observed, which is related to the shrinking Fermi sea for scattering, as confirmed by time-dependent density functional theory simulation. This work gives insight into hot carrier dynamics in graphene, which is crucial for promoting the application of photoelectric devices.

13.
Cancer Cell Int ; 23(1): 156, 2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37542290

RESUMO

BACKGROUND: N6-methyladenosine (m6A), 5-methylcytosine (m5C) and N1-methyladenosine (m1A) are the main RNA methylation modifications involved in the progression of cancer. However, it is still unclear whether RNA methylation-related long noncoding RNAs (lncRNAs) affect the prognosis of glioma. METHODS: We summarized 32 m6A/m5C/m1A-related genes and downloaded RNA-seq data and clinical information from The Cancer Genome Atlas (TCGA) database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to identify differentially expressed (DE-) RNA methylation-related lncRNAs in order to construct a prognostic signature of glioma and in order to determine their correlation with immune function, immune therapy and drug sensitivity. In vitro and in vivo assays were performed to elucidate the effects of RNA methylation-related lncRNAs on glioma. RESULTS: A total of ten RNA methylation-related lncRNAs were used to construct a survival and prognosis signature, which had good independent prediction ability for patients. It was found that the high-risk group had worse overall survival (OS) than the low-risk group in all cohorts. In addition, the risk group informed the immune function, immunotherapy response and drug sensitivity of patients with glioma in different subgroups. Knockdown of RP11-98I9.4 and RP11-752G15.8 induced a more invasive phenotype, accelerated cell growth and apparent resistance to temozolomide (TMZ) both in vitro and in vivo. We observed significantly elevated global RNA m5C and m6A levels in glioma cells. CONCLUSION: Our study determined the prognostic implication of RNA methylation-related lncRNAs in gliomas, established an RNA methylation-related lncRNA prognostic model, and elucidated that RP11-98I9.4 and RP11-752G15.8 could suppress glioma proliferation, migration and TMZ resistance. In the future, these RNA methylation-related lncRNAs may become a new choice for immunotherapy of glioma.

14.
BJU Int ; 131(4): 443-451, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36053730

RESUMO

OBJECTIVES: To investigate the association of polygenic risk score (PRS) and bladder cancer (BC) risk and whether this PRS can be offset by a healthy lifestyle. METHODS: Individuals with BC (n = 563) and non-BC controls (n = 483 957) were identified in the UK Biobank, and adjusted Cox regression models were used. A PRS was constructed based on 34 genetic variants associated with BC development, while a healthy lifestyle score (HLS) was constructed based on three lifestyle factors (i.e., smoking, physical activity, and diet). RESULTS: Overall, a negative interaction was observed between the PRS and the HLS (P = 0.02). A 7% higher and 28% lower BC risk per 1-standard deviation (SD) increment in PRS and HLS were observed, respectively. A simultaneous increment of 1 SD in both HLS and PRS was associated with a 6% lower BC risk. In addition, individuals with a high genetic risk and an unfavourable lifestyle showed an increased BC risk compared to individuals with low genetic risk and a favourable lifestyle (hazard ratio 1.55, 95% confidence interval 1.16-1.91; P for trend <0.001). Furthermore, population-attributable fraction (PAF) analysis showed that 12%-15% of the BC cases might have been prevented if individuals had adhered to a healthy lifestyle. CONCLUSION: This large-scale cohort study shows that a genetic predisposition combined with unhealthy behaviours have a joint negative effect on the risk of developing BC. Behavioural lifestyle changes should be encouraged for people through comprehensive, multifactorial approaches, although high-risk individuals may be selected based on genetic risk.


Assuntos
Predisposição Genética para Doença , Neoplasias da Bexiga Urinária , Humanos , Predisposição Genética para Doença/genética , Estudos de Coortes , Fatores de Risco , Estilo de Vida , Neoplasias da Bexiga Urinária/genética
15.
Helicobacter ; 28(5): e13003, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37565458

RESUMO

BACKGROUND: According to the Maastricht VI/Florence consensus report, potassium-competitive acid blockers (P-CAB) may improve Helicobacter pylori eradication treatment. MATERIALS AND METHODS: A total of 213 H. pylori treatment-naive patients aged between 18 and 70 years were treated with two regimens. The two regimens are VDT: 20 mg vonoprazan twice a day and 1 g amoxicillin three times daily and EDT: 20 mg esomeprazole four times a day and 750 mg amoxicillin four times daily. 13 C-urea breath tests were used to evaluate eradication rate 4-6 weeks after treatment. Based on propensity score matching (PSM), this retrospective study analyzed the eradication rates, adverse events (AEs), compliance, and antibiotic resistance rates in VDT and EDT groups. RESULTS: On intention-to-treat (ITT) analysis, the eradication rate in VDT group (89.0%; 95% CI 81.7-96.3) was non-inferior to that in EDT group (87.7%; 95% CI 80.1-95.3; p = 0.796). The corresponding per-protocol (PP) eradication rates were 94.1% (95% CI 88.4-99.8) and 92.8% (95% CI 86.7-98.9; p = 1.000), respectively. There were no significant between-group differences with respect to compliance or incidence of AEs. CONCLUSIONS: The efficacy and safety of 14-day VDT and EDT were comparable. Therefore, 14-day VDT or EDT may be recommended for the first-line treatment of H. pylori infection.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Infecções por Helicobacter/tratamento farmacológico , Esomeprazol/uso terapêutico , Antibacterianos/efeitos adversos , Estudos Retrospectivos , Pontuação de Propensão , Inibidores da Bomba de Prótons/efeitos adversos , Amoxicilina/uso terapêutico , Quimioterapia Combinada , Resultado do Tratamento , Claritromicina/uso terapêutico
16.
Helicobacter ; 28(4): e12970, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37160689

RESUMO

BACKGROUND: Potassium-competitive acid blockers (P-CAB) are recommended for the treatment of Helicobacter pylori infections, but dual therapy of P-CAB with amoxicillin has been poorly studied. The current study compared the efficacy, adverse reactions, compliance, and effects on gut microbiota of 14-day vonoprazan-amoxicillin (VA) dual therapy with esomeprazole, bismuth potassium citrate, amoxicillin, and metronidazole (EBAM) quadruple therapy in treatment-naive patients with H. pylori. MATERIALS AND METHODS: This was a multicenter, open-label, randomized, and controlled, non-inferiority study. Patients (n = 194) enrolled from six centers were randomly divided into either the VA or EBAM group. H. pylori eradication was determined using 13 C urea breath tests (UBT) 4-6 weeks post-treatment. Fecal samples were collected, and gut microbial populations were analyzed by 16S rDNA and metagenomic sequencing technology. RESULTS: Eradication rates of H. pylori in the VA and EBAM groups were 88.7% and 91.8%, respectively, according to intention-to-treat (ITT) analysis; 95.6% and 96.7% with per-protocol (PP) analysis; and 94.5% and 96.7% with modified ITT (mITT) analysis (all p > 0.05). The incidence of adverse reactions in the VA group was significantly lower compared to the EBAM group, and compliance within both groups was good. There was no difference in α-diversity or microbial composition in the VA and EBAM groups at one-month post-treatment compared to baseline, except for a markedly reduced abundance of Bacteroides in the EBAM group. CONCLUSION: VA therapy achieved excellent eradication rates with low adverse reactions, good compliance, and little impact on gut microbiota. VA therapy should be recommended as a first-line treatment against H. pylori.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Amoxicilina/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Antibacterianos , Quimioterapia Combinada , Bismuto/uso terapêutico , Resultado do Tratamento , Inibidores da Bomba de Prótons/uso terapêutico , Claritromicina/uso terapêutico
17.
J Chem Phys ; 158(16)2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37096850

RESUMO

Atomic stabilization is a universal phenomenon that occurs when atoms interact with intense and high-frequency laser fields. In this work, we systematically study the influence of the ponderomotive (PM) force, present around the laser focus, on atomic stabilization. We show that the PM force could induce tunneling and even over-barrier ionization to the otherwise stabilized atoms. Such effect may overweigh the typical multiphoton ionization under moderate laser intensities. Our work highlights the importance of an improved treatment of atomic stabilization that includes the influence of the PM force.

18.
Biochem Genet ; 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37812283

RESUMO

Breast cancer (BC) is the most abundant and aggressive cancer that impacts millions of women with poorly understood mechanisms. Here, we aimed to investigate the function of LINC01806 in BC development. Human BC tissues and nearby normal specimens were taken from diagnosed BC patients. The expression levels of LINC01806, miR-1286, ZEB1, and EMT-related markers were evaluated by qRT-PCR and western blotting. FISH was used to visualize the subcellular localization of LINC01806. The viability, proliferation, migration and invasion capacities of BC cells were assessed by MTT, colony formation, and transwell assays. Interactions among LINC01806, miR-1286 and ZEB1 were validated by dual luciferase assay. The unpaired Student t-test (for two groups) or one-way ANOVA following with Tukey post-hoc test (for more than three groups) was employed for statistical analysis. LINC01806 level was elevated in BC tissues. Knockdown of LINC01806 suppressed EMT process and BC cell proliferation, migration, and invasion. LINC01806 co-localized and directly bound with miR-1286 in the cytoplasm. MiR-1286 inhibitor blocked the effects of LINC01806 knockdown on BC cell EMT, proliferation and migration. MiR-1286 targeted ZEB1 and overexpression of ZEB1 blocked the regulatory functions of miR-1286 mimics in BC. LINC01806 facilitates EMT and accelerates BC cell proliferation, migration, and invasion via acting as miR-1286 sponge to disinhibit ZEB1 expression.

19.
Sensors (Basel) ; 23(16)2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37631789

RESUMO

The grounding network is a significant component of substations, and the corrosion of its ground resistance is predominantly detected using the electromagnetic method. However, the application of electromagnetic methods for detecting corrosion within earthing networks has received relatively limited attention in research. Currently, the prevailing method utilizes electromagnetic techniques to identify the breakage points within the given earthing network. In this study, we propose a corrosion detection method for grounding networks based on the low-frequency electromagnetic method, which measures the resistance value between individual nodes of the network. Specifically, an excitation source signal of a predetermined frequency was transmitted to the measurement segment of the grounding network, which facilitated the direct measurement of the strength of the induced magnetic field above the center of the measuring conductor. The recorded electromagnetic data were subsequently uploaded to the host computer for data processing, and the computer interface was constructed based on a LABVIEW design. By leveraging the relationship between the induced electric potential, current strength, excitation source strength, and additional voltage detection devices, the resistance of the conductor under examination could be determined. Furthermore, the proposed method was tested under suitable conditions, and it demonstrated favorable results. Thus, the proposed method can serve as a foundation for developing electromagnetic testing instruments tailored to the investigated grounding network.

20.
Int J Mol Sci ; 24(4)2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36835437

RESUMO

The pancreas represents an important organ that has not been comprehensively studied in many fields. To fill this gap, many models have been generated, and traditional models have shown good performance in addressing pancreatic-related diseases, but are increasingly struggling to keep up with the need for further research due to ethical issues, genetic heterogeneity and difficult clinical translation. The new era calls for new and more reliable research models. Therefore, organoids have been proposed as a novel model for the evaluation of pancreatic-related diseases such as pancreatic malignancy, diabetes, and pancreatic cystic fibrosis. Compared with common traditional models, including 2D cell culture and gene editing mice, organoids derived from living humans or mice cause minimal harm to the donor, raise fewer ethical concerns, and reasonably address the claims of heterogeneity, which allows for the further development of pathogenesis studies and clinical trial analysis. In this review, we analyse studies on the use of pancreatic organoids in research on pancreatic-related diseases, discuss the advantages and disadvantages, and hypothesize future trends.


Assuntos
Fibrose Cística , Neoplasias Pancreáticas , Humanos , Animais , Camundongos , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Fibrose Cística/patologia , Técnicas de Cultura de Células , Organoides/patologia
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