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Epidemiological investigations show that noise exposure in early life is associated with health and cognitive impairment. The gut microbiome established in early life plays a crucial role in modulating developmental processes that subsequently affect brain function and behavior. Here, we examined the impact of early-life exposure to noise on cognitive function in adolescent rats by analyzing the gut microbiome and metabolome to elucidate the underlying mechanisms. Chronic noise exposure during early life led to cognitive deficits, hippocampal injury, and neuroinflammation. Early-life noise exposure showed significant difference on the composition and function of the gut microbiome throughout adolescence, subsequently causing axis-series changes in fecal short-chain fatty acid (SCFA) metabolism and serum metabolome profiles, as well as dysregulation of endothelial tight junction proteins, in both intestine and brain. We also observed sex-dependent effects of microbiota depletion on SCFA-related beneficial bacteria in adolescence. Experiments on microbiota transplantation and SCFA supplementation further confirmed the role of intestinal bacteria and related SCFAs in early-life noise-exposure-induced impairments in cognition, epithelial integrity, and neuroinflammation. Overall, these results highlight the homeostatic imbalance of microbiota-gut-brain axis as an important physiological response toward environmental noise during early life and reveals subtle differences in molecular signaling processes between male and female rats.
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Disfunção Cognitiva , Microbioma Gastrointestinal , Masculino , Feminino , Ratos , Animais , Eixo Encéfalo-Intestino , Doenças Neuroinflamatórias , Microbioma Gastrointestinal/fisiologia , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/farmacologia , HomeostaseRESUMO
Horticulture productivity has been increasingly restricted by heat stress from growing global warming, making it far below the optimum production capacity. As a popular ornamental cultivar of tree peony, Paeonia suffruticosa 'Yu Hong' has also been suffering from heat stress not suitable for its optimal growth. To better understand the response mechanisms against heat stress of tree peony, investigations of phenotypic changes, physiological responses, and quantitative proteomics were conducted. Phenotypic and physiological changes indicated that 24 h of exposure to heat stress (40 °C) was the critical duration of heat stress in tree peony. The proteomic analyses revealed a total of 100 heat-responsive proteins (HRPs). According to bioinformatic analysis of HRPs, the heat tolerance of tree peony might be related to signal transduction, synthesis/degradation, heat kinetic proteins, antioxidants, photosynthesis, energy conversion, and metabolism. Our research will provide some new insights into the molecular mechanism under the response against the heat stress of tree peony, which will benefit the future breeding of heat-resistant ornamental plants.
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Evolutionary game dynamics in finite populations can be described by a frequency-dependent, stochastic Wright-Fisher process. The fitness of individuals in a population is not only linked to environmental conditions but also tightly coupled to the types and frequencies of competitors, leading to different types of individuals with different selection intensities. We studied a 2â¯×â¯2 symmetric game in a finite population and established a dynamic model of the Wright-Fisher process by introducing different selection intensities for different strategies. Thus, we provided another effective way to study the evolutionary dynamics of a finite population and obtained the analytical expressions of fixation probabilities under weak selection. The fixation probability of a strategy is not only related to a game matrix but also to different selection intensities. The conditions required for natural selection to favor one strategy and for that strategy to be an evolutionary stable strategy (ESSN) are specified in our model. We compared our results with those of a Moran dynamic process with different selection intensities to explore these two processes better. In the two processes, the conditions conducive to the strategy's taking fixation are the same. By simulation analysis, the dynamic relationships between the fixation probabilities and selection intensities were intuitively observed in the prisoner's dilemma, coordination, and coexistence games. The fixation probability of the cooperative strategy in the prisoner's dilemma decreases with the increase of its own selection intensity. In the coexistence and coordination games, the fixation probability of the cooperative strategy increases with its own selection intensity. For the three types of games, the fixation probability of the cooperative strategy decreases with the increase of the selection intensity of the defection strategy.
Assuntos
Algoritmos , Evolução Biológica , Teoria dos Jogos , Aptidão Genética/genética , Modelos Teóricos , Seleção Genética/genética , Animais , Genética Populacional/métodos , Humanos , Densidade Demográfica , Dinâmica Populacional , Processos EstocásticosRESUMO
Porous and single-crystalline ZnO nanobelts have been prepared through annealing precursors of ZnSe · 0.5N2H4 well-defined and smooth nanobelts, which have been synthesized via a simple hydrothermal method. The composition and morphology evolutions with the calcination temperatures have been investigated in detail for as-prepared precursor nanobelts, suggesting that they can be easily transformed into ZnO nanobelts by preserving their initial morphology via calcination in air. In contrast, the obtained ZnO nanobelts are densely porous, owing to the thermal decomposition and oxidization of the precursor nanobelts. More importantly, the achieved porous ZnO nanobelts are single-crystalline, different from previously reported ones. Motivated by the intrinsic properties of the porous structure and good electronic transporting ability of single crystals, their gas-sensing performance has been further explored. It is demonstrated that porous ZnO single-crystalline nanobelts exhibit high response and repeatability toward volatile organic compounds, such as ethanol and acetone, with a short response/recovery time. Furthermore, their optoelectronic behaviors indicate that they can be promisingly employed to fabricate photoelectrochemical sensors.
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Lagerstroemia villosa is a kind of ornamental tree with surprising potential for applying in the landscape. We characterized the complete chloroplast genome of this scarce species and analyzed its phylogeny within Lythraceae. The result showed that the genome possessed a typical quadripartite structure, in more detail, a lager single-copy region (LSC, 88,702bp), a small single-copy region (SSC, 18,255bp), and a pair of inverted repeat regions (IRa and IRb, 26,906 bp). 78 protein-coding genes, four ribosomal RNA (rRNA) genes, and 30 transfer RNA (tRNA) genes were detected. Phylogenetic analysis based on maximum likelihood (ML) supported the closest relationship between L. villosa and Lagerstroemia limii plus Lagerstroemia subcostata.
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Trapa bispinosa Roxb. is an annual aquatic herb with great significance of medicinal, edible and economic value. Here, we reported the complete chloroplast genome sequence of Trapa bispinosa and conducted preliminary investigation of its phylogenetic relationship with other related species. As the result showed, the whole chloroplast genome size was 155,556 bp consisting of four adjoining regions, i.e., a large/small single copy (LSC, 88,506 bp/SSC, 18,274 bp) region and two inverted repeat (IRs, 24,388 bp) regions. Among 112 identified unique genes were 78 protein coding genes, 30 transfer RNA (tRNA) genes, and four ribosomal RNA (rRNA) genes. Trapa spp. were precisely clustered as a monophyly, and simultaneously, the closest relation between Trapa bispinosa and Trapa natans were strongly supported in the maximum likelihood analysis.
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OBJECTIVE: To explore a chemotherapeutic regimen suitable for non-small cell lung cancer (NSCLC) in elderly patients. METHODS: A total of 68 elderly patients with NSCLC (stage IIIb/IV) were equally and randomly divided into single-agent and combined groups. Patients in single-agent group received gemcitabine 1000 mg/m(2) at Days 1 and 8 for a 21-day cycle. Those in combined group received gemcitabine 1000 mg/m(2) at Days 1 and 8 in combination carboplatin AUC5 at Day 2 for a 21-day cycle. The drugs were intravenously administered. All patients received 3 cycles of treatment. RESULTS: In single-agent and combined groups, CR 1 and 1, PR 12 and 13, response rates 38% and 41% were respectively observed. There was no statistically significant difference between two groups (P > 0.05). The 1-year and 2-year survival rates of single-agent and combined groups were 31% vs 32% and 12% vs 14% with a median survival of 9.9 and 9.8 months without a statistically significant difference (P > 0.05). The rates of leucopenia and thrombocytopenia (III-IV degree) were 47% and 38% in combined group and they were higher than 24% and 15% in single-agent group with a statistically significant difference (P < 0.05). The observer scale of lung cancer symptom scale showed that the post-treatment scores of appetite, fatigue and pain significantly improved in single-agent group while no improvement was observed in combined group. Also the scores of appetite, fatigue and pain of single-agent group were higher than those of combined group after chemotherapy (P < 0.05). CONCLUSION: Single-agent gemcitabine regimen is more suitable for advanced NSCLC in elderly patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , GencitabinaRESUMO
Pomegranate (Punica granatum L.) is of great significance both as a fruit tree and an ornamental plant. Hereon, we sequenced and characterized the complete chloroplast genome of Punica granatum 'Nana' and performed phylogenetic analysis concerning related species. It turned out that the length of chloroplast genome sequence reached 158,639 bp and exhibited a four-conjoined structure, i.e., a large single copy region (LSC, 89,022 bp), a small single copy region (SSC, 18,685 bp) and twain inverted repeat regions (IRa and IRb, 25,466 bp). 112 unique genes were identified, consisting of 78 protein-coding genes, four ribosomal RNA (rRNA) genes and 30 transfer RNA (tRNA) genes. The result of phylogenetic analysis based on Neighbor-joining (NJ) method was consistent with that of Bayesian inference (BI), which strongly supported that Punica granatum 'Nana' was close to its original species Punica granatum and they together had a close relationship with Heimia myrtifolia within Lythraceae.
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OBJECTIVE: To explore the curative efficacy of methotrexate(MTX) combined with rituxan for treating patients with primary central nervous system(CNS) lymphoma. METHODS: One hundred patients with primary CNS lymphoma in our hospital were randomly divided into targeted treatment group(50 cases) and traditional treatment group (50 cases). Targeted treatment group adopted the therapy of high-dose methotrexate combined with rituxan, the traditional treatment group adopted the high-dose methotrexate combined with whole brain radiotherapy. The results of relevant imaging examination, clinical data, imaging, follow-up and the survival time were analysed and compared between these 2 groups. RESULTS: In the targeted therapy group, there were 33 cases in CR, 9 cases were in stable condition, and 5 cases were in partial response, and 3 cases in the progressive stage. In the group of traditional treatment group, 29 cases reached complete remission, 5 cases were in stable condition, 11 cases were in partial response, and 5 cases were in the progressive stage. In the targeted treatment group and traditional treatment group, the median progression-free survival time was 28 and 11 months, respectively. CONCLUSION: The first choice for treatment scheme of PCNSL is high-dose methotrexate chemotherapy combined with whole brain radiotherapy, that showed a certain curative effect, but the adverse reactions are larger, and a big late neuro toxic reaction may occur, while high-dose methotrexate combined PCNSL rituxan treatment shows high curative effect, less adverse reaction and low side effects. This treatment also has a more positive value for the elderly patients with PCNSL.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Linfoma/tratamento farmacológico , Rituximab/uso terapêutico , Humanos , Metotrexato , Resultado do TratamentoRESUMO
The latest neuroimaging studies about implicit memory (IM) have revealed that different IM types may be processed by different parts of the brain. However, studies have rarely examined what subtypes of IM processes are affected in patients with various brain injuries. Twenty patients with frontal lobe injury, 25 patients with occipital lobe injury, and 29 healthy controls (HC) were recruited for the study. Two subtypes of IM were investigated by using structurally parallel perceptual (picture identification task) and conceptual (category exemplar generation task) IM tests in the three groups, as well as explicit memory (EM) tests. The results indicated that the priming of conceptual IM and EM tasks in patients with frontal lobe injury was poorer than that observed in HC, while perceptual IM was identical between the two groups. By contrast, the priming of perceptual IM in patients with occipital lobe injury was poorer than that in HC, whereas the priming of conceptual IM and EM was similar to that in HC. This double dissociation between perceptual and conceptual IM across the brain areas implies that occipital lobes may participate in perceptual IM, while frontal lobes may be involved in processing conceptual memory.
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Preclinical studies have shown synergism between epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and antifolates in solid tumors. This study is to investigate the efficacy and tolerability of erlotinib plus capecitabine as first-line treatment in older Chinese patients (≥ 65 years) with lung adenocarcinoma. This is an open-label, single arm, multicenter phase II clinical trial. Sixty- two patients with previously untreated stage IIIB/IV adenocarcinoma and age 65 years or above were enrolled at four tertiary teaching hospitals and 2 provincial hospitals in China; 58 patients fulfilled the study requirements. Erlotinib (150 mg/day) and capecitabine (1000 mg/m2 twice daily on days 1-14) were administered during every 21-day cycle. The primary endpoint was the non-progression rate at 12 weeks. EGFR and K-ras mutation rates were determined using PCR. Tumor expression of different biomarkers was assessed using immunohistochemistry. In a cohort of 58 patients, 34 patients had no disease progression at 12 weeks following treatment. The objective response rate was 29.3%, and the disease control rate was 75.9%. The objective response rate was significantly higher in patients with EGFR mutations than in those with wild-type EGFR. Patients with thymidine phosphorylase-negative tumors had significantly longer overall survival after one year than patients with thymidine phosphorylase-positive tumors. Forty-four patients had at least one primary adverse events (AEs), including skin rash (n = 30), grade 3 AEs (n = 17), and grade 4 AEs (n = 7). This is the first phase II clinical trial to assess erlotinib plus capecitabine combination therapy as first-line treatment in older patients with lung adenocarcinoma. Erlotinib/capecitabine chemotherapy was significantly better in patients with EGFR mutations and in those with thymidine phosphorylase-negative tumors. The use of fluorouracil derivatives for the treatment of lung adenocarcinoma warrants further study.
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Adenocarcinoma/tratamento farmacológico , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Genes erbB-1/genética , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Biomarcadores , Capecitabina , China , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Intervalo Livre de Doença , Sinergismo Farmacológico , Quimioterapia Combinada , Cloridrato de Erlotinib , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Genes ras/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Mutação , Estadiamento de Neoplasias , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Timidina Fosforilase/metabolismo , Resultado do TratamentoRESUMO
OBJECTIVE: To determine the effects of 5-hydroxymethyl furfural (5-HMF), an extract of Rehmannia glutinosa Libosch, on several down-regulated signaling molecules involved in learning and memory in hippocampal neurons. METHODS: After cultured for 7 days, primary hippocampal neurons were divided into 5 groups: normal, corticosterone model, RU38486, 5-HMF, and donepezil group. Neuron survival rates were calculated 24 h later using SYTO13-PI double-fluorescence staining and an 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. ß-galactosidase activity was also assayed. Protein expressed by the glucocorticoid receptor (GCR), brainderived neurotrophic factor (BDNF), and N-methyl-D-aspartate receptor 2B (NR2B), as well as phosphorylationcyclic adenosine monophosphate (cAMP) response element binding protein (p-CREB), phosphorylation-extracellular signal-regulated kinase (p-ERK), and phosphorylation-synapsin (p-synapsin) were quantified with Western blot. RESULTS: Hippocampal neuron survival rates and the above-mentioned proteins were dramatically decreased (P<0.05), ß-galactosidase activity was significantly increased in the model group. but the effect was reversed by 5-HMF, RU38486, and to a lesser extent by donepezil (P<0.05). CONCLUSION: 5-HMF extracts from the Chinese herb Rehmannia glutinosa Libosch could protect hippocampal neurons from glucocorticoid injury and from down-regulated signaling molecules in the GCR-BDNF-NR2B-p-ERK-p-CREB-p-synapsin signal transduction pathway.
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Corticosterona/farmacologia , Furaldeído/análogos & derivados , Hipocampo/efeitos dos fármacos , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Rehmannia/química , Transdução de Sinais/efeitos dos fármacos , Animais , Western Blotting , Furaldeído/isolamento & purificação , Furaldeído/farmacologia , Hipocampo/citologia , Neurônios/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
Egg-shell membrane (ESM) is a promising adsorbent for heavy metal uptake. However, carboxylic groups on ESM surface barrier arsenic adsorption. Herein, ESM is modified by esterification and the methyl esterified egg-shell membrane (MESM) possesses positive charge within pH 1-9. As a novel green sorbent material, MESM exhibits 200-fold improvement on sorption capacity of arsenate with respect to bare ESM. It presents an ultra-high selectivity of 256:1 toward arsenate against arsenite. At pH 6, 100% sorption efficiency is achieved for 2 µg L(-1) As(V) by 10 mg MESM, while virtually no adsorption of As(III) is observed. This provides great potential for selective sorption of arsenate in the presence of arsenite. By loading 4.0 mL sample within 0.05-5.00 µg L(-1) As(V) followed by elution with 300 µL HCl (1.5 mol L(-1)), a detection limit of 15 ng L(-1) is obtained along with a RSD of 3.5% at 0.5 µg L(-1). Total inorganic arsenic is achieved by converting As(III) to As(V) and following the same sorption process. This procedure is applied for arsenate determination and inorganic arsenic speciation in Hijiki and water samples. The results are confirmed by graphite furnace atomic absorption spectrometry and spiking recovery.