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Background: Multiple studies from countries with relatively lower PM 2.5 level demonstrated that acute and chronic exposure even at lower than recommended level, e.g., 9 µg/m 3 in the US increased the risk of cardiovascular (CV) events. However, limited studies using individual level data exist from countries with a wider range of PM levels to illustrate shape of the exposure-response curve throughout the range including > 20 µg/m 3 PM 2·5 concentrations. Taiwan with its policies reduced PM 2.5 over time provide opportunities to illustrate the dose response curves and how reductions of PM 2.5 over time correlated with CV events incidence in a nationwide sample. Methods: Using data from the 2009-2019 Taiwan National Health Insurance Database linked to nationwide PM2.5 data. We examined the shape and magnitude of the exposure-response curve between seasonal average PM 2·5 level and CV events-related hospitalizations among older adults at high-risk for CV events. We used history-adjusted marginal structural models including potential confounding by individual demographic factors, baseline comorbidities, and health service measures. To quantify the risk below and above 20 µg/m 3 we conducted stratified Cox regression. We also plotted PM 2.5 and CV events from 2009-2019 as well as average temperature as a comparison. Findings: Using the PM 2.5 concentration <15 µg/m 3 (Taiwan regulatory standard) as a reference, the seasonal average PM 2.5 concentration (15-23.5µg/m 3 and > 23.5 µg/m 3 ) were associated with hazard ration of 1.13 (95%CI 1.09-1.18) and 1.19 (95%CI 1.14-1.24), 1.07 (95%CI 1.03-1.11) and 1.14 (95%CI 1.10-1.18), 1.22 (95%CI 1.08-1.38) and 1.31 (95%CI 1.16-1.48), 1.04 (95%CI 0.98-1.10) and 1.10 (95%CI 1.04-1.16) respectively for HF, IS/TIA,PE/DVT and MI/ACS. A nonlinear relationship between PM 2·5 and CV events outcomes was observed at PM 2·5 levels above 20 µg/m 3 . Interpretation: A nonlinear exposure-response relationship between PM2·5 concentration and the incidence of cardiovascular events exists when PM2.5 is higher than the levels recommended by WHO Air Quality Guidelines. Further lowering PM2·5 levels beyond current regulatory standards may effectively reduce the incidence of cardiovascular events, particularly HF and DVT, and can lead to tangible health benefits in high-risk elderly population.
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Colorectal cancer (CRC) is notable for its high mortality and high metastatic characteristics. The shear force generated by bloodstream provides mechanical signals regulating multiple responses of cells, including metastatic cancer cells, dispersing in blood vessels. We, therefore, studied the effect of shear flow on circulating CRC cells in the present study. The CRC cell line SW620 was subjected to shear flow of 12.5 dynes/cm2 for 1 and 2 h separately. Resulting elevated caspase-9 and -3 indicated that shear flow initiated the apoptosis of SW620. Enlarged cell size associated with a higher level of cyclin D1 was coincident with the flow cytometric results indicating that the cell cycle was arrested at the G1 phase. An elevated phosphor-eNOSS1177 increased the production of nitric oxide and led to reactive oxygen species-mediated oxidative stress. Shear flow also regulated epithelial-mesenchymal transition (EMT) by increasing E-cadherin and ZO-1 while decreasing Snail and Twist1. The migration and invasion of sheared SW620 were also substantially decreased. Further investigations showed that mitochondrial membrane potential was significantly decreased, whereas mitochondrial mass and ATP production were not changed. In addition to the shear flow of 12.5 dynes/cm2, the expressions of EMT were compared at lower (6.25 dynes/cm2) and at higher (25 dynes/cm2) shear flow. The results showed that lower shear flow increased mesenchymal characteristics and higher shear flow increased epithelial characteristics. Shear flow reduces the malignancy of CRC in their metastatic dispersal that opens up new ways to improve cancer therapies by applying a mechanical shear flow device.
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Apoptose , Movimento Celular , Neoplasias Colorretais , Transição Epitelial-Mesenquimal , Espécies Reativas de Oxigênio , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Estresse Mecânico , Potencial da Membrana Mitocondrial , Ciclina D1/metabolismo , Estresse Oxidativo , Caderinas/metabolismo , Óxido Nítrico/metabolismo , Caspase 9/metabolismo , Caspase 3/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo , Proteína 1 Relacionada a Twist/metabolismoRESUMO
Four ethanol fractionated crude extracts (EFCEs [A-D]) purified from the leaves of Cinnamomum macrostemon Hayata were screened for antioxidative effects and mitochondrial function in HaCaT cells. The higher cell viability indicated that EFCE C was mildly toxic. Under the treatment of 50 ng/mL EFCE C, the hydrogen peroxide (H2O2)-induced cytosolic and mitochondrial reactive oxygen species levels were reduced as well as the H2O2-impaired cell viability, mitochondrial membrane potential (MMP), ATP production, and mitochondrial mass. The conversion of globular mitochondria to tubular mitochondria is coincident with EFCE C-restored mitochondrial function. The mitophagy activator rapamycin showed similar effects to EFCE C in recovering the H2O2-impaired cell viability, MMP, ATP production, mitochondrial mass, and also mitophagic proteins such as PINK1, Parkin, LC3 II, and biogenesis protein PGC-1α. We thereby propose the application of EFCE C in the prevention of oxidative stress in skin cells.
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Sobrevivência Celular , Cinnamomum , Peróxido de Hidrogênio , Queratinócitos , Potencial da Membrana Mitocondrial , Mitocôndrias , Mitofagia , Estresse Oxidativo , Extratos Vegetais , Espécies Reativas de Oxigênio , Humanos , Mitofagia/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/citologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Cinnamomum/química , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Trifosfato de Adenosina/metabolismo , Folhas de Planta/química , Antioxidantes/farmacologia , Ubiquitina-Proteína Ligases/metabolismo , Sirolimo/farmacologia , Células HaCaT , Proteínas Quinases/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genéticaRESUMO
BACKGROUND: Circulating metabolites (CM) play a pivotal role in our overall health, yet the current evidence concerning the involvement of diverse CM in benign prostatic hyperplasia (BPH) remains limited. Mendelian randomization (MR) offers a promising avenue to explore the potential impact of CM on BPH. METHODS: In a forward MR analysis, a cohort of 249 circulating metabolites was employed as exposures to investigate their potential associations with BPH risk. Conversely, in a reverse MR analysis, BPH was employed as an exposure to assess its effects on CM. RESULTS: The forward MR analysis discerned a linkage between six metabolites and BPH, with careful consideration to excluding heterogeneity and pleiotropy. Subsequently, the reverse MR analysis unveiled that nine metabolic compounds, mainly comprising phospholipids and triglycerides, potentially exhibit elevated levels in BPH patients. CONCLUSION: Bidirectional MR analysis furnishes genetic insight into the interplay between CM and BPH. The prominence of lipids and triglycerides emerges as significant factors intricately linked to BPH risk.
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Hiperplasia Prostática , Masculino , Humanos , Hiperplasia Prostática/genética , Hiperplasia , Análise da Randomização Mendeliana , Próstata , TriglicerídeosRESUMO
OBJECTIVE: To measure the association between ambient heat and hypoglycemia-related emergency department visit or hospitalization in insulin users. RESEARCH DESIGN AND METHODS: We identified cases of serious hypoglycemia among adults using insulin aged ≥65 in the U.S. (via Medicare Part A/B/D-eligible beneficiaries) and Taiwan (via National Health Insurance Database) from June to September, 2016-2019. We then estimated odds of hypoglycemia by heat index (HI) percentile categories using conditional logistic regression with a time-stratified case-crossover design. RESULTS: Among â¼2 million insulin users in the U.S. (32,461 hypoglycemia case subjects), odds ratios of hypoglycemia for HI >99th, 95-98th, 85-94th, and 75-84th percentiles compared with the 25-74th percentile were 1.38 (95% CI, 1.28-1.48), 1.14 (1.08-1.20), 1.12 (1.08-1.17), and 1.09 (1.04-1.13) respectively. Overall patterns of associations were similar for insulin users in the Taiwan sample (â¼283,000 insulin users, 10,162 hypoglycemia case subjects). CONCLUSIONS: In two national samples of older insulin users, higher ambient temperature was associated with increased hypoglycemia risk.
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Diabetes Mellitus , Hipoglicemia , Idoso , Humanos , Estados Unidos/epidemiologia , Insulina/efeitos adversos , Estudos Cross-Over , Hipoglicemiantes , Temperatura Alta , Taiwan/epidemiologia , Estudos Retrospectivos , Medicare , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Insulina Regular HumanaRESUMO
Background: To explore the clinical significance of miR-125b-5p and its potential mechanisms in lung squamous cell carcinoma (LUSC). Materials and Methods: An integrated analysis of data from in-house quantitative real-time polymerase chain reaction (qRT-PCR), microRNA-sequencing, and microarray assays to appraise the expression level of miR-125b-5p in LUSC tissues compared to adjacent noncancerous controls. The authors identified the candidate targets of miR-125b-5p and conducted functional analysis using computational biology strategies from gene ontology, the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, disease ontology (DO), and protein-protein interaction (PPI) network analyses to investigate the prospective mechanisms. Results: According to qRT-PCR results, the expression level of miR-125b-5p was markedly decreased in LUSC tissues compared to noncancerous control tissues. Receiver operating characteristic and summary receiver operating characteristic analyses showed that miR-125b-5p had good specificity and sensitivity for distinguishing LUSC tissue from noncancerous lung tissue. The standard mean difference revealed that men and women with lower expression levels of miR-125b-5p may have a higher risk for LUSC. KEGG analysis and DO analysis intimated that target genes were evidently enriched in pyrimidine metabolism and pancreatic carcinoma. The PPI network of the top assembled KEGG pathway indicated that RRM2, UMPS, UCK2, and CTPS1 were regarded as crucial target genes for miR-125b-5p, and RRM2 was eventually deemed a key target. Conclusions: The authors' findings implicate a low expression level of miR-125b-5p in LUSC. A tumor-suppressive role of miR-125b-5p is proposed, based on its effects on LUSC tumor growth, clinical stage progression, and lymph node metastasis.
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Carcinoma de Células Escamosas , Neoplasias Pulmonares , MicroRNAs , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
After many years of the excessive use of praziquantel against Schistosoma mansoni (S. mansoni), it has already led to the development of drug resistance. While schistosomiasis is still affecting millions of people every year, vaccination may be one realistic alternative way to control the disease. Currently, S. mansoni 14-kDa fatty acid-binding protein (Sm14) has shown promising results as a vaccine antigen. Yet, the use of an adjuvant may be necessary to further increase the effectiveness of the vaccine. Herein, we investigated the potential of using heat-killed Cutibacterium acnes (C. acnes) as an adjuvant for recombinant Sm14 (rSm14). Immunization of mice with C. acnes-adjuvanted rSm14 showed increased humoral immune responses, compared with mice immunized with rSm14 alone. Additionally, C. acnes-adjuvanted rSm14 vaccination provided higher protection to mice against S. mansoni infection and liver injuries. These results suggest that C. acnes increases the immunogenicity of rSm14, which leads to better protection against S. mansoni infection. Therefore, heat-killed C. acnes may be a promising adjuvant to use with rSm14.
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Proteínas de Transporte de Ácido Graxo/imunologia , Proteínas de Helminto/imunologia , Imunogenicidade da Vacina , Propionibacteriaceae/química , Schistosoma mansoni/imunologia , Esquistossomose mansoni/prevenção & controle , Vacinas/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Climate warming may have an impact on invasive species and their ecological consequences. Invasive reptiles, which have temperature-dependent physiology, are expected to be greatly impacted by climate warming, though data supporting this is limited. We investigated the potential impact of a warmer climate on an invasive lizard, Eutropis multifasciata, in Taiwan. A mechanistic model, NicheMapR, was used to simulate the maximum activity time available at three elevations, with varying forest densities, under the current climate and a warmer scenario. The results show that climate warming will provide this species more time for activity in the currently occupied lowland region but not in the mountain areas, which are covered with dense forests. However, if the landscape becomes more open in mountain areas, it will become more suitable for this species and may enable an expansion upslope. Our results show that climate warming has a positive impact on this species, and that landscape's characteristics profoundly modulate its impact and the possibilities for elevational expansion in the future.
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Mudança Climática , Espécies Introduzidas , Lagartos/fisiologia , Altitude , Animais , Temperatura Corporal , Feminino , Florestas , Masculino , Modelos Teóricos , Solo , Taiwan , TemperaturaRESUMO
Ni-rich layered oxides, like LiNi0.8Co0.1Mn0.1O2 (NCM811), have been widely investigated as cathodes due to their high energy density. However, gradual structural transformation during cycling can lead to capacity degradation and potential decay of cathode materials. Herein, we doped high-valence transition metal (TM) ions (V5+, Nb5+, and Zr4+) at the Ni site of NCM811 by first principles simulations and explored the mechanism of doping TMs in NCMs for enhancing the electrochemical performance. Analysis of the calculations shows that doping V, Nb and Zr has an efficient influence on alleviating the Ni oxidation, reducing the loss of oxygen, and facilitating Li+ migration. Moreover, V doping can further suppress the lattice distortion due to the radius of V5+ being close to the radius of Mn4+. In particular, compared with the barrier of the pristine NCM in Li divacancy, the barrier of V-doped NCM reaches the lowest. In conclusion, V is the most favorable dopant for NCM811 to improve the electrochemical properties and achieve both high capacity and cycling stability.
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1: The decrease of temperatures along an elevation gradient imposes physiological constraints on reptiles that ultimately determine their distribution ranges. Forest patterns are likely to interact with this process, but very few studies have examined their contribution in determining distribution limits. 2: We examined the role played by thermal physiology and forest cover in determining the elevational ranges of a lizard, Eutropis longicaudata. We integrated this species' thermal traits in simulating its maximum activity time under different conditions of forest cover and elevation using a NicheMapR model. In addition, we evaluated the influence of winter temperatures on the range limit by examining the simulated soil temperatures at the occurrence sites. 3: Laboratory experiments showed that E. longicaudata has a high preferred body temperature and low cold tolerance. The model predicts that maximum activity time decreases with elevation and forest cover. Although unforested areas may provide longer active time in all simulated elevations, mountain areas in Taiwan are heavily forested and are predicted to allow only a very short period of activity above 1000 m elevation. 4: All sightings were indeed located in areas below 1000 m elevation, in which the predicted average soil temperature is above 10 °C in January in cold years. 5: Our results show that reptile physiological response does respond strongly to the change of microclimate induced by forest cover and elevation. Overall, this suggests that forest cover is a major determinant of some reptiles' elevational range.
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Aclimatação , Altitude , Temperatura Corporal , Lagartos/fisiologia , Temperatura , Distribuição Animal , Animais , Florestas , TaiwanRESUMO
Lung squamous cell carcinoma (LUSC) is the main pathological type of pulmonary malignant tumors; at present, less than 10% of patients with advanced metastatic LUSC live for more than 5 years. We previously reported that low expression of miRNA-126-3p is associated with the occurrence and progression of lung adenocarcinoma (LUAD). Here, we examined expression of miRNA-126-3p in 23 samples from patients with LUSCs and 23 normal control specimens by quantitative real-time PCR (RT-qPCR). Associations between miRNA-126-3p expression and clinical features were studied from materials derived from Gene Expression Omnibus (GEO) chips and The Cancer Genome Atlas (TCGA) database. Twelve online platforms were used to identify candidate target genes of miRNA-126-3p. Further analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and protein-protein interaction (PPI) network were performed on the target genes. GEO microarray analysis, TCGA data mining, RT-qPCR, and integration analysis consistently reported low expression of miRNA-126-3p in LUSC. A total of 42 genes were identified as potential target genes of miRNA-126-3p from online platforms, GEO microarrays, and the TCGA database. GO and KEGG analyses demonstrated that the target genes are involved in several biological processes that promote the progression of LUSC. SOX2, E2F2, and E2F3 were selected as hub genes from the PPI network for further analysis. In summary, our results suggest that the low expression of miRNA-126-3p may play a role in promoting the development of LUSC and miRNA-126-3p may be a biomarker for LUSC early diagnosis and prognosis.
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Carcinoma de Células Escamosas/metabolismo , Regulação para Baixo , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , MicroRNAs/genética , MicroRNAs/isolamento & purificação , Pessoa de Meia-IdadeRESUMO
The clinical characteristics of patients with COVID-19 were analysed to determine the factors influencing the prognosis and virus shedding time to facilitate early detection of disease progression. Logistic regression analysis was used to explore the relationships among prognosis, clinical characteristics and laboratory indexes. The predictive value of this model was assessed with receiver operating characteristic curve analysis, calibration and internal validation. The viral shedding duration was calculated using the Kaplan-Meier method, and the prognostic factors were analysed by univariate log-rank analysis and the Cox proportional hazards model. A retrospective study was carried out with patients with COVID-19 in Tianjin, China. A total of 185 patients were included, 27 (14.59%) of whom were severely ill at the time of discharge and three (1.6%) of whom died. Our findings demonstrate that patients with an advanced age, diabetes, a low PaO2/FiO2 value and delayed treatment should be carefully monitored for disease progression to reduce the incidence of severe disease. Hypoproteinaemia and the fever duration warrant special attention. Timely interventions in symptomatic patients and a time from symptom onset to treatment <4 days can shorten the duration of viral shedding.
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Betacoronavirus/fisiologia , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Eliminação de Partículas Virais/fisiologia , Adulto , Análise de Variância , COVID-19 , China , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Progressão da Doença , Feminino , Humanos , Hipoproteinemia , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Fatores de TempoRESUMO
1. Temperature rise due to climate change affects seasonal activity times, leading to a discordance of phenology among species and changing the strength of interaction between species. Understanding how temperature changes will affect the length of a species' activity period is essential in order to forecast its response to climate warming. 2. We investigated the thermal physiology and monthly activity of a skink from subtropical areas in Taiwan, Scincella formosensis. In addition, we predicted its response to climate warming and potential landscape vegetation changes using a mechanistic model, Niche MapperTM. We incorporated the animals' thermal traits and climatic data to simulate thermally suitable time for activity each month in two sites (open area, dense forest). 3. We found that this species restricts its activity to the cool months of the year, and that juveniles emerge in June. The thermally suitable period for activity is predicted to be longer in cool months than warm months. 4. Our model predicts that a 3 °C increase in temperature will curtail the thermally suitable time for activity in open areas in late spring and result in very minimal time for activity in the summer, even when dense forest is available. These results add to the growing body of literature indicating that a temperature rise will have a widespread impact on sub/tropical forest reptiles.
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Comportamento Animal , Mudança Climática , Lagartos/fisiologia , Aclimatação , Animais , Temperatura Corporal , Movimento , Estações do Ano , Taiwan , Clima TropicalRESUMO
Accurate evaluation of habitat availability for wildlife is relevant for ecological applications. Researchers have frequently used models to simulate habitats thermally suitable for reptiles, but these results have limited application for species highly selective for habitat humidity. Here, we use the biophysical Niche Mapper™ model to investigate impacts of vegetation cover on the habitat quality of a high-elevation forest skink, Sphenomorphus taiwanensis, and to predict changes in habitat suitability in a future warmer climate (3 °C increase in air temperature). We assess habitat suitability with different densities of canopy cover in our study areas using two ecologically relevant estimates for lizards: maximum activity time and evaporative water loss (EWL) during the activity season. We measured preferred body temperature and EWL of this species for model parameterization, and behavioral response to EWL to supplement habitat quality assessment. The results indicated that this species is sensitive to EWL and reduces its activity when dehydrated. The model predicted that denser canopy levels increase microclimate cooling and humidity, and that most canopy levels are thermally suitable for this species, as the lizard can thermoregulate to manage adverse temperatures. Nevertheless, increasing canopy density could significantly decrease EWL during activity. In the warmer climate scenario, simulated maximum activity time and EWL changed little because of thermoregulation behavior. Our results suggest that habitat preference of this species is a consequence of water and energy requirements, and we note that combining EWL and maximum activity time data can enhance model accuracy of lizards' habitat quality in a warmer climate.
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Lagartos , Água , Animais , Ecossistema , Florestas , MicroclimaRESUMO
1. The invasive many-lined sun skink, Eutropis multifasciata, is established in much of southern Taiwan and is spreading northward. We investigated whether winter temperatures constrain further dispersion of this skink by comparing its cold tolerance to the spatial distribution of winter temperatures in Taiwan. 2. We measured the 28-day survival rate of this species at 4 constant temperatures (10-16 °C in 2 °C increments) and its critical thermal minimum (CTmin), i.e., the body temperature at which the righting reflex is lost during the cooling process. For comparison with the spatial distribution of temperatures over Taiwan, we used the biophysical model Niche Mapper™ in order to simulate the soil temperatures, where lizards are inactive in the winter, during the coldest month of the year, January, under three climatic scenarios (average temperature, average-3 °C, average+3 °C). 3. Our results indicate that this species has low tolerance to cold. Combining cold tolerance data with soil temperature data suggests that its upper elevation limit could range from 1000â¯m to 1500â¯m, above which the weather is lethal and precludes overwintering. The locations of sightings of E. multifasciata are consistent with this prediction, with no known locations above 500â¯m elevation. 4. This study highlights that the winter climate is a major factor in determining population establishment and hence in limiting this species' range. Future studies would benefit from accounting for low winter temperatures and their potential influence on range limits of invasive species.
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Resposta ao Choque Frio , Espécies Introduzidas , Lagartos/fisiologia , Aclimatação , Distribuição Animal , Animais , Temperatura Baixa , Feminino , Masculino , Estações do Ano , Taiwan , TermotolerânciaRESUMO
BACKGROUND: Previous studies have shown that miR-144-3p might be a potential biomarker in non-small cell lung cancer (NSCLC). Nevertheless, the comprehensive mechanism behind the effects of miR-144-3p on the origin, differentiation, and apoptosis of NSCLC, as well as the relationship between miR-144-3p and clinical parameters, has been rarely reported. METHODS: We investigated the correlations between miR-144-3p expression and clinical characteristics through data collected from Gene Expression Omnibus (GEO) microarrays, the relevant literature, The Cancer Genome Atlas (TCGA), and real-time quantitative real-time PCR (RT-qPCR) analyses to determine the clinical role of miR-144-3p in NSCLC. Furthermore, we investigated the biological function of miR-144-3p by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Protein-protein interaction (PPI) network was created to identify the hub genes. RESULTS: From the comprehensive meta-analysis, the combined SMD of miR-144-3p was - 0.95 with 95% CI of (- 1.37, - 0.52), indicating that less miR-144-3p was expressed in the NSCLC tissue than in the normal tissue. MiR-144-3p expression was significantly correlated with stage, lymph node metastasis and vascular invasion (all P < 0.05). As for the bioinformatics analyses, a total of 37 genes were chosen as the potential targets of miR-144-3p in NSCLC. These promising target genes were highly enriched in various key pathways such as the protein digestion and absorption and the thyroid hormone signaling pathways. Additionally, PPI revealed five genes-C12orf5, CEP55, E2F8, STIL, and TOP2A-as hub genes with the threshold value of 6. CONCLUSIONS: The current study validated that miR-144-3p was lowly expressed in NSCLC. More importantly, miR-144-3p might function as a latent tumor biomarker in the prognosis prediction for NSCLC. The results of bioinformatics analyses may present a new method for investigating the pathogenesis of NSCLC.
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Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Análise de Sequência de RNA/métodos , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Bases de Dados Genéticas , Regulação para Baixo/fisiologia , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , MicroRNAs/biossíntese , Pessoa de Meia-Idade , Análise Serial de Proteínas/métodos , Mapas de Interação de Proteínas/fisiologiaRESUMO
In many species, males tend to behave more aggressively than females and female aggression often occurs during particular life stages such as maternal defence of offspring. Though many studies have revealed differences in aggression between the sexes, few studies have compared the sexes in terms of their neuroendocrine responses to contest experience. We investigated sex differences in the endocrine response to social challenge using mangrove rivulus fish, Kryptolebias marmoratus. In this species, sex is determined environmentally, allowing us to produce males and hermaphrodites with identical genotypes. We hypothesized that males would show elevated androgen levels (testosterone and 11-ketotestosterone) following social challenge but that hermaphrodite responses might be constrained by having to maintain both testicular and ovarian tissue. To test this hypothesis, we staged fights between males and between hermaphrodites, and then compared contest behaviour and hormone responses between the sexes. Hermaphrodites had significantly higher oestradiol but lower 11-ketotestosterone than males before contests. Males took longer to initiate contests but tended to fight more aggressively and sustain longer fights than hermaphrodites. Males showed a dramatic post-fight increase in 11-ketotestosterone but hermaphrodites did not. Thus, despite being genetically identical, males and hermaphrodites exhibit dramatically different fighting strategies and endocrine responses to contests.
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Rifampicin (RIF) induces cytochrome P450, which in turn catalyzes drug metabolism; however, pharmacokinetic studies on this phenomenon in the Chinese population, especially in the context of disease, are limited. Therefore, we sought to establish population-based pharmacokinetic models of RIF in a Chinese population with pulmonary tuberculosis (TB). Clinical data were retrospectively collected from 54 patients with pulmonary TB and analyzed alongside RIF blood levels from 95 samples collected prior to RIF administration and between 2 and 12 hours after treatment. HPLC was used to measure serum RIF concentrations. A nonlinear mixed model used to characterize RIF pharmacokinetics and the data generated from the present study were validated using a bootstrap method. Covariates, including demographics, as well as hematological and biological indicators were analyzed. We observed a 1-compartment model with first-order absorption. Typical population values of apparent clearance (CL/F) and apparent volume of distribution (VD /F) were 4.02 L/h and 57.8 L, respectively. No covariate significantly changed the parameters of CL/F and VD . The present study may serve as a foundation for individualized therapy and offer a basis for pharmacokinetic-pharmacodynamic (PK-PD) analysis.
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Antibióticos Antituberculose/farmacocinética , Modelos Biológicos , Rifampina/farmacocinética , Tuberculose Pulmonar/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antituberculose/sangue , Povo Asiático , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rifampina/sangue , Tuberculose Pulmonar/sangue , Adulto JovemRESUMO
Interfacial electronic structures of copper-phthalocyanine (CuPc), cobalt-phthalocyanine (CoPc), and graphene were investigated experimentally by using photoelectron spectroscopy. While the CuPc/graphene interface shows flat band structure and negligible interfacial dipole indicating quite weak molecule-substrate interaction, the CuPc/CoPc/graphene interface shows a large interfacial dipole and obvious energy level bending. Controlled experiments ruled out possible influences from the change in film structure of CuPc and pure π-π interaction between CoPc and CuPc. Analysis based on X-ray photoelectron spectroscopy and density functional theory reveals that the decrease in the work function for the CuPc/CoPc/graphene system is induced by the intermolecular interaction between CuPc and CoPc which is enhanced owning to the peculiar electronic properties at the CoPc-graphene interface.
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The significance of discontinuous gas-exchange cycles (DGC) in reducing respiratory water loss (RWL) in insects is contentious. Results from single-species studies are equivocal in their support of the classic 'hygric hypothesis' for the evolution of DGC, whereas comparative analyses generally support a link between DGC and water balance. In this study, we investigated DGC prevalence and characteristics and RWL in three grasshopper species (Acrididae, subfamily Pamphaginae) across an aridity gradient in Israel. In order to determine whether DGC contributes to a reduction in RWL, we compared the DGC characteristics and RWL associated with CO2 release (transpiration ratio, i.e. the molar ratio of RWL to CO2 emission rates) among these species. Transpiration ratios of DGC and continuous breathers were also compared intraspecifically. Our data show that DGC characteristics, DGC prevalence and the transpiration ratios correlate well with habitat aridity. The xeric-adapted Tmethis pulchripennis exhibited a significantly shorter burst period and lower transpiration ratio compared with the other two mesic species, Ocneropsis bethlemita and Ocneropsis lividipes. However, DGC resulted in significant water savings compared with continuous exchange in T. pulchripennis only. These unique DGC characteristics for T. pulchripennis were correlated with its significantly higher mass-specific tracheal volume. Our data suggest that the origin of DGC may not be adaptive, but rather that evolved modulation of cycle characteristics confers a fitness advantage under stressful conditions. This modulation may result from morphological and/or physiological modifications.