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GLS1 orchestrates glutaminolysis and promotes cell proliferation when glutamine is abundant by regenerating TCA cycle intermediates and supporting redox homeostasis. CB-839, an inhibitor of GLS1, is currently under clinical investigation for a variety of cancer types. Here, we show that GLS1 facilitates apoptosis when glutamine is deprived. Mechanistically, the absence of exogenous glutamine sufficiently reduces glutamate levels to convert dimeric GLS1 to a self-assembled, extremely low-Km filamentous polymer. GLS1 filaments possess an enhanced catalytic activity, which further depletes intracellular glutamine. Functionally, filamentous GLS1-dependent glutamine scarcity leads to inadequate synthesis of asparagine and mitogenome-encoded proteins, resulting in ROS-induced apoptosis that can be rescued by asparagine supplementation. Physiologically, we observed GLS1 filaments in solid tumors and validated the tumor-suppressive role of constitutively active, filamentous GLS1 mutants K320A and S482C in xenograft models. Our results change our understanding of GLS1 in cancer metabolism and suggest the therapeutic potential of promoting GLS1 filament formation.
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Glutaminase , Glutamina , Apoptose , Asparagina/genética , Glutaminase/genética , Glutaminase/metabolismo , Glutamina/metabolismo , Humanos , Espécies Reativas de OxigênioRESUMO
Type 2 diabetes (T2D) is on a notable rise worldwide, which leads to unfavorable outcomes during implant treatments. Surface modification of implants and exosome treatment have been utilized to enhance osseointegration. However, there has been insufficient approach to improve adverse osseointegration in T2D conditions. In this study, we successfully loaded TNF-α-treated mesenchymal stem cell (MSC)-derived exosomes onto micro/nano-network titanium (Ti) surfaces. TNF-α-licensed exosome-integrated titanium (TNF-exo-Ti) effectively enhanced M2 macrophage polarization in hyperglycemic conditions, with increased secretion of anti-inflammatory cytokines and decreased secretion of pro-inflammatory cytokines. In addition, TNF-exo-Ti pretreated macrophage further enhanced angiogenesis and osteogenesis of endothelial cells and bone marrow MSCs. More importantly, TNF-exo-Ti markedly promoted osseointegration in T2D mice. Mechanistically, TNF-exo-Ti activated macrophage autophagy to promote M2 polarization through inhibition of the PI3K/AKT/mTOR pathway, which could be abolished by PI3K agonist. Thus, this study established TNF-α-licensed exosome-immobilized titanium surfaces that could rectify macrophage immune states and accelerate osseointegration in T2D conditions.
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Autofagia , Diabetes Mellitus Tipo 2 , Exossomos , Macrófagos , Camundongos Endogâmicos C57BL , Osseointegração , Titânio , Fator de Necrose Tumoral alfa , Titânio/química , Titânio/farmacologia , Animais , Exossomos/metabolismo , Autofagia/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Osseointegração/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Camundongos , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Polaridade Celular/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismoRESUMO
Droplet impact on soft surfaces (PDMS) was experimentally studied with particular interest in the complete rebound of droplets. This study focuses on the effect of liquid viscosity and the elastic modulus of the substrate on the critical rebound Weber number, maximum spreading, and contact time. Specifically, the lower and upper critical Weber numbers increase with an increasing droplet viscosity. With decreasing PDMS elastic modulus, the upper critical Weber number increases, while the lower critical Weber number decreases. The PDMS elastic modulus does not significantly affect the maximum spreading time and contact time. An interesting phenomenon of discontinuous contact time was experimentally observed and was theoretically interpreted.
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Aiming at challenges such as low efficiency, high missing rate, difficulty in identifying contour defects, and difficulty in extracting tiny defects, a defect detection method for extracting micro and macro scale defects is proposed in this paper. After preprocessing the image, contour detection is performed to identify the contours. Subsequently, a contour complementation algorithm is employed to complement the unclosed contours. Finally, the detection of micro scale defects is conducted based on the grayscale variation of the center of the micro scale defects. The experimental results show that compared with the traditional method, the proposed algorithm can accurately detect the bubble defects of different scales in silicon carbide castings and can identify the complex defects better.
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Currently, natural products are one of the priceless options for finding novel chemical pharmaceutical entities. Ellipticine is a naturally occurring alkaloid isolated from the leaves of Ochrosia elliptica Labill. Ellipticine and its derivatives are characterized by multiple biological activities. The purpose of this review was to provide a critical and systematic assessment of ellipticine and its derivatives as bioactive molecules over the last 60â years. Publications focused mainly on the total synthesis of alkaloids of this type without any evaluation of bioactivity have been excluded. We have reviewed papers dealing with the synthesis, bioactivity evaluation and mechanism of action of ellipticine and its derivatives. It was found that ellipticine and its derivatives showed cytotoxicity, antimicrobial ability, and anti-inflammatory activity, among which cytotoxicity toward cancer cell lines was the most investigated aspect. The inhibition of DNA topoisomerase II was the most relevant mechanism for cytotoxicity. The PI3K/AKT pathway, p53 pathway, and MAPK pathway were also closely related to the antiproliferative ability of these compounds. In addition, the structure-activity relationship was deduced, and future prospects were outlined. We are confident that these findings will lay a scientific foundation for ellipticine-based drug development, especially for anticancer agents.
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Elipticinas , Elipticinas/farmacologia , Elipticinas/química , Humanos , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Estrutura Molecular , Animais , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificaçãoRESUMO
BACKGROUND AND OBJECTIVE: Our study aimed to evaluate the associations between platelet count (PC) and in-hospital outcomes for patients with stroke after rt-PA intravenous thrombolysis. METHODS: We identified patients who had been hospitalized with a primary diagnosis of stroke and had received rt-PA intravenous thrombolysis from June 2015 to July 2019 at participating hospitals in the Chinese Stroke Center Alliance. PC measured before intravenous thrombolysis was categorized into the following four groups: severe thrombocytopenia (PC < 100 × 109/L), mild thrombocytopenia (100 ≤ PC < 150 × 109/L), normal PC (150 ≤ PC ≤ 450 × 109/L), and thrombocythemia (PC > 450 × 109/L). Outcomes were determined from clinical data collected during hospitalization. The primary clinical outcome was symptomatic intracranial hemorrhage (sICH). Secondary outcomes were mortality, bleeding events, gastrointestinal (GI) hemorrhage, and in-hospital stroke recurrence. We used multivariate logistic regression models to evaluate the associations between PC and outcomes. RESULTS: We included 44,882 individuals with a median age of 66 years, of whom 34.7 % were female, 951 (2.1 %) had severe thrombocytopenia, 7218 (16.1 %) had mild thrombocytopenia, 36,522 (81.4 %) had a normal PC, and 191 (0.4 %) had thrombocythemia. Both severe and mild thrombocytopenia groups had higher risks of bleeding events (adjusted OR 1.30; 95 % CI,1.01-1.67; p = 0.045; adjusted OR 1.32; 95 % CI,1.19-1.46; p < 0.001) and sICH (adjusted OR 1.48;95 % CI,1.13-1.94; p = 0.005; adjusted OR 1.43;95 % CI,1.27-1.60; p < 0.001) than the normal PC group. Patients with 100 ≤ PC < 150 × 109/L also had a higher risk of in-hospital stroke recurrence (adjusted OR 1.12; 95 % CI,1.02-1.22; p = 0.02). CONCLUSIONS: Intravenous thrombolysis brings a high risk of sICH given PC < 150 × 109/L, especially PC < 100 × 109/L. It indicated that PC < 100 × 109/L is a reasonable contraindication to thrombolysis.
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Fibrinolíticos , AVC Isquêmico , Sistema de Registros , Trombocitopenia , Terapia Trombolítica , Humanos , Feminino , Masculino , Idoso , Trombocitopenia/diagnóstico , Trombocitopenia/induzido quimicamente , Pessoa de Meia-Idade , AVC Isquêmico/diagnóstico , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/mortalidade , Resultado do Tratamento , China/epidemiologia , Contagem de Plaquetas , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/mortalidade , Fatores de Risco , Fibrinolíticos/administração & dosagem , Fibrinolíticos/efeitos adversos , Fatores de Tempo , Medição de Risco , Recidiva , Ativador de Plasminogênio Tecidual/administração & dosagem , Ativador de Plasminogênio Tecidual/efeitos adversos , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/etiologia , Hemorragias Intracranianas/mortalidade , Mortalidade Hospitalar , Administração Intravenosa , Hemorragia Gastrointestinal/mortalidade , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/diagnósticoRESUMO
Accurate calculation of flow discharge for sluice gates is essential in irrigation, water supply, and structure safety. The measurement of discharge with the requirement of distinguishing flow regimes is not conducive to application. In this study, a novel approach that considers both free and submerged flow was proposed. The energy-momentum method was employed to derive the coefficient of discharge. Subsequently, the discharge coefficient was determined through the experiment which was performed on the physical model of a vertical sluice gate with a broad-crested weir. Feature engineering, incorporating dimensional analysis, feature construction, and correlation-based selection were performed. The best subset regression method was employed to develop regression equations of the discharge coefficient with the generated features. The derived formula was applied to compute the discharge coefficient in the vertical sluice gate and determine the flow discharge. The accuracy of adopted method was assessed by comparing it with recent studies on submerged flow, and the results demonstrate that the developed approach achieves a high level of accuracy in calculating flow discharge. The coefficient of determination for the calculated flow rate is 0.993, and the root mean square percentage error is 5.04%.
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Abastecimento de ÁguaRESUMO
BACKGROUND: To systematically assess the association between cognitive frailty (CF) and malnutrition in older adults. METHODS: 8 databases were retrieved up until April 2023 by two reviewers in dependently, and meta-analysis was performed by Stata 16.0 software. RESULTS: A total of 19 studies were meta-analyzed to assess the relationship between CF and malnutrition in older adults. The pooled prevalence of CF from 17 studies was 23 %, and the pooled prevalence of malnutrition among patients with CF from 12 studies was 57 %. Data from 13 studies on the association between CF and malnutrition unveiled a high risk of CF in older adults with malnutrition (OR = 3.77, 95 % CI: 2.49-5.69). CONCLUSION: The prevalence of malnutrition is high in older adults with CF, and there is a significant delve into targeted treatment and preventive measures to ameliorate the quality of life of older adults.
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Desnutrição , Humanos , Desnutrição/epidemiologia , Idoso , Prevalência , Fragilidade/complicações , Idoso Fragilizado/psicologia , Qualidade de Vida , Avaliação Geriátrica , Disfunção Cognitiva/epidemiologiaRESUMO
Red blood cells are destroyed when the shear stress in the blood pump exceeds a threshold, which in turn triggers hemolysis in the patient. The impeller design of centrifugal blood pumps significantly influences the hydraulic characteristics and hemolytic properties of these devices. Based on this premise, the present study employs a multiphase flow approach to numerically simulate centrifugal blood pumps, investigating the performance of pumps with varying numbers of blades and blade deflection angles. This analysis encompassed the examination of flow field characteristics, hydraulic performance, and hemolytic potential. Numerical results indicated that the concentration of red blood cells and elevated shear stresses primarily occurred at the impeller and volute tongue, which drastically increased the risk of hemolysis in these areas. It was found that increasing the number of blades within a certain range enhanced the hydraulic performance of the pump but also raised the potential for hemolysis. Moreover, augmenting the blade deflection angle could improve the hemolytic performance, particularly in pumps with a higher number of blades. The findings from this study can provide valuable insights for the structural improvement and performance enhancement of centrifugal blood pumps.
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Desenho de Equipamento , Coração Auxiliar , Hemólise , Estresse Mecânico , Humanos , Coração Auxiliar/efeitos adversos , Eritrócitos/citologia , Centrifugação , Simulação por ComputadorRESUMO
Resumption of the increase in atmospheric methane (CH4 ) concentrations since 2007 is of global concern and may partly have resulted from emissions from rice cultivation. Estimates of CH4 emissions from rice fields and abatement potential are essential to assess the contribution of improved rice management in achieving the targets of the Global Methane Pledge agreed upon by over 100 countries at COP26. However, the contribution of CH4 emissions from rice fields to the resumed CH4 growth and the global abatement potential remains unclear. In this study, we estimated the global CH4 emissions from rice fields to be 27 ± 6 Tg CH4 year-1 in the recent decade (2008-2017) based on the 2019 Refinement to the 2006 IPCC Guidelines for National Greenhouse Gas Inventories. The trend of CH4 emissions from rice cultivation showed an increase followed by no significant change and then, a stabilization over 1990-2020. Consequently, the contribution of CH4 emissions from rice fields to the renewed increase in atmospheric CH4 concentrations since 2007 was minor. We summarized the existing low-cost measures and showed that improved water and straw management could reduce one-third of global CH4 emissions from rice fields. Straw returned as biochar could reduce CH4 emissions by 12 Tg CH4 year-1 , equivalent to 10% of the total reduction of all anthropogenic emissions. We conclude that other sectors than rice cultivation must have contributed to the renewed increase in atmospheric CH4 concentrations, and that optimizing multiple mitigation measures in rice fields could contribute significantly to the abatement goal outlined in the Global Methane Pledge.
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Gases de Efeito Estufa , Oryza , Agricultura/métodos , Solo , Metano/análiseRESUMO
Despite the increasing impact of atmospheric nitrogen (N) deposition on terrestrial greenhouse gas (GHG) budget, through driving both the net atmospheric CO2 exchange and the emission or uptake of non-CO2 GHGs (CH4 and N2 O), few studies have assessed the climatic impact of forests and grasslands under N deposition globally based on different bottom-up approaches. Here, we quantify the effects of N deposition on biomass C increment, soil organic C (SOC), CH4 and N2 O fluxes and, ultimately, the net ecosystem GHG balance of forests and grasslands using a global comprehensive dataset. We showed that N addition significantly increased plant C uptake (net primary production) in forests and grasslands, to a larger extent for the aboveground C (aboveground net primary production), whereas it only caused a small or insignificant enhancement of SOC pool in both upland systems. Nitrogen addition had no significant effect on soil heterotrophic respiration (RH ) in both forests and grasslands, while a significant N-induced increase in soil CO2 fluxes (RS , soil respiration) was observed in grasslands. Nitrogen addition significantly stimulated soil N2 O fluxes in forests (76%), to a larger extent in grasslands (87%), but showed a consistent trend to decrease soil uptake of CH4 , suggesting a declined sink capacity of forests and grasslands for atmospheric CH4 under N enrichment. Overall, the net GHG balance estimated by the net ecosystem production-based method (forest, 1.28 Pg CO2 -eq year-1 vs. grassland, 0.58 Pg CO2 -eq year-1 ) was greater than those estimated using the SOC-based method (forest, 0.32 Pg CO2 -eq year-1 vs. grassland, 0.18 Pg CO2 -eq year-1 ) caused by N addition. Our findings revealed that the enhanced soil C sequestration by N addition in global forests and grasslands could be only marginally offset (1.5%-4.8%) by the combined effects of its stimulation of N2 O emissions together with the reduced soil uptake of CH4 .
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Gases de Efeito Estufa , Ecossistema , Pradaria , Dióxido de Carbono/análise , Metano/análise , Óxido Nitroso/análise , Florestas , Solo , NitrogênioRESUMO
The emergence and spread of antibiotic resistance genes (ARGs) in soil due to animal excreta and organic waste is a major threat to human health and ecosystems, and global efforts are required to tackle the issue. However, there is limited knowledge of the variation in ARG prevalence and diversity resulting from different land-use patterns and underlying driving factors in soils. This study aimed to comprehensively characterize the profile of ARGs and mobile genetic elements and their drivers in soil samples collected from 11 provinces across China, representing three different land-use types, using high-throughput quantitative polymerase chain reaction and 16S rRNA amplicon sequencing. Our results showed that agricultural soil had the highest abundance and diversity of ARGs, followed by tea plantation and forest land. A total of 124 unique ARGs were detected in all samples, with shared subtypes among different land-use patterns indicating a common origin or high transmission frequency. Moreover, significant differences in ARG distribution were observed among different geographical regions, with the greatest enrichment of ARGs found in southern China. Biotic and abiotic factors, including soil properties, climatic factors, and bacterial diversity, were identified as the primary drivers associated with ARG abundance, explaining 71.8% of total ARG variation. The findings of our study demonstrate that different land-use patterns are associated with variations in ARG abundance in soil, with agricultural practices posing the greatest risk to human health and ecosystems regarding ARGs. Our identification of biotic and abiotic drivers of ARG abundance provides valuable insights into strategies for mitigating the spread of these genes. This study emphasizes the need for coordinated and integrated approaches to address the global antimicrobial resistance crisis.
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Ecossistema , Solo , Animais , Humanos , Prevalência , RNA Ribossômico 16S , Antibacterianos , Resistência Microbiana a Medicamentos/genéticaRESUMO
Natural products are treasure houses for modern drug discovery. Diphyllin is a natural arylnaphthalene lignan lactone isolated from the leaf of Astilboides tabularis. Studies have found that it possesses plenty of bioactivity characteristics. In this paper, we reviewed the structure, bioactivity, and mechanism of action of diphyllin and its derivatives. The references were obtained from PubMed, Web of Science, and Science Direct databases up to August 2023. Papers without a bio-evaluation were excluded. Diphyllin and its derivatives have demonstrated V-ATPase inhibition, anti-tumor, anti-virus, anti-biofilm, anti-inflammatory, and anti-oxidant activities. The most studied activities of diphyllin and its derivatives are V-ATPase inhibition, anti-tumor activities, and anti-virus activities. Furthermore, V-ATPase inhibition activity is the mechanism of many bioactivities, including anti-tumor, anti-virus, and anti-inflammatory activities. We also found that the galactosylated modification of diphyllin is a common phenomenon in plants, and therefore, galactosylated modification is applied by researchers in the laboratory to obtain more excellent diphyllin derivatives. This review will provide useful information for the development of diphyllin-based anti-tumor and anti-virus compounds.
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Lignanas , Adenosina Trifosfatases , Anti-Inflamatórios/farmacologia , Lactonas , Lignanas/farmacologia , Lignanas/químicaRESUMO
Climate change and air pollution are one of the global environmental problems. It is significant to grasp the air pollution situation of Western Europe in recent 10 years for its or the global pollution control. Based on the OMI tropospheric nitrogen dioxide (NO2) column density data, the spatial and temporal distribution characteristics, variation trend, transmission path, and influencing factors of NO2 in 15 countries in Western Europe from 2011 to 2022 are discussed in this paper. Meanwhile, the annual average spatial and temporal distribution in 2023 is predicted by the random forest (RF) model. The results showed that (1) the 12-year spatial distribution map showed an increasing trend from southwest to northeast, with the border area of the Netherlands and Germany and Milan as two high-value areas, and the overall trend over time was that the high-concentration area gradually shrank, the low-concentration area gradually expanded, and the annual average concentration gradually decreased. (2) The inter-month trend presents a "U" shape, with the mean NO2 pollution ranking in winter > autumn > spring > summer. (3) Natural factors are one of the reasons affecting NO2; for instance, NO2 pollution has a strong positive correlation with the lifted index, relative humidity, and wind speed and a moderately strong negative correlation with precipitable water and air temperature. (4) Exogenous atmospheric transport is another important factor affecting the change of NO2 pollution in Western Europe. The HYSPLIT model is used to analyze the backward trajectory of Milan, Italy, and Nijmegen, Netherlands, in the four seasons of 2022. Both are mainly influenced by westerly airflows, and therefore, the transport effect in the atmosphere brings air pollutants from westerly regions in the atmosphere.
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Poluentes Atmosféricos , Poluição do Ar , Dióxido de Nitrogênio/análise , Monitoramento Ambiental/métodos , Poluição do Ar/análise , Poluentes Atmosféricos/análise , Europa (Continente) , Material Particulado/análise , China , Estações do AnoRESUMO
Inland waters (rivers, reservoirs, lakes, ponds, streams) and estuaries are significant emitters of methane (CH4 ) and nitrous oxide (N2 O) to the atmosphere, while global estimates of these emissions have been hampered due to the lack of a worldwide comprehensive data set of CH4 and N2 O flux components. Here, we synthesize 2997 in-situ flux or concentration measurements of CH4 and N2 O from 277 peer-reviewed publications to estimate global CH4 and N2 O emissions from inland waters and estuaries. Inland waters including rivers, reservoirs, lakes, and streams together release 95.18 Tg CH4 year-1 (ebullition plus diffusion) and 1.48 Tg N2 O year-1 (diffusion) to the atmosphere, yielding an overall CO2 -equivalent emission total of 3.06 Pg CO2 year-1 . The estimate of CH4 and N2 O emissions represents roughly 60% of CO2 emissions (5.13 Pg CO2 year-1 ) from these four inland aquatic systems, among which lakes act as the largest emitter for both CH4 and N2 O. Ebullition showed as a dominant flux component of CH4 , contributing up to 62%-84% of total CH4 fluxes across all inland waters. Chamber-derived CH4 emission rates are significantly greater than those determined by diffusion model-based methods for commonly capturing of both diffusive and ebullitive fluxes. Water dissolved oxygen (DO) showed as a dominant factor among all variables to influence both CH4 (diffusive and ebullitive) and N2 O fluxes from inland waters. Our study reveals a major oversight in regional and global CH4 budgets from inland waters, caused by neglecting the dominant role of ebullition pathways in those emissions. The estimated indirect N2 O EF5 values suggest that a downward refinement is required in current IPCC default EF5 values for inland waters and estuaries. Our findings further indicate that a comprehensive understanding of the magnitude and patterns of CH4 and N2 O emissions from inland waters and estuaries is essential in defining the way of how these aquatic systems will shape our climate.
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Gases de Efeito Estufa , Óxido Nitroso , Dióxido de Carbono/análise , Estuários , Gases de Efeito Estufa/análise , Metano/análise , Óxido Nitroso/análiseRESUMO
BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) prior to surgery is the standard treatment for patients with locally advanced rectal cancer (LARC), while parts of them show poor therapeutic response accompanied by therapy adverse effects. Predictive biomarkers for nCRT response could facilitate the guidance on treatment decisions but are still insufficient until now, which limits the clinical applications of nCRT in LARC patients. METHODS: In our study, 37 formalin-fixed paraffin-embedded tumor biopsies were obtained from patients with LARC before receiving 5-fluorouracil based nCRT. Proteomics analyses were conducted to identify the differentially expressed proteins (DEPs) between total responders (TR) and poor responders (PR). The DEPs were validated via ROC plotter web tool and their predictive performance was evaluated by receiver operating characteristic analysis. Functional enrichment analyses were performed to further explore the potential mechanisms underlying nCRT response. RESULTS: Among 3,998 total proteins, 91 DEPs between TR and PR were screened out. HSPA4, NIPSNAP1, and SPTB all with areas under the curve (AUC) ~ 0.8 in the internal discovery cohort were independently validated by the external mRNA datasets (AUC ~ 0.7), and their protein levels were linearly correlated with the graded responses to nCRT in the internal cohort. The combination of HSPA4 and SPTB could distinctly discriminate the TR and PR groups (AUC = 0.980, p < 0.0001). Moreover, multiple combinations of the three proteins realized increased specificity and/or sensitivity, while achieving favorable predictive value when moderate responders were introduced into the ROC analysis. Pathways including DNA damage repair, cell cycle, and epithelial mesenchymal transition were involved in nCRT response according to the enrichment analysis results. CONCLUSIONS: HSPA4, SPTB and NIPSNAP1 in tumor biopsies and/or their optional combinations might be potential predictive markers for nCRT response in patients with LARC. The DEPs and their related functions have implications for the potential mechanisms of treatment response to nCRT in patients with LARC.
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Increasing tropospheric ozone poses a potential threat to both above- and belowground components of the terrestrial biosphere. Microorganisms are the main drivers of soil ecological processes, however, the link between soil microbial communities and ecological functions under elevated ozone remains poorly understood. In this study, we assessed the responses of three crop seedlings (i.e., soybean, maize, and wheat) growth and soil microbial communities to elevated ozone (40 ppb O3 above ambient air) in a pot experiment in the solardomes. Results showed that elevated ozone adversely affected ecosystem multifunctionality by reducing crop biomass, inhibiting soil extracellular enzyme activities, and altering nutrient availability. Elevated ozone increased bacterial and fungal co-occurrence network complexity, negatively correlated with ecosystem multifunctionality. Changes in the relative abundance of some specific bacteria and fungi were associated with multiple ecosystem functioning. In addition, elevated ozone significantly affected fungal community composition but not bacterial community composition and microbial alpha-diversity. Crop type played a key role in determining bacterial alpha-diversity and microbial community composition. In conclusion, our findings suggest that short-term elevated ozone could lead to a decrease in ecosystem multifunctionality associated with changes in the complexity of microbial networks in soils.
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Microbiota , Ozônio , Bactérias , Ecossistema , Fungos , Ozônio/análise , Ozônio/toxicidade , Solo , Microbiologia do SoloRESUMO
Zebrafish Liver-enriched gene 1a (Leg1a) and Leg1b are liver-produced serum proteins encoded by two adjacently linked homologous genes leg1a and leg1b, respectively. We previously showed that maternal-zygotic (MZ) leg1a null mutant developed a small liver at 3.5 days post-fertilization (dpf) during winter-time or under UV-treatment and displayed an abnormal stature at its adulthood. It is puzzling why Leg1b, which shares 89.3% identity with Leg1a and co-expressed with Leg1a, cannot fully compensate for the loss-of-function of Leg1a in the leg1azju1 MZ mutant. Here we report that Leg1a and Leg1b share eight cysteine residues but differ in amino acid residue 358, which is a serine in Leg1a but cysteine (C358) in Leg1b. We find that Leg1b forms an intermolecular disulfide bond through C358. Mutating C358 to Methionine (M358) does not affect Leg1b secretion whereas mutating other conserved cysteine residues do. We propose that the intermolecular disulfide bond in Leg1b might establish a rigid structure that makes it functionally different from Leg1a under certain oxidative conditions.
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Dissulfetos/química , Regulação da Expressão Gênica , Fígado/crescimento & desenvolvimento , Proteínas de Peixe-Zebra/química , Animais , Proteínas Sanguíneas/química , Cisteína/genética , Masculino , Mutagênese Sítio-Dirigida , Oxigênio/química , Análise de Componente Principal , Conformação Proteica , Serina/química , Regulação para Cima , Peixe-ZebraRESUMO
Neuromyelitis optica spectrum disorders (NMOSD) are a demyelinating disorder of the central nervous system based on the involvement of the optic nerve and/or spinal cord. The disease is characterized by high recurrence and disability. NMOSD is mainly diagnosed by AQP4-IgG and MOG-IgG. However, there are still some patients with negative or undetermined double-antibody, and AQP4-IgG and MOG-IgG cannot indicate the clinical disease activity. Therefore, it is urgent to explore interesting biomarkers in serum and cerebrospinal fluid to promote early clinical diagnosis and/or as a target for diagnosis and treatment. This article summarized the research progress in serum and cerebrospinal fluid biomarkers of astrocytes, neurons, myelin sheath, and other damage after the onset of NMOSD. Besides the value of microglial activation-related proteins in the diagnosis and treatment of NMOSD was prospected, so as to promote the research progress of NMOSD.
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Biomarcadores/metabolismo , Neuromielite Óptica/diagnóstico , Biomarcadores/análise , Humanos , Neuromielite Óptica/metabolismoRESUMO
Synchronous measurement of temperature and deformation at elevated temperatures is highly critical, yet challenging in evaluating mechanical properties of thermal protection systems. An ultraviolet (UV) imaging system is proposed to obtain noncontact, in situ, synchronous, and full-field temperature and deformation. The established system consists of a monochromatic UV illumination with a bandpass filter for radiation suppressing, a UV CCD camera for image capturing, and an infrared pyrometer for temperature recording. Additionally, an improved monochromatic radiation pyrometry method is proposed, while a deformation measuring method using the UV digital image correlation (UV-DIC) and natural textures-generated speckle is introduced. Furthermore, through camera calibration at room temperature and real-time exposure time adjusted at elevated temperatures, the influence of reflection on radiation pyrometry and unfiltered radiation on DIC analysis is eliminated. Synchronous temperature and deformation fields of C/SiC subjected to flame heating are experimentally measured with a temperature range of 500°C-1500°C, and results demonstrate the efficacy and potential of the proposed system and method. Finally, the importance of exposure time on balancing the light intensity of radiation and reflection is also discussed.