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PURPOSE: This study aimed to evaluate whether axillary lymph node dissection (ALND) can be omitted in patients with 1-2 positive sentinel lymph nodes (SLNs) who received total mastectomy (TM). METHODS: Consecutive breast cancer patients with 1-2 positive SLNs were retrospectively reviewed from a multi-institutional database. Patients were divided into sentinel lymph node biopsy (SLNB) group and ALND group. Administration of adjuvant chemotherapy and survival were compared between groups. To further verify the results, a meta-analysis was also conducted. RESULTS: Among the 1161 enrolled patients, 893 (76.9%) received ALND and 268 (23.1%) underwent SLNB alone. Administration of chemotherapy was comparable between the two groups (91.1% vs. 90.6%, P = 0.798), which was consistent in TM (P = 0.638) and BCS cohort (P = 0.576). After a median follow-up of 36 months, no significant difference was observed between the two groups in recurrence-free survival (P = 0.583) regardless of surgery of breast. During further meta-analysis, 13 out of 4733 relative studies reported the association of axillary surgery and disease-free survival (DFS) or overall survival (OS) in 1-2 positive SLNs patients. Pooled analysis showed no difference in adjusted DFS (HR 0.84, 95% CI 0.70-1.02) or OS (HR 1.02, 95% CI 0.93-1.11) between SLNB and ALND groups. Survival benefit of ALND remained non-significant after restricting the analysis in four studies with patients only receiving BCS, or in three studies with patients only receiving TM. CONCLUSION: Further ALND does not impact adjuvant chemotherapy administration or disease outcome in breast cancer patients with 1-2 positive SLNs treated with TM.
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Neoplasias da Mama , Linfonodo Sentinela , Axila/patologia , Neoplasias da Mama/patologia , Feminino , Humanos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Linfonodos/cirurgia , Mastectomia/efeitos adversos , Estudos Retrospectivos , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela/métodosRESUMO
The alpine grasslands of the Tibetan Plateau store 23.2 Pg soil organic carbon, which becomes susceptible to microbial degradation with climate warming. However, accurate prediction of how the soil carbon stock changes under future climate warming is hampered by our limited understanding of belowground complex microbial communities. Here, we show that 4 years of warming strongly stimulated methane (CH4 ) uptake by 93.8% and aerobic respiration (CO2 ) by 11.3% in the soils of alpine grassland ecosystem. Due to no significant effects of warming on net ecosystem CO2 exchange (NEE), the warming-stimulated CH4 uptake enlarged the carbon sink capacity of whole ecosystem. Furthermore, precipitation alternation did not alter such warming effects, despite the significant effects of precipitation on NEE and soil CH4 fluxes were observed. Metagenomic sequencing revealed that warming led to significant shifts in the overall microbial community structure and the abundances of functional genes, which contrasted to no detectable changes after 2 years of warming. Carbohydrate utilization genes were significantly increased by warming, corresponding with significant increases in soil aerobic respiration. Increased methanotrophic genes and decreased methanogenic genes were observed under warming, which significantly (R2 = .59, p < .001) correlated with warming-enhanced CH4 uptakes. Furthermore, 212 metagenome-assembled genomes were recovered, including many populations involved in the degradation of various organic matter and a highly abundant methylotrophic population of the Methyloceanibacter genus. Collectively, our results provide compelling evidence that specific microbial functional traits for CH4 and CO2 cycling processes respond to climate warming with differential effects on soil greenhouse gas emissions. Alpine grasslands may play huge roles in mitigating climate warming through such microbially enhanced CH4 uptake.
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Ecossistema , Metano , Metano/análise , Pradaria , Sequestro de Carbono , Solo/química , Carbono , Dióxido de Carbono/análise , TibetRESUMO
BACKGROUND: Invasive ductal carcinoma (IDC) is often accompanied by ductal carcinoma in situ (DCIS). Whether the DCIS component affects the 21-gene recurrence score (RS) is unclear. METHODS: Consecutive ER-positive, HER2-negative, N0-1 patients with RS results were included. Patients were divided into pure IDC and IDC with DCIS (IDC/DCIS) groups. The RS, the expression of its 16 cancer genes and prognosis were compared between IDC and IDC/DCIS patients. RESULTS: A total of 1458 patients were enrolled, 320 of whom had concomitant DCIS. DCIS component was independently associated with lower RS (P = 0.038). IDC/DCIS patients more often had a low-risk RS (P = 0.018) or intermediate-risk RS (P = 0.024). Regarding individual genes in the RS panel, Ki67, CCNB1 and MYBL2 in the proliferation group and MMP11 and CTSL2 in the invasion group were significantly lower among IDC/DCIS patients than pure IDC patients. Among IDC/DCIS patients, lower RS was independently correlated with a higher DCIS proportion and lower DCIS grade. Within a median follow-up of 31 months, the DCIS component in IDC did not significantly influence prognosis. CONCLUSIONS: IDC with DCIS component is associated with a lower 21-gene RS, possibly due to lower expression of proliferation and invasion genes. DCIS proportion and grade independently influenced the 21-gene RS in IDC/DCIS patients. Due to the relatively short follow-up period and low recurrence rate, the impact of the DCIS component in IDC on prognosis needs further evaluation.
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Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma Intraductal não Infiltrante/genética , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
PURPOSE: Given the histological special types (HST) of breast carcinoma accounted for minority of the Z0011 study population, this study aimed to assess the rates of axillary lymph node (ALN) involvement and non-sentinel lymph node (SLN) metastasis in patients with invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), or other HST. METHODS: Patients with cT1-2N0M0 breast cancer treated between 2009 and 2018 were retrospectively included from a multi-institutional database. Rates of nodal involvement were analyzed among different histological subgroups. The impact of ALN dissection (ALND) on adjuvant treatment decisions and prognosis were also analyzed among patients with 1-2 + SLNs. RESULTS: A total of 8294 patients were included: 6854 (82.6%), 257 (3.1%), and 1183 (14.3%) patients with IDC, ILC, and other HST, respectively. IDC patients had a significantly higher rate of ALN metastasis compared with ILC or other HST (31.9% vs. 22.6% vs. 16.4%, P < 0.001). However, in patients with 1-2 + SLNs, rates of non-SLN metastasis were similar among three groups (IDC: n = 182, 28.6% vs. ILC: n = 5, 31.2% vs. other HST: n = 29, 34.9%, P = 0.481). For patients with 1-2 + SLNs, rates of adjuvant chemotherapy and the estimated 3-year recurrence-free survival were similar between the SLN biopsy and ALND arms, regardless of the histological types. CONCLUSION: Among patients with 1-2 + SLNs, ILC or other HST had similar rates of non-SLN metastasis compared with IDC. Omission of ALND may not influence adjuvant chemotherapy usage or disease outcome regardless of histological types.
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Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Axila , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos , Metástase Linfática , Estudos Retrospectivos , Biópsia de Linfonodo SentinelaRESUMO
Findings for the roles of dairy products, Ca and vitamin D on ovarian cancer risk remain controversial. We aimed to assess these associations by using an updated meta-analysis. Five electronic databases (e.g. PubMed and Embase) were searched from inception to 24 December 2019. Pooled relative risks (RR) with 95 % CI were calculated. A total of twenty-nine case-control or cohort studies were included. For comparisons of the highest v. lowest intakes, higher whole milk intake was associated with increased ovarian cancer risk (RR 1·35; 95 % CI 1·15, 1·59), whereas decreased risks were observed for higher intakes of low-fat milk (RR 0·84; 95 % CI 0·73, 0·96), dietary Ca (RR 0·71; 95 % CI 0·60, 0·84) and dietary vitamin D (RR 0·80; 95 % CI 0·67, 0·95). Additionally, for every 100 g/d increment, increased ovarian cancer risks were found for total dairy products (RR 1·03; 95 % CI 1·01, 1·04) and for whole milk (RR 1·07; 95 % CI 1·03, 1·11); however, decreased risks were found for 100 g/d increased intakes of low-fat milk (RR 0·95; 95 % CI 0·91, 0·99), cheese (RR 0·87; 95 % CI 0·76, 0·98), dietary Ca (RR 0·96; 95 % CI 0·95, 0·98), total Ca (RR 0·98; 95 % CI 0·97, 0·99), dietary vitamin D (RR 0·92; 95 % CI 0·87, 0·97) and increased levels of circulating vitamin D (RR 0·84; 95 % CI 0·72, 0·97). These results show that whole milk intake might contribute to a higher ovarian cancer risk, whereas low-fat milk, dietary Ca and dietary vitamin D might reduce the risk.
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Cálcio da Dieta/administração & dosagem , Laticínios , Dieta , Neoplasias Ovarianas/epidemiologia , Vitamina D/administração & dosagem , Animais , Cálcio/sangue , Estudos de Casos e Controles , Estudos de Coortes , Laticínios/efeitos adversos , Dieta/efeitos adversos , Feminino , Humanos , Leite/química , Risco , Vitamina D/sangueRESUMO
Bacteria have been applied for the bioremediation of cadmium-contaminated environment. Less is known about the bioaccumulation of high concentration of Cd over time under the oligotrophic environment. Burkholderia cepacia GYP1, which was isolated from multiple heavy metal contaminated farmland, was studied for its bioaccumulation mechanism of Cd under oligotrophic condition. GYP1 possessed highly accumulation capacity for cadmium reaching 116â¯mg Cd/g biomass (dry weight). ATR-FTIR, electron microscopy, flow cytometry along with subcellular fraction demonstrated that the uptake and distribution of cadmium varied with the increased amount of cadmium of GYP1 cell during the 7-day treatment time: the accumulation of cadmium was mainly on the outer membrane at the beginning (within 1 day), and the intracellular cadmium kept increased and held stable after 2 days, after that, the increased amount of cadmium mainly located extracellularly, related to the secreted EPS. Further mechanism analysis of bioaccumulation of Cd by GYP1 based on iTRAQ-based proteomics showed that Cd(II) could trigger the up-regulation of the Cd2+/Zn2+-exporting ATPase, type VI protein secretion systems, and glutathione-S-transferase that are related to cadmium response, which may contribute to maintain the intracellular cadmium homeostasis. In summary, the immobilization of Cd(II) by B. cepacia GYP1 contains three steps:(1) fast immobilization of Cd(II) on the cell surface coordinated with functional groups, (2) transport of Cd(II) to cells and accumulation in cytoplasm, and (3) efflux of intracellular Cd(II) depended on energy and the entrapped or adsorbed of extracellular Cd(II) by EPS. Our study provided the understanding of the cadmium accumulation process of B. cepacia GYP1 under oligotrophic condition, which would be helpful in bioremediation of natural cadmium contaminated environment.
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Proteínas de Bactérias/metabolismo , Burkholderia cepacia/metabolismo , Cádmio/metabolismo , Poluentes Ambientais/metabolismo , Proteoma/metabolismo , Biodegradação Ambiental , Transporte Biológico , Biomassa , Nutrientes/deficiência , Frações Subcelulares/metabolismoRESUMO
The relationships between α-diversity and ecosystem functioning (BEF) have been extensively examined. However, it remains unknown how spatial heterogeneity of microbial community, i.e., microbial ß-diversity within a region, shapes ecosystem functioning. Here, we examined microbial community compositions and soil respiration (Rs) along an elevation gradient of 853-4420 m a.s.l. in the southeastern Tibetan Plateau, which is renowned as one of the world's biodiversity hotspots. There were significant distance-decay relationships for both bacterial and fungal communities. Stochastic processes played a dominant role in shaping bacterial and fungal community compositions, while soil temperature was the most important environmental factor that affected microbial communities. We evaluated BEF relationships based on α-diversity measured by species richness and ß-diversity measured by community dispersions, revealing significantly positive correlations between microbial ß-diversities and Rs. These correlations became stronger with increasing sample size, differing from those between microbial α-diversities and Rs. Using Structural Equation Modeling (SEM), we found that soil temperature, soil moisture, and total nitrogen were the most important edaphic properties in explaining Rs. Meanwhile, stochastic processes (e.g., homogenous dispersal and dispersal limitation) significantly mediated effects between microbial ß-diversities and Rs. Microbial α-diversity poorly explained Rs, directly or indirectly. In a nutshell, we identified a previously unknown BEF relationship between microbial ß-diversity and Rs. By complementing common practices to examine BEF with α-diversity, we demonstrate that a focus on ß-diversity could be leveraged to explain Rs.
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Microbiota , Microbiologia do Solo , Solo , Solo/química , Tibet , Biodiversidade , Ecossistema , Bactérias/classificação , FungosRESUMO
Biostimulation (providing favorable environmental conditions for microbial growth) and bioaugmentation (introducing exogenous microorganisms) are effective approaches in the bioremediation of petroleum-contaminated soil. However, uncertainty remains in the effectiveness of these two approaches in practical application. In this study, we constructed mesocosms using petroleum hydrocarbon-contaminated soil. We compared the effects of adding nutrients, introducing exogenous bacterial degraders, and their combination on remediating petroleum contamination in the soil. Adding nutrients more effectively accelerated total petroleum hydrocarbon (TPH) degradation than other treatments in the initial 60 days' incubation. Despite both approaches stimulating bacterial richness, the community turnover caused by nutrient addition was gentler than bacterial degrader introduction. As TPH concentrations decreased, we observed a succession in microbial communities characterized by a decline in copiotrophic, fast-growing bacterial r-strategists with high rRNA operon (rrn) copy numbers. Ecological network analysis indicated that both nutrient addition and bacterial degrader introduction enhanced the complexity and stability of bacterial networks. Compared to the other treatment, the bacterial network with nutrient addition had more keystone species and a higher proportion of negative associations, factors that may enhance microbial community stability. Our study demonstrated that nutrient addition effectively regulates community succession and ecological interaction to accelerate the soil TPH degradation.
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Bactérias , Biodegradação Ambiental , Petróleo , Microbiologia do Solo , Poluentes do Solo , Poluentes do Solo/metabolismo , Petróleo/metabolismo , Bactérias/metabolismo , Bactérias/genética , Bactérias/efeitos dos fármacos , Hidrocarbonetos/metabolismo , Nutrientes/metabolismo , Poluição por PetróleoRESUMO
Unravelling biosphere feedback mechanisms is crucial for predicting the impacts of global warming. Soil priming, an effect of fresh plant-derived carbon (C) on native soil organic carbon (SOC) decomposition, is a key feedback mechanism that could release large amounts of soil C into the atmosphere. However, the impacts of climate warming on soil priming remain elusive. Here, we show that experimental warming accelerates soil priming by 12.7% in a temperate grassland. Warming alters bacterial communities, with 38% of unique active phylotypes detected under warming. The functional genes essential for soil C decomposition are also stimulated, which could be linked to priming effects. We incorporate lab-derived information into an ecosystem model showing that model parameter uncertainty can be reduced by 32-37%. Model simulations from 2010 to 2016 indicate an increase in soil C decomposition under warming, with a 9.1% rise in priming-induced CO2 emissions. If our findings can be generalized to other ecosystems over an extended period of time, soil priming could play an important role in terrestrial C cycle feedbacks and climate change.
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Ecossistema , Pradaria , Solo , Carbono , Mudança ClimáticaRESUMO
Background: Local treatment for ductal carcinoma in situ (DCIS) remains controversial for elderly patients. This study aims to evaluate the association of local treatment, clinicopathological factors, and survival in elderly DCIS patients. Methods: Patients ≥ 60 years diagnosed with DCIS from January 2009 to December 2018 were retrospectively included. Local treatment including breast surgery, axillary lymph node (ALN) surgery, and radiotherapy were analyzed among subgroups (age of 60-69, 70-79, and ≥ 80 years), and their associations with clinicopathological features and prognostic outcome were further evaluated. Results: A total of 331 patients were included. Eventually 86 patients received breast conserving surgery (BCS) and 245 patients received mastectomy. ALN surgery was omitted in 62 patients. Age and tumor size were independent factors that influenced the breast and ALN surgery (P < 0.05). Compared with patients aging 60-69, patients ≥ 80 years were more likely to receive BCS (OR 4.28, 95% CI 1.33-13.78, P = 0.015) and be exempt from ALN surgery (OR 0.19, 95% CI 0.05-0.69, P = 0.011). Patients with tumor >1.5â cm were significantly less likely to receive BCS (OR 0.45, 95%CI 0.25-0.83, P = 0.011) and more likely to receive ALN surgery (OR 4.41, 95%CI 1.96-10.48, P = 0.001) compared to patients with tumor ≤ 1.5â cm. Postoperative radiotherapy was performed in 48.8% patients who received BCS. Age was the only factor that associated with the radiotherapy decision after BCS in elderly DCIS patients (P = 0.025). No significant recurrence-free survival difference was observed among patients receiving different local treatments. Conclusions: Age was related to the choice of local treatment in elderly DCIS patients, but different treatment patterns didn't impact disease outcome.
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The wastewater treatment plant (WWTP) effluent discharge affects the microorganisms in the receiving water bodies. Despite the ecological significance of microbial communities in pollutant degradation and element cycling, how the community diversity is affected by effluent remains obscure. Here, we compared the sediment bacterial communities exposed to different intensities of WWTP effluent discharge in Hangzhou Bay, China: i) a severely polluted area that receives effluent from an industrial WWTP, ii) a moderately polluted area that receives effluent from a municipal WWTP, and iii) less affected area that inner the bay. We found that the sediment bacterial diversity decreased dramatically with pollution levels of inorganic nutrients, heavy metals, and organic halogens. Microbial community assembly model analysis revealed increased environmental selection and decreased species migration rate in the severely polluted area, resulting in high phylogenetic clustering of the bacterial communities. The ecological networks were less complex in the two WWTP effluent receiving areas than in the inner bay area, as suggested by the smaller network size and lower modularity. Fewer negative network associations were detected in the severely (6.7%) and moderately (8.3%) polluted areas than in the less affected area (16.7%), indicating more collaborative inter-species behaviors are required under stressful environmental conditions. Overall, our results reveal the fundamental impacts of WWTP effluents on the ecological processes shaping coastal microbial communities and point to the potential adverse effects of diversity loss on ecosystem functions.
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Microbiota , Purificação da Água , Filogenia , Águas Residuárias , Sedimentos Geológicos/microbiologia , BactériasRESUMO
Introduction: Petroleum pollution resulting from spills and leakages in oil refinery areas has been a significant environmental concern for decades. Despite this, the effects of petroleum pollutants on soil microbial communities and their potential for pollutant biodegradation still required further investigation. Methods: In this study, we collected 75 soil samples from 0 to 5 m depths of 15 soil profiles in an abandoned refinery to analyze the effect of petroleum pollution on soil microbial diversity, community structure, and network co-occurrence patterns. Results: Our results suggested soil microbial a-diversity decreased under high C10-C40 levels, coupled with significant changes in the community structure of soil profiles. However, soil microbial network complexity increased with petroleum pollution levels, suggesting more complex microbial potential interactions. A module specific for methane and methyl oxidation was also found under high C10-C40 levels of the soil profile, indicating stronger methanotrophic and methylotrophic metabolic activities at the heavily polluted soil profile. Discussion: The increased network complexity observed may be due to more metabolic pathways and processes, as well as increased microbial interactions during these processes. These findings highlight the importance of considering both microbial diversity and network complexity in assessing the effects of petroleum pollution on soil ecosystems.
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BACKGROUND: The 21-gene recurrence score (RS) assay has been validated to predict the risk of disease-free survival in estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer patients. However, its relation with locoregional recurrence (LRR) risk is unclear. OBJECTIVE: This study aimed to explore the ability of RS to predict LRR risk. METHODS: Consecutive ER-positive, HER2-negative, pT1, pN0-1, and M0 early breast cancer patients were analyzed retrospectively. According to RS, patients were divided into low- (RS < 18), intermediate- (RS 18-30), and high-risk (RS ⩾ 31) groups. The primary endpoint was LRR. Subgroup analysis was conducted according to different nodal statuses and surgery types. RESULTS: A total of 1558 patients were enrolled: 354 (22.7%), 788 (50.6%), and 416 (26.7%) patients in the low-, intermediate-, and high-risk groups, respectively. The median follow-up time was 53 months, and 2, 8, and 14 LRR events were observed in the low-, intermediate-, and high-risk groups, respectively (P= 0.004). Both univariate (P= 0.009) and multivariate (P= 0.010) analyses demonstrated that 21-gene RS was correlated with LRR. Compared to low-risk patients, high-risk patients were at greater risk of LRR (HR 5.75, 95% CI 1.30-25.31, P= 0.021). Among pN0 (P= 0.033), pN1 (P= 0.049) and postmastectomy patients (P= 0.012), 21-gene RS remained predictive of the risk of LRR. CONCLUSION: The 21-gene RS assay was significantly associated with the risk of LRR in ER-positive, HER2-negative early breast cancer patients. Among patients with different nodal statuses and patients receiving mastectomy, RS remained predictive of the risk of LRR.
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Neoplasias da Mama , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/cirurgia , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Estudos RetrospectivosRESUMO
Antibiotic resistance genes, collectively termed as antibiotic resistome, are regarded as emerging contaminants. Antibiotics resistome can be highly variable in different environments, imposing environmental safety concern and public health risk when it is in conjunction with pathogenic bacteria. However, it remains elusive how pathogenic bacteria interact with antibiotic resistome, making it challenging to assess microbial risk. Here, we examined the presence and relative abundance of bacterial virulence genes representing potential pathogens in swine manure, compost, compost-amended soil, and unamended agricultural soil in five suburban areas of Beijing, China. The absolute abundances of virulence genes were marginally significantly (p < 0.100) increased in compost-amended soils than unamended soil, revealing potential health risks in manure fertilization. The composition of potential pathogens differed by sample types and was linked to temperature, antibiotics, and heavy metals. As antibiotics can confer pathogens the resistance to clinic treatment, it was alarming to note that virulence genes tended to co-exist with antibiotic resistance genes, as shown by prevalently positive links among them. Collectively, our results demonstrate that manure fertilization in agriculture might give rise to the development of potentially antibiotic-resistant pathogens, unveiling an environmental health risk that has been frequently overlooked.
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Antibacterianos , Esterco , Animais , Antibacterianos/farmacologia , Bactérias/genética , Fertilização , Genes Bacterianos , Solo , Microbiologia do Solo , Suínos , Virulência/genéticaRESUMO
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among all types of diseases in the world, affecting many millions of individuals every year. CVD includes hypertension, atherosclerosis, pulmonary hypertension, heart failure, cardiomyopathy, coronary heart disease, etc., which are involved in complex etiology, pathogenesis and many risk factors. Modern pharmacological studies have revealed that Epimedium possesses a variety of beneficial effects in regulating cardiovascular inflammation and other biological activities, which provides a therapeutic value for the prevention and treatment of these cardiovascular diseases. In this review, we discuss the cardiovascular protective effects of icariin, an active component from Epimedium, and its metabolites. We summarize a range of studies showing that the modes of action of icariin on CVD relate to its inhibition of myocardial apoptosis and prevention of inflammation on endothelial cell injury, emphasizing the multiple effects of icariin and its metabolites in the repair of common heart failure and myocardial infarction, as well as the formation of neointima. In particular, an emphasis is placed on the discussion of the action mechanism of icariin in combination with new advances in the understanding of the pathology of CVD with potential application of icariin in the treatment of this human disorder.
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Doenças Cardiovasculares/prevenção & controle , Epimedium/química , Flavonoides/farmacologia , Compostos Fitoquímicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Flavonoides/farmacocinética , Humanos , Mediadores da Inflamação/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Neovascularização Patológica/patologia , Calcificação Vascular/patologiaRESUMO
Nowadays, lung cancer is still the deadliest oncological disease in the world. Among them, non-small cell lung cancer (NSCLC) accounts for 80%â¼85% of all lung cancers, and its 5-year survival rate is less than 15%, making the situation critical. In the past decades, despite some clinical advances in conventional treatments, the overall survival rate of NSCLC is still not optimistic due to its unique physiological conditions and the frequent occurrence of tumor escape. In recent years, immunotherapy has become a new hot spot in lung cancer research, including antibody therapy and cell therapy, which have been developed and utilized one after another, especially immune checkpoint inhibitor (ICI). These approaches have effectively improved the overall survival rate and objective response rate of NSCLC patients by enhancing the immune capacity of the body and targeting tumor cells more effectively, which is more specific and less toxic compared with conventional chemotherapy, and providing more strategies for NSCLC treatment. In this paper, we reviewed the relevant targets, clinical progress and adverse reaction in monoclonal antibodies, antibody-drug conjugates, ICI, bispecific antibodies, T-cell receptor engineered T cell therapy (TCR-T), Chimeric antigen receptor T-cell immunotherapy (CAR-T), and also report on their combination therapy from the immune-related background to provide better NSCLC treatment and prospective.
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The mangrove ecosystem is an important CO2 sink with an extraordinarily high primary productivity. However, it is vulnerable to the impact of climate warming and eutrophication. While there has been extensive research on plant growth and greenhouse gas emission in mangrove ecosystems, microbial communities, the primary biogeochemical cycling drivers, are much less understood. Here, we examined whether short-term experimental treatments: (1) eutrophication with a supplement of 185 g N m-2·year-1 (N), (2) 3°C warming (W), and (3) the dual treatment of N and W (NW) were sufficient to alter microbial communities in the sediment. After 4 months of experiments, most environmental factors remained unchanged. However, N had significant, strong effects on bacterial, fungal, and functional community compositions, while the effects of W on microbial communities were weaker. N increased bacterial richness, phylogenetic diversity, and evenness, owing to stronger stochastic processes induced by eutrophication. There were no interactive effects of N and W on bacterial, fungal, and functional community compositions, suggesting that joint effects of N and W were additive. Concomitant with higher N2O efflux induced by N, the relative abundances of most bacterial nitrogen cycling genes were increased or remained changed by N. In contrast, N decreased or did not change those of most bacterial carbon degradation genes, while W increased or did not change the relative abundances of most of bacterial and fungal carbon degradation genes, implying higher carbon degradation potentials. As the most abundant inorganic nitrogenous species in mangrove sediment, ammonium was a key factor in shaping microbial functional communities. Collectively, our findings showed that microbial community compositions in the mangrove sediment were highly sensitive to short-term N and W treatments, giving rise to ecological consequences such as higher N2O efflux.
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Compostos de Amônio , Gases de Efeito Estufa , Microbiota , Compostos de Amônio/metabolismo , Bactérias/metabolismo , Carbono/metabolismo , Dióxido de Carbono/metabolismo , Ecossistema , Gases de Efeito Estufa/metabolismo , Nitrogênio/análise , FilogeniaRESUMO
Specific roles of gut microbes in COVID-19 progression are critical. However, the circumstantial mechanism remains elusive. In this study, shotgun metagenomic or metatranscriptomic sequencing was performed on fecal samples collected from 13 COVID-19 patients and controls. We analyzed the structure of gut microbiota, identified the characteristic bacteria, and selected biomarkers. Further, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations were employed to correlate the taxon alterations and corresponding functions. The gut microbiota of COVID-19 patients was characterized by the enrichment of opportunistic pathogens and depletion of commensals. The abundance of Bacteroides spp. displayed an inverse relationship with COVID-19 severity, whereas Actinomyces oris, Escherichia coli, and Streptococcus parasanguini were positively correlated with disease severity. The genes encoding oxidoreductase were significantly enriched in gut microbiome of COVID-19 group. KEGG annotation indicated that the expression of ABC transporter was upregulated, while the synthesis pathway of butyrate was aberrantly reduced. Furthermore, increased metabolism of lipopolysaccharide, polyketide sugar, sphingolipids, and neutral amino acids were found. These results suggested the gut microbiome of COVID-19 patients was in a state of oxidative stress. Healthy gut microbiota may enhance antiviral defenses via butyrate metabolism, whereas the accumulation of opportunistic and inflammatory bacteria may exacerbate COVID-19 progression.
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As the second-largest terrestrial carbon (C) flux, soil respiration (RS) has been stimulated by climate warming. However, the magnitude and dynamics of such stimulations of soil respiration are highly uncertain at the global scale, undermining our confidence in future climate projections. Here, we present an analysis of global RS observations from 1987-2016. RS increased (P < 0.001) at a rate of 27.66 g C m-2 yr-2 (equivalent to 0.161 Pg C yr-2) in 1987-1999 globally but became unchanged in 2000-2016, which were related to complex temporal variations of temperature anomalies and soil C stocks. However, global heterotrophic respiration (Rh) derived from microbial decomposition of soil C increased in 1987-2016 (P < 0.001), suggesting accumulated soil C losses. Given the warmest years on records after 2015, our modeling analysis shows a possible resuscitation of global RS rise. This study of naturally occurring shifts in RS over recent decades has provided invaluable insights for designing more effective policies addressing future climate challenges.
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Microorganisms are essential for soil rehabilitation and long-term sustainability of established plants. However, the recovery process of microorganisms in AMD-irrigated paddy soil is poorly understood at present. To verify this, we sampled AMD-irrigated paddy soils before at different rehabilitation stages by characterizing bacteria and archaea community from a chronosequence of AMD-irrigated rehabilitation to pre-disturbance levels from references sites. Next-generation sequencing is used to describe shifts in diversity and taxonomic composition of bacterial and archaeal. Co-occurrence networks are constructed to reveal potential microbial interaction patterns. The result showed bacterial community followed an observable taxonomic transition overtimes, with community structure becoming more similar to that of unmined reference sites. But the archaeal community only showed a seasonal change, which may hint that the archaeal community needs more time in rehabilitation. Both bacterial and archaeal community composition changes were apparent at high taxonomic levels, bacterial communities become dominated by Proteobacteria phylum, and archaeal community was dominated by Crenarchaeota, we proposed the possible reason is bacterial community were mainly derived by soil pH while the archaeal community was impacted by heavy metal. The bacterial co-occurrence networks increased in complexity during succession, improving the community's resistance to environmental disturbance, while the archaeal did not change monotonically with time. This study highlights the distinct recovery pattern of the bacterial and archaeal community during AMD-irrigated paddy soil rehabilitation, which provides a deep understanding of their role in paddy soil, and subsequent harnessing of their potential to pave the way in future rehabilitation strategies for mined sites.