RESUMEN
BACKGROUND: Patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC), which accounts for 85% of all CRC cases, display a poor respond to immune checkpoint inhibitors (i.e., anti-PD-1 antibodies). pMMR/MSS CRC patients with locally advanced cancers need effective combined therapies. METHODS: In this pilot study, we administered six preoperative doses of each 2-week cycle of the anti-PD-1 antibody sintilimab (at a fixed dose of 200 mg), oxaliplatin, and 5-FU/CF (mFOLFOX6) combined with five doses of bevacizumab (the number of doses was reduced to prevent surgical delays) to patients with cT4NxM0 colon or upper rectal cancers. And radical surgery was performed approximately 2 weeks after the last dose of neoadjuvant therapy. The primary endpoint was a pathologic complete response (pCR). We also evaluated major pathologic response (MPR, ≤10% residual viable tumor), radiological and pathological regression, safety, and tumor mutation burden (TMB), and tumor microenvironment (TME) characteristics. RESULTS: By the cutoff date (September 2023), 22 patients with cT4NxM0 pMMR/MSS colon or upper rectal cancers were enrolled and the median follow-up was 24.7 months (IQR: 21.1-26.1). All patients underwent R0 surgical resection without treatment-related surgical delays. pCR occurred in 12 of 22 resected tumors (54.5%) and MPR occurred in 18 of 22 (81.8%) patients. At the cutoff date, all patients were alive, and 21/22 were recurrence-free. Treatment-related adverse events of grade 3 or higher occurred in of 2/22 (9.1%) patients. Among the pCR tumors, two were found to harbor POLE mutations. The degree of pathological regression was significantly greater than that of radiological regression (p = 1.35 × 10-8). The number of CD3+/CD4+ cells in the tumor and stroma in pretreated biopsied tissues was markedly lower in pCR tumors than in non-pCR tumors (p = 0.038 and p = 0.015, respectively). CONCLUSIONS: Neoadjuvant sintilimab combined with bevacizumab and mFOLFOX6 was associated with few side effects, did not delay surgery, and led to pCR and non-pCR in 54.5% and 81.8% of the cases, respectively. Downregulation of CD3/CD4 expression in the tumor and stroma is related to pCR. However, the molecular mechanisms underlying PD-1 blockade-enhanced targeted chemotherapy require further investigation.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Neoplasias Colorrectales , Fluorouracilo , Inhibidores de Puntos de Control Inmunológico , Humanos , Masculino , Femenino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Anciano , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Fluorouracilo/uso terapéutico , Fluorouracilo/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Proyectos Piloto , Bevacizumab/uso terapéutico , Bevacizumab/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Leucovorina/uso terapéutico , Leucovorina/administración & dosificación , Reparación de la Incompatibilidad de ADN , Adulto , Inestabilidad de Microsatélites , Oxaliplatino/uso terapéutico , Oxaliplatino/administración & dosificación , Terapia Neoadyuvante/métodos , Microambiente Tumoral/inmunología , Compuestos Organoplatinos/uso terapéutico , Compuestos Organoplatinos/administración & dosificación , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Resultado del TratamientoRESUMEN
Excessive application of mineral fertilizers has accelerated soil acidification in China, affecting crop production when the pH drops below a critical value. However, the contributions of natural soil acidification, induced by leaching of bicarbonate, and anthropogenic causes of soil acidification, induced by nitrogen (N) transformations and removal of base cations over acid anions, are not well quantified. In this study, we quantified soil acidification rates, in equivalents (eq) of acidity, by assessing the inputs and outputs of all major cations and anions, including calcium, magnesium, potassium, sodium, ammonium, nitrate, bicarbonate, sulphate, phosphate and chloride, for 13 long-term experimental sites in southern China. The acidification rates strongly varied among fertilizer treatments and with the addition of animal manure. Bicarbonate leaching was the dominant acid production process in calcareous soils (23 keq ha-1 yr-1) and in non-calcareous paddy soils (9.6 keq ha-1 yr-1), accounting for 80 % and 68 % of the total acid production rate, respectively. The calcareous soils were strongly buffered, and acidification led no or a limited decline in pH. In contrast, N transformations were the most important driver for soil acidification at one site with upland crops on a non-calcareous soil, accounting for 72 % of total acid production rate of 8.4 keq ha-1 yr-1. In this soil, the soil pH considerably decreased being accompanied by a substantial decline in exchangeable base cation. Reducing the N surplus decreased the acidification rate with 10 to 54 eq per kg N surplus with the lowest value occurring in paddy soils and the highest in the upland soil. The use of manure, containing base cations, partly mitigated the acidifying impact of N fertilizer inputs and crop removal, but enhanced phosphorus (P) accumulation. Combining mineral fertilizer, manure and lime in integrative management strategies can mitigate soil acidification and minimize N and P losses.
RESUMEN
Appropriate nitrogen (N) management system is essential for effective crop productivity and minimizing agricultural pollution. However, the underlying mechanistic understanding of how N fertilizer regulates crop yield via soil properties in soils with different fertilities remains unresolved. Here, we used a field experiment that spanned 3 cropping seasons to evaluate the grain yield (GY), aboveground biomass and N recovery efficiency (NRE) after treatment with five N fertilizer application rates (N0, N75, N112, N150, and N187) in soils with three levels of fertility. Our results indicated that the highest GY across low, moderate, and high fertility soils were 1.5 t hm-2 (N150), 4.9 t hm-2 (N187), and 5.4 t hm-2 (N112), respectively. The highest aboveground biomass and NRE were observed at N150 for all three levels of soil fertility, while only the N uptake by aboveground biomass of low and high fertility soils decreased at N187, confirming that excessive N fertilization results in a further decline in crop N uptake. The relationship between GY, NRE and N fertilizer application rates fit the unary quadratic polynomial model. To achieve a balance between grain production and environmental benefits in N fertilizer, appropriate N fertilizer rates were determined to be 97.5 kg hm-2, 140 kg hm-2 and 131 kg hm-2 for low, moderate and high fertility soils, respectively. Structural equation modeling suggested that GY was significant correlated with soil microbial biomass carbon (SMBC) and N directly in low fertility field, with SMBC directly in moderate fertility field, and via SOC and NO3 -N in high fertility field. Therefore, a soil-based management strategy for N fertilizers could enhance food security while reducing agricultural N fertilizer inputs to mitigate environmental impacts.
RESUMEN
Unraveling the influence of community assembly processes on soil ecosystem functioning presents a major challenge in the field of theoretical ecology, as it has received limited attention. Here, we used a series of long-term experiments spanning over 25 years to explore the assembly processes of bacterial, fungal, protist, and nematode communities using high-throughput sequencing. We characterized the soil microbial functional potential by the abundance of microbial genes associated with carbon, nitrogen, phosphorus, and sulfur cycling using GeoChip-based functional gene profiling, and determined how the assembly processes of organism groups regulate soil microbial functional potential through community diversity and network stability. Our results indicated that balanced fertilization (NPK) treatment improved the stochastic assembly of bacterial, fungal, and protist communities compared to phosphorus-deficient fertilization (NK) treatment. However, there was a nonsignificant increase in the normalized stochasticity ratio of the nematode community in response to fertilization across sites. Our findings emphasized that soil environmental factors influenced the assembly processes of the biotic community, which regulated soil microbial functional potential through dual mechanisms. One mechanism indicated that the high phosphorus levels and low soil nutrient stoichiometry may increase the stochasticity of bacterial, fungal, and protist communities and the determinism of the nematode community under NPK treatment, ultimately enhancing soil microbial functional potential by reinforcing the network stability of the biotic community. The other mechanism indicated that the low phosphorus levels and high soil nutrient stoichiometry may increase the stochastic process of the bacterial community and the determinism of the fungal, protist, and nematode communities under NK treatment, thereby enhancing soil microbial functional potential by improving the ß-diversity of the biotic community. Taken together, these results provide valuable insights into the mechanisms underlying the assembly processes of the biotic community that regulate ecosystem functioning.
Asunto(s)
Ecosistema , Suelo , Microbiología del Suelo , Bacterias/genética , FósforoRESUMEN
To reduce reliance on synthetic nitrogen (N) fertilizer and sustain food production, replacing synthetic N fertilizer with animal manure as an effective method is widely used. However, the effects of replacing synthetic N fertilizer with animal manure on crop yield and nitrogen use efficiency (NUE) remain uncertain under varying fertilization management practices, climate conditions, and soil properties. Here, we performed a meta-analysis of wheat (Triticum aestivum L.), maize (Zea mays L.), and rice (Oryza sativa L.) based on 118 published studies conducted in China. Overall, the results indicated that substituting synthetic N fertilizer with manure increased yield by 3.3%-3.9% for the three grain crops and increased NUE by 6.3%-10.0%. Crop yields and NUE did not significantly increase at a low N application rate (≤120 kg ha-1) or high substitution rate (>60%). Yields and NUE values had higher increases for upland crops (wheat and maize) in temperate monsoon climate/temperate continental climate regions with less average annual rainfall (AAR) and lower mean annual temperature (MAT), while rice had higher increases in subtropical monsoon climate regions with more AAR and higher MAT. The effect of manure substitution was better in soil with low organic matter and available phosphorus. Our study shows that the optimal substitution rate was 44% and the total N fertilizer input cannot be less than 161 kg ha-1 when substituting synthetic N fertilizer with manure. Moreover, site-specific conditions should also be considered.
RESUMEN
BACKGROUND: For achieving long-term sustainability of intensive agricultural practices, it is pivotal to understand belowground functional stability as belowground organisms play essential roles in soil biogeochemical cycling. It is commonly believed that resource availability is critical for controlling the soil biodiversity and belowground organism interactions that ultimately lead to the stabilization or collapse of terrestrial ecosystem functions, but evidence to support this belief is still limited. Here, we leveraged field experiments from the Chinese National Ecosystem Research Network (CERN) and two microcosm experiments mimicking high and low resource conditions to explore how resource availability mediates soil biodiversity and potential multi-trophic interactions to control functional trait stability. RESULTS: We found that agricultural practice-induced higher resource availability increased potential cross-trophic interactions over 316% in fields, which in turn had a greater effect on functional trait stability, while low resource availability made the stability more dependent on the potential within trophic interactions and soil biodiversity. This large-scale pattern was confirmed by fine-scale microcosm systems, showing that microcosms with sufficient nutrient supply increase the proportion of potential cross-trophic interactions, which were positively associated with functional stability. Resource-driven belowground biodiversity and multi-trophic interactions ultimately feedback to the stability of plant biomass. CONCLUSIONS: Our results indicated the importance of potential multi-trophic interactions in supporting belowground functional trait stability, especially when nutrients are sufficient, and also suggested the ecological benefits of fertilization programs in modern agricultural intensification. Video Abstract.
Asunto(s)
Biodiversidad , Ecosistema , Biomasa , Suelo/química , Estado NutricionalRESUMEN
Wheat breeding has progressively increased yield potential through decades of selection, markedly increased the capacity for food production. Nitrogen (N) fertilizer is essential for wheat production and N agronomic efficiency (NAE) is commonly index used for evaluate the effects of N fertilizer on crop yield, calculated as the difference of wheat yield between N fertilizer treatment and non-N fertilizer treatment divided by the total N application rate. However, the impact of variety on NAE and its interaction with soil fertility remain unknown. Here, to clarify whether and how wheat variety contributes to NAE, and to determine if soil conditions should be considered in variety selection, we conduct a large-scale analysis of data from 12,925 field trials spanning ten years and including 229 wheat varieties, 5 N fertilizer treatments, and a range of soil fertility across China's major wheat production zones. The national average NAE was 9.57 kg kg-1, but significantly differed across regions. At both the national and regional scales, variety significantly affected NAE, and different varieties showed high variability in their performance among low, moderate, and high fertility soils. Here, superior varieties with both high yield and high NAE were identified at each soil fertility fields. The comprehensive effect of selecting regionally superior varieties, optimizing N management, and improving soil fertility could potentially decrease the yield gap by 67 %. Therefore, variety selection based on soil conditions could facilitate improved food security while reducing fertilizer inputs to alleviate environmental impacts.
Asunto(s)
Suelo , Triticum , Nitrógeno/análisis , Fertilizantes/análisis , Fitomejoramiento , AgriculturaRESUMEN
In the past decade, biochar has been widely regarded as a new type of soil conditioner that can effectively control soil acidification and alleviate Al toxicity. Hydrochar is identified as a more economical carbon material than pyrochar, but its effect on Al toxicity and the associated mechanism have not been studied. Thus, a two-stage indoor incubation experiment was conducted to investigate the effect of rice-straw hydrochar (HC, application rate: 1/2/3 %) on maize seedling root growth, soil solution Al activity, soil exchangeable Al and pH buffering ability in acidic red soils from two sites. We also used pyrochar (PC, application rate: 3 %) produced from the same rice straw for comparison. Except for HC-1 %, both hydrochar and pyrochar addition significantly stimulated relative root elongation (136.36 % ~ 284.09 %), diminished the cell death ratio (27.96 % ~ 85.56 %) and Al content in root tips (18.80 % ~ 80.11 %) by decreasing the total Al content (44.78 % ~ 76.10 %) and the proportion of Al3+ species (27 % ~ 32 %) in soil solution. Hydrochar did not significantly promote the soil pH buffer capacity (pH-BC) or effective cation exchange capacity (ECEC), while PC-3 % did. The DOC (dissolved organic carbon) content of soil solution was dramatically elevated by 203.9 % ~ 783.2 % after hydrochar addition. Hydrochar mitigates Al activity in soil solution mainly through Al-DOC complexation and adsorption, thus suppressing the Al toxicity of maize roots. Hydrochar may be an economical soil amendment for ameliorating Al toxicity despite its overall alleviation effect on Al toxicity being lower than pyrochar.
Asunto(s)
Oryza , Contaminantes del Suelo , Suelo/química , Oryza/metabolismo , Contaminantes del Suelo/análisis , Carbón Orgánico/química , Carbono/metabolismo , Zea mays/metabolismoRESUMEN
Although the enrichment of antibiotic resistance genes (ARGs) in diverse organic soils have been explored, understanding of the ecological processes governing the composition of ARGs in long-term organically fertilized soils still remains limited across typical agricultural regions. Thus, the distribution and assembly of ARG profile in three typical agricultural soils (black soil, fluvo-aquic soil, and red soil) under long-term contrasting fertilization regimes (chemical-only vs organic-only) were investigated using high-throughput qPCR (HT-qPCR). The application of organic manure significantly increased the abundance and number of ARGs across soils, as compared to those with chemical fertilizer. Organic manure application enriched the abundance of mobile genetic elements (MGEs), which were positively associated with ARGs. In addition, it is long-term organic fertilizer that enriched the number and abundance of opportunist and specialist ARGs in the fluvo-aquic and red soils, but not black soils. The number and abundance of most generalist ARGs did not change significantly among different fertilization or soil types. The assembly process of the ARG profiles tends to be more deterministic in organically fertilized soils than in chemically fertilized soils. These results suggest that long-term organic fertilizer application may contribute to the persistence and health risk of the soil antibiotic resistomes (especially specialist ARGs).
Asunto(s)
Estiércol , Suelo , Antibacterianos/farmacología , Fertilizantes/análisis , Genes Bacterianos , Estiércol/análisis , Suelo/química , Microbiología del SueloRESUMEN
Understanding the decomposition dynamics and driving factors of manure in the soil subjected to different reclaimed years could provide theoretical basis to rational utilization of manure and soil fertility improvement in coal mining area. Cattle manure and pig manure were mixed with soils subjected to different reclaimed years (one year, R1; 10 years, R10; and 30 years, R30) at the ratio of manure carbon to soil mass of 4 to 100, so as to examine manure decomposition characteristics using the nylon mesh bag (15 cm deep of soil buried) in the Shanxi coal mine reclamation area, with no manure addition as control (CK). Soil samples were collected at day 12, 23, 55, 218, 281, and 365 to measure the contents of soil manure residual, soil microbial biomass carbon (MBC), and dissolved organic carbon (DOC). The contributions of soil properties, manure properties, and hydrothermal condition to manure decomposition were quantified. The results showed that the decomposition rates of pig manure were significantly higher than cattle manure. The humification coefficient of pig manure (average 46.3%) was lower than that of cattle manure (average 71.7%). The humification coefficient of pig manure was significantly lower in the 30-year reclaimed soil (44.5%) compared to the 1-year and 10-year reclaimed soil (average 47.2%). There was no significant difference in the humification coefficient of cattle manure among the three reclaimed soils. The proportion and decomposition rate constant of labile carbon pool of pig manure and cattle manure were significantly different, with values of 52% and 26%, and 0.00085 and 0.00074 â-1, respectively. The positive effect of pig manure on MBC and DOC in reclaimed soil was significantly higher than that of cattle manure over 0-218 days, but no difference over 281-365 days. The magnitude of the enhancement of MBC and DOC in those three reclaimed soils after manure amendments showed a similar trend of R1 >R10 ≈ R30. Results of variance partitioning analysis showed that manure decomposition was mainly controlled by manure properties (17.9%) when considering soil properties, manure properties, and hydrothermal condition. In conclusion, the decomposition of pig manure but not cattle manure was regulated by reclamation year. Cattle manure, with higher humification coefficient than pig manure, was recommended for reclaimed mining area to improve soil fertility.
Asunto(s)
Minas de Carbón , Suelo , Animales , Carbono/análisis , Bovinos , Materia Orgánica Disuelta , Estiércol , Minería , PorcinosRESUMEN
Fertilization regimes are known to drive succession of the soil microbial community, whereas the assembly rules involved remain elusive. Moreover, the ecological roles of microbial "generalists" and "specialists" in soils with contrasting fertilization regimes have not been characterized. We explored how long-term fertilization regimes (i.e., treatments conducted for at least 30 years) impact the soil bacteria by modifying species richness, diversity, bacterial assembly, and niche breadth. Compared with long-term organic fertilizer input, the soils having undergone chemical-only fertilization contained smaller amounts of carbon resources and had a more acidic environment. This strong environmental constraint lowered the soil bacterial reservoir and resulted in a detectable ecoevolutionary transformation, with both a higher proportion of specialists and a stronger signature of deterministic processes. Overall, this study provided a new comprehensive understanding of the assembly rules of bacterial generalists and specialists under long-term fertilization regimes. This study also highlighted that chemical-only fertilization, a ubiquitous agricultural practice of current conventional agriculture, induced a strong and similar environmental force that transformed the soil microbiota from 28°N to 46°N included in this study.IMPORTANCE Chemical-only fertilization is ubiquitous in contemporary conventional agriculture despite the fact that sustainability of this agricultural practice is increasingly being questioned because of the current observed soil degradation. We explored how long-term chemical-only versus organic-only fertilizations impacted the soil microbiota reservoir in terms of both diversity and induced assembly processes. The results showed that long-term chemical-only fertilization resulted in deep selection pressure on the soil microbial community reservoir, with both a higher proportion of specialists and a stronger signature of deterministic processes. The soil microbiota has clearly changed as a consequence of the fertilization regime. The diagnoses of the functional consequences of these ecoevolutionary changes in relation to agricultural practices are key to imagining agriculture in the time ahead and especially regarding future efforts for the conservation, restoration, and management of the soil microbiota reservoir which is key to the fertility of the ecosystem.
RESUMEN
Soil amended with biochar has many potential environmental benefits, but its influence on the fate of nitrogen (N) under irrigated conditions is unclear. The objective of this research was to determine the effects of biochar and interactions with irrigation on N movement in soil, gas emissions, and leaching. A three-year study was conducted in an onion field with three main irrigation treatments (50, 75, and 100% of a reference that provided sufficient water for plant growth) and three biochar amendment rates (0 or control, low char - applied first year at 29 Mg ha-1, and high char - added both first and second year for a total 58 Mg ha-1) as sub-treatments in a split-plot design. Nitrogen fertilizer was applied three times during first year growing season, but weekly the second year. Ammonia (NH3) volatilization, nitrous oxide (N2O) emission, and nitrate (NO3-) in soil pore water were monitored during growing season, and annual N (total and NO3-) changes in soil profile were determined for first two years. Nitrate leaching was measured in the third year. Ammonia volatilization was affected by fertilization frequency with higher loss (5-8% of total applied) when fertilizer was applied in large doses during the first year compared to the second year (4-5%). Nitrous oxide emissions were ≤0.1% of applied N for both years and not affected by any treatments or fertilization frequency. Nitrate concentration in soil profile increased significantly as irrigation level dropped, but most of the NO3- was leached by winter rain. There was no significant biochar effect on total N gas emissions or soil NO3- accumulation, but significant irrigation effect and interaction with biochar were determined on soil NO3- accumulation. High leaching was associated with biochar amendment and higher irrigation level. Irrigation strategies are the key to improving N management and developing the best practices associated with biochar.
Asunto(s)
Cebollas , Carbón Orgánico , Fertilizantes , Nitrógeno , Óxido Nitroso , SueloRESUMEN
The effects of soil type and organic material quality on the microbial biomass and functional diversity of cropland soils were studied in a transplant experiment in the same climate during a 1-year field experiment. Six organic materials (WS: wheat straw, CS: corn straw, WR: wheat root, CR: corn root, PM: pig manure, CM: cattle manure), and three contrasting soils (Ferralic Cambisol, Calcaric Cambisol and Luvic Phaeozem) were chosen. At two time points (at the end of the 1st and 12th months), soil microbial biomass carbon (C) and nitrogen (N) (MBC and MBN) and Biolog Ecoplate substrate use patterns were determined, and the average well color development and the microbial functional diversity indices (Shannon, Simpson and McIntosh indices) were calculated. Organic material quality explained 29.5-50.9% of the variance in MBC and MBN when compared with the minor role of soil type (1.4-9.3%) at the end of the 1st and 12th months, and C/N ratio and total N of organic material were the main parameters. Soil properties, e.g., organic C and clay content were the predominant influence on microbial functional diversity in particular at the end of the 12th month (61.8-82.8% of the variance explained). The treatments of WS and CS significantly improved the MBC and microbial functional diversity indices over the control in the three soils in both sampling periods (P < 0.05). These results suggest that the application of crop straw is a long-term effective measure to increase microbial biomass, and can further induce the changes of soil properties to regulate soil microbial community.
Asunto(s)
Biodiversidad , Biomasa , Carbono/análisis , Productos Agrícolas/microbiología , Fertilizantes , Microbiología del Suelo , Animales , Bovinos , Estiércol , Nitrógeno/análisis , Lluvia , Suelo/química , Sus scrofa , Temperatura , Triticum , Zea maysRESUMEN
PURPOSE: The prognostic value of the tumor-to-liver uptake ratio (TLR) from 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the early stage of colorectal cancer (CRC) is unclear. Notably, some stage IIA CRC patients experience early recurrence even after curative resection and might benefit from neoadjuvant or adjuvant chemotherapy. This study aims to evaluate whether elevated TLR from 18F-FDG-PET/CT can predict poor prognosis in stage IIA CRC patients undergoing curative resection. METHODS: From April 2010 to December 2013, 504 consecutive CRC patients with different TNM stages (I-IV) underwent 18F-FDG-PET/CT scans at the 6th Affiliated Hospital of Sun Yat-Sen University. Among the patients, 118 with stage IIA CRC who accepted preoperative 18F-FDG-PET/CT scanning and were treated with curative surgery alone were reviewed retrospectively. The maximum standardized uptake value (SUVmax) in the primary tumor, TLR, and demographic, clinical, histopathological, and laboratory data were analyzed. Receiver operating characteristic (ROC) curve, univariate and multivariate analyses were performed to identify prognostic factors associated with patient disease-free survival (DFS) and overall survival (OS). RESULTS: ROC curve analysis demonstrated that TLR was superior to primary tumor SUVmax in predicting the risk of recurrence in stage IIA CRC. The optimal TLR cutoff was 6.2. Univariate analysis indicated that elevated TLR, tumor size, and lymphovascular/neural invasion correlated with DFS (P = 0.001, P = 0.002, and P = 0.001, respectively) and OS (P = 0.001, P = 0.003, and P < 0.001, respectively). The 1-, 3-, and 5-year DFS rates were 98.4%, 96.9%, and 96.9% for stage IIA CRC patients with lower TLR (≤6.2) versus 77.8%, 60.6%, and 60.6% for those with elevated TLR (>6.2), respectively. The 1-, 3-, and 5-year OS rates were 100.0%, 100.0%, and 98.3% for the patients with lower TLR versus 98.1%, 83.3%, and 74.3% for those with elevated TLR. Cox regression analysis showed that elevated TLR [>6.2; hazard ratio (HR): 3.109-57.463; P < 0.001] and tumor size (>4.4 cm; HR: 1.636-19.155; P = 0.006) were independent risk factors for DFS. Meanwhile, elevated TLR (>6.2; HR: 1.398-84.945; P = 0.023) and lymphovascular/neural invasion (positive; HR: 1.278-12.777; P = 0.017) were independent risk factors for OS. CONCLUSION: Elevated TLR predicted worse DFS and OS for stage IIA CRC patients and might serve as a potential radiological index to identify candidates for neoadjuvant or adjuvant chemotherapy. Stage IIA CRC patients with elevated TLR should be monitored carefully for early detection of possible recurrence.
Asunto(s)
Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/metabolismo , Fluorodesoxiglucosa F18 , Hígado/metabolismo , Tomografía Computarizada por Tomografía de Emisión de Positrones , Adulto , Anciano , Anciano de 80 o más Años , Transporte Biológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Hígado/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Análisis Multivariante , Terapia Neoadyuvante , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Mitogen-activated protein kinase kinase 4 (MKK4) is a key mediator of Jun N-terminal kinase signaling and influences malignant metastasis. Here, we used immunohistochemistry to assess phosphorylated MMK4 (pMKK4) levels and examine their association with the clinicopathological features of a pilot set of patient samples consisting of normal colonic mucosa (NCM), colorectal adenoma (CA), and colorectal cancer (CRC) tissues. pMKK4 levels were also assessed in a validation set of CRC cases with accompanying follow-up data to confirm their clinicopathological and prognostic significance. pMKK4 levels, which were high in 79.17% of NCM samples, were downregulated in 33.33% of CA and 63.54% of CRC samples. pMKK4 downregulation was associated with metastasis, especially to the liver. In the validation set, pMKK4 downregulation was associated with increases in invasive depth, lymph node metastasis, distant metastasis, and TNM stage. Univariate analysis indicated that pMKK4 score, tumor differentiation, and TNM stage were correlated with disease-free survival and overall survival. Multivariate analysis indicated that decreased pMKK4 expression was an independent risk factor for disease-free survival in CRC patients. These results suggest that CRC patients with low pMKK4 immunochemistry scores should be monitored carefully for early detection of possible recurrences, especially liver metastasis.
Asunto(s)
Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Regulación hacia Abajo , MAP Quinasa Quinasa 4/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Fosforilación , Proyectos Piloto , Pronóstico , Adulto JovenRESUMEN
Antibiotics have significant and long-lasting impacts on the intestinal microbiota and consequently reduce colonization resistance against Clostridium difficile infection (CDI). Standard therapy using antibiotics is associated with a high rate of disease recurrence, highlighting the need for novel treatment strategies that target toxins, the major virulence factors, rather than the organism itself. Human monoclonal antibodies MK-3415A (actoxumab-bezlotoxumab) to C. difficile toxin A and toxin B, as an emerging non-antibiotic approach, significantly reduced the recurrence of CDI in animal models and human clinical trials. Although the main mechanism of protection is through direct neutralization of the toxins, the impact of MK-3415A on gut microbiota and its restoration has not been examined. Using a CDI murine model, we compared the bacterial diversity of the gut microbiome of mice under different treatments including MK-3415A, vancomycin, or vancomycin combined with MK-3415A, sampled longitudinally. Here, we showed that C. difficile infection resulted in the prevalence of Enterobacter species. Sixty percent of mice in the vehicle group died after 2 days and their microbiome was almost exclusively formed by Enterobacter. MK-3415A treatment resulted in lower Enterobacter levels and restoration of Blautia, Akkermansia, and Lactobacillus which were the core components of the original microbiota. Vancomycin treatment led to significantly lower survival rate than the combo treatment of MK-3415A and vancomycin. Vancomycin treatment decreased bacterial diversity with predominant Enterobacter and Akkermansia, while Staphylococcus expanded after vancomycin treatment was terminated. In contrast, mice treated by vancomycin combined with MK-3415A also experienced decreased bacterial diversity during vancomycin treatment. However, these animals were able to recover their initial Blautia and Lactobacillus proportions, even though episodes of Staphylococcus overgrowth were detected by the end of the experiments. In conclusion, MK-3415A (actoxumab-bezlotoxumab) treatment facilitates normalization of the gut microbiota in CDI mice. It remains to be examined whether or not the prevention of recurrent CDI by the antitoxin antibodies observed in clinical trials occurs through modulation of microbiota.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Neutralizantes/administración & dosificación , Antitoxinas/administración & dosificación , Clostridioides difficile/aislamiento & purificación , Infecciones por Clostridium/microbiología , Infecciones por Clostridium/terapia , Microbioma Gastrointestinal/efectos de los fármacos , Animales , Antibacterianos/administración & dosificación , Anticuerpos ampliamente neutralizantes , Modelos Animales de Enfermedad , Estudios Longitudinales , Ratones , Análisis de Supervivencia , Resultado del Tratamiento , Vancomicina/administración & dosificaciónRESUMEN
Improving soil fertility/productivity and reducing environmental impact of nitrogen (N) fertilization are essential for sustainable agriculture. Quantifying the contribution of various fertilization regimes to soil N storage and loss has been lacking in a wide range of spatiotemporal scales. Based on data collected from field experiments at three typical agricultural zones in China, soil N dynamics and N changes in soil profile (0-100 cm) were examined during 1990-2009 under chemical fertilization, manure incorporation with fertilizer, and fertilizer with straw return treatments. We employed a mass balance approach to estimate the N loss to the environment after taking into account soil N change. Results showed a significant increase in soil N storage under manure incorporation treatments, accompanied with the lowest N loss (ave.20-24% of total N input) compared to all other treatments (ave.35-63%). Both soil N distribution and mass balance data suggested higher leaching risk from chemical fertilization in acidic soil of southern China with higher precipitation than the other two sites. This research concludes that manure incorporation with chemical fertilizer not only can achieve high N use efficiency and improve soil fertility, but also leads to the lowest total N loss or damage to the environment.
RESUMEN
To investigate potential interactions between the soil ionome and enzyme activities affected by fertilization with or without organic fertilizer, soil samples were collected from four long-term experiments over China. Irrespective of variable interactions, fertilization type was the major factor impacting soil ionomic behavior and accounted for 15.14% of the overall impact. Sampling site was the major factor affecting soil enzymatic profile and accounted for 34.25% of the overall impact. The availabilities of Pb, La, Ni, Co, Fe and Al were significantly higher in soil with only chemical fertilizer than the soil with organic amendment. Most of the soil enzyme activities, including α-glucosidase activity, were significantly activated by organic amendment. Network analysis between the soil ionome and the soil enzyme activities was more complex in the organic-amended soils than in the chemical fertilized soils, whereas the network analysis among the soil ions was less complex with organic amendment. Moreover, α-glucosidase was revealed to generally harbor more corrections with the soil ionic availabilities in network. We concluded that some of the soil enzymes activated by organic input can make the soil more vigorous and stable and that the α-glucosidase revealed by this analysis might help stabilize the soil ion availability.
Asunto(s)
Enzimas/metabolismo , Fertilizantes , Compuestos Orgánicos , Suelo , Concentración de Iones de HidrógenoRESUMEN
The significance of mycorrhizas (fungal roots in 90% of land plants) in plant nutrient acquisition and growth, element biogeochemical cycling and maintaining of terrestrial ecosystem structures has been globally established for more than 120 years. Great progress in mycorrhizal research in the past 60 years (1950-2009, 1981-2009 in particular) has also been made across China, particularly in the mainland, Hong Kong and Taiwan. For instance, a total of 20 new and approximately 120 records of arbuscular mycorrhizal (AM) fungal species, 30 new and approximately 800 records of ectomycorrhizal (EM) fungal species, a dozen of new and approximately 100 records of orchid mycorrhizal (OM) fungal species have been isolated by morphological observation and/or molecular identification in China since the 1950s. Great accomplishment has also been made in the following area, including fungal species richness and genetic structure, relationships between species composition and plant taxa, effects of mycorrhizal fungi on plant nutrient uptake and growth, resistances to pathogens and interactions with other soil microorganisms, potential of mycorrhizal fungi in phytoremediation and/or land reclamation, alterations of enzymatic activities in mycorrhizal plants, and elevated CO(2) and O(3) on root colonization and species diversity. Unfortunately, the international community cannot easily appreciate almost all Chinese mycorrhizal studies since the vast majority of them have been published in Chinese and/or in China-based journals. The aim of this review is to make a comprehensive exposure of the past and present China's major mycorrhizal research to the whole world, and then to suggest potential directions for the enhancement of future mycorrhizal research within and/or between the Chinese and international mycorrhizal community.