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Introduction: Crop straw, a major by-product of agricultural production, is pivotal in maintaining soil health and preserving the ecological environment. While straw incorporation is widely recognized as a sustainable practice, the incomplete decomposition of crop residues poses challenges to plant growth, increasing the risk of pests and diseases. This necessitates a comprehensive investigation. Methods: The current study employs a 28-day pot experiment to simulate the degradation of rice straw in paddy soils. The impacts of bioaugmentation and biostimulation on lignocellulose degradation are systematically evaluated. Results: Results indicate a high lignocellulose degradation ability in paddy soil, with over 80% straw weight loss within 28 days. Bioaugmentation with a lignocellulolytic microbial consortium enhances straw degradation during the initial stage (0-14 days). In contrast, biostimulation with readily available nutrients leads to soil acidification, hindering straw degradation and reducing microbial diversity. Furthermore, pH emerges as a critical factor influencing microbial community stability and function during lignocellulose degradation. Microbial co-occurrence network analysis reveals that microorganisms occupy ecological niches associated with different cellulose components. Notably, Module M2, comprising Proteobacteria, Firmicutes, Gemmatimonadota, Actinobacteriota, Bacteroidota, Myxococcota, Halobacterota, and Acidobacteriota, positively correlates with pH and weight loss. Discussion: This study significantly advances our understanding of microbial mechanisms in soil decomposition, emphasizing the pivotal role of pH in community stability and function in paddy soil. These findings can inform future strategies for managing rice straw while safeguarding soil ecosystem health.
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As mariculture develops, wastewater treatment becomes crucial. In this study, fixed-bed baffled reactors (FBRs) packed with carbon fiber (CFBR) or polyurethane (PFBR) as biofilm carriers were used for mariculture wastewater treatment. Under salinity shocks between 0.10 and 30.00 g/L, the reactors showed efficient and stable nitrogen removal capacities, and the maximum NH4+-N removal rates were 107.31 and 105.42 mg/(L·d) for CFBR and PFBR, respectively, with an initial NH4+-N concentration of 120.00 mg/L. Further, in the independent aerobic chambers of the FBRs for nitrogen removal, taxa enrichment varied depending on the biofilm carrier, and the assembly process was more deterministic in CFBR than in PFBR. Two distinct clusters representing the spatial distribution of the adhering and deposited sludge in CFBR and the front and rear compartments in PFBR were noted. Furthermore, microbial interactions were more numerous and stable in CFBR. These findings improve the application prospects of FBRs in mariculture wastewater treatment.
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Microbiota , Nitrificación , Aguas Residuales , Desnitrificación , Reactores Biológicos , Nitrógeno , Biopelículas , Eliminación de Residuos LíquidosRESUMEN
BACKGROUND: Assessment of segregating populations for their ability to withstand drought stress conditions is one of the best approaches to develop breeding lines and drought tolerant varieties. Bambara groundnut (Vigna subterranea L. Verdc.) is a leguminous crop, capable of growing in low-input agricultural systems in semi-arid areas. An F4 bi-parental segregating population obtained from S19-3 × DodR was developed to evaluate the effect of drought stress on photosynthetic parameters and identify QTLs associated with these traits under drought-stressed and well-watered conditions in a rainout shelter. RESULTS: Stomatal conductance (gs), photosynthesis rate (A), transpiration rate (E) and intracellular CO2 (Ci) were significantly reduced (p < 0.05) while water use efficiency (WUE) was significantly increased (p < 0.05) under drought-stressed conditions. A strong linear correlation was observed between gs, WUE, A, E and Ci under both water regimes. The variability between different water treatment, among individual lines and the interaction between lines and environment for photosynthetic parameters provides resources for superior lines selection and drought resistant variety improvement. Significant QTL for gs and FV/FM under well-watered conditions were mapped on LG5 and LG3, respectively, with more than 20% of the PVE, which could be considered as the major QTL to control these traits. Five clustered QTLs for photosynthetic traits under drought-stressed and well-watered conditions were mapped on LG5, LG6A, LG10 and LG11, respectively. CONCLUSIONS: Significant and putative QTLs associated with photosynthetic parameters and the effect of drought stress on these traits have been revealed by QTL linkage mapping and field experiment in the F4 segregating population derived from S19-3 × DodR in bambara groundnut. The study provides fundamental knowledge of how photosynthetic traits response to drought stress and how genetic features control these traits under drought-stressed and well-watered conditions in bambara groundnut.
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Vigna , Vigna/genética , Sequías , Fitomejoramiento , Mapeo Cromosómico , Fotosíntesis/genéticaRESUMEN
Oral cancer has a high mortality rate, and its treatment often causes debilitating complications. More than 90% of oral cancers are oral squamous cell carcinomas (OSCCs) that may develop from clinically recognizable oral premalignant lesions (OPLs). To eradicate OPLs before they turn into cancers, a non-invasive topical formulation is developed based on a novel combination of synergistically acting oxaliplatin (OXP) and mycophenolate (MPS) embedded in a controlled-release mucoadhesive patch fabricated by computer-aided 3D printing. After multiple rounds of testing and optimization, a v6.4 ChemoPatch is designed, which shows sustained release of OXP and MPS in vitro, minimal side leakage of drugs, an average elastic modulus of 2.38 MPa, and suitable drug stability at 4 °C or below for up to 12 months. In vivo analyses show almost all patches adhere to the dorsal tongue surface for 4 hours, and display a sustained release of OXP and MPS to tongue tissue for 3-4 hours. When applied in the 4-nitroquinoline-1-oxide-induced OPL rat model, the OXP-MPS patch significantly ablates dysplastic lesions with no damage to normal epithelial cells and minimal systemic absorption and side effects. This study reports the design of a novel mucoadhesive ChemoPatch as a noninvasive therapy to treat OPLs.
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Neoplasias , Animales , Preparaciones de Acción Retardada , Hiperplasia , RatasRESUMEN
Eprinomectin (EPM), a macrocyclic lactone with low excretion in milk and high efficacy against endoparasites and ectoparasites, is widely used in veterinary medicine. In this paper, EPM pharmacokinetics and anthelmintic efficacy previously established in one study with lactating female goats and three studies with male castrated growing dairy breed goats (all with induced mixed adult gastrointestinal nematode parasitism and treated with a single 1-mg/kg pour-on administration of EPM) were retrospectively evaluated using pharmacokinetic-pharmacodynamic (PK-PD) modeling. The PK-PD analyses between EPM exposure (Cmax and AUClast) and anthelmintic response (percent efficacy) were performed for lactating female goats only and pooled lactating female and male castrated goats. The Cmax and AUClast showed no significant difference between lactating female goats and combined male castrated goats. PK-PD modeling demonstrated Trichostrongylus colubriformis, a small-intestine nematode, as a suitable indicator of the EPM nematocidal efficacy. The EC90 values obtained by modeling Cmax vs T. colubriformis were 3.50 and 2.43 ng/mL for lactating female goats only and pooled lactating female and male castrated goats, respectively. The values of AUClast needed for 90% efficacy of T. colubriformis were 25.4 and 21.1 day*ng/mL for lactating female goats only and pooled lactating female and male castrated goats, respectively. Overall, the predicted pharmacological response against T. colubriformis is similar for lactating goats only and pooled lactating female and male castrated goats and correlates with observed efficacy. In conclusion, a dosage of 1-mg/kg EPM as a pour-on is sufficient to ensure efficacy against common nematodes in both lactating female and male castrated goats.
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Antihelmínticos , Enfermedades de las Cabras , Animales , Femenino , Enfermedades de las Cabras/tratamiento farmacológico , Enfermedades de las Cabras/parasitología , Cabras , Ivermectina/análogos & derivados , Lactancia , Masculino , Estudios Retrospectivos , TrichostrongylusRESUMEN
Promising preliminary clinical data have stimulated research on the use of the mammalian target of rapamycin (mTOR) inhibitors in lung cancer. AC1LPSZG is an mTOR inhibitor that can significantly reduce the viability in lung adenosquamous carcinoma cell line HTB-178 cells, showing potential benefits in effective control of non-small cell lung carcinomas. In this study, a sensitive LC-MS/MS analytical method for quantification of AC1LPSZG has been developed and optimized to a running time of 3 min per sample. A linear dose-response for quantification was observed over the range of 10-5000 ng/mL in rat plasma with required precision and accuracy. High extraction recovery was achieved in the ranges of 86.87-102.51% at QC levels from rat plasma without significant matrix effect. Stability profile of AC1LPSZG in rat plasma and in extract after protein precipitation suggested that samples should be processed within 6 h after collection and stored at -80 °C until analysis within 30 days. The method was successfully applied to plasma pharmacokinetics (PK) study of AC1LPSZG in rat, showing the plasma drug concentration followed a two-compartment model.
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Plasma , Espectrometría de Masas en Tándem , Animales , Cromatografía Liquida , Ratas , Reproducibilidad de los ResultadosRESUMEN
Mycophenolic acid (MPA) is commonly used for organ rejection prophylaxis via oral administration in the clinic. Recent studies have shown that MPA also has anticancer activities. To explore new therapeutic options for oral precancerous/cancerous lesions, MPA was designed to release topically on the dorsal tongue surface via a mucoadhesive patch. The objective of this study was to establish the pharmacokinetic (PK) and tongue tissue distribution of mucoadhesive MPA patch formulation after supralingual administration in rats and also compare the PK differences between oral, intravenous, and supralingual administration of MPA. Blood samples were collected from Sprague Dawley rats before and after a single intravenous bolus injection, a single oral dose, or a mucoadhesive patch administration on the dorsal tongue surface for 4 h, all with a dose of 0.5 mg/kg of MPA. Plots of MPA plasma concentration versus time were obtained. As multiple peaks were found in all three curves, the enterohepatic recycling (EHR) model in the Phoenix software was adapted to describe their PK parameters with an individual PK analysis method. The mean half-lives of intravenous and oral administrations were 10.5 h and 7.4 h, respectively. The estimated bioavailability after oral and supralingual administration was 72.4% and 7.6%, respectively. There was a 0.5 h lag-time presented after supralingual administration. The results suggest that the systemic plasma MPA concentrations were much lower in rats receiving supralingual administration compared to those receiving doses from the other two routes, and the amount of MPA accumulated in the tongue after patch application showed a sustained drug release pattern. Studies on the dynamic of drug retention in the tongue after supralingual administration showed that ~3.8% of the dose was accumulated inside of tongue right after the patch removal, ~0.11% of the dose remained after 20 h, and ~20.6% of MPA was not released from the patches 4 h after application. The data demonstrate that supralingual application of an MPA patch can deliver a high amount of drug at the site of administration with little systemic circulation exposure, hence lowering the potential gastrointestinal side effects associated with oral administration. Thus, supralingual administration is a potential alternative route for treating oral lesions.
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Oxaliplatin (OXP), a third-generation platinum-based chemotherapy drug, was often indirectly analyzed via total platinum by an ICP-MS because it was difficult to directly quantify using an LC-MS/MS method, due to its instability, bad column separability and severe MS signal inhibition. Here, we developed and validated a specific, sensitive and reproducible LC-MS/MS method for the quantification of OXP itself in rat plasma and tongue tissue on a SCIEX 4000 QTRAP® MS/MS system equipped with a Phenomenex Lux 5u Cellulose-1 column (250 × 4.6 mm, 5 µm). This method was validated at the lower limit of detection (LOD) and the lower limit of quantitation (LLOQ) of 5 ng/mL and 10 ng/mL, with linearity of 10-5000 ng/mL (r2 > 0.99) and 10-2500 ng/mL (r2 > 0.99), in rat plasma and tongue homogenates, respectively. The intra- and inter-day precision (CV%) and accuracy (RE%) were within 15% for LLOQ, low-, medium- and high-quality control samples. The mean extraction recoveries were around 50% and 80% for plasma and tongue homogenates, respectively. This assay was successfully applied to pharmacokinetics study following intravenous administration of OXP, as well as tongue tissue distribution after 1 h and 4 h of a novel oral mucosal patch application.
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BACKGROUND: A peripherally inserted central catheter (PICC) is often necessary for patients receiving chemotherapy, but there is a risk of PICC-related venous thrombosis (VT). We sought to use the Caprini thrombosis risk model and color Doppler flow imaging for the dynamic monitoring of an eventual thrombosis in patients receiving chemotherapy. METHODS: This prospective study was carried out from January 2018 to May 2019 in patients who underwent PICC implantation and maintenance at the First Affiliated Hospital of Fujian Medical University. The outcome event was the occurrence of PICC-related upper extremity venous thrombosis confirmed by color Doppler flow imaging. RESULTS: A total of 201 participants were enrolled, of whom 108 (53.7%) developed VT. Three participants (1.5%) developed symptomatic VT. Univariable logistic regression analysis suggested that the Caprini score (odds ratio [OR], 1.243; 95% confidence interval [CI], 1.074-1.438; P = .003), the PICC model (OR, 0.448; 95% CI, 0.223-0.901; P = .024), and a previous history of PICC-related deep vein thrombosis (OR, 9.388; 95% CI, 1.178-74.786; P = .034) were associated with PICC-related upper extremity VT. Multivariable logistic regression analysis showed that only the Caprini score (OR, 1.188; 95% CI, 1.018-1.386; P = .029) was an independent risk factor for PICC-related venous thrombus. A receiver operating characteristic curve analysis showed the Caprini risk assessment model had a predictive value for upper extremity VT, with an area under the curve of 0.615 (95% CI, 0.538-0.693), 74.1% sensitivity, and 44.1% specificity. CONCLUSIONS: The Caprini score is an independent predictor of the development of PICC-related VT in patients with cancer. However, the moderate sensitivity and low specificity of the Caprini risk assessment model may limit its predictive value in the clinical setting.
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Cateterismo Venoso Central/efectos adversos , Cateterismo Periférico/efectos adversos , Neoplasias/complicaciones , Medición de Riesgo , Trombosis Venosa Profunda de la Extremidad Superior/etiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Sensibilidad y Especificidad , Ultrasonografía Doppler en Color , Trombosis Venosa Profunda de la Extremidad Superior/diagnóstico por imagenRESUMEN
OBJECTIVE: The purpose of this study was to determine whether cervical cancer is a risk factor for early mortality among women with HIV and whether racial/ethnic disparity predicted in-hospital death among women living with HIV and diagnosed with cervical cancer. METHODS: We conducted a population-based study using the National Inpatient Sample (NIS) database comprising hospitalized HIV-positive women with or without cervical cancer diagnosis, from 2003 through 2015. We compared trends in the rates of cervical cancer, in-hospital death, and years of potential life lost (YPLL) by race/ethnicity. RESULTS: We identified 2,613,696 women with HIV, and among them, 5398 had cervical cancer. The prevalence of cervical cancer (per 10,000) was 9.3 for NH-Whites, 30.9 among NH-Blacks, and 30.2 for Hispanics. Rates of cervical cancer over time diminished significantly only among NH-Whites (average annual percent change (AAPC), - 5.8 (- 9.7, - 1.8)), and YPLL in women with cervical cancer decreased significantly only in NH-Whites (AAPC, - 6.2 (- 10.1, - 2.0)). Cervical cancer was associated with increased odds of in-hospital death overall (OR 2.24 (1.59-3.15)) and among NH-Blacks (OR 2.03 (1.30-3.18)) only. CONCLUSIONS: NH-Blacks and Hispanics with HIV remain at increased risk for concurrent diagnosis of cervical cancer compared with NH-Whites. Moreover, NH-Black women with HIV and cervical cancer are at greatest risk for in-hospital death. The findings emphasize the need for a more robust prevention strategy among minority women to reduce the high burden of HIV/cervical cancer and related mortality.
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Negro o Afroamericano/estadística & datos numéricos , Infecciones por VIH/etnología , Disparidades en el Estado de Salud , Hispánicos o Latinos/estadística & datos numéricos , Mortalidad Hospitalaria/etnología , Neoplasias del Cuello Uterino/etnología , Adulto , Anciano , Anciano de 80 o más Años , Comorbilidad , Bases de Datos Factuales , Femenino , Humanos , Persona de Mediana Edad , Factores de Riesgo , Estados Unidos/epidemiología , Población Blanca/estadística & datos numéricos , Adulto JovenRESUMEN
INTRODUCTION: CLBQ14, a derivative of 8-hydroxyquinoline, exerts its chemotherapeutic effect by inhibiting methionine aminopeptidase (MetAP), the enzyme responsible for the post-translational modification of several proteins and polypeptides. MetAP is a novel target for infectious diseases. CLBQ14 is selective and highly potent against replicating and latent Mycobacterium tuberculosis making it an appealing lead for further development. METHODS: The physicochemical properties (solubility, pH stability and lipophilicity), in vitro plasma stability and metabolism, pre-clinical pharmacokinetics, plasma protein binding and tissue distribution of CLBQ14 in adult male Sprague-Dawley rats were characterized. RESULTS: At room temperature, CLBQ14 is practically insoluble in water (<0.07 mg/mL) but freely soluble in dimethyl acetamide (>80 mg/mL); it has a log P value of 3.03 ± 0.04. CLBQ14 exhibits an inverse Z-shaped pH decomposition profile; it is stable at acidic pH but is degraded at a faster rate at basic pH. It is highly bound to plasma proteins (>91%), does not partition to red blood cells (B/P ratio: 0.83 ± 0.03), and is stable in mouse, rat, monkey and human plasma. CLBQ14 exhibited a bi-exponential pharmacokinetics after intravenous administration in rats, bioavailability of 39.4 and 90.0%, respectively from oral and subcutaneous route. We observed a good correlation between predicted and observed rat clearance, 1.90 ± 0.17 L/kg/h and 1.67 ± 0.08 L/kg/h, respectively. Human hepatic clearance predicted from microsomal stability data and from the single species scaling were 0.80 L/hr/kg and 0.69 L/h/kg, respectively. CLBQ14 is extensively distributed in rats; following a 5 mg/kg intravenous administration, lowest and highest concentrations of 15.6 ± 4.20 ng/g of heart and 405.9 ± 77.11 ng/g of kidneys, respectively, were observed. In vitro CYP reaction phenotyping demonstrates that CLBQ14 is metabolized primarily by CYP 1A2. CONCLUSION: CLBQ14 possess appealing qualities of a drug candidate. The studies reported herein are imperative to the development of CLBQ14 as a new chemical entity for infectious diseases.
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Enfermedades Transmisibles/tratamiento farmacológico , Inhibidores Enzimáticos/farmacocinética , Metionil Aminopeptidasas/antagonistas & inhibidores , Oxiquinolina/análogos & derivados , Animales , Química Física , Enfermedades Transmisibles/metabolismo , Inhibidores Enzimáticos/sangre , Inhibidores Enzimáticos/química , Corazón , Humanos , Riñón , Macaca fascicularis , Masculino , Metionil Aminopeptidasas/metabolismo , Ratones , Estructura Molecular , Oxiquinolina/sangre , Oxiquinolina/química , Oxiquinolina/farmacocinética , Ratas , Ratas Sprague-Dawley , Termodinámica , Distribución TisularRESUMEN
INTRODUCTION: Diabetes mellitus (DM) and metabolic syndrome (MetS) are systemic metabolic disorders, which have risk factors for diabetic cardiovascular and cerebral microvascular disease. It is very important to screen the metabolic biomarkers between DM and MetS patients, which can make patients benefit to a greater extent and prevent the occurrence of disease in advance. OBJECTIVES: Diabetes mellitus (DM) and metabolic syndrome are a complex, chronic illness with a pronounced impact on the quality of life of many people. However, understanding the metabolic changes in patients and identifying high-risk individuals is crucial for prevention and disease management strategies. METHODS: In this study, a nontargeted metabolomics approach based on UPLC-Q-TOF/MS was used to find the differential metabolites in serum samples from patients with DM and MetS. RESULTS: Metabonomic analysis reveals metabolic differences between DM and HC with significant differences more than 60 metabolites. While, more than 65 metabolites have significant differences between MetS and HC. The independent disturbed pathway in the DM group was the FoxO signaling pathway. The independent disturbed pathways in the MetS group were the alpha-linolenic acid metabolism, glycerophospholipid metabolism and pyrimidine metabolism. The independent disturbed metabolites and the logistic regression result showed that betaine, alpha-linolenic acid, d-mannose, l-glutamine and methylmalonic acid can be used as a combinatorial biomarker to distinguish DM from healthy control. L-isoleucine, l-glutamine, PC(16:0/16:0), alpha-d-glucose, ketoisocaproic acid, d-mannose, uridine can be used as a combinatorial biomarker in MetS. CONCLUSION: Our findings, on one hand, provide critical insight into the pathological mechanism of DM and MetS. On the other hand, supply a combinatorial biomarker to aid the diagnosis of diseases in clinical usage.
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Cromatografía Líquida de Alta Presión/métodos , Diabetes Mellitus/sangre , Espectrometría de Masas/métodos , Síndrome Metabólico/sangre , Metaboloma , Anciano , Biomarcadores/sangre , Femenino , Humanos , Metabolismo de los Lípidos , Modelos Logísticos , Masculino , Metabolómica/métodos , Persona de Mediana Edad , Estudios Prospectivos , Pirimidinas/metabolismo , Calidad de Vida , Factores de RiesgoRESUMEN
Mycophenolic acid (MPA) has being used clinically for organ rejection prophylaxis. Recent studies have revealed that MPA can also act as a chemo-sensitizing agent when used in combination with various chemotherapeutic agents in a cancer type-specific manner, including with oxaliplatin on oral squamous cell carcinoma (OSCC) cells. To prepare for the analysis of a novel drug delivery route for MPA absorption via oral mucosa as a potential therapeutic product, it is essential to develop and validate a highly sensitive analytical method for the quantification of MPA in biological samples for pharmacokinetic and tissue distribution studies. Herein, we report a sensitive, specific and reproducible UPLC-MS/MS method to do so. Blank rat plasma or tongue tissue homogenates coupled with griseofulvin, as internal standard, was used for generating standard curves ranging from 0.5 to 1000 ng/mL (r > 0.9990) for both plasma and tongue tissue homogenates. The chromatographic separation was achieved by a reverse phase ACE Excel 2 Super C18 column with a flow rate of 0.4 mL/min under gradient elution. Mass detection was performed under positive ionization electrospray. Inter- and intra-day accuracy and precision of the assay were ≤15% in both plasma and tongue tissue homogenates. The matrix effect was non-significant and extraction recovery rates were within 87.99% and 109.69% in plasma and tongue homogenates, respectively. The validity of this assay has been confirmed by measuring MPA in rat plasma for pharmacokinetics following intravenous administration of 0.5 mg/kg of mycophenolate sodium, as well as monitoring MPA in rat tongues for tissue distribution and detecting MPA that diffused into systemic circulation following a 4-h transmucosal delivery of 357 µg/cm2 of mycophenolate sodium.
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Cromatografía Líquida de Alta Presión/métodos , Ácido Micofenólico/análisis , Ácido Micofenólico/farmacocinética , Espectrometría de Masas en Tándem/métodos , Lengua/metabolismo , Animales , Modelos Lineales , Masculino , Ácido Micofenólico/sangre , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Distribución Tisular , Lengua/químicaRESUMEN
MAIN CONCLUSION: Bambara groundnut has the potential to be used to contribute more the climate change ready agriculture. The requirement for nitrogen fixing, stress tolerant legumes is clear, particularly in low input agriculture. However, ensuring that existing negative traits are tackled and demand is stimulated through the development of markets and products still represents a challenge to making greater use of this legume. World agriculture is currently based on very limited numbers of crops, representing a significant risk to food supplies, particularly in the face of climate change which is expected to increase the frequency of extreme events. Minor and underutilised crops can help to develop a more resilient and nutritionally dense future agriculture. Bambara groundnut [Vigna subterranea (L.) Verdc.[, as a drought resistant, nitrogen-fixing, legume has a role to play. However, as with most underutilised crops, there are significant gaps in knowledge and also negative traits such as 'hard-to-cook' and 'photoperiod sensitivity to pod filling' associated with the crop which future breeding programmes and processing methods need to tackle, to allow it to make a significant contribution to the well-being of future generations. The current review assesses these factors and also considers what are the next steps towards realising the potential of this crop.
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Cambio Climático , Productos Agrícolas , Vigna , Culinaria/métodos , Producción de Cultivos/métodos , Productos Agrícolas/genética , Productos Agrícolas/crecimiento & desarrollo , Vigna/genética , Vigna/crecimiento & desarrolloRESUMEN
Enhancing soybean (Glycine max) oil production is crucial to meet the market demand of vegetable oil. Diacylglycerol acyltransferase (DGAT) catalyzes the final acylation reaction of triacylglycerol (TAG) synthesis, acting as one of the rate-limiting enzymes for oil biosynthesis in plant seeds. Here, a cDNA clone VgDGAT1A encoding the DGAT1 protein was isolated from the high oil plant Vernonia galamensis. VgDGAT1A was specifically overexpressed in soybean seeds, and several high-generation transgenic lines (T7) were obtained by continuous selection. qPCR analysis showed that VgDGAT1A was highly expressed in the mid-development stage (30-45 DAF) of the transgenic seeds. Accordingly, the DGAT enzyme activity in the transgenic seeds was increased by 7.8 folds in comparison with the wild-type controls. Seed oil and starch contents were, respectively, increased by 5.1% (Dry weight) and reduced by 2%-3% in the transgenic soybeans. Importantly, protein content was not significantly different between transgenic and control seeds. Seed weight and germination rate of the transgenic lines exhibited no negative effect. Fatty acid profiling demonstrated that antioxidant oleic acid (C18:1Δ9) content in the transgenic seed oil was elevated by 8.2% compared to the control, and correspondingly, easily-oxidized linoleic acid (C18:2Δ9,12) and linolenic acid (C18:3Δ9,12,15) were decreased by 6% and 2% respectively. Taken together, seed-specific overexpression of an exogenous VgDGAT1A gene can break the negative linkage of oil and protein contents in soybean seeds, indicating that engineering of this highly-active DGAT enzyme is an effective strategy to improve oil yield and nutritional value in oilseeds.
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Diacilglicerol O-Acetiltransferasa/genética , Glycine max/química , Aceites de Plantas/química , Proteínas de Plantas/genética , Semillas/química , Valor Nutritivo , Plantas Modificadas Genéticamente/química , Plantas Modificadas Genéticamente/genética , Glycine max/genética , Vernonia/genéticaRESUMEN
Tumor hypoxia is a well-recognized driver of resistance to traditional cancer therapies such as chemotherapy and radiation therapy. We describe development of a new nanoconstruct composed of gold nanorods (GNRs) conjugated to carbonic anhydrase IX (CAIX) antibody that specifically binds to CAIX, a biomarker of hypoxia, to facilitate targeting tumor hypoxic areas for focused photothermal ablation. Physicochemical characterization studies confirmed the size, shape, monodispersity, surface charge, and serum stability of the GNRs. Enzyme-linked immunosorbent assays and cellular binding and uptake studies confirmed successful conjugation of antibody to the GNRs and specificity for CAIX. Near-infrared irradiation of CAIX-overexpressing cells treated with GNR/anti-CAIX resulted in significantly higher cell death than cells treated with control GNRs. In vivo biodistribution studies using hyperspectral imaging and inductively coupled plasma mass spectrometry confirmed intravenous administration results not only in greater accumulation of GNR/anti-CAIX in tumors than control GNRs but also greater penetration into hypoxic areas of tumors. Near-infrared ablation of these tumors showed no tumor regression in the sham-treated group, regression but recurrence in the non-targeted-GNR group, and complete tumor regression in the targeted-GNR group. GNR/anti-CAIX nanoconstructs show promise as hypoxia targeting and photothermal ablation agents for cancer treatment.