Cancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants that regulate colorectal cancer (CRC) ...metastasis and chemoresistance have not been fully characterized.
CAFs and NFs were obtained from fresh CRC and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs in exosomes secreted by CAFs or NFs. The internalization of exosomes, transfer of miR-92a-3p was observed by immunofluorescence. Boyden chamber migration and invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection and primary colon cancer liver metastasis assays were employed to explore the effect of NFs, CAFs and exosomes secreted by them on epithelial-mesenchymal transition, stemness, metastasis and chemotherapy resistance of CRC. Luciferase report assay, real-time qPCR, western blot, immunofluorescence, and immunohistochemistry staining were employed to explore the regulation of CRC metastasis and chemotherapy resistance by miR-92a-3p, FBXW7 and MOAP1.
CAFs promote the stemness, epithelial-mesenchymal transition (EMT), metastasis and chemotherapy resistance of CRC cells. Importantly, CAFs exert their roles by directly transferring exosomes to CRC cells, leading to a significant increase of miR-92a-3p level in CRC cells. Mechanically, increased expression of miR-92a-3p activates Wnt/β-catenin pathway and inhibits mitochondrial apoptosis by directly inhibiting FBXW7 and MOAP1, contributing to cell stemness, EMT, metastasis and 5-FU/L-OHP resistance in CRC. Clinically, miR-92a-3p expression is significantly increased in CRC tissues and negatively correlated with the levels of FBXW7 and MOAP1 in CRC specimens, and high expression of exosomal miR-92a-3p in serum was highly linked with metastasis and chemotherapy resistance in CRC patients.
CAFs secreted exosomes promote metastasis and chemotherapy resistance of CRC. Inhibiting exosomal miR-92a-3p provides an alternative modality for the prediction and treatment of metastasis and chemotherapy resistance in CRC.
Biopolymers are considered a potential alternative to conventional chemical polymers because of their ease of biodegradability, high efficiency, non-toxicity and non-secondary pollution. Recently, ...extracellular polymeric substances (EPS, biopolymers produced by the microorganisms) have been recognised by many researchers as a potential flocculent for their applications in various water, wastewater and sludge treatment processes. In this context, literature information on EPS is widely dispersed and is very scarce. Thus, this review marginalizes various studies conducted so far about EPS nature-production-recovery, properties, environmental applications and moreover, critically examines future research needs and advanced application prospective of the EPS. One of the most important aspect of chemical composition and structural details of different moieties of EPS in terms of carbohydrates, proteins, extracellular DNA, lipid and surfactants and humic substances are described. These chemical characteristics of EPS in relation to formation and properties of microbial aggregates as well as degradation of EPS in the matrix (biomass, flocs etc) are analyzed. The important engineering properties (based on structural characteristics) such as adsorption, biodegradability, hydrophilicity/hydrophobicity of EPS matrix are also discussed in details. Different aspects of EPS production process such as bacterial strain maintenance; inoculum and factors affecting EPS production were presented. The important factors affecting EPS production include growth phase, carbon and nitrogen sources and their ratio, role of other nutrients (phosphorus, micronutrients/trace elements, and vitamins), impact of pH, temperature, metals, aerobic versus anaerobic conditions and pure and mixed culture. The production of EPS in high concentration with high productivity is essential due to economic reasons. Therefore, the knowledge about all the aspects of EPS production (listed above) is highly essential to formulate a logical and scientific basis for the research and industrial activities. One of the very important issues in the production/application/biodegradation of EPS is how the EPS is extracted from the matrix or a culture broth. Moreover, EPS matrix available in different forms (crude, loosely bound, tightly bound, slime, capsular and purified) can be used as a bioflocculant material. Several chemical and physical methods for the extraction of EPS (crude form or purified form) from different sources have been analyzed and reported. There is ample information available in the literature about various EPS extraction methods. Flocculability, dewaterability and biosorption ability are the very attractive engineering properties of the EPS matrix. Recent information on important aspects of these properties qualitatively as well as quantitatively has been described. Recent information on the mechanism of flocculation mediated by EPS is presented. Potential role of EPS in sludge dewatering and biosorption phenomenon has been discussed in details. Different factors influencing the EPS ability to flocculate and dewaterability of different suspensions have been included. The factors considered for the discussion are cations, different forms of EPS, concentration of EPS, protein and carbohydrate content of EPS, molecular weight of EPS, pH of the suspension, temperature etc. These factors were selected for the study based upon their role in the flocculation and dewatering mechanism as well the most recent available literature findings on these factors. For example, only recently it has been demonstrated that there is an optimum EPS concentration for sludge flocculation/dewatering. High or low concentration of EPS can lead to destabilization of flocs. Role of EPS in environmental applications such as water treatment, wastewater flocculation and settling, colour removal from wastewater, sludge dewatering, metal removal and recovery, removal of toxic organic compounds, landfill leachate treatment, soil remediation and reclamation has been presented based on the most recent available information. However, data available on environmental application of EPS are very limited. Investigations are required for exploring the potential of field applications of EPS. Finally, the limitations in the knowledge gap are outlined and the research needs as well as future perspectives are highlighted.
•Bacterial extracellular polymeric substances (EPS) are of bioengineering interest.•Biochemical nature and important properties of EPS were reviewed and discussed.•EPS have attractive engineering properties and they are the potential flocculants.•Important EPS production aspects were critically analysed and thoroughly discussed.•EPS can play important role in several environmental pollution control strategies.
Summary Objective Disruptions of extracellular matrix (ECM) homeostasis are key events in the pathogenesis of osteoarthritis (OA). MicroRNA-140 (miRNA-140) is expressed specifically in cartilage and ...regulates ECM-degrading enzymes. Our objective in this study was to determine if intra-articular injection of miRNA-140 can attenuate OA progression in rats. Design miRNA-140 levels in human normal and OA cartilage derived chondrocytes and synovial fluid were assessed by polymerase chain reaction (PCR). After primary human chondrocytes were transfected with miRNA-140 mimic or inhibitor, PCR and western blotting were performed to quantify Collagen II, MMP-13, and ADAMTS-5 expression. An OA model was induced surgically in rats, and subsequently treated with one single intra-articular injection of miRNA-140 agomir. At 4, 8, and 12 weeks after surgery, OA progression were evaluated macroscopically, histologically, and immunohistochemically in these rats. Results miRNA-140 levels were significantly reduced in human OA cartilage derived chondrocytes and synovial fluid compared with normal chondrocytes and synovial fluid. Overexpressing miRNA-140 in primary human chondrocytes promoted Collagen II expression and inhibited MMP-13 and ADAMTS-5 expression. miRNA-140 levels in rat cartilage were significantly higher in the miRNA-140 agomir group than in the control group. Moreover, behavioural scores, chondrocyte numbers, cartilage thickness and Collagen II expression levels in cartilage were significantly higher, while pathological scores and MMP-13 and ADAMTS-5 expression levels were significantly lower in the miRNA-140 agomir group than in the control group. Conclusion Intra-articular injection of miRNA-140 can alleviate OA progression by modulating ECM homeostasis in rats, and may have potential as a new therapy for OA.
This review summarizes the effect of high- and low-temperature thermal pretreatment (TPT) on sludge dewaterability, anaerobic digestion (AD), and biogas production efficiencies. The AD of the TPT ...sludge has demonstrated the following observations: reduced sludge retention time, increased biogas generation, higher organics degradation, improved dewaterability, and lower digester volume than the conventional AD of sludge. Energy balance of the TPT process was energetically self-sustainable and produced surplus energy at solids concentration greater than 3%. Net energy and energy ratio of TPT and AD revealed that net energy and energy ratio are increased with increase in total solids concentration.
Ultrasonic pretreatment of sludge: A review Pilli, Sridhar; Bhunia, Puspendu; Yan, Song ...
Ultrasonics sonochemistry,
2011, 2011-Jan, 2011-01-00, 20110101, Volume:
18, Issue:
1
Journal Article
Peer reviewed
Open access
Ultrasonication is an emerging and very effective mechanical pretreatment method to enhance the biodegradability of the sludge, and it would be very useful to all wastewater treatment plants in ...treating and disposing sewage sludge. Ultrasonication enhances the sludge digestibility by disrupting the physical, chemical and biological properties of the sludge. The degree of disintegration depends on the sonication parameters and also on sludge characteristics, therefore the evaluation of the optimum parameters varies with the type of sonicater and sludge to be treated. The full-scale installations of ultrasonication have demonstrated that there is 50% increase in the biogas generation, and in addition evaluation of energy balance showed that the average ratio of the net energy gain to electric consumed by the ultrasound device is 2.5. This review article summarizes the benefits of ultrasonication of sludge, the effect of sonication parameters, impact of sludge characteristics on sludge disintegration, and thereby the increase in biogas production in anaerobic digester. Due to uncertainty in the unit representation by many researchers and nonavailability of the data, comparison of these results is complicated. Comparison of ultrasonication with other pretreatment options is necessary to evaluate the best economical and environmental pretreatment technology for sludge treatment and disposal. The optimum parameters for the ultrasonication vary with sludge characteristics.
Despite intense interests in developing blood measurements of Alzheimer's disease (AD), the progress has been confounded by limited sensitivity and poor correlation to brain pathology. Here, we ...present a dedicated analytical platform for measuring different populations of circulating amyloid β (Aβ) proteins - exosome-bound vs. unbound - directly from blood. The technology, termed amplified plasmonic exosome (APEX), leverages in situ enzymatic conversion of localized optical deposits and double-layered plasmonic nanostructures to enable sensitive, multiplexed population analysis. It demonstrates superior sensitivity (~200 exosomes), and enables diverse target co-localization in exosomes. Employing the platform, we find that prefibrillar Aβ aggregates preferentially bind with exosomes. We thus define a population of Aβ as exosome-bound (Aβ42+ CD63+) and measure its abundance directly from AD and control blood samples. As compared to the unbound or total circulating Aβ, the exosome-bound Aβ measurement could better reflect PET imaging of brain amyloid plaques and differentiate various clinical groups.
Background
Hepatic vein tumour thrombus (HVTT) is a major determinant of survival outcomes for patients with hepatocellular carcinoma (HCC). An Eastern Hepatobiliary Surgery Hospital (EHBH)‐HVTT ...model was established to predict the prognosis of patients with HCC and HVTT after liver resection, in order to identify optimal candidates for liver resection.
Methods
Patients with HCC and HVTT from 15 hospitals in China were included. The EHBH‐HVTT model with contour plot was developed using a non‐linear model in the training cohort, and subsequently validated in internal and external cohorts.
Results
Of 850 patients who met the inclusion criteria, there were 292 patients who had liver resection and 198 who did not in the training cohort, and 124 and 236 in the internal and external validation cohorts respectively. Contour plots for the EHBH‐HVTT model were established to predict overall survival (OS) rates of patients visually, based on tumour diameter, number of tumours and portal vein tumour thrombus. This differentiated patients into low‐ and high‐risk groups with distinct long‐term prognoses in the liver resection cohort (median OS 34·7 versus 12·0 months; P < 0·001), internal validation cohort (32·8 versus 10·4 months; P = 0·002) and external validation cohort (15·2 versus 6·5 months; P = 0·006). On subgroup analysis, the model showed the same efficacy in differentiating patients with HVTT in peripheral and major hepatic veins, the inferior vena cava, or in patients with coexisting portal vein tumour thrombus.
Conclusion
The EHBH‐HVTT model was accurate in predicting prognosis in patients with HCC and HVTT after liver resection. It identified optimal candidates for liver resection among patients with HCC and HVTT, including tumour thrombus in the inferior vena cava, or coexisting portal vein tumour thrombus.
Antecedentes
La trombosis tumoral de la vena hepática (hepatic vein tumour thrombus, HVTT) es un determinante importante de los resultados de supervivencia en pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC). Se desarrolló el modelo llamado Eastern Hepatobiliary Surgery Hospital (EHBH)‐HVTT para predecir el pronóstico de los pacientes con HCC y HVTT después de la resección hepática (liver resection, LR), con el fin de identificar los candidatos óptimos para LR entre estos pacientes.
Métodos
Se incluyeron pacientes con HCC y HVTT de 15 hospitales en China. El modelo EHBH‐HVTT con gráfico de contorno se desarrolló utilizando un modelo no lineal en la cohorte de entrenamiento, siendo posteriormente validado en cohortes internas y externas.
Resultados
De 850 pacientes que cumplieron con los criterios de inclusión, hubo 292 pacientes en el grupo LR y 198 pacientes en el grupo no LR en la cohorte de entrenamiento, y 124 y 236 en las cohortes de validación interna y externa. Los gráficos de contorno del modelo EHBH‐HVTT se establecieron para predecir visualmente las tasas de supervivencia global (overall survival, OS) de los pacientes, en función del diámetro del tumor, número de tumores y del trombo tumoral de la vena porta (portal vein tumour thrombus, PVTT). Esto diferenciaba a los pacientes en los grupos de alto y bajo riesgo, con distinto pronóstico a largo plazo en las 3 cohortes (34,7 versus 12,0 meses, 32,8 versus 10,4 meses y 15,2 versus 6,5 meses, P < 0,001). En el análisis de subgrupos, el modelo mostró la misma eficacia en la diferenciación de pacientes con HVTT, con trombo tumoral en la vena cava inferior (inferior vena cava tumour thrombus, IVCTT) o en pacientes con PVTT coexistente.
Conclusión
El modelo EHBH‐HVTT fue preciso para la predicción del pronóstico en pacientes con HCC y HVTT después de la LR. Identificó candidatos óptimos para LR en pacientes con HCC y HVTT, incluyendo IVCTT o PVTT coexistente.
The Eastern Hepatobiliary Surgery Hospital–hepatic vein tumour thrombus (EHBH‐HVTT) model was accurate in predicting prognosis in patients with hepatocellular carcinoma (HCC) and HVTT after liver resection. It identified optimal candidates for liver resection among patients with HCC and HVTT, including inferior vena cava tumour thrombus, or coexisting portal vein tumour thrombus (PVTT).
predicts prognosis
Wastewater treatment plants often face the problems of sludge settling mainly due to sludge bulking. Generally, synthetic organic polymer and/or inorganic coagulants (ferric chloride, alum and quick ...lime) are used for sludge settling. These chemicals are very expensive and further pollute the environment. Whereas, the bioflocculants are environment friendly and may be used to flocculate the sludge. Extracellular polymeric substances (EPS) produced by sludge microorganisms play a definite role in sludge flocculation. In this study, 25 EPS producing strains were isolated from municipal wastewater treatment plant. Microorganisms were selected based on EPS production properties on solid agar medium. Three types of EPS (slime, capsular and bacterial broth mixture of both slime and capsular) were harvested and their characteristics were studied. EPS concentration (dry weight), viscosity and their charge (using a Zetaphoremeter) were also measured. Bioflocculability of obtained EPS was evaluated by measuring the kaolin clay flocculation activity. Six bacterial strains (BS2, BS8, BS9, BS11, BS15 and BS25) were selected based on the kaolin clay flocculation. The slime EPS was better for bioflocculation than capsular EPS and bacterial broth. Therefore, extracted slime EPS (partially purified) from six bacterial strains was studied in terms of sludge settling sludge volume index (SVI) and dewatering capillary suction time (CST). Biopolymers produced by individual strains substantially improved dewaterability. The extracted slime EPS from six different strains were partially characterized.
The byproduct of cheese-producing industries, cheese whey, is considered as an environmental pollutant due to its high BOD and COD concentrations. The high organic load of whey arises from the ...presence of residual milk nutrients. As demand for milk-derived products is increasing, it leads to increased production of whey, which poses a serious management problem. To overcome this problem, various technological approaches have been employed to convert whey into value-added products. These technological advancements have enhanced whey utilization and about 50% of the total produced whey is now transformed into value-added products such as whey powder, whey protein, whey permeate, bioethanol, biopolymers, hydrogen, methane, electricity bioprotein (single cell protein) and probiotics. Among various value-added products, the transformation of whey into proteinaceous products is attractive and demanding. The main important factor which is attractive for transformation of whey into proteinaceous products is the generally recognized as safe (GRAS) regulatory status of whey. Whey and whey permeate are biotransformed into proteinaceous feed and food-grade bioprotein/single cell protein through fermentation. On the other hand, whey can be directly processed to obtain whey protein concentrate, whey protein isolate, and individual whey proteins. Further, whey proteins are also transformed into bioactive peptides via enzymatic or fermentation processes. The proteinaceous products have applications as functional, nutritional and therapeutic commodities. Whey characteristics, and its transformation processes for proteinaceous products such as bioproteins, functional/nutritional protein and bioactive peptides are covered in this review.
•Cheese whey as a potential resource for various value-added products•Routes of transformation and biotransformation of whey•Bioconversion of whey into yeast bioprotein for feed and food applications•Transformation of whey into functional and nutritional whey proteins•Transformation and biotransformation of whey proteins into bioactive peptides.
Optimal control of quantum system is significant for information science and technology. Here, an efficient scheme is proposed for implementing fast population transfer in a spin qutrit of ...nitrogen-vacancy center via shortcuts to adiabaticity (STA) with simplified drivings. At two-photon resonance, a
-configuration interaction between the spin qutrit and driving fields can be obtained effectively. By the invariant-based STA, the reversible population transfer can be realized using the Rabi pulses with sine and cosine waveforms. Compared with the superadiabatic transitionless driving, the present pulses in our strategy become simplified technically, contributing to reduce the error effect of control parameter deviations. Moreover, the high-fidelity quantum operations can be performed with the accessible decoherence rates. The protocol could offer an optimized avenue towards the STA-based quantum control of spin qutrit experimentally.
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