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Pancreatic adenocarcinoma (PAAD) is one of the most hazardous cancers in digestive system, and the prognosis is notoriously bad. Increasing evidences indicate that Laminin Subunit Gamma 2 (LAMC2) is critical for the initiation and the growth of various sorts of human cancers. However, the involved molecular pathways of LAMC2 in PAAD are still poorly understood. In this study, prediction programs and databases were employed to conduct pan-cancer analysis. Multiple variations of human malignancies showed increased LAMC2 expression, which was positively correlated to a poor prognosis in PAAD. Moreover, LAMC2 was positively correlated with the biomarkers of immune cells including CD19, CD163, and NOS2 in PAAD. The lncRNA C5orf66 /PTPRG-AS1- miR-128-3p -LAMC2 axis was identified to be a potential upstream regulatory pathway of LAMC2 in PAAD. Furthermore, LAMC2 upregulation in PAAD was associated with PD-L1 expression, indicating promoting carcinoma immune cell infiltration. Our study elucidated prognostic and immunological values of LAMC2 in PAAD, providing a promise target for PAAD treatment.
Assuntos
Adenocarcinoma , Carcinoma , Neoplasias Pancreáticas , RNA Longo não Codificante , Humanos , Adenocarcinoma/genética , Prognóstico , Neoplasias Pancreáticas/genética , RNA Longo não Codificante/genética , LamininaRESUMO
BG45 is a class â histone deacetylase inhibitor (HDACI) with selectivity for HDAC3. Our previous study demonstrated that BG45 can upregulate the expression of synaptic proteins and reduce the loss of neurons in the hippocampus of APPswe/PS1dE9 (APP/PS1) transgenic mice (Tg). The entorhinal cortex is a pivotal region that, along with the hippocampus, plays a critical role in memory in the Alzheimer's disease (AD) pathology process. In this study, we focused on the inflammatory changes in the entorhinal cortex of APP/PS1 mice and further explored the therapeutic effects of BG45 on the pathologies. The APP/PS1 mice were randomly divided into the transgenic group without BG45 (Tg group) and the BG45-treated groups. The BG45-treated groups were treated with BG45 at 2 months (2 m group), at 6 months (6 m group), or twice at 2 and 6 months (2 and 6 m group). The wild-type mice group (Wt group) served as the control. All mice were killed within 24 h after the last injection at 6 months. The results showed that amyloid-ß (Aß) deposition and IBA1-positive microglia and GFAP-positive astrocytes in the entorhinal cortex of the APP/PS1 mice progressively increased over time from 3 to 8 months of age. When the APP/PS1 mice were treated with BG45, the level of H3K9K14/H3 acetylation was improved and the expression of histonedeacetylase1, histonedeacetylase2, and histonedeacetylase3 was inhibited, especially in the 2 and 6 m group. BG45 alleviated Aß deposition and reduced the phosphorylation level of tau protein. The number of IBA1-positive microglia and GFAP-positive astrocytes decreased with BG45 treatment, and the effect was more significant in the 2 and 6 m group. Meanwhile, the expression of synaptic proteins synaptophysin, postsynaptic density protein 95, and spinophilin was upregulated and the degeneration of neurons was alleviated. Moreover, BG45 reduced the gene expression of inflammatory cytokines interleukin-1ß and tumor necrosis factor-α. Closely related to the CREB/BDNF/NF-kB pathway, the expression of p-CREB/CREB, BDNF, and TrkB was increased in all BG45 administered groups compared with the Tg group. However, the levels of p-NF-kB/NF-kB in the BG45 treatment groups were reduced. Therefore, we deduced that BG45 is a potential drug for AD by alleviating inflammation and regulating the CREB/BDNF/NF-kB pathway, and the early, repeated administration of BG45 can play a more effective role.
Assuntos
Doença de Alzheimer , Precursor de Proteína beta-Amiloide , Córtex Entorrinal , Inibidores de Histona Desacetilases , Inflamação , Microglia , Animais , Camundongos , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Córtex Entorrinal/metabolismo , Hipocampo/metabolismo , Inflamação/metabolismo , Camundongos Transgênicos , Microglia/metabolismo , NF-kappa B/metabolismo , Presenilina-1/genética , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêuticoRESUMO
A vacuum membrane distillation (VMD) followed by crystallization (VMD-C) was developed for the recovery of water and salts from shale gas produced water (SGPW). Before VMD, the pretreatment of SGPW with Fenton oxidation-flocculation is applied, with the chemical oxygen demand (COD) concentration reduction of 75% and the total removal of the total suspended solids (TSS), Ca2+, and Mg2+ in SGPW. The pretreatment of SGPW mitigated the membrane fouling in the VMD and effectively prevented the reduction of membrane flux over time. The average flux of the PTFE membrane reached 12.1 kg m-2 h-1 during the separation of the pretreated SGPW at a feed flux of 40 L h-1 and a feed temperature of 40 °C. The rejection rate of the membrane to TDS in SGPW was over 99%. Fresh water with a conductivity of below 20 µs cm-1 was produced by VMD-C. The salts concentrated upstream of the membrane were recovered by a stirring crystallization process. The VMD-C system resulted in a 61% cost savings compared to conventional SGPW treatment.
Assuntos
Purificação da Água , Água , Água/química , Vácuo , Sais/química , Gás Natural , Purificação da Água/métodos , Destilação/métodos , Cristalização , Membranas Artificiais , Cloreto de SódioRESUMO
As a neurodegenerative disease, Alzheimer's disease (AD) seriously affects the health of older people. Changes in synapses occur first over the course of the disease, perhaps even before the formation of Aß plaques. Histone deacetylase (HDAC) mediates the damage of Aß oligomers to dendritic spines. Therefore, we examined the relationship between HDAC activity and synaptic defects using an HDAC inhibitor (HDACI), BG45, in the human neuroblastoma SH-SY5Y cell line with stable overexpression of Swedish mutant APP (APPsw) and in APP/PS1 transgenic mice during this study. The cells were treated with 15 µM BG45 and the APP/PS1 mice were treated with 30 mg/kg BG45. We detected the levels of synapse-related proteins, HDACs, tau phosphorylation, and amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors using Western blotting and immunohistochemistry. We also measured the expression of cytoskeletal proteins in the cell model. The mRNA levels of the glutamate ion receptor alginate subunit 2 (GRIK2), sodium voltage-gated channel beta subunit (SCN3B), synaptophysin (SYP), Grm2 (the gene encoding glutamate receptor subunit 2 (GluR2)), Grid2IP, glutamate receptor interacting protein 1 (GRIP1), and GRIP2 were detected to explore the effects of the HDACI on regulating the expression of synaptic proteins and AMPA receptors. According to our studies, the expressions of HDAC1, HDAC2, and HDAC3 were increased, which were accompanied by the downregulation of the synapse-related proteins SYP, postsynaptic dendritic protein (PSD-95), and spinophilin as early as 24 h after transfection with the APPsw gene. BG45 upregulated the expression of synapse-related proteins and repaired cytoskeletal damage. In vivo, BG45 alleviated the apoptosis-mediated loss of hippocampal neurons, upregulated synapse-related proteins, reduced Aß deposition and phosphorylation of tau, and increased the levels of the synapse-related genes GRIK2, SCN3B, SYP, Grm2, and Grid2IP. BG45 increased the expression of the AMPA receptor subunits GluA1, GluA2, and GluA3 on APPsw-transfected cells and increased GRIP1 and GRIP2 expression and AMPA receptor phosphorylation in vivo. Based on these results, HDACs are involved in the early process of synaptic defects in AD models, and BG45 may rescue synaptic damage and the loss of hippocampal neurons by specifically inhibiting HDAC1, HDAC2, and HDAC3, thereby modulating AMPA receptor transduction, increasing synapse-related gene expression, and finally enhancing the function of excitatory synapses. BG45 may be considered a potential drug for the treatment of early AD in further studies.
Assuntos
Doença de Alzheimer , Neuroblastoma , Doenças Neurodegenerativas , Proteínas Adaptadoras de Transdução de Sinal , Idoso , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Proteínas de Transporte , Modelos Animais de Doenças , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Camundongos Transgênicos , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Receptores de AMPA/genética , Receptores de AMPA/metabolismo , Receptores de AMPA/uso terapêutico , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/uso terapêuticoRESUMO
Aeration is one of the most important methods to keep stored grain safe and maintain its quality. Experimental platforms are used for stored grain aeration study in a laboratory-scale. The purpose of this paper was to provide the real-time data acquisition and control system design of a new experimental platform with multifunction for stored grain study. Requirements of the aeration experiments were analyzed, and multi running modes were designed. The aeration inlet air conditions were designed to be adjustable and multi variables need to be controlled simultaneously, which was a key problem to be solved for the platform. An ON/OFF-PID based multivariable cooperative control method was proposed, and two control loops were formed where inlet air temperature and humidity were considered separately while could be controlled simultaneously with a logic judgement strategy. Real-time data needed to be monitored was acquired with different sensors and displayed intuitively. Experiments were carried out to test the static and dynamic characteristics of the control method and three inlet air flow rates of 0.03, 0.08 and 0.13 m·s-1were used. Performance of the data acquisition system was also tested. The results showed that, the inlet air conditions control error was within ±1 °C and 10% for temperature and relative humidity, respectively. The real-time data acquisition of multi parameters during aeration process was realized. The experimental platform can be used for studies of different aeration objectives.
Assuntos
Grão Comestível , Umidade , TemperaturaRESUMO
Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) are well-known cytokines with pro-inflammatory capabilities, and have been shown to be involved in adaptation to exercise as multifaceted myokines. However, the precise role of IL-6 and TNF-α during exercise-induced skeletal muscle injury and subsequent repair processes is not fully understood. In this study, IL-6 and TNF-α were examined in soleus muscles at the gene and protein levels using in situ hybridization and immunohistochemical staining, respectively, and serum levels of IL-6 and TNF-α were determined before and after a 90-min downhill running session in rats. There were no changes in serum levels of IL-6 and TNF-α after exercise, but IL-6 and TNF-α mRNA increased and maintained high expression in muscles for 1-2 weeks after exercise. IL-6 and TNF-a mRNAs were identified in both the cytoplasm and the nuclei of myocytes, as well as in invading inflammatory cells. IL-6 and TNF-α protein mainly distributed in cytoplasm unevenly and had a prolonged expression until 2 weeks after eccentric exercise. Our results demonstrate that there is increased IL-6 and TNF-α expression in skeletal muscle that is induced by eccentric exercise and that the high expression of IL-6 and TNF-α in the long-term phase after eccentric exercise may be more involved in the subsequent recovery of damaged muscle.
Assuntos
Interleucina-6/metabolismo , Músculo Esquelético/fisiologia , Condicionamento Físico Animal/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Masculino , RatosRESUMO
Delayed absorption of oxidized cellulose (Surgicel; Johnson & Johnson, New Brunswick, NJ) may mimic a pseudoabscess or a recurrent mass on sonography after tumor surgery. Here we present 3 cases of thyroidectomy in which Surgicel was still apparent on sonography after 26 to 47 months of follow-up. We show sonographic findings and discuss the utility of sonography for diagnosis of delayed absorption of Surgicel in post-thyroidectomy patients.
Assuntos
Celulose Oxidada/farmacocinética , Corpos Estranhos/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Tireoidectomia , Ultrassonografia/métodos , Adulto , Idoso , Feminino , Seguimentos , Hemostáticos/farmacocinética , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A novel copper-catalyzed regioselective double carbonylation of imidazo[1,2-a]pyridines with N,N-disubstituted acetamide or acetone using molecular oxygen has been described. It has provided a new approach to synthesize 1,2-carbonyl imidazo[1,2-a]pyridines, which are important substrates and intermediates in preparation of fine chemicals. The product shares a skeleton similar to that of Zolpidem, one of the most prescribed drugs in the world. (18)O-labeling experiments unambiguously established that the oxygen source of products originated from O2 rather than H2O.
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Due to the increasing number of international exchanges, foreign users have gradually become a significant consumer segment. Many of them are not proficient in the local language. Providing them with native language services will be an important trend, both from a business and a humanistic perspective. The purpose of this study is to investigate the fast-food restaurant ordering system that can provide multilingual services for foreigners, and to investigate factors that influence fast food restaurant consumers to adopt multilingual self-service ordering systems. Based on the characteristics of foreign users, we have proposed experience factors such as convenience, translation quality, social anxiety, and the Flow. According to research, the convenience of the service has a strong direct impact on consumers' intention to use, social anxiety has a weak direct impact on consumers' intention to use, and translation quality has a weak direct impact on consumers' intention to use through the intermediate variable of social anxiety. Particularly, Flow experience is not associated with intention to use. The Flow state is one in which users are completely immersed and do not notice time or the surroundings when the perceived difficulty of a task matches their abilities. The purpose of this study is to improve our understanding of the customer evaluation criteria for multilingual self-service systems, as well as to establish the MSSS model for future research on multilingual self-service systems.
Assuntos
Multilinguismo , Restaurantes , Humanos , Fast Foods , Inquéritos e Questionários , Intenção , Comportamento do ConsumidorRESUMO
Caricature generation aims to translate portrait photos into caricatures with exaggerated and hand-drawn artistic styles. Previous methods faced challenges in creating diverse and meaningful exaggeration effects, yielding unsatisfactory and uncontrollable results. To overcome this, we proposed ETCari, a novel weakly supervised exaggeration transfer network. ETCari enables the learning of diverse exaggeration caricature styles from various artists, better meeting individual customization requirements and achieving diversified exaggeration while retaining identity features. Specifically, we use the TPS control point deformation field as the ground truth, serving as the loss for weakly supervised learning to address the challenge of no labels. We convert input to an intermediate modality for domain adaptation, training a teacher model. Subsequently, we perform cross-modal knowledge distillation to train the student model, simplifying preprocessing during inference and avoiding the impact of face parser errors. Experiments on the WebCaricature dataset demonstrate that ETCari effectively performs exaggeration transfer, generating appealing caricatures.
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Ganoderma lucidum polysaccharides are valuable natural compounds possessing significant biological activity, with glycosyltransferases playing a crucial role in their biosynthesis. Although the function of ß-1,3-glucosyltransferase in polysaccharides production is well understood, the role of α-1,3-glucosyltransferase in edible fungi remains unclear. In this study, over-expression of the α-1,3-glucosyltransferase gene in G. lucidum (glagt) was found to suppress the growth, with the maximum biomass and mycelial growth rate decreasing by 21.78 % and 79.61 %, respectively, a behavior distinct from ß-1,3-glucosyltransferase. The fungal pellet diameter decreased by 38 % and the cell-wall thickness by 32.44 %, whereas intracellular and extracellular polysaccharides production increased by 27.58 % and 66.08 %, respectively. In the transcription level, overexpressing the glagt gene i) downregulated the citrate synthase and isocitrate dehydrogenase gene in the TCA cycle, disrupting energy metabolism and fungal growth; ii) upregulated key enzymes involved in UDP-glucose synthesis and glycosyltransferases (gl24465, gl24971, and gl22535); and iii) universally increased the transcriptional level of glucosidases gl21451, gl30087, and gl24581 by 22 %-397 %, contributing to cell-wall thinning to facilitate polysaccharides export. Conversely, the glagt gene downregulation promoted G. lucidum growth and decreased polysaccharides production. The results elucidate the roles of GLAGT and are expected to inspire in-depth exploration of polysaccharides biosynthesis pathways.
Assuntos
Regulação Fúngica da Expressão Gênica , Glucosiltransferases , Reishi , Reishi/genética , Reishi/enzimologia , Reishi/crescimento & desenvolvimento , Reishi/metabolismo , Glucosiltransferases/metabolismo , Glucosiltransferases/genética , Polissacarídeos/biossíntese , Biomassa , Polissacarídeos Fúngicos/biossíntese , Parede Celular/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismoRESUMO
Pseudolaric acid B (PAB), an acid isolated from the roots of Pseudolarix kaempferi gorden, has shown antitumour effects through multiple mechanisms of action. The objective of this study was to investigate the anticancer effect of PAB on non-small cell lung cancer (NSCLC) and its underlying mechanism. In our experiments, we observed that PAB decreased cell viability, inhibited colony formation, induced cell cycle arrest, impeded scratch healing, and increased apoptosis in H1975 and H1650 cells. Additionally, PAB treatment enhanced the fluorescence intensity of MDC staining in NSCLC cells, upregulated the protein expression of microtubule-associated protein light chain 3 II (LC3 II), and downregulated the expression of sequestosome 1 (SQSTM1/P62). Combined treatment with PAB and chloroquine (CQ) increased the protein expression levels of LC3 II and P62 while decreasing the apoptosis of H1975 and H1650 cells. Moreover, treatment with PAB led to significant mTOR inhibition and AMPK activation. PAB combined with compound C (CC) inhibited autophagy and apoptosis. Furthermore, PAB treatment increased intracellular reactive oxygen species (ROS) levels in NSCLC cells, which correlated with the modulation of the AMPK/mTOR signalling pathway and was associated with autophagy and apoptosis. Finally, we validated the antitumour growth activity and mechanism of PAB in vivo using athymic nude mice bearing H1975 tumour cells. In conclusion, our findings suggest that PAB can induce apoptosis and autophagic cell death in NSCLC through the ROS-triggered AMPK/mTOR signalling pathway, making it a promising candidate for future NSCLC treatment.
Assuntos
Proteínas Quinases Ativadas por AMP , Apoptose , Autofagia , Carcinoma Pulmonar de Células não Pequenas , Diterpenos , Neoplasias Pulmonares , Camundongos Nus , Espécies Reativas de Oxigênio , Transdução de Sinais , Serina-Treonina Quinases TOR , Serina-Treonina Quinases TOR/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Humanos , Animais , Autofagia/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Diterpenos/farmacologia , Apoptose/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos , Progressão da Doença , Ensaios Antitumorais Modelo de Xenoenxerto , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacosRESUMO
BACKGROUND: The ubiquitous, non-proteinaceous amino acid GABA (γ-aminobutyrate) accumulates in plants subjected to abiotic stresses such as chilling, O2 deficiency and elevated CO2. Recent evidence indicates that controlled atmosphere storage causes the accumulation of GABA in apple (Malus x domestica Borkh.) fruit, and now there is increasing interest in the biochemical mechanisms responsible for this phenomenon. Here, we investigated whether this phenomenon could be mediated via Ca(2+)/calmodulin (CaM) activation of glutamate decarboxylase (GAD) activity. RESULTS: GAD activity in cell-free extracts of apple fruit was stimulated by Ca(2+)/CaM at physiological pH, but not at the acidic pH optimum. Based on bioinformatics analysis of the apple genome, three apple GAD genes were identified and their expression determined in various apple organs, including fruit. Like recombinant Arabidopsis GAD1, the activity and spectral properties of recombinant MdGAD1 and MdGAD2 were regulated by Ca(2+)/CaM at physiological pH and both enzymes possessed a highly conserved CaM-binding domain that was autoinhibitory. In contrast, the activity and spectral properties of recombinant MdGAD3 were not affected by Ca(2+)/CaM and they were much less sensitive to pH than MdGAD1, MdGAD2 and Arabidopsis GAD1; furthermore, the C-terminal region neither bound CaM nor functioned as an autoinhibitory domain. CONCLUSIONS: Plant GADs typically differ from microbial and animal GAD enzymes in possessing a C-terminal 30-50 amino acid residue CaM-binding domain. To date, rice GAD2 is the only exception to this generalization; notably, the C-terminal region of this enzyme still functions as an autoinhibitory domain. In the present study, apple fruit were found to contain two CaM-dependent GADs, as well as a novel CaM-independent GAD that does not possess a C-terminal autoinhibitory domain.
Assuntos
Calmodulina/metabolismo , Frutas/enzimologia , Glutamato Descarboxilase/metabolismo , Malus/enzimologia , Proteínas de Plantas/metabolismo , Calmodulina/genética , Frutas/genética , Glutamato Descarboxilase/genética , Malus/genética , Proteínas de Plantas/genéticaRESUMO
BACKGROUND: Primary breast lymphoma (PBL) is a rare malignant breast tumor. The literature concerning PBL ultrasound is based primarily on case reports, with only a few cases reported to date. PURPOSE: This study aimed to elucidate the sonographic characteristics of PBL and explore the value of ultrasonography in the preoperative diagnosis of PBL using the Breast Imaging Reporting and Data System (BI-RADS). METHODS: A retrospective review of files involving a diagnosis of PBL (2013-2020) was conducted in the Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou, and the First Affiliated Hospital of Wenzhou Medical University, Wenzhou. The clinical characteristics and sonographic features of 12 lesions in 10 patients were analyzed and discussed in light of the literature. RESULTS: All patients, aged 50.40 ± 14.31 years (range 30-66 years), had clinically palpable lumps. Most cases were on the right breast and were unilateral. Only one patient had mucosa-associated lymphoma. The histological type of the other patients was diffuse large B-cell lymphoma (DLBCL). Ultrasonography revealed nodular and diffuse PBL lesions without internal calcification. The nodular PBL was hypoechoic or mixed hypo- to hyperechoic, with a differential lobulated shape and horizontal growth. Although color Doppler flow imaging (CDFI) showed no significant features, the ultrasound findings were categorized as BI-RADS 4 in 10 of the 12 lesions and BI-RADS 5 in two lesions. All patients were suspected of having malignancies (BI-RADS 4 or 5). CONCLUSION: PBL was mostly found in middle-aged and elderly women, and the right breast was more prone to the development of malignancies. PBL lesions were classified as either nodular or diffuse based on the boundaries of the tumors in the ultrasound images. Typical PBL was characterized by hypoechoic or heterogeneous lesions with circumscribed or microlobulated margins and horizontal growth. The sonographic features of the PBL lesions and the BI-RADS categorizations of the lesions analyzed suggested malignancy.
Assuntos
Neoplasias da Mama , Linfoma Difuso de Grandes Células B , Pessoa de Meia-Idade , Idoso , Humanos , Feminino , Ultrassonografia Mamária/métodos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Ultrassonografia , Estudos Retrospectivos , Linfoma Difuso de Grandes Células B/diagnóstico por imagemRESUMO
Enzyme-mediated hydrolysis of cellulose always starts with an initial rapid phase, which gradually slows down, sometimes resulting in incomplete cellulose hydrolysis even after prolonged incubation. Although mechanisms such as end-product inhibition are known to play a role, the predominant mechanism appears to be reduced cellulose accessibility to the enzymes. When using Simon's stain to quantify accessibility, the accessibility of mechanically disintegrated and phosphoric acid-swollen cellulose substrates decreased as hydrolysis proceeded. In contrast, the poor initial accessibility of Avicel remained low throughout hydrolysis. However, washing the residual cellulose increased cellulose accessibility, likely due to the removal of tightly bound but non-productive enzymes which blocked access to more active enzymes in solution. Atomic force microscopy (AFM) analysis of the initial and residual cellulose collected when the hydrolysis plateaued, showed an increase in the roughness of the cellulose surface, possibly resulting in the tighter binding of less active cellulases.
Assuntos
Celulase , Celulases , Celulose/metabolismo , Celulase/metabolismo , Hidrólise , Celulases/metabolismo , CorantesRESUMO
The pre-adsorption of non-catalytic/blocking proteins onto the lignin component of pretreated biomass has been shown to significantly increase the effectiveness of subsequent enzyme-mediated hydrolysis of the cellulose by limiting non-productive enzyme adsorption. Layer-by-layer adsorption of non-catalytic proteins and enzymes onto lignin was monitored using Quartz Crystal Micro balancing combined with Dissipation monitoring (QCM-D) and conventional protein adsorption. These methods were used to assess the interaction between soft/hardwood lignins, cellulases and the three non-catalytic proteins BSA, lysozyme and ovalbumin. The QCM-D analysis showed higher adsorption rates for all of the non-catalytic proteins onto the lignin films as compared to cellulases. This suggested that the "blocking" proteins would preferentially adsorb to the lignin rather than the enzymes. Pre-incubation of the lignin films with blocking proteins resulted in reduced adsorption of cellulases onto the lignin, significantly enhancing cellulose hydrolysis.
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Celulase , Celulases , Lignina/química , Celulase/metabolismo , Hidrólise , Celulose/química , Adsorção , Celulases/metabolismo , ProteínasRESUMO
Candida albicans is an important opportunistic pathogenic fungus that frequently causes serious systemic infection in humans. Due to the vital roles of biofilm formation and the yeast-to-hypha transition in the infection process, we have selected a series of diaryl chalcogenides and tested their efficacy against C. albicans SC5314 pathogenicity by the inhibition of biofilm formation and the yeast-to-hypha transition. The compounds 5-sulfenylindole and 5-selenylindole were found to have excellent abilities to inhibit both biofilm formation and hyphal formation in C. albicans SC5314. Intriguingly, the two leading compounds also markedly attenuated C. albicans SC5314 virulence in human cell lines and mouse infection models at micromolar levels. Furthermore, our results showed that the presence of the compounds at 100 µM resulted in a marked decrease in the expression of genes involved in the cAMP-PKA and MAPK pathways in C. albicans SC5314. Intriguingly, the compounds 5-sulfenylindole and 5-selenylindole not only attenuated the cytotoxicity of Candida species strains but also showed excellent synergistic effects with antifungal agents against the clinical drug-resistant C. albicans strain HCH12. The compound 5-sulfenylindole showed an obvious advantage over fluconazole as it could also restore the composition and richness of the intestinal microbiota in mice infected by C. albicans. Together, these results suggest that diaryl chalcogenides can potentially be designed as novel clinical therapeutic agents against C. albicans infection. The diaryl chalcogenides of 5-sulfenylindole and 5-selenylindole discovered in this study can provide new direction for developing antifungal agents against C. albicans infection.
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Candida albicans , Candidíase , Camundongos , Humanos , Animais , Candida albicans/genética , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Virulência , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Fluconazol/farmacologia , Hifas , BiofilmesRESUMO
Background: Surgical resection is the main method to treat pituitary adenoma. Cerebrospinal fluid leakage (CSF Leak) is the main complication after transsphenoidal surgery. The impact of postoperative CSF Leak can be predicted in advance, and preventive measures can be taken in time. Clinically, a variety of factors may affect the occurrence of postoperative CSF Leak. In this study, meta-analysis was used to investigate the risk factors of postoperative CSF Leak as a clinical reference. Methods: The databases PubMed, Medline, Embrase, Cochrane library, CNKI, and CBM were searched for all studies on the risk factors of postoperative CSF Leak. Studies were screened and finally included. The quality of the included studies was assessed by the Newcastle-Ottawa scale. We used Revman 5.4 software to conduct the pooled effect size of every potential statistically significant factor. Results: 13 articles with a total of 5967 patients with pituitary adenoma and 405 cases of postoperative CSF Leak were finally included, accounting for 6.79%. All of the 13 articles had a quality score > 5, indicating good quality. Meta-analysis showed that patient age (OR = 0.71, 95% CI (0.41, 1.20), P = 0.20) was not a factor influencing postoperative CSF Leak, while BMI (MD = 2.26, 95% CI (1.31, 3.20), P < 0.00001), tumor size (MD = 1.35, 95% CI (0.22, 2.49), P = 0.02), whether a second operation was performed (OR = 2.20, 95% CI (1.45, 3.33), P = 0.0002), and intraoperative CSF Leak (OR = 8.88, 95% CI (3.64, 21.69), P < 0.00001) were risk factors for postoperative CSF Leak in patients. Discussion. BMI, tumor size, reoperation, and intraoperative CSF Leak are the risk factors of postoperative CSF Leak. However, not all the factors were covered in this study, it is still worth continuing to deeply investigate in this topic.
Assuntos
Adenoma , Neoplasias Hipofisárias , Adenoma/complicações , Adenoma/cirurgia , Vazamento de Líquido Cefalorraquidiano/epidemiologia , Vazamento de Líquido Cefalorraquidiano/etiologia , Vazamento de Líquido Cefalorraquidiano/cirurgia , Humanos , Neoplasias Hipofisárias/patologia , Complicações Pós-Operatórias/etiologia , Reoperação , Estudos RetrospectivosRESUMO
Bacteria are the main cause of spoilage for fish and fishery products. Through the inactivation of the quorum sensing (QS) system, quorum quenching (QQ) enzymes can block the synthesis of bacterial virulence factors and effectively inhibit bacteria-induced food spoilage. This study analyzed the changes of microbiota in red sea bream filets during refrigerated storage. The results showed a decrease in microbial diversity with storage time, with Aeromonas veronii becoming the dominant bacteria on day 4. A novel N-acyl homoserine lactones (AHL) acylase PF2571, from the screened QQ bacterium Pseudomonas fluorescens PF08, was identified and expressed in Escherichia coli to evaluate its QQ efficiency and effects on spoilage potential. Spoilage-related QS factors of A. veronii BY-8, including biofilm formation, motility, and protease, lipase, and alginate production, were inhibited by PF2571. Its inhibitory effect on red sea bream spoilage was demonstrated by the lower freshness indicators for PF2571 treated filets. Our study demonstrates the potential of the QQ enzyme for prolonging the shelf life of fish and fishery products.
Assuntos
Pseudomonas fluorescens , Dourada , Acil-Butirolactonas , Animais , Percepção de Quorum , Alimentos MarinhosRESUMO
Cadmium (Cd) contamination in the environment is a major public health concern since it has been linked to osteoporosis and other bone deformities. Linarin is a flavonoid glycoside, and it can promote osteoblastogenesis. This research aimed to investigate the potential role of linarin against Cd-exposed bone deformations in mice model. In our research, male mice were randomly allocated into four groups: control, Cd-exposed, and Cd + linarin (20 and 40mg/kg/bw, respectively). Linarin prevented body weight loss, increased serum calcium (Ca) and phosphorus (P), and bone alkaline phosphatase (BAP) levels in Cd-exposed groups. Furthermore, linarin treatment at 20 and 40mg/kg/bw significantly decreased RANK and OPG, resulting in an increase in RANKL mRNA levels and protein distribution in the bone of Cd-exposed mice. In addition, the bone of Cd-exposed mice administered with linarin showed higher TRAP, NFATc1, MMP9, and RUNX2 mRNA levels and protein distribution. Linarin significantly decreased oxidative stress in Cd-exposed mice bone by decreasing MDA, a lipid peroxidation product. Moreover, linarin protects Cd-exposed mice antioxidant enzymes by increasing bone SOD, CAT, and GPx levels. Besides, linarin suppresses alterations in the inflammatory system, i.e., NF-κB p65/IKKß, by reducing NF-κB p65, IKKß, IL-6, and TNF-α in the bone of Cd-exposed animals. This study concluded that linarin has potential to cure osteoporosis in Cd-exposed mice by reducing oxidative stress and inflammation and modulating the RANK/RANKL/OPG pathway.