RESUMO
Subsoil is a large organic carbon reservoir, storing more than half of the total soil organic carbon (SOC) globally. Conventionally, subsoil is assumed to not be susceptible to climate change, but recent studies document that climate change could significantly alter subsoil carbon cycling. However, little is known about subsoil microbial responses to the interactive effects of climate warming and altered precipitation. Here, we investigated carbon cycling and associated microbial responses in both subsoil (30-40 cm) and topsoil (0-10 cm) in a Tibetan alpine grassland over 4 years of warming and altered precipitation. Compared to the unchanged topsoil carbon (ß = .55, p = .587), subsoil carbon exhibited a stronger response to the interactive effect of warming and altered precipitation (ß = 2.04, p = .021), that is, warming decreased subsoil carbon content by 28.20% under decreased precipitation while warming increased subsoil carbon content by 18.02% under increased precipitation.Furthermore, 512 metagenome-assembled genomes (MAGs) were recovered, including representatives of phyla with poor genomic representation. Compared to only one changed topsoil MAG, 16 subsoil MAGs were significantly affected by altered precipitation, and 5 subsoil MAGs were significantly affected by the interactive effect of warming and precipitation. More than twice as many populations whose MAG abundances correlated significantly with the variations of carbon content, components and fluxes were observed in the subsoil than topsoil, suggesting their potential contribution in mediating subsoil carbon cycling. Collectively, our findings highlight the more sensitive responses of specific microbial lineages to the interactive effects of warming and altered precipitation in the subsoil than topsoil, and provide key information for predicting subsoil carbon cycling under future climate change scenarios.
Assuntos
Ciclo do Carbono , Mudança Climática , Pradaria , Chuva , Microbiologia do Solo , Solo , Solo/química , Tibet , Carbono/análise , Carbono/metabolismo , Aquecimento Global , Bactérias/genética , Bactérias/classificaçãoRESUMO
BACKGROUND: Calcific aortic valve disease (CAVD) is the most prevalent valvular disease and has high morbidity and mortality. CAVD is characterized by complex pathophysiological processes, including inflammation-induced osteoblastic differentiation in aortic valve interstitial cells (AVICs). Novel anti-CAVD agents are urgently needed. Protein tyrosine phosphatase nonreceptor type 22 (PTPN22), an intracellular nonreceptor-like protein tyrosine phosphatase, is involved in several chronic inflammatory diseases, including rheumatoid arthritis and diabetes. However, it is unclear whether PTPN22 is involved in the pathogenesis of CAVD. METHODS: We obtained the aortic valve tissue from human and cultured AVICs from aortic valve. We established CAVD mice model by wire injury. Transcriptome sequencing, western bolt, qPCR, and immunofluorescence were performed to elucidate the molecular mechanisms. RESULTS: Here, we determined that PTPN22 expression was upregulated in calcific aortic valve tissue, AVICs treated with osteogenic medium, and a mouse model of CAVD. In vitro, overexpression of PTPN22 induced osteogenic responses, whereas siRNA-mediated PTPN22 knockdown abolished osteogenic responses and mitochondrial stress in the presence of osteogenic medium. In vivo, PTPN22 ablation ameliorated aortic valve lesions in a wire injury-induced CAVD mouse model, validating the pathogenic role of PTPN22 in CAVD. Additionally, we discovered a novel compound, 13-hydroxypiericidin A 10-O-α-D-glucose (1 â 6)-ß-D-glucoside (S18), in a marine-derived Streptomyces strain that bound to PTPN22 with high affinity and acted as a novel inhibitor. Incubation with S18 suppressed osteogenic responses and mitochondrial stress in human AVICs induced by osteogenic medium. In mice with aortic valve injury, S18 administration markedly alleviated aortic valve lesions. CONCLUSION: PTPN22 plays an essential role in the progression of CAVD, and inhibition of PTPN22 with S18 is a novel option for the further development of potent anti-CAVD drugs. Therapeutic inhibition of PTPN22 retards aortic valve calcification through modulating mitochondrial dysfunction in AVICs.
Assuntos
Estenose da Valva Aórtica , Valva Aórtica , Humanos , Animais , Camundongos , Valva Aórtica/metabolismo , Valva Aórtica/patologia , Monoéster Fosfórico Hidrolases , Estenose da Valva Aórtica/tratamento farmacológico , Estenose da Valva Aórtica/genética , Células Cultivadas , Proteína Tirosina Fosfatase não Receptora Tipo 22/metabolismoRESUMO
Higher activity and alkaline α-amylases are desired for textile desizing and detergent additive. Here, rational design was used to improve the specific activity and thermostability of the α-amylase BLA from Bacillus licheniformis. Seventeen mutants of BLA were designed based on sequence consensus analysis and folding free energy calculation, and characterized by measuring their respective activity and thermostability at pH 8.5. Among them, mutant Q360C exhibited nearly threefold improved activity than that of wild-type and retained a higher residual activity (75% vs 59% for wild-type) after preincubation at 70 â for 30 min. The modeled structures and molecular dynamics simulations analysis demonstrated that the enhanced hydrophobic interaction near residue 360 and reduced disturbance to the conformation of catalytic residues are the possible reasons for the improved thermostability and activity of Q360C. The results suggest that 360th of BLA may act as a hotspot for engineering other enzymes in the GH13 superfamily.
Assuntos
alfa-Amilases , alfa-Amilases/genética , alfa-Amilases/química , Estabilidade Enzimática , TemperaturaRESUMO
The Chinese government has developed an ambitious project to promote the application of ethanol gasoline (E10) on a national scale since 2017. Given the difference in fuel properties between E10 and traditional gasoline, it is necessary to evaluate the volatile organic compound (VOC) emissions from E10-fuelled vehicles. In this study, a two-week sampling campaign was conducted in an urban tunnel, in which E10-fuelled vehicles were dominant, to evaluate the characteristics of VOC emissions from the mixed fleet. In total, 105 VOC species were identified, and the ozone formation potential (OFP) and secondary organic aerosol formation potential (SOAFP) were estimated. The results showed that for vehicular VOC concentrations in the tunnel, alkanes, oxygenated VOCs (OVOCs) and alkenes were the most abundant VOC groups, with the average proportion being more than 80% of the total VOCs. The fleet-average VOC emission factor (EF) was 14.8 mg/km/veh, which was much lower than that from traditional gasoline-fuelled vehicle fleets, and alkanes, OVOCs, alkenes and aromatics were the major VOC groups. Because of the large number of E10-fuelled vehicles in the mixed fleet, a high proportion of OVOCs among the vehicular VOC emissions was observed. Ethane, acrolein, ethanol, ethylene and toluene were the top five VOC species with the largest EF in VOC emissions from the fleet. Alkenes were the main contributors with an average contribution of 43.9% of the total OFP, whereas aromatics dominated the total SOAFP by 95.8% on average. These results may provide a reference for the extensive application of ethanol gasoline and the development of vehicular emission models.
Assuntos
Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Aerossóis/análise , Poluentes Atmosféricos/análise , China , Monitoramento Ambiental , Ozônio/análise , Emissões de Veículos/análise , Compostos Orgânicos Voláteis/análiseRESUMO
Textile wastewater has been recognized as one of the most difficult to treat environmental problems. Aiming to acquire an excellent treatment effect that could meet the stringent discharge regulations, a series of Cu- and Fe-doped Al-MCM-41 heterogeneous Fenton catalysts with different metal contents (1.21-3.45 wt%) were successfully synthesized by co-precipitation method to degrade Rhodamine B. Their physicochemical properties were analysed by X-ray diffraction, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, nitrogen physisorption and scanning electron microscopy. The incorporation of metal did not alter MCM-41's mesostructure, but increasing the contents of metal would decrease the order of MCM-41s' structure. The effects of temperature, pH, H2O2 dosage, dye concentration and the dosage of catalysts on Rhodamine B degradation were also investigated. It was found that M2 with 2.71 wt% of active metals performed best on Rhodamine B degradation. For the high concentration of Rhodamine B (400 mg/L), the decolorization efficiency could reach 96.0% using only 40 mM H2O2 within 50 min at 60 °C. Further adding 40 mM of H2O2, the chemical oxygen demand removal reached 75.1% after 100 min. M2 showed excellent stability and could be reused at least three times without any obvious deterioration in catalytic activity. M2 fitted well with the Freundlich isotherms and the first-order rate model.
Assuntos
Peróxido de Hidrogênio , Dióxido de Silício , Catálise , RodaminasRESUMO
In this report, we designed conjugates of an antigen peptide with the immunosuppressive vitamins all-trans retinoic acid (ATRA) and vitamin D3 for efficient induction of antigen-specific immunotolerance. We established a synthetic scheme for the preparation of the peptide-vitamin conjugates, which the chemically unstable vitamins tolerated. Among the obtained conjugates, the ATRA conjugate successfully suppressed inflammatory effects in macrophages and dendritic cells and induced antigen presentation in dendritic cells. This synthetic method of conjugate is conceivably applicable to other antigen peptides for induction of antigen-specific immunotolerance.
Assuntos
Colecalciferol/farmacologia , Células Dendríticas/efeitos dos fármacos , Tolerância Imunológica/efeitos dos fármacos , Tolerância Imunológica/imunologia , Imunossupressores/farmacologia , Macrófagos/efeitos dos fármacos , Peptídeos/farmacologia , Tretinoína/farmacologia , Animais , Apresentação de Antígeno/efeitos dos fármacos , Apresentação de Antígeno/imunologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Colecalciferol/química , Células Dendríticas/imunologia , Relação Dose-Resposta a Droga , Imunossupressores/química , Imunossupressores/imunologia , Inflamação/tratamento farmacológico , Inflamação/imunologia , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/imunologia , Camundongos , Estrutura Molecular , Peptídeos/síntese química , Peptídeos/química , Células RAW 264.7 , Tretinoína/químicaRESUMO
Sixteen lanostane-type triterpene glycosides including eight new ones, named lyonicarposides A-H (1-8), were isolated from the flowers of Lyonia ovalifolia var. hebecarpa (Franch. ex F.B. Forbes & Hemsl.) Chun (Ericaceae). The chemical structures of the new compounds were elucidated by the comprehensive spectroscopic techniques and chemical methods. The Mo2(OAc)4-induced electronic circular dichroism method was used to determine the absolute configurations of C-24 in lyonicarposides A (1), C (3), and E (5). This is the first phytochemical study on the flowers of L. ovalifolia var. hebecarpa. All the isolates were evaluated for their antiproliferative activities against SMMC-7721, HL-60, SW480, MCF-7, and A-549 cell lines. Lyonicarposides A (1) and B (2) showed moderate antiproliferative activities against five cancer cell lines with IC50 values ranging from 12.39 to 28.71 µM. Lyonicarposides C (3) and G (7) and lyonifoloside M (12) selectively inhibited the proliferation of HL-60 and MCF-7 cell lines with IC50 values ranging from 13.03 to 17.71 µM. Interestingly, lyonifoloside L (13) selectively inhibited the proliferation of MCF-7 cell line with an IC50 value of 16.27 µM. Their structure-activity-relationships were discussed.
Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Ericaceae/química , Triterpenos/química , Triterpenos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Flores/química , Glicosídeos/química , Glicosídeos/farmacologia , Humanos , Neoplasias/tratamento farmacológico , Relação Estrutura-AtividadeRESUMO
Acetolactate synthase catalyzes two molecules of pyruvates to form α-acetolactate, which is further converted to acetoin and 2,3-butanediol. In this study, by heterologous expression in Escherichia coli, the enzymatic properties of acetolactate synthase (AlsS) from Bacillus licheniformis WX-02 were characterized. Its K m and k cat for pyruvate were 3.96 mM and 514/s, respectively. It has the optimal activity at pH 6.5, 37 °C and was feedback inhibited by L-valine, L-leucine and L-isoleucine. Furthermore, the alsS-deficient strain could not produce acetoin, 2,3-butanediol, and L-valine, while the complementary strain was able to restore these capacities. The alsS overexpressing strain produced higher amounts of acetoin/2,3-butanediol (57.06 g/L) and L-valine (2.68 mM), which were 10.90 and 92.80% higher than those of the control strain, respectively. This is the first report regarding the in-depth understanding of AlsS enzymatic properties and its functions in B. licheniformis, and overexpression of AlsS can effectively improve acetoin/2,3-butanediol and L-valine production in B. licheniformis. We envision that this AlsS can also be applied in the improvement of acetoin/2,3-butanediol and L-valine production in other microbes.
Assuntos
Acetoína/metabolismo , Acetolactato Sintase , Bacillus licheniformis/genética , Proteínas de Bactérias , Butileno Glicóis/metabolismo , Escherichia coli , Valina/metabolismo , Acetolactato Sintase/biossíntese , Acetolactato Sintase/genética , Bacillus licheniformis/enzimologia , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Escherichia coli/enzimologia , Escherichia coli/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/genéticaRESUMO
Microencapsulation technology has the potential to protect probiotics and to deliver them to the gut, and extrusion is one of the most commonly used methods. However, the rather large diameters of 1~5 mm produced tend to cause oral grittiness and result in low compliance. In this article, Streptococcus thermophilus IFFI 6038 (IFFI 6038) microcapsules were prepared using an ultra-fine particle processing system (UPPS) previously developed by this research group. IFFI 6038 suspension was pumped by a peristaltic pump to the feeding inlet nozzle and then dispersed into micro-droplets by a rotating disk, followed by solidification. Trehalose (16%) was used as a cryoprotectant to protect IFFI 6038 from damage by lyophilization used in the process. Alginate (3%) resulted in IFFI 6038 microcapsules with a median particle diameter (d 50) of 29.32 ± 0.12 µm and a span value of 1.00 ± 0.02, indicating uniform particle size distribution. To evaluate the potential of microencapsulation in protecting IFFI 6038 from the gastric conditions, the viable counts of IFFI 6038 following incubation of IFFI 6038 microcapsules in simulated gastric juices for 120 min were determined and compared with those of free IFFI 6038. The stability of microencapsulated IFFI 6038 upon storage for 3 months at 4°C and 25°C, respectively, was also determined. The results showed that microcapsules prepared by UPPS protected IFFI 6038 from gastric conditions. The results from a rat diarrhea model showed that microcapsules prepared by the UPPS method were able to effectively improve the diarrhea conditions in rats.
Assuntos
Probióticos/administração & dosagem , Streptococcus thermophilus , Alginatos/química , Animais , Cápsulas , Crioprotetores , Diarreia/terapia , Composição de Medicamentos/métodos , Feminino , Liofilização , Suco Gástrico , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Masculino , Tamanho da Partícula , Probióticos/uso terapêutico , Ratos , TrealoseRESUMO
Edwardsiella ictaluri is one of the most important pathogens posing a serious threat for yellow catfish (Pelteobagrus fulvidraco), a highly valuable fish species of increasing commercial interest in China. Here, a transcriptomic strategy was undertaken to investigate the yellow catfish gene expression profile against infection by the bacterial pathogen E. ictaluri. Comparison of the transcriptome profiles between the infected and uninfected samples showed that a massive gene expression change occurred in yellow catfish following bacterial exposure. A total of 5527 differentially expressed genes (DEGs) were detected, of which 2265 showed up-regulation and 3262 down-regulation. Gene set enrichment analysis revealed the presence of canonical pathways directly linked to innate and adaptive immune response, such as pattern recognition receptor (PRR) signaling pathways, complement and coagulation cascades, as well as T-cell receptor (TCR) and B-cell receptor (BCR) signaling pathways. Additionally, 47,526 putative EST-liked simple sequence repeats (SSRs) markers were retrieved for use in genetic studies. This study establishes the first molecular clues to understand the potential mechanisms of yellow catfish resistance to E. ictaluri, thus enabling future efforts on disease control programs in this valuable aquaculture species.
Assuntos
Peixes-Gato/genética , Peixes-Gato/imunologia , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Imunidade Inata/genética , Transcriptoma , Animais , Edwardsiella ictaluri/fisiologia , Infecções por Enterobacteriaceae/imunologia , Perfilação da Expressão Gênica/veterinária , Proteínas NLR/genética , Filogenia , Receptores Toll-Like/genéticaRESUMO
1-Hexadecyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide is a solid-phase ionic organic material under ambient temperature and is considered as a kind of "frozen" ionic liquid. Because of their solid-state and ultra-hydrophobicity, "frozen" ionic liquids are able to be confined in the pores of hollow fiber, based on which a simple method was developed for the hollow-fiber solid-phase microextraction of dichlorodiphenyltrichloroethane and its main metabolites. Under optimized conditions, the proposed method results in good linearity (R2 > 0.9965) over the range of 0.5-50 µg/L, with low limits of detection and quantification in the range of 0.33-0.38 and 1.00-1.25 µg/L, respectively. Intra- and interday precisions evaluated by relative standard deviation were 3-6 and 1-6%, respectively. The spiked recoveries of dichlorodiphenyltrichloroethane and its main metabolites from real water samples were in the range of 64-113 and 79-112%, respectively, at two different concentration levels. The results suggest that "frozen" ionic liquids are promising for use as a class of novel sorbents.
RESUMO
OBJECTIVES: To improve target protein production by manipulating expression levels of alanine racemase in Bacillus licheniformis. RESULTS: The gene of dal was identified to be responsible for alanine racemase function. Based on the selection marker of dal, a food-grade expression system was constructed in B. licheniformis, and effects of different dal expression levels mediated by promoters on α-amylase production were investigated. The highest α-amylase activity (155 U/ml) was obtained in BL10D/pP43SAT-PtetDal, increased by 27% compared with that of the control strain BL10/pP43SAT in tetracycline-based system (123 U/ml). Moreover, the dal transcriptional level was not correlated positively with that of amyL. CONCLUSIONS: A food-grade system for high-level production of α-amylase was constructed in B. licheniformis, revealing that expression levels of selection marker significantly affected target protein production.
Assuntos
Alanina Racemase/genética , Alanina Racemase/metabolismo , Bacillus licheniformis/enzimologia , Bacillus licheniformis/genética , Engenharia Metabólica/métodos , alfa-Amilases/biossíntese , Expressão Gênica , Vetores Genéticos , Plasmídeos , Regiões Promotoras GenéticasRESUMO
Chinese sturgeon (Acipenser sinensis), one of the oldest extant actinopterygian fishes with very high evolutionary, economical and conservation interest, is considered to be one of the critically endangered aquatic animals in China. Up to date, the immune system of this species remains largely undetermined with little sequence information publicly available. Herein, the first comprehensive transcriptome of immune tissues for Chinese sturgeon was characterized using Illumina deep sequencing. Over 67 million high-quality reads were generated and de novo assembled into the final set of 91,739 unique sequences. The annotation pipeline revealed that 25,871 unigenes were successfully annotated in the public databases, of which only 2002 had significant match to the existing sequences for the genus Acipenser. Overall 22,827 unigenes were categorized into 52 GO terms, 12,742 were classified into 26 KOG categories, and 4968 were assigned to 339 KEGG pathways. A more detailed annotation search showed the presence of a notable representation of immune-related genes, which suggests that this non-teleost actinopterygian fish harbors the same intermediates as in the well known immune pathways from mammals and teleosts, such as pattern recognition receptor (PRR) signaling pathway, JAK-STAT signaling pathway, complement and coagulation pathway, T-cell receptor (TCR) and B-cell receptor (BCR) signaling pathways. Additional genetic marker discovery led to the retrieval of 20,056 simple sequence repeats (SSRs) and 327,140 single nucleotide polymorphisms (SNPs). This immune-enriched transcriptome of Chinese sturgeon represents a rich resource that adds to the currently nascent field of chondrostean fish immunogenetics and furthers the conservation and management of this valuable fish.
Assuntos
Proteínas de Peixes/genética , Peixes/genética , Receptores Toll-Like/genética , Transcriptoma , Animais , Evolução Molecular , Proteínas de Peixes/metabolismo , Repetições de Microssatélites , Anotação de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Receptores Toll-Like/metabolismoRESUMO
New 2-6 wt% RuO2-ZnO heterojunction nanocatalysts were synthesized by a straightforward two-step procedure. They were composed of a porous network of aggregated 25 nm wurtzite ZnO nanocrystallites modified with RuO2 and showed enhanced light absorption in the visible region due to surface plasmon resonance. In order to investigate the energetic structure of the photocatalyst XPS core line and valence band spectra of in situ in UHV prepared heterointerfaces were compared to results obtained from the particles. The shift of Zn 2p3/2 and O 1s core level spectra was determined to be at least 0.80 ± 0.05 eV for the in situ prepared heterojunction whereas it was found to be 0.40 ± 0.05 and 0.45 ± 0.05 eV, respectively, in the photocatalysts. The different values were ascribed to the reduced size of the particles and the different measurability of band bending at the interface of the heterojunction RuO2-ZnO compared to the nanoparticles. The RuO2/ZnO photocatalysts showed higher photocatalytic activity and recyclability than pure ZnO for the degradation of various dyes under UV light irradiation due to vectorial charge separation of photogenerated electrons and holes resulting from internal electric field, the ruthenium oxide acting as a quasi-metallic contact.
RESUMO
Magnetic resonance imaging (MRI) is the leading imaging technique for disease diagnostics, providing high resolution, three-dimensional images noninvasively. MRI contrast agents are designed to improve the contrast and sensitivity of MRI. However, current clinically used MRI contrast agents have relaxivities far below the theoretical upper limit, which largely prevent advancing molecular imaging of biomarkers with desired sensitivity and specificity. This review describes current progress in the development of a new class of protein-based MRI contrast agents (ProCAs) with high relaxivity using protein design to optimize the parameters that govern relaxivity. Further, engineering with targeting moiety allows these contrast agents to be applicable for molecular imaging of prostate cancer biomarkers by MRI. The developed protein-based contrast agents also exhibit additional in vitro and in vivo advantages for molecular imaging of disease biomarkers, such as high metal-binding stability and selectivity, reduced toxicity, proper blood circulation time, and higher permeability in tumor tissue in addition to improved relaxivities.
Assuntos
Biomarcadores Tumorais/análise , Meios de Contraste , Gadolínio/administração & dosagem , Imageamento por Ressonância Magnética/métodos , Relação Dose-Resposta a Droga , Gadolínio/químicaRESUMO
A two-stage biofilter was built, augmented with polydimethylsiloxane (PDMS), to enhance the degradation of ortho xylene (o-xylene), and evaluate the feasibility of different PDMS concentrations for improving the removal effect. The results showed that PDMS concentration of 0.50 % significantly enhanced the purification efficiency and mineralization rate of o-xylene to 85(±1)% and 81 %, respectively. Simultaneously, the surface tension of the circulating liquid was reduced by 31.91 mN/m. Furthermore, the polysaccharide concentration of biofilters were increased by 6.90 mg/g and 7.38 mg/g, respectively, while the protein concentration was enhanced by 7.98 mg/g and 9.29 mg/g, respectively. It is worth noting that Sphingomonas and Sphingobium emerged as the dominant bacterial genera after intensification. Fusarium and Cladosporium became the predominant fungal genera in BTF1 and BTF2, respectively. Therefore, the two-stage biofilter containing bacteria and fungi combined with the addition of PDMS can effectively improve the degradation effect.
RESUMO
The "sol-gel method" was used to prepare spherical chitosan-modified bentonite (SCB) hydrogels in this study. The SCB hydrogels were characterized and used as sorbents to remove tetracycline (TC) from aqueous solutions. The adsorbents were characterized by SEM, XRD, FTIR, TG, and BET techniques. Various characterization results showed that the SCB adsorbent had fewer surface pores and a specific surface area that was 96.6% lower than the powder, but the layered mesoporous structure of bentonite remained unchanged. The adsorption process fit to both the Freundlich model and the pseudo-second-order kinetic model showed that it was a non-monolayer chemical adsorption process affected by intra-particle diffusion. The maximum monolayer adsorption capacity determined by the Langmuir model was 39.49 mg/g. Thermodynamic parameters indicated that adsorption was a spontaneous, endothermic, and entropy-increasing process. In addition, solid-liquid separation was easy with the SCB adsorbent, providing important reference information for the synthesis of SCB as a novel and promising adsorbent for the removal of antibiotics from wastewater at the industrial level.
RESUMO
Nanoparticles (NPs) for allergen immunotherapy have garnered attention for their high efficiency and safety compared with naked antigen proteins. In this work, we present mannan-coated protein NPs, incorporating antigen proteins for antigen-specific tolerance induction. The heat-induced formation of protein NPs is a one-pot preparation method and can be applied to various proteins. Here, the NPs were formed spontaneously via heat denaturation of three component proteins: an antigen protein, human serum albumin (HSA) as a matrix protein, and mannoprotein (MAN) as a targeting ligand for dendritic cells (DCs). HSA is non-immunogenic, therefore suitable as a matrix protein, while MAN coats the surface of the NP. We applied this method to various antigen proteins and found that the self-disperse after heat denaturation was a requirement for incorporation into the NPs. We also established that the NPs could target DCs, and the incorporation of rapamycin into the NPs enhanced the induction of a tolerogenic phenotype of DC. The MAN coating provided steric hindrance and heat denaturation destroyed recognition structures, successfully preventing anti-antigen antibody binding, indicating the NPs may avoid anaphylaxis induction. The MAN-coated NPs proposed here, prepared by a simple method, have the potential for effective and safe allergies treatment for various antigens.
Assuntos
Mananas , Nanopartículas , Humanos , Albumina Sérica Humana , Antígenos/química , Tolerância Imunológica , Nanopartículas/químicaRESUMO
Fatty-acid binding protein 4 (FABP4) is an essential driver for the progression of metabolic-related inflammatory diseases including obesity, diabetes, atherosclerosis, and various lipid metabolism-related tumors. However, FABP4 inhibitors are not yet available for clinical use, which may be associated with their poor selectivity of FABP3, unsatisfactory efficacy and physicochemical properties. Herein, we reported a systematic optimization of a class of biphenyl scaffold molecules as potent FABP4 inhibitors. Further in vitro and in vivo pharmacokinetic studies identified a selective and orally bioavailable compound 10g, with Ki of 0.51 µM against FABP4, Ki of 33.01 µM against FABP3 and bioavailability F% value of 89.4%. In vivo anti-inflammatory efficacy and multi-organ protection study in LPS-induced inflammatory mice model highlighted the potential of compound 10g as a therapeutic candidate in inflammation-related diseases.
Assuntos
Compostos de Bifenilo , Proteínas de Ligação a Ácido Graxo , Camundongos , Animais , Compostos de Bifenilo/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/metabolismoRESUMO
In view of the characteristics and risks of ammonia, its removal is important for industrial production and environmental safety. In this study, viscose-based activated carbon fiber (ACF) was used as a substrate and chemically modified by nitric acid impregnation to enhance the adsorption capacity of the adsorbent for ammonia. A series of modified ACF-based adsorbents were prepared and characterized using BET, FTIR, XPS, and Boehm titration. Isotherm tests (293.15 K, 303.15 K, 313.15 K) and dynamic adsorption experiments were performed. The characterization results showed that impregnation with low concentrations of nitric acid not only increased the surface acidic functional group content but also increased the specific surface area, while impregnation with high concentrations of nitric acid could be able to decrease the specific surface area. ACF-N-6 significantly increased the surface functional group content without destroying the physical structure of the activated carbon fibers. The experimental results showed that the highest adsorption of ammonia by ACFs was 14.08 mmol-L-1 (ACF-N-6) at 293 K, and the adsorption capacity was increased by 165% compared with that of ACF-raw; by fitting the adsorption isotherm and calculating the equivalent heat of adsorption and thermodynamic parameters using the Langmuir-Freundlich model, the adsorption process could be found to exist simultaneously. Regarding physical adsorption and chemical adsorption, the results of the correlation analysis showed that the ammonia adsorption performance was strongly correlated with the carboxyl group content and positively correlated with the relative humidity (RH) of the inlet gas. This study contributes to the development of an efficient ammonia adsorption system with important applications in industrial production and environmental safety.