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Tetramethylammonium hydroxide (TMAH), an extensively utilized photoresist developer, is frequently present in ammonium-rich wastewater from semiconductor manufacturing, and its substantial ecotoxicity should not be underestimated. This study systematically investigated the effects of TMAH on the anammox granular sludge (AnGS) system and elucidated its inhibitory mechanisms. The results demonstrated that the median inhibitory concentration of TMAH for anammox was 84.85 mg/L. The nitrogen removal performance of the system was significantly decreased after long-term exposure to TMAH (0-200 mg/L) for 30 days (p < 0.05), but it showed adaptability to certain concentrations (≤50 mg/L). Concurrently, the stability of the granules decreased dramatically, resulting in the breakdown of AnGS. Further investigations indicated that TMAH exposure increased the secretion of extracellular polymeric substances but weakened their defense function. The increase in reactive oxygen species resulted in damage to the cell membrane. Reduced activity of anammox bacteria, impeded electron transfer, and changes in enzyme activity suggested that TMAH affected the metabolic activity. Microbiological analysis revealed that TMAH caused a decrease in the abundance of anammox bacteria and a weakening of symbiotic interactions within the microbial community. These results provide valuable guidance for the AnGS system application in chip wastewater treatment.
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Glycoside hydrolases (GHs, also called glycosidases) catalyze the hydrolysis of glycosidic bonds in polysaccharides. Numerous GH genes have been identified from various organisms and are classified into 188 families, abbreviated GH1 to GH188. Enzymes in the GH32 family hydrolyze fructans, which are present in approximately 15% of flowering plants and are widespread across microorganisms. GH32 genes are rarely found in animals, as fructans are not a typical carbohydrate source utilized in animals. Here, we report the discovery of 242 GH32 genes identified in 84 animal species, ranging from nematodes to crabs. Genetic analyses of these genes indicated that the GH32 genes in various animals were derived from different bacteria via multiple, independent horizontal gene transfer events. The GH32 genes in animals appear functional based on the highly conserved catalytic blades and triads in the active center despite the overall low (35-60%) sequence similarities among the predicted proteins. The acquisition of GH32 genes by animals may have a profound impact on sugar metabolism for the recipient organisms. Our results together with previous reports suggest that the acquired GH32 enzymes may not only serve as digestive enzymes, but also may serve as effectors for manipulating host plants, and as metabolic enzymes in the non-digestive tissues of certain animals. Our results provide a foundation for future studies on the significance of horizontally transferred GH32 genes in animals. The information reported here enriches our knowledge of horizontal gene transfer, GH32 functions, and animal-plant interactions, which may result in practical applications. For example, developing crops via targeted engineering that inhibits GH32 enzymes could aid in the plant's resistance to animal pests.
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Bacterias , Transferencia de Gen Horizontal , Glicósido Hidrolasas , Filogenia , Glicósido Hidrolasas/genética , Glicósido Hidrolasas/metabolismo , Animales , Bacterias/genética , Bacterias/enzimología , Invertebrados/genética , Adaptación Fisiológica/genética , Ecosistema , Evolución MolecularRESUMEN
MRG domain binding protein (MRGBP) has been proposed to participate in the development of multiple tumors. However, the role of MRGBP in colorectal cancer (CRC) still remains largely unknown. Here, we found that MRGBP expression is significantly elevated in CRC, and that higher MRGBP expression correlates with poorer survival in CRC patients. Experiments in vivo and in vitro indicated that MRGBP promotes CRC cells proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) and xenograft tumor growth. Mechanically, for one thing, we discovered that MRGBP suppresses DKK1 expression, thus further activating the Wnt/ß-catenin pathway in CRC cells. For another, MRGBP also enhances acetylation of NF-kB/p65 pathway. Treatment with Wnt/ß-catenin and NF-kB pathways inhibitors further confirmed the mediation of these two pathways in MRGBP-promoted CRC cell processes. In conclusion, these findings together suggest that MRGBP promotes CRC progression via DKK1/Wnt/ß-catenin and NF-kB/p65 pathways mediated EMT, identifying MRGBP as a promising prognostic and therapeutic target for CRC.
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Neoplasias Colorrectales , Transición Epitelial-Mesenquimal , Histona Acetiltransferasas , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Metástasis de la Neoplasia , FN-kappa B/genética , FN-kappa B/metabolismo , Vía de Señalización Wnt/genética , Proteínas Nucleares/metabolismo , Histona Acetiltransferasas/metabolismoRESUMEN
We present a high-absorption optical stack design for aluminum (Al) kinetic inductance detectors (KIDs). Aluminum can be easily processed in micro-fabrication and is the most conventional superconducting material for KIDs. However, it is challenging to achieve high absorption in the Al absorber because of its high reflection at optical wavelengths. By embedding the thin Al film between an anti-reflection (AR) coating layer and a dielectric-based distributed Bragg reflector, we show that close-to-unity absorption can be achieved around a single wavelength (e.g., ≈98.9% at 1518 nm). The reflection and transmission measurements agree well with the calculation based on the transmission matrix model. We also show our preliminary results of absorption ≥70% in a broader wavelength range (≈230n m) with multilayer AR coatings. The absorber design in a lumped-element KID is discussed. Our work paves the way to high-efficiency photon-counting and energy-resolving Al-based KIDs in the optical to NIR range.
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BACKGROUND: In Tibet, the two most important breeds are Tibetan chicken and Lhasa white chicken, and the duo exhibit specific adaptations to the high altitude thereby supplying proteins for humans living in the plateau. These breeds are partly included in the conservation plans because they represent important chicken genetic resources. However, the genetic diversity of these chickens is rarely investigated. Based on whole-genome sequencing data of 113 chickens from 4 populations of Tibetan chicken including Shigatse (SH), Nyemo (NM), Dagze (DZ) and Nyingchi (LZ), as well as Lhasa white (LW) chicken breed, we investigated the genetic diversity of these chicken breeds by genetic differentiation, run of homozygosity (ROH), genomic inbreeding and selection signature analyses. RESULTS: Our results revealed high genetic diversity across the five chicken populations. The linkage disequilibrium decay was highest in LZ, while subtle genetic differentiation was found between LZ and other populations (Fst ranging from 0.05 to 0.10). Furthermore, the highest ROH-based inbreeding estimate (FROH) of 0.11 was observed in LZ. In other populations, the FROH ranged from 0.04 to 0.06. In total, 74, 111, 62, 42 and 54 ROH islands containing SNPs ranked top 1% for concurrency were identified in SH, NM, DZ, LZ and LW, respectively. Genes common to the ROH islands in the five populations included BDNF, CCDC34, LGR4, LIN7C, GLS, LOC101747789, MYO1B, STAT1 and STAT4. This suggested their essential roles in adaptation of the chickens. We also identified a common candidate genomic region harboring AMY2A, NTNG1 and VAV3 genes in all populations. These genes had been implicated in digestion, neurite growth and high-altitude adaptation. CONCLUSIONS: High genetic diversity is observed in Tibetan native chickens. Inbreeding is more intense in the Nyingchi population which is also genetically distant from other chicken populations. Candidate genes in ROH islands are likely to be the drivers of adaptation to high altitude exhibited by the five Tibetan native chicken populations. Our findings contribute to the understanding of genetic diversity offer valuable insights for the genetic mechanism of adaptation, and provide veritable tools that can help in the design and implementation of breeding and conservation strategies for Tibetan native chickens.
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Pollos , Genoma , Animales , Pollos/genética , Genómica , Homocigoto , Miosina Tipo I , TibetRESUMEN
Streptococcus agalactiae mastitis is one of the significant threats to the milk industry. The traditional antibiotic treatment method is easy to cause the emergence of resistant strains, and the problem of drug residue is increasingly severe. In this study, we designed and synthesized five lipopeptides. The antibacterial activity of different molecular structure lipopeptides against Streptococcus agalactiae was detected. Furthermore, the mouse mastitis model was established using Streptococcus agalactiae. The lipopeptides with better antibacterial effect were selected for the treatment experiment to evaluate the application value in the treatment of mastitis. The results showed that 4 of the synthesized lipopeptides had specific antibacterial activity. SLP3 and SLP4 have an excellent antibacterial effect and can treat murine mastitis caused by Streptococcus agalactiae infection within the safe concentration range. The results of this study can provide an excellent experimental basis for new antibiotics and clinical application in the treatment of dairy cow mastitis.
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Mastitis Bovina , Infecciones Estreptocócicas , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bovinos , Femenino , Humanos , Lipopéptidos/farmacología , Lipopéptidos/uso terapéutico , Mastitis Bovina/tratamiento farmacológico , Mastitis Bovina/microbiología , Ratones , Leche/química , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus agalactiaeRESUMEN
Breast cancer is one of the most frequently diagnosed cancers and the leading cause of cancer death in women. MIER3 (Mesoderm induction early response 1, family member3) is considered as a potential oncogene for breast cancer. However, the role of MIER3 in breast cancer remain largely unknown. The expression of MIER3 was detected and the relationship between its expression and clinicopathological characteristics was also analyzed. The effect of MIER3 on proliferation and migration of breast cancer cells was detected in vitro and in vivo. Western blot, IF, and Co-IP were employed to detect the relationship between MIER3, HDAC1, HDAC2, and Snail. ChIP assay was performed to determine the binding of MIER3/HDAC1/HDAC2/Snail complex to the promoter of E-cadherin. In this study, we found that MIER3 was upregulated in breast cancer tissue and closely associated with poor prognosis of patients. MIER3 could promote the proliferation, migration, and epithelial-mesenchymal transition (EMT) of breast cancer cells. Further studies showed that MIER3 interacted with HDAC1/HDAC2 and Snail to form a repressive complex which could bind to E-cadherin promoter and was related to its deacetylation. Our study concluded that MIER3 was involved in forming a co-repressor complex with HDAC1/HDAC2/Snail to promote EMT by silencing E-cadherin.
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Neoplasias de la Mama/genética , Histona Desacetilasa 1/genética , Histona Desacetilasa 2/genética , Proteínas Nucleares/genética , Factores de Transcripción de la Familia Snail/genética , Anciano , Animales , Antígenos CD/genética , Antígenos CD/metabolismo , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Cadherinas/genética , Cadherinas/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Células Epiteliales/metabolismo , Células Epiteliales/patología , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Histona Desacetilasa 1/metabolismo , Histona Desacetilasa 2/metabolismo , Humanos , Ratones Desnudos , Persona de Mediana Edad , Proteínas Nucleares/antagonistas & inhibidores , Proteínas Nucleares/metabolismo , Regiones Promotoras Genéticas , Unión Proteica , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Transducción de Señal/genética , Factores de Transcripción de la Familia Snail/metabolismo , Análisis de Supervivencia , Carga Tumoral , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Escherichia coli serogroups O157, O26, O45, O103, O111, O121, and O145, when carrying major virulence genes, the Shiga toxin genes stx1 and stx2 and the intimin gene eae, are important foodborne pathogens. They are referred to as the "top 7" Shiga toxin-producing E. coli (STEC) serogroups and were declared by the USDA as adulterants to human health. Since top 7 serogroup-positive cattle feces and ground beef can also contain nonadulterant E. coli strains, regular PCR cannot confirm whether the virulence genes are carried by adulterant or nonadulterant E. coli serogroups. Thus, traditional gold-standard STEC detection requires bacterial isolation and characterization, which are not compatible with high-throughput settings and often take a week to obtain a definitive result. In this study, we demonstrated that the partition-based multichannel digital PCR (dPCR) system can be used to detect and associate the E. coli serogroup-specific gene with major virulence genes and developed a single-cell-based dPCR approach for rapid (within 1 day) and accurate detection and confirmation of major STEC serogroups in high-throughput settings. Major virulence genes carried by each of the top 7 STEC serogroups were detected by dPCR with appropriately diluted intact bacterial cells from pure cultures, culture-spiked cattle feces, and culture-spiked ground beef. Furthermore, from 100 randomly collected, naturally shed cattle fecal samples, 3 O103 strains carrying eae and 2 O45 strains carrying stx1 were identified by this dPCR assay and verified by the traditional isolation method. This novel and rapid dPCR assay is a culture-independent, high-throughput, accurate, and sensitive method for STEC detection and confirmation.
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Reacción en Cadena de la Polimerasa/métodos , Toxina Shiga I/genética , Toxina Shiga II/genética , Escherichia coli Shiga-Toxigénica/aislamiento & purificación , Análisis de la Célula Individual/métodos , Factores de Virulencia/genética , Animales , Bovinos , ADN Bacteriano , Proteínas de Escherichia coli/genética , Heces/microbiología , Microbiología de Alimentos , Genes Bacterianos , Carne/microbiología , Antígenos O/genética , Serogrupo , Toxina Shiga , Escherichia coli Shiga-Toxigénica/genéticaRESUMEN
BACKGROUND: CTLA-4 is a well-studied immune checkpoint protein that negatively regulates T cell-mediated immune responses. However, the expression of CTLA-4 in glioma and the effects of CTLA-4 on prognosis in patients with glioma have not yet been examined. METHODS: We investigated the protein level of CTLA-4 in human glioma samples, extracted genetic and clinical data from 1024 glioma patients to characterize CTLA-4 expression and its relationship with immune functions in gliomas. R language was used for statistical analysis. RESULTS: Higher CTLA-4 expression was found in patients with higher grade, isocitrate dehydrogenase (IDH)-wild-type, and mesenchymal-molecular subtype gliomas than in patients with lower grade, IDH-mutant, and other molecular subtype gliomas. Further analysis showed that there was a strong positive correlation between CTLA-4 and the specific marker gene expression of immune cells, including CD8+ T cells, regulatory T cells, and macrophages in both databases, suggesting that higher CTLA-4 expression in the glioma microenvironment induced greater immune cell infiltration compared with that in gliomas with lower CTLA-4 expression. We further explored the associations between CTLA-4 and other immune-related molecules. Pearson correlation analysis showed that CTLA-4 was associated with PD-1, CD40, ICOS, CXCR3, CXCR6, CXCL12 and TIGIT. Patients with glioma with lower CTLA-4 expression exhibited significantly longer overall survival. Thus, these findings suggested that increased CTLA-4 expression conferred a worse outcome in glioma. CONCLUSIONS: In summary, our findings revealed the expression patterns and clinical characteristics of CTLA-4 in glioma and may be helpful for expanding our understanding of antitumor immunotherapy in gliomas.
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KEY MESSAGE: The recessive Hessian fly resistance gene h4 and flanking SNP markers were located to a 642 kb region in chromosome 1A of the wheat cultivar 'Java.' Hessian fly (HF), Mayetiola destructor, is one of the most destructive insect pests in wheat worldwide. The wheat cultivar 'Java' was reported to carry a recessive gene (h4) for HF resistance; however, its chromosome location has not been determined. To map the HF resistance gene in Java, two populations of recombinant inbred lines (RILs) were developed from 'Bobwhite' × Java and 'Overley' × Java, respectively, and were phenotyped for responses to infestation of HF Great Plains biotype. Analysis of phenotypic data from the F1 and the RIL populations confirmed that one recessive gene conditioned HF resistance in Java. Two linkage maps were constructed using single-nucleotide polymorphism (SNP) markers generated by genotyping-by-sequencing (GBS). The h4 gene was mapped to the distal end of the short arm of chromosome 1A, which explained 60.4 to 70.5% of the phenotypic variation for HF resistance in the two populations. The GBS-SNPs in the h4 candidate interval were converted into Kompetitive Allele-Specific Polymerase Chain Reaction (KASP) markers to eliminate the missing data points in GBS-SNPs. Using the revised maps with KASP markers, h4 was further located to a 642 kb interval (6,635,984-7,277,935 bp). The two flanking KASP markers, KASP3299 and KASP1871, as well as four other closely linked KASP markers, may be useful for pyramiding h4 with other HF resistance genes in breeding.
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Dípteros , Genes Recesivos , Triticum/genética , Alelos , Animales , Mapeo Cromosómico , Cromosomas de las Plantas , Genes de Plantas , Ligamiento Genético , Marcadores Genéticos , Genotipo , Herbivoria , Polimorfismo de Nucleótido Simple , Sitios de Carácter CuantitativoRESUMEN
OBJECTIVES: To investigate the regio-selective demethylation of papaverine by CYP105D1 and develop a whole-cell biocatalytic system for the preparative synthesis of 6-O-demethyl-papaverine. RESULTS: CYP105D1 from Streptomyces griseus ATCC 13273 was used for the regioselective demethylation of papaverine at C-6 using putidaredoxin reductase (PDR) and putidaredoxin (Pdx) as the electron transport system. The Km value of CYP105D1 towards papaverine was estimated to be 92.24 µM. Furthermore, a CYP105D1-based whole-cell system was established in E. coli BL21(DE3). The whole cell biotransformation condition was optimized as 25 °C, pH 7.5, 8 g (cell dry weight) L-1 whole cell biomass and 3% (v/v) PEG-200 as cosolvent. Under the optimal condition, the conversion yield of papaverine reached to 61.15% within 24 h. CONCLUSIONS: The selective demethylation of papaverine by CYP105D1 was accomplished. The CYP105D1-based whole-cell biocatalyst has a potential used for the efficient synthesis of 6-O-demethyl-papaverine.
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Proteínas Bacterianas/química , Desmetilación , Oxigenasas/química , Papaverina/química , Streptomyces griseus/enzimologíaRESUMEN
Early planting is one of the strategies used to increase grain yield in temperate regions. However, poor cold tolerance in castor inhibits seed germination, resulting in lower seedling emergence and biomass. Here, the elite castor variety Tongbi 5 was used to identify the differential abundance protein species (DAPS) between cold stress (4 °C) and control conditions (30 °C) imbibed seeds. As a result, 127 DAPS were identified according to isobaric tag for relative and absolute quantification (iTRAQ) strategy. These DAPS were mainly involved in carbohydrate and energy metabolism, translation and posttranslational modification, stress response, lipid transport and metabolism, and signal transduction. Enzyme-linked immunosorbent assays (ELISA) demonstrated that the quantitative proteomics data collected here were reliable. This study provided some invaluable insights into the cold stress responses of early imbibed castor seeds: (1) up-accumulation of all DAPS involved in translation might confer cold tolerance by promoting protein synthesis; (2) stress-related proteins probably protect the cell against damage caused by cold stress; (3) up-accumulation of key DAPS associated with fatty acid biosynthesis might facilitate resistance or adaptation of imbibed castor seeds to cold stress by the increased content of unsaturated fatty acid (UFA). The data has been deposited to the ProteomeXchange with identifier PXD010043.
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Respuesta al Choque por Frío , Proteómica/métodos , Ricinus/metabolismo , Ricinus/fisiología , Semillas/metabolismo , Estrés Fisiológico , Regulación de la Expresión Génica de las Plantas , Ontología de Genes , Genes de Plantas , Germinación , Marcaje Isotópico , Modelos Biológicos , Anotación de Secuencia Molecular , Proteínas de Plantas/metabolismo , Reproducibilidad de los Resultados , Ricinus/genética , Transcripción GenéticaRESUMEN
We identified influenza C virus (ICV) in samples from US cattle with bovine respiratory disease through real-time PCR testing and sequencing. Bovine ICV isolates had high nucleotide identities (≈98%) with each other and were closely related to human ICV strains (≈95%). Further research is needed to determine bovine ICV's zoonotic potential.
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Enfermedades de los Bovinos/epidemiología , Enfermedades de los Bovinos/virología , Gammainfluenzavirus/clasificación , Gammainfluenzavirus/genética , Infecciones por Orthomyxoviridae/veterinaria , Infecciones del Sistema Respiratorio/veterinaria , Animales , Bovinos , Enfermedades de los Bovinos/historia , Historia del Siglo XXI , Filogenia , Estados Unidos/epidemiología , Proteínas de la Matriz Viral/genéticaRESUMEN
Myeloperoxidase and its product hypochlorous acid are endogenous substances that are involved in the pathogenesis of many inflammatory diseases. In the present study, a novel evaluation strategy has been developed to screen for myeloperoxidase inhibitors and hypochlorous acid scavengers in natural products. The evaluation strategy uses two methods: a multi-hyphenated high-performance liquid chromatography-photodiode array detection-chemiluminescence online method, and an ultrafiltration-high-performance liquid chromatography-mass spectrometry method. Both were used for screening hypochlorous acid scavengers and myeloperoxidase inhibitors. After optimization of operating conditions, including pH of mobile phase and concentrations of myeloperoxidase, hypochlorous acid and luminol, the evaluation strategy was applied to Gardenia jasminoides Ellis (Rubiaceae) extract. Gardenia jasminoides Ellis (Rubiaceae) extract was found to both scavenge hypochlorous acid and inhibit myeloperoxidase. These different bioactivities originate from iridoid glycosides and quinic acid derivatives (25 hypochlorous acid scavengers) and crocetin derivatives (4 myeloperoxidase inhibitors). In a mouse model of acute lung injury, pulmonary histopathology showed that different constituents of Gardenia jasminoides Ellis (Rubiaceae) extract could also attenuate lung injury. Although the screening strategy has two arms, it is still simple, rapid, and effective. The strategy can also potentially be used to discriminate different activities of different constituents contained in the same natural product.
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Productos Biológicos/análisis , Ácido Hipocloroso/química , Luminiscencia , Peroxidasa/química , Extractos Vegetales/análisis , Rubiaceae/química , Productos Biológicos/metabolismo , Cromatografía Líquida de Alta Presión/instrumentación , Inhibidores Enzimáticos/farmacología , Espectrometría de Masas/instrumentación , Estructura Molecular , Peroxidasa/antagonistas & inhibidores , Peroxidasa/metabolismo , Extractos Vegetales/metabolismoRESUMEN
It has always been a challenge to obtain a 360° panoramic imaging system with a high-resolution and non-visible seam. In this study, a 360° panoramic and high-performance system has been developed based on two tiled imaging channels with a field of view of 190° and F/# of 2.0. In this study, some issues regarding 360° panoramic tiled methods, such as relative illuminance and ghost images, were analyzed in detail and taken into consideration during the design procedure. In the final design, the stop has been fulfilled for each field angle, and the ghost images have also been well optimized. A proof-of-concept prototype producing a high-performance 360° panoramic video has been developed.
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Enzyme inhibitors from natural products are becoming an attractive target for drug discovery and development; however, separating enzyme inhibitors from natural-product extracts is highly complex. In this study, we developed a strategy based on tyrosinase-site blocking ultrafiltration integrated with HPLC-QTOF-MS/MS and optimized molecular docking to screen tyrosinase inhibitors from Puerariae lobatae Radix extract. Under optimized ultrafiltration parameters, we previously used kojic acid, a known tyrosinase inhibitor, to block the tyrosinase active site in order to eliminate false-positive results. Using this strategy, puerarin, mirificin, daidzin and genistinc were successfully identified as potential ligands, and after systematic evaluation by several docking programs, the rank of the identified compounds predicted by computational docking was puerarin > mirificin > kojic acid > daidzin ≈ genistin, which agreed with the results of tyrosinase-inhibition assays. Structure-activity relationships indicated that C-glycosides showed better tyrosinase inhibition as compared with O-glycosides, with reduced inhibition achieved through the addition of glycosyl, which provides ideas about the screen of leading compounds and structural modification.
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Medicamentos Herbarios Chinos/química , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Monofenol Monooxigenasa/química , Pueraria/química , Sitios de Unión , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Medicamentos Herbarios Chinos/farmacología , Activación Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Espectrometría de Masas , Monofenol Monooxigenasa/antagonistas & inhibidores , Unión Proteica , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Relación Estructura-ActividadRESUMEN
The interaction between proprotein convertase subtilisin/kexin type 9 (PCSK9) and the low-density lipoprotein receptor (LDLR) is a promising target for the treatment of hyperc-holesterolemia. In this study, a new method based on competitive affinity and tag detection was developed, which aimed to evaluate potent natural inhibitors preventing the interaction of PCSK9/LDLR directly. Herein, natural compounds with efficacy in the treatment of hypercholesterolemia were chosen to investigate their inhibitory activities on the PCSK9/LDLR interaction. Two of them, polydatin (1) and tetrahydroxydiphenylethylene-2-O-glucoside (2), were identified as potential inhibitors for the PCSK9/LDLR interaction and were proven to prevent PCSK9-mediated LDLR degradation in HepG2 cells. The results suggested that this strategy could be applied for evaluating potential bioactive compounds inhibiting the interaction of PCSK9/LDLR and this strategy could accelerate the discovery of new drug candidates for the treatment of PCSK9-mediated hypercholesterolemia.
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Productos Biológicos/farmacología , Glucósidos/farmacología , Inhibidores de PCSK9 , Receptores de LDL/antagonistas & inhibidores , Estilbenos/farmacología , Línea Celular Tumoral , Medicamentos Herbarios Chinos/farmacología , Glucósidos/química , Glucósidos/aislamiento & purificación , Células Hep G2 , Humanos , Hipercolesterolemia/tratamiento farmacológico , Hipercolesterolemia/genética , Proproteína Convertasa 9/metabolismo , Unión Proteica/efectos de los fármacos , Receptores de LDL/metabolismoRESUMEN
Hydrogel-based supercapacitors are an up-and-coming candidate for safe and portable energy storage. However, it is challenging for hydrogel electrolytes to achieve high conductivity and rapid self-healing at subzero temperatures because the movements of polymer chains and the reconstruction capability of broken dynamic bonds are limited. Herein, a highly conductive proton polyacrylamide-phytic acid (PAAm-PA) hydrogel electrolyte with rapid and autonomous self-healing ability and excellent adhesion over a wide temperature range is developed. PA, as a proton donor center, endows the hydrogels with high conductivity (102.0 mS cm-1) based on the Grotthuss mechanism. PA can also prevent the crystallization of water and form multiple reversible hydrogen bonds in the polymer network, which solves the dysfunction of self-healing hydrogels in a cryogenic environment. Accordingly, the hydrogel electrolytes demonstrate fast low-temperature self-healing ability with a self-healing efficiency of 79.4% within 3 h at -20 °C. In addition, the hydrogel electrolytes present outstanding adhesiveness on electrodes due to the generation of hydrogen bonds between PA and activated carbon electrodes. As a result, the integrated hydrogel-based supercapacitors with tight bonding electrode/electrolyte interface deliver a 139.5 mF cm-2 specific capacitance at 25 °C. Moreover, the supercapacitors display superb self-healing ability, achieving 92.1% of capacitance recovery after three cutting-healing cycles at -20 °C. Furthermore, the supercapacitors demonstrate only 6.4% capacitance degradation after 5000 charging-discharging cycles at -20 °C. This work provides a roadmap for designing all-in-one flexible energy storage devices with excellent self-healing ability over a wide temperature range.
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The scarcity of cryogenic thermometers often stems from their high cost and lengthy lead times for calibration. Establishing an in-lab temperature calibration system is necessary to quickly make use of uncalibrated sensors or self-made sensors. This paper introduces a straightforward and high-accuracy thermometer calibration system. By employing copper screws as thermal links between the sensor platform and the cryogen-free refrigerator, temperature oscillation on the sensor platform is suppressed to a few millikelvins. In addition, this paper presents a data processing model based on clustering algorithms. These algorithms sort and group data based on distance, which is similar to human visual judgment of data. This paper discusses the parameter optimization process of the clustering algorithm to interpret the automated data process. The cryogenic temperature sensors calibrated by this system exhibited high accuracy, with relative errors of less than 1% compared to standard thermometers. Moreover, automatically processing calibration data from two uncalibrated thermometers takes just over 10 min, highlighting the effectiveness of this calibration system.
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Conductive gels have greatly facilitated the development of flexible energy storage devices, including supercapacitors, batteries, and triboelectric nanogenerators. However, it is challenging for gel electrolytes to tackle the trade-off issues between mechanical properties and conductivity. Herein, a strategy of all inorganic salt-driven supramolecular networks is presented to construct gel electrolytes with high conductivity and reliable mechanical performance for flexible supercapacitors. The salt gel is successfully fabricated by combining a salt supramolecular network constructed by NH4Mo7O24·4H2O and FeCl3·6H2O and a polymer network of poly(vinyl alcohol). The inorganic salt supramolecular network serves as a rigid self-supporting framework in the hydrogel system for improving the mechanical properties and providing abundant active sites for accelerating ion transport. Furthermore, the salt gel-enabled supercapacitors are equipped and exhibit a high specific capacitance (199.4 mF cm-2) and excellent energy density (27.69 µWh cm-2). Moreover, the flexible supercapacitors not only present remarkable cyclic stability after 3000 charging/discharging cycles but also exhibit good electrochemical stability even under severe deformation conditions. The strategy of salt-gel-driven flexible supercapacitors would provide fresh thinking for the development of advanced flexible energy storage fields.