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Pyrrolo[1,2-a]indoles are structurally important scaffolds in many natural products and bioactive compounds. Herein, we report a novel synthetic method for pyrrolo[1,2-a]indole derivatives through visible-light-induced cascade dearomatizative cyclization of indoles with external nucleophiles. Moderate yields, good diastereoselectivities, and excellent regioselectivities were generally observed with the resultant indole-fused polycyclic compounds.
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Influenza A viruses evolve at a high rate of nucleotide substitution, thereby requiring continuous monitoring to determine the efficacy of vaccines and antiviral drugs. In the current study, we performed whole-genome sequencing analyses of 253 influenza A/H3N2 strains from Yunnan Province, China, during 2017-2022. The hemagglutinin (HA) segments of Yunnan A/H3N2 strains isolated during 2017-2018 harbored a high genetic diversity due to heterogeneous distribution across branches. The mutation regularity of the predominant antigenic epitopes of HA segments in Yunnan was inconsistent in different years. Some important functional mutations in gene segments associated with viral adaptation and drug tolerance were revealed. The rapid genomic evolution of Yunnan A/H3N2 strains from 2017 to 2022 mainly concentrated on segments, i.e., matrix protein 2 (M2), non-structural protein 1 (NS1), neuraminidase (NA), NS2, and HA, with a high overall non-synonymous/synonymous substitution ratio (dN/dS). Our results highlighted a decline in vaccine efficacy against the A/H3N2 circulating strains, particularly against the Yunnan 2021-2022 A/H3N2 strains. These findings aid our understanding of evolutionary characteristics and epidemiological monitoring of the A/H3N2 viruses and provide in-depth insights into the protective efficacy of influenza vaccines.
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Virus de la Influenza A , Gripe Humana , Humanos , Gripe Humana/epidemiología , Subtipo H3N2 del Virus de la Influenza A/genética , China/epidemiología , GenómicaRESUMEN
The rapid rise of two-dimensional (2D) materials has aroused increasing interest in the fields of microelectronics and optoelectronics; various types of 2D van der Waals heterostructures (vdWHs), especially those based on MoS2, have been widely investigated in theory and experiment. However, the interfacial properties of MoS2 and the uncommon crystal surface of traditional three-dimensional (3D) metals are yet to be explored. In this paper, we studied heterostructures composed of MoS2 and metal(001) slabs, based on the first-principles calculations, and we uncovered that MoS2/Au(001) and MoS2/Ag(001) vdWHs reveal Schottky contacts, and MoS2/Cu(001) belongs to Ohmic contact and possesses ultrahigh electron tunneling probability at the equilibrium distance. Thus, the MoS2/Cu(001) heterostructure exhibits the best contact performance. Further investigations demonstrate that external longitudinal strain can modulate interfacial contact to engineer the Schottky-Ohmic contact transition and regulate interfacial charge transport. We believe that it is a general strategy to exploit longitudinal strain to improve interfacial contact performance to design and fabricate a multifunctional MoS2-based electronic device.
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In this work, a solute retention optimization method (SRO) was proposed to exploit the purification potential of two-dimensional liquid chromatography (2D-LC). According to our findings, the complementarity of 2D-LC correlates with some specific impurities. In the two methods used in 2D-LC, the retention order of these impurities and target compound is completely opposite. Taking full advantage of the complementarity is crucial to enhance the saturation capacity (wmax) of 2D-LC by SRO. For the purpose of validating the effectiveness of SRO, a reverse-phase liquid chromatography (RPLC) coupled with hydrophilic interaction chromatography (HILIC) was developed to purify p-chlorobenzoic acid from substituted benzenes. By using the overloading effects of analytes as indicators, the wmax of RPLC × HILIC was determined by the bisection method, and finally defined by the extremely high loading volume of 4.9 mL. A touch-peak separation of impurities and the target compound occurred precisely during the secondary separation. The effectiveness of SRO was also verified by the greater purification efficiency of RPLC × HILIC than that of HILIC × RPLC. Subsequently, a RPLC × RPLC method was developed by SRO to prepare the reference materials of caffeine from tea extracts. Only by an analytical C18 column, 15.6 mg of caffeine with the purity of 98.3% was obtained at once with the recovery up to 82.3%. However, without the aid of SRO, the purity rapidly decreased to 62.0%. Compared to other methods, SRO-based 2D-LC offers certain advantages in terms of purity, recovery, and the purification efficiency, suggesting that it is particularly effective in developing preparative 2D-LC facing complex matrices.
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Cafeína , Cromatografía de Fase Inversa , Cromatografía de Fase Inversa/métodos , Interacciones Hidrofóbicas e HidrofílicasRESUMEN
A new strategy of improving boronate avidity with good accessibility of sites was suggested by utilizing a dendrimer-like structure of boron materials based on octavinyl-polyhedral oligomeric silsesquioxanes (Ov-POSS). 3-(Acrylamido)phenylboronic acid (AAPBA) was used as a functional monomer and ethylene glycol dimethacrylate (EDMA) and Ov-POSS as cross-linkers. The resulting Ov-POSS cross-linked boron monolith exhibited 27 times stronger affinity for glycoproteins than the Ov-POSS-free monolith. Importantly, the bonding strength of the poly(AAPBA-co-Ov-POSS-co-EDMA) monolith to the glycoproteins with multiple sugars, horseradish peroxidase (HRP) was 4 orders of magnitude higher than that of the single cis-diol-containing compound. The resulting monolith was used as a part of a microfluidic platform for online processing of the protein extracts from mouse liver, which integrated five functions, including protein grading, denaturation, enzymatic hydrolysis, and enrichment of glycopeptides and ubiquitin-modified peptides. The sample processing time can be reduced by nearly half compared to the offline method. Moreover, 86.7% of glycopeptides and 75% of glycoproteins were newly identified after treatment. All of the results indicated that the synergistic strategy of Ov-POSS cross-linking can significantly improve trace glycosylation's binding capacity and enrichment performance. The microfluidic platform developed may provide a promising technical tool for automated, high-efficiency, high-throughput analysis for post-translational modification proteomics.
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Dendrímeros , Animales , Ratones , Glicosilación , Microfluídica , Boro , Glicoproteínas/química , Glicopéptidos/química , UbiquitinaciónRESUMEN
@#Abstract: Objective To investigate the molecular characteristics of the H9N2 avian influenza virus (AIV) causing human infection in Yunnan Province in 2019, and to provide the scientific basis for the prevention and control of avian influenza in Yunnan Province. Methods Influenza virus typing was performed by real-time RT-PCR in two influenza-like illness samples, and the Illumina Miseq high-throughput sequencer was used to determine the viral genome sequence. HA and NA gene sequence alignment and phylogenetic tree construction were performed using Mega7.0 software. Results Real-time RT-PCR results showed that two influenza-like illness samples were positive for H9N2 subtype. The full length of HA and NA were obtained by genomic sequencing. Sequence system evolution analysis showed that the HA and NA of the two AIVs in Yunnan Province were in the same evolutionary clade as A/Chicken/Zhejiang/HJ/2007 and belonged to the G57 type. The HA nucleotide and amino acid homology of the two AIVs were 93.92% and 95.00%, respectively, and the NA nucleotide and amino acid homology was 93.31% and 82.03%, respectively. The nucleotide (amino acid) homology of HA was 92.29%-96.94% (93.77%-98.43%) and 92.84%-94.92% (94.18%-96.23%), respectively, and NA nucleotide homology (amino acid) were 91.81%-97.60% (77.82%-94.83%), 94.38%-97.22% (85.47%-94.55%), respectively, compared with that of human infected H9N2 epidemic strains obtained in China from 2015 to 2020. Both AIVs HA protein cleavage site sequences were PSRSSR↓GLF, which was in line with the characteristics of low pathogenic influenza. The analysis of HA protein receptor binding site showed that amino acids at positions 109, 161, 163, 191, 202, 203 and 234 were consistent with the reference strains, while amino acids at position 198 were mutated to T. N166D and 168N mutations were also found in HA protein, and both AIVs had 7 potential glycosylation sites. Analysis of the erythrocyte binding site of NA gene found that there were amino acid mutations at positions 369, 402, 403, and 432, and amino acid deletion at positions 63-65 was found in the NA genes. There were 4 and 5 potential glycosylation sites in the two AIVs, respectively, and no drug resistance site mutations were found. Conclusions The receptor binding sites, erythrocyte binding sites and glycosylation sites of HA and NA genes of H9N2 AIV in Yunnan Province have different degrees of variation, and monitoring and prevention and control should be strengthened.
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The Omicron variants spread rapidly worldwide after being initially detected in South Africa in November 2021. It showed increased transmissibility and immune evasion with far more amino acid mutations in the spike (S) protein than the previously circulating variants of concern (VOCs). Notably, on 15 July 2022, we monitored the first VOC / Omicron subvariant BA.2.75 in China from an imported case. Moreover, nowadays, this subvariant still is predominant in India. It has nine additional mutations in the S protein compared to BA.2, three of which (W152R, G446S, and R493Q reversion) might contribute to higher transmissibility and immune escape. This subvariant could cause wider spread and pose a threat to the global situation. Our timely reporting and continuous genomic analysis are essential to fully elucidate the characteristics of the subvariant BA.2.75 in the future.
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In this study, a strategy of improving imprinting performance was developed using an enhanced cooperation effect of functional monomers based on deep eutectic solvents (DESs) monomer for the specific enrichment of benzoylation modified peptides. Zinc acrylate and DESs monomers were used as binary functional monomers, and ethylene glycol dimethacrylate was used as the cross-linking agent with SGRGKbz as template to prepare an imprinted monolith. It was observed that the use of DESs monomer significantly improveed the affinity of benzoylation imprinted monolith and increased the adsorption capacity. Under optimal conditions, the recovery and imprinting factor (IF) of the imprinted monolith for SGRGKbz can reach 93.0% and 10.58, respectively. The average recovery of SGRGKbz extracted from the spiked histone digestion solution can reach 88.4% (n = 5, RSD = 3.4%). After treatment with the benzoylation imprinted monolith, 12 benzoylation modified peptides, 13 benzoylation modified sites and 12 benzoylation proteins could be identified in the digestion of mouse liver protein, while only one of each benzoylation modified peptide, benzoylation modified site and benzoylation protein could be identified in the untreated digestion of mouse liver protein. The results indicated that the prepared imprinted monolith using DESs-based functional monomer was an effective method to increase the affinity of the resulting MIP.
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Impresión Molecular , Adsorción , Animales , Disolventes Eutécticos Profundos , Ratones , Impresión Molecular/métodos , Péptidos , Polímeros , SolventesRESUMEN
This paper reported a feasible method to prepare molecularly imprinted polymer (MIPs) using 4-vinylpyridine (4-VP) and Allyl-ß-cyclodextrin (ß-CD) as binary functional monomer in the presence of polystyrene (PS). This is the first time that a surrounding of macromolecular crowding was established to improve the imprinting effect of cyclodextrins as monomer in organic solvents. The morphological and characteristics of the polymers with macromolecular crowding reagents were investigated by scanning electron microscope (SEM), fourier-transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA) and nitrogen adsorption experiments. The MIPs were synthesized with 4-VP and ß-CD as binary functional monomers, a series of experiments were conducted to compare with the control groups. Furthermore, the selectivity of MIP for analogues experiment showed that the ß-CD/4-VP MIP has higher specific recognition for arctiin than ß-CD/4-VP NIP. A purification method by ß-CD/4-VP MIPs coupled with macromolecular crowding reagents was developed for extraction arctiin from Arctium lappa L. In the MIP-SPE process, the optimal washing and eluting reagents are methanol/water (5:5) and methanol/acid (9:1), respectively. When using the ß-CD/4-VP MIPs as SPE absorbent, the mean recoveries for arctiin were 87% with purity of 95%. All the results indicate that this synthetic method using 4-VP and ß-CD as binary functional monomers in the presence of PS is a promising method for the preparation of selective adsorbents for arctiin analysis in Arctium lappa L.
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For the first time a hybrid molecularly imprinted polymer (MIP) doped with 3-(trimethoxysilyl) propyl methacrylate (γ-MPS)-modified mesoporous molecular sieve SBA-15 for target peptide recognition has been developed. Zinc acrylate and methacrylic acid were used as binary functional monomers, and ethylene dimethacrylate was used as cross-linking agent to prepare an imprinted monolith against Val-Tyr-Ala-Leu-Lys(glutarylation) (VYALKglu). The morphology of the polymers was characterized by scanning electron microscopy, FT-IR spectroscopy, energy dispersive spectroscopy, and 1H NMR. The SBA-15-MPS MIP showed high recovery of 87.1% and the IF of 12.9 for the enrichment of the template peptide. When the template peptide concentration ranged from 5 to 90 µg mL-1, the correlation coefficients (R2) for the calibration function obtained was better 0.999. The limit of detection (LOD, 0.30 µg mL-1) and limit of quantification (LOQ, 1.0 µg mL-1) were achieved for signal-to-noise ratios of 3:1 and 10:1, respectively. When other kinds of synthetic peptides were used as analogs, the selectivity of the SBA-15-MPS MIP was much better than the SBA-15-MPS NIP (without template peptides) with relative selectivity coefficients of 52.8-265. In contrast, little quinolones and biogenic amines are adsorbed with the SBA-15-MPS MIP. The SBA-15-MPS MIP could enrich VYALKglu from spiked histone digestion with the average recovery of 87.8% and the relative standard deviation (RSD) of 0.99%. As a conclusion, doping of SBA-15 is an effective approach to the improvement of performance of molecularly imprinted monolith.
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Metacrilatos/química , Polímeros Impresos Molecularmente/química , Compuestos de Organosilicio/química , Péptidos/análisis , Dióxido de Silicio/química , Adsorción , Tamaño de la Partícula , Porosidad , Propiedades de SuperficieRESUMEN
A new dual-function enzyme reactor was prepared based on a dopamine/graphene oxide coated boron affinity monolithic column, which can be used for simultaneous protein enzymatic hydrolysis and glycopeptide enrichment. Firstly, a boron affinity monolithic column was prepared as the carrier for enzyme reactor. Secondly, the monolithic column was coated with dopamine/graphene oxide to provide higher specific surface area for the increase in the amount of trypsin bound. Then, dopamine can self-polymerize under alkaline conditions to produce multiple reaction sites. By the Schiff base reaction and Michael addition reaction with amino, sulfhydryl groups to trypsin, enzyme were immobilized on the boron affinity monolithic carrier. The enzyme activity was characterized by kinetic parameters maximum rate (Vmax) of the enzyme reaction and Michaelis constant (Km). Km of the dual-function enzyme reactors doped with PDA/GO and without PDA/GO were 34.37 and 120.93 mM, Vmax were 1.35 and 3.35 mM/min, respectively. The performance of the dual-function enzyme reactor was evaluated by protein extraction of mouse liver. After digested by the dual-function enzyme reactor, the number of peptides was 4,801, which was 960 more than the number of peptides in the solution digestion. At the same time, the dual-function enzyme reactor displayed the ability to capture cis-dihydroxy compounds specificly. A total of 55 glycopeptides were enriched in the dual-functional enzyme reactor, corresponding to 33 glycoproteins. The dual-function enzyme reactor provided repeatable performance and robust with long-term storage.
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Dopamina , Glicopéptidos , Animales , Enzimas Inmovilizadas/metabolismo , Glicoproteínas/química , Grafito , Hidrólisis , Ratones , Tripsina/metabolismoRESUMEN
To overcome the identification challenge of low-abundance lysine acetylation (Kac), a novel approach based on a molecularly imprinted polymer (MIP) was developed to improve the extraction capacity of Kac peptides in real samples. Green deep eutectic solvents (DESs) were introduced and used as one of the synergistic functional monomers with zinc acrylate (ZnA). Glycine-glycine-alanine-lysine(ac)-arginine (GGAKacR) was chosen as a template and N,N'-methylenbisacrylamide (MBAA) was used as a cross-linker. The obtained GGAKacR-MIP had excellent selectivity for the template with an imprinting factor (IF) of up to 21.4. The histone digest addition experiment demonstrated that GGAKacR-MIP could successfully extract GGAKacR from a complex sample. Finally, the application to the extraction of Kac peptides from mouse liver protein digestion was studied in detail. The number of Kac peptides and Kac proteins identified was 130 and 110, which were 3.71-fold and 3.93-fold higher than those of the untreated sample. In addition, the number of peptides and proteins identified after treatment increased from 5535 and 1092 to 17â¯149 and 4037 (3.10-fold and 3.70-fold, respectively). The results showed that the obtained MIP may provide an effective technical tool for the identification of Kac-modification and peptide fractionation, as well as a potential approach for simultaneously identifying post-translational-modified proteomic and proteomic information.
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Impresión Molecular , Animales , Disolventes Eutécticos Profundos , Lisina , Ratones , Impresión Molecular/métodos , Péptidos , Polímeros , Proteómica , Extracción en Fase Sólida , SolventesRESUMEN
In this paper, an enhanced imprinting effect of utilizing single wall carbon nanotubes (SWCNT) and polyhedral oligomeric silsesquioxanes (POSS) was suggested to improve drug delivery. The combination of 1-butyl-3-methylimidazoliumtetrafluoroborate ([BMIM]BF4), tetrahydrofuran (THF) and choline chloride-ethylene glycol (ChCl / EG) was used as a ternary porogen to prepare molecularly imprinted polymer (MIPs) doped with SWCNT and POSS. In the presence of gallic acid (GAL), 4-vinylpyridine (4-VP) and ethylene glycol dimethacrylate (EDMA) were used as functional monomer and crosslinker, respectively. The structure and morphological parameters of the MIP composite, such as surface area and pore size distribution, were also measured. In the studies of in vitro releases, superior controlled release characteristics can be achieved due to the enhanced imprinting effect of the MIPs doped with POSS and SWCNT. In vivo release studies showed that the POSS-SWCNT MIP had the maximum plasma concentration after 4 h. Compared with the control MIPs and NIP, the POSS-SWCNT MIP displayed a maximum AUC0-9 of 544.73 (ng h mL-1), while only 327.48, 212.91, 230.35 and 275.13 (ng h mL-1) for the POSS MIP, SWCNT MIP, MIP and POSS-SWCNT NIP, respectively.
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Impresión Molecular , Nanotubos de Carbono , Preparaciones Farmacéuticas , Ácido Gálico , Polímeros Impresos MolecularmenteRESUMEN
Metal- and additive-free photoredox cyclization of N-arylacrylamides is herein reported that provides a concise access to the formation of dihydroquinolinones. In this protocol, sustainable visible light was used as the energy source, and the organic light-emitting molecule 4CzIPN served as the efficient photocatalyst. This reaction system features exclusive 6-endo-trig cyclization selectivity with a generally good yield of a range of functionalized dihydroquinolinones and dihydrobenzoquinolinones. Mechanistical studies reveal the feasibility of both 1,3-H shift and intersystem crossing of the diradical intermediate.
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Multi-template imprinting is one of the challenge for molecular imprinting since the selectivity and binding affinity for each analyte decrease significantly compared with the corresponding molecularly imprinting polymers (MIPs) against single template. In this work, molecular crowding effect was tried to remedy the problem of imprinting reduction caused by the competition of two templates. Methacrylic acid (ACR) was used as functional monomer, ethylene dimethacrylate (EDMA) as crosslinker, and polystyrene (PS) as macromolecular crowding agent. With levofloxacin (S-OFX) as the first template, a number of compounds with varied chemical structure were chosen as the second template to investigate the imprinting effect of dual-template. When S-OFX and naproxen (S-NAP) was used as the dual-template, the imprinting factor (IF) of the resulting MIP for S-OFX was 20.1 and IF for S-NAP was 10.9. In contrast, for the single-template MIPs, IF for S-OFX was 22.4, and IF for S-NAP was 11.9. As a comparison, the IF of the DT-MIP prepared in absence of PS was only 2.3 for S-OFX and 1.0 for S-NAP. To analyze recognition mechanism of the molecular crowding-based imprinting system, molecular dynamics simulations to the chain structure of PS and binding modes between template and functional monomers was conducted by NAMD software. All the results displayed that molecular crowding is a promising method to improve the affinity of the dual-template imprinted polymer.
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Impresión Molecular , Polímeros Impresos Molecularmente , Sustancias Macromoleculares , Polímeros , PoliestirenosRESUMEN
Molecularly imprinted polymers (MIPs) incorporated with liquid crystalline monomers can imprint and recognize templates at a very low level of crosslinking, thus addressing challenges associated with conventional MIPs, such as the embedding of the imprinted sites, low binding capacity, and slow mass transfer due to the high degree of crosslinking. Compared with traditional MIPs, the prepared MIPs have a greater number of easily binding sites, which can effectively overcome the embedding and low utilization of imprinting sites. Simultaneously, with a decrease in the level of chemical crosslinking, the mass transfer of template molecules can be significantly improved. However, the imprinting effect of liquid crystalline MIPs is generally weaker than that of traditional MIPs due to the low degree of crosslinking. Therefore, to obtain liquid crystalline MIPs with a good imprinting effect, a series of low-crosslinked liquid crystalline molecularly imprinted monoliths were prepared by graft polymerization and evaluated by high performance liquid chromatography (HPLC) to systematically determine the relation between the polymerization parameters and the affinity of the resulting liquid crystalline MIPs. In this experiment, trimethylolpropane trimethacrylate (TRIM) was used to synthesize a monolithic column skeleton with toluene and dodecyl alcohol as porogens. (S)-Naproxen was used as a template and liquid crystalline monomer 4-(4-cyanophenyl)-cyclohexyl ethylene (CPCE) was added for grafting to synthesize the liquid crystalline MIP monolith. The influence of the acetonitrile content and pH in the mobile phase on the chromatographic retention of the template molecule was investigated. The results showed that the main force of MIP recognizing naproxen changed from hydrogen bonding to hydrophobic interaction by the addition of the liquid crystalline monomer. Frontal analysis and adsorption isotherm fitting, including Langmuir, Freundlich, and Scatchard fitting, showed that when the crosslinking degree was 15%, the liquid crystalline MIPs exhibited the highest imprinting factor and heterogeneity, and the specific adsorption was stronger than non-specific adsorption. By analyzing the stoichiometric displacement model, the total affinity of the MIP monoliths for the template molecules (ln A) was determined to be 0.645, significantly higher than that of its analogues, indicating that the liquid crystalline imprinted monolith had a higher total affinity for the template molecule. The spatial matching degree (nß) of the template molecule to the cavity structures of MIPs was also very high, and only inferior to that of ketoprofen. Nevertheless, the ln A value of ketoprofen was only 0.242, which indicated that the spatial effect was not the key factor in determining the recognition ability of liquid crystalline imprinting systems. An analysis of the separation thermodynamics revealed that the separation of the liquid crystalline MIPs was an entropy-controlled process, while that of conventional liquid crystalline-free MIPs was an enthalpy-controlled process. Based on the above results, the addition of a liquid crystalline monomer may alter the recognition mechanism of MIPs, and an appropriately low crosslinking degree can significantly improve the recognition performance of liquid crystalline MIPs, paving the way for a new generation of MIPs.
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Cristales Líquidos , Impresión Molecular , Polimerizacion , Polímeros , TermodinámicaRESUMEN
To limit the spread of severe acute respiratory syndrome coronavirus 2, the government of China has been monitoring infected travelers and minimizing cold-chain contamination. However, other factors might contribute to recurring outbreaks. We analyze the role of undocumented migrants as potential transmitters of severe acute respiratory syndrome coronavirus 2 in China.
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COVID-19 , Migrantes , China/epidemiología , Brotes de Enfermedades , Humanos , SARS-CoV-2RESUMEN
Microfluidic system with multi-functional integration of high-throughput protein/peptide separation ability has great potential for improving the identification capacity of biological samples in proteomics. In this paper, a sample treatment platform was constructed by integrating reversed phase chromatography, immobilized enzyme reactor (IMER) and imprinted monolith through a microfluidic chip to achieve the online proteins fractionation, denaturation, digestion and peptides enrichment. We firstly synthesized a poly-allyl phenoxyacetate (AP) monolith and a lysine-glycine-glycine (KGG) imprinted monolith separately, and investigated in detail their performance in fractionating proteins and extracting KGG from the protein digests of MCF-7 cell. The removal percentage of 94.6% for MCF-7 cell protein and the recovery of 90.8% for KGG were obtained. The number of proteins and peptides identified on this microfluidic platform was 2,004 and 8,797, respectively, which was 2.8-fold and 3.0-fold higher than that of untreatment sample. The time consumed by this platform for a sample treatment was about 9.6 h, less than that of conventional method (approximate 13.3 h). In addition, this platform can enrich some peptide fragments containing KGG based on imprinted monolith, which can be served for the identification of ubiquitin-modified proteomics. The successful construction of this integrated microfluidic platform provides a considerable and efficient technical tool for simultaneous identification of proteomics and post-translational modification proteomics information.
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Microfluídica , Proteínas , Digestión , Péptidos , TripsinaRESUMEN
An organic-inorganic hybrid monolith incorporated with titanium dioxide nanotubes (TNTs) and hydrophilic deep eutectic solvents (DESs) was prepared and evaluated by the isolation of proteins using solid phase microextraction. A typical polymerization system was composed of choline chloride/methacrylic acid (ChCl/MAA, DESs monomer), glycidyl methacrylate (GMA), as well as ethylene glycol dimethacrylate (EDMA) in the presence of TNTs. Then the epoxy groups on the surface of the resulting monolith were modified with amino groups. The synergistic effect of TNTs and DESs monomer to improve the enrichment performance of the sorbent significantly was demonstrated. Compared with the corresponding TNTs/DESs-free monolith, the recoveries of BSA and OVA were increased to 98.6% and 92.7% (RSDs < 2.0%), with an improvement of more than 60.0%. With a correlation coefficient of determination (R2) higher than 0.9995, the enrichment factors (EFs) were 21.9-28.3-fold. In addition, the resulting monolith was further applied to specifically capture proteins from rat liver according to their pI value, followed by HPLC-MS/MS analysis. The results indicated that the developed monolith was an effective material to isolate protein species of interest according to the pI value of target proteins.
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Nanotubos , Polímeros , Solventes , Espectrometría de Masas en Tándem , TitanioRESUMEN
PURPOSE: The incidence of breast cancer worldwide has been on the rise since the late 1970s, and it has become a common tumor that threatens women's health. Aminoglutethimide (AG) is a common treatment of breast cancer. However, current treatments require frequent dosing that results in unstable plasma concentration and low bioavailability, risking serious adverse reactions. Our goal was to develop a molecularly imprinted polymer (MIP) based delivery system to control the release of AG and demonstrate the availability of this drug delivery system (DDS), which was doped with carbon nanotube with aid of metal-organic gel. METHODS: Preparation of MIP was optimized by key factors including composition of formula, ratio of monomers and drug loading concentration. RESULTS: By using multi-walled carbon nanotubes (MWCNT) and metal-organic gels (MOGs), MIP doubled the specific surface area, pore volume tripled and the IF was 1.6 times than the reference. Compared with commercial tablets, the relative bioavailability was 143.3% and a more stable release appeared. CONCLUSIONS: The results highlight the influence of MWCNT and MOGs on MIP, which has great potential as a DDS.