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1.
Sci Robot ; 5(43)2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-33022613

RESUMO

Transforming natural cells into functional biocompatible robots capable of active movement is expected to enhance the functions of the cells and revolutionize the development of synthetic micromotors. However, present cell-based micromotor systems commonly require the propulsion capabilities of rigid motors, external fields, or harsh conditions, which may compromise biocompatibility and require complex actuation equipment. Here, we report on an endogenous enzyme-powered Janus platelet micromotor (JPL-motor) system prepared by immobilizing urease asymmetrically onto the surface of natural platelet cells. This Janus distribution of urease on platelet cells enables uneven decomposition of urea in biofluids to generate enhanced chemophoretic motion. The cell surface engineering with urease has negligible impact on the functional surface proteins of platelets, and hence, the resulting JPL-motors preserve the intrinsic biofunctionalities of platelets, including effective targeting of cancer cells and bacteria. The efficient propulsion of JPL-motors in the presence of the urea fuel greatly enhances their binding efficiency with these biological targets and improves their therapeutic efficacy when loaded with model anticancer or antibiotic drugs. Overall, asymmetric enzyme immobilization on the platelet surface leads to a biogenic microrobotic system capable of autonomous movement using biological fuel. The ability to impart self-propulsion onto biological cells, such as platelets, and to load these cellular robots with a variety of functional components holds considerable promise for developing multifunctional cell-based micromotors for a variety of biomedical applications.

2.
BMC Bioinformatics ; 21(1): 409, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938389

RESUMO

An amendment to this paper has been published and can be accessed via the original article.

4.
Nano Lett ; 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: covidwho-604507

RESUMO

We report cellular nanosponges as an effective medical countermeasure to the SARS-CoV-2 virus. Two types of cellular nanosponges are made of the plasma membranes derived from human lung epithelial type II cells or human macrophages. These nanosponges display the same protein receptors, both identified and unidentified, required by SARS-CoV-2 for cellular entry. It is shown that, following incubation with the nanosponges, SARS-CoV-2 is neutralized and unable to infect cells. Crucially, the nanosponge platform is agnostic to viral mutations and potentially viral species, as well. As long as the target of the virus remains the identified host cell, the nanosponges will be able to neutralize the virus.

5.
Genes (Basel) ; 11(6)2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32485962

RESUMO

Keratin-associated proteins are important components of wool fibers. The gene encoding the high-sulfur keratin-associated protein 2-1 has been described in humans, but it has not been described in sheep. A basic local alignment search tool nucleotide search of the Ovine Genome Assembly version 4.0 using a human keratin-associated protein 2-1 gene sequence revealed a 399-base pair open reading frame, which was clustered among nine previously identified keratin-associated protein genes on chromosome 11. Polymerase chain reaction-single strand conformation polymorphism analysis revealed four different banding patterns, with these representing four different sequences (A-D) in Chinese sheep breeds. These sequences had the highest similarity to human keratin-associated protein 2-1 gene, suggesting that they represent variants of ovine keratin-associated protein 2-1 gene. Nine single nucleotide variations were detected in the gene, including one non-synonymous nucleotide substitution. Differences in variant frequencies between fine-wool sheep breeds and coarse-wool sheep breeds were detected. The gene was found to be expressed in various tissues, with the highest expression level in skin, and moderate expression levels in heart and lung tissue. These results reveal that the ovine keratin-associated protein 2-1 gene is variable and suggest the gene might affect variation in mean fiber diameter.

6.
Sheng Li Xue Bao ; 72(3): 285-298, 2020 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-32572427

RESUMO

The current study was aimed to investigate the potential effects of perinatal exposure to therapeutic dose of penicillin and cefixime on the cognitive behaviors, gastrointestinal (GI) motility and serum 5-hydroxytryptamine (5-HT) level in the offspring. Pregnant rats were continuously treated with cefixime or penicillin in the period between 1 week before and 1 week after labor. Behavior tests, including social preference, self-grooming and elevated plus maze tests, and intestinal motility tests were carried out on the offspring at age of 4 to 10 weeks. Serum 5-HT levels were detected with ELISA, and potassium/sodium hyperpolarization activated cyclic nucleotide-gated channel 2 (HCN2) and tryptophan hydroxylase 1 (TPH1) expression levels in colon epithelium of offspring were detected by Western blot and RT-qPCR. The results showed that, compared with the naive group, cefixime increased social behavior in the female offspring, but did not affect the male offspring. Compared with the naive group, cefixime significantly decreased colonic and intestinal transits, and increased cecum net weight and standardized cecum net weight in the male offspring, but did not affect the female offspring. The serum 5-HT levels in the male offspring, rather than the female offspring, in cefixime and penicillin groups were significantly increased compared with that in the naive group. The protein expression level of HCN2 in colon epithelium of the offspring in cefixime group was significantly down-regulated, and the TPH1 expression level was not significantly changed, compared with that in the naive group. These results suggest that perinatal antibiotics exposure may affect neural development and GI functions of the offspring, and the mechanism may involve peripheral 5-HT and gender-dependent factor.


Assuntos
Serotonina , Triptofano Hidroxilase , Animais , Antibacterianos/farmacologia , Colo , Feminino , Motilidade Gastrointestinal , Masculino , Camundongos , Gravidez , Ratos
7.
Artigo em Inglês | MEDLINE | ID: mdl-32551679

RESUMO

We report cellular nanosponges as an effective medical countermeasure to the SARS-CoV-2 virus. Two types of cellular nanosponges are made of the plasma membranes derived from human lung epithelial type II cells or human macrophages. These nanosponges display the same protein receptors, both identified and unidentified, required by SARS-CoV-2 for cellular entry. It is shown that, following incubation with the nanosponges, SARS-CoV-2 is neutralized and unable to infect cells. Crucially, the nanosponge platform is agnostic to viral mutations and potentially viral species, as well. As long as the target of the virus remains the identified host cell, the nanosponges will be able to neutralize the virus.


Assuntos
Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Nanoestruturas , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Betacoronavirus/patogenicidade , Betacoronavirus/fisiologia , Membrana Celular/virologia , Infecções por Coronavirus/virologia , Células Epiteliais/virologia , Interações entre Hospedeiro e Microrganismos , Humanos , Pulmão/citologia , Pulmão/virologia , Macrófagos/virologia , Nanoestruturas/ultraestrutura , Nanotecnologia , Pneumonia Viral/virologia , Receptores Virais/fisiologia , Internalização do Vírus
8.
Aging (Albany NY) ; 12(10): 9882-9914, 2020 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-32461378

RESUMO

Considerable evidence suggests that metabolic abnormalities are associated with neurodegenerative diseases. This study aimed to conduct a systematic metabolic analysis of Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). Human and mouse model microarray datasets were downloaded from the Gene Expression Omnibus database. The metabolic genes and pathways were collected from the Recon 3D human metabolic model. Drug and target information was obtained from the DrugBank database. This study identified ATP1A1, ATP6V1G2, GOT1, HPRT1, MAP2K1, PCMT1 and PLK2 as key metabolic genes that were downregulated in AD, PD and HD. We screened 57 drugs that target these genes, such as digoxin, ouabain and diazoxide. This study constructed multigene diagnostic models for AD, PD and HD by using metabolic gene expression profiles in blood, all models showed high accuracy (AUC > 0.8) both in the experimental and validation sets. Furthermore, analysis of animal models showed that there was almost no consistency among the metabolic changes between mouse models and human diseases. This study systematically revealed the metabolic damage among AD, PD, and HD and uncovered the differences between animal models and human diseases. This information may be helpful for understanding the metabolic mechanisms and drug development for neurodegenerative diseases.

9.
Sci Adv ; 6(13): eaaz6108, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32258408

RESUMO

Small interfering RNA (siRNA) is a powerful tool for gene silencing that has been used for a wide range of biomedical applications, but there are many challenges facing its therapeutic use in vivo. Here, we report on a platelet cell membrane-coated metal-organic framework (MOF) nanodelivery platform for the targeted delivery of siRNA in vivo. The MOF core is capable of high loading yields, and its pH sensitivity enables endosomal disruption upon cellular uptake. The cell membrane coating provides a natural means of biointerfacing with disease substrates. It is shown that high silencing efficiency can be achieved in vitro against multiple target genes. Using a murine xenograft model, significant antitumor targeting and therapeutic efficacy are observed. Overall, the biomimetic nanodelivery system presented here provides an effective means of achieving gene silencing in vivo and could be used to expand the applicability of siRNA across a range of disease-relevant applications.


Assuntos
Plaquetas/metabolismo , Membrana Celular/metabolismo , Vesículas Revestidas/metabolismo , Inativação Gênica , Nanopartículas Metálicas , Estruturas Metalorgânicas , Animais , Linhagem Celular Tumoral , Portadores de Fármacos , Técnicas de Silenciamento de Genes , Técnicas de Transferência de Genes , Genes Reporter , Humanos , Camundongos , RNA Interferente Pequeno , Survivina/genética , Survivina/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Epigenetics Chromatin ; 13(1): 8, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093759

RESUMO

BACKGROUND: An increasing number of nucleic acid modifications have been profiled with the development of sequencing technologies. DNA N6-methyladenine (6mA), which is a prevalent epigenetic modification, plays important roles in a series of biological processes. So far, identification of DNA 6mA relies primarily on time-consuming and expensive experimental approaches. However, in silico methods can be implemented to conduct preliminary screening to save experimental resources and time, especially given the rapid accumulation of sequencing data. RESULTS: In this study, we constructed a 6mA predictor, p6mA, from a series of sequence-based features, including physicochemical properties, position-specific triple-nucleotide propensity (PSTNP), and electron-ion interaction pseudopotential (EIIP). We performed maximum relevance maximum distance (MRMD) analysis to select key features and used the Extreme Gradient Boosting (XGBoost) algorithm to build our predictor. Results demonstrated that p6mA outperformed other existing predictors using different datasets. CONCLUSIONS: p6mA can predict the methylation status of DNA adenines, using only sequence files. It may be used as a tool to help the study of 6mA distribution pattern. Users can download it from https://github.com/Konglab404/p6mA.

12.
BMC Bioinformatics ; 21(1): 67, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32085724

RESUMO

BACKGROUND: Constraint-based metabolic modeling has been applied to understand metabolism related disease mechanisms, to predict potential new drug targets and anti-metabolites, and to identify biomarkers of complex diseases. Although the state-of-art modeling toolbox, COBRA 3.0, is powerful, it requires substantial computing time conducting flux balance analysis, knockout analysis, and Markov Chain Monte Carlo (MCMC) sampling, which may limit its application in large scale genome-wide analysis. RESULTS: Here, we rewrote the underlying code of COBRA 3.0 using C/C++, and developed a toolbox, termed FastMM, to effectively conduct constraint-based metabolic modeling. The results showed that FastMM is 2~400 times faster than COBRA 3.0 in performing flux balance analysis and knockout analysis and returns consistent outputs. When applied to MCMC sampling, FastMM is 8 times faster than COBRA 3.0. FastMM is also faster than some efficient metabolic modeling applications, such as Cobrapy and Fast-SL. In addition, we developed a Matlab/Octave interface for fast metabolic modeling. This interface was fully compatible with COBRA 3.0, enabling users to easily perform complex applications for metabolic modeling. For example, users who do not have deep constraint-based metabolic model knowledge can just type one command in Matlab/Octave to perform personalized metabolic modeling. Users can also use the advance and multiple threading parameters for complex metabolic modeling. Thus, we provided an efficient and user-friendly solution to perform large scale genome-wide metabolic modeling. For example, FastMM can be applied to the modeling of individual cancer metabolic profiles of hundreds to thousands of samples in the Cancer Genome Atlas (TCGA). CONCLUSION: FastMM is an efficient and user-friendly toolbox for large-scale personalized constraint-based metabolic modeling. It can serve as a complementary and invaluable improvement to the existing functionalities in COBRA 3.0. FastMM is under GPL license and can be freely available at GitHub site: https://github.com/GonghuaLi/FastMM.


Assuntos
Redes e Vias Metabólicas , Software , Genoma , Humanos , Modelos Biológicos , Neoplasias/genética , Neoplasias/metabolismo
13.
Genes (Basel) ; 11(2)2020 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-32019077

RESUMO

Wool and hair fibres consist of a variety of proteins, including the keratin-associated proteins (KAPs). In this study, a putative ovine homologue of the human KAP21-2 gene (KRTAP21-2) was identified. It was located on chromosome 1 as a 201-bp open reading frame (ORF) in the ovine genome assembly from a Texel sheep (v.4 NC_019458.2: nt122932727 to 122932927). A polymerase chain reaction- single strand conformation polymorphism (PCR-SSCP) analysis of this ORF, and subsequent DNA sequencing, identified five sequences (named A-E). The putative amino acid sequences that would be produced, shared some identity with each other and with other KAPs, but they were most similar to ovine KAP21-1, and phylogenetically related to human KAP21-2. The location of the ovine KRTAP21-2 sequence was consistent with the location of human KRTAP21-2, and this suggests they represent different variant forms of ovine KRTAP21-2. Variation in this gene was investigated in 389 Merino (sire) × Southdown-cross (ewe) lambs. These were derived from four independent sire-lines. The sequence variation was found to be associated with variation in five wool traits: including mean staple length (MSL), mean fibre diameter (MFD), fibre diameter standard deviation (FDSD), prickle factor (PF), and greasy fleece weight (GFW). The most persistent effect of KRTAP21-2 variation was with variation in MSL; with the MSL of sheep of genotype AC being 12.5% greater than those of genotype CE. A similar effect was observed from individual variant absence/presence models. This suggests that KRTAP21-2 should be further investigated as a possible gene-marker for improving MSL.

14.
Environ Pollut ; 260: 113969, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31991350

RESUMO

Interaction between silver nanoparticles (AgNPs) and iron plaque, which forms at the root surface of wetland plants under waterlogging conditions, is a critical process that controls the bioavailability of AgNPs. In this study, we comparatively evaluated how and to what extent iron plaque affected silver uptake sourced from metallic (Ag0NPs) and sulfidized (Ag2S-NPs) silver nanoparticles under hydroponic conditions. After the formation of iron plaque at the root surface upon exposure to Fe2+ at 0-100 µg mL-1, rice (Oryza sativa L.) seedlings were transferred to AgNP suspensions. Silver uptake depended on the amount of iron plaque and AgNP species (Ag0NPs vs. Ag2S-NPs): Ag2S-NP exposure had lower or comparable Ag uptake to that of Ag0NP exposure at low levels of Fe2+ (0-80 µg mL-1), but significantly higher Ag uptake at 100 µg Fe2+ mL-1. Such contrasting effects of iron plaque on the bioavailability of Ag0NPs and Ag2S-NPs were attributed to their influences on AgNP dissolution. However, the translocation factors (TFs) and particle size distribution of NPs in planta (as determined by single-particle inductively coupled plasma-mass spectrometry analysis) were not affected by the amount of iron plaque. These results reveal contrasting effects of iron plaque on the bioavailability of Ag0NPs and Ag2S-NPs, and raise concerns about the exposure of wetland plants to Ag2S-NPs in Fe-rich environments, where high Fe levels may facilitate Ag2S-NP bioavailability.


Assuntos
Ferro/química , Nanopartículas Metálicas/análise , Oryza/fisiologia , Prata/metabolismo , Disponibilidade Biológica
15.
Genes (Basel) ; 11(2)2020 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-31979055

RESUMO

The keratin-associated proteins (KAPs) are constituents of cashmere fibers and variation in many KAP genes (KRTAPs) has been found to be associated with fiber traits. The gene encoding the high-sulphur KAP28-1 has been described in sheep, but it has not been identified in the goat genome. In this study, a 255-bp open reading frame on goat chromosome 1 was identified using a search of similar sequence to ovine KRTAP28-1, and that would if transcribed and translated encode a high sulphur KAP. Based on the analysis of polymerase chain reaction (PCR) amplicons for the goat nucleotide sequences in 385 Longdong cashmere goats in China, five unique banding patterns were detected using single-stranded conformational polymorphism (SSCP). These represented five DNA sequences (named variants A to E) and they had the highest resemblance to KRTAP28-1 sequences from sheep, suggesting A-E are variants of caprine KRTAP28-1. DNA sequencing revealed a 2 or 4-bp deletion and eleven nucleotide sequence differences, including four non-synonymous substitutions. Of the four common variants (A, B, C and D) found in these goats, the presence of variant A was associated with decreased mean fiber diameter and this effect appeared to be additive. These results indicate that caprine KRTAP28-1 variation might have value as a molecular marker for reducing cashmere mean fiber diameter.

16.
Genomics ; 112(3): 2186-2193, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31866420

RESUMO

CircRNA is a specific type of non-coding RNA that has been shown to have an important role in mammary gland (MG) activity, but no study of MG circRNA activity in sheep so far. In this study, the expression profile of circRNAs was investigated using RNA-Seq in MG parenchyma at peak lactation from Small-Tailed Han sheep and Gansu Alpine Merino sheep with phenotypic differences in milk yield and components. A total of 4, 906 circRNAs were found and 33 of these were differentially expressed between breeds. GO and KEGG results showed that the parental genes of differentially expressed circRNAs were mainly enriched in heterocyclic compound binding, kinase activity, adherens junction, the TGF-ß signaling pathway, and the MAPK signaling pathway. This study provides an overview of circRNA expression in the ovine MG and the interaction between some key circRNAs and their target miRNAs. It improves our knowledge of the role of circRNA in sheep milk synthesis.

17.
J Org Chem ; 85(4): 2716-2724, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-31886664

RESUMO

Copper-catalyzed multicomponent borylacylation of imines with acid chlorides and bis(pinacolato)diboron was developed for the preparation of synthetically useful and pharmacologically relevant α-amino boronic acid derivatives. Starting from a range of acid chlorides and imines with aryl, heteroaryl, and alkyl substituents, most of these ligand-free reactions proceeded smoothly at room temperature in moderate to good yields. Furthermore, a facile and convenient one-pot, multistep access to the direct synthesis of α-amino boronic acid derivatives from available aldehydes and amines was also developed.

18.
Arch Anim Breed ; 62(1): 125-133, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31807622

RESUMO

Keratin-associated proteins (KAPs) are a structural component of cashmere fibre, and variation in some KAP genes (KRTAPs) has been associated with a number of caprine fibre traits. In this study, we report the identification of KRTAP15-1 in goats. Sequence variation in the gene was detected using the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) technique in 250 Longdong goats, and six variants (named A to F) containing eight single nucleotide polymorphisms (SNPs) were identified. Five of the SNPs were non-synonymous and would lead to putative amino acid changes. Reverse-transcription polymerase chain reaction (RT-PCR) analysis revealed that KRTAP15-1 was expressed in secondary hair follicles but not in heart tissue, liver tissue, lung tissue, kidney tissue or the longissimus dorsi muscle. Despite being rich in cysteine, the caprine KAP15-1 protein possesses a high content of serine and moderate content of glycine and phenylalanine. Association analyses revealed that KRTAP15-1 variant A was associated with decreased mean fibre diameter (MFD), and this effect appeared to be dominant; while variant C was found to be associated with increased MFD, the effect being recessive. The findings suggest that caprine KRTAP15-1 is highly polymorphic and that variation in this gene affects cashmere MFD.

19.
Arch Anim Breed ; 62(2): 509-515, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31807662

RESUMO

Variation in KRTAP6-1 has been reported to affect wool fibre traits in Merino cross-breed sheep and Chinese Tan sheep, but little is known about whether these effects persist in other breeds. In this study, variation in KRTAP6-1 was investigated in 290 New Zealand (NZ) Romney ewes sired by 16 different rams. Polymerase chain reaction single-stranded conformational polymorphism (PCR-SSCP) analysis revealed four variants ( A , B , E and F ) of KRTAP6-1, and nine genotypes (AA, AB, AE, AF, BB, BE, BF, EE and FF) in these ewes. Among the 243 ewes that had genotypes with a frequency of over 5 % (i.e. AA, AB and BB), the presence of A was found to be associated with reduced mean fibre diameter (MFD) and increased coefficient of variation in fibre diameter (CVFD), whereas the presence of B had a trend of association with decreased coarse edge measurement (CEM). A genotype effect was also detected for MFD and CVFD. No associations were detected for fibre diameter standard deviation (FDSD), mean fibre curvature (MFC) and medulation. These results suggest that variation in KRTAP6-1 affects wool fibre diameter in NZ Romney ewes, confirming the finding in Merino cross-breed sheep.

20.
Genes (Basel) ; 10(11)2019 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-31717789

RESUMO

The keratin-associated proteins (KAPs) are structural components of hair/wool fibres. All of the KAPs identified to date contain cysteine, which is thought to form disulphide bonds cross-linking the keratin intermediate filaments. Here, we report the identification of a KAP gene in sheep that would produce a protein that contains a high proportion (63.2 mol%) of glycine and tyrosine, but would not contain any cysteine. This suggests that other forms of intra- and inter-strand interaction may occur with this KAP, such as interactions via ring-stacking and hydrogen-bonding. The gene was dissimilar to any previously reported KAP gene, and was therefore assigned to a new family, and named KRTAP36-1. The KRTAP36-1 genome sequence was almost identical to some EST sequences from sheep and goat skin follicles, suggesting that it is present and expressed in sheep and goats. A BLAST search of the human genome assembly sequence did not reveal any human homologue. Three variant sequences (named A to C) of ovine KRTAP36-1 were identified and four single nucleotide polymorphisms (SNPs) were detected. One SNP was located 32 bp upstream of the coding region, and all of the others were in the coding region and were nonsynonymous. After correcting for potential linkage to the proximal KRTAP20-1, variant B of KRTAP36-1 was found to be associated with increased prickle factor (PF) in wool, suggesting that variation in the gene may have the potential to be used as gene marker for breeding sheep with lower PF.


Assuntos
Queratinas/genética , Polimorfismo de Nucleotídeo Único , Ovinos/genética , Lã/química , Substituição de Aminoácidos , Animais , Cisteína/genética , Feminino , Glicina/genética , Ligação de Hidrogênio , Queratinas/química , Domínios Proteicos , Tirosina/genética , Fibra de Lã/normas
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