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Foxtail millet (Setaria italica) is an important cereal crop with rich nutritional value. Distinctness, Uniformity, and Stability (DUS) are the prerequisites for the application of new variety rights for foxtail millet. In this study, we investigated 32 DUS test characteristics of 183 foxtail millet resources, studied their artificial selection trends, and identified the varieties that conform to breeding trends. The results indicated significant differences in terms of the means, ranges, and coefficients of variation for each characteristic. A correlation analysis was performed to determine the correlations between various DUS characteristics. A principal component analysis was conducted on 31 test characteristics to determine their primary characteristics. By plotting PC1 and PC2, all the germplasm resources could be clearly distinguished. The trends in foxtail millet breeding were identified through a differential analysis of the DUS test characteristics between the landrace and cultivated varieties. Based on these breeding trends, the optimal solution types for multiple evaluation indicators were determined; the weight allocation was calculated; and a specific TOPSIS algorithm was designed to establish a comprehensive multi-criteria decision-making model. Using this model, the breeding potential of foxtail millet germplasm resources were ranked. These findings provided important reference for foxtail millet breeding in the future.
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Chronic osteomyelitis is a chronic bone infection characterized by progressive osteonecrosis and dead bone formation, which is closely related to persistent infection and chronic inflammation. Exosomes derived from bone marrow-derived mesenchymal stem cells (BMSC) play an important role in bone tissue regeneration and the modulation of inflammatory processes. However, their role and mechanism of action in osteomyelitis have not been reported so far. This paper explores the potential effect of BMSC-derived exosomes on osteomyelitis in vitro model with the aim of providing a theoretical basis for the treatment of osteomyelitis in the future. In this study, exosomes were isolated and extracted from BMSCs and identified. MC3T3-E1 cells were treated with Staphylococcal protein A (SPA) to establish an in vitro model of osteomyelitis. Next, the effects of BMSC-derived exosomes on cell proliferation, apoptosis, angiogenesis, and autophagy in MC3T3-E1 cells treated with SPA were evaluated. Results showed that the proliferation ability of MC3T3-E1 cells increased after co-culture with BMSC-derived exosomes. Moreover, exosomes induced autophagy and osteogenic differentiation in MC3T3-E1 cells. The mRNA and protein levels of factors related to proliferation, differentiation, apoptosis, autophagy, and angiogenesis including ß-Catenin, Runx2, Bcl-2, VEGFA, and Beclin-1 upregulated in SPA-treated MC3T3-E1 cells, whereas the levels of inflammatory cytokines including TNF-α, IL-1ß, and IL-6 decreased in the supernatant. The results showed that exosomes derived from BMSCs may participate in the attenuation of osteomyelitis by inducing proliferation and osteogenic differentiation and regulating the inflammatory state in bone cells.
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The safety of energy storage devices is increasingly crucial due to the growing requirements for application under harsh conditions. Effective methods for enhancing robustness without compromising functionality are necessary. Here we present an impact-resistant, ready-to-use supercapacitor constructed from self-healable hydrogel electrolyte-infused lattice electrodes. Three-dimensional-printed carbon-coated silicon oxycarbide current collectors provide mechanical protection, with compressive stress, Young's modulus, and energy absorption up to 70.61 MPa, 2.75 GPa, and 92.15 kJ/m3, respectively. Commercially viable polyaniline and self-healable polyvinyl alcohol hydrogel are used as active coatings and electrolytes. I-wrapped package structured supercapacitor electrode exhibits a static specific capacitance of 585.51 mF/cm3 at 3 mA/cm3, with an energy density of 97.63 µWh/cm3 at a power density of 0.5 mW/cm3. It maintains operational integrity under extreme conditions, including post-impact with energy of 0.3 J/cm3, dynamic loading ranging from 0 to 18.83 MPa, and self-healing after electrolyte damage, demonstrating its promise for applications in extreme environments.
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Mycobacterium abscessus pulmonary infections are increasingly problematic, especially for immunocompromised individuals and those with underlying lung conditions. Currently, there is no reliable standardized treatment, underscoring the need for improved preclinical drug testing. We present a simplified immunosuppressed mouse model using only four injections of cyclophosphamide, which allows for sustained M. abscessus lung burden for up to 16 days. This model proved effective for antibiotic efficacy evaluation, as demonstrated with imipenem or amikacin.
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Amicacina , Antibacterianos , Ciclofosfamida , Modelos Animales de Enfermedad , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Animales , Ciclofosfamida/farmacología , Mycobacterium abscessus/efectos de los fármacos , Ratones , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Amicacina/farmacología , Amicacina/uso terapéutico , Imipenem/farmacología , Imipenem/uso terapéutico , Pulmón/microbiología , Pulmón/efectos de los fármacos , Huésped Inmunocomprometido , FemeninoRESUMEN
Fragile X syndrome (FXS) is caused by epigenetic silencing of the Fmr1 gene, leading to the deletion of the coding protein FMRP. FXS induces abnormal hippocampal autophagy and mTOR overactivation. However, it remains unclear whether FMRP regulates hippocampal autophagy through the AKT/mTOR pathway, which influences the neural behavior of FXS. Our study revealed that FMRP deficiency increased the protein levels of p-ULK-1 and p62 and decreased LC3II/LC3I level in Fmr1 knockout (KO) mice. The mouse hippocampal neuronal cell line HT22 with knockdown of Fmr1 by lentivirus showed that the protein levels of p-ULK-1 and p62 were increased, whereas LC3II/LC3I was unchanged. Further observations revealed that FMRP deficiency obstructed autophagic flow in HT22 cells. Therefore, FMRP deficiency inhibited autophagy in the mouse hippocampus and HT22 cells. Moreover, FMRP deficiency increased reactive oxygen species (ROS) level, decreased the co-localization between the mitochondrial outer membrane proteins TOM20 and LC3 in HT22 cells, and caused a decrease in the mitochondrial autophagy protein PINK1 in HT22 cells and Fmr1 KO mice, indicating that FMRP deficiency caused mitochondrial autophagy disorder in HT22 cells and Fmr1 KO mice. To explore the mechanism by which FMRP deficiency inhibits autophagy, we examined the AKT/mTOR signaling pathway in the hippocampus of Fmr1 KO mice, found that FMRP deficiency caused overactivation of the AKT/mTOR pathway. Rapamycin-mediated mTOR inhibition activated and enhanced mitochondrial autophagy. Finally, we examined whether rapamycin affected the neurobehavior of Fmr1 KO mice. The Fmr1 KO mice exhibited stereotypical behavior, impaired social ability, and learning and memory impairment, while rapamycin treatment improved behavioral disorders in Fmr1 KO mice. Thus, our study revealed the molecular mechanism by which FMRP regulates autophagy function, clarifying the role of hippocampal neuron mitochondrial autophagy in the pathogenesis of FXS, and providing novel insights into potential therapeutic targets of FXS.
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Autofagia , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Síndrome del Cromosoma X Frágil , Hipocampo , Ratones Noqueados , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/metabolismo , Hipocampo/metabolismo , Hipocampo/patología , Autofagia/fisiología , Serina-Treonina Quinasas TOR/metabolismo , Síndrome del Cromosoma X Frágil/metabolismo , Síndrome del Cromosoma X Frágil/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/fisiología , Ratones , Masculino , Ratones Endogámicos C57BL , Línea CelularRESUMEN
This study investigated the effects of the conjugate reaction sequences of whey protein concentrate (WPC), epigallocatechin gallate (EGCG) and dextran (DEX) on the structure and emulsion properties of conjugates and the bioaccessibility of astaxanthin (AST). Two types of ternary covalent complexes were synthesised using WPC, EGCG and DEX, which were regarded as emulsifiers of AST nanoemulsions. Results indicated that the WPC-DEX-EGCG conjugate (referred to as 'con') exhibits a darker SDS-PAGE dispersion band and higher contents of α-helix (6%), ß-angle (24%) and random coil (32%), resulting in a greater degree of unfolding structure and fluorescence quenching. These findings suggested WPC-DEX-EGCG con had the potential to exhibit better emulsification properties than WPC-EGCG-DEX con. AST encapsulation efficiency (76.22%) and bioavailability (31.89%) also demonstrated the superior performance of the WPC-DEX-EGCG con emulsifier in nanoemulsion delivery systems. These findings indicate that altering reaction sequences changes protein conformation, enhancing the emulsification properties and bioavailability of AST.
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Disponibilidad Biológica , Catequina/análogos & derivados , Emulsionantes , Emulsiones , Proteína de Suero de Leche , Xantófilas , Xantófilas/química , Emulsiones/química , Emulsionantes/química , Proteína de Suero de Leche/química , Animales , Catequina/química , Dextranos/química , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Infections caused by nontuberculous mycobacteria have increased more than 50% in the past two decades and more than doubled in the elderly population. Mycobacterium abscessus (Mab), one of the most prevalent of these rapidly growing species, is intrinsically resistant to numerous antibiotics. Current standard-of-care treatments are not satisfactory, with high failure rate and notable adverse effects. We report here a potent anti-Mab compound from the flexible molecular framework afforded by conjugated oligoelectrolytes (COEs). A screen of structurally diverse, noncytotoxic COEs identified a lead compound, COE-PNH2, which was bactericidal against replicating, nonreplicating persisters and intracellular Mab.COE-PNH2 had low propensity for resistance development, with a frequency of resistance below 1.25 × 10-9 and showed no detectable resistance upon serial passaging. Mechanism of action studies were in line with COE-PNH2 affecting the physical and functional integrity of the bacterial envelope and disrupting the mycomembrane and associated essential bioenergetic pathways. Moreover, COE-PNH2 was well-tolerated and efficacious in a mouse model of Mab lung infection. This study highlights desirable in vitro and in vivo potency and safety index of this COE structure, which represents a promising anti-mycobacterial to tackle an unmet medical need.
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Mycobacterium abscessus , Mycobacterium , Humanos , Anciano , Animales , Ratones , Modelos Animales de Enfermedad , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antibacterianos/química , Pruebas de Sensibilidad MicrobianaRESUMEN
Conventional polymeric phase change materials (PCMs) have been widely used due to their high heat storage density, small temperature variation, and nontoxicity. However, the high flammability and unrecyclable problems restrict their applications in energy storage devices (ESDs). Although it is facile to introduce a flame retardant into phase change materials to improve fire resistance, the physical blending will deteriorate the mechanical performance and thermal stability of PCMs. Herein, flame-retardant solid-solid PCMs (FRPCMs) with intrinsic flame retardancy, phase change property, self-healing, and recyclability were synthesized by simultaneously integrating tetrabromobisphenol A (TBBPA) and poly(ethylene glycol) (PEG) into polyurethane network skeletons. PEG ingredients acted as phase change materials, and TBBPA not only worked as an efficient flame retardant but also provided dynamic covalent bonds for thermally induced self-healing and recyclability. FRPCMs possess the highest latent heat of 124.7 J/g, high self-healing ability, and high thermal reliability and recyclability. Besides, with the introduction of TBBPA, the limiting oxygen index (LOI) value and char residue significantly increased, the heat release rate (HRR) and total heat release (THR) values decreased, and most of the FRPCMs reached UL94 V-2 rating as well. Hence, the synthesized FRPCMs could expand the application scope of PCMs for thermal energy storage.
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Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that can cause high-morbidity infections. Due to its robust, flexible genome and ability to form biofilms, it can evade and rapidly develop resistance to antibiotics. Cationic conjugated oligoelectrolytes (COEs) have emerged as a promising class of antimicrobials. Herein, we report a series of amidine-containing COEs with high selectivity for bacteria. From this series, we identified 1b as the most active compound against P. aeruginosa (minimum inhibitory concentration (MIC) = 2 µg/mL) with low cytotoxicity (IC50 (HepG2) = 1024 µg/mL). The activity of 1b was not affected by known drug-resistant phenotypes of 100 diverse P. aeruginosa isolates. Moreover, 1b is bactericidal with a low propensity for P. aeruginosa to develop resistance. Furthermore, 1b is also able to inhibit biofilm formation at subinhibitory concentrations and kills P. aeruginosa in established biofilms. The in vivo efficacy of 1b was demonstrated in biofilm-associated murine wound infection models.
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Infecciones por Pseudomonas , Pseudomonas aeruginosa , Ratones , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Biopelículas , Pruebas de Sensibilidad Microbiana , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiologíaRESUMEN
Golden pompano (Trachinotus blochii) is an economically important fish which exhibits sexual size dimorphism and is widely cultivated in the southern seas of China. To evaluate the nutritional composition of T. blochii of different mariculture areas, growth stages, and genders, the moisture, ash, amino acids, and fatty acids in the muscle were measured using national standard biochemical assay. The analysis found 16 kinds of amino acids in the muscle of T. blochii. The EAA contents of fish from Guangdong (GD) and Guangxi (GX) were significantly lower than those of Hainan (HN) and Fujian (FJ) (p < 0.05). The unsaturated fatty acids were higher in T. blochii cultured in HN and FJ (p < 0.05). Within the same sea area, the contents of TAA, EAA, DAA, and PUFA increased with growth in T. blochii, but the differences were not significant (p > 0.05). EAA/TAA and EAA/NEAA conformed to the ideal FAO/WHO model. The AAS, CS, and EAAI scores of amino acids within groups gradually increased with growth. The TAA, EAA and PUFA contents in females were higher than in males (p > 0.05). The slightly higher amounts of amino acids and fatty acids in female T. blochii indicated females had higher nutritional value. In conclusion, the HN and FJ groups, the later growth stages, and the female T. blochii had generally higher nutritional values than their respective counterparts. These results provide fundamental data supporting all-female T. blochii breeding and culture, and optimized marketing body size.
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Invited for the cover of this issue is the group of Guillermoâ C. Bazan, Kaixi Zhang and co-workers at the National University of Singapore The image depicts the activity of lead compound DM6P acting on a model bacteria membrane. Read the full text of the article at 10.1002/chem.202203803.
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Conjugated oligoelectrolytes (COEs) are an emerging class of amphiphilic antimicrobial compounds with a modular molecular framework suitable for simple chemical derivatization. Here, a series of COE derivatives with a stilbene-conjugated segment and triphenylphosphonium (TPP) pendant groups was designed and synthesized to understand how lipophilic cationic groups impact antimicrobial activity. In vitro evaluations against ESKAPE pathogens showed broad-spectrum activity towards multi-drug resistant (MDR) bacteria and mycobacteria, with TPP groups enhancing antimicrobial activity towards clinically relevant Gram-negative strains compared to their ammonium analogues. We studied the interactions of DM6P, the most active TPP-COE compound, with various membrane assays. Treatment of bacterial cells with DM6P showed enhanced permeability of cell membranes without inducing the development of significant bacterial resistance. Moreover, DM6P eliminated 99.99 % of methicillin-resistant Staphyloccocus aureus (MRSA) in an inâ vivo wound model. These results represent a promising chemical strategy for increasing the activity spectrum of membrane-active COE antibiotics to tackle challenging drug-resistant targets.
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Antiinfecciosos , Staphylococcus aureus Resistente a Meticilina , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/química , Membrana CelularRESUMEN
The artificial breeding of golden pompano (Trachinotus blochii) has expanded greatly in recent years, and after long-term breeding efforts, clear sexual dimorphisms have been observed in T. blochii growth traits, with females growing faster. As sponges of microRNA (miRNAs), circular RNAs (CircRNAs) can alleviate miRNA inhibition of target mRNA. However, few studies have examined sex-related CircRNAs and none of those have looked at T. blochii. To further understand the role of CircRNAs in sex differentiation and sexual size dimorphism in T. blochii, six CircRNA libraries were constructed from the testes and ovaries of T. blochii. A total of 1522 CircRNAs were found distributed over all 24 chromosomes of T. blochii. 135 differentially expressed CircRNAs (DECs) were identified by screening, These DECs were then subjected to GO enrichment, which found 47 enriched pathways. A number of CircRNAs were enriched in cellular processes and metabolic processes. According to the KEGG pathway analysis, a series of sex differentiation pathways were enriched, including the GnRH, calcium, and MAPK signaling pathways. Furthermore, we selected two CircRNAs from the DECs named circ-cacna1b and circ-octc. We found that the cacna1b gene is regulated by 7 miRNAs, 3 of which were regulated by circ-cacna1b, i.e., mmu-miR-138-5p, fru-miR-138, and pma-miR-138b. In addition, the miRNA named pma-miR-138b can regulate sex-related genes, such as sox9 and dmrt1, among others. The co-expression network of CircRNA-miRNA-mRNA showed circ-cacna1b may play a crucial role in T. blochii sex differentiation by regulating pma-miR-138b to affect the expression of sex differentiation genes. The circ-octc may be one of the largest contributors to sexual size dimorphism during growth through its effect on lipid metabolism. These findings could broaden our understanding of CircRNAs and provide new insight into their function in sex differentiation and growth.
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MicroARNs , ARN Circular , Masculino , Femenino , Animales , ARN Circular/genética , Ovario/metabolismo , Testículo/metabolismo , MicroARNs/genética , Perfilación de la Expresión Génica , ARN MensajeroRESUMEN
The golden pompano (Trachinotus blochii) is a marine fish of considerable commercial importance in China. It shows notable sexual size dimorphism; the growth rate of females is faster than that of males. Therefore, sex-biased research is of great importance in T. blochii breeding. However, there have been few studies on sex differentiation and mechanisms underlying sex determination in T. blochii. MicroRNAs (miRNAs) play crucial roles in sex differentiation and determination in animals. However, limited miRNA data are available on fish. In this study, two small RNA libraries prepared from the gonads of T. blochii were constructed and sequenced. The RNA-seq analysis yielded 1366 known and 69 novel miRNAs with 289 significantly differentially expressed miRNAs (p < 0.05). Gene ontology (GO) analysis confirmed that the TFIIA transcription factor complex (GO: 0005672) was the most significantly enriched GO term. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the differentially expressed miRNAs and target genes were mainly related to sex determination and gonadal developmental signaling pathways, specifically the Wnt signaling pathway, MAPK signaling pathway, and steroid biosynthetic pathway. MiRNA-mRNA co-expression network analysis strongly suggested a role for sex-biased miRNAs in sex determination/differentiation and gonadal development. For example, gata4, foxo3, wt1, and sf1 genes were found to be regulated by bta-miR-2898; esr2 and foxo3 by novel_176, and ar by oar-let-7b. Quantitative real-time polymerase chain reaction analysis of selected mRNAs and miRNAs validated the integrated analysis. This study established a set of sex-biased miRNAs that are potential regulatory factors in gonadal development in T. blochii. These results provide new insight into the function of miRNAs in sex differentiation and determination in T. blochii and highlight some key miRNAs for future studies.
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Fish skin color is usually strongly affected by the background color of their environment. The study investigated the effects of five different background colors on the skin color of leopard coral groupers (Plectropomus leopardus). More than 450 juveniles were reared in Blue, Red, Black, White, and Transparent background tanks for 56 days. The paraffin section showed that the skin melanin zone of fish in the White group was smaller, whereas the Black and Red groups (especially Black) were nearly the largest. The apparent skin color of P. leopardus was red on the white background, which darkened in response to the other color backgrounds. The Black group revealed the blackest skin color, followed by the transparent group. Moreover, the White group had the highest L*, a*, and b* values. The melanin content and tyrosinase activity in the dorsal and ventral skin of the Black group were significantly higher than those in the other groups (p < 0.05), and the serum α-MSH level was higher in the Black group as well. The carotenoid and lutein contents showed completely different trends among the experimental groups, as carotenoid content was higher in the Red and White groups, while lutein content was higher in the Transparent group. The expression level of scarb1 was highest in the Blue and White groups, followed by the Transparent group, and lowest in the Black group (p < 0.05). The expression trend of scarb1 was similar to the skin color in different backgrounds, indicating that the background color regulated scarb1 expression level through visual center, then influenced the uptake and transport of carotenoids, then influenced the skin color formation of P. leopardus. Moreover, lighter colors inhibited the formation of melanocytes and had a significant effect on carotenoid and lutein contents. Pigment-related genes were involved in the regulation of fish skin color, and they were affected by background color in P. leopardus. These results indicate that a white background is more conducive to maintaining red skin color in juvenile P. leopardus.
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Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder which is associated with the dysregulation of autoimmune response. In recent years, early diagnosis, aggressive treatment and alternative therapeutic options of disease-modifying anti-rheumatic drugs (DMARDs) markedly improve both the management and long-term prognosis of RA. Since the discovery of non-coding RNA (ncRNA) including microRNA (miRNA), long non-coding RNA (lncRNA) and others, their altered expressions have been unraveled to be deregulated in various diseases including RA. Several lines of evidence are emerging that ncRNA may contribute to the pathogenesis, disease progression and treatment of RA. For example, SNP rs2850711 within lnc00305 was indicated to associate with RA development susceptibility, whereas a higher level of miR-10a represented a good response to methotrexate (MTX) treatment in RA patients. In the aspect of refractory RA, ncRNA also plays an important role by affecting or regulating drug sensitivity in RA patients. Of note, lower expression of miR-20a in rheumatoid arthritis synovial fibroblast (RASFs) was demonstrated to activate the Janus Kinase (JAK)- signal transducer and activator of transcription 3(STAT3)-mediated inflammation, thereby promoting cell proliferation and apoptosis-resistant. In this review, we have illustrated the changes of ncRNAs and their underlying mechanisms in the whole developing period of RA pathogenesis and disease progression, as well as highlighted the novel therapeutic targets/strategies and bio-markers for RA therapy.
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Antirreumáticos , Artritis Reumatoide , MicroARNs , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/uso terapéutico , MicroARNs/metabolismo , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Artritis Reumatoide/metabolismo , Antirreumáticos/uso terapéutico , ARN no Traducido/uso terapéutico , Progresión de la EnfermedadRESUMEN
Fish skin color is often strongly affected by background color. We hypothesized that the regulatory mechanism of variations in skin color in P. leopardus is linked to the background color. In this study, we conducted transcriptome analysis of Plectropomus leopardus cultured under different background colors to compare gene expression levels and the important signaling pathways. The RNA-seq analysis yielded 26,675 known mRNAs, 3278 novel mRNAs, and 3179 differentially expressed genes (DEGs). The DEGs related to melanin synthesis were screened out. Some key melanin-related genes were identified, specifically tyr, slc7a11, mc1r, ednrb, dct, tat, and wnt1. These DEGs were mainly involved in melanogenesis, including tyrosine metabolism, the Wnt signaling pathway, and the cAMP signaling pathway. The expression levels of some key genes were upregulated when background color deepened, such as α-msh, wnt, and gf. The α-MSH/cAMP-dependent, Wnt/ß-catenin, and PI3K/Akt signaling pathways were activated, resulting in the accumulation of intracellular mitf. mitf promoted melanin production by binding to the tyr/tyrp1/dct promoter region. In the present study, we explored the molecular mechanism underlying the darkened skin color pattern of P. leopardus, providing a theoretical basis for the molecular mechanism underlying pigmentation in P. leopardus.
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Melaninas , Pigmentación de la Piel , Animales , Perfilación de la Expresión Génica , Melaninas/genética , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Pigmentación de la Piel/genética , Transcriptoma , alfa-MSH , beta Catenina/genéticaRESUMEN
In recent years, infectious diseases have again become a critical threat to global public health largely due to the challenges posed by antimicrobial resistance. Conventional antibiotics have played a crucial role in combating bacterial infections; however, their efficacy is significantly impaired by widespread drug resistance. Natural antimicrobial peptides (AMPs) and their polymeric mimics demonstrate great potential for killing bacteria with low propensity of resistance as they target the microbial membrane rather than a specific molecular target, but they are also toxic to the host eukaryotic cells. To minimize antibiotics systemic spread and the required dose that promote resistance and to advocate practical realization of the promising activity of AMPs and polymers, smart systems to target bacteria are highly sought after. This review presents bacterial recognition by various specific targeting molecules and the delivery systems of active components in supramolecules. Bacteria-induced activations of antimicrobial-based nanoformulations are also included. Recent advances in the bacteria targeting and delivery of synthetic antimicrobial agents may assist in developing new classes of highly selective antimicrobial systems which can improve bactericidal efficacy and greatly minimize the spread of bacterial resistance.
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Antiinfecciosos , Infecciones Bacterianas , Polímeros de Estímulo Receptivo , Antibacterianos/química , Antiinfecciosos/farmacología , Péptidos Catiónicos Antimicrobianos/química , Péptidos Catiónicos Antimicrobianos/farmacología , Bacterias , Infecciones Bacterianas/tratamiento farmacológico , Humanos , Polímeros/química , Polímeros/farmacologíaRESUMEN
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease which affects about 0.5-1% of people with symptoms that significantly impact a sufferer's lifestyle. The cells involved in propagating RA tend to display pro-inflammatory and cancer-like characteristics. Medical drug treatment is currently the main avenue of RA therapy. However, drug options are limited due to severe side effects, high costs, insufficient disease retardation in a majority of patients, and therapeutic effects possibly subsiding over time. Thus there is a need for new drug therapies. Endoplasmic reticulum (ER) stress, a condition due to accumulation of misfolded proteins in the ER, and subsequent cellular responses have been found to be involved in cancer and inflammatory pathologies, including RA. ER stress protein markers and their modulation have therefore been suggested as therapeutic targets, such as GRP78 and CHOP, among others. Some current RA therapeutic drugs have been found to have ER stress-modulating properties. Traditional Chinese Medicines (TCMs) frequently use natural products that affect multiple body and cellular targets, and several medicines and/or their isolated compounds have been found to also have ER stress-modulating capabilities, including TCMs used in RA treatment by Chinese Medicine practitioners. This review encourages, in light of the available information, the study of these RA-treating, ER stress-modulating TCMs as potential new pharmaceutical drugs for use in clinical RA therapy, along with providing a list of other ER stress-modulating TCMs utilized in treatment of cancers, inflammatory diseases and other diseases, that have potential use in RA treatment given similar ER stress-modulating capacity.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Articulaciones/efectos de los fármacos , Animales , Antiinflamatorios/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Antirreumáticos/efectos adversos , Artritis Reumatoide/inmunología , Artritis Reumatoide/metabolismo , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Articulaciones/inmunología , Articulaciones/metabolismo , Medicina Tradicional ChinaRESUMEN
We report the first demonstration of the efficient bacteria targeting properties of DNA-based polymeric micelles with high-density DNA corona. Nanoscale polymer micelles derived from DNA-b-polystyrene (DNA-b-PS) efficiently selected most tested Gram-positive strains over Gram-negative strains; single-strand DNAs were 20-fold less selective. We demonstrate that these targeting properties were derived from the interaction between densely packed DNA strands of the micelle corona and the peptidoglycan layers of Gram-positive bacteria. DNA-b-PS micelles incorporating magnetic nanoparticles (MNPs) can efficiently capture and concentrate Gram-positive bacteria suggesting the simple applications of these DNA block copolymer micelles for concentrating bacteria. Adenine (A), thymine (T), cytosine (C), and guanine (G)-rich nanostructures were fabricated, respectively, for investigating the effect of sequence on Gram-selective bacteria targeting. T-rich micelles showed the most efficient targeting properties. The targeting properties of these DNA nanostructures toward Gram-positive bacteria may have applications as a targeted therapeutic delivery system.