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Tobacco consumption in China remains the primary cause of preventable mortality, with Shanghai being particularly affected by issues related to secondhand smoke exposure. This study explores the role of the public service hotline 12345, a grassroots initiative in Shanghai, in capturing public sentiment and assessing the effectiveness of anti-smoking regulations. Our research aims to accurately and deeply understand the implementation and feedback of smoking control policies: by identifying high-frequency points and prominent issues in smoking control work based on the smoking control work order data received by the health hotline 12320. The results of this study will assist government enforcement agencies in improving smoking monitoring and clarify the direction for improving smoking control measures. Text-mining techniques were employed to analyze a dataset comprising 78011 call sheets, all related to tobacco control and collected from the hotline between 1 January 2015 and 31 December 2019. This methodological approach aims to uncover prevalent themes and sentiments in the public discourse on smoking and its regulation, as reflected in the hotline interactions. Our study identified hotspots and the issues of greatest concern to citizens. Additionally, it provided recommendations to enforcement agencies to enhance their capabilities, optimize the allocation of human resources for smoking control monitoring, reduce enforcement costs and support for anti-smoking campaigns, thereby contributing to more effective tobacco control policies in the region.
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This study aims to investigate the effects of ultrasound coupled with alkali cycling on the structural properties, digestion characteristics, biological activity, and peptide profiling of flaxseed protein isolates (FPI). The digestibility of FPI obtained by ultrasound coupled with pH 10/12 cycling (UFPI-10/12) (74.56 % and 79.12 %) was significantly higher than that of native FPI (64.40 %), and UFPI-10 showed higher hydrolysis degree (35.76 %) than FPI (30.65 %) after intestinal digestion. The combined treatment induced transition from α-helix to ß-sheet with an orderly structure. Large FPI aggregates broke down into small-sized FPI particles, which induced the increase of specific surface area of particles. This might expose more cutting sites and contact area with enzymes. Furthermore, UFPI-10 showed high antioxidant activity (29.18 %) and lipid-lowering activity (70.52 %). Peptide profiling revealed that UFPI-10 exhibited a higher proportion of 300-600 Da peptides and significantly higher abundance of antioxidant peptides than native FPI, which might promote its antioxidant activity. Those results suggest that the combined treatment is a promising modification method to improve the digestion characteristics and biological activity of FPI. This work provides new ideas for widespread use of FPI as an active stabilizer in food systems.
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Álcalis , Antioxidantes , Digestión , Lino , Péptidos , Proteínas de Plantas , Lino/química , Péptidos/metabolismo , Péptidos/química , Antioxidantes/química , Antioxidantes/análisis , Proteínas de Plantas/metabolismo , Álcalis/química , Concentración de Iones de Hidrógeno , Hidrólisis , Semillas/química , Manipulación de Alimentos/métodos , Ondas UltrasónicasRESUMEN
The microencapsulation of polysaturated fatty acids by spray drying remains a challenge due to their susceptibility to oxidation. In this work, antioxidant Pickering emulsions were attempted as feeds to produce oxidation stable tuna oil microcapsules. The results indicated that the association between chitosan (CS) and ovalbumin (OVA) was a feasible way to fabricate antioxidant and wettable complexes and a high CS percentage favored these properties. The particles could yield tuna oil Pickering emulsions with enhanced oxidation stability through high-pressure homogenization, which were successfully spray dried to produce microcapsules with surface oil content of 8.84 % and microencapsulation efficiency of 76.65 %. The microcapsules exhibited significantly improved oxidation stability and their optimum peroxide values after storage at 50 °C, 85 % relative humidity, or natural light for 15 d were 48.67 %, 60.07 %, and 39.69 % respectively lower than the powder derived from the OVA-stabilized emulsion. Hence, Pickering emulsions stabilized by the CS/OVA polyelectrolyte complexes are potential in the production of oxidation stable polyunsaturated fatty acid microcapsules by spray drying.
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Cápsulas , Quitosano , Emulsiones , Ovalbúmina , Oxidación-Reducción , Secado por Pulverización , Atún , Quitosano/química , Emulsiones/química , Ovalbúmina/química , Animales , Aceites de Pescado/química , Polielectrolitos/química , Antioxidantes/química , Tamaño de la PartículaRESUMEN
Peptide-bile acid hybrids offer promising drug candidates due to enhanced pharmacological properties, such as improved protease resistance and oral bioavailability. However, it remains unknown whether bile acids can be incorporated into peptide chains by the ribosome to produce a peptide-bile acid hybrid macrocyclic peptide library for target-based de novo screening. In this study, we achieved the ribosomal incorporation of lithocholic acid (LCA)-d-tyrosine into peptide chains. This led to the construction of a peptide-LCA hybrid macrocyclic peptide library, which enabled the identification of peptides TP-2C-4L3 (targeting Trop2) and EP-2C-4L5 (targeting EphA2) with strong binding affinities. Notably, LCA was found to directly participate in binding to EphA2 and confer on the peptides improved stability and resistance to proteases. Cell staining experiments confirmed the high specificity of the peptides for targeting Trop2 and EphA2. This study highlights the benefits of LCA in peptides and paves the way for de novo discovery of stable peptide-LCA hybrid drugs.
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Ácido Litocólico , Biblioteca de Péptidos , Péptidos , Ribosomas , Ácido Litocólico/química , Ácido Litocólico/análogos & derivados , Ácido Litocólico/metabolismo , Ribosomas/metabolismo , Humanos , Péptidos/química , Péptidos/metabolismo , Receptor EphA2/metabolismo , Receptor EphA2/química , Descubrimiento de Drogas , Péptidos Cíclicos/química , Péptidos Cíclicos/metabolismoRESUMEN
Cytokinesis is required for faithful division of cytoplasmic components and duplicated nuclei into two daughter cells. Midbody, a protein-dense organelle that forms at the intercellular bridge, is indispensable for successful cytokinesis. However, the regulatory mechanism of cytokinesis at the midbody still remains elusive. Here, we unveil a critical role for NudC-like protein 2 (NudCL2), a co-chaperone of heat shock protein 90 (Hsp90), in cytokinesis regulation by stabilizing regulator of chromosome condensation 2 (RCC2) at the midbody in mammalian cells. NudCL2 localizes at the midbody, and its downregulation results in cytokinesis failure, multinucleation and midbody disorganization. Using iTRAQ-based quantitative proteomic analysis, we find that RCC2 levels are decreased in NudCL2 knockout (KO) cells. Moreover, Hsp90 forms a complex with NudCL2 to stabilize RCC2, which is essential for cytokinesis. RCC2 depletion mirrors phenotypes observed in NudCL2-downregulated cells. Importantly, ectopic expression of RCC2 rescues the cytokinesis defects induced by NudCL2 deletion, but not vice versa. Together, our data reveal the significance of the NudCL2/Hsp90/RCC2 pathway in cytokinesis at the midbody.
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Introduction Multiple myeloma (MM) is a malignant proliferative disease of plasma cells. Abnormally cloned plasma cells secrete large amounts of monoclonal immunoglobulins in the bone marrow of MM patients. Serum urea nitrogen (sUN) is a byproduct of protein metabolism, and its effect on MM patients' prognoses remains unknown. Therefore, we analysed MM patients' clinical data to explore the role of sUN and serum urea nitrogen/serum albumin (sUAR) in the baseline tumor load and MM prognosis of MM patients. Methods We downloaded the clinical data of 762 MM patients from the MMRF database. After excluding those without baseline sUN, 452 patients were finally included in the study. Smoothed curve fitting, threshold analysis, Tamhane's T2 test, multivariate adjusted Cox regression analysis, KaplanâMeier (K-M) curves, and receiver operating characteristic (ROC) analysis were applied in the study. Results There were 452 newly diagnosed MM patients included in this study. In most patient groups, sUN and sUAR were positively linked with ß2-microglobulin (ß2-MG) and lactic dehydrogenase (LDH) according to smoothing curve fitting and threshold analysis. The higher the ISS stage, the greater the values of sUN and sUAR. Furthermore, smoothed curve fitting and threshold analysis showed that sUN was correlated with OS, although sUAR had a stronger correlation with OS and could be applied to a broader group. The results of a multivariate adjusted Cox regression analysis demonstrated that sUN and sUAR were independent prognostic factors for OS. The K-M curve confirmed the correlation between higher sUN and sUAR levels and worse OS. ß2-MG and LDH are generally recognized prognostic factors of OS. ROC analysis revealed that sUN might boost ß2-MG and LDH's predictive value and sUAR had a higher predictive value. Conclusion This retrospective study based on the MMRF database showed that high sUN and sUAR levels were positively associated with ß2-MG, LDH, and ISS staging, and sUAR exhibited a stronger correlation with OS than sUN alone.
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Cancer-associated fibroblast (CAF) has emerged as a key contributor to the remodeling of tumor microenvironment through the expression and secretion of extracellular matrix (ECM) proteins, thereby promoting carcinogenesis. However, the precise contribution of ECM proteins from CAFs to gastric carcinogenesis remains poorly understood. In this study, we find that matrilin-3 (MATN3), an upregulated ECM protein associated with poorer prognosis in gastric cancer patients, originates from CAFs in gastric cancer tissues. Ectopic expression of MATN3 in CAFs significantly promotes the invasion of gastric cancer cells, which can be attenuated by neutralizing MATN3 with its antibody. Notably, a portion of MATN3 protein is found to form puncta in gastric cancer tissues ECM. MATN3 undergoes phase separation, which is mediated by its low complexity (LC) and coiled-coil (CC) domains. Moreover, overexpression of MATN3 deleted with either LC or CC in CAFs is unable to promote the invasion of gastric cancer cells, suggesting that LC or CC domain is required for the effect of CAF-secreted MATN3 in gastric cancer cell invasion. Additionally, orthotopic co-injection of gastric cancer cells and CAFs expressing MATN3, but not its ΔLC and ΔCC mutants, leads to enhanced gastric cancer cell invasion in mouse models. Collectively, our works suggest that MATN3 is secreted by CAFs and undergoes phase separation, which promotes gastric cancer invasion.
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Fibroblastos Asociados al Cáncer , Proteínas Matrilinas , Neoplasias Gástricas , Animales , Humanos , Ratones , Carcinogénesis , Proteínas Matrilinas/genética , Invasividad Neoplásica , Separación de Fases , Neoplasias Gástricas/genética , Microambiente TumoralRESUMEN
Enrichment of plant proteins with functionality is of great importance for expanding their application in food formulations. This study proposed an innovation to co-enrich soy protein and flaxseed protein to act as efficient interfacial stabilizers for generating foams and emulsions. The structure, interfacial properties, and functionalities of the soy protein-flaxseed protein natural nanoparticles (SFNPs) obtained by alkali extraction-isoelectric precipitation (AE) and salt extraction-dialysis (SE) methods were investigated. Overall, the foamability of AE-SFNPs (194.67 %) was 1.45-fold that of SE-SFNPs, due to their more flexible structure, smaller particle size, and suitable surface wettability, promoting diffusion and adsorption at the air-water interface. AE-SFNPs showed higher emulsion stability (140.89 min), probably because the adsorbed AE-SFNPs with smaller size displayed soft particle-like properties and stronger interfacial flexibility, and therefore could densely and evenly arrange at the interface, facilitating the formation of a stiff and solid-like interfacial layer, beneficial for more stable emulsion formation. The findings may innovatively expand the applications of SFNPs as food ingredients.
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Lino , Proteínas de Soja , Proteínas de Soja/química , Emulsiones/química , Diálisis Renal , Proteínas de Plantas/químicaRESUMEN
Acceptance of artificial pelleted diets contributes to increasing the cultured areas and output of carnivorous fish. However, the mechanism of acceptance of artificial pelleted diets remains largely unknown. In this study, the easy acceptance of artificial pelleted diets (EAD) group and the not easy acceptance of artificial pelleted diets (NAD) group of Largemouth bass (Micropterus salmoides) were divided based on the ratios of stomach weight/body weight (SB) after 0.5 h feeding, which was bigger than 18% in the EAD group and ranged from 8 to 12% in the NAD group. Through transcriptome and proteome sequencing, a total of 2463 differentially expressed genes (DEGs) and 230 differentially expressed proteins (DEPs) were identified, respectively. Integrated analyses of transcriptome and proteome data revealed that 152 DEPs were matched with the corresponding DEGs (named co-DEGs-DEPs), and 54 co-DEGs-DEPs were enriched in 16 KEGG pathways, including the metabolic pathways, steroid biosynthesis, fatty acid biosynthesis, etc. Furthermore, 3 terpenoid backbone biosynthesis-related genes (Hmgcr, Hmgcs, and Fdps) in metabolic pathways, 10 steroid biosynthesis-related genes (Fdft1, Sqle, Lss, Cyp51a1, Tm7sf2, Nsdhl, Hsd17b7, Dhcr24, Sc5d, and Dhcr7), and 3 fatty acid biosynthesis-related genes (Acaca, Fasn, and Ascl) were all up-regulated in the EAD group, suggesting that the lipid metabolism pathway and steroid biosynthesis pathway play important roles in early food habit domestication in Largemouth bass. In addition, the detection results of randomly selected 15 DEGs and 15 DEPs indicated that both transcriptome and proteome results in the study were reliable. Our study provides useful information for further research on the mechanisms of food habit domestication in fish.
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Lubina , Transcriptoma , Animales , Lubina/genética , Lubina/metabolismo , Proteoma/metabolismo , Proteómica , Domesticación , NAD/metabolismo , Dieta , Conducta Alimentaria , Ácidos Grasos/metabolismo , Esteroides/metabolismoRESUMEN
Malignant melanoma (MM) is the most metastatic and aggressive form of skin cancer, and carries a high risk of death. Immune-checkpoint inhibitor therapy and molecular-targeted therapy can prolong the survival of patients with advanced MM significantly. However, the low response rate and inevitable drug resistance prevent further improvements in efficacy, which is closely related to the tumor microenvironment (TME). The TME refers to the tumor stroma, including fibroblasts, keratinocytes, immune cells, soluble molecules, and extracellular matrix (ECM). The dynamic interaction between the TME and tumor cells is very important for the growth, local invasion, and metastatic spread of tumor cells. A patient-derived organoid (PDO) model involves isolation of tumor tissue from patients with MM and culturing it in vitro in a three-dimensional pattern. Compared with traditional cultivation methods, the PDO model preserves the heterogeneity of the tissue structure of MM and demonstrates the interaction between MM cells and the TME. It can reproduce the characteristics of proliferation, migration, and invasion of MM cells, and better simulate the structural function of MM in vivo. This review explores the role of each TME component in development of the PDO model. This review will provide a reference for research on the drug screening and targeted treatment using PDOs, particularly for the immunotherapy of MM.
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Electrochemical conversion of nitrate (NO3 - ) into ammonia (NH3 ) represents a potential way for achieving carbon-free NH3 production while balancing the nitrogen cycle. Herein we report a high-performance Cu nanosheets catalyst which delivers a NH3 partial current density of 665â mA cm-2 and NH3 yield rate of 1.41â mmol h-1 cm-2 in a flow cell at -0.59â V vs. reversible hydrogen electrode. The catalyst showed a high stability for 700â h with NH3 Faradaic efficiency of ≈88 % at 365â mA cm-2 . In situ spectroscopy results verify that Cu nanosheets are in situ derived from the as-prepared CuO nanosheets under electrochemical NO3 - reduction reaction conditions. Electrochemical measurements and density functional theory calculations indicate that the high performance is attributed to the tandem interaction of Cu(100) and Cu(111) facets. The NO2 - generated on the Cu(100) facets is subsequently hydrogenated on the Cu(111) facets, thus the tandem catalysis promotes the crucial hydrogenation of *NO to *NOH for NH3 production.
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Amoníaco , Nitratos , Catálisis , Electrodos , HidrogenaciónRESUMEN
Osteoimmunomodulation has been considered to play a key role in osteointegration of orthopedic biomaterials. However, regulation of the macrophage phenotype in vivo with a spatiotemporal controllable way still remains a challenge. In this study, we designed a novel magnetic-responsive mineralized collagen coating to exert remotely controlled magneto-mechanical stimulation on macrophages using an external magnetic field. The magneto-mechanical stimulation exhibited immunomodulatory capability to activate M2 macrophage polarization via triggering the integrin-related cascade pathway and suppressing the phosphorylation of JNK in the MAPK pathway. The optimized inflammatory microenvironment subsequently promoted the osteogenic differentiation of bone marrow-derived mesenchymal stem cells and the osteointegration in vivo. This work, therefore, provides a remote spatiotemporal controllable strategy to promote the osteointegration of orthopedic biomaterials via regulation of the osteoimmune microenvironment.
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Células Madre Mesenquimatosas , Osteogénesis , Macrófagos/metabolismo , Materiales Biocompatibles , Células Madre Mesenquimatosas/metabolismo , Diferenciación CelularRESUMEN
A new focus with respect to the extraction of plant protein is that ingredient enrichment should target functionality instead of pursuing purity. Herein, the sequence aqueous extraction method was used to co-enrich five protein-polysaccharide natural fractions from flaxseed meal, and their composition, structure, and functional properties were investigated. The total recovery rate of flaxseed protein obtained by the sequence extraction approach was more than 80%, which was far higher than the existing reports. The defatted flaxseed meal was soaked by deionized water to obtain fraction 1 (supernatant), and the residue was further treated to get fraction 2 (supernatant) and 3 (precipitate) through weak alkali solubilization. Part of the fraction 2 was taken out, followed by adjusting its pH to 4.2. After centrifuging, the albumin-rich supernatant and precipitate with protein content of 73.05% were gained and labeled as fraction 4 and fraction 5. The solubility of fraction 2 and 4 exceeded 90%, and the foaming ability and stability of fraction 5 were 12.76 times and 9.89 times higher than commercial flaxseed protein, respectively. The emulsifying properties of fractions 1, 2, and 5 were all greater than that of commercial sodium caseinate, implying that these fractions could be utilized as high-efficiency emulsifiers. Cryo-SEM results showed that polysaccharides in fractions were beneficial to the formation of network structure and induced the formation of tighter and smoother interfacial layers, which could prevent emulsion flocculation, disproportionation, and coalescence. This study provides a reference to promote the high-value utilization of flaxseed meals.
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Background: The largemouth bass (Micropterus salmoides), an economically important freshwater fish species widely farmed in China, is traditionally cultured using a diet of forage fish. However, given the global decline in forage fish fisheries and increasing rates of waterbody pollution and disease outbreaks during traditional culturing, there is a growing trend of replacing forage fish with formulated feed in the largemouth bass breeding industry. The specific molecular mechanisms associated with such dietary transition in this fish are, nevertheless, poorly understood. Methods: To identify single nucleotide polymorphisms (SNPs) related to food habit domestication traits and growth traits in largemouth bass fry, we initially genotyped fry using eight candidate SNPs based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, with genetic parameters being determined using Popgen32 and Cervus 3.0. Subsequently, we assessed the associations between food habit domestication traits of largemouth bass fry and these SNPs using the Chi-square test or Fisher's exact test. Furthermore, we used a general linear model to assess the relationships between the growth traits of largemouth bass fry and these SNPs. The Pearson correlation coefficient between growth traits and the SNPs was also determined using bivariate correlation analysis in IBM SPSS Statistics 22. Finally, the phenotypic variation explained (PVE) by the SNPs was calculated by regression analysis in Microsoft Excel. Results: The genotyping results obtained based on PCR-RFLP analysis were consistent with those of direct sequencing. Five SNPs (SNP01, SNP02, SNP04, SNP05, and SNP06) were found to be significantly correlated with the food habit domestication traits of fry (P < 0.05); SNP01 (P = 0.0011) and SNP04 (P = 0.0055) particularly, had showed highly significant associations. With respect to growth traits, we detected significant correlations with the two SNPs (SNP01 and SNP07) (P < 0.05), with SNP01 being significantly correlated with body length, and height (P < 0.05), and SNP07 being significantly correlated with body height only (P < 0.05). Conclusions: Our findings indicated that the PCR-RFLP can be used as a low-cost genotyping method to identify SNPs related to food habit domestication and growth traits in largemouth bass, and that these trait-related SNPs might provide a molecular basis for the future breeding of new varieties of largemouth bass.
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Lubina , Animales , Lubina/genética , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple/genética , Domesticación , Reacción en Cadena de la PolimerasaRESUMEN
Background: Functional orthoses are commonly used to treat skeletal Class II malocclusion, but the specific mechanism through which they do this has been a challenging topic in orthodontics. In the present study, we aimed to explore the effect of tensile stress on the osteogenic differentiation of condylar chondrocytes from an exosomal perspective. Methods: We cultured rat condylar chondrocytes under resting and tensile stress conditions and subsequently extracted cellular exosomes from them. We then screened miRNAs that were differentially expressed between the two exosome extracts by high-throughput sequencing and performed bioinformatics analysis and osteogenesis-related target gene prediction using the TargetScan and miRanda softwares. Exosomes cultured under resting and tensile stress conditions were co-cultured with condylar chondrocytes for 24 h to form the Control-Exo and Force-Exo exosome groups, respectively. Quantitative real time PCR(RT-qPCR) and western blotting were then used to determine the mRNA and protein expression levels of Runx2 and Sox9 in condylar chondrocytes. Results: The mRNA and protein expression levels of Runx2 and Sox9 in the Force-Exo group were significantly higher than those in the Control-Exo group (p < 0.05). The differential miRNA expression results were consistent with our sequencing results. Bioinformatics analysis and target gene prediction results showed that the main biological processes and molecular functions involved in differential miRNA expression in exosomes under tensile stress were biological processes and protein binding, respectively. Kyoto Gene and Genome Data Bank (KEGG) pathway enrichment analysis showed significant enrichment of differentially expressed miRNAs in the mTOR signaling pathway. The differentially expressed miRNAs were found to target osteogenesis-related genes. Conclusion: These results suggest that stimulation of rat condylar chondrocytes with tensile stress can alter the expression levels of certain miRNAs in their exosomes and promote their osteogenic differentiation. Exosomes under tensile stress culture conditions thus have potential applications in the treatment of Osteoarthritis (OA).
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The optoelectronic properties of two-dimensional (2D) transition metal dichalcogenide (TMD) thin layers prepared by exfoliation or chemical vapour deposition are strongly modulated by defects at the nanoscale. The mediated electronic and optical properties are expected to be spatially localised in a nanoscale width neighbouring the defects. Characterising such localised properties requires an analytical tool with nanoscale spatial resolution and high optical sensitivity. In recent years, tip-enhanced nanoscopy, represented by tip-enhanced Raman spectroscopy (TERS) and tip-enhanced photoluminescence (TEPL), has emerged as a powerful tool to characterise the localised phonon and exciton behaviours of 2D TMDs and heterojunctions (HJs) at the nanoscale. Herein, we first summarise the recent progress of TERS and TEPL in the characterisation of several typical defects in TMDs, such as edges, wrinkles, grain boundaries and other defects generated in transfer and growth processes. Then the local strain and its dynamic control of phonon and exciton behaviours characterised by TERS and TEPL will be reviewed. The recent progress in characterising TMD HJs using TERS and TEPL will be subsequently summarised. Finally, the progress of TERS and TEPL combined with optoelectronic sensitive electronic scanning probe microscopy (SPM) in the applications of TMDs will be reviewed.
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Largemouth bass (Micropterus salmoides L.) is generally considered to comprise two subspecies, Florida bass (M. floridanus) and Northern Largemouth bass (M. salmoides), which have biological characteristic differences because of their geographical distribution. In this study, whole-genome re-sequencing was performed among 10 Florida and 10 Northern largemouth bass, respectively. In total, 999,793 SNPs and 227,797 InDels were finally identified, and 507,401 SNPs (50.75%) and 116,213 InDels (51.01%) were successfully mapped to annotated 18,629 genes and 14,060 genes, respectively. KEGG classification indicated that most of these genes were focused on the pathways including signal transduction, transport and catabolism, and endocrine system. Genetic diversity analysis indicated that Florida largemouth bass had higher genetic diversity than Northern largemouth bass, indicating that the germplasm quality of Northern largemouth bass had markedly reduced in China. To examine the accuracies of the identified markers, 23 SNPs and eight InDels (the insertions or deletions of more than 45 bp) were randomly selected and detected among Florida largemouth bass, Northern largemouth bass, and their F1 hybrids. The detection efficiencies of all the markers were higher than 95%; nineteen SNPs and three InDels could accurately distinguish the two subspecies and their F1 hybrids with 100% efficiencies. Moreover, the three InDel markers could clearly distinguish the two subspecies and their F1 hybrids with a PCR-based agarose gel electrophoresis. In conclusion, our study established a simple PCR-based method for the germplasm identification of largemouth bass, which will be useful in the germplasm protection, management, and hybridization breeding of largemouth bass.
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BACKGROUND: Brachydactyly type B is an autosomal dominant disorder that is characterized by hypoplasia of the distal phalanges and nails and can be divided into brachydactyly type B1 (BDB1) and brachydactyly type B2 (BDB2). BDB1 is the most severe form of brachydactyly and is caused by truncating variants in the receptor tyrosine kinase-like orphan receptor 2 (ROR2) gene. CASE PRESENTATION: Here, we report a five-generation Chinese family with brachydactyly with or without syndactyly. The proband and her mother underwent digital separation in syndactyly, and the genetic analyses of the proband and her parents were provided. The novel heterozygous frameshift variant c.1320dupG, p.(Arg441Alafs*18) in the ROR2 gene was identified in the affected individuals by whole-exome sequencing and Sanger sequencing. The c.1320dupG variant in ROR2 is predicted to produce a truncated protein that lacks tyrosine kinase and serine/threonine- and proline-rich structures and remarkably alters the tertiary structures of the mutant ROR2 protein. CONCLUSION: The c.1320dupG, p.(Arg441Alafs*18) variant in the ROR2 gene has not been reported in any databases thus far and therefore is novel. Our study extends the gene variant spectrum of brachydactyly and may provide information for the genetic counselling of family members.
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Braquidactilia , Sindactilia , Braquidactilia/diagnóstico , Braquidactilia/genética , Huesos del Carpo/anomalías , Femenino , Deformidades Congénitas del Pie , Deformidades Congénitas de la Mano , Humanos , Linaje , Receptores Huérfanos Similares al Receptor Tirosina Quinasa/genética , Receptores Huérfanos Similares al Receptor Tirosina Quinasa/metabolismo , Estribo/anomalías , Sinostosis , Huesos Tarsianos/anomalíasRESUMEN
Precise timing of macrophage polarization plays a pivotal role in immunomodulation of tissue regeneration, yet most studies mainly focus on M2 macrophages for their anti-inflammatory and regenerative effects while the essential proinflammatory role of the M1 phenotype on the early inflammation stage is largely underestimated. Herein, a superparamagnetic hydrogel capable of timely controlling macrophage polarization is constructed by grafting superparamagnetic nanoparticles on collagen nanofibers. The magnetic responsive hydrogel network enables efficient polarization of encapsulated macrophage to the M2 phenotype through the podosome/Rho/ROCK mechanical pathway in response to static magnetic field (MF) as needed. Taking advantage of remote accessibility of magnetic field together with the superparamagnetic hydrogels, a temporal engineered M1 to M2 transition course preserving the essential role of M1 at the early stage of tissue healing, as well as enhancing the prohealing effect of M2 at the middle/late stages is established via delayed MF switch. Such precise timing of macrophage polarization matching the regenerative process of injured tissue eventually leads to optimized immunomodulatory bone healing in vivo. Overall, this study offers a remotely time-scheduled approach for macrophage polarization, which enables precise manipulation of inflammation progression during tissue healing.
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Regeneración Ósea , Macrófagos , Colágeno/metabolismo , Humanos , Hidrogeles/farmacología , Inmunomodulación , Inflamación/metabolismo , Macrófagos/metabolismo , FenotipoRESUMEN
PURPOSE: To evaluate the plaque removal efficacy of a compacted dual-head power toothbrush (DH) in comparison with a single-head power toothbrush (SH). METHODS: 24 healthy university students were included in this split-mouth and single-center clinical trial. The DH and SH were randomly assigned to brush the left/right half mouth in the first visit. Testing time points were 30 and 60 seconds. Additionally, 15 and 45 seconds were set for the DH period. The overall, buccal, lingual, gingival marginal, and proximal plaque scores at different time points were recorded and determined by Rustogi Modification of the Navy Plaque Index. To avoid the influence of the right handedness, subjects were brushed in the second visit after 4 weeks, and the SH and the DH were assigned to the right/left half mouth in an opposite period to that of the first visit. RESULTS: 21 participants completed this study. Overall plaque score reductions of the SH and DH were 29% and 59% (P< 0.05) at 30 seconds, and the reductions were 47% and 77% respectively (P< 0.05) at 60 seconds. Using the DH for 45 seconds reduced significantly more overall, buccal, lingual, and gingival marginal plaque than that of using SH for 60 seconds (P< 0.05). The SH reduced plaque scores significantly less in the right and lower dentitions than left and upper dentitions respectively, while DH reduced comparable plaque scores between these dentitions. The DH is more effective in removing overall, buccal, lingual, gingival marginal, and proximal plaque in healthy university students than the SH, meanwhile DH showed comparable overall plaque reduction rates between different regions of the dentitions. CLINICAL SIGNIFICANCE: This compact dual-head power toothbrush provides a new option to carry out daily plaque control effectively.