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Hypoplastic left heart syndrome (HLHS) is a rare but fatal birth defect in which the left side of the heart is underdeveloped. HLHS accounts for 2% to 4% of congenital heart anomalies. Whole genome sequencing (WGS) was conducted for a family trio consisting of a proband and his parents. A homozygous rare variant was detected in the PTPRB (Protein Tyrosine Phosphatase Receptor Type B) gene of the proband by functional annotation and co-segregation analysis. Sanger sequencing was used to confirm genotypes of the variant. The in silico prediction tools, including Mutation Taster, SpliceAI, and CADD, were used to predict the impact of the mutation. The allele frequencies across populations were compared based on multiple databases, including "1000 genomes" and "gnomAD". We used two vectors (pcMINI and pcDNA3.1) to generate a minigene construct to validate the mutational effect at the transcriptional level. Family-based WGS analyses showed that only a homozygous splice acceptor variant (NC_000012.12: g.70636068T>G, NM_001109754.4: c.56-2A>C, NG_029940.2: g.6373A>C) at the exon-intron border of PTPRB gene associates with HLHS. This variant is also within the region with the enhancer activity based on UCSC genome annotation. Genotyping and Sanger sequencing revealed that the proband's parents are heterozygous for this variant. Evolutionary conservation analysis revealed that the site (NC_000012.12: g.70636068) is extremely conserved across species, supporting the evolutionary functional constraints of the ancestral wild type (T). In silico tools universally predicted a deleterious or disease-causing impact of the mutation from T to G. The mutation was not found in the 1000 genomes and gnomAD databases, which indicates that this mutation is very rare in most human populations. A splicing assay indicated that the mutated minigene caused aberrant splicing of mRNA, in which a 3 bp missing in the second exon resulted in the deletion of one amino acid (NP_001103224.1:p.Glu19del) compared to the normal protein of PRPTB (also the VE-PTP). Structure prediction revealed that the deletion occurred within the C-region of the signal peptide of VE-PTP, suggesting signal peptide-related defects as a potential mechanism for the HLHS cellular pathogeny. We report a rare homozygous variant with splicing error in PTPRB associated with HLHS. Previous model species studies revealed conserved functions of PTPRB in cardiovascular and heart development in mice and zebrafish. Our study is the first report to show the association between PTPRB and HLHS in humans.
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Síndrome do Coração Esquerdo Hipoplásico , Humanos , Camundongos , Animais , Síndrome do Coração Esquerdo Hipoplásico/genética , Peixe-Zebra , Família , Pais , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a ReceptoresRESUMO
Systemic lupus erythematosus (SLE, OMIM 152700) is a rare autoimmune disease with high heritability that affects ~0.1% of the population. Previous studies have revealed several common variants with small effects in European and East Asian SLE patients. However, there is still no rare variant study on Chinese SLE patients using the whole-genome sequencing technology (WGS). Here, we designed a family based WGS study to identify novel rare variants with large effects. Based on large-scale allele frequency data from the gnomAD database, we identified rare protein-coding gene variants with disruptive and sequence-altering impacts in SLE patients. We found that the burden of rare variants was significantly higher than that of common variants in patients, suggesting a larger effect of rare variants on the SLE pathogenesis. We identified the pathogenic risk of rare missense variants with significant odds ratios (p < 0.05) in two genes, including WNT16 (NC_000007.14:g.121329757G > C, NP_057171.2:p.(Ala86Pro) and 7 g.121329760G > C, NP_057171.2:p.(Ala87Pro)), which explains five out of seven patients covering all three families but are absent from all controls, and ERVW-1 (NC_000007.14:g.92469882A > G, NP_001124397.1:p.(Leu167Pro), rs74545114; NC_000007.14:g.92469907G > A, NP_001124397.1:p.(Arg159Cys), rs201142302; NC_000007.14:g.92469919G > A, NP_001124397.1:p.(His155Tyr), rs199552228), which explains the other two patients. None of these variants were identified in any of the controls. These associations are supported by known gene expression studies in SLE patients based on literature review. We further tested the wild and mutant types using the luciferase assays and qPCR in cells. We found that WNT16 can activate the canonical Wnt/ß-catenin pathway while the mutant cannot. Additionally, the wild ERVW-1 expression can be significantly up-regulated by cAMP while the mutant cannot. Our study provides the first direct genetic and in vitro evidence for the pathogenic risk of mutant WNT16 and ERVW-1, which may facilitate the design of precision therapy for SLE.
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Lúpus Eritematoso Sistêmico , Humanos , Frequência do Gene , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/epidemiologia , Mutação de Sentido Incorreto , Polimorfismo de Nucleotídeo Único , Sequenciamento Completo do Genoma , Proteínas Wnt/genéticaRESUMO
The rapid progress of sequencing technology has greatly facilitated the de novo genome assembly of pig breeds. However, the assembly of the wild boar genome is still lacking, hampering our understanding of chromosomal and genomic evolution during domestication from wild boars into domestic pigs. Here, we sequenced and de novo assembled a European wild boar genome (ASM2165605v1) using the long-range information provided by 10× Linked-Reads sequencing. We achieved a high-quality assembly with contig N50 of 26.09 Mb. Additionally, 1.64% of the contigs (222) with lengths from 107.65 kb to 75.36 Mb covered 90.3% of the total genome size of ASM2165605v1 (~2.5 Gb). Mapping analysis revealed that the contigs can fill 24.73% (93/376) of the gaps present in the orthologous regions of the updated pig reference genome (Sscrofa11.1). We further improved the contigs into chromosome level with a reference-assistant scaffolding method. Using the 'assembly-to-assembly' approach, we identified intra-chromosomal large structural variations (SVs, length >1 kb) between ASM2165605v1 and Sscrofa11.1 assemblies. Interestingly, we found that the number of SV events on the X chromosome deviated significantly from the linear models fitting autosomes (R2 > 0.64, p < 0.001). Specifically, deletions and insertions were deficient on the X chromosome by 66.14 and 58.41% respectively, whereas duplications and inversions were excessive on the X chromosome by 71.96 and 107.61% respectively. We further used the large segmental duplications (SDs, >1 kb) events as a proxy to understand the large-scale inter-chromosomal evolution, by resolving parental-derived relationships for SD pairs. We revealed a significant excess of SD movements from the X chromosome to autosomes (p < 0.001), consistent with the expectation of meiotic sex chromosome inactivation. Enrichment analyses indicated that the genes within derived SD copies on autosomes were significantly related to biological processes involving nervous system, lipid biosynthesis and sperm motility (p < 0.01). Together, our analyses of the de novo assembly of ASM2165605v1 provides insight into the SVs between European wild boar and domestic pig, in addition to the ongoing process of meiotic sex chromosome inactivation in driving inter-chromosomal interaction between the sex chromosome and autosomes.
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Duplicações Segmentares Genômicas , Motilidade dos Espermatozoides , Animais , Cromossomos , Genoma , Masculino , Sus scrofa/genética , Suínos/genéticaRESUMO
BACKGROUND: Although reclaimed wastewater drip irrigation (RWDI) is an effective technology for alleviating agricultural crop water stress and protecting the environment, the reclaimed wastewater (RW) may cause emitter clogging. Discharge ratio variation (Dra) and coefficient of uniformity (CU) play a key role in exploring the clogging degree of the emitter. Therefore, a meta-analysis was conducted to identify optimal management methods with an acceptable Dra and CU under RWDI. RESULTS: The results indicate that the higher the concentration of various substances in RW, the higher is the risk of the emitter clogging. Suitable concentrations of iron (Fe), manganese (Mn), total suspended solids (TSS), chemical oxygen demand (COD), water hardness and calcium ions (Ca2+ ) in RW were determined to be 0-0.2, 0-0.02, 0-50, 20-30, 200-250 and 0-40 mg L-1 , respectively. Pressure-compensating emitters with relatively high discharge (>2 L h-1 ) could prevent clogging in RWDI systems. CONCLUSION: Based on the data analysis, a cumulative RWDI operation time of 375 h was determined as the most suitable time for lateral flushing to prevent clogging. This study identifies the conditions under which an increase in the service life of RWDI systems can be achieved. © 2022 Society of Chemical Industry.
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Irrigação Agrícola , Águas Residuárias , Produtos Agrícolas , Águas Residuárias/químicaRESUMO
We compared the electrical conductivity from two different aggregates of whey protein concentrates (WPC) film: conventional amorphous aggregation at natural pH (pH 6.5) and amyloid fibrils at a low pH (pH 2.0) far away from the isoelectric point. The two types of film fabricated by these solutions with different aggregate structures showed large variations in electrical conductivity and other properties. The WPC fibril film (pH 2.0) exhibited higher electrical conductivity than that of the conventional WPC film (pH 6.5), improved mechanical properties and oil resistance, due to varying morphology, higher surface hydrophobicity and more (absolute value) surface charge of film-forming solutions. The evidence from this study suggests that fibrilized WPC with high-ordered and ß-sheets-rich structures fabricated high electrical conductivity film, which broadens the potential application of fibrils as functional bio-nanomaterials.
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Condutividade Elétrica , Proteínas do Soro do Leite/química , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Ponto Isoelétrico , Microscopia Eletrônica de Transmissão , Nanoestruturas , SolubilidadeRESUMO
PURPOSE: To explore the relationship between the bleb vasculature and surgical outcome after trabeculectomy (TRAB) using optical coherence tomography angiography (OCT-A). METHODS: A prospective study was conducted, which included 26 eyes of 26 primary glaucoma patients in the final analysis. Thereinto, six patients underwent TRAB combined 5-FU and 12 patients received subconjunctival 5-FU injection postoperation. The bleb vessel was evaluated using OCT-A 1 week, 2 weeks, 1 month, 3 months, and 6 months after TRAB. Intraocular pressure (IOP), filtering bleb height, and bleb wall thickness were recorded at the same time. Pearson's correlation analysis and linear regression analysis were performed to determine the correlation of the vessel area data with other parameters. RESULTS: Compared with vessel area 1 week after surgery, there was significant increase of the vessel area (â³vessel area) 2 weeks (11.13 ± 11.91%, p < 0.05) and 1 month (16.91 ± 14.85%, p < 0.0001) after surgery in all patients. The â³vessel area was significantly greater in acute angle closure (AAC) and primary angle closure glaucoma (PACG) 1-month post-TRAB as compared with that 1 week (p < 0.05). The results indicated that the â³vessel area 1-month post-TRAB was positive correlated with IOP 6-month post-TRAB (ß = 3.88, p = 0.042). CONCLUSIONS: Filtering bleb vascularization evaluation using OCT-A could potentially predict IOP 6-month post-TRAB. Surgery effect predicted by filtering bleb vascularization detection is conducive to the select specific postoperative intervention to improve the success rate of TRAB.
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Angiofluoresceinografia/métodos , Glaucoma/cirurgia , Pressão Intraocular/fisiologia , Complicações Pós-Operatórias/diagnóstico , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Trabeculectomia/efeitos adversos , Feminino , Seguimentos , Fundo de Olho , Glaucoma/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de TempoRESUMO
OBJECTIVE: To explore the effect of CCR3 antagonist on the development of experimental corneal neovascularization. METHODS: Mouse corneas were burned by NaOH to induce corneal neovascularization.Fifty four clean male BABL/c mice aged 7-8 weeks were divided into control group, CCR3 antagonist group and VEGF antibody positive group according to randomized number table. The gene expression of CCR3 and its ligand eotaxin in burned corneas was examined by Real-time PCR. CCR3 antagonist was locally administrated after alkali injury and the formation of corneal neovascular 2 weeks after injury was examined using a digital camera linked to a slit lamp microscope and corneal whole mount staining with CD31. The mRNA and protein expression of chemokines in burned corneas was detected by Real-time PCR and western blot. RESULTS: Compared to control group, CCR3 antagonist treated mice resulted in significantly decreased corneal neovascularization. The related CNV area was 0.51 ± 0.03 in the CCR3 antagonist group, and that in the control group was 0.77 ± 0.15, with significant difference between them (t = 12.91, P = 0.00).Western blot detection did not show significant difference of VEGF protein expression between two groups.Expression level of VEGF in the CCR3 antagonist group was 0.91 ± 0.24, and that in the control group was 1.15 ± 0.30, showing no significant difference (t = 1.08, P = 0.34). CONCLUSIONS: Alkali-induced corneal neovascularization was inhibited by CCR3 antagonist. The mechanism that CCR3 pathway plays an important role in corneal neovascularization needs further exploration.
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Neovascularização da Córnea/prevenção & controle , Receptores CCR3/antagonistas & inibidores , Animais , Queimaduras Químicas/complicações , Neovascularização da Córnea/induzido quimicamente , Modelos Animais de Doenças , Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro/metabolismo , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real , Receptores CCR3/metabolismo , Hidróxido de Sódio , Fator A de Crescimento do Endotélio VascularRESUMO
The mechanism by which algal organic matter (AOM) affects the clogging of ceramic emitters remains unclear, which partially reduces the operational life of agricultural water distribution systems. This paper systematically investigated the clogging phenomenon of ceramic emitters under three different AOM concentrations. The results of irrigation tests revealed that the AOM significantly affects the degree of clogging of ceramic emitters, with higher AOM concentrations leading to faster flow reduction. By analyzing the original irrigation water and effluent and characterizing the clogged emitter surface, it was demonstrated that AOM was intercepted by the ceramic emitter, forming a dense biofilm. Infrared spectroscopy analysis revealed that polysaccharides and humic substances were the main clogging components. The clogging kinetics showed that as the AOM concentration increased, the clogging of the filter cake layer gradually become dominant. Further, the mechanism of interaction between AOM and silica ceramic emitters was explored from a microscopic perspective using molecular dynamics (MD) simulation with bovine serum albumin (BSA), sodium alginate (SA), and humic acid (HA) as model clogging substances in AOM. The simulation results indicated a strong interaction between AOM molecules and silica molecules dominated by electrostatic attraction, with the strength of the interaction as SA > HA > BSA. It was hypothesized that early clogging was mainly formed by polysaccharides and humic substances combining with silica molecules, while BSA was retained later by combining with organics on the clogging layer or through size exclusion. This study provides insights into bio-clogging in microporous ceramic emitters and may offer a theoretical basis for developing measures to control emitter clogging.
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As bacterial keratitis progresses rapidly, prompt intervention is necessary. Current diagnostic processes are time-consuming and invasive, leading to improper antibiotics for treatment. Therefore, innovative strategies for diagnosing and treating bacterial keratitis are urgently needed. In this study, Cu2-xSe@BSA@NTRP nanoparticles were developed by loading nitroreductase-responsive probes (NTRPs) onto Cu2-xSe@BSA. These nanoparticles exhibited integrated fluorescence imaging and antibacterial capabilities. In vitro and in vivo experiments showed that the nanoparticles produced responsive fluorescence signals in bacteria within 30 min due to an interaction between the released NTRP and bacterial endogenous nitroreductase (NTR). When combined with low-temperature photothermal therapy (PTT), the nanoparticles effectively eliminated E. coli and S. aureus, achieved antibacterial efficacy above 95% and facilitated the re-epithelialization process at the corneal wound site in vivo. Overall, the Cu2-xSe@BSA@NTRP nanoparticles demonstrated potential for rapid, noninvasive in situ diagnosis, treatment, and visualization assessment of therapy effectiveness in bacterial keratitis.
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Antibacterianos , Escherichia coli , Ceratite , Nanopartículas , Nitrorredutases , Animais , Nitrorredutases/metabolismo , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/uso terapêutico , Nanopartículas/química , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Escherichia coli/efeitos dos fármacos , Imagem Óptica/métodos , Staphylococcus aureus/efeitos dos fármacos , Camundongos , Terapia Fototérmica/métodos , Humanos , Cobre/químicaRESUMO
Recently, organic Sb(III)-based metal halides have achieved significant results in the visible light region due to their efficient emission. However, realizing efficient broadband near-infrared (NIR) emission in such materials is a great challenge. Herein, we developed three different NIR emitters via a coordination structure modulation strategy in Sb3+-doped zero-dimensional organic metal chlorides of (C20H20P)2MnCl4, (C20H20P)2ZnCl4, and (C20H20P)2CdCl4 with tetrahedral structure. More specifically, after the dopant Sb3+ is inserted into the host lattice, the coordination structures of Sb3+ ions can change from [SbCl5]2- square-pyramidal configuration to [SbCl4]- clusters, which will bring a larger lattice distortion degree to the excited state compared to the ground state, resulting in a larger Stokes shift. Thus, efficient NIR emission with near-unity photoluminescence quantum yield (PLQY) can be obtained in Sb3+-doped compounds under 365 nm excitation. Moreover, Sb3+-doped NIR emitters also show remarkable stabilities, which prompts us to fabricate NIR phosphor conversion light-emitting diodes (pc-LEDs) and demonstrate their application in night vision. More interestingly, the Sb3+-doped (C20H20P)2MnCl4 shows tunable emission characteristics, which can be tuned from green to greenish-yellow, orange, red, and NIR emission under different external stimuli, and thus we can demonstrate the applications of this compound in quintuple-mode fluorescence anti-counterfeiting and information encryption.
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The increasing pathogenic bacteria threat in irrigation water has become a worldwide concern, prompting efforts to discover a new cost-effective method for pathogenic bacteria eradication, different than those currently in use. In this study, a novel copper-loaded porous ceramic emitter (CPCE) was developed via molded sintering method to kill bacteria from irrigation water. The material performance and hydraulic properties of CPCE are discussed herein, and the antibacterial effect against Escherichia coli (E. coli) and Staphylococcusaureus (S. aureus) was evaluated. The incremental copper content in CPCE improved flexural strength and pore size, which was conducive to enhancing CPCE discharge. Moreover, antibacterial tests showed that CPCE displayed efficient antimicrobial activity, killing 99.99% and more than 70% of S. aureus and E. coli, respectively. The results reveal that CPCE, with both irrigation and sterilization functions, can provide a low-cost and effective solution for bacterial removal from irrigation water.
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Cobre , Escherichia coli , Cobre/farmacologia , Staphylococcus aureus , Porosidade , Antibacterianos , Cerâmica , Água , Testes de Sensibilidade MicrobianaRESUMO
Nitrogen fertilization (NF) is one of the common practices to increase crop production worldwide over the past several decades. Nevertheless, unreasonable NF results in massive greenhouse gas (GHG) emissions, leading to climate change and global warming. Many studies have already reported the impact of NF on crop yield, global warming potential (GWP) and greenhouse gas intensity (GHGI), but the studies were limited to only some parameters. In this study, a total of 174 studies from 16 countries were collected and then a regression analysis was conducted to obtain the appropriate N fertilization rates that enhance crop yield while reducing GWP and GHGI. After that, a meta-analysis was performed to evaluate the effects of NF on crop yield, GHGI, GWP and GHG emissions and identify NF management strategies that benefit crop yield and maintain GWP. The results showed that the suitable N fertilization rate was 180, 150, 130 and 200 kg ha-1 for wheat, maize, rice and vegetables or industrial crops, respectively. Overall, NF resulted in positive effect size in crop yield (0.56) and negative effect size in GHGI (-0.14) compared to NNF. GWP showed positive effect size (0.37) due to an increase in N2O emissions (0.91) relative to NNF, which is higher than the increase of CH4 emissions (0.01) and CO2 emissions (0.22). It was recommended that split and banded application of urea or urea plus manure is employed for cereals (especially wheat) in the arid and semi-arid regions with medium-textured and neutral or alkaline soil.
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Gases de Efeito Estufa , Oryza , Agricultura/métodos , Fertilizantes/análise , Aquecimento Global , Gases de Efeito Estufa/análise , Metano/análise , Nitrogênio , Óxido Nitroso/análise , Solo , Triticum , UreiaRESUMO
The arms race between humans and pathogens drives the evolution of the human genome. It is thus expected that genes from the interferon-regulatory factors family (IRFs), a critical family for anti-viral immune response, should be undergoing episodes of positive selection. Herein, we tested this hypothesis and found multiple lines of evidence for positive selection on the amino acid site Val129 (NP_006075.3:p.Ser129Val) of human IRF9. Interestingly, the ancestral reconstruction and population distribution analyses revealed that the ancestral state (Ser129) is conserved among mammals, while the derived positively selected state (Val129) was fixed before the "out-of-Africa" event ~ 500,000 years ago. The motif analysis revealed that this young amino acid (Val129) may serve as a dephosphorylation site of IRF9. Structural parallelism between homologous genes further suggested the functional effects underlying the dephosphorylation that may affect the immune activity of IRF9. This study provides a model in which a strong positive Darwinian selection drives a recent fixation of a hominin-specific amino acid leading to molecular adaptation involving dephosphorylation in an immune-responsive gene.
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Hominidae , Animais , Humanos , Hominidae/metabolismo , Aminoácidos/genética , Fatores Reguladores de Interferon/química , Seleção Genética , Mutação , Mamíferos/metabolismo , Fator Gênico 3 Estimulado por Interferon, Subunidade gama/genéticaRESUMO
BACKGROUND: With the emerging information and communication technology, the field of medical informatics has dramatically evolved in health care and medicine. Thus, it is crucial to explore the global scientific research landscape on medical informatics. OBJECTIVE: This study aims to present a visual form to clarify the overall scientific research trends of medical informatics in the past decade. METHODS: A bibliometric analysis of data retrieved and extracted from the Web of Science Core Collection (WoSCC) database was performed to analyze global scientific research trends on medical informatics, including publication year, journals, authors, institutions, countries/regions, references, and keywords, from January 1, 2011, to December 31, 2020. RESULTS: The data set recorded 34,742 articles related to medical informatics from WoSCC between 2011 and 2020. The annual global publications increased by 193.86% from 1987 in 2011 to 5839 in 2020. Journal of Medical Internet Research (3600 publications and 63,932 citations) was the most productive and most highly cited journal in the field of medical informatics. David W Bates (99 publications), Harvard University (1161 publications), and the United States (12,927 publications) were the most productive author, institution, and country, respectively. The co-occurrence cluster analysis of high-frequency author keywords formed 4 clusters: (1) artificial intelligence in health care and medicine; (2) mobile health; (3) implementation and evaluation of electronic health records; (4) medical informatics technology application in public health. COVID-19, which ranked third in 2020, was the emerging theme of medical informatics. CONCLUSIONS: We summarize the recent advances in medical informatics in the past decade and shed light on their publication trends, influential journals, global collaboration patterns, basic knowledge, research hotspots, and theme evolution through bibliometric analysis and visualization maps. These findings will accurately and quickly grasp the research trends and provide valuable guidance for future medical informatics research.
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Zero-dimensional (0D) organic metal halides have captured extensive attention for their various structures and distinguished optical characteristics. However, achieving efficient emission through rational crystal structure design remains a great challenge, and how the crystal structure affects the photophysical properties of 0D metal halides is currently unclear. Herein, a rational crystal structure regulation strategy in 0D Sb(III)-based metal halides is proposed to realize near-unity photoluminescence quantum yield (PLQY). Specifically, two 0D organic Sb(III)-based compounds with different coordination configurations, namely, (C25H22P)2SbCl5 and (C25H22P)SbCl4 (C25H22P+ = benzyltriphenylphosphonium), were successfully obtained by precisely controlling the ratio of the initial raw materials. (C25H22P)2SbCl5 adopts an octahedral coordination geometry and shows highly efficient broadband yellow emission with a PLQY of 98.6%, while (C25H22P)SbCl4 exhibits a seesaw-shaped [SbCl4]- cluster and does not emit light under photoexcitation. Theoretical calculations reveal that, by rationally controlling the coordination structure, the indirect bandgap of (C25H22P)SbCl4 can be converted to the direct bandgap of (C25H22P)2SbCl5, thus ultimately boosting the emission intensity. Together with efficient emission and outstanding stability of (C25H22P)2SbCl5, a high-performance white-light emitting diode (WLED) with a high luminous efficiency of 31.2 lm W-1 is demonstrated. Our findings provide a novel strategy to regulate the coordination structure of the crystals, so as to rationally optimize the luminescence properties of organic metal halides.
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PURPOSE: To address the roles of the stromal derived factor-1 (SDF-1) α in the course of experimental corneal neovascularization (CNV). METHODS: CNV was induced by alkali injury and compared in SDF-1α- or vehicle-treated mice two weeks after injury. Angiogenic factor expression in the early phase after injury was quantified by reverse transcription polymerase chain reaction (RT-PCR). Progenitor cell, macrophage, and monocyte intracorneal accumulation in the early phase after injury was evaluated by flow cytometric analysis. RESULTS: The mRNA expression of SDF-1α was augmented, together with infiltration of c-kit-positive progenitor cells in the corneas after the alkali injury. Compared with vehicle-treated mice, SDF-1α-treated mice exhibited enhanced CNV two weeks after injury, as evidenced by enlarged cluster of differentiation 31 (CD31)-positive areas. Concomitantly, the intracorneal infiltration of c-kit-positive progenitor cells but not F4/80+ macrophages or Ly-6G+ monocytes was significantly enhanced in SDF-1α-treated mice compared to vehicle-treated mice. SDF-1α enhanced vascular endothelial growth factor (VEGF) expression by murine peritoneal macrophages. Enhancement in intraocular VEGF expression was greater in SDF-1α-treated mice than in control mice after injury. Moreover, local administration of C-X-C chemokine receptor type 4 (CXCR4) antagonist after alkali injury reduced alkali-induced CNV. CONCLUSIONS: SDF-1α-treated mice exhibited enhanced alkali-induced CNV through enhanced intracorneal progenitor cell infiltration and increased VEGF expression by macrophages.
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Movimento Celular/efeitos dos fármacos , Quimiocina CXCL12 , Córnea/efeitos dos fármacos , Neovascularização da Córnea/metabolismo , Neovascularização da Córnea/patologia , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/biossíntese , Administração Tópica , Álcalis/efeitos adversos , Indutores da Angiogênese/imunologia , Indutores da Angiogênese/metabolismo , Animais , Quimiocina CXCL12/efeitos adversos , Quimiocina CXCL12/farmacologia , Córnea/imunologia , Córnea/metabolismo , Córnea/patologia , Neovascularização da Córnea/induzido quimicamente , Neovascularização da Córnea/imunologia , Modelos Animais de Doenças , Citometria de Fluxo , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Monócitos/imunologia , Monócitos/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Receptores CXCR4/antagonistas & inibidores , Receptores CXCR4/imunologia , Receptores CXCR4/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células-Tronco/imunologia , Células-Tronco/metabolismo , Fator A de Crescimento do Endotélio Vascular/imunologiaRESUMO
Parkinson's disease is one of the most common adult-onset, a chronic disorder involving neurodegeneration, which progressively leads to deprivation of dopaminergic neurons in substantia nigra, causing a subsequent reduction of dopamine levels in the striatum resulting in tremor, myotonia, and dyskinesia. Genetics and environmental factors are believed to be responsible for the onset of Parkinson's disease. The exact pathogenesis of Parkinson's disease is quite complicated and the present anti-Parkinson's disease treatments appear to be clinically insufficient. Comprehensive researches have demonstrated the use of natural products such as ginseng, curcumin, ashwagandha, baicalein, etc. for the symptomatic treatment of this disease. The neuroprotective effects exhibited by these natural products are mainly due to their ability to increase dopamine levels in the striatum, manage oxidative stress, mitochondrial dysfunction, glutathione levels, clear the aggregation of α- synuclein, induce autophagy and decrease the pro-inflammatory cytokines and lipid peroxidation. This paper reviews various natural product studies conducted by scientists to establish the role of natural products (both metabolite extracts as well as pure metabolites) as adjunctive neuroprotective agents.
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Fármacos Neuroprotetores , Doença de Parkinson , Preparações de Plantas , Dopamina , Neurônios Dopaminérgicos , Humanos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Preparações de Plantas/farmacologia , Preparações de Plantas/uso terapêutico , alfa-SinucleínaRESUMO
BACKGROUND: Neuropathic pain (NP) is an egregious problem worldwide. Due to the side-effects of oral drugs, drugs delivered directly to the affected area of pain are preferred. OBJECTIVE: Capsaicin, a chemical compound isolated from chili peppers, is used as an analgesic in topical ointments and dermal patches to alleviate pain. Objective of the study is to review the application and functionality of topical capsaicin in treatment of neuropathic pain. DATA SOURCES: To systematically review capsaicin's functions on NP, we retrieved articles from the PubMed database published in the last ten years. STUDY ELIGIBILITY CRITERIA: The inclusion criteria were capsaicin and the use of capsaicin for the treatment of NP; on the other hand, articles were excluded according to the mentioned criteria such as abstracts, articles written in any language other than English, incomplete articles, and conference papers. PARTICIPANTS AND INTERVENTIONS: Out of 265 articles, 108 articles were selected after filtering through the inclusion and exclusion criteria. The data and knowledge currently existing for capsaicin treatment in NP are summarized. RESULTS: This review indicates that capsaicin effectively improves NP treatment without affecting the motor and large nerve fibres involved in sensory function. Transient receptor potential channel vanilloid type 1 (TRPV1) is the capsaicin receptor expressed in central and peripheral terminals of a sensitive primary nerve cell. Conclusions and implications of key findings: Topical capsaicin has a sensible safety profile and is effective in reducing NP. Therefore, studies over the last decade suggest that capsaicin might be a potential drug for NP treatment.
Assuntos
Analgésicos/administração & dosagem , Capsaicina/administração & dosagem , Neuralgia/tratamento farmacológico , Administração Cutânea , Analgésicos/efeitos adversos , Analgésicos/farmacocinética , Animais , Capsaicina/efeitos adversos , Capsaicina/farmacocinética , Modelos Animais de Doenças , Humanos , Células Receptoras Sensoriais/efeitos dos fármacos , Células Receptoras Sensoriais/metabolismo , Canais de Cátion TRPV/metabolismo , Resultado do TratamentoRESUMO
Background: The world has been unprecedentedly hit by a global pandemic which broke the record of deadly pandemics that faced humanity ever since its existence. Even kids are well-versed in the terminologies and basics of the SARS-CoV-2 virus and COVID-19 now. The vaccination program has been successfully launched in various countries, given that the huge global population of concern is still far behind to be vaccinated. Furthermore, the scarcity of any potential drug against the COVID-19-causing virus forces scientists and clinicians to search for alternative and complementary medicines on a war-footing basis. Aims and Objectives: The present review aims to cover and analyze the etiology and epidemiology of COVID-19, the role of intestinal microbiota and pro-inflammatory markers, and most importantly, the natural products to combat this deadly SARS-CoV-2 virus. Methods: A primary literature search was conducted through PubMed and Google Scholar using relevant keywords. Natural products were searched from January 2020 to November 2020. No timeline limit has been imposed on the search for the biological sources of those phytochemicals. Interactive mapping has been done to analyze the multi-modal and multi-target sources. Results and Discussion: The intestinal microbiota and the pro-inflammatory markers that can serve the prognosis, diagnosis, and treatment of COVID-19 were discussed. The literature search resulted in yielding 70 phytochemicals and ten polyherbal formulations which were scientifically analyzed against the SARS-CoV-2 virus and its targets and found significant. Retrospective analyses led to provide information about 165 biological sources that can also be screened if not done earlier. Conclusion: The interactive analysis mapping of biological sources with phytochemicals and targets as well as that of phytochemical class with phytochemicals and COVID-19 targets yielded insights into the multitarget and multimodal evidence-based complementary medicines.
RESUMO
Using 13C pulsed labeling technique, we examined the biomass and carbon accumulation of different organs as well as the distribution characteristics of 13C assimilate of 6-year-old Korla fragrant pear trees under three nitrogen application levels, i.e., 150, 300, and 450 kg N·hm-2 (marked as N1, N2, and N3, respectively). Results showed that the biomass, carbon accumulation, 13C fixation and leaf assimilation capacity of the whole pear tree increased while root to shoot ratio decreased with increasing nitrogen application. Both biomass and carbon accumulation amount of reproductive organs (i.e., fruits) were the highest under N2 treatment. The 13C content and distribution rate of each organ changed dynamically along with increasing nitrogen application. At the new shoot growing stage, leaves and roots had stronger competitive abilities for photosynthate, with 13C distribution rates being the highest under N1 treatment. During fruit swelling and mature stages, leaves and fruits were more competitive, with 13C content and distribution rate in leaves being the highest under N3 treatment and those in fruits being the highest under N2 treatment. According to the absorption and distribution characteristics of carbon assimilate across organs under the three nitrogen application levels, the optimal nitrogen application level for achieving high fruit yield in the 6-year-old Korla fragrant pear tree orchard is recommended as 300 kg·hm-2 .