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Non-invasive prenatal testing (NIPT) is a quite popular approach for detecting fetal genomic aneuploidies. However, due to the limitations on sequencing read length and coverage, NIPT suffers a bottleneck on further improving performance and conducting earlier detection. The errors mainly come from reference biases and population polymorphism. To break this bottleneck, we proposed NIPT-PG, which enables the NIPT algorithm to learn from population data. A pan-genome model is introduced to incorporate variant and polymorphic loci information from tested population. Subsequently, we proposed a sequence-to-graph alignment method, which considers the read mis-match rates during the mapping process, and an indexing method using hash indexing and adjacency lists to accelerate the read alignment process. Finally, by integrating multi-source aligned read and polymorphic sites across the pan-genome, NIPT-PG obtains a more accurate z-score, thereby improving the accuracy of chromosomal aneuploidy detection. We tested NIPT-PG on two simulated datasets and 745 real-world cell-free DNA sequencing data sets from pregnant women. Results demonstrate that NIPT-PG outperforms the standard z-score test. Furthermore, combining experimental and theoretical analyses, we demonstrate the probably approximately correct learnability of NIPT-PG. In summary, NIPT-PG provides a new perspective for fetal chromosomal aneuploidies detection. NIPT-PG may have broad applications in clinical testing, and its detection results can serve as a reference for false positive samples approaching the critical threshold.
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Aneuploidia , Pruebas Prenatales no Invasivas , Humanos , Femenino , Embarazo , Pruebas Prenatales no Invasivas/métodos , Algoritmos , Genómica/métodos , Diagnóstico Prenatal/métodos , Análisis de Secuencia de ADN/métodosRESUMEN
In cancer genomics, variant calling has advanced, but traditional mean accuracy evaluations are inadequate for biomarkers like tumor mutation burden, which vary significantly across samples, affecting immunotherapy patient selection and threshold settings. In this study, we introduce TMBstable, an innovative method that dynamically selects optimal variant calling strategies for specific genomic regions using a meta-learning framework, distinguishing it from traditional callers with uniform sample-wide strategies. The process begins with segmenting the sample into windows and extracting meta-features for clustering, followed by using a pre-trained meta-model to select suitable algorithms for each cluster, thereby addressing strategy-sample mismatches, reducing performance fluctuations and ensuring consistent performance across various samples. We evaluated TMBstable using both simulated and real non-small cell lung cancer and nasopharyngeal carcinoma samples, comparing it with advanced callers. The assessment, focusing on stability measures, such as the variance and coefficient of variation in false positive rate, false negative rate, precision and recall, involved 300 simulated and 106 real tumor samples. Benchmark results showed TMBstable's superior stability with the lowest variance and coefficient of variation across performance metrics, highlighting its effectiveness in analyzing the counting-based biomarker. The TMBstable algorithm can be accessed at https://github.com/hello-json/TMBstable for academic usage only.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Genómica/métodos , Genoma , AlgoritmosRESUMEN
BACKGROUND: Mitochondrial diseases (MDs) can be caused by single nucleotide variants (SNVs) and structural variants (SVs) in the mitochondrial genome (mtDNA). Presently, identifying deletions in small to medium-sized fragments and accurately detecting low-percentage variants remains challenging due to the limitations of next-generation sequencing (NGS). METHODS: In this study, we integrated targeted long-range polymerase chain reaction (LR-PCR) and PacBio HiFi sequencing to analyze 34 participants, including 28 patients and 6 controls. Of these, 17 samples were subjected to both targeted LR-PCR and to compare the mtDNA variant detection efficacy. RESULTS: Among the 28 patients tested by long-read sequencing (LRS), 2 patients were found positive for the m.3243 A > G hotspot variant, and 20 patients exhibited single or multiple deletion variants with a proportion exceeding 4%. Comparison between the results of LRS and NGS revealed that both methods exhibited similar efficacy in detecting SNVs exceeding 5%. However, LRS outperformed NGS in detecting SNVs with a ratio below 5%. As for SVs, LRS identified single or multiple deletions in 13 out of 17 cases, whereas NGS only detected single deletions in 8 cases. Furthermore, deletions identified by LRS were validated by Sanger sequencing and quantified in single muscle fibers using real-time PCR. Notably, LRS also effectively and accurately identified secondary mtDNA deletions in idiopathic inflammatory myopathies (IIMs). CONCLUSIONS: LRS outperforms NGS in detecting various types of SNVs and SVs in mtDNA, including those with low frequencies. Our research is a significant advancement in medical comprehension and will provide profound insights into genetics.
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ADN Mitocondrial , Secuenciación de Nucleótidos de Alto Rendimiento , Enfermedades Mitocondriales , Humanos , ADN Mitocondrial/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Enfermedades Mitocondriales/genética , Enfermedades Mitocondriales/diagnóstico , Femenino , Masculino , Análisis de Secuencia de ADN/métodos , Adulto , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Reacción en Cadena de la Polimerasa/métodosRESUMEN
BACKGROUND: Mitochondrial tRNA (mt-tRNA) variants have been found to cause disease. Post-transcriptional queuosine (Q) modifications of mt-tRNA can promote efficient mitochondrial mRNA translation. Q modifications of mt-tRNAAsn have recently been identified. Here, the therapeutic effectiveness of queuine was investigated in cells from patients with mt-tRNAAsn variants. METHODS: Six patients (from four families) carrying mt-tRNAAsn variants were included in the study. Queuine levels were quantified by mass spectrometry. Clinical, genetic, histochemical, biochemical, and molecular analysis was performed on muscle tissues and lymphoblastoid cell lines (LCLs) from patients to investigate the pathogenicity of the novel m.5708 C > T variant. The use of queuine in mitigating mitochondrial dysfunction resulting from the mt-tRNAAsn variants was evaluated. RESULTS: The variants included the m.5701 delA, m.5708 C > T, m.5709 C > T, and m.5698 G > A variants in mt-tRNAAsn. The pathogenicity of the novel m.5708 C > T variant was confirmed, as demonstrated by a decreased steady-state level of mt-tRNAAsn, mtDNA-encoded protein levels, oxygen consumption rate (OCR), and the respiratory complex activity. Notably, the serum queuine level was significantly reduced in these patients and in vitro queuine supplementation was found to restore the reductions in mitochondrial protein activities, mitochondrial membrane potential, OCR, and increases in reactive oxygen species. CONCLUSIONS: The study not only confirmed the pathogenicity of the m.5708 C > T variant but also explored the therapeutic potential of queuine in individuals with mt-tRNAAsn variants. The recognition of the novel m.5708 C > T variant's pathogenic nature contributes to our comprehension of mitochondrial disorders. Furthermore, the results emphasize queuine supplementation as a promising approach to enhance the stability of mt-tRNAAsn and rescue mitochondrial dysfunction caused by mt-tRNAAsn variants, indicating potential implications for the development of targeted therapies for patients with mt-tRNAAsn variants.
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Mitocondrias , Humanos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Masculino , Femenino , Adulto , Persona de Mediana Edad , ADN Mitocondrial/genética , Variación Genética , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Nucleósido Q/metabolismo , ARN Mitocondrial/genética , ARN Mitocondrial/metabolismo , ARN de Transferencia de Alanina/genética , ARN de Transferencia de Alanina/metabolismoRESUMEN
New chiral targets of orientational chirality have been designed and asymmetrically synthesized by taking advantage of N-sulfinyl imine-directed nucleophilic addition/oxidation, Suzuki-Miyaura, and Sonogashira cross-coupling reactions. Orientation of single isomers has been selectively controlled by using aryl/alkynyl levers [C(sp2)-C(sp) axis] and tBuSO2- protecting group on nitrogen as proven by X-ray diffraction analysis. The key structural characteristic of resulting orientational products is shown by remote through-space blocking manner. Seventeen examples of multi-step synthesis were obtained with modest to good chemical yields and complete orientational selectivity.
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COQ8A plays an important role in the biosynthesis of coenzyme Q10 (CoQ10), and variations in COQ8A gene are associated with primary CoQ10 deficiency-4 (COQ10D4), also known as COQ8A-ataxia. The current understanding of the association between the specific variant type, the severity of CoQ10 deficiency, and the degree of oxidative stress in individuals with primary CoQ10 deficiencies remains uncertain. Here we provide a comprehensive analysis of the clinical and genetic characteristics of an 18-year-old patient with COQ8A-ataxia, who exhibited novel compound heterozygous variants (c.1904_1906del and c.637C > T) in the COQ8A gene. These variants reduced the expression levels of COQ8A and mitochondrial proteins in the patient's muscle and skin fibroblast samples, contributed to mitochondrial respiration deficiency, increased ROS production and altered mitochondrial membrane potential. It is worth noting that the optimal treatment for COQ8A-ataxia remains uncertain. Presently, therapy consists of CoQ10 supplementation, however, it did not yield significant improvement in our patient's symptoms. Additionally, we reviewed the response of CoQ10 supplementation and evolution of patients in previous literatures in detail. We found that only half of patients could got notable improvement in ataxia. This research aims to expand the genotype-phenotype spectrum of COQ10D4, address discrepancies in previous reviews regarding the effectiveness of CoQ10 in these disorders, and help to establish a standardized treatment protocol for COQ8A-ataxia.
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General and convenient visible-light-promoted alkylsulfonylation and cyanoalkylsulfonylation of MBH adducts have been developed through the multicomponent insertion of sulfur dioxide, enabling the assembly of two C-S bonds to generate structurally diverse allylic alkylsulfones (43 examples in total). The reaction of MBH adducts with potassium alkyltrifluoroborates and 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct afforded sulfones with generally good yields. Notably, the addition of N,N,N',N'-tetramethylethylenediamine as a base into the photocatalytic system led to yielding an alkyl sulfonyl unit and cyano group-anchored trisubstituted alkenes by utilizing cycloketone oxime esters as C-radical precursors. Both of these reactions have constructed two C-S bonds, and all desired products were obtained in moderate to excellent yields with complete stereospecificity.
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Large yellow croaker (Larimichthys crocea) is a vital marine-cultured species in China. Large yellow croaker iridovirus (LYCIV) can cause a high mortality rate in L. crocea. Rapid and convenient detection of LYCIV is an urgent demand for diagnosis. In this study, rapid and simple recombinase polymerase amplification (RPA), real-time RPA and RPA combined with lateral flow dipstick (RPA-LFD) methods were developed for the detection of LYCIV based on the conserved sequence of the LYCIV major capsid protein (MCP) gene. With these optimized RPA analyses, LYCIV detection could be completed within 20 min at 40°C. Both RPA and real-time RPA could detect viral DNA as low as 102 copies/µL, while the detection limit of RPA-LFD was 101 copies/µL, and there was no cross-reaction with other aquatic pathogens (KHV, CyHV-2, GCRV-JX01, SVCV, LCDV and LMBV). In practical evaluation of RPA, real-time RPA and RPA-LFD methods, the results showed consistency with the general PCR detection. In short, the developed RPA, real-time RPA and RPA-LFD analyses could be simple, rapid, sensitive and reliable methods for field diagnosis of LYCIV infection and have significant potential in the protection of LYCIV infection.
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Infecciones por Virus ADN , Enfermedades de los Peces , Iridovirus , Técnicas de Amplificación de Ácido Nucleico , Perciformes , Sensibilidad y Especificidad , Animales , Perciformes/virología , Enfermedades de los Peces/virología , Enfermedades de los Peces/diagnóstico , Infecciones por Virus ADN/veterinaria , Infecciones por Virus ADN/diagnóstico , Infecciones por Virus ADN/virología , Iridovirus/aislamiento & purificación , Iridovirus/genética , Técnicas de Amplificación de Ácido Nucleico/veterinaria , Técnicas de Amplificación de Ácido Nucleico/métodos , ADN Viral/genética , Proteínas de la Cápside/genéticaRESUMEN
OBJECTIVE: To observe the efficacy and safety of sodium valproate (VPA) compared to levetiracetam (LEV) in the treatment of severe traumatic brain injury (sTBI). METHODS: In this blind, prospective study, eighty-four sTBI patients who had craniotomy from August 2021 to August 2023 were randomly split into two groups through random number table method: LEV and VPA, each with 42 patients. Both received comprehensive treatment post-craniotomy. LEV group: LEV injection on surgery day, transitioning to LEV tablets from day two. VPA group: VPA injection on surgery day, switching to VPA extended-release tablets from day two. The study compared hospital stay, neurological function, clinical outcomes, seizures, and drug reactions between groups. RESULTS: The length of hospital stay showed no significant difference between the LEV and VPA groups. Both groups demonstrated improved neurological function post-treatment (NIHSS and BI scores), with no significant between-group differences. Clinical outcomes at 3 months post-treatment were similar in both groups. Seizure occurrence within 3 months after treatment showed no significant difference between the LEV (19.05%) and VPA (23.81%) groups. However, the VPA group experienced a significantly higher rate of drug-related adverse reactions (40.48%) compared to the LEV group (21.43%). CONCLUSION: Both VPA and LEV are effective in treating sTBI, showing no significant difference in improving neurological function, daily life abilities, treatment outcomes, and seizure occurrence. However, VPA treatment exhibited a significantly higher incidence of drug-related adverse reactions compared to LEV, indicating that LEV might be a safer option for sTBI treatment.
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BBX protein is a class of zinc finger transcription factors that have B-box domains at the N-terminus, and some of these proteins contain a CCT domain at the C-terminus. It plays an important role in plant growth, development, and metabolism. However, the expression pattern of BBX genes in alfalfa under hormonal and salt stresses is still unclear. In this study, we identified a total of 125 BBX gene family members by the available Medicago reference genome in diploid alfalfa (Medicago sativa spp. Caerulea), a model plant (M. truncatula), and tetraploid alfalfa (M. sativa), and divided these members into five subfamilies. We found that the conserved motifs of BBXs of the same subfamily reveal similarities. We analyzed the collinearity relationship and duplication mode of these BBX genes and found that the expression pattern of BBX genes is specific in different tissues. Analysis of the available transcriptome data suggests that some members of the BBX gene family are involved in multiple abiotic stress responses, and the highly expressed genes are often clustered together. Furthermore, we identified different expression patterns of some BBX genes under salt, ethylene, salt and ethylene, salicylic acid, and salt and salicylic acid treatments, verified by qRT-PCR, and analyzed the subcellular localization of MsBBX2, MsBBX17, and MsBBX32 using transient expression in tobacco. The results showed that BBX genes were localized in the nucleus. This study systematically analyzed the BBX gene family in Medicago plants, which provides a basis for the study of BBX gene family tolerance to abiotic stresses.
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Regulación de la Expresión Génica de las Plantas , Familia de Multigenes , Filogenia , Proteínas de Plantas , Estrés Salino , Factores de Transcripción , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estrés Salino/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Genoma de Planta , Medicago sativa/genética , Medicago sativa/metabolismo , Medicago sativa/efectos de los fármacos , Medicago/genética , Reguladores del Crecimiento de las Plantas/farmacología , Reguladores del Crecimiento de las Plantas/metabolismo , Perfilación de la Expresión Génica , Estudio de Asociación del Genoma Completo , Estrés Fisiológico/genéticaRESUMEN
Taraxacum kok-saghyz (TKS) is a model plant and a potential rubber-producing crop for the study of natural rubber (NR) biosynthesis. The precise analysis of the NR biosynthesis mechanism is an important theoretical basis for improving rubber yield. The small rubber particle protein (SRPP) and rubber elongation factor (REF) are located in the membrane of rubber particles and play crucial roles in rubber biosynthesis. However, the specific functions of the SRPP/REF gene family in the rubber biosynthesis mechanism have not been fully resolved. In this study, we performed a genome-wide identification of the 10 TkSRPP and 2 TkREF genes' family members of Russian dandelion and a comprehensive investigation on the evolution of the ethylene/methyl jasmonate-induced expression of the SRPP/REF gene family in TKS. Based on phylogenetic analysis, 12 TkSRPP/REFs proteins were divided into five subclades. Our study revealed one functional domain and 10 motifs in these proteins. The SRPP/REF protein sequences all contain typical REF structural domains and belong to the same superfamily. Members of this family are most closely related to the orthologous species T. mongolicum and share the same distribution pattern of SRPP/REF genes in T. mongolicum and L. sativa, both of which belong to the family Asteraceae. Collinearity analysis showed that segmental duplication events played a key role in the expansion of the TkSRPP/REFs gene family. The expression levels of most TkSRPP/REF members were significantly increased in different tissues of T. kok-saghyz after induction with ethylene and methyl jasmonate. These results will provide a theoretical basis for the selection of candidate genes for the molecular breeding of T. kok-saghyz and the precise resolution of the mechanism of natural rubber production.
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Acetatos , Ciclopentanos , Etilenos , Regulación de la Expresión Génica de las Plantas , Familia de Multigenes , Oxilipinas , Filogenia , Proteínas de Plantas , Taraxacum , Oxilipinas/farmacología , Ciclopentanos/farmacología , Taraxacum/genética , Taraxacum/metabolismo , Taraxacum/efectos de los fármacos , Etilenos/farmacología , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Acetatos/farmacología , Genoma de Planta , Estudio de Asociación del Genoma CompletoRESUMEN
We present the first example of visible-light-mediated multicomponent annulation of 1,7-diynes by taking advantage of quadruple cleavage olf carbon-halogen bonds of BrCCl3 to generate a C1 synthon, which was adeptly applied to the preparation of skeletally diverse 3-benzoyl-quinolin-2(1H)-one acetates in moderate to good yields. Controlled experiments demonstrated that H2O acted as both oxygen and hydrogen sources, and gem-dichlorovinyl carbonyl compound exhibited as a critical intermediate in this process. The mechanistic pathway involves Kharasch-type addition/6-exo-dig cyclization/1,5-(SN")-substitution/elimination/binucleophilic 1,6-addition/proton transfer/tautomerization sequence.
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In this study, the design and asymmetric synthesis of a series of chiral targets of orientational chirality were conducted by taking advantage of N-sulfinylimine-assisted nucleophilic addition and modified Sonogashira catalytic coupling systems. Orientational isomers were controlled completely using alkynyl/alkynyl levers [C(sp)-C(sp) axis] with absolute configuration assignment determined by X-ray structural analysis. The key structural element of the resulting orientational chirality is uniquely characterized by remote through-space blocking. Forty examples of multi-step synthesis were performed, with modest to good yields and excellent orientational selectivity. Several chiral orientational amino targets are attached with scaffolds of natural and medicinal products, showing potential pharmaceutical and medical applications in the future.
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Objective To analyze the correlations between platelet-related parameters and the incidence of anxiety and depression in the patients undergoing peritoneal dialysis(PD),and evaluate the efficacy of the parameters in the diagnosis of anxiety and depression in PD patients. Methods A total of 245 patients undergoing PD in the First Affiliated Hospital of Hebei North University from September 2022 to February 2023 were enrolled.The generalized anxiety scale(GAD-7) and the patient health questionnaire(PHQ-9) were used to evaluate the anxiety and depression of the patients,respectively.The personal information and biochemical indicators of the patients were collected,and the platelet count(PLT),mean platelet volume(MPV),and platelet distribution width(PDW) were measured.Logistic regression was adopted to analyze the relationships of platelet-related parameters with anxiety and depression in PD patients. Results Among the 245 patients undergoing PD,the incidences of anxiety and depression were 15.9% and 38.0%,respectively.There were differences in the dialysis period(Z=-2.358,P=0.018;Z=-3.079,P=0.002),MPV(Z=-4.953,P<0.001;Z=-7.878,P<0.001),and PDW(Z=-4.587,P<0.001;Z=-7.367,P<0.001) between the anxiety group and the non-anxiety group as well as between the depression group and the non-depression group.The correlation analysis showed that MPV(r=0.358,P<0.001;r=0.489,P<0.001) and PDW(r=0.340,P<0.001;r=0.447,P<0.001) were positively correlated with anxiety and depression in the patients undergoing PD.The Logistic regression model showed that MPV(P=0.022,P=0.011),PDW(P=0.041,P=0.018),and dialysis period(P=0.011,P=0.030) were independent risk factors for the anxiety and depressive state in PD patients.The areas under the receiver operating characteristic curve of MPV in the diagnosis of anxiety and depression in PD patients were 0.750 and 0.800,respectively,and those of PDW were 0.732 and 0.780,respectively. Conclusion MPV and PDW have high efficacy in the diagnosis of anxiety and depression associated with PD and can be used as objective indicators to evaluate the anxiety and depression in the patients undergoing PD.
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Ansiedad , Diálisis Peritoneal , Humanos , Diálisis Peritoneal/efectos adversos , Hospitales , Modelos Logísticos , Curva ROCRESUMEN
To investigate the toxic mechanism of SiO2 nanoparticles (nSiO2) and polystyrene microplastics (mPS) on microalgae Nitzschia closterium f. minutissima, growth inhibition tests were carried out. The growth and biological responses of the algae exposed to nSiO2 (0.5, 1, 2, 5, 10, 30 mg L-1) and mPS (1, 5, 10, 30 and 75 mg L-1) were explored in f/2 media for 96 h. Both micro-/nano-particles (MNPs) inhibited the growth of N. closterium f. minutissima in a concentration- and time-dependent manner. The toxic effect of mPS on N. closterium f. minutissima is higher than that of nSiO2, because silicon is essential for diatoms to maintain cell wall integrity, and the addition of appropriate amounts of nSiO2 can be absorbed and used as a nutrient to promote diatom growth and protect the integrity of the siliceous shell to some extent. Both MNPs induce the production of excess oxidation and activate the cellular antioxidant defense system, leading to increased SOD and CAT activity as a means to resist oxidative damage to the cell, and eliminating excess ROS and maintaining normal cell morphology and metabolism. SEM is consistent with the results of MDA, showing that mPS with high concentrations attach to the surface of algal cells to produce heterogeneous aggregates and disrupt the cell wall and cell membrane, causing the cells to expand and rupture. This study contributes to the understanding of the size effect of MNPs on the growth of marine diatom.
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Closterium , Diatomeas , Contaminantes Químicos del Agua , Microplásticos , Dióxido de Silicio/toxicidad , Dióxido de Silicio/metabolismo , Plásticos , Contaminantes Químicos del Agua/metabolismoRESUMEN
The first photocatalytic trichloromethyl radical-triggered annulative reactions of amide-linked 1,7-diynes with polyhalomethanes were established for the flexible assembly of functionalized quinolin-2(1H)-ones with generally acceptable yields. With the installation of the aryl group (R1) into the alkynyl moiety, C-center radical-initiated Kharasch-type addition/nucleophilic substitution/elimination cascade to produce quinolin-2(1H)-ones-incorporating gem-dihaloalkene, whereas three examples of polyhalogenated quinolin-2(1H)-ones were afforded when amide-linked 1,7-diynes bearing two terminal alkyne units were subjected to BrCX3 by exploiting dry acetonitrile as a solvent.
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In this paper, we successfully synthesize phosphoric acid functionalized graphene oxide (PGO) based on acid modification of graphene oxide. The composite membrane is further prepared by adding PGO into sulfonated poly(aryl ether ketone sulfone) containing carboxyl groups matrix (C-SPAEKS). The PGO as well as the composite membranes were characterized by a series of tests. The prepared composite proton exchange membranes (PEMs) have good mechanical and electrochemical properties. Compared to the C-SPAEKS membrane, the best composite membrane has a tensile strength of 40.7 MPa while exhibiting superior proton conductivity (110.17 mS cm-1 at 80 °C). In addition, the open-circuit voltage and power density of C-SPAEKS@1% PGO are 0.918 V and 792.17 mW cm-2, respectively. Compared with C-SPAEKS (0.867 V and 166 mW cm-2), it can be seen that our work has a certain effect on the improvement of the single cell performance. The above results demonstrate that the functionalized graphene oxide has greatly improved the electrochemical performance and even the overall performance of PEMs.
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Hydrogels incorporating natural biopolymer and adhesive substances have extensively been used to develop bioactive drugs and to design cells encapsulating sturdy structure for biomedical applications. However, the conjugation of the adhesive in most hydrogels is insufficient to maintain long-lasting biocompatibility inadequate to accelerate internal organ tissue repair in the essential native cellular microenvironment. The current work elaborates the synthesis of charged choline-catechol ionic liquid (BIL) adhesive and a hydrogel with an electronegative atom rich polyphenol (PU)-laden gelatinmethacryloyl (GelMA) to improve the structural bioactivities for in vivo tracheal repair by inducing swift crosslinking along with durable mechanical and tissue adhesive properties. It was observed that bioactive BIL and PU exhibited potent antioxidant (IC 50 % of 7.91 µg/mL and 24.55 µg/mL) and antibacterial activity against E. coli, P. aeruginosa and S. aureus. The novel integration of photocurable GelMA-BIL-PU revealed outstanding mechanical strength, biodegradability and sustained drug release. The in vitro study showed exceptional cell migration and proliferation in HBECs, while in vivo investigation of the GelMA-BIL-PU hydrogel on a rat's tracheal model revealed remarkable tracheal reconstruction, concurrently reducing tissue inflammation. Furthermore, the optimized GelMA-BIL-PU injectable adhesive bioink blend demonstrated superior MSCs migration and proliferation, which could be a strong candidate for developing stem cell-rich biomaterials to address multiple organ defects.