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1.
ACS Appl Mater Interfaces ; 16(26): 34156-34166, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38902850

RESUMO

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.

2.
Eur J Med Res ; 29(1): 311, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38845036

RESUMO

OBJECTIVE: Our study aimed to determine whether there exists an association between low-grade systemic inflammation, as measured by serum C-reactive protein (CRP), and the risk of lower-extremity deep venous thrombosis (LEDVT) in patients with primary intracerebral hemorrhage (ICH). METHODS: This observational study was retrospectively conducted on patients with primary ICH who were presented to two tertiary medical centers between January 2021 and August 2022. The primary outcome was detecting LEDVT occurrence within 14 days from the onset of the acute ICH episode. Weighted logistic regression and restricted cubic spline models were employed to estimate the association between CRP and LEDVT following 1:1 propensity score matching (PSM). RESULTS: Of the 538 patients with primary ICH who met the inclusion criteria, 76 (14.13%) experienced LEDVT. Based on the cut-off levels of CRP measured upon admission from the receiver operating characteristic (ROC) curve, patients with primary ICH were categorized into two groups: (i) CRP < 1.59 mg/L and (ii) CRP ≥ 1.59 mg/L. After 1:1 PSM, the LEDVT events occurred in 24.6% of patients with CRP ≥ 1.59 mg/L and 4.1% of patients with CRP < 1.59 mg/L (P < 0.001). ROC curve revealed the area under the ROC curve of 0.717 [95% confidence interval (CI) 0.669-0.761, P < 0.001] for CRP to predict LEDVT with a sensitivity of 85.71% and specificity of 56.29%. After adjusting for all confounding variables, the occurrence of LEDVT in ICH patients with higher CRP levels (≥ 1.59 mg/L) was 10.8 times higher compared to those with lower CRP levels (95% CI 4.5-25.8, P < 0.001). A nonlinear association was observed between CRP and an increased risk of LEDVT in the fully adjusted model (P for overall < 0.001, P for nonlinear = 0.001). The subgroup results indicated a consistent positive link between CRP and LEDVT events following primary ICH. CONCLUSIONS: Higher initial CRP levels (CRP as a dichotomized variable) in patients with primary ICH are significantly associated with an increased risk of LEDVT and may help identify high-risk patients with LEDVT. Clinicians should be vigilant to enable early and effective intervention in patients at high risk of LEDVT.


Assuntos
Proteína C-Reativa , Hemorragia Cerebral , Extremidade Inferior , Trombose Venosa , Humanos , Proteína C-Reativa/metabolismo , Proteína C-Reativa/análise , Masculino , Feminino , Trombose Venosa/sangue , Trombose Venosa/etiologia , Hemorragia Cerebral/sangue , Hemorragia Cerebral/etiologia , Pessoa de Meia-Idade , Extremidade Inferior/irrigação sanguínea , Estudos Retrospectivos , Idoso , Biomarcadores/sangue , Curva ROC , Fatores de Risco
3.
Brief Bioinform ; 25(4)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38836702

RESUMO

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.


Assuntos
Aneuploidia , Teste Pré-Natal não Invasivo , Humanos , Feminino , Gravidez , Teste Pré-Natal não Invasivo/métodos , Algoritmos , Genômica/métodos , Diagnóstico Pré-Natal/métodos , Análise de Sequência de DNA/métodos
4.
Front Vet Sci ; 11: 1409084, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38872797

RESUMO

Northwest Xizang White Cashmere Goat (NXWCG) is the first new breed of cashmere goat in the Xizang Autonomous Region. It has significant characteristics of extremely high fineness, gloss, and softness. Genome-wide association analysis is an effective biological method used to measure the consistency and correlation of genotype changes between two molecular markers in the genome. In addition, it can screen out the key genes affecting the complex traits of biological individuals. The aim of this study was to analyze the genetic mechanism of cashmere trait variation in NXWCG and to discover SNP locus and key genes closely related to traits such as superfine cashmere. Additionally, the key genes near the obtained significant SNPs were analyzed by gene function annotation and biological function mining. In this study, the phenotype data of the four traits (cashmere length, fiber length, cashmere diameter, and cashmere production) were collected. GGP_Goat_70K SNP chip was used for genotyping the ear tissue DNA of the experimental group. Subsequently, the association of phenotype data and genotype data was performed using Gemma-0.98.1 software. A linear mixed model was used for the association study. The results showed that four fleece traits were associated with 18 significant SNPs at the genome level and 232 SNPs at the chromosome level, through gene annotated from Capra hircus genome using assembly ARS1. A total of 107 candidate genes related to fleece traits were obtained. Combined with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, we can find that CLNS1A, CCSER1, RPS6KC1, PRLR, KCNRG, KCNK9, and CLYBL can be used as important candidate genes for fleece traits of NXWCG. We used Sanger sequencing and suitability chi-square test to further verify the significant loci and candidate genes screened by GWAS, and the results show that the base mutations loci on the five candidate genes, CCSER1 (snp12579, 34,449,796, A → G), RPS6KC1 (snp41503, 69,173,527, A → G), KCNRG (snp41082, 67,134,820, G → A), KCNK9 (14:78472665, 78,472,665, G → A), and CLYBL (12: 9705753, 9,705,753, C → T), significantly affect the fleece traits of NXWCG. The results provide a valuable basis for future research and contribute to a better understanding of the genetic structure variation of the goat.

5.
Int J Mol Sci ; 25(11)2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38891967

RESUMO

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.


Assuntos
Regulação da Expressão Gênica de Plantas , Família Multigênica , Filogenia , Proteínas de Plantas , Estresse Salino , Fatores de Transcrição , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Salino/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Genoma de Planta , Medicago sativa/genética , Medicago sativa/metabolismo , Medicago sativa/efeitos dos fármacos , Medicago/genética , Reguladores de Crescimento de Plantas/farmacologia , Reguladores de Crescimento de Plantas/metabolismo , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Estresse Fisiológico/genética
6.
JCI Insight ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916953

RESUMO

Autosomal dominant optic atrophy plus (ADOA+) is characterized by primary optic nerve atrophy accompanied by a spectrum of degenerative neurological symptoms. Despite ongoing research, no effective treatments are currently available for this condition. Our study provided evidence for the pathogenicity of an unreported c.1780T>C variant in the OPA1 gene through patient-derived skin fibroblasts and an engineered HEK293T cell line with OPA1 downregulation. We demonstrated that OPA1 insufficiency promoted mitochondrial fragmentation and increased DRP1 expression, disrupting mitochondrial dynamics. Consequently, this disruption enhanced mitophagy and caused mitochondrial dysfunction, contributing to the ADOA+ phenotype. Notably, the Drp1 inhibitor, mitochondrial division inhibitor-1 (Mdivi-1), effectively mitigated the adverse effects of OPA1 impairment. These effects included reduced Drp1 phosphorylation, decreased mitochondrial fragmentation, and balanced mitophagy. Thus, we propose that intervening in DRP1 with Mdivi-1 could correct mitochondrial abnormalities, offering a promising therapeutic approach for managing ADOA+.

7.
Molecules ; 29(10)2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38792134

RESUMO

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.

8.
Int J Biol Macromol ; 271(Pt 2): 132506, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38772466

RESUMO

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.


Assuntos
Gelatina , Hidrogéis , Células-Tronco Mesenquimais , Metacrilatos , Polifenóis , Traqueia , Traqueia/efeitos dos fármacos , Gelatina/química , Polifenóis/farmacologia , Polifenóis/química , Animais , Ratos , Metacrilatos/química , Metacrilatos/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Hidrogéis/química , Hidrogéis/farmacologia , Regeneração/efeitos dos fármacos , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Proliferação de Células/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/química , Movimento Celular/efeitos dos fármacos , Adesivos Teciduais/química , Adesivos Teciduais/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia
9.
J Agric Food Chem ; 72(21): 12146-12155, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38747516

RESUMO

In this study, an α-amylase-responsive controlled-release formulation was developed by capping polydopamine onto ß-cyclodextrin-modified abamectin-loaded hollow mesoporous silica nanoparticles. The prepared Aba@HMS@CD@PDA were subjected to characterization using various analytical techniques. The findings revealed that Aba@HMS@CD@PDA, featuring a loading rate of 18.8 wt %, displayed noteworthy release behavior of abamectin in the presence of α-amylase. In comparison to abamectin EC, Aba@HMS@CD@PDA displayed a significantly foliar affinity and improved rainfastness on lotus leaves. The results of field trail demonstrated a significantly higher control efficacy against Spodoptera litura Fabricius compared to abamectin EC at all concentrations after 7, 14, and 21 days of spaying, showcasing the remarkable persistence of Aba@HMS@CD@PDA. These results underscore the potential of Aba@HMS@CD@PDA as a novel and persistently effective strategy for sustainable on-demand crop protection. The application of nanopesticides can enhance the effectiveness and efficiency of pesticide utilization, contributing to more sustainable agricultural practices.


Assuntos
Proteção de Cultivos , Inseticidas , Nanopartículas , Spodoptera , alfa-Amilases , Animais , alfa-Amilases/química , alfa-Amilases/metabolismo , alfa-Amilases/antagonistas & inibidores , Nanopartículas/química , Proteção de Cultivos/métodos , Spodoptera/efeitos dos fármacos , Inseticidas/química , Inseticidas/farmacologia , Ivermectina/análogos & derivados , Ivermectina/química , Ivermectina/farmacologia , Polímeros/química , Dióxido de Silício/química , Controle de Insetos , Praguicidas/química , Praguicidas/farmacologia , Indóis/química , Indóis/farmacologia
10.
BMC Genomics ; 25(1): 538, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822239

RESUMO

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.


Assuntos
DNA Mitocondrial , Sequenciamento de Nucleotídeos em Larga Escala , Doenças Mitocondriais , Humanos , DNA Mitocondrial/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Doenças Mitocondriais/genética , Doenças Mitocondriais/diagnóstico , Feminino , Masculino , Análise de Sequência de DNA/métodos , Adulto , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase/métodos
11.
Front Chem ; 12: 1371978, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38595704

RESUMO

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.

12.
Org Lett ; 26(18): 3828-3833, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38684050

RESUMO

The photocatalyzed radical-triggered thio/selenosulfonylation-bicyclization of indole-tethered 1,6-enynes has been established for the first time, enabling the synthesis of various previously unreported thio/selenosulfonylated benzo[c]pyrrolo[1,2,3-lm]carbazoles with moderate to good yields under mild conditions. The reaction pathway was proposed, consisting of energy transfer, homolytic cleavage, radical addition, 5-exo-dig, radical coupling, and a Mallory reaction cascade. This approach exhibits a wide substrate compatibility and excellent tolerability toward various functional groups and is characterized by its remarkable efficiency in both bond formation and annulation.

13.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38632951

RESUMO

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.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Genômica/métodos , Genoma , Algoritmos
14.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(1): 43-48, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38433630

RESUMO

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.


Assuntos
Ansiedade , Diálise Peritoneal , Humanos , Diálise Peritoneal/efeitos adversos , Hospitais , Modelos Logísticos , Curva ROC
15.
Cerebellum ; 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38429489

RESUMO

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.

16.
J Org Chem ; 89(7): 4877-4887, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38457276

RESUMO

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.

17.
Chemistry ; 30(28): e202400005, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38497560

RESUMO

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.

18.
Front Immunol ; 15: 1345586, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38515756

RESUMO

Introduction: T cell receptor (TCR) repertoires provide valuable insights into complex human diseases, including cancers. Recent advancements in immune sequencing technology have significantly improved our understanding of TCR repertoire. Some computational methods have been devised to identify cancer-associated TCRs and enable cancer detection using TCR sequencing data. However, the existing methods are often limited by their inadequate consideration of the correlations among TCRs within a repertoire, hindering the identification of crucial TCRs. Additionally, the sparsity of cancer-associated TCR distribution presents a challenge in accurate prediction. Methods: To address these issues, we presented DeepLION2, an innovative deep multi-instance contrastive learning framework specifically designed to enhance cancer-associated TCR prediction. DeepLION2 leveraged content-based sparse self-attention, focusing on the top k related TCRs for each TCR, to effectively model inter-TCR correlations. Furthermore, it adopted a contrastive learning strategy for bootstrapping parameter updates of the attention matrix, preventing the model from fixating on non-cancer-associated TCRs. Results: Extensive experimentation on diverse patient cohorts, encompassing over ten cancer types, demonstrated that DeepLION2 significantly outperformed current state-of-the-art methods in terms of accuracy, sensitivity, specificity, Matthews correlation coefficient, and area under the curve (AUC). Notably, DeepLION2 achieved impressive AUC values of 0.933, 0.880, and 0.763 on thyroid, lung, and gastrointestinal cancer cohorts, respectively. Furthermore, it effectively identified cancer-associated TCRs along with their key motifs, highlighting the amino acids that play a crucial role in TCR-peptide binding. Conclusion: These compelling results underscore DeepLION2's potential for enhancing cancer detection and facilitating personalized cancer immunotherapy. DeepLION2 is publicly available on GitHub, at https://github.com/Bioinformatics7181/DeepLION2, for academic use only.


Assuntos
Neoplasias , Receptores de Antígenos de Linfócitos T , Humanos , Peptídeos , Imunoterapia , Neoplasias/genética
19.
Int J Neurosci ; : 1-10, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38497924

RESUMO

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.

20.
Food Chem ; 446: 138880, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38432140

RESUMO

Biodegradable food packaging films with good antimicrobial properties are highly sought after for prolonging the shelf-life of fruits and vegetables whilst minimizing waste streams originating from the food sector. In this work, a series of PBAT/PLA food packaging films containing sodium dehydroacetate-loaded diatomite (SD/D) as an antimicrobial agent were fabricated. Structural analyses showed that the sodium dehydroacetate was incorporated into the pores of the diatomite. A uniform dispersion of SD/D in the composite films effectively enhanced water and gas permeability, whilst also giving the films good mechanical properties. The slow release of SD endowed the composite films with long-acting antibacterial ability (>90 % bacteriostasis rate for E. coli and >85 % bacteriostasis rate for S. aureus). The composite films were able to effectively maintain the quality of banana fruits during storage at room temperature, encouraging their use in food applications where non-biodegradable petrochemical-derived packaging films have traditionally been used.


Assuntos
Anti-Infecciosos , Terra de Diatomáceas , Embalagem de Alimentos , Pironas , Antibacterianos/farmacologia , Antibacterianos/química , Água , Escherichia coli , Staphylococcus aureus , Poliésteres/química , Anti-Infecciosos/farmacologia
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