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1.
Plant Physiol ; 195(3): 2073-2093, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38563472

RESUMO

The Arabidopsis (Arabidopsis thaliana) constitutive triple response1-10 (ctr1-10) mutant produces a reduced level of CTR1 protein and exhibits a weak ctr1 mutant phenotype. Sequence analysis revealed highly active translation of the upstream open reading frame (uORF) at the extended 5'-UTR of the ctr1-10 mRNA, resulting from T-DNA insertion. Enhancer screening for ctr1-10 isolated the fragile histidine triad-1 (fhit-1) mutation. The fhit-1 ctr1-10 mutant phenotypically resembled strong ctr1 mutants and barely produced CTR1, and the fhit-1 mutation reduced the translation efficiency of ctr1-10 but not that of CTR1 mRNA. The human (Homo sapiens) Fhit that involves tumorigenesis and genome instability has the in vitro dinucleotide 5',5'″-P1, P3-triphosphate hydrolase activity, and expression of the human HsFHIT or the hydrolase-defective HsFHITH96N transgene reversed the fhit-1 ctr1-10 mutant phenotype and restored CTR1 levels. Genetic editing that in situ disrupts individual upstream ATG codons proximal to the ctr1-10 mORF elevated CTR1 levels in ctr1-10 plants independent of FHIT. EUKARYOTIC INITIATION FACTOR3G (eIF3G), which is involved in translation and reinitiation, interacted with FHIT, and both were associated with the polysome. We propose that FHIT resumes early terminated ctr1-10 mORF translation in the face of active and complex uORF translation. Our study unveils a niche that may lead to investigations on the molecular mechanism of Fhit-like proteins in translation reinitiation. The biological significance of FHIT-regulated translation is discussed.


Assuntos
Hidrolases Anidrido Ácido , Proteínas de Arabidopsis , Arabidopsis , Regulação da Expressão Gênica de Plantas , Biossíntese de Proteínas , RNA Mensageiro , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Hidrolases Anidrido Ácido/genética , Hidrolases Anidrido Ácido/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Mutação/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Regiões 5' não Traduzidas/genética , Humanos , Fenótipo , Fases de Leitura Aberta/genética
2.
Cancer Sci ; 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39420583

RESUMO

Microsatellite stability (MSS) colorectal cancer (CRC) exhibits a low mutation load and poor immunogenicity, contributing to immune escape of tumor cells and less benefit from immune checkpoint blockade (ICB) treatment. The mechanisms underlying immunotherapeutic resistance in MSS CRC remain to be elucidated. Here, we identified that nuclear proto-oncogene SET is significantly higher expressed in MSS CRC compared to microsatellite instability (MSI) CRC and facilitates immune escape of MSS CRC. Mechanistically, SET represses the expression of C-C motif chemokine ligand 5 (CCL5) and upregulates mismatch repair (MMR) proteins expression in a c-Myc-dependent manner, which inhibits infiltration and migration of CD8+ T cells to tumor tissues and results in low immunogenicity in MSS CRC. In addition, we found that SET impairs ubiquitination and proteasomal degradation of c-Myc by disrupting the interaction between E3 ligase FBXW7 and c-Myc. Moreover, SET inhibition enhances the response to immunotherapy in MSS CRC in vivo. Overall, this study reveals the critical roles and posttranslational regulatory mechanism of SET in immune escape and highlights the SET/c-Myc axis as a potential target for immunotherapy of MSS CRC that have implications for targeting a unique aspect of this disease.

3.
Anal Chem ; 96(5): 1872-1879, 2024 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-38225884

RESUMO

Detecting proteins in ultralow concentrations in complex media is important for many applications but often relies on complicated techniques. Herein, a single-molecule protein analyzer with the potential for high-throughput applications is reported. Gold-coated magnetic nanoparticles with DNA-labeled antibodies were used for target recognition and separation. The immunocomplex was loaded into microdroplets generated with centrifugation. Immuno-PCR amplification of the DNA enabled the quantification of proteins at the level of single molecules. As an example, ultrasensitive detection of α-synuclein, a biomarker for neurodegenerative diseases, is achieved. The limit of detection was determined to be ∼50 aM in buffer and ∼170 aM in serum. The method exhibited high specificity and could be used to analyze post-translational modifications such as protein phosphorylation. This study will inspire wider studies on single-molecule protein detection, especially in disease diagnostics, biomarker discovery, and drug development.


Assuntos
Nanopartículas de Magnetita , Nanopartículas Metálicas , Testes Imunológicos , DNA , Magnetismo , Biomarcadores/análise , Ouro
4.
Chembiochem ; : e202400512, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39192477

RESUMO

Bovine milk exosomes (BmExo) have been identified as versatile nanovesicles for anti-cancer drugs delivery due to their natural availability and biocompatibility. However, tumor-specific delivery based on BmExo often requires post-isolation modifications of the membrane surface with active-targeting ligands. In this study, we report an alternative approach to functionalize BmExo with nanobody combining facile chemical modification and Sortase A-mediated site-specific ligation, as demonstrated by the development of an epidermal growth factor receptor (EGFR)-targeted drug delivery system. The BmExo membrane was first coated with a diglycine-containing amphiphile molecule, NH2-GG-PEG2000-DSPE, by hydrophobic insertion. The diglycine as nucleophiles displayed on the membrane enabled the subsequent ligation of the EGFR nanobody (7D12) by Sortase A (SrtA)-mediated site-specific transpeptidation. The successful construction of BmExo-7D12 was confirmed by Western blotting analysis, electron microscopy, and dynamic light scattering (DLS). As a demonstration model, BmExo-7D12 loaded with the chemotherapeutic drug doxorubicin (Dox) was shown to be able to deliver Dox to cancer cells in response to the expression of EGFR as manifested by immunocytochemistry and flow cytometry analysis. Finally, the cytotoxicity assay showed that BmExo-7D12-Dox was more effective in killing tumor cells with high EGFR expression while significantly reduced the non-specific toxicity to EGFR negative cells. In conclusion, these results demonstrate that 7D12-functionalized BmExo can serve as a target-specific delivery system for Dox to selectively kill EGFR-expressing tumor cells. This approach should prove to be versatile and efficient for the generation of protein-ligands modified BmExo.

5.
Mol Carcinog ; 63(9): 1750-1767, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38860604

RESUMO

The incidence and mortality rates of gastric cancer (GC) remain alarmingly high worldwide, imposing a substantial healthcare burden. In this study, we utilized data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A 4-gene prognostic model was developed to predict patient prognosis, and its accuracy was validated across multiple datasets. Patients with a low-risk score exhibited improved prognosis, elevated tumor mutation burden, heightened sensitivity to both immunotherapy and conventional chemotherapy. Notably, our investigation revealed that the key gene RGS5 positively modulates the expression of mismatch repair proteins via c-Myc. Furthermore, co-immunoprecipitation (COIP) assays demonstrated the interaction between RGS5 and c-Myc. Additionally, we confirmed that RGS5 regulates c-Myc through the ubiquitin-proteasome pathway. Moreover, RGS5 was identified as a positive regulator of PD-L1 expression and exhibited a negative correlation with the majority of immune cells. These findings underscore the potential of RGS5 as a novel biomarker and therapeutic target in the context of GC.


Assuntos
Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas c-myc , Proteínas RGS , Neoplasias Gástricas , Humanos , Proteínas RGS/genética , Proteínas RGS/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Reparo de Erro de Pareamento de DNA , Complexo de Endopeptidases do Proteassoma/metabolismo , Complexo de Endopeptidases do Proteassoma/genética
6.
New Phytol ; 241(6): 2464-2479, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38287207

RESUMO

Abscisic acid (ABA) and gibberellins (GA) antagonistically mediate several biological processes, including seed germination, but the molecular mechanisms underlying ABA/GA antagonism need further investigation, particularly any role mediated by a transcription factors module. Here, we report that the DELLA protein RGL2, a repressor of GA signaling, specifically interacts with ABI4, an ABA signaling enhancer, to act as a transcription factor complex to mediate ABA/GA antagonism. The rgl2, abi3, abi4 and abi5 mutants rescue the non-germination phenotype of the ga1-t. Further, we demonstrate that RGL2 specifically interacts with ABI4 to form a heterodimer. RGL2 and ABI4 stabilize one another, and GA increases the ABI4-RGL2 module turnover, whereas ABA decreases it. At the transcriptional level, ABI4 enhances the RGL2 expression by directly binding to its promoter via the CCAC cis-element, and RGL2 significantly upregulates the transcriptional activation ability of ABI4 toward its target genes, including ABI5 and RGL2. Abscisic acid promotes whereas GA inhibits the ability of ABI4-RGL2 module to activate transcription, and ultimately ABA and GA antagonize each other. Genetic analysis demonstrated that both ABI4 and RGL2 are essential for the activity of this transcription factor module. These results suggest that the ABI4-RGL2 module mediates ABA/GA antagonism by functioning as a double agent.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Ácido Abscísico/farmacologia , Ácido Abscísico/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Germinação , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Giberelinas/farmacologia , Giberelinas/metabolismo , Sementes/genética
7.
J Hum Genet ; 69(1): 33-39, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37853116

RESUMO

Duane retraction syndrome (DRS) is a rare congenital eye movement disorder causing by the dysplasia of abducens nerve, and has highly variable phenotype. MRI can reveal the endophenotype of DRS. Most DRS cases are sporadical and isolated, while some are familial or accompanied by other ocular disorders and systemic congenital abnormalities. CHN1 was the most common causative gene for familial DRS. Until now, 13 missense variants of CHN1 have been reported. In this study, we enrolled two unrelated pedigrees with DRS. Detailed clinical examinations, MRI, and the whole exome sequencing (WES) were performed to reveal their clinical and genetic characteristics. Patients from pedigree-1 presented with isolated DRS, and a novel heterozygous variant c.650 A > G, p. His217Arg was identified in CHN1 gene. Patients from pedigree-2 presented with classic DRS and abnormalities in auricle morphology, and the pedigree segregated another novel heterozygous CHN1 variant c.637 T > C, p. Phe213Leu. A variety of bioinformatics software predicted that the two variants had deleterious or disease-causing effects. After injecting of two mutant CHN1 mRNAs into zebrafish embryos, the dysplasia of ocular motor nerves (OMN) was observed. Our present findings expanded the phenotypic and genotypic spectrum of CHN1 related DRS, as well as provided new insights into the role of CHN1 in OMN development. Genetic testing is strongly recommended for patients with a DRS family history or accompanying systemic congenital abnormalities.


Assuntos
Síndrome da Retração Ocular , Anormalidades do Olho , Animais , Humanos , Síndrome da Retração Ocular/genética , Peixe-Zebra/genética , Linhagem , Mutação de Sentido Incorreto
8.
Plant Physiol ; 191(1): 265-279, 2023 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-36047837

RESUMO

Cell cycle progression and the phytohormones auxin and abscisic acid (ABA) play key roles in primary root growth, but how ABA mediates the transcription of cell cycle-related genes and the mechanism of crosstalk between ABA and auxin requires further research. Here, we report that ABA inhibits primary root growth by regulating the ABA INSENSITIVE4 (ABI4)-CYCLIN-DEPENDENT KINASE B2;2 (CDKB2;2)/CYCLIN B1;1 (CYCB1;1) module-mediated cell cycle as well as auxin biosynthesis in Arabidopsis (Arabidopsis thaliana). ABA induced ABI4 transcription in the primary root tip, and the abi4 mutant showed an ABA-insensitive phenotype in primary root growth. Compared with the wild type (WT), the meristem size and cell number of the primary root in abi4 increased in response to ABA. Further, the transcription levels of several cell-cycle positive regulator genes, including CDKB2;2 and CYCB1;1, were upregulated in abi4 primary root tips. Subsequent chromatin immunoprecipitation (ChIP)-seq, ChIP-qPCR, and biochemical analysis revealed that ABI4 repressed the expression of CDKB2;2 and CYCB1;1 by physically interacting with their promoters. Genetic analysis demonstrated that overexpression of CDKB2;2 or CYCB1;1 fully rescued the shorter primary root phenotype of ABI4-overexpression lines, and consistently, abi4/cdkb2;2-cr or abi4/cycb1;1-cr double mutations largely rescued the ABA-insensitive phenotype of abi4 with regard to primary root growth. The expression levels of DR5promoter-GFP and PIN1promoter::PIN1-GFP in abi4 primary root tips were significantly higher than those in WT after ABA treatment, with these changes being consistent with changes in auxin concentration and expression patterns of auxin biosynthesis genes. Taken together, these findings indicated that ABA inhibits primary root growth through ABI4-mediated cell cycle and auxin-related regulatory pathways.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Ácido Abscísico/farmacologia , Ácido Abscísico/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Arabidopsis/metabolismo , Divisão Celular , Ácidos Indolacéticos/metabolismo , Regulação da Expressão Gênica de Plantas
9.
Electrophoresis ; 45(5-6): 463-473, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37946554

RESUMO

Next-generation sequencing (NGS) allows for better identification of insertion and deletion polymorphisms (InDels) and their combination with adjacent single nucleotide polymorphisms (SNPs) to form compound markers. These markers can improve the polymorphism of microhaplotypes (MHs) within the same length range, and thus, boost the efficiency of DNA mixture analysis. In this study, we screened InDels and SNPs across the whole genome and selected highly polymorphic markers composed of InDels and/or SNPs within 300 bp. Further, we successfully developed and evaluated an NGS-based panel comprising 55 loci, of which 24 were composed of both SNPs and InDels. Analysis of 124 unrelated Southern Han Chinese revealed an average effective number of alleles (Ae ) of 7.52 for this panel. The cumulative power of discrimination and cumulative probability of exclusion values of the 55 loci were 1-2.37 × 10-73 and 1-1.19 × 10-28 , respectively. Additionally, this panel exhibited high allele detection rates of over 97% in each of the 21 artificial mixtures involving from two to six contributors at different mixing ratios. We used EuroForMix to calculate the likelihood ratio (LR) and evaluate the evidence strength provided by this panel, and it could assess evidence strength with LR, distinguishing real and noncontributors. In conclusion, our panel holds great potential for detecting and analyzing DNA mixtures in forensic applications, with the capability to enhance routine mixture analysis.


Assuntos
Impressões Digitais de DNA , Polimorfismo de Nucleotídeo Único , Humanos , Polimorfismo de Nucleotídeo Único/genética , Análise de Sequência de DNA , DNA/genética , DNA/análise , Sequenciamento de Nucleotídeos em Larga Escala , Frequência do Gene
10.
Cancer Treat Res ; 192: 233-263, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39212924

RESUMO

In USA, colorectal cancer is the third most commonly diagnosed cancer in men, second in women, as well as the third leading cause of cancer deaths (Siegel et al. in Cancer J Clin 73:1-112, 2023 [109]). Worldwide, colorectal cancer is the second leading cause of death and causes almost 916,000 deaths each year (Ferlay in Global cancer observatory: cancer today. International Agency for Research on Cancer, Lyon, 2020 [28]). Fortunately, due to the colon's surgical and endoscopic accessibility and functional redundancy, colorectal cancer is very treatable. Colonoscopic surveillance has the potential for not only providing tissue for the diagnosis of precancerous polyps and invasive carcinoma, but also preventing development of invasive carcinoma by the removal of precancerous lesions. This chapter discusses the clinical and pathologic features of the spectrum of epithelial, hematolymphoid, and mesenchymal malignant tumors of the colon, rectum, appendix, and anus.


Assuntos
Neoplasias do Ânus , Neoplasias Retais , Humanos , Neoplasias do Ânus/patologia , Neoplasias do Ânus/terapia , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Neoplasias Retais/diagnóstico , Neoplasias do Colo/patologia
11.
J Pineal Res ; 76(5): e13004, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39145574

RESUMO

Both seed germination and subsequent seedling establishment are key checkpoints during the life cycle of seed plants, yet flooding stress markedly inhibits both processes, leading to economic losses from agricultural production. Here, we report that melatonin (MT) seed priming treatment enhances the performance of seeds from several crops, including soybean, wheat, maize, and alfalfa, under flooding stress. Transcriptome analysis revealed that MT priming promotes seed germination and seedling establishment associated with changes in abscisic acid (ABA), gibberellin (GA), and reactive oxygen species (ROS) biosynthesis and signaling pathways. Real-time quantitative RT-PCR (qRT-PCR) analysis confirmed that MT priming increases the expression levels of GA biosynthesis genes, ABA catabolism genes, and ROS biosynthesis genes while decreasing the expression of positive ABA regulatory genes. Further, measurements of ABA and GA concentrations are consistent with these trends. Following MT priming, quantification of ROS metabolism-related enzyme activities and the concentrations of H2O2 and superoxide anions (O2 -) after MT priming were consistent with the results of transcriptome analysis and qRT-PCR. Finally, exogenous application of GA, fluridone (an ABA biosynthesis inhibitor), or H2O2 partially rescued the poor germination of non-primed seeds under flooding stress. Collectively, this study uncovers the application and molecular mechanisms underlying MT priming in modulating crop seed vigor under flooding stress.


Assuntos
Ácido Abscísico , Inundações , Germinação , Giberelinas , Melatonina , Espécies Reativas de Oxigênio , Plântula , Sementes , Melatonina/farmacologia , Melatonina/metabolismo , Germinação/efeitos dos fármacos , Ácido Abscísico/metabolismo , Giberelinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Plântula/metabolismo , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Plântula/genética , Sementes/efeitos dos fármacos , Sementes/metabolismo , Sementes/crescimento & desenvolvimento , Sementes/genética , Estresse Fisiológico , Produtos Agrícolas/metabolismo , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos
12.
Nanotechnology ; 35(28)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38574484

RESUMO

Nitrogen dioxide (NO2) is a major pollutant that poses significant risks to sustainable human life. As a result, a growing focus has been placed on the development of highly selective and sensitive gas sensors for NO2. Traditional cutting-edge non-organic NO2gas detectors often necessitate stringent production conditions and potentially harmful materials, which are not environmentally friendly, and these shortcomings have limited their widespread practical use. To overcome these challenges, we synthesized self-assembled peptide nanotubes (SPNTs) through a molecular self-assembly process. The SPNTs were then combined with SnO2in varying proportions to construct NO2gas sensors. The design of this sensor ensured efficient electron transfer and leverage the extensive surface area of the SPNTs for enhanced gas adsorption and the effective dispersion of SnO2nanoparticles. Notably, the performance of the sensor, including its sensitivity, response time, and recovery rate, along with a lower detection threshold, could be finely tuned by varying the SPNTs content. This approach illustrated the potential of bioinspired methodologies, using peptide self-assemblies, to develop integrated sensors for pollutant detection, providing a significant development in environmentally conscious sensor technology.


Assuntos
Nanocompostos , Nanotubos de Peptídeos , Dióxido de Nitrogênio , Compostos de Estanho , Compostos de Estanho/química , Dióxido de Nitrogênio/análise , Nanotubos de Peptídeos/química , Nanocompostos/química , Temperatura
13.
Phys Chem Chem Phys ; 26(37): 24564-24576, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39268710

RESUMO

Transforming growth factor ß type 1 receptor (TGFßR1), a crucial serine-threonine kinase, is central to the TGFß/Smad signaling pathway, governing cellular processes like growth, differentiation, apoptosis, and immune response. This pathway is closely linked to the epithelial-mesenchymal transition (EMT) process, which plays an important role in the metastasis of hepatocellular carcinoma (HCC). To date, only limited inhibitors targeting TGFßR1 have entered clinical trials, yet they encounter challenges, notably high toxicity, in clinical applications. Herein, an efficient virtual screening pipeline was developed. Eighty compounds were screened from a pool of over 17 million molecules based on docking scores and binding free energy. Four compounds were manually selected with the assistance of enhanced sampling method BPMD (binding pose metadynamics). The binding stability of these four compounds complexed with TGFßR1 was subsequently studied through long-timescale conventional molecular dynamics simulations. The three most promising compounds were subjected to in vitro bioactivity assays. Cpd272 demonstrated moderate inhibitory activity against TGFßR1, with an IC50 value of 1.57 ± 0.33 µM. Moreover, it exhibited cytotoxic effects on human hepatocellular carcinoma cell line Bel-7402. By shedding light on the binding mode of the receptor-ligand complexes, Cpd272 was identified as a hit compound featuring a novel urea-based scaffold capable of effectively inhibiting TGFßR1.


Assuntos
Simulação de Dinâmica Molecular , Receptor do Fator de Crescimento Transformador beta Tipo I , Ureia , Humanos , Receptor do Fator de Crescimento Transformador beta Tipo I/antagonistas & inibidores , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/química , Ureia/química , Ureia/farmacologia , Ureia/análogos & derivados , Simulação de Acoplamento Molecular , Descoberta de Drogas , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Linhagem Celular Tumoral , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia
14.
J Chem Ecol ; 50(3-4): 185-196, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38441803

RESUMO

Sea cucumbers frequently expel their guts in response to predators and an aversive environment, a behavior perceived as releasing repellents involved in chemical defense mechanisms. To investigate the chemical nature of the repellent, the viscera of stressed sea cucumbers (Apostichopus japonicus) in the Yellow Sea of China were collected and chemically analyzed. Two novel non-holostane triterpene glycosides were isolated, and the chemical structures were elucidated as 3ꞵ-O-[ꞵ-D-glucopyranosyl-(1→2)-ꞵ-D-xylopyranosyl]-(20S)-hydroxylanosta-7,25-diene-18(16)-lactone (1) and 3ꞵ-O-[ꞵ-D-quinovopyranosyl-(1→2)-ꞵ-D-xylopyranosyl]-(20S)-hydroxylanosta-7,25-diene-18(16)-lactone (2) by spectroscopic and mass-spectrometric analyses, exemplifying a triterpene glycoside constituent of an oligosaccharide containing two sugar-units and a non-holostane aglycone. Zebrafish embryos were exposed to various doses of 1 and 2 from 4 to 96 hpf. Compound 1 exposure showed 96 h-LC50 41.5 µM and an increased zebrafish mortality rates in roughly in a dose- and time-dependent manner. Compound 2, with different sugar substitution, exhibited no mortality and moderate teratogenic toxicity with a 96 h-EC50 of 173.5 µM. Zebrafish embryos exhibited teratogenic effects, such as reduced hatchability and total body length. The study found that triterpene saponin from A. japonicus viscera had acute toxicity in zebrafish embryos, indicating a potential chemical defense role in the marine ecosystem.


Assuntos
Glicosídeos , Pepinos-do-Mar , Triterpenos , Vísceras , Peixe-Zebra , Animais , Peixe-Zebra/fisiologia , Glicosídeos/química , Glicosídeos/toxicidade , Glicosídeos/metabolismo , Vísceras/química , Vísceras/efeitos dos fármacos , Triterpenos/química , Triterpenos/farmacologia , Triterpenos/metabolismo , Pepinos-do-Mar/química , Embrião não Mamífero/efeitos dos fármacos , Toxinas Marinhas/toxicidade , Toxinas Marinhas/química
15.
Chem Biodivers ; 21(6): e202400335, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38456571

RESUMO

Sea cucumbers release chemical repellents from their guts when they are in danger from predators or a hostile environment. To investigate the chemical structure of the repellent, we collected and chemically analyzed the viscera of stressed sea cucumbers (Apostichopus japonicus) in the Yellow Sea of China. Two undescribed triterpene glycosides (1 and 2), together with a known cladoloside A (3), were identified and elucidated as 3ß-O-{2-O-[ß-d-quinovopyranosyl]-4-O-[3-O-methyl-ß-d-glucopyranosyl-(1→3)-ß-d-glucopyranosyl]-ß-d-xylopyranosyl}-holosta-9(11),25(26)-dien-16-one (1), 3ß-O-{2-O-[ß-d-glucopyranosyl]-4-O-[3-O-methyl-ß-d-glucopyranosyl-(1→3)-ß-d-glucopyranosyl]-ß-d-xylopyranosyl}-holosta-9(11),25(26)-dien-16-one (2), 3ß-O-{2-O-[3-O-methyl-ß-d-glucopyranosyl-(1→3)-ß-d-xylopyranosyl-(1→4)-ß-d-quinovopyranosyl]-ß-d-xylopyranosyl}-holosta-9(11),25(26)-dien-16-one (3) by spectroscopic analysis, including HR-ESI-MS and NMR spectra. Compounds 1, 2, and 3 display embryonic toxicity, as indicated by their 96-hour post-fertilization lethal concentration (96 hpf-LC50) values of 0.289, 0.536, and 0.091 µM, respectively. Our study discovered a class of triterpene glycoside compounds consisting of an oligosaccharide with four sugar units and a holostane aglycone. These compounds possess embryotoxicity and may serve as chemical defense molecules in marine benthic ecosystems.


Assuntos
Glicosídeos , Triterpenos , Animais , Glicosídeos/química , Glicosídeos/isolamento & purificação , Glicosídeos/toxicidade , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Stichopus/química , Vísceras/química , Pepinos-do-Mar/química , Embrião não Mamífero/efeitos dos fármacos
16.
J Wound Care ; 33(Sup6): S4-S7, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38843046

RESUMO

OBJECTIVE: Non-lactational mastitis (NLM) is a benign inflammatory disease of the mammary gland, with pain, swelling and redness as the main clinical manifestations. There is no unified and effective standard treatment plan for this disease at present. In addition to breast cancer, non-lactational mastitis is also becoming a presenting complaint in an increasing number of outpatients at the authors' clinic. This case report summarises the treatment and management of a 35-year-old female patient with NLM complicated with multiple sinus wounds after surgery. METHOD: The patient was treated as follows, with: timely debridement according to the local condition of the wound, with manual compression to drain exudate from the sinus wound; selected wound dressings according to their performance and characteristics to fill the sinus tract for drainage and infection control; psychological care of the patient and their family to ensure that patients actively participate in the treatment; family support to the patient to deal with negative emotions; integrated traditional Chinese and Western medicine to prevent/manage infection; dietary care and control; posture management and health education to facilitate the patient's wound healing process. RESULTS: After local management with systemic treatment and management using integrated traditional Chinese and Western medicine, the wound healed after 46 days, with no recurrence during a follow-up period of one year. CONCLUSION: As shown in this case report, the wound should be cut and drained as soon as possible in order to prevent obstruction of the sinus drainage. Modern wound dressings are selected for the 'external' treatment of local wounds. Integrated traditional Chinese and Western medicine may help in systemic therapy of the whole patient.


Assuntos
Mastite , Cicatrização , Humanos , Feminino , Adulto , Mastite/terapia , Medicina Tradicional Chinesa , Desbridamento , Drenagem
17.
J Integr Plant Biol ; 66(5): 909-927, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38328870

RESUMO

Transcriptional regulation plays a key role in the control of seed dormancy, and many transcription factors (TFs) have been documented. However, the mechanisms underlying the interactions between different TFs within a transcriptional complex regulating seed dormancy remain largely unknown. Here, we showed that TF PHYTOCHROME-INTERACTING FACTOR4 (PIF4) physically interacted with the abscisic acid (ABA) signaling responsive TF ABSCISIC ACID INSENSITIVE4 (ABI4) to act as a transcriptional complex to promote ABA biosynthesis and signaling, finally deepening primary seed dormancy. Both pif4 and abi4 single mutants exhibited a decreased primary seed dormancy phenotype, with a synergistic effect in the pif4/abi4 double mutant. PIF4 binds to ABI4 to form a heterodimer, and ABI4 stabilizes PIF4 at the protein level, whereas PIF4 does not affect the protein stabilization of ABI4. Subsequently, both TFs independently and synergistically promoted the expression of ABI4 and NCED6, a key gene for ABA anabolism. The genetic evidence is also consistent with the phenotypic, physiological and biochemical analysis results. Altogether, this study revealed a transcriptional regulatory cascade in which the PIF4-ABI4 transcriptional activator complex synergistically enhanced seed dormancy by facilitating ABA biosynthesis and signaling.


Assuntos
Ácido Abscísico , Proteínas de Arabidopsis , Arabidopsis , Regulação da Expressão Gênica de Plantas , Dormência de Plantas , Transdução de Sinais , Fatores de Transcrição , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologia , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/genética , Dormência de Plantas/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Ligação Proteica , Sementes/metabolismo , Sementes/genética , Mutação/genética
18.
Opt Express ; 31(16): 26807-26814, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37710531

RESUMO

We report a pulse Fe: ZnSe laser pumped by an optical chopper Q-switched Er: YAG laser. By analyzed the spatial and temporal match of the gain and chopper, the maximum energy of the optical chopper Q-switched Er: YAG laser is 31mJ with the pulse width of 165 ns. By employing this Er: YAG laser as pump laser of Fe: ZnSe crystal, the maximum output energy of Fe: ZnSe laser is 10mJ with the pulse width of 80 ns at room temperature, that is the maximum energy of Fe: ZnSe laser at this Q-switched system to the best of our knowledge. We also study the directly Q-switched Fe: ZnSe laser, and the 2.7mJ mid-infrared laser with the pulse width of 200 ns is obtained at 80 K.

19.
Opt Express ; 31(20): 33435-33448, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37859126

RESUMO

Due to a great many superior features of infrared light communication (ILC), like high capacity and strong privacy, ILC is considered a potential candidate for serving the high demands of beyond fifth-generation/sixth-generation (B5G/6 G) communication systems. However, the terminal's limited field-of-view (FOV) induces great difficulty in establishing line-of-sight (LoS) link between the transceiver and the terminal. In this paper, we propose a wide-FOV auto-coupling optical antenna system that utilizes a wide-FOV telecentric lens to collect incident infrared beams and automatically couple them into a specific single-mode-fiber (SMF) channel of fiber array and optical switch. The performance of this optical antenna system is assessed through simulation and manual alignment operation, and validated by automatic alignment results. A coupling loss of less than 10.6 dB within a FOV of 100° for both downstream and upstream beams in C band is demonstrated by the designed system. Furthermore, we establish a bidirectional optical wireless communications (OWC) system employing this antenna and a fiber-type modulating retro-reflector (MRR) system in the terminal. Both 10-Gbps on-off keying (OOK) downstream and upstream transmissions are successfully realized with the FOV of up to 100° in C band where the measured bit-error-rate (BER) is lower than 3.8 × 10-3. To the best of our knowledge, this is a brand-new auto-coupling optical antenna system with the largest FOV in ILC automatic alignment works in terminals that have ever been reported.

20.
BMC Infect Dis ; 23(1): 333, 2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37198537

RESUMO

BACKGROUND: Sneathia amnii is a conditional pathogen of the female genital tract that is involved in bacterial vaginosis and poor reproductive and perinatal outcomes. Few studies have reported subcutaneous cysts following invasive infection caused by S amnii. CASE PRESENTATION: Here we report the case of a 27-year-old woman who presented with Bartholin's gland cyst due to S amnii infection, and was successfully treated with surgical neostomy and antibiotic agents. The isolate was gram-negative, bacillary, anaerobic, and was identified by polymerase chain reaction (PCR) amplification of the 16 S rRNA. CONCLUSIONS: S amni is an important but underappreciated pathogen that needs further investigation. This report describes the microbial and pathogenic characteristics of S amnii and is expected to provide a valuable reference in obstetric and gynecologic clinical practice.


Assuntos
Glândulas Vestibulares Maiores , Cistos , Feminino , Humanos , Adulto , Glândulas Vestibulares Maiores/microbiologia , Glândulas Vestibulares Maiores/patologia , Glândulas Vestibulares Maiores/cirurgia , Antibacterianos/uso terapêutico , Fusobactérias , Cistos/diagnóstico
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