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1.
Biomed Pharmacother ; 174: 116470, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38565061

RESUMO

ERCC2 plays a pivotal role in DNA damage repair, however, its specific function in cancer remains elusive. In this study, we made a significant breakthrough by discovering a substantial upregulation of ERCC2 expression in glioblastoma (GBM) tumor tissue. Moreover, elevated levels of ERCC2 expression were closely associated with poor prognosis. Further investigation into the effects of ERCC2 on GBM revealed that suppressing its expression significantly inhibited malignant growth and migration of GBM cells, while overexpression of ERCC2 promoted tumor cell growth. Through mechanistic studies, we elucidated that inhibiting ERCC2 led to cell cycle arrest in the G0/G1 phase by blocking the CDK2/CDK4/CDK6/Cyclin D1/Cyclin D3 pathway. Notably, we also discovered a direct link between ERCC2 and CDK4, a critical protein in cell cycle regulation. Additionally, we explored the potential of TRAIL, a low-toxicity death ligand cytokine with anticancer properties. Despite the typical resistance of GBM cells to TRAIL, tumor cells undergoing cell cycle arrest exhibited significantly enhanced sensitivity to TRAIL. Therefore, we devised a combination strategy, employing TRAIL with the nanoparticle DMC-siERCC2, which effectively suppressed the GBM cell proliferation and induced apoptosis. In summary, our study suggests that targeting ERCC2 holds promise as a therapeutic approach to GBM treatment.

2.
Anal Bioanal Chem ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38568233

RESUMO

Iodoacetic acid (IAA) is a halogenated disinfection by-product of growing concern due to its high cytotoxicity, genotoxicity, endocrine disruptor effects, and potential carcinogenicity. However, the data on distribution and excretion of IAA after ingestion by mammals are still scarce. Here, we developed a reliable and validated method for detecting IAA in biological specimens (plasma, urine, feces, liver, kidney, and tissues) based on modified QuEChERS sample preparation combined with gas chromatography-tandem triple quadrupole mass spectrometry (GC-MS/MS). The detection method for IAA exhibited satisfactory recovery rates (62.6-108.0%) with low relative standard deviations (RSD < 12.3%) and a low detection limit for all biological matrices ranging from 0.007 to 0.032 ng/g. The study showed that the proposed method was reliable and reproducible for analyzing IAA in biological specimens. It was successfully used to detect IAA levels in biological samples from rats given gavage administration. The results indicated that IAA was found in various tissues and organs, including plasma, thyroid, the liver, the kidney, the spleen, gastrointestinal tract, and others, 6 h after exposure. This study provides the first data on the in vivo distribution in and excretion of IAA by mammals following oral exposure.

3.
Adv Sci (Weinh) ; : e2306871, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38569495

RESUMO

RNA splicing dysregulation and the involvement of specific splicing factors are emerging as common factors in both obesity and metabolic disorders. The study provides compelling evidence that the absence of the splicing factor SRSF1 in mature adipocytes results in whitening of brown adipocyte tissue (BAT) and impaired thermogenesis, along with the inhibition of white adipose tissue browning in mice. Combining single-nucleus RNA sequencing with transmission electron microscopy, it is observed that the transformation of BAT cell types is associated with dysfunctional mitochondria, and SRSF1 deficiency leads to degenerated and fragmented mitochondria within BAT. The results demonstrate that SRSF1 effectively binds to constitutive exon 6 of Ndufs3 pre-mRNA and promotes its inclusion. Conversely, the deficiency of SRSF1 results in impaired splicing of Ndufs3, leading to reduced levels of functional proteins that are essential for mitochondrial complex I assembly and activity. Consequently, this deficiency disrupts mitochondrial integrity, ultimately compromising the thermogenic capacity of BAT. These findings illuminate a novel role for SRSF1 in influencing mitochondrial function and BAT thermogenesis through its regulation of Ndufs3 splicing within BAT.

4.
Int J Biol Macromol ; 266(Pt 2): 131425, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38583830

RESUMO

Nano-MoS2 exhibit oxidoreductase-like activities, and has been shown to effectively eliminate excessive intracellular ROS and inhibit Aß aggregation, thus demonstrating promising potential for anti-Alzheimer's disease (anti-AD) intervention. However, the low water dispersibility and high toxicity of nano-MoS2 limits its further application. In this study, we developed a chondroitin sulphate (CS)-modified MoS2 nanoenzyme (CS@MoS2) by harnessing the excellent biocompatibility of CS and the exceptional activities of nano-MoS2 to explore its potential in anti-AD research. Promisingly, CS@MoS2 significantly inhibited Aß1-40 aggregation and prevented toxic injury in SH-SY5Y cells caused by Aß1-40. In addition, CS@MoS2 protected these cells from oxidative stress damage by regulating ROS production, as well as promoting the activities of SOD and GSH-Px. CS@MoS2 also modulated the intracellular Ca2+ imbalance and downregulated Tau hyperphosphorylation by activating GSK-3ß. CS@MoS2 suppressed p-NF-κB (p65) translocation to the nucleus by inhibiting MAPK phosphorylation, and modulated the expression of downstream anti- and proinflammatory cytokines. Owing to its multifunctional activities, CS@MoS2 effectively improved spatial learning, memory, and anxiety in D-gal/AlCl3-induced AD mice. Taken together, these results indicate that CS@MoS2 has significant potential for improving the therapeutic efficacy of the prevention and treatment of AD, while also presenting a novel framework for the application of nanoenzymes.

5.
Acad Radiol ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38614827

RESUMO

RATIONALE AND OBJECTIVES: Gliomas are aggressive brain tumors with a poor prognosis. Assessing treatment response is challenging because magnetic resonance imaging (MRI) may not distinguish true progression (TP) from pseudoprogression (PsP). This review aims to discuss imaging techniques and liquid biopsies used to distinguish TP from PsP. MATERIALS AND METHODS: This review synthesizes existing literature to examine advances in imaging techniques, such as magnetic resonance diffusion imaging (MRDI), perfusion-weighted imaging (PWI) MRI, and liquid biopsies, for identifying TP or PsP through tumor markers and tissue characteristics. RESULTS: Advanced imaging techniques, including MRDI and PWI MRI, have proven effective in delineating tumor tissue properties, offering valuable insights into glioma behavior. Similarly, liquid biopsy has emerged as a potent tool for identifying tumor-derived markers in biofluids, offering a non-invasive glimpse into tumor evolution. Despite their promise, these methodologies grapple with significant challenges. Their sensitivity remains inconsistent, complicating the accurate differentiation between TP and PSP. Furthermore, the absence of standardized protocols across platforms impedes the reliability of comparisons, while inherent biological variability adds complexity to data interpretation. CONCLUSION: Their potential applications have been highlighted, but gaps remain before routine clinical use. Further research is needed to develop and validate these promising methods for distinguishing TP from PsP in gliomas.

6.
Front Microbiol ; 15: 1360225, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38450163

RESUMO

Colorectal cancer (CRC) is a common malignancy affecting the gastrointestinal tract worldwide. The etiology and progression of CRC are related to factors such as environmental influences, dietary structure, and genetic susceptibility. Intestinal microbiota can influence the integrity of the intestinal mucosal barrier and modulate intestinal immunity by secreting various metabolites. Dysbiosis of the intestinal microbiota can affect the metabolites of the microbial, leading to the accumulation of toxic metabolites, which can trigger chronic inflammation or DNA damage and ultimately lead to cellular carcinogenesis and the development of CRC. Postbiotics are preparations of inanimate microorganisms or their components that are beneficial to the health of the host, with the main components including bacterial components (e.g., exopolysaccharides, teichoic acids, surface layer protein) and metabolites (e.g., short-chain fatty acids, tryptophan metabolite, bile acids, vitamins and enzymes). Compared with traditional probiotics, it has a more stable chemical structure and higher safety. In recent years, it has been demonstrated that postbiotics are involved in regulating intestinal microecology and improving the progression of CRC, which provides new ideas for the prevention and diagnosis of CRC. In this article, we review the changes in intestinal microbiota in different states of the gut and the mechanisms of anti-tumor activity of postbiotic-related components, and discuss the potential significance of postbiotics in the diagnosis and treatment of CRC. This reviews the changes and pathogenesis of intestinal microbiota in the development of CRC, and summarizes the relevant mechanisms of postbiotics in resisting the development of CRC in recent years, as well as the advantages and limitations of postbiotics in the treatment process of CRC.

7.
Seizure ; 116: 87-92, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38523034

RESUMO

OBJECTIVES: The APC2 gene, encoding adenomatous polyposis coli protein-2, is involved in cytoskeletal regulation in neurons responding to endogenous extracellular signals and plays an important role in brain development. Previously, the APC2 variants have been reported to be associated with cortical dysplasia and intellectual disability. This study aims to explore the association between APC2 variants and epilepsy. METHODS: Whole-exome sequencing (WES) was performed in cases (trios) with epilepsies of unknown causes. The damaging effects of variants were predicted by protein modeling and in silico tools. Previously reported APC2 variants were reviewed to analyze the genotype-phenotype correlations. RESULTS: Four pairs of compound heterozygous missense variants were identified in four unrelated patients with epilepsy without brain malformation/intellectual disability. All variants presented no or low allele frequencies in the controls. The missense variants were predicted to be damaging by silico tools, and affect hydrogen bonding with surrounding amino acids or decreased protein stability. Patients with variants that resulted in significant changes in protein stability exhibited more severe and intractable epilepsy, whereas patients with variants that had minor effect on protein stability exhibited relatively mild phenotypes. The previously reported APC2 variants in patients with complex cortical dysplasia with other brain malformations-10 (CDCBM10; MIM: 618677) were all truncating variants; in contrast, the variants identified in epilepsy in this study were all missense variants, suggesting a potential genotype-phenotype correlation. SIGNIFICANCE: This study suggests that APC2 is potentially associated with epilepsy without brain malformation/intellectual disability. The genotype-phenotype correlation helps to understand the underlying mechanisms of phenotypic heterogeneity.


Assuntos
Epilepsia , Deficiência Intelectual , Malformações do Desenvolvimento Cortical , Transtornos do Neurodesenvolvimento , Humanos , Deficiência Intelectual/genética , Epilepsia/genética , Transtornos do Neurodesenvolvimento/genética , Mutação de Sentido Incorreto , Fenótipo , Proteínas do Citoesqueleto/genética
8.
Chemosphere ; 354: 141739, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38503383

RESUMO

Considering the persistent and covert nature of heavy metal soil contamination, the sustainable development of ecological environments and food safety is at significant risk. Our study focuses on remediating soils contaminated with chromium (Cr); we introduce an advanced remediation material, iron oxide phosphoric acid-loaded activated biochar (HFBC), synthesized through pyrolysis. This HFBC displays greater microporosity, fewer impurities, and enhanced efficiency for the remediation process. Our research utilized a comprehensive set of analytical techniques, including Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray Photoelectron Spectroscopy (XPS), alongside adsorption studies to elucidate the Cr removal mechanism. The effectiveness of HFBC in remediation was influenced by several factors: the pH level, dosage of HFBC, the initial concentration of Cr, and the ambient temperature. Our results indicated an optimal chromium (VI) adsorption capacity of 55.5 mg/g by HFBC at a pH of 6.0 and a temperature of 25 °C, with the process adhering to the pseudo-second-order kinetic model and the Langmuir adsorption isotherm, thus suggesting spontaneity in the uptake method. Moreover, this mechanism encompasses both adsorption and reduction reactions. Using HFBC in pot experiments with cabbage indicated not only an increase in soil pH and cation exchange capacity (CEC), but also a surge in bacterial community abundance. Significant reductions in bioavailable chromium were also recorded. Interestingly, HFBC addition bolstered the growth of cabbage, while concurrently diminishing chromium accumulation within the plant, particularly notable as the HFBC application rate increased. In summation, the HFBC produced in our study has demonstrated convincing efficacy in removing chromium from aqueous solutions and soil. Moreover, the positive agronomic implications of its use, such as enhanced plant growth and reduced heavy metal uptake by plants, indicate its high potential for operational value in the domain of environmental remediation of heavy metals.


Assuntos
Cloretos , Compostos Férricos , Ácidos Fosfóricos , Typhaceae , Poluentes Químicos da Água , Água , Solo/química , Cromo/química , Carvão Vegetal/química , Adsorção , Poluentes Químicos da Água/análise , Cinética
9.
J Cancer Res Clin Oncol ; 150(3): 168, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38546908

RESUMO

OBJECTIVES: The aim of this study was to investigate the anti-tumor effect of resveratrol (RSV) on glioblastoma (GBM) and its specific mechanism in improving the inflammatory response of the tumor microenvironment. The tumor microenvironment of GBM is highly neuroinflammatory, inducing tumor immunosuppression. Therefore, ameliorating the inflammatory response is an important focus for anti-tumor research. METHODS: The anti-tumor effect of RSV on GBM was demonstrated through in vitro cellular assays, including CCK-8, EdU, PI staining, Transwell, wound healing assay, and flow cytometry. Potential mechanisms of RSV's anti-GBM effects were identified through network pharmacological analysis. In addition, the relationship of RSV with the JAK2/STAT3 signaling pathway and the inflammasome NLRP3 was verified using Western blot. RESULTS: RSV significantly inhibited cell viability in GBM cell lines LN-229 and U87-MG. Furthermore, it inhibited the proliferation and invasive migration ability of GBM cells, while promoting apoptosis. Network pharmacological analysis revealed a close association between the anti-GBM effects of RSV and the JAK/STAT signaling pathway, as well as inflammatory responses. Western blot analysis confirmed that RSV inhibited the over-activation of the inflammasome NLRP3 through the JAK2/STAT3 signaling pathway. Partial reversal of RSV's inhibition of inflammasome NLRP3 was observed with the addition of the JAK/STAT agonist RO8191. CONCLUSIONS: In vitro, RSV can exert anti-tumor effects on GBM and improve the inflammatory response in the GBM microenvironment by inhibiting the activation of the JAK2/STAT3 signaling pathway. These findings provide new insights into potential therapeutic targets for GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/patologia , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neoplasias Encefálicas/patologia , Fator de Transcrição STAT3/metabolismo , Linhagem Celular Tumoral , Janus Quinase 2/metabolismo , Microambiente Tumoral
10.
J Interferon Cytokine Res ; 44(4): 158-169, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38498032

RESUMO

Interleukin 12 (IL-12) is a heterodimer consisting of 2 subunits, p35 and p40, with unique associations and interacting functions with its family members. IL-12 is one of the most important cytokines regulating the immune system response and is integral to adaptive immunity. IL-12 has shown marked therapeutic potential in a variety of tumor types. This review therefore summarizes the characteristics of IL-12 and its application in tumor treatment, focusing on its antitumor effects in colorectal cancer (CRC) and potential radiosensitization mechanisms. We aim to provide a current reference for IL-12 and other potential CRC treatment strategies.


Assuntos
Neoplasias Colorretais , Interleucina-12 , Humanos , Neoplasias Colorretais/terapia , Citocinas , Interleucina-12/imunologia , Interleucina-12/uso terapêutico , Subunidade p35 da Interleucina-12 , Subunidade p40 da Interleucina-12 , Interleucina-23
11.
BMJ Open ; 14(3): e078719, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38508625

RESUMO

OBJECTIVE: To construct a scientific and systematic competency evaluation tool for master of nursing specialists (MNS) and to provide a reference for the training, assessment and competency evaluation of MNS. METHODS: A first draft of the indicators for assessing MNS core competencies was developed on the basis of published research and group discussions. Between June and December 2020, the indicators were revised using two rounds of the Delphi expert consultation method, with questionnaires completed by 16 experts from five provinces in China. RESULTS: The valid retrieval rate of the two questionnaires was 100.00%, and the coefficient of expert authority was 0.931. The Kendall's concordance coefficients of the two rounds of questionnaires were 0.136 (p<0.05) and 0.147 (p<0.05), respectively. Consensus was reached on the seven dimensions and 52 items of the MNS competency assessment instrument. The instrument dimensions included nurse‒patient communication (9 items), health assessment (7 items), clinical decision-making (8 items), operational skills (7 items), health promotion (6 items), humanistic care (9 items) and organisational effectiveness (6 items). CONCLUSIONS: The MNS competency assessment tool constructed in this study is focused and highly credible. The findings can be used as a guide for the training, assessment and competence evaluation of MNS in the future.


Assuntos
Competência Clínica , Estudantes de Enfermagem , Humanos , Técnica Delfos , Inquéritos e Questionários , Encaminhamento e Consulta
12.
Cell Discov ; 10(1): 28, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472169

RESUMO

Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

13.
Alcohol ; 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38467168

RESUMO

BACKGROUND: To understand why some individuals who develop alcohol use disorders (AUD) first begin to drink heavily, a number of scales have been developed that index aspects of alcohol craving and restraint from drinking. We developed a new measure called the Alcohol Consumption Questionnaire (ACQ), based in part on items modified from scales used to index binge eating because there are data to suggest that binge eating and binge drinking may share common antecedents. We present an initial validity study using data from a sample of Mexican Americans. METHODS: Data were from 699 Mexican American young adults in San Diego County, CA. A subsample (n=60) had short-term test-retest data. Factor analysis and reliability assessment guided item reduction. Item response theory (IRT) analyses quantified item severity and identified questions with differential item functioning (DIF). Logistic regression assessed associations of mean scale scores with AUD, adjusting for key demographics, alcohol expectancies and subjective response to alcohol. We also examined associations with a protective genetic variant downstream from the alcohol dehydrogenase 7 gene (ADH7). RESULTS: The scale was reduced from 20 to 14 questions, which can be summarized by a single overall score (Cronbach's alpha=0.896) or by two sub-scores (Consumption: 12 items, Cronbach's alpha=0.896; Enjoyment: 2 items, Cronbach's alpha=0.780). Test-retest reliability was very high (0.80-0.98) in this sample. The overall ACQ score and each subdomain score were strongly associated with AUD (ORs= 5.95 mild; 11.41 moderate; 48.56 severe) and family history of AUD. Respondents with the protective genetic variant had significantly lower overall ACQ scores (p<.001). CONCLUSION: The ACQ is a novel measure of alcohol consumption with strong relationships with both the AUD phenotype and ADH7 gene variants in a sample of Mexican American young adults.

14.
Zhongguo Gu Shang ; 37(3): 264-70, 2024 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-38515413

RESUMO

OBJECTIVE: To explore risk factors of post-operative traumatic arthritis in patients with ankle fracture,and to establish risk prediction model. METHODS: Totally 550 patients with ankle fracture treated from May 2020 to May 2022 were selected as research objects and divided into modeling group (385 patients) and verification group (165 patients) according to 7:3. In modeling group,patients were classified as occurrence group (112 patients) and non-occurrence group (273 patients) according to whether traumatic arthritis occurred after opertaion. Age,body mass index(BMI),gender,smoking history,diabetes history,injury type,fracture type,operation time,manual labor,open injury,osteoporosis,poor reduction,postoperative weight-bearing time,vascular injury,and surgical method were recorded; risk factors of traumatic arthritis in ankle fracture patients were analyzed by single factor and multi factor logistic regression analyses; R software was used to build the prediction model of line graph;receiver operating characteristic (ROC) curve and calibration graph were applied to verify the discrimination and consistency of the model. RESULTS: One hundred and twelve of 385 patients with ankle fracture were developed to post-operative traumatic arthritis,and 275 did not. Univariate analysis showed that there were significant differences in age,BMI,fracture type,operation time,physical labor aboveⅡ,open injury,osteoporosis and poor reduction between two groups (P<0.05). Multivariate Logistic regression analysis showed that age (OR=2.887),BMI (OR=4.042),fracture type (OR=4.244),operation time (OR=2.665),physical labor above gradeⅡ(OR=5.099),osteoporosis (OR=10.219),and poor reduction (OR=3.112) were independent risk factors for traumatic arthritis after ankle fracture (P<0.05). Based on the above risk factors,an nomogram model was established to predict the risk of postoperative traumatic arthritis in ankle fracture patients,and internal and external verification was conducted. The results showed calibration curve of modeling group and verification group showed a good fit between correction curve and ideal curve,indicating that the predicted risk of postoperative traumatic arthritis by the model was basically consistent with actual risk. Area runder ROC curve analysis results showed 0.867[(95%CI(0.826,0.908)] and 0.882 [95%CI(0.827,0.938)],respectively,indicating that the prediction model had good prediction ability. CONCLUSION: Age,BMI,fracture type,operation time,physical labor above gradeⅡ,osteoporosis and poor reduction are all risk factors for post-operative traumatic arthritis in patients with ankle fracture. The prediction model based on the above risk factors could effectively evaluate risk of post-operative traumatic arthritis in patients with ankle fracture.


Assuntos
Fraturas do Tornozelo , Osteoporose , Lesões do Sistema Vascular , Humanos , Fraturas do Tornozelo/cirurgia , Fatores de Risco , Índice de Massa Corporal , Estudos Retrospectivos
15.
Int J Mol Sci ; 25(6)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38542092

RESUMO

Photodynamic therapy (PDT) has been a topic of interest since the first report in 1900 but has yet to become a 'mainstream' treatment protocol in the medical field. There are clear indications for which PDT might be the 'method of choice', but it is unlikely that there will be protocols for the treatment of systemic disease. This report discusses recent developments for promoting PDT efficacy, in the context of what is already known. Factors that can limit the scope of these applications are also indicated. Among the more interesting of these developments is the use of formulation techniques to target specific organelles for photodamage. This can enhance responses to PDT and circumvent situations where an impaired death pathway interferes with PDT efficacy.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico
16.
Cell Rep ; 43(2): 113725, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38300800

RESUMO

Flavonoids are a class of secondary metabolites widely distributed in plants. Regiospecific modification by methylation and glycosylation determines flavonoid diversity. A rare flavone glycoside, diosmin (luteolin-4'-methoxyl-7-O-glucosyl-rhamnoside), occurs in Chrysanthemum indicum. How Chrysanthemum plants evolve new biosynthetic capacities remains elusive. Here, we assemble a 3.11-Gb high-quality C. indicum genome with a contig N50 value of 4.39 Mb and annotate 50,606 protein-coding genes. One (CiCOMT10) of the tandemly repeated O-methyltransferase genes undergoes neofunctionalization, preferentially transferring the methyl group to the 4'-hydroxyl group of luteolin with ortho-substituents to form diosmetin. In addition, CiUGT11 (UGT88B3) specifically glucosylates 7-OH group of diosmetin. Next, we construct a one-pot cascade biocatalyst system by combining CiCOMT10, CiUGT11, and our previously identified rhamnosyltransferase, effectively producing diosmin with over 80% conversion from luteolin. This study clarifies the role of transferases in flavonoid diversity and provides important gene elements essential for producing rare flavone.


Assuntos
Chrysanthemum , Diosmina , Flavonas , Metiltransferases/genética , Luteolina , Glucosiltransferases/genética , Chrysanthemum/genética , Genômica , Flavonoides
17.
BMC Genomics ; 25(1): 136, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308218

RESUMO

Microbial remediation of heavy metal polluted environment is ecofriendly and cost effective. Therefore, in the present study, Shewanella putrefaciens stain 4H was previously isolated by our group from the activated sludge of secondary sedimentation tank in a dyeing wastewater treatment plant. The bacterium was able to reduce chromate effectively. The strains showed significant ability to reduce Cr(VI) in the pH range of 8.0 to 10.0 (optimum pH 9.0) and 25-42 ℃ (optimum 30 ℃) and were able to reduce 300 mg/L of Cr(VI) in 72 h under parthenogenetic anaerobic conditions. In this paper, the complete genome sequence was obtained by Nanopore sequencing technology and analyzed chromium metabolism-related genes by comparative genomics The genomic sequence of S. putrefaciens 4H has a length of 4,631,110 bp with a G + C content of 44.66% and contains 4015 protein-coding genes and 3223,  2414, 2343 genes were correspondingly annotated into the COG, KEGG, and GO databases. The qRT-PCR analysis showed that the expression of chrA, mtrC, and undA genes was up-regulated under Cr(VI) stress. This study explores the Chromium Metabolism-Related Genes of S. putrefaciens 4H and will help to deepen our understanding of the mechanisms of Cr(VI) tolerance and reduction in this strain, thus contributing to the better application of S. putrefaciens 4H in the field of remediation of chromium-contaminated environments.


Assuntos
Shewanella putrefaciens , Shewanella putrefaciens/genética , Shewanella putrefaciens/metabolismo , Oxirredução , Cromo/toxicidade , Cromo/metabolismo , Bactérias/metabolismo
18.
Angew Chem Int Ed Engl ; : e202402195, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38410020

RESUMO

Chiral trisubstituted vicinal diols are a type of important organic compounds, serving as both common structure units in bioactive natural products and chiral auxiliaries in asymmetric synthesis. Herein, by using siloxypropadienes as the precursors of allyl copper(I) species, a copper(I)-catalyzed diastereoselective and enantioselective reductive allylation of ketones was achieved, providing both syn-diols and anti-diols in good to excellent enantioselectivity. DFT calculations show that cis-γ-siloxy-allyl copper species are generated favorably with either 1-TBSO-propadiene or 1-TIPSO-propadiene. Moreover, the steric difference of TBS group and TIPS group distinguishes the face selectivity of acetophenone, leading to syn-selectivity for 1-TBSO-propadiene and anti-selectivity for 1-TIPSO-propadiene. Easy transformations of the products were performed, demonstrating the synthetic utility of the present method. Moreover, one chiral diol prepared in the above transformations was used as a suitable organocatalyst for the catalytic asymmetric reductive self-coupling of aldimines generated in situ with B2(neo)2.

19.
J Food Prot ; 87(3): 100234, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38295987

RESUMO

To investigate the distribution, contamination status, and antibiotic resistance of Listeria monocytogenes in four types of retail poultry meat, including chicken, duck, goose, and pigeon, sold in Jiading District, Shanghai, a total of 236 retail poultry meat samples were collected, and L. monocytogenes isolates were obtained for identification and antibiotic susceptibility testing against 14 common antibiotics. Forty-one L. monocytogenes isolates were detected from the 236 retail poultry meat samples, with detection rates of 24.47%, 19.44%, 14.75%, and 4.44% in chicken, goose, duck, and pigeon meat, respectively. Among refrigerated, frozen, and room temperature samples, refrigerated poultry had the highest detection rate at 25.40%, while frozen poultry had the lowest at 13.33%. The detection rate of L. monocytogenes in chicken meat differed significantly between the storage temperatures, while no significant differences were found for other poultry types. No significant differences in detection rates were observed between different retail locations or packaging methods. Isolates exhibited complete resistance to cefoxitin (FOX) and increasing resistance over time to tetracycline (TET) and clindamycin (CLI), while low levels of resistance were found for penicillin (PEN), oxacillin (OXA), and erythromycin (ERY). Resistance to ERY and TET suggests the potential for multidrug resistance. Significant differences in antibiotic resistance profiles were observed among L. monocytogenes from the various poultry types. In summary, contamination status and antibiotic resistance profiles differed among retail chicken, duck, goose, and pigeon meat sold and the resistance rate of strains continues to increase in Jiading District, Shanghai. Targeted control measures should be implemented to reduce the emergence of resistant strains, as retail conditions had minimal impact on L. monocytogenes prevalence in poultry meat.


Assuntos
Antibacterianos , Listeria monocytogenes , Animais , Antibacterianos/farmacologia , Aves Domésticas , Contaminação de Alimentos/análise , Microbiologia de Alimentos , Farmacorresistência Bacteriana , China , Carne , Tetraciclina , Eritromicina , Galinhas , Testes de Sensibilidade Microbiana
20.
Nanomedicine (Lond) ; 19(2): 109-125, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38197393

RESUMO

Purpose: We constructed biomimetic nanoparticles with biocompatible, tumor-targeting, laser-responsive properties for ferroptosis-induced colorectal cancer chemo-photothermal therapy, with the aim to realize double-hit ferroptosis treatment for colorectal cancer. Methods: The nanoparticles were prepared by first loading the chemotherapy drug bufotalin (CS-5) with Prussian blue (PB), then combining a hybridized erythrocyte-tumor membrane (M) with PB@CS-5 to produce PB@CS-5@M. The chemo-photothermal therapy efficiency of PB@CS-5@M was tested by in vitro and in vivo experiments. Results and conclusion: The combined PB and CS-5 act as promising ferroptosis inducers to enhance ferroptosis efficacy. The hyperthermia induced by laser stimulation can trigger PB to release CS-5 and iron and ferrous ions, which further promotes ferroptosis.


Assuntos
Bufanolídeos , Neoplasias Colorretais , Ferrocianetos , Ferroptose , Hipertermia Induzida , Nanopartículas , Humanos , Terapia Fototérmica , Biomimética , Fototerapia/métodos , Hipertermia Induzida/métodos , Nanopartículas/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Doxorrubicina/farmacologia , Linhagem Celular Tumoral
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